OPZELURA is indicated for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adult and pediatric patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

OPZELURA is indicated for the topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and older.

Use of OPZELURA in combination with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants such as azathioprine or cyclosporine is not recommended.

Do not use more than one 60 gram tube per week or one 100 gram tube per 2 weeks.

OPZELURA is for topical use only. OPZELURA is not for ophthalmic, oral, or intravaginal use.

Instruct patients to apply a thin layer of OPZELURA twice daily to affected areas of up to 20% body surface area.

Stop using when signs and symptoms (e.g., itch, rash, and redness) of atopic dermatitis resolve. If signs and symptoms do not improve within 8 weeks, patients should be re-examined by their healthcare provider [see Clinical Studies (14.1)].

Instruct patients to apply a thin layer of OPZELURA twice daily to affected areas of up to 10% body surface area.

Satisfactory patient response may require treatment with OPZELURA for more than 24 weeks. If the patient does not find the repigmentation meaningful by 24 weeks, the patient should be re‑evaluated by the healthcare provider [see Clinical Studies (14.2)].

Cream: 15 mg of ruxolitinib per gram (1.5%) of white to off-white cream.

{ "type": "p", "children": [], "text": "Cream: 15 mg of ruxolitinib per gram (1.5%) of white to off-white cream.\n" }

None.

{ "type": "p", "children": [], "text": "None.\n" }

Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving oral Janus kinase inhibitors.

Serious lower respiratory tract infections were reported in the clinical development program with topical ruxolitinib.

Avoid use of OPZELURA in patients with an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating OPZELURA in patients:

Closely monitor patients for the development of signs and symptoms of infection during and after treatment with OPZELURA. Interrupt OPZELURA if a patient develops a serious infection, an opportunistic infection, or sepsis. Do not resume OPZELURA until the infection is controlled.

Tuberculosis

No cases of active tuberculosis (TB) were reported in clinical trials with OPZELURA. Cases of active TB were reported in clinical trials of oral Janus kinase inhibitors used to treat inflammatory conditions. Consider evaluating patients for latent and active TB infection prior to administration of OPZELURA.

During OPZELURA use, monitor patients for the development of signs and symptoms of TB.

Viral Reactivation

Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical trials with Janus kinase inhibitors used to treat inflammatory conditions including OPZELURA. If a patient develops herpes zoster, consider interrupting OPZELURA treatment until the episode resolves.

Hepatitis B and C

The impact of Janus kinase inhibitors used to treat inflammatory conditions including OPZELURA on chronic viral hepatitis reactivation is unknown. Patients with a history of hepatitis B or C infection were excluded from clinical trials.

Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, have been reported in patients with chronic HBV infections taking oral ruxolitinib.

OPZELURA initiation is not recommended in patients with active hepatitis B or hepatitis C.

In a large, randomized, postmarketing safety study of an oral JAK inhibitor in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the JAK inhibitor compared with TNF blockers.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA.

Malignancies, including lymphomas, were observed in clinical trials of oral JAK inhibitors used to treat inflammatory conditions. Patients who are current or past smokers are at additional increased risk.

Malignancies, including lymphomas, have occurred in patients receiving JAK inhibitors used to treat inflammatory conditions. In a large, randomized, postmarketing safety study of an oral JAK inhibitor in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. In this study, current or past smokers had an additional increased risk of overall malignancies.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients with a known malignancy (other than successfully treated non-melanoma skin cancers), patients who develop a malignancy when on treatment, and patients who are current or past smokers.

Non-melanoma Skin Cancers

Non-melanoma skin cancers including basal cell and squamous cell carcinoma have occurred in patients treated with OPZELURA. Perform periodic skin examinations during OPZELURA treatment and following treatment as appropriate. Exposure to sunlight and UV light should be limited by wearing protective clothing and using broad-spectrum sunscreen.

In a large, randomized, postmarketing safety study of an oral JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with OPZELURA, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue OPZELURA in patients that have experienced a myocardial infarction or stroke.

Thromboembolic events were observed in clinical trials with OPZELURA.

Thrombosis, including deep vein thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death.

In a large, randomized, postmarketing safety study of an oral JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers.

Avoid OPZELURA in patients who may be at increased risk of thrombosis. If symptoms of thrombosis occur, discontinue OPZELURA and evaluate and treat patients appropriately.

Thrombocytopenia, anemia, and neutropenia were reported in the clinical trials with OPZELURA. Consider the benefits and risks for individual patients who have a known history of these events prior to initiating therapy with OPZELURA. Perform CBC monitoring as clinically indicated. If signs and/or symptoms of clinically significant thrombocytopenia, anemia, and neutropenia occur, patients should discontinue OPZELURA.

Treatment with oral ruxolitinib has been associated with increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Atopic Dermatitis

In two double-blind, vehicle-controlled clinical trials (TRuE-AD1 and TRuE-AD2), 499 adult and pediatric subjects 12 years of age and older with atopic dermatitis were treated with OPZELURA twice daily for 8 weeks. In the OPZELURA group, 62% of subjects were females, and 71% of subjects were White, 23% were Black, and 4% were Asian. The adverse reactions reported by ≥ 1% of OPZELURA treated subjects and at a greater incidence than in the vehicle arm are listed in Table 1.

<div class="scrollingtable"><table width="657.16px"> <caption> <span>Table 1: Adverse Reactions Occurring in ≥ 1% of Subjects Treated with OPZELURA for Atopic Dermatitis through Week 8 in TRuE-AD1 and TRuE-AD2</span> </caption> <col/> <col width="35%"/> <col width="35%"/> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>TEAE – treatment emergent adverse events</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold"> Adverse Reaction</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">OPZELURA<br/> (N = 499)<br/> n (%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Vehicle<br/> (N = 250)<br/> n (%)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Italics">Subjects with any TEAE<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> </span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Italics">132 (27)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Italics">83 (33)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Nasopharyngitis</td><td align="center" class="Botrule Lrule Rrule Toprule">13 (3)</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (1)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Bronchitis</td><td align="center" class="Botrule Lrule Rrule Toprule">4 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">0 (0)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Ear infection</td><td align="center" class="Botrule Lrule Rrule Toprule">4 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">0 (0)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Eosinophil count increased</td><td align="center" class="Botrule Lrule Rrule Toprule">4 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">0 (0)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Urticaria</td><td align="center" class="Botrule Lrule Rrule Toprule">4 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">0 (0)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Diarrhea</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (&lt; 1)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Folliculitis</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">0 (0)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Tonsillitis </td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">0 (0)</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> Rhinorrhea</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (&lt; 1)</td> </tr> </tbody> </table></div>

Adverse reactions that occurred in TRuE-AD1 and TRuE-AD2 in < 1% of subjects in the OPZELURA group and none in the vehicle group were: neutropenia, allergic conjunctivitis, pyrexia, seasonal allergy, herpes zoster, otitis externa, Staphylococcal infection, and acneiform dermatitis.

Nonsegmental Vitiligo

In two double-blind, vehicle-controlled clinical trials (TRuE-V1 and TRuE-V2), 449 adult and pediatric subjects 12 years of age and older with nonsegmental vitiligo were treated with OPZELURA twice daily for 24 weeks. In the OPZELURA group, 55% of subjects were females, and 81% of subjects were White, 5% were Black, and 4% were Asian. The adverse reactions reported by OPZELURA treated subjects with an incidence of ≥ 1% and at least 1% greater incidence than in the vehicle arm in the 24-week double-blind period are listed in Table 2.

<div class="scrollingtable"><table width="660.2px"> <caption> <span>Table 2: Adverse Reactions Occurring in ≥ 1% of Subjects Treated with OPZELURA for Nonsegmental Vitiligo through Week 24 in TRuE-V1 and TRuE-V2</span> </caption> <col/> <col/> <col/> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>TEAE – treatment emergent adverse events</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Adverse Reaction</span> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">OPZELURA<br/> (N = 449)<br/> n (%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">Vehicle<br/> (N = 224)<br/> n (%)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <span class="Italics">Subjects with any TEAE<a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a> </span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Italics">214 (48)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Italics">79 (35)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Application site acne</td><td align="center" class="Botrule Lrule Rrule Toprule">26 (6)</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (1)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Application site pruritus</td><td align="center" class="Botrule Lrule Rrule Toprule">23 (5)</td><td align="center" class="Botrule Lrule Rrule Toprule">6 (3)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Nasopharyngitis</td><td align="center" class="Botrule Lrule Rrule Toprule">19 (4)</td><td align="center" class="Botrule Lrule Rrule Toprule">5 (2)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Headache</td><td align="center" class="Botrule Lrule Rrule Toprule">17 (4)</td><td align="center" class="Botrule Lrule Rrule Toprule">6 (3)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Urinary tract infection</td><td align="center" class="Botrule Lrule Rrule Toprule">7 (2)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (&lt; 1)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Application site erythema</td><td align="center" class="Botrule Lrule Rrule Toprule">7 (2)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (&lt; 1)</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> Pyrexia</td><td align="center" class="Botrule Lrule Rrule Toprule">6 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> </tbody> </table></div>

Adverse reactions that occurred in TRuE-V1 and TRuE-V2 in ≥ 0.5% to < 1% of subjects in the OPZELURA group and none in the vehicle group were: application site dermatitis, hypertension, anxiety, application site discoloration, application site folliculitis, contusion, dermatitis contact, diarrhea, ear infection, gastritis, gastroenteritis, hordeolum, influenza-like illness, insomnia, nasal congestion, and vomiting.

Drug interaction studies with OPZELURA have not been conducted.

{ "type": "p", "children": [], "text": "Drug interaction studies with OPZELURA have not been conducted." }

Ruxolitinib is known to be a substrate for cytochrome P450 3A4 (CYP3A4). Inhibitors of CYP3A4 may increase ruxolitinib systemic concentrations whereas inducers of CYP3A4 may decrease ruxolitinib systemic concentrations [see Clinical Pharmacology (12.3)].

{ "type": "p", "children": [], "text": "Ruxolitinib is known to be a substrate for cytochrome P450 3A4 (CYP3A4). Inhibitors of CYP3A4 may increase ruxolitinib systemic concentrations whereas inducers of CYP3A4 may decrease ruxolitinib systemic concentrations [see Clinical Pharmacology (12.3)]." }

Strong Inhibitors of CYP3A4

{ "type": "p", "children": [], "text": "\nStrong Inhibitors of CYP3A4\n" }

Avoid concomitant use of OPZELURA with strong inhibitors of CYP3A4 as there is a potential to increase the systemic exposure of ruxolitinib and could increase the risk of OPZELURA adverse reactions [see Clinical Pharmacology (12.3)].

{ "type": "p", "children": [], "text": "Avoid concomitant use of OPZELURA with strong inhibitors of CYP3A4 as there is a potential to increase the systemic exposure of ruxolitinib and could increase the risk of OPZELURA adverse reactions [see Clinical Pharmacology (12.3)].\n" }

Pregnancy Exposure Registry

There is a pregnancy registry that monitors pregnancy outcomes in pregnant persons exposed to OPZELURA during pregnancy. Pregnant persons exposed to OPZELURA and healthcare providers should report OPZELURA exposure by calling 1-855-463-3463 or visiting www.opzelura.pregnancy.incyte.com.

Risk Summary

Available data from pregnancies reported in clinical trials with OPZELURA are not sufficient to evaluate a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of ruxolitinib to pregnant rats and rabbits during the period of organogenesis resulted in adverse developmental outcomes at doses associated with maternal toxicity (see Data).

The background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. The background risk in the U.S. general population of major birth defects and miscarriage is 2-4% and 15-20%, respectively.

Data

Animal Data

Ruxolitinib was administered orally to pregnant rats or rabbits during the period of organogenesis, at doses of 15, 30, or 60 mg/kg/day in rats and 10, 30, or 60 mg/kg/day in rabbits. There were no treatment-related malformations at any dose. A decrease in fetal weight of approximately 9% was noted in rats at the highest and maternally toxic dose of 60 mg/kg/day. This dose resulted in systemic exposure approximately 22 times the clinical systemic exposure at the maximum recommended human dose (MRHD; the clinical systemic exposure from ruxolitinib cream, 1.5% applied twice daily to 25-40% atopic dermatitis-affected body surface area is used for calculation of multiples of human exposure). In rabbits, lower fetal weights of approximately 8% and increased late resorptions were noted at the highest and maternally toxic dose of 60 mg/kg/day. This dose resulted in systemic exposure approximately 70% the MRHD clinical systemic exposure.

In a pre-and post-natal development study in rats, pregnant animals were dosed with ruxolitinib from implantation through lactation at doses up to 30 mg/kg/day. There were no drug-related adverse effects on embryofetal survival, postnatal growth, development parameters or offspring reproductive function at the highest dose evaluated (3.1 times the MRHD clinical systemic exposure).

Risk Summary

There are no data on the presence of ruxolitinib in human milk, the effects on the breastfed child, or the effects on milk production. Ruxolitinib was present in the milk of lactating rats (see Data). When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the serious adverse findings in adults, including risks of serious infections, thrombocytopenia, anemia, and neutropenia, advise women not to breastfeed during treatment with OPZELURA and for approximately four weeks after the last dose (approximately 5-6 elimination half-lives).

Data

Lactating rats were administered a single dose of [14C]-labeled ruxolitinib (30 mg/kg) on postnatal Day 10, after which plasma and milk samples were collected for up to 24 hours. The AUC for total radioactivity in milk was approximately 13 times the maternal plasma AUC. Additional analysis showed the presence of ruxolitinib and several of its metabolites in milk, all at levels higher than those in maternal plasma.

Atopic Dermatitis

The safety and effectiveness of OPZELURA for the topical treatment of mild-to-moderate atopic dermatitis have been established in pediatric patients aged 12 to 17 years of age. Use of OPZELURA in this age group is supported by evidence from TRuE-AD1 and TRuE-AD2, which included 92 pediatric subjects aged 12 to 17 years with mild-to-moderate atopic dermatitis [see Clinical Pharmacology (12.3) and Clinical Studies (14.1)]. No clinically meaningful differences in safety or effectiveness were observed between adult and pediatric subjects.

The safety and effectiveness of OPZELURA in pediatric patients younger than 12 years of age with atopic dermatitis have not been established.

Nonsegmental Vitiligo

The safety and effectiveness of OPZELURA for the topical treatment of nonsegmental vitiligo have been established in pediatric patients aged 12 to 17 years of age. Use of OPZELURA in this age group is supported by evidence from TRuE-V1 and TRuE-V2, which included 55 pediatric subjects aged 12 to 17 years with nonsegmental vitiligo [see Clinical Studies (14.2)]. No clinically meaningful differences in safety or effectiveness were observed between adult and pediatric subjects.

The safety and effectiveness of OPZELURA in pediatric patients younger than 12 years of age with nonsegmental vitiligo have not been established.

Juvenile Animal Toxicity Data

Oral administration of ruxolitinib to juvenile rats resulted in effects on growth and bone measures. When administered starting at postnatal day 7 (the equivalent of a human newborn) at doses of 1.5 to 75 mg/kg/day, evidence of fractures occurred at doses ≥ 30 mg/kg/day, and effects on body weight and other bone measures [e.g., bone mineral content, peripheral quantitative computed tomography, and x-ray analysis] occurred at doses ≥ 5 mg/kg/day. When administered starting at postnatal day 21 (the equivalent of a human 2-3 years of age) at doses of 5 to 60 mg/kg/day, effects on body weight and bone occurred at doses ≥ 15 mg/kg/day, which were considered adverse at 60 mg/kg/day. Males were more severely affected than females in all age groups, and effects were generally more severe when administration was initiated earlier in the postnatal period. These findings were observed at systemic exposures that are at least 40% the MRHD clinical systemic exposure.

Of the 1249 total subjects with atopic dermatitis in clinical trials with OPZELURA, 115 (9%) were 65 years of age and older [see Clinical Studies (14.1)]. No clinically meaningful differences in safety or effectiveness were observed between subjects less than 65 years and subjects 65 years and older.

Of the 831 total subjects enrolled with nonsegmental vitiligo in clinical trials with OPZELURA, 65 (8%) were 65 years of age and older [see Clinical Studies (14.2)]. Clinical trials of OPZELURA in subjects with nonsegmental vitiligo did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

Ruxolitinib phosphate is a Janus kinase inhibitor with the chemical name (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate and a molecular weight of 404.36 g/mol. Ruxolitinib phosphate has the following structural formula: Ruxolitinib phosphate is a white to off-white to light yellow to light pink powder.   OPZELURA (ruxolitinib) cream is a white to off-white oil-in-water, solubilized emulsion cream for topical use. Each gram of OPZELURA contains 15 mg of ruxolitinib (equivalent to 19.8 mg of ruxolitinib phosphate) in a cream containing cetyl alcohol, dimethicone 350, edetate disodium, glyceryl stearate SE, light mineral oil, medium chain triglycerides, methylparaben, phenoxyethanol, phosphoric acid, polyethylene glycol 200, polysorbate 20, propylene glycol, propylparaben, stearyl alcohol, purified water, white petrolatum, and xanthan gum.

{ "type": "p", "children": [], "text": "Ruxolitinib phosphate is a Janus kinase inhibitor with the chemical name (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate and a molecular weight of 404.36 g/mol. Ruxolitinib phosphate has the following structural formula:\n\n\n\nRuxolitinib phosphate is a white to off-white to light yellow to light pink powder.\n \nOPZELURA (ruxolitinib) cream is a white to off-white oil-in-water, solubilized emulsion cream for topical use.\n\nEach gram of OPZELURA contains 15 mg of ruxolitinib (equivalent to 19.8 mg of ruxolitinib phosphate) in a cream containing cetyl alcohol, dimethicone 350, edetate disodium, glyceryl stearate SE, light mineral oil, medium chain triglycerides, methylparaben, phenoxyethanol, phosphoric acid, polyethylene glycol 200, polysorbate 20, propylene glycol, propylparaben, stearyl alcohol, purified water, white petrolatum, and xanthan gum." }

Ruxolitinib, a Janus kinase (JAK) inhibitor, inhibits JAK1 and JAK2 which mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. JAK signaling involves recruitment of STATs (signal transducers and activators of transcription) to cytokine receptors, activation and subsequent localization of STATs to the nucleus leading to modulation of gene expression. The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.

Cardiac Electrophysiology

Under the conditions of clinical use, OPZELURA is not expected to prolong the QT interval.

The pharmacokinetics of ruxolitinib were evaluated in a study involving 20 adult subjects and 21 pediatric subjects 13 years and older with atopic dermatitis with a mean ± SD BSA involvement of 37.5 ± 16.1% (range 25% to 90%). Subjects applied approximately 1.5 mg/cm2 of OPZELURA (dose range was approximately 1.2 grams to 37.6 grams per application) twice daily for 28 days. 

Absorption

Plasma concentrations of ruxolitinib were quantifiable in all subjects. In adult subjects, the mean ± SD maximum plasma concentration (Cmax) and area under the concentration time curve from 0 to 12 hours post dose (AUC0 – 12) for ruxolitinib on Day 1 were 449 ± 883 nM and 3215 ± 6184 h*nM, respectively.

There is no evidence of ruxolitinib accumulation after daily application of OPZELURA for 28 days in subjects with atopic dermatitis.

Distribution

Plasma protein binding is approximately 97%.

Elimination

The mean terminal half-life of ruxolitinib following topical application of OPZELURA was estimated in 9 subjects and is approximately 116 hours. 

Metabolism

Ruxolitinib is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C9 in vitro.

Excretion

Ruxolitinib and its metabolites are primarily excreted by urine (74%) and feces (22%). Less than 1% is excreted as unchanged drug.

Specific Populations

Pediatric Patients

In adolescent subjects with atopic dermatitis (13 – 17 years of age), the mean ± SD Cmax and AUC0 – 12 for ruxolitinib on Day 1 were 110 ± 255 nM and 801 ± 2019 h*nM, respectively.

Drug Interactions

Clinical Studies

Drug interaction studies with OPZELURA have not been conducted.

Strong CYP3A4 inhibitors

The Cmax and AUC of ruxolitinib increased 33% and 91%, respectively, with administration of 10 mg single dose orally following ketoconazole 200 mg twice daily for four days, compared to receiving the oral ruxolitinib dose alone in healthy subjects.

Mild or moderate CYP3A4 inhibitors

There was an 8% and 27% increase in the Cmax and AUC of ruxolitinib, respectively, with the administration of 10 mg single dose orally following erythromycin, a moderate CYP3A4 inhibitor, at 500 mg twice daily for 4 days, compared to receiving the oral ruxolitinib dose alone in healthy subjects. There are no clinical studies conducted with mild CYP3A4 inhibitor.

CYP3A4 inducers

The Cmax and AUC of ruxolitinib decreased 32% and 61%, respectively, with the oral administration of 50 mg single dose of ruxolitinib following rifampin 600 mg once daily for 10 days, compared to receiving the oral ruxolitinib dose alone in healthy subjects.

In Vitro Studies

Cytochrome P450 (CYP) Enzymes: Ruxolitinib is not expected to inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and CYP3A4 or induce CYP1A2, 2B6 and 3A4 following topical application.

Transporter Systems: Ruxolitinib is not expected to inhibit P-gp, BCRP, OATP1B1, OATP1B3, OCT1, OCT2, OAT1, or OAT3 transporter systems following topical application. Ruxolitinib is not a substrate for the P-gp transporter.

Ruxolitinib was not carcinogenic when administered orally in the 6-month Tg.rasH2 transgenic mouse model. In a 2-year oral rat carcinogenicity study, no drug-related tumors were observed at oral doses of ruxolitinib up to 60 mg/kg/day (3.5 times the MRHD clinical systemic exposure). In a 2-year dermal mouse carcinogenicity study, no drug-related tumors were observed at topical doses of ruxolitinib cream up to 1.5% applied at 100 μl/day (2.8 times the MRHD clinical systemic exposure).

Ruxolitinib was not mutagenic in a bacterial mutagenicity assay (Ames test) or clastogenic in an in vitro chromosomal aberration assay (cultured human peripheral blood lymphocytes) or an in vivo rat bone marrow micronucleus assay.

In a fertility study, ruxolitinib was administered orally to male rats prior to and throughout mating and to female rats prior to mating and up to the implantation day (gestation day 7). Ruxolitinib had no effect on fertility or reproductive function in male or female rats at doses up to 60 mg/kg/day (22 times the MRHD clinical systemic exposure). However, in female rats, doses of greater than or equal to 30 mg/kg/day (3.5 times the MRHD clinical systemic exposure) resulted in increased post-implantation loss.

Two double-blind, randomized, vehicle-controlled trials of identical design (TRuE-AD1 and TRuE-AD2, NCT03745638 and NCT03745651, respectively) enrolled a total of 1249 adult and pediatric subjects aged 12 and older. A total of 20% of subjects were 12 to 17 years of age and 9% were 65 years or older. Females constituted 62% of subjects, 70% of subjects were White, 23% were Black, and 4% were Asian. Subjects had affected body surface area (BSA) of 3 to 20%, and an Investigator’s Global Assessment (IGA) score of 2 (mild) to 3 (moderate) on a severity scale of 0 to 4. At baseline, subjects had a mean affected BSA of 9.8% and 39% had affected areas on the face, 25% of subjects had an IGA score of 2 and 75% had a score of 3. The baseline Itch Numerical Rating Scale (Itch NRS), defined as the 7-day average of the worst level of itch intensity in the last 24 hours, was 5 on a scale of 0 to 10.

In both trials, subjects were randomized 2:2:1 to treatment with OPZELURA, ruxolitinib cream, 0.75%, or vehicle cream twice daily (BID) for 8 weeks. The primary efficacy endpoint was the proportion of subjects at week 8 achieving IGA treatment success (IGA-TS) defined as a score of 0 (clear) or 1 (almost clear) with ≥ 2 grade improvement from baseline. Efficacy was also assessed using a ≥ 4-point improvement in Itch NRS.

Efficacy results for OPZELURA from the two trials are summarized in Table 3.

<div class="scrollingtable"><table> <caption> <span>Table 3: Efficacy Results at Week 8 in Subjects with Atopic Dermatitis (TRuE-AD1 and TRuE-AD2)</span> </caption> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <tfoot> <tr> <td align="left" colspan="7"> <dl class="Footnote"> <dt> <a href="#footnote-reference-3" name="footnote-3">*</a> </dt> <dd>Defined as an IGA score of 0 or 1 with a ≥ 2-grade improvement from baseline</dd> <dt> <a href="#footnote-reference-4" name="footnote-4">†</a> </dt> <dd>N = subjects with a baseline Itch NRS score ≥ 4.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" rowspan="2"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3"><span class="Bold">TRuE-AD1</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3"><span class="Bold">TRuE-AD2</span></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">OPZELURA<br/>(N = 253)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Vehicle<br/>(N = 126)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Treatment Difference and<br/> 95% Confidence Interval</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold"><span class="Bold">  OPZELURA  <br/>(N = 228)</span></span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold"><span class="Bold">Vehicle<br/>  (N = 118)  </span></span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Treatment Difference and<br/> 95% Confidence Interval</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">IGA-TS<a class="Sup" href="#footnote-3" name="footnote-reference-3">*</a></td><td align="center" class="Botrule Lrule Rrule Toprule">53.8%<br/>     (136/253)     </td><td align="center" class="Botrule Lrule Rrule Toprule">15.1%<br/>     (19/126)     </td><td align="center" class="Botrule Lrule Rrule Toprule">38.9%<br/>             (30.3%, 47.4%)            </td><td align="center" class="Botrule Lrule Rrule Toprule">51.3%<br/>(117/228)</td><td align="center" class="Botrule Lrule Rrule Toprule">7.6%<br/>(9/118)</td><td align="center" class="Botrule Lrule Rrule Toprule">44.1%<br/>            (36.2%, 52.0%)            </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Itch NRS<br/>(≥ 4 point<br/>reduction) (n/N)<a class="Sup" href="#footnote-4" name="footnote-reference-4">†</a></td><td align="center" class="Botrule Lrule Rrule Toprule">52.2%<br/>(84/161)</td><td align="center" class="Botrule Lrule Rrule Toprule">15.4%<br/>(12/78)</td><td align="center" class="Botrule Lrule Rrule Toprule">36.7%<br/>(25.5%, 48.0%)</td><td align="center" class="Botrule Lrule Rrule Toprule">50.7%<br/>(74/146)</td><td align="center" class="Botrule Lrule Rrule Toprule">16.3%<br/>(13/80)</td><td align="center" class="Botrule Lrule Rrule Toprule">35.8%<br/>(24.4%, 47.2%)</td> </tr> </tbody> </table></div>

Two double-blind, randomized, vehicle-controlled trials of identical design (TRuE‑V1 and TRuE‑V2, NCT04052425 and NCT04057573, respectively) enrolled a total of 674 adult and pediatric subjects aged 12 years and older (11% of subjects were 12 to 17 years of age and 7% were 65 years or older). Females constituted 53% of subjects, 82% of subjects were White, 5% were Black, and 4% were Asian. Fitzpatrick skin types included I (2%), II (30%), III (40%), IV (19%), V (7%), or VI (2%). Subjects had depigmented areas affecting ≥ 0.5% facial body surface area (F-BSA), ≥ 3% non-facial BSA, and total body vitiligo area (facial and non-facial, including hands, feet, upper and lower extremities, and trunk body areas) of up to 10% BSA. At baseline, subjects had a mean affected F-BSA of 1% and a mean affected total BSA of 7.4%. Phototherapy was not permitted during the trial. The mean time since diagnosis of nonsegmental vitiligo was 14.8 years prior to subjects enrolling in the trials.

In both trials, subjects were randomized 2:1 to treatment with OPZELURA or vehicle cream twice daily (BID) for 24 weeks followed by an additional 28 weeks of treatment with OPZELURA BID for all subjects. Lesions on the face were assessed with the facial Vitiligo Area Scoring Index (F-VASI) and lesions on the total body (including the face) were assessed with the total body Vitiligo Area Scoring Index (T-VASI). The primary efficacy endpoint was the proportion of subjects achieving at least 75% improvement in F-VASI (F-VASI75) at Week 24. The proportion of participants achieving at least 90% improvement in F-VASI (F-VASI90) was also evaluated.

Efficacy results for OPZELURA at Week 24 from the two trials are summarized in Table 4. The percentage of subjects who achieved F-VASI75 and T-VASI75 (at least 75% improvement in T‑VASI) over the 52-week treatment period in both trials are shown in Figure 1 and Figure 2.

<div class="scrollingtable"><table> <caption> <span>Table 4: Efficacy Results at Week 24 in Subjects with Nonsegmental Vitiligo (TRuE-V1 and TRuE-V2)</span> </caption> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3"><span class="Bold">TRuE-V1</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3"><span class="Bold">TRuE-V2</span></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">OPZELURA<br/>(N = 221)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Vehicle<br/>(N = 109)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Treatment Difference and<br/>95% Confidence Interval</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">OPZELURA<br/>(N = 229)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Vehicle<br/>(N = 115)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Treatment Difference and<br/>95% Confidence Interval</span></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">F-VASI75    </td><td align="center" class="Botrule Lrule Rrule Toprule">        29.9%       </td><td align="center" class="Botrule Lrule Rrule Toprule">       7.5%       </td><td align="center" class="Botrule Lrule Rrule Toprule">22.5%<br/>           (14.2%, 30.8%)            </td><td align="center" class="Botrule Lrule Rrule Toprule">        29.9%       </td><td align="center" class="Botrule Lrule Rrule Toprule">       12.9%     </td><td align="center" class="Botrule Lrule Rrule Toprule">16.9%<br/>              (7.8%, 26.0%)             </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule">F-VASI90    </td><td align="center" class="Botrule Lrule Rrule Toprule">15.5%</td><td align="center" class="Botrule Lrule Rrule Toprule">2.2%</td><td align="center" class="Botrule Lrule Rrule Toprule">13.3%<br/>(7.5%, 19.1%)</td><td align="center" class="Botrule Lrule Rrule Toprule">15.4%</td><td align="center" class="Botrule Lrule Rrule Toprule">1.9%</td><td align="center" class="Botrule Lrule Rrule Toprule">13.5%<br/>(7.7%, 19.3%)</td> </tr> </tbody> </table></div>

How Supplied

{ "type": "p", "children": [], "text": "\nHow Supplied\n" }

OPZELURA is a white to off-white cream containing 1.5% ruxolitinib and is supplied in 60 g and 100 g tubes.

{ "type": "p", "children": [], "text": "OPZELURA is a white to off-white cream containing 1.5% ruxolitinib and is supplied in 60 g and 100 g tubes." }

60 g tube: NDC 50881-007-05

{ "type": "p", "children": [], "text": "60 g tube: NDC 50881-007-05" }

100 g tube: NDC 50881-007-07

{ "type": "p", "children": [], "text": "100 g tube: NDC 50881-007-07" }

Storage and Handling

{ "type": "p", "children": [], "text": "\nStorage and Handling\n" }

Store OPZELURA at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted from 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store OPZELURA at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted from 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature]." }

Advise the patient or caregivers to read the FDA-approved patient labeling (Medication Guide).

{ "type": "p", "children": [], "text": "Advise the patient or caregivers to read the FDA-approved patient labeling (Medication Guide)." }

Infections

{ "type": "p", "children": [], "text": "\nInfections\n" }

Inform patients that they may be at increased risk for developing infections, including serious infections, when taking Janus kinase inhibitors. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of an infection [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Inform patients that they may be at increased risk for developing infections, including serious infections, when taking Janus kinase inhibitors. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of an infection [see Warnings and Precautions (5.1)]." }

Advise patients that Janus kinase inhibitors increase the risk of herpes zoster, and some cases can be serious [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Advise patients that Janus kinase inhibitors increase the risk of herpes zoster, and some cases can be serious [see Warnings and Precautions (5.1)]." }

Malignancies and Lymphoproliferative Disorders

{ "type": "p", "children": [], "text": "\nMalignancies and Lymphoproliferative Disorders\n" }

Inform patients that Janus kinase inhibitors may increase the risk for developing lymphomas and other malignancies including skin cancer [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Inform patients that Janus kinase inhibitors may increase the risk for developing lymphomas and other malignancies including skin cancer [see Warnings and Precautions (5.3)].\n" }

Instruct patients to inform their health care provider if they have ever had any type of cancer. Inform patients that periodic skin examinations should be performed while using OPZELURA. Advise patients that exposure to sunlight, and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Instruct patients to inform their health care provider if they have ever had any type of cancer. Inform patients that periodic skin examinations should be performed while using OPZELURA. Advise patients that exposure to sunlight, and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen [see Warnings and Precautions (5.3)]." }

Major Adverse Cardiovascular Events

{ "type": "p", "children": [], "text": "\nMajor Adverse Cardiovascular Events \n" }

Advise patients that events of major adverse cardiovascular events (MACE) including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, have been reported in clinical studies with Janus kinase inhibitors used to treat inflammatory conditions. Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "Advise patients that events of major adverse cardiovascular events (MACE) including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, have been reported in clinical studies with Janus kinase inhibitors used to treat inflammatory conditions. Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions (5.4)]." }

Thrombosis

{ "type": "p", "children": [], "text": "\nThrombosis\n" }

Advise patients that events of DVT and PE have been reported in clinical studies with Janus kinase inhibitors used to treat inflammatory conditions. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of a DVT or PE [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "Advise patients that events of DVT and PE have been reported in clinical studies with Janus kinase inhibitors used to treat inflammatory conditions. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of a DVT or PE [see Warnings and Precautions (5.5)]." }

Thrombocytopenia, Anemia, and Neutropenia

{ "type": "p", "children": [], "text": "\nThrombocytopenia, Anemia, and Neutropenia\n" }

Advise patients of the risk of thrombocytopenia, anemia, and neutropenia with OPZELURA. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of thrombocytopenia, anemia, or neutropenia [see Warnings and Precautions (5.6)].

{ "type": "p", "children": [], "text": "Advise patients of the risk of thrombocytopenia, anemia, and neutropenia with OPZELURA. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of thrombocytopenia, anemia, or neutropenia [see Warnings and Precautions (5.6)]. " }

Administration Instructions

{ "type": "p", "children": [], "text": "\nAdministration Instructions\n" }

Advise patients or caregivers that OPZELURA is for topical use only [see Dosage and Administration (2.1)].

{ "type": "p", "children": [], "text": "Advise patients or caregivers that OPZELURA is for topical use only [see Dosage and Administration (2.1)].\n" }

Advise patients to limit treatment to one 60 gram tube per week or one 100 gram tube per 2 weeks [see Dosage and Administration (2.1)].

{ "type": "p", "children": [], "text": "Advise patients to limit treatment to one 60 gram tube per week or one 100 gram tube per 2 weeks [see Dosage and Administration (2.1)]." }

Pregnancy Registry

{ "type": "p", "children": [], "text": "\nPregnancy Registry\n" }

Inform patients to report their pregnancy to Incyte Corporation at 1-855-463-3463 or by visiting www.opzelura.pregnancy.incyte.com [see Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "Inform patients to report their pregnancy to Incyte Corporation at 1-855-463-3463 or by visiting www.opzelura.pregnancy.incyte.com [see Use in Specific Populations (8.1)].\n" }

Lactation

{ "type": "p", "children": [], "text": "\nLactation \n" }

Advise a patient not to breastfeed during treatment with OPZELURA and for about four weeks after the last dose [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "Advise a patient not to breastfeed during treatment with OPZELURA and for about four weeks after the last dose [see Use in Specific Populations (8.2)].\n" }

Manufactured for: Incyte Corporation 1801 Augustine Cut-off Wilmington, DE 19803

{ "type": "p", "children": [], "text": "Manufactured for:\nIncyte Corporation\n1801 Augustine Cut-off\nWilmington, DE 19803" }

OPZELURA is a registered trademark of Incyte. All rights reserved. Patent Information: www.incyte.com/patents © 2021-2024 Incyte Corporation. All rights reserved.

{ "type": "p", "children": [], "text": "OPZELURA is a registered trademark of Incyte. All rights reserved.\nPatent Information: www.incyte.com/patents\n© 2021-2024 Incyte Corporation. All rights reserved." }

<div class="scrollingtable"><table> <col/> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="6"> <p class="First"> <span class="Bold">MEDICATION GUIDE<br/> </span><span class="Bold">OPZELURA<span class="Sup">®</span> (</span><span class="Bold">OP-zuh-LUR-ah</span><span class="Bold">)<br/> </span><span class="Bold"><span class="Bold">(ruxolitinib) </span><span class="Bold">Cream</span></span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="6"><span class="Bold">Important:</span> OPZELURA is for use on the skin only. Do not use OPZELURA in your eyes, mouth, or vagina.<br/> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="6"> <p class="First"> <span class="Bold">What is the most important information I should know about OPZELURA?</span> </p> <p> <span class="Bold">OPZELURA may cause serious side effects, including:</span> </p> <ul class="Disk"> <li> <span class="Bold">Serious Infections.</span> OPZELURA contains ruxolitinib. Ruxolitinib belongs to a class of medicines called Janus kinase (JAK) inhibitors. JAK inhibitors are medicines that affect your immune system. JAK inhibitors can lower the ability of your immune system to fight infections. Some people have had serious infections while taking JAK inhibitors by mouth, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have been hospitalized or died from these infections. Some people have had serious infections of their lungs while using OPZELURA. <ul class="Circle"> <li>Your healthcare provider should watch you closely for signs and symptoms of TB during treatment with OPZELURA.</li> </ul> </li> </ul> <p>OPZELURA should not be used in people with an active, serious infection, including localized infections. You should not start using OPZELURA if you have any kind of infection unless your healthcare provider tells you it is okay. You may be at a higher risk of developing shingles (herpes zoster) while using OPZELURA.</p> <p> <span class="Bold">Before starting OPZELURA, tell your healthcare provider if you</span>:</p> <ul class="Disk"> <li>are being treated for an infection</li> <li>have had an infection that does not go away or that keeps coming back</li> <li>have diabetes, chronic lung disease, HIV, or a weak immune system</li> <li>have TB or have been in close contact with someone with TB</li> <li>have had shingles (herpes zoster)</li> <li>have or have had hepatitis B or C</li> <li>live in an area, or have lived in an area, or have traveled to certain parts of the country (such as the Ohio and Mississippi River valleys and the Southwest) where there is an increased chance for getting certain kinds of fungal infections. These infections may happen or become more severe if you use OPZELURA. Ask your healthcare provider if you do not know if you have lived in an area where these infections are common.</li> <li>think you have an infection or have symptoms of an infection such as:</li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="2"> <ul class="Disk"> <li>fever, sweating, or chills</li> <li>muscle aches</li> <li>cough or shortness of breath</li> </ul> </td><td colspan="2"> <ul class="Disk"> <li>blood in your phlegm</li> <li>weight loss</li> <li>warm, red, or painful skin or sores on your body</li> </ul> </td><td class="Rrule" colspan="2"> <ul class="Disk"> <li>diarrhea or stomach pain</li> <li>burning when you urinate or urinating more often than usual</li> <li>feeling very tired</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="6"> <p class="First">After starting OPZELURA, call your healthcare provider right away if you have any symptoms of an infection.<br/> OPZELURA can make you more likely to get infections or make worse any infections that you have. If you get a serious infection, your healthcare provider may stop your treatment with OPZELURA until your infection is controlled.</p> <ul class="Disk"> <li> <span class="Bold">Increased risk of death <span class="Bold">due to any reason (</span>all causes). </span>Increased risk of death has happened in people 50 years of age and older who have at least 1 heart disease (cardiovascular) risk factor and are taking a medicine in the class of medicines called JAK inhibitors by mouth.<br/> <br/> </li> <li> <span class="Bold">Cancer </span><span class="Bold">and immune system problems. </span>OPZELURA may increase your risk of certain cancers by changing the way your immune system works. <ul class="Circle"> <li>Lymphoma and other cancers have happened in people taking a medicine in the class of medicines called JAK inhibitors by mouth.</li> <li>People taking JAK inhibitors by mouth have a higher risk of certain cancers including lymphoma and lung cancer, especially if they are a current or past smoker. </li> <li>Some people have had skin cancers while using OPZELURA. Your healthcare provider will regularly check your skin during your treatment with OPZELURA. Limit the amount of time you spend in the sunlight. Wear protective clothing when you are in the sun and use a broad-spectrum sunscreen.</li> <li> Tell your healthcare provider if you have ever had any type of cancer.</li> </ul> </li> </ul> <ul class="Disk"> <li> <span class="Bold">Increased risk of major cardiovascular events.</span> Increased risk of major cardiovascular events such as heart attack, stroke, or death have happened in people 50 years of age and older who have at least 1 heart disease (cardiovascular) risk factor and taking a medicine in the class of medicines called JAK inhibitors by mouth, especially in current or past smokers.</li> </ul> <p>Get emergency help right away if you have any symptoms of a heart attack or stroke while using OPZELURA, including:</p> <ul class="Circle"> <li>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</li> <li>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</li> <li>pain or discomfort in your arms, back, neck, jaw, or stomach</li> <li>shortness of breath with or without chest discomfort</li> <li>breaking out in a cold sweat</li> <li>nausea or vomiting</li> <li>feeling lightheaded</li> <li>weakness in one part or on one side of your body</li> <li>slurred speech</li> </ul> <ul class="Disk"> <li> <span class="Bold">Blood clots. </span>Blood clots in the veins of your legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) can happen in some people taking OPZELURA. This may be life-threatening. Blood clots in the vein of the legs (deep vein thrombosis, DVT) and lungs (pulmonary embolism, PE) have happened more often in people who are 50 years of age and older and with at least 1 heart disease (cardiovascular) risk factor taking a medicine in the class of medicines called JAK inhibitors by mouth.<br/> <ul class="Circle"> <li>Tell your healthcare provider if you have had blood clots in the veins of your legs or lungs in the past.</li> <li>Tell your healthcare provider right away if you have any signs and symptoms of blood clots during treatment with OPZELURA, including: <ul class="Square"> <li>swelling, pain, or tenderness in one or both legs</li> <li>sudden, unexplained chest or upper back pain</li> <li>shortness of breath or difficulty breathing</li> </ul> </li> </ul> </li> </ul> <p>See <span class="Bold">“What are the possible side effects of OPZELURA?”</span> for more information about side effects.</p> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="6"> <p class="First"> <span class="Bold">What is OPZELURA?</span> </p> <p>OPZELURA is a prescription medicine used on the skin (topical) for:</p> <ul class="Disk"> <li> short-term and non-continuous chronic treatment of mild to moderate eczema (atopic dermatitis) in non‑immunocompromised adults and children 12 years of age and older whose disease: <ul class="Circle"> <li>is not well controlled with topical prescription therapies or</li> <li>when those therapies are not recommended</li> </ul> </li> </ul> <ul class="Disk"> <li>the treatment of a type of vitiligo called nonsegmental vitiligo in adults and children 12 years of age and older.</li> </ul> <p>The use of OPZELURA along with therapeutic biologics, other JAK inhibitors, or strong immunosuppressants such as azathioprine or cyclosporine is not recommended.</p> <p>It is not known if OPZELURA is safe and effective in children less than 12 years of age with atopic dermatitis or nonsegmental vitiligo.</p> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="6"> <p class="First"> <span class="Bold">Before using OPZELURA, tell your healthcare provider about all of your medical conditions, including if you:</span> </p> <ul class="Disk"> <li>See <span class="Bold">“What is the most important information I should know about OPZELURA?”</span> </li> <li>have an infection</li> <li>are a current or past smoker</li> <li>have had a heart attack, other heart problems, or a stroke</li> <li>have or have had low white or red blood cell counts</li> <li>have high levels of fat in your blood (high cholesterol or triglycerides)</li> <li>are pregnant or plan to become pregnant. It is not known if OPZELURA will harm your unborn baby. <ul class="Circle"> <li> <span class="Bold">Pregnancy Exposure Registry. </span>There is a pregnancy exposure registry for individuals who use OPZELURA during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. If you become exposed to OPZELURA during pregnancy, you and your healthcare provider should report exposure to Incyte Corporation at 1-855-463-3463 or by visiting www.opzelura.pregnancy.incyte.com.</li> </ul> </li> <li>are breastfeeding or plan to breastfeed. It is not known if OPZELURA passes into your breast milk. Do not breastfeed during treatment with OPZELURA and for about 4 weeks after the last dose.</li> </ul> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take</span>, including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p> <p>Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="6"> <p class="First"> <span class="Bold">How should I use OPZELURA?</span> </p> <ul class="Disk"> <li>OPZELURA is for use on the skin only. Do not use OPZELURA in your eyes, mouth, or vagina.</li> <li>Use OPZELURA exactly as your healthcare provider tells you.</li> <li>Apply a thin layer of OPZELURA 2 times a day to affected areas. <span class="Bold">Do not</span> use more than one 60 gram tube each week or more than one 100 gram tube every 2 weeks. Ask your healthcare provider if you have questions about applying OPZELURA.</li> <li>If you are using OPZELURA for atopic dermatitis, stop using OPZELURA when your signs and symptoms of atopic dermatitis, such as itching, rash, and redness go away, or as directed by your healthcare provider. Tell your healthcare provider if your symptoms do not improve within 8 weeks of treatment.</li> <li>If you are using OPZELURA for nonsegmental vitiligo, tell your healthcare provider if your treated skin does not improve within 24 weeks of treatment.</li> <li>Wash your hands after applying OPZELURA, unless hands are being treated. If someone else applies OPZELURA, they should wash their hands after applying OPZELURA.</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="6"> <p class="First"> <span class="Bold">What are the possible side effects of OPZELURA?</span> </p> <p> <span class="Bold">OPZELURA may cause serious side effects, including:</span> </p> <ul class="Disk"> <li>See <span class="Bold">“What is the most important information I should know about OPZELURA?”</span> </li> <li> <span class="Bold">Low blood cell counts.</span> OPZELURA may cause low platelet counts (thrombocytopenia), low red blood cell counts (anemia), and low white blood cell counts (neutropenia). If needed, your healthcare provider will do a blood test to check your blood cell counts during your treatment with OPZELURA and may stop your treatment if signs or symptoms of low blood cell counts happen. Tell your healthcare provider right away if you develop or have worsening of any of these symptoms: </li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="3"> <ul class="Disk"> <li>unusual bleeding</li> <li>bruising</li> <li>tiredness</li> </ul> </td><td class="Rrule" colspan="3"> <ul class="Disk"> <li>shortness of breath</li> <li>fever</li> </ul> <br/> </td> </tr> <tr> <td class="Lrule Rrule" colspan="6"> <ul class="Disk"> <li> <span class="Bold">Cholesterol increases. </span>Cholesterol increase has happened in people when ruxolitinib is taken by mouth. Tell your healthcare provider if you have high levels of fat in your blood (high cholesterol or triglycerides).</li> </ul> <p class="First"> <span class="Bold">The most common side effects of OPZELURA <span class="Bold">in people treated for atopic dermatitis </span>include:</span> </p> <br/> </td> </tr> <tr> <td class="Lrule" colspan="3"> <ul class="Disk"> <li>common cold (nasopharyngitis)</li> <li>diarrhea</li> <li>bronchitis</li> <li>ear infection</li> <li>increase in a type of white blood cell (eosinophil) count</li> </ul> </td><td class="Rrule" colspan="3"> <ul class="Disk"> <li>hives</li> <li>inflamed hair pores (folliculitis)</li> <li>swelling of the tonsils (tonsillitis)</li> <li>runny nose (rhinorrhea)</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="6"> <p class="First"> <span class="Bold">The most common side effects of OPZELURA in people treated for nonsegmental vitiligo include:</span> </p> </td> </tr> <tr> <td class="Lrule" colspan="3"> <ul class="Disk"> <li>acne at the application site</li> <li>itching at the application site</li> <li>common cold (nasopharyngitis)</li> <li>headache</li> </ul> </td><td class="Rrule" colspan="3"> <ul class="Disk"> <li>urinary tract infection</li> <li>redness at the application site</li> <li>fever</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="6">These are not all of the possible side effects of OPZELURA. <p class="First">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800-FDA-1088.</p> <p>You may also report side effects to Incyte Corporation at 1-855-463-3463.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="6"> <span class="Bold">How should I store OPZELURA?</span> <ul class="Disk"> <li>Store OPZELURA at room temperature between 68°F to 77°F (20°C to 25°C).</li> </ul> <span class="Bold">Keep OPZELURA and all medicines out of the reach of children.</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="6"> <p class="First"> <span class="Bold">General information about the safe and effective use of OPZELURA.</span> </p> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use OPZELURA for a condition for which it is not prescribed. Do not give OPZELURA to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about OPZELURA that is written for healthcare professionals.<br/> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" colspan="6"> <p class="First"> <span class="Bold">What are the ingredients in OPZELURA?</span> </p> <p> <span class="Bold">Active ingredient:</span> ruxolitinib phosphate<br/> <span class="Bold">Inactive ingredients:</span> cetyl alcohol, dimethicone 350, edetate disodium, glyceryl stearate SE, light mineral oil, medium chain triglycerides, methylparaben, phenoxyethanol, phosphoric acid, polyethylene glycol 200, polysorbate 20, propylene glycol, propylparaben, stearyl alcohol, purified water, white petrolatum, and xanthan gum.</p> <p>Manufactured for: Incyte Corporation, 1801 Augustine Cut-off, Wilmington, DE 19803<br/> OPZELURA is a registered trademark of Incyte. All rights reserved.<br/> Patent Information: www.incyte.com/patents</p> <p>For more information go to www.Opzelura.com or call 1-855-463-3463</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col/>\n<col/>\n<col/>\n<col/>\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"6\">\n<p class=\"First\">\n<span class=\"Bold\">MEDICATION GUIDE<br/>\n</span><span class=\"Bold\">OPZELURA<span class=\"Sup\">®</span> (</span><span class=\"Bold\">OP-zuh-LUR-ah</span><span class=\"Bold\">)<br/>\n</span><span class=\"Bold\"><span class=\"Bold\">(ruxolitinib) </span><span class=\"Bold\">Cream</span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"6\"><span class=\"Bold\">Important:</span> OPZELURA is for use on the skin only. Do not use OPZELURA in your eyes, mouth, or vagina.<br/>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"6\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about OPZELURA?</span>\n</p>\n<p>\n<span class=\"Bold\">OPZELURA may cause serious side effects, including:</span>\n</p>\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">Serious Infections.</span> OPZELURA contains ruxolitinib. Ruxolitinib belongs to a class of medicines called Janus kinase (JAK) inhibitors. JAK inhibitors are medicines that affect your immune system. JAK inhibitors can lower the ability of your immune system to fight infections. Some people have had serious infections while taking JAK inhibitors by mouth, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have been hospitalized or died from these infections. Some people have had serious infections of their lungs while using OPZELURA.\n <ul class=\"Circle\">\n<li>Your healthcare provider should watch you closely for signs and symptoms of TB during treatment with OPZELURA.</li>\n</ul>\n</li>\n</ul>\n<p>OPZELURA should not be used in people with an active, serious infection, including localized infections. You should not start using OPZELURA if you have any kind of infection unless your healthcare provider tells you it is okay. You may be at a higher risk of developing shingles (herpes zoster) while using OPZELURA.</p>\n<p>\n<span class=\"Bold\">Before starting OPZELURA, tell your healthcare provider if you</span>:</p>\n<ul class=\"Disk\">\n<li>are being treated for an infection</li>\n<li>have had an infection that does not go away or that keeps coming back</li>\n<li>have diabetes, chronic lung disease, HIV, or a weak immune system</li>\n<li>have TB or have been in close contact with someone with TB</li>\n<li>have had shingles (herpes zoster)</li>\n<li>have or have had hepatitis B or C</li>\n<li>live in an area, or have lived in an area, or have traveled to certain parts of the country (such as the Ohio and Mississippi River valleys and the Southwest) where there is an increased chance for getting certain kinds of fungal infections. These infections may happen or become more severe if you use OPZELURA. Ask your healthcare provider if you do not know if you have lived in an area where these infections are common.</li>\n<li>think you have an infection or have symptoms of an infection such as:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"2\">\n<ul class=\"Disk\">\n<li>fever, sweating, or chills</li>\n<li>muscle aches</li>\n<li>cough or shortness of breath</li>\n</ul>\n</td><td colspan=\"2\">\n<ul class=\"Disk\">\n<li>blood in your phlegm</li>\n<li>weight loss</li>\n<li>warm, red, or painful skin or sores on your body</li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disk\">\n<li>diarrhea or stomach pain</li>\n<li>burning when you urinate or urinating more often than usual</li>\n<li>feeling very tired</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"6\">\n<p class=\"First\">After starting OPZELURA, call your healthcare provider right away if you have any symptoms of an infection.<br/>\n OPZELURA can make you more likely to get infections or make worse any infections that you have. If you get a serious infection, your healthcare provider may stop your treatment with OPZELURA until your infection is controlled.</p>\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">Increased risk of death <span class=\"Bold\">due to any reason (</span>all causes). </span>Increased risk of death has happened in people 50 years of age and older who have at least 1 heart disease (cardiovascular) risk factor and are taking a medicine in the class of medicines called JAK inhibitors by mouth.<br/>\n<br/>\n</li>\n<li>\n<span class=\"Bold\">Cancer </span><span class=\"Bold\">and immune system problems. </span>OPZELURA may increase your risk of certain cancers by changing the way your immune system works.\n <ul class=\"Circle\">\n<li>Lymphoma and other cancers have happened in people taking a medicine in the class of medicines called JAK inhibitors by mouth.</li>\n<li>People taking JAK inhibitors by mouth have a higher risk of certain cancers including lymphoma and lung cancer, especially if they are a current or past smoker. </li>\n<li>Some people have had skin cancers while using OPZELURA. Your healthcare provider will regularly check your skin during your treatment with OPZELURA. Limit the amount of time you spend in the sunlight. Wear protective clothing when you are in the sun and use a broad-spectrum sunscreen.</li>\n<li> Tell your healthcare provider if you have ever had any type of cancer.</li>\n</ul>\n</li>\n</ul>\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">Increased risk of major cardiovascular events.</span> Increased risk of major cardiovascular events such as heart attack, stroke, or death have happened in people 50 years of age and older who have at least 1 heart disease (cardiovascular) risk factor and taking a medicine in the class of medicines called JAK inhibitors by mouth, especially in current or past smokers.</li>\n</ul>\n<p>Get emergency help right away if you have any symptoms of a heart attack or stroke while using OPZELURA, including:</p>\n<ul class=\"Circle\">\n<li>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</li>\n<li>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</li>\n<li>pain or discomfort in your arms, back, neck, jaw, or stomach</li>\n<li>shortness of breath with or without chest discomfort</li>\n<li>breaking out in a cold sweat</li>\n<li>nausea or vomiting</li>\n<li>feeling lightheaded</li>\n<li>weakness in one part or on one side of your body</li>\n<li>slurred speech</li>\n</ul>\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">Blood clots. </span>Blood clots in the veins of your legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) can happen in some people taking OPZELURA. This may be life-threatening. Blood clots in the vein of the legs (deep vein thrombosis, DVT) and lungs (pulmonary embolism, PE) have happened more often in people who are 50 years of age and older and with at least 1 heart disease (cardiovascular) risk factor taking a medicine in the class of medicines called JAK inhibitors by mouth.<br/>\n<ul class=\"Circle\">\n<li>Tell your healthcare provider if you have had blood clots in the veins of your legs or lungs in the past.</li>\n<li>Tell your healthcare provider right away if you have any signs and symptoms of blood clots during treatment with OPZELURA, including:\n <ul class=\"Square\">\n<li>swelling, pain, or tenderness in one or both legs</li>\n<li>sudden, unexplained chest or upper back pain</li>\n<li>shortness of breath or difficulty breathing</li>\n</ul>\n</li>\n</ul>\n</li>\n</ul>\n<p>See <span class=\"Bold\">“What are the possible side effects of OPZELURA?”</span> for more information about side effects.</p>\n<br/>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"6\">\n<p class=\"First\">\n<span class=\"Bold\">What is OPZELURA?</span>\n</p>\n<p>OPZELURA is a prescription medicine used on the skin (topical) for:</p>\n<ul class=\"Disk\">\n<li> short-term and non-continuous chronic treatment of mild to moderate eczema (atopic dermatitis) in non‑immunocompromised adults and children 12 years of age and older whose disease:\n <ul class=\"Circle\">\n<li>is not well controlled with topical prescription therapies or</li>\n<li>when those therapies are not recommended</li>\n</ul>\n</li>\n</ul>\n<ul class=\"Disk\">\n<li>the treatment of a type of vitiligo called nonsegmental vitiligo in adults and children 12 years of age and older.</li>\n</ul>\n<p>The use of OPZELURA along with therapeutic biologics, other JAK inhibitors, or strong immunosuppressants such as azathioprine or cyclosporine is not recommended.</p>\n<p>It is not known if OPZELURA is safe and effective in children less than 12 years of age with atopic dermatitis or nonsegmental vitiligo.</p>\n<br/>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"6\">\n<p class=\"First\">\n<span class=\"Bold\">Before using OPZELURA, tell your healthcare provider about all of your medical conditions, including if you:</span>\n</p>\n<ul class=\"Disk\">\n<li>See <span class=\"Bold\">“What is the most important information I should know about OPZELURA?”</span>\n</li>\n<li>have an infection</li>\n<li>are a current or past smoker</li>\n<li>have had a heart attack, other heart problems, or a stroke</li>\n<li>have or have had low white or red blood cell counts</li>\n<li>have high levels of fat in your blood (high cholesterol or triglycerides)</li>\n<li>are pregnant or plan to become pregnant. It is not known if OPZELURA will harm your unborn baby.\n <ul class=\"Circle\">\n<li>\n<span class=\"Bold\">Pregnancy Exposure Registry. </span>There is a pregnancy exposure registry for individuals who use OPZELURA during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. If you become exposed to OPZELURA during pregnancy, you and your healthcare provider should report exposure to Incyte Corporation at 1-855-463-3463 or by visiting www.opzelura.pregnancy.incyte.com.</li>\n</ul>\n</li>\n<li>are breastfeeding or plan to breastfeed. It is not known if OPZELURA passes into your breast milk. Do not breastfeed during treatment with OPZELURA and for about 4 weeks after the last dose.</li>\n</ul>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take</span>, including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p>\n<p>Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"6\">\n<p class=\"First\">\n<span class=\"Bold\">How should I use OPZELURA?</span>\n</p>\n<ul class=\"Disk\">\n<li>OPZELURA is for use on the skin only. Do not use OPZELURA in your eyes, mouth, or vagina.</li>\n<li>Use OPZELURA exactly as your healthcare provider tells you.</li>\n<li>Apply a thin layer of OPZELURA 2 times a day to affected areas. <span class=\"Bold\">Do not</span> use more than one 60 gram tube each week or more than one 100 gram tube every 2 weeks. Ask your healthcare provider if you have questions about applying OPZELURA.</li>\n<li>If you are using OPZELURA for atopic dermatitis, stop using OPZELURA when your signs and symptoms of atopic dermatitis, such as itching, rash, and redness go away, or as directed by your healthcare provider. Tell your healthcare provider if your symptoms do not improve within 8 weeks of treatment.</li>\n<li>If you are using OPZELURA for nonsegmental vitiligo, tell your healthcare provider if your treated skin does not improve within 24 weeks of treatment.</li>\n<li>Wash your hands after applying OPZELURA, unless hands are being treated. If someone else applies OPZELURA, they should wash their hands after applying OPZELURA.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"6\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of OPZELURA?</span>\n</p>\n<p>\n<span class=\"Bold\">OPZELURA may cause serious side effects, including:</span>\n</p>\n<ul class=\"Disk\">\n<li>See <span class=\"Bold\">“What is the most important information I should know about OPZELURA?”</span>\n</li>\n<li>\n<span class=\"Bold\">Low blood cell counts.</span> OPZELURA may cause low platelet counts (thrombocytopenia), low red blood cell counts (anemia), and low white blood cell counts (neutropenia). If needed, your healthcare provider will do a blood test to check your blood cell counts during your treatment with OPZELURA and may stop your treatment if signs or symptoms of low blood cell counts happen. Tell your healthcare provider right away if you develop or have worsening of any of these symptoms: </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\">\n<ul class=\"Disk\">\n<li>unusual bleeding</li>\n<li>bruising</li>\n<li>tiredness</li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"3\">\n<ul class=\"Disk\">\n<li>shortness of breath</li>\n<li>fever</li>\n</ul>\n<br/>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"6\">\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">Cholesterol increases. </span>Cholesterol increase has happened in people when ruxolitinib is taken by mouth. Tell your healthcare provider if you have high levels of fat in your blood (high cholesterol or triglycerides).</li>\n</ul>\n<p class=\"First\">\n<span class=\"Bold\">The most common side effects of OPZELURA <span class=\"Bold\">in people treated for atopic dermatitis </span>include:</span>\n</p>\n<br/>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\">\n<ul class=\"Disk\">\n<li>common cold (nasopharyngitis)</li>\n<li>diarrhea</li>\n<li>bronchitis</li>\n<li>ear infection</li>\n<li>increase in a type of white blood cell (eosinophil) count</li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"3\">\n<ul class=\"Disk\">\n<li>hives</li>\n<li>inflamed hair pores (folliculitis)</li>\n<li>swelling of the tonsils (tonsillitis)</li>\n<li>runny nose (rhinorrhea)</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"6\">\n<p class=\"First\">\n<span class=\"Bold\">The most common side effects of OPZELURA in people treated for nonsegmental vitiligo include:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"3\">\n<ul class=\"Disk\">\n<li>acne at the application site</li>\n<li>itching at the application site</li>\n<li>common cold (nasopharyngitis)</li>\n<li>headache</li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"3\">\n<ul class=\"Disk\">\n<li>urinary tract infection</li>\n<li>redness at the application site</li>\n<li>fever</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"6\">These are not all of the possible side effects of OPZELURA.\n <p class=\"First\">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800-FDA-1088.</p>\n<p>You may also report side effects to Incyte Corporation at 1-855-463-3463.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"6\"> <span class=\"Bold\">How should I store OPZELURA?</span>\n<ul class=\"Disk\">\n<li>Store OPZELURA at room temperature between 68°F to 77°F (20°C to 25°C).</li>\n</ul>\n<span class=\"Bold\">Keep OPZELURA and all medicines out of the reach of children.</span></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"6\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of OPZELURA.</span>\n</p>\n Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use OPZELURA for a condition for which it is not prescribed. Do not give OPZELURA to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about OPZELURA that is written for healthcare professionals.<br/>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" colspan=\"6\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in OPZELURA?</span>\n</p>\n<p>\n<span class=\"Bold\">Active ingredient:</span> ruxolitinib phosphate<br/>\n<span class=\"Bold\">Inactive ingredients:</span> cetyl alcohol, dimethicone 350, edetate disodium, glyceryl stearate SE, light mineral oil, medium chain triglycerides, methylparaben, phenoxyethanol, phosphoric acid, polyethylene glycol 200, polysorbate 20, propylene glycol, propylparaben, stearyl alcohol, purified water, white petrolatum, and xanthan gum.</p>\n<p>Manufactured for: Incyte Corporation, 1801 Augustine Cut-off, Wilmington, DE 19803<br/>\n OPZELURA is a registered trademark of Incyte. All rights reserved.<br/>\n Patent Information: www.incyte.com/patents</p>\n<p>For more information go to www.Opzelura.com or call 1-855-463-3463</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Medication Guide has been approved by the U.S. Food and Drug Administration.                                          Revised: 08/2024

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Opzelura® (ruxolitinib) cream 1.5%

{ "type": "p", "children": [], "text": "\nOpzelura®\n\n(ruxolitinib) cream 1.5%" }

For Topical Use Only.

{ "type": "p", "children": [], "text": "\nFor Topical Use Only.\n" }

NDC 50881-007-07

{ "type": "p", "children": [], "text": "NDC 50881-007-07" }

100 g Rx only

{ "type": "p", "children": [], "text": "100 g\n\nRx only\n" }

Opzelura® (ruxolitinib) cream 1.5%

{ "type": "p", "children": [], "text": "\nOpzelura®\n\n(ruxolitinib) cream 1.5%" }

For Topical Use Only.

{ "type": "p", "children": [], "text": "\nFor Topical Use Only.\n" }

NDC 50881-007-07

{ "type": "p", "children": [], "text": "NDC 50881-007-07" }

100 g Rx only

{ "type": "p", "children": [], "text": "100 g\n\nRx only\n" }

Opzelura® (ruxolitinib) cream 1.5%

{ "type": "p", "children": [], "text": "\nOpzelura®\n\n(ruxolitinib) cream 1.5%" }

For Topical Use Only.

{ "type": "p", "children": [], "text": "\nFor Topical Use Only.\n" }

NDC 50881-007-05

{ "type": "p", "children": [], "text": "NDC 50881-007-05" }

60 g Rx only

{ "type": "p", "children": [], "text": "60 g\n\nRx only\n" }

Opzelura® (ruxolitinib) cream 1.5%

{ "type": "p", "children": [], "text": "\nOpzelura®\n\n(ruxolitinib) cream 1.5%" }

For Topical Use Only.

{ "type": "p", "children": [], "text": "\nFor Topical Use Only.\n" }

NDC 50881-007-05

{ "type": "p", "children": [], "text": "NDC 50881-007-05" }

60 g Rx only

{ "type": "p", "children": [], "text": "60 g\n\nRx only\n\n" }

Opzelura® (ruxolitinib) cream 1.5%

{ "type": "p", "children": [], "text": "\nOpzelura®\n\n(ruxolitinib) cream 1.5%" }

Sample - Topical Use Only.

{ "type": "p", "children": [], "text": "\nSample - Topical Use Only.\n" }

NDC 50881-007-04

{ "type": "p", "children": [], "text": "NDC 50881-007-04" }

5 g Rx only

{ "type": "p", "children": [], "text": "5 g\n\nRx only\n" }

Opzelura® (ruxolitinib) cream 1.5%

{ "type": "p", "children": [], "text": "\nOpzelura®\n\n(ruxolitinib) cream 1.5%" }

Sample - Topical Use Only.

{ "type": "p", "children": [], "text": "\nSample - Topical Use Only.\n" }

NDC 50881-007-04

{ "type": "p", "children": [], "text": "NDC 50881-007-04" }

5 g Rx only

{ "type": "p", "children": [], "text": "5 g\nRx only\n" }

Jakafi is indicated for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults.

Jakafi is indicated for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.

Jakafi is indicated for treatment of steroid-refractory acute graft-versus-host disease (aGVHD) in adult and pediatric patients 12 years and older.

Jakafi is indicated for treatment of chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

Prior to Jakafi treatment:

During treatment with Jakafi:

The recommended starting dose of Jakafi is based on platelet count (Table 1). Doses may be titrated based on safety and efficacy.

<div class="scrollingtable"><table> <caption> <span>Table 1: Jakafi Starting Doses for Myelofibrosis</span> </caption> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <span class="Bold">Platelet Count</span></td><td class="Botrule Lrule Rrule Toprule"> <span class="Bold">Starting Dose</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Greater than 200 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule"> 20 mg orally twice daily</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> 100 x 10<span class="Sup">9</span>/L to 200 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule"> 15 mg orally twice daily</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> 50 x 10<span class="Sup">9</span>/L to less than 100 x 10<span class="Sup">9</span>/L      </td><td class="Botrule Lrule Rrule Toprule"> 5 mg orally twice daily      </td> </tr> </tbody> </table></div>

Treatment Interruption and Restarting Dosing

Interrupt treatment for platelet counts less than 50 x 109/L or absolute neutrophil count (ANC) less than 0.5 x 109/L.

After recovery of platelet counts above 50 x 109/L and ANC above 0.75 x 109/L, dosing may be restarted. Table 2 illustrates the maximum allowable dose that may be used in restarting Jakafi after a previous interruption.

<div class="scrollingtable"><table width="60%"> <caption> <span>Table 2: Myelofibrosis: Maximum Restarting Doses for Jakafi after Safety Interruption for Thrombocytopenia for Patients Starting Treatment with a Platelet Count of 100 x 10<span class="Sup">9</span>/L or Greater</span> </caption> <col width="1px"/> <col width="1px"/> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Maximum doses are displayed. When restarting, begin with a dose at least 5 mg twice daily below the dose at interruption.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule" valign="bottom"> <span class="Bold">Current Platelet Count</span></td><td align="center" class="Rrule Toprule"> <span class="Bold">Maximum Dose When <br/>Restarting Jakafi Treatment<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> </span></td> </tr> <tr> <td class="Lrule Rrule Toprule"> Greater than or equal to 125 x 10<span class="Sup">9</span>/L</td><td class="Rrule Toprule">20 mg twice daily</td> </tr> <tr> <td class="Lrule Rrule Toprule"> 100 to less than 125 x 10<span class="Sup">9</span>/L</td><td class="Rrule Toprule">15 mg twice daily</td> </tr> <tr> <td class="Lrule Rrule Toprule"> 75 to less than 100 x 10<span class="Sup">9</span>/L</td><td class="Rrule Toprule">10 mg twice daily for at least 2 weeks; if stable, may increase to 15 mg twice daily</td> </tr> <tr> <td class="Lrule Rrule Toprule"> 50 to less than 75 x 10<span class="Sup">9</span>/L</td><td class="Rrule Toprule">5 mg twice daily for at least 2 weeks; if stable, may increase to 10 mg twice daily</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> Less than 50 x 10<span class="Sup">9</span>/L</td><td class="Botrule Rrule Toprule">Continue hold</td> </tr> </tbody> </table></div>

Following treatment interruption for ANC below 0.5 x 109/L, after ANC recovers to 0.75 x 109/L or greater, restart dosing at the higher of 5 mg once daily or 5 mg twice daily below the largest dose in the week prior to the treatment interruption.

Dose Reductions Dose reductions should be considered if the platelet counts decrease as outlined in Table 3 with the goal of avoiding dose interruptions for thrombocytopenia.

<div class="scrollingtable"><table width="600px"> <caption> <span>Table 3: Myelofibrosis: Dosing Recommendations for Thrombocytopenia for Patients Starting Treatment with a Platelet Count of 100 x 10<span class="Sup">9</span>/L or Greater</span> </caption> <col/> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule">  </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="5"> <span class="Bold">Dose at Time of Platelet Decline</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <span class="Bold">Platelet Count</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold"> 25 mg  <br/>twice<br/>daily</span></td><td align="center" class="Botrule Lrule Rrule Toprule">  <span class="Bold">20 mg  <br/>twice<br/>daily</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">15 mg  <br/>twice<br/>daily</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">10 mg  <br/>twice<br/>daily</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">5 mg  <br/>twice<br/>daily</span></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">New<br/>Dose</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">New<br/>Dose</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">New<br/>Dose</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">New<br/>Dose</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">New<br/>Dose</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">100 to less than <br/>125 x 10<span class="Sup">9</span>/L</td><td align="center" class="Botrule Lrule Rrule Toprule"> 20 mg <br/>twice<br/>daily </td><td align="center" class="Botrule Lrule Rrule Toprule"> 15 mg <br/>twice<br/>daily </td><td align="center" class="Botrule Lrule Rrule Toprule"> No<br/> Change  </td><td align="center" class="Botrule Lrule Rrule Toprule"> No<br/> Change  </td><td align="center" class="Botrule Lrule Rrule Toprule"> No<br/> Change  </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">75 to less than <br/>100 x 10<span class="Sup">9</span>/L</td><td align="center" class="Botrule Lrule Rrule Toprule"> 10 mg <br/>twice<br/>daily </td><td align="center" class="Botrule Lrule Rrule Toprule"> 10 mg <br/>twice<br/>daily </td><td align="center" class="Botrule Lrule Rrule Toprule"> 10 mg <br/>twice<br/>daily </td><td align="center" class="Botrule Lrule Rrule Toprule"> No<br/>Change</td><td align="center" class="Botrule Lrule Rrule Toprule"> No<br/>Change</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">50 to less than <br/>75 x 10<span class="Sup">9</span>/L</td><td align="center" class="Botrule Lrule Rrule Toprule"> 5 mg <br/>twice<br/>daily </td><td align="center" class="Botrule Lrule Rrule Toprule"> 5 mg <br/>twice<br/>daily </td><td align="center" class="Botrule Lrule Rrule Toprule"> 5 mg <br/>twice<br/>daily </td><td align="center" class="Botrule Lrule Rrule Toprule"> 5 mg <br/>twice<br/>daily </td><td align="center" class="Botrule Lrule Rrule Toprule"> No<br/>Change</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Less than 50 x 10<span class="Sup">9</span>/L   </td><td align="center" class="Botrule Lrule Rrule Toprule"> Hold</td><td align="center" class="Botrule Lrule Rrule Toprule"> Hold</td><td align="center" class="Botrule Lrule Rrule Toprule"> Hold</td><td align="center" class="Botrule Lrule Rrule Toprule"> Hold</td><td align="center" class="Botrule Lrule Rrule Toprule"> Hold</td> </tr> </tbody> </table></div>

If the response is insufficient and platelet and neutrophil counts are adequate, doses may be increased in 5 mg twice daily increments to a maximum of 25 mg twice daily. Doses should not be increased during the first 4 weeks of therapy and not more frequently than every 2 weeks.

Consider dose increases in patients who meet all of the following conditions:

Based on limited clinical data, long-term maintenance at a 5 mg twice daily dose has not shown responses and continued use at this dose should be limited to patients in whom the benefits outweigh the potential risks. Discontinue Jakafi if there is no spleen size reduction or symptom improvement after 6 months of therapy.

This section applies only to patients with platelet counts of 50 x 109/L to less than 100 x 109/L prior to any treatment with Jakafi. See dose modifications in Section 2.2 (Dose Modification Guidelines for Hematological Toxicity for Patients with Myelofibrosis Starting Treatment with a Platelet Count of 100 x 109/L or Greater) for hematological toxicity in patients whose platelet counts were 100 x 109/L or more prior to starting treatment with Jakafi.

Treatment Interruption and Restarting Dosing

Interrupt treatment for platelet counts less than 25 x 109/L or ANC less than 0.5 x 109/L.

After recovery of platelet counts above 35 x 109/L and ANC above 0.75 x 109/L, dosing may be restarted. Restart dosing at the higher of 5 mg once daily or 5 mg twice daily below the largest dose in the week prior to the decrease in platelet count below 25 x 109/L or ANC below 0.5 x 109/L that led to dose interruption.

Dose Reductions

Reduce the dose of Jakafi for platelet counts less than 35 x 109/L as described in Table 4.

<div class="scrollingtable"><table width="650px"> <caption> <span>Table 4: Myelofibrosis: Dosing Modifications for Thrombocytopenia for Patients with Starting Platelet Count of 50 x 10<span class="Sup">9</span>/L to Less Than 100 x 10<span class="Sup">9</span>/L</span> </caption> <col width="1px"/> <col width="1px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule"><span class="Bold">Platelet Count</span></td><td class="Botrule Lrule Rrule" valign="top"> <span class="Bold">  Dosing Recommendations</span></td> </tr> <tr> <td class="Botrule Lrule Rrule">Less than 25 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule" valign="top"> <ul class="Disk"> <li>Interrupt dosing.</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule"> <p class="First">25 x 10<span class="Sup">9</span>/L to less than 35 x 10<span class="Sup">9</span>/L<br/> <br/>AND the platelet count decline is  <br/>less than 20% during the prior four <br/>weeks</p> </td><td class="Botrule Lrule Rrule" valign="top"> <ul class="Disk"> <li>Decrease dose by 5 mg once daily.</li> <li>For patients on 5 mg once daily, maintain dose at 5 mg once daily.</li> </ul> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">25 x 10<span class="Sup">9</span>/L to less than 35 x 10<span class="Sup">9</span>/L<br/> <br/>AND the platelet count decline is   <br/>20% or greater during the prior four weeks</p> </td><td class="Botrule Lrule Rrule" valign="top"> <ul class="Disk"> <li>Decrease dose by 5 mg twice daily.</li> <li>For patients on 5 mg twice daily, decrease the dose to 5 mg once daily.</li> <li>For patients on 5 mg once daily, maintain dose at 5 mg once daily.</li> </ul> </td> </tr> </tbody> </table></div>

Do not increase doses during the first 4 weeks of therapy, and do not increase the dose more frequently than every 2 weeks.

If the response is insufficient as defined in Section 2.2 (see Dose Modification Based on Insufficient Response with Myelofibrosis Starting Treatment with a platelet count of 100 x 109/L or Greater), doses may be increased by increments of 5 mg daily to a maximum of 10 mg twice daily if:

Continuation of treatment for more than 6 months should be limited to patients in whom the benefits outweigh the potential risks. Discontinue Jakafi if there is no spleen size reduction or symptom improvement after 6 months of therapy.

Interrupt treatment for bleeding requiring intervention regardless of current platelet count. Once the bleeding event has resolved, consider resuming treatment at the prior dose if the underlying cause of bleeding has been controlled. If the bleeding event has resolved but the underlying cause persists, consider resuming treatment with Jakafi at a lower dose.

The recommended starting dose of Jakafi is 10 mg twice daily. Doses may be titrated based on safety and efficacy.

Dose Reductions

Dose reductions should be considered for hemoglobin and platelet count decreases as described in Table 5.

<div class="scrollingtable"><table> <caption> <span>Table 5: Polycythemia Vera: Dose Reductions</span> </caption> <col width="300px"/> <col width="350px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Hemoglobin and/or Platelet Count</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Dosing Recommendations </span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Hemoglobin greater than or equal to 12 g/dL AND platelet count greater than or equal to 100 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule"> <ul class="Disk"> <li>No change required.</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Hemoglobin 10 to less than 12 g/dL AND platelet count 75 to less than 100 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule"> <ul class="Disk"> <li>Dose reductions should be considered with the goal of avoiding dose interruptions for anemia and thrombocytopenia. </li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Hemoglobin 8 to less than 10 g/dL OR platelet count 50 to less than 75 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule"> <ul class="Disk"> <li>Reduce dose by 5 mg twice daily.</li> <li>For patients on 5 mg twice daily, decrease the dose to 5 mg once daily.</li> </ul> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Hemoglobin less than 8 g/dL OR platelet count less than 50 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule"> <ul class="Disk"> <li>Interrupt dosing.</li> </ul> </td> </tr> </tbody> </table></div>

Treatment Interruption and Restarting Dosing

Interrupt treatment for hemoglobin less than 8 g/dL, platelet counts less than 50 x 109/L or ANC less than 1.0 x 109/L.

After recovery of the hematologic parameter(s) to acceptable levels, dosing may be restarted.

Table 6 illustrates the dose that may be used in restarting Jakafi after a previous interruption.

Table 6: Polycythemia Vera: Restarting Doses for Jakafi after Safety Interruption for Hematologic Parameter(s)

Use the most severe category of a patient’s hemoglobin, platelet count, or ANC abnormality to determine the corresponding maximum restarting dose.

<div class="scrollingtable"><table> <col/> <col/> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>Continue treatment for at least 2 weeks; if stable, may increase dose by 5 mg twice daily.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Hemoglobin, Platelet Count, or ANC</span></td><td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Maximum Restarting Dose</span></td> </tr> <tr> <td class="Botrule Lrule Rrule">Hemoglobin less than 8 g/dL OR <br/> platelet count less than 50 x 10<span class="Sup">9</span>/L OR <br/> ANC less than 1 x 10<span class="Sup">9</span>/L </td><td class="Botrule Lrule Rrule" valign="top">Continue hold</td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top">Hemoglobin 8 to less than 10 g/dL OR <br/> platelet count 50 to less than 75 x 10<span class="Sup">9</span>/L OR <br/> ANC 1 to less than 1.5 x 10<span class="Sup">9</span>/L </td><td class="Botrule Lrule Rrule" valign="top">5 mg twice daily<a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a>or no more than<br/>5 mg twice daily less than the dose <br/>which resulted in dose interruption</td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top">Hemoglobin 10 to less than 12 g/dL OR <br/> platelet count 75 to less than 100 x 10<span class="Sup">9</span>/L OR <br/> ANC 1.5 to less than 2 x 10<span class="Sup">9</span>/L </td><td class="Botrule Lrule Rrule" valign="top">10 mg twice daily<a class="Sup" href="#footnote-2">*</a>or no more than<br/>5 mg twice daily less than the dose<br/>which resulted in dose interruption</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top">Hemoglobin greater than or equal to 12 g/dL OR <br/> platelet count greater than or equal to 100 x 10<span class="Sup">9</span>/L OR<br/>ANC greater than or equal to 2 x 10<span class="Sup">9</span>/L </td><td class="Botrule Lrule Rrule" valign="top">15 mg twice daily<a class="Sup" href="#footnote-2">*</a>or no more than<br/>5 mg twice daily less than the dose<br/>which resulted in dose interruption       </td> </tr> </tbody> </table></div>

Patients who had required dose interruption while receiving a dose of 5 mg twice daily, may restart at a dose of 5 mg twice daily or 5 mg once daily, but not higher, once hemoglobin is greater than or equal to 10 g/dL, platelet count is greater than or equal to 75 x 109/L, and ANC is greater than or equal to 1.5 x 109/L.

Dose Management after Restarting Treatment

After restarting Jakafi following treatment interruption, doses may be titrated, but the maximum total daily dose should not exceed 5 mg less than the dose that resulted in the dose interruption. An exception to this is dose interruption following phlebotomy-associated anemia, in which case the maximal total daily dose allowed after restarting Jakafi would not be limited.

If the response is insufficient and platelet, hemoglobin, and neutrophil counts are adequate, doses may be increased in 5 mg twice daily increments to a maximum of 25 mg twice daily. Doses should not be increased during the first 4 weeks of therapy and not more frequently than every two weeks.

Consider dose increases in patients who meet all of the following conditions:

The recommended starting dose of Jakafi is 5 mg given orally twice daily. Consider increasing the dose to 10 mg twice daily after at least 3 days of treatment if the ANC and platelet counts are not decreased by 50% or more relative to the first day of dosing with Jakafi.

Consider tapering Jakafi after 6 months of treatment in patients with response who have discontinued therapeutic doses of corticosteroids. Taper Jakafi by one dose level approximately every 8 weeks (10 mg twice daily to 5 mg twice daily to 5 mg once daily). If aGVHD signs or symptoms recur during or after the taper of Jakafi, consider retreatment.

Dose Modification Guidelines for Patients with Acute Graft-Versus-Host Disease

Monitor complete blood counts (CBC), including platelet count and ANC, and bilirubin prior to initiating therapy, every 2 to 4 weeks until doses are stabilized, and then as indicated clinically.

Modify the dose of Jakafi for adverse reactions as described in Table 7. For dose reductions, patients who are currently receiving Jakafi 10 mg twice daily may have their dose reduced to 5 mg twice daily; patients receiving 5 mg twice daily may have their dose reduced to 5 mg once daily. Patients who are unable to tolerate Jakafi at a dose of 5 mg once daily should have treatment interrupted until their clinical and/or laboratory parameters recover.

<div class="scrollingtable"><table> <caption> <span>Table 7: Dose Modifications for Adverse Reactions in Patients with Acute GVHD</span> </caption> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Laboratory Parameter</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Dosing Recommendations</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Clinically significant<br/>thrombocytopenia after supportive<br/>measures</td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Reduce dose by 1 dose level.<br/>When platelets recover to previous values, dosing may<br/>return to prior dose level. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">ANC less than 1 x 10<span class="Sup">9</span>/L<br/>considered related to Jakafi</td><td class="Botrule Lrule Rrule Toprule">Hold Jakafi for up to 14 days; resume at 1 dose level<br/>lower upon recovery. </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Total Bilirubin elevation, no liver<br/>GVHD</td><td class="Botrule Lrule Rrule Toprule">3.0−5.0 x ULN:  Continue Jakafi at 1 dose level lower<br/>until recovery. <p class="First">&gt; 5.0−10.0 x ULN:  Hold Jakafi for up to 14 days until<br/>bilirubin ≤ 1.5 x ULN; resume at current dose upon<br/>recovery.</p> <p> Total bilirubin &gt; 10.0 x ULN: Hold Jakafi for up to<br/>14 days until bilirubin ≤ 1.5 x ULN; resume at 1 dose<br/>level lower upon recovery.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Total Bilirubin elevation, liver<br/>GVHD</td><td class="Botrule Lrule Rrule Toprule">&gt; 3.0 × ULN:  Continue Jakafi at 1 dose level lower<br/>until recovery.</td> </tr> </tbody> </table></div>

The recommended starting dose of Jakafi is 10 mg given orally twice daily.

Consider tapering Jakafi after 6 months of treatment in patients with response who have discontinued therapeutic doses of corticosteroids. Taper Jakafi by one dose level approximately every 8 weeks (10 mg twice daily to 5 mg twice daily to 5 mg once daily). If GVHD signs or symptoms recur during or after the taper of Jakafi, consider retreatment.

Dose Modification Guidelines for Patients with Chronic Graft-Versus-Host Disease

Monitor complete blood counts (CBC), including platelet count and ANC, and bilirubin prior to initiating therapy, every 2 to 4 weeks until doses are stabilized, and then as indicated clinically.

Modify the dose of Jakafi for adverse reactions as described in Table 8. For dose reductions, patients who are currently receiving Jakafi 10 mg twice daily may have their dose reduced to 5 mg twice daily; patients receiving 5 mg twice daily may have their dose reduced to 5 mg once daily. Patients who are unable to tolerate Jakafi at a dose of 5 mg once daily should have treatment interrupted until their clinical and/or laboratory parameters recover.

<div class="scrollingtable"><table> <caption> <span>Table 8: Dose Modifications for Adverse Reactions in Patients with Chronic GVHD</span> </caption> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Parameter</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Dosing Recommendations</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Platelet count less than 20 × 10<span class="Sup">9</span>/L </td><td class="Botrule Lrule Rrule Toprule">Reduce Jakafi by 1 dose level. If resolved within 7 days, dosing may return to initial dose level. If not resolved within 7 days, then maintain at 1 dose level lower.</td> </tr> <tr> <td class="Lrule Rrule"> <p class="First">ANC less than 0.75 × 10<span class="Sup">9</span>/L considered related to Jakafi</p> </td><td class="Rrule"> <p class="First">Reduce Jakafi by 1 dose level; resume at initial dose level upon recovery.</p> </td> </tr> <tr> <td class="Botrule Lrule"> <p class="First">ANC less than 0.5 × 10<span class="Sup">9</span>/L considered related to Jakafi</p> </td><td class="Botrule Lrule Rrule"> <p class="First">Hold Jakafi for up to 14 days; resume at 1 dose level lower upon recovery. May resume initial dose level when ANC greater than 1.0 × 10<span class="Sup">9</span>/L.</p> </td> </tr> <tr> <td class="Lrule"> <p class="First">Total Bilirubin: 3.0-5.0 × ULN</p> </td><td class="Lrule Rrule"> <p class="First">Continue Jakafi at 1 dose level lower until recovery. If resolved within 14 days, then increase by one dose level. If not resolved within 14 days, then maintain the decreased dose level.<br/> </p> </td> </tr> <tr> <td class="Lrule"> <p class="First">Total Bilirubin: &gt; 5.0-10.0 × ULN</p> </td><td class="Lrule Rrule"> <p class="First">Hold Jakafi for up to 14 days until resolved; resume at current dose upon recovery. If not resolved within 14 days, then resume at 1 dose level lower upon recovery.<br/> </p> </td> </tr> <tr> <td class="Lrule">Total Bilirubin: &gt; 10.0 × ULN</td><td class="Lrule Rrule"> <p class="First">Hold Jakafi for up to 14 days until resolved; resume at 1 dose level lower upon recovery. If not resolved within 14 days, discontinue.<br/> </p> </td> </tr> <tr> <td class="Lrule Rrule Toprule">Other Adverse Reactions: Grade 3</td><td class="Rrule Toprule">Continue Jakafi at 1 dose level lower until recovery.<br/> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule">Other Adverse Reactions: Grade 4<br/> </td><td class="Botrule Rrule">Discontinue Jakafi.</td> </tr> </tbody> </table></div>

Modify the Jakafi dosage when coadministered with strong CYP3A4 inhibitors or doses of less than or equal to 200 mg of fluconazole [see Drug Interactions (7)], according to Table 9. Avoid concomitant use of Jakafi with fluconazole doses of greater than 200 mg daily.

<div class="scrollingtable"><table width="650px"> <caption> <span>Table 9: Dose Modifications for Concomitant Use with Strong CYP3A4 Inhibitors or Fluconazole</span> </caption> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold"><span class="Bold">For patients coadministered strong CYP3A4 inhibitors or doses of less than or equal to 200 mg of fluconazole</span></span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Recommended <span class="Bold">Jakafi </span>Dose Modification</span></td> </tr> <tr> <td class="Botrule Lrule Rrule"><span class="Bold">Starting dose for patients with MF with a platelet count:   </span></td><td class="Botrule Lrule Rrule"> </td> </tr> <tr> <td class="Botrule Lrule Rrule"> <ul class="Disk"> <li>Greater than or equal to 100 x 10<span class="Sup">9</span>/L</li> </ul> </td><td align="center" class="Botrule Lrule Rrule">10 mg twice daily</td> </tr> <tr> <td class="Botrule Lrule Rrule"> <ul class="Disk"> <li>50 x 10<span class="Sup">9</span>/L to less than 100 x 10<span class="Sup">9</span>/L</li> </ul> </td><td align="center" class="Botrule Lrule Rrule">5 mg once daily</td> </tr> <tr> <td class="Botrule Lrule Rrule"><span class="Bold">Starting dose for patients with PV:</span></td><td align="center" class="Botrule Lrule Rrule">5 mg twice daily</td> </tr> <tr> <td class="Botrule Lrule Rrule"><span class="Bold">If on stable dose for patients with MF or PV:</span></td><td class="Botrule Lrule Rrule"> </td> </tr> <tr> <td class="Botrule Lrule Rrule"> <ul class="Disk"> <li>Greater than or equal to 10 mg twice daily</li> </ul> </td><td align="center" class="Botrule Lrule Rrule">Decrease dose by 50% <br/> (round up to the closest available tablet strength) </td> </tr> <tr> <td class="Botrule Lrule Rrule"> <ul class="Disk"> <li>5 mg twice daily</li> </ul> </td><td align="center" class="Botrule Lrule Rrule">5 mg once daily</td> </tr> <tr> <td class="Botrule Lrule Rrule"> <ul class="Disk"> <li>5 mg once daily</li> </ul> </td><td align="center" class="Botrule Lrule Rrule">Avoid strong CYP3A4 inhibitor or fluconazole treatment or interrupt Jakafi treatment for the duration of strong CYP3A4 inhibitor or fluconazole use</td> </tr> <tr> <td class="Botrule Lrule Rrule"><span class="Bold"><span class="Bold">Starting dose</span><span class="Bold">for patients with aGVHD or cGVHD:</span></span></td><td align="center" class="Botrule Lrule Rrule"></td> </tr> <tr> <td class="Botrule Lrule Rrule">Fluconazole doses of less than or equal to 200 mg</td><td align="center" class="Botrule Lrule Rrule"> <p class="First">5 mg once daily for patients with aGVHD;<br/>5 mg twice daily for patients with cGVHD </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule">Other CYP3A4 inhibitors</td><td align="center" class="Botrule Lrule Rrule">Monitor blood counts more frequently for toxicity and modify the Jakafi dosage for adverse reactions if they occur <span class="Italics">[see Dosage and Administration (<a href="#www.splportal.comLINK_73306a47-692c-4d42-a8e9-a97fae787195">2.4</a></span><span class="Italics">, <a href="#www.splportal.comLINK_f893c970-6c92-4300-90f7-cf44ab70cb9d">2.5</a></span><span class="Italics">)</span><span class="Italics">].</span></td> </tr> </tbody> </table></div>

Moderate to Severe Renal Impairment or End Stage Renal Disease on Dialysis

Modify the Jakafi dosage for patients with moderate (CLcr 30 to 59 mL/min) to severe (CLcr 15 to 29 mL/min) renal impairment or end stage renal disease (ESRD) on dialysis according to Table 10. Avoid use of Jakafi in patients with ESRD (CLcr less than 15 mL/min) not requiring dialysis [see Use in Specific Populations (8.6)].

<div class="scrollingtable"><table width="650px"> <caption> <span>Table 10: Dose Modifications for Renal Impairment</span> </caption> <col/> <col/> <col/> <tfoot> <tr class="First Last"> <td class="Toprule" colspan="3" valign="top"> ESRD = end stage renal disease, and CLcr = creatinine clearance</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Renal Impairment Status</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Platelet Count</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Recommended Starting Dosage  </span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="3"><span class="Bold">Patients with MF</span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="4"> <p class="First">Moderate or Severe</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top">Greater than 150 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule" valign="top">No dose adjustment</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">100 to 150 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule">10 mg twice daily</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">50 to less than 100 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule">5 mg daily</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Less than 50 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Avoid use <span class="Italics">[see Use in Specific <br/> </span><span class="Italics">Populations (<a href="#LINK_3679786c-dc89-43d0-9583-dfa99e842ff9">8.6</a>)]</span>      </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2" valign="top"> <p class="First">ESRD on dialysis</p> </td><td class="Botrule Lrule Rrule Toprule">100 to 200 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule">15 mg once after dialysis session</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Greater than 200 x 10<span class="Sup">9</span>/L</p> </td><td class="Botrule Lrule Rrule Toprule">20 mg once after dialysis session</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Patients with PV</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top">Moderate or Severe </td><td class="Botrule Lrule Rrule Toprule">Any</td><td class="Botrule Lrule Rrule Toprule">5 mg twice daily</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top">ESRD on dialysis</td><td class="Botrule Lrule Rrule Toprule">Any</td><td class="Botrule Lrule Rrule Toprule">10 mg once after dialysis session</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Patients with aGVHD</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top">Moderate or Severe</td><td class="Botrule Lrule Rrule Toprule">Any</td><td class="Botrule Lrule Rrule Toprule">5 mg once daily</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top">ESRD on dialysis</td><td class="Botrule Lrule Rrule Toprule">Any</td><td class="Botrule Lrule Rrule Toprule">5 mg once after dialysis session</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Patients with cGVHD</span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top">Moderate or Severe <br/> </td><td class="Botrule Lrule Rrule Toprule">Any<br/> </td><td class="Botrule Lrule Rrule Toprule">5 mg twice daily<br/> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top">ESRD on dialysis</td><td class="Botrule Lrule Rrule Toprule">Any<br/> </td><td class="Botrule Lrule Rrule Toprule">10 mg once after dialysis session<br/> </td> </tr> </tbody> </table></div>

Hepatic Impairment

Modify the Jakafi dosage for patients with hepatic impairment according to Table 11.

<div class="scrollingtable"><table width="650px"> <caption> <span>Table 11: Dose Modifications for Hepatic Impairment</span> </caption> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Hepatic Impairment Status</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Platelet Count             </span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Recommended Starting Dosage</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="4"> <p class="First"> <span class="Bold">Patients with MF</span> <br/> Mild, Moderate, or Severe (Child-Pugh Class A, B, C)           </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top">Greater than 150 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule" valign="top">No dose adjustment</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">100 x 10<span class="Sup">9</span>/L to 150 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule">10 mg twice daily </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">50 to less than 100 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule">5 mg daily </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Less than 50 x 10<span class="Sup">9</span>/L</td><td class="Botrule Lrule Rrule Toprule">Avoid use <span class="Italics">[see Use in Specific<br/>Populations (<a href="#www.splportal.comLINK_72d18376-7a08-4c26-b710-568c6b57a5a9">8.7</a>)]</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Patients with PV</span> <br/>Mild, Moderate, or Severe (Child-Pugh Class A, B, C)</td><td class="Botrule Lrule Rrule Toprule">Any</td><td class="Botrule Lrule Rrule Toprule">5 mg twice daily</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Patients with aGVHD</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Mild, Moderate, or Severe based on NCI criteria without liver GVHD</p> </td><td class="Botrule Lrule Rrule Toprule">Any</td><td class="Botrule Lrule Rrule Toprule">No dose adjustment</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Stage 1, 2 or 3 Liver aGVHD<br/> </p> </td><td class="Botrule Lrule Rrule Toprule">Any<br/> </td><td class="Botrule Lrule Rrule Toprule">No dose adjustment<br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Stage 4 Liver aGVHD</p> </td><td class="Botrule Lrule Rrule Toprule">Any</td><td class="Botrule Lrule Rrule Toprule">5 mg once daily</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Patients with cGVHD</span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Mild, Moderate, or Severe based on NCI criteria without liver GVHD</p> </td><td class="Botrule Lrule Rrule Toprule">Any</td><td class="Botrule Lrule Rrule Toprule">No dose adjustment<br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Score 1 or 2 Liver cGVHD<br/> </p> </td><td class="Botrule Lrule Rrule Toprule">Any</td><td class="Botrule Lrule Rrule Toprule">No dose adjustment<br/> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Score 3 Liver cGVHD<br/> </p> </td><td class="Botrule Lrule Rrule Toprule">Any</td><td class="Botrule Lrule Rrule Toprule">Monitor blood counts more frequently for toxicity and modify the Jakafi dosage for adverse reactions if they occur <span class="Italics">[see Dosage and Administration (<a href="#www.splportal.comLINK_73306a47-692c-4d42-a8e9-a97fae787195">2.4</a>, <a href="#www.splportal.comLINK_f893c970-6c92-4300-90f7-cf44ab70cb9d">2.5</a>)]</span>.<br/> </td> </tr> </tbody> </table></div>

Jakafi is dosed orally and can be administered with or without food.

If a dose is missed, the patient should not take an additional dose, but should take the next usual prescribed dose.

When discontinuing Jakafi therapy for reasons other than thrombocytopenia, gradual tapering of the dose of Jakafi may be considered, for example by 5 mg twice daily each week.

For patients unable to ingest tablets, Jakafi can be administered through a nasogastric tube (8 French or greater) as follows:

The tube should be rinsed with approximately 75 mL of water. The effect of tube feeding preparations on Jakafi exposure during administration through a nasogastric tube has not been evaluated.

5 mg tablets - round and white with "INCY" on one side and "5" on the other.

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10 mg tablets - round and white with "INCY" on one side and "10" on the other.

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15 mg tablets - oval and white with "INCY" on one side and "15" on the other.

{ "type": "p", "children": [], "text": "15 mg tablets - oval and white with \"INCY\" on one side and \"15\" on the other." }

20 mg tablets - capsule-shaped and white with "INCY" on one side and "20" on the other.

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25 mg tablets - oval and white with "INCY" on one side and "25" on the other.

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None.

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Treatment with Jakafi can cause thrombocytopenia, anemia and neutropenia [see Adverse Reactions (6.1)].

Manage thrombocytopenia by reducing the dose or temporarily interrupting Jakafi. Platelet transfusions may be necessary [see Dosage and Administration (2)].

Patients developing anemia may require blood transfusions and/or dose modifications of Jakafi.

Severe neutropenia (ANC less than 0.5 × 109/L) was generally reversible by withholding Jakafi until recovery.

Perform a pre-treatment complete blood count (CBC) and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated [see Dosage and Administration (2)].

Serious bacterial, mycobacterial, fungal and viral infections have occurred [see Adverse Reactions (6.1)]. Delay starting therapy with Jakafi until active serious infections have resolved. Observe patients receiving Jakafi for signs and symptoms of infection and manage promptly. Use active surveillance and prophylactic antibiotics according to clinical guidelines.

Tuberculosis

Tuberculosis infection has been reported in patients receiving Jakafi. Observe patients receiving Jakafi for signs and symptoms of active tuberculosis and manage promptly.

Prior to initiating Jakafi, patients should be evaluated for tuberculosis risk factors, and those at higher risk should be tested for latent infection. Risk factors include, but are not limited to, prior residence in or travel to countries with a high prevalence of tuberculosis, close contact with a person with active tuberculosis, and a history of active or latent tuberculosis where an adequate course of treatment cannot be confirmed.

For patients with evidence of active or latent tuberculosis, consult a physician with expertise in the treatment of tuberculosis before starting Jakafi. The decision to continue Jakafi during treatment of active tuberculosis should be based on the overall risk-benefit determination.

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) has occurred with Jakafi treatment. If PML is suspected, stop Jakafi and evaluate.

Herpes Zoster and Herpes Simplex

Herpes zoster infection has been reported in patients receiving Jakafi [see Adverse Reactions (6.1)]. Advise patients about early signs and symptoms of herpes zoster and to seek treatment as early as possible if suspected.

Herpes simplex virus reactivation and/or dissemination has been reported in patients receiving Jakafi [see Adverse Reactions (6.2)]. Monitor patients for the development of herpes simplex infections. If a patient develops evidence of dissemination of herpes simplex, consider interrupting treatment with Jakafi; patients should be promptly treated and monitored according to clinical guidelines.

Hepatitis B

Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, have been reported in patients with chronic HBV infections taking Jakafi. The effect of Jakafi on viral replication in patients with chronic HBV infection is unknown. Patients with chronic HBV infection should be treated and monitored according to clinical guidelines.

Following discontinuation of Jakafi, symptoms from myeloproliferative neoplasms may return to pretreatment levels over a period of approximately one week. Some patients with MF have experienced one or more of the following adverse events after discontinuing Jakafi: fever, respiratory distress, hypotension, DIC, or multi-organ failure. If one or more of these occur after discontinuation of, or while tapering the dose of Jakafi, evaluate for and treat any intercurrent illness and consider restarting or increasing the dose of Jakafi. Instruct patients not to interrupt or discontinue Jakafi therapy without consulting their physician. When discontinuing or interrupting therapy with Jakafi for reasons other than thrombocytopenia or neutropenia [see Dosage and Administration (2.8)], consider tapering the dose of Jakafi gradually rather than discontinuing abruptly.

Non-melanoma skin cancers including basal cell, squamous cell, and Merkel cell carcinoma have occurred in patients treated with Jakafi. Perform periodic skin examinations.

Treatment with Jakafi has been associated with increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides [see Adverse Reactions (6.1)]. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined in patients treated with Jakafi. Assess lipid parameters approximately 8-12 weeks following initiation of Jakafi therapy. Monitor and treat according to clinical guidelines for the management of hyperlipidemia.

Another JAK-inhibitor has increased the risk of MACE, including cardiovascular death, myocardial infarction, and stroke (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Jakafi particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur.

Another JAK-inhibitor has increased the risk of thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. In patients with MF and PV treated with Jakafi in clinical trials, the rates of thromboembolic events were similar in Jakafi and control treated patients.

Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately.

Another JAK-inhibitor has increased the risk of lymphoma and other malignancies excluding NMSC (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. Patients who are current or past smokers are at additional increased risk.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Jakafi, particularly in patients with a known secondary malignancy (other than a successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Myelofibrosis

The safety of Jakafi was assessed in 617 patients in six clinical studies with a median duration of follow-up of 10.9 months, including 301 patients with MF in two Phase 3 studies.

In these two Phase 3 studies, patients had a median duration of exposure to Jakafi of 9.5 months (range 0.5 to 17 months), with 89% of patients treated for more than 6 months and 25% treated for more than 12 months. One hundred and eleven (111) patients started treatment at 15 mg twice daily and 190 patients started at 20 mg twice daily. In patients starting treatment with 15 mg twice daily (pretreatment platelet counts of 100 to 200 x 109/L) and 20 mg twice daily (pretreatment platelet counts greater than 200 x 109/L), 65% and 25% of patients, respectively, required a dose reduction below the starting dose within the first 8 weeks of therapy.

In a double-blind, randomized, placebo-controlled study of Jakafi, among the 155 patients treated with Jakafi, the most frequent adverse reactions were thrombocytopenia and anemia [see Table 13]. Thrombocytopenia, anemia and neutropenia are dose-related effects. The three most frequent nonhematologic adverse reactions were bruising, dizziness and headache [see Table 12].

Discontinuation for adverse events, regardless of causality, was observed in 11% of patients treated with Jakafi and 11% of patients treated with placebo.

Table 12 presents the most common nonhematologic adverse reactions occurring in patients who received Jakafi in the double-blind, placebo-controlled study during randomized treatment.

<div class="scrollingtable"><table width="675px"> <caption> <span>Table 12: Myelofibrosis: Nonhematologic Adverse Reactions Occurring in Patients on Jakafi in the Double-blind, Placebo-controlled Study During Randomized Treatment</span> </caption> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <tfoot> <tr> <td align="left" colspan="7"> <dl class="Footnote"> <dt> <a href="#footnote-reference-3" name="footnote-3">*</a> </dt> <dd>National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0</dd> <dt> <a href="#footnote-reference-4" name="footnote-4">†</a> </dt> <dd>includes contusion, ecchymosis, hematoma, injection site hematoma, periorbital hematoma, vessel puncture site hematoma, increased tendency to bruise, petechiae, purpura</dd> <dt> <a href="#footnote-reference-5" name="footnote-5">‡</a> </dt> <dd>includes dizziness, postural dizziness, vertigo, balance disorder, Meniere’s Disease, labyrinthitis</dd> <dt> <a href="#footnote-reference-6" name="footnote-6">§</a> </dt> <dd>includes urinary tract infection, cystitis, urosepsis, urinary tract infection bacterial, kidney infection, pyuria, bacteria urine, bacteria urine identified, nitrite urine present</dd> <dt> <a href="#footnote-reference-7" name="footnote-7">¶</a> </dt> <dd> <p class="First">includes weight increased, abnormal weight gain</p> </dd> <dt> <a href="#footnote-reference-8" name="footnote-8">#</a> </dt> <dd>includes herpes zoster and post-herpetic neuralgia</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule">  </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3"><span class="Bold">Jakafi<br/>(N=155)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3"><span class="Bold">Placebo<br/>(N=151)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <span class="Bold">Adverse Reactions</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">All<br/>Grades<a class="Sup" href="#footnote-3" name="footnote-reference-3">*</a> <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"><span class="Bold">Grade 3 <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"><span class="Bold">Grade 4 <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">All<br/>Grades <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"><span class="Bold">Grade 3 <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"><span class="Bold">Grade 4 <br/>(%)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Bruising<a class="Sup" href="#footnote-4" name="footnote-reference-4">†</a> </td><td align="center" class="Botrule Lrule Rrule Toprule">23</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">15</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Dizziness<a class="Sup" href="#footnote-5" name="footnote-reference-5">‡</a> </td><td align="center" class="Botrule Lrule Rrule Toprule">18</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">7</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Headache</td><td align="center" class="Botrule Lrule Rrule Toprule">15</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">5</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Urinary Tract Infections<a class="Sup" href="#footnote-6" name="footnote-reference-6">§</a> </td><td align="center" class="Botrule Lrule Rrule Toprule">9</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">5</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Weight Gain<a class="Sup" href="#footnote-7" name="footnote-reference-7">¶</a> </td><td align="center" class="Botrule Lrule Rrule Toprule">7</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">1</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Flatulence</td><td align="center" class="Botrule Lrule Rrule Toprule">5</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> Herpes Zoster<a class="Sup" href="#footnote-8" name="footnote-reference-8">#</a> </td><td align="center" class="Botrule Lrule Rrule Toprule">2</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> </tbody> </table></div>

Description of Selected Adverse Reactions

Anemia

In the two Phase 3 clinical studies, median time to onset of first CTCAE Grade 2 or higher anemia was approximately 6 weeks. One patient (< 1%) discontinued treatment because of anemia. In patients receiving Jakafi, mean decreases in hemoglobin reached a nadir of approximately 1.5 to 2.0 g/dL below baseline after 8 to 12 weeks of therapy and then gradually recovered to reach a new steady state that was approximately 1.0 g/dL below baseline. This pattern was observed in patients regardless of whether they had received transfusions during therapy.

In the randomized, placebo-controlled study, 60% of patients treated with Jakafi and 38% of patients receiving placebo received red blood cell transfusions during randomized treatment. Among transfused patients, the median number of units transfused per month was 1.2 in patients treated with Jakafi and 1.7 in placebo treated patients.

Thrombocytopenia

In the two Phase 3 clinical studies, in patients who developed Grade 3 or 4 thrombocytopenia, the median time to onset was approximately 8 weeks. Thrombocytopenia was generally reversible with dose reduction or dose interruption. The median time to recovery of platelet counts above 50 x 109/L was 14 days. Platelet transfusions were administered to 5% of patients receiving Jakafi and to 4% of patients receiving control regimens. Discontinuation of treatment because of thrombocytopenia occurred in < 1% of patients receiving Jakafi and < 1% of patients receiving control regimens. Patients with a platelet count of 100 x 109/L to 200 x 109/L before starting Jakafi had a higher frequency of Grade 3 or 4 thrombocytopenia compared to patients with a platelet count greater than 200 x 109/L (17% versus 7%).

Neutropenia

In the two Phase 3 clinical studies, 1% of patients reduced or stopped Jakafi because of neutropenia.

Table 13 provides the frequency and severity of clinical hematology abnormalities reported for patients receiving treatment with Jakafi or placebo in the placebo-controlled study.

<div class="scrollingtable"><table> <caption> <span>Table 13: Myelofibrosis: Worst Hematology Laboratory Abnormalities in the Placebo-Controlled Study<a class="Sup" href="#footnote-9" name="footnote-reference-9">*</a> </span> </caption> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <tfoot> <tr> <td align="left" colspan="7"> <dl class="Footnote"> <dt> <a href="#footnote-reference-9" name="footnote-9">*</a> </dt> <dd> <p class="First">Presented values are worst Grade values regardless of baseline</p> </dd> <dt> <a href="#footnote-reference-10" name="footnote-10">†</a> </dt> <dd> <p class="First">National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0</p> </dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule">  </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3"> <span class="Bold">Jakafi<br/>(N=155)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3"> <span class="Bold">Placebo<br/>(N=151)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Laboratory Parameter</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">All<br/>Grades<a class="Sup" href="#footnote-10" name="footnote-reference-10">†</a> <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <span class="Bold">Grade 3 <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <span class="Bold">Grade 4 <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">All<br/>Grades <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <span class="Bold">Grade 3 <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <span class="Bold">Grade 4 <br/>(%)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Thrombocytopenia</td><td align="center" class="Botrule Lrule Rrule Toprule"> 70</td><td align="center" class="Botrule Lrule Rrule Toprule"> 9</td><td align="center" class="Botrule Lrule Rrule Toprule"> 4</td><td align="center" class="Botrule Lrule Rrule Toprule"> 31</td><td align="center" class="Botrule Lrule Rrule Toprule"> 1</td><td align="center" class="Botrule Lrule Rrule Toprule"> 0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Anemia</td><td align="center" class="Botrule Lrule Rrule Toprule"> 96</td><td align="center" class="Botrule Lrule Rrule Toprule"> 34</td><td align="center" class="Botrule Lrule Rrule Toprule"> 11</td><td align="center" class="Botrule Lrule Rrule Toprule"> 87</td><td align="center" class="Botrule Lrule Rrule Toprule"> 16</td><td align="center" class="Botrule Lrule Rrule Toprule"> 3</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> Neutropenia</td><td align="center" class="Botrule Lrule Rrule Toprule"> 19</td><td align="center" class="Botrule Lrule Rrule Toprule"> 5</td><td align="center" class="Botrule Lrule Rrule Toprule"> 2</td><td align="center" class="Botrule Lrule Rrule Toprule"> 4</td><td align="center" class="Botrule Lrule Rrule Toprule"> &lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule"> 1</td> </tr> </tbody> </table></div>

Additional Data from the Placebo-Controlled Study

Polycythemia Vera

In a randomized, open-label, active-controlled study, 110 patients with PV resistant to or intolerant of hydroxyurea received Jakafi and 111 patients received best available therapy [see Clinical Studies (14.2)]. The most frequent adverse reaction was anemia. Discontinuation for adverse events, regardless of causality, was observed in 4% of patients treated with Jakafi. Table 14 presents the most frequent nonhematologic adverse reactions occurring up to Week 32.

<div class="scrollingtable"><table width="675px"> <caption> <span>Table 14: Polycythemia Vera: Nonhematologic Adverse Reactions Occurring in ≥ 5% of Patients on Jakafi in the Open-Label, Active-controlled Study up to Week 32 of Randomized Treatment</span> </caption> <col/> <col/> <col/> <col/> <col/> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-11" name="footnote-11">*</a> </dt> <dd>National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0</dd> <dt> <a href="#footnote-reference-12" name="footnote-12">†</a> </dt> <dd>includes dizziness and vertigo</dd> <dt> <a href="#footnote-reference-13" name="footnote-13">‡</a> </dt> <dd>includes dyspnea and dyspnea exertional</dd> <dt> <a href="#footnote-reference-14" name="footnote-14">§</a> </dt> <dd>includes herpes zoster and post-herpetic neuralgia</dd> <dt> <a href="#footnote-reference-15" name="footnote-15">¶</a> </dt> <dd>includes weight increased and abnormal weight gain</dd> <dt> <a href="#footnote-reference-16" name="footnote-16">#</a> </dt> <dd> <p class="First">includes urinary tract infection and cystitis</p> </dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Jakafi<br/>(N=110)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Best Available Therapy<br/>(N=111)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Adverse Reactions<br/> </span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">All Grades<a class="Sup" href="#footnote-11" name="footnote-reference-11">*</a> <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Grade 3-4<br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">All Grades<br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Grade 3-4<br/>(%)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Diarrhea</td><td align="center" class="Botrule Lrule Rrule Toprule">15</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">7</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Dizziness<a class="Sup" href="#footnote-12" name="footnote-reference-12">†</a> </td><td align="center" class="Botrule Lrule Rrule Toprule">15</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">13</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Dyspnea<a class="Sup" href="#footnote-13" name="footnote-reference-13">‡</a> </td><td align="center" class="Botrule Lrule Rrule Toprule">13</td><td align="center" class="Botrule Lrule Rrule Toprule">3</td><td align="center" class="Botrule Lrule Rrule Toprule">4</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Muscle Spasms</td><td align="center" class="Botrule Lrule Rrule Toprule">12</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">5</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Constipation</td><td align="center" class="Botrule Lrule Rrule Toprule">8</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">3</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Herpes Zoster<a class="Sup" href="#footnote-14" name="footnote-reference-14">§</a> </td><td align="center" class="Botrule Lrule Rrule Toprule">6</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Nausea</td><td align="center" class="Botrule Lrule Rrule Toprule">6</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">4</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Weight Gain<a class="Sup" href="#footnote-15" name="footnote-reference-15">¶</a> </td><td align="center" class="Botrule Lrule Rrule Toprule">6</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Urinary Tract Infections<a class="Sup" href="#footnote-16" name="footnote-reference-16">#</a> </td><td align="center" class="Botrule Lrule Rrule Toprule">6</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">3</td><td align="center" class="Botrule Lrule Rrule Toprule"> 0</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Hypertension</td><td align="center" class="Botrule Lrule Rrule Toprule">5</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">3</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td> </tr> </tbody> </table></div>

Clinically relevant laboratory abnormalities are shown in Table 15.

<div class="scrollingtable"><table> <caption> <span>Table 15: Polycythemia Vera: Selected Laboratory Abnormalities in the Open-Label, Active-controlled Study up to Week 32 of Randomized Treatment<a class="Sup" href="#footnote-17" name="footnote-reference-17">*</a> </span> </caption> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <tfoot> <tr> <td align="left" colspan="7"> <dl class="Footnote"> <dt> <a href="#footnote-reference-17" name="footnote-17">*</a> </dt> <dd> <p class="First">Presented values are worst Grade values regardless of baseline</p> </dd> <dt> <a href="#footnote-reference-18" name="footnote-18">†</a> </dt> <dd> <p class="First">National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0</p> </dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3"><span class="Bold">Jakafi<br/>(N=110)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3"><span class="Bold">Best Available Therapy<br/>(N=111)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Laboratory Parameter</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">All<br/>Grades<a class="Sup" href="#footnote-18" name="footnote-reference-18">†</a> <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Grade 3<br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Grade 4<br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">All<br/>Grades<br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Grade 3<br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Grade 4<br/>(%)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="7"><span class="Bold">Hematology</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Anemia</td><td align="center" class="Botrule Lrule Rrule Toprule">72</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">58</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Thrombocytopenia</td><td align="center" class="Botrule Lrule Rrule Toprule">27</td><td align="center" class="Botrule Lrule Rrule Toprule">5</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">24</td><td align="center" class="Botrule Lrule Rrule Toprule">3</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Neutropenia</td><td align="center" class="Botrule Lrule Rrule Toprule">3</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">10</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="7"><span class="Bold">Chemistry</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Hypercholesterolemia</td><td align="center" class="Botrule Lrule Rrule Toprule">35</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">8</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Elevated ALT</td><td align="center" class="Botrule Lrule Rrule Toprule">25</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">16</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Elevated AST</td><td align="center" class="Botrule Lrule Rrule Toprule">23</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">23</td><td align="center" class="Botrule Lrule Rrule Toprule">&lt; 1</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Hypertriglyceridemia</td><td align="center" class="Botrule Lrule Rrule Toprule">15</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">13</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> </tbody> </table></div>

Acute Graft-Versus-Host Disease

In a single-arm, open-label study, 71 adults (ages 18-73 years) were treated with Jakafi for aGVHD failing treatment with steroids with or without other immunosuppressive drugs [see Clinical Studies (14.3)]. The median duration of treatment with Jakafi was 46 days (range, 4‑382 days).

There were no fatal adverse reactions to Jakafi. An adverse reaction resulting in treatment discontinuation occurred in 31% of patients. The most common adverse reaction leading to treatment discontinuation was infection (10%). Table 16 shows the adverse reactions other than laboratory abnormalities.

<div class="scrollingtable"><table cellspacing="0" width="557.28px"> <caption> <span>Table 16: Acute Graft-Versus-Host Disease: Nonhematologic Adverse Reactions Occurring in ≥ 15% of Patients in the Open-Label, Single-Cohort Study</span> </caption> <col width="179.57px"/> <col/> <col/> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-19" name="footnote-19">*</a> </dt> <dd>Selected laboratory abnormalities are listed in Table 17 below</dd> <dt> <a href="#footnote-reference-20" name="footnote-20">†</a> </dt> <dd>National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Jakafi (N=71)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Adverse Reactions<a class="Sup" href="#footnote-19" name="footnote-reference-19">*</a> </span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">All Grades<a class="Sup" href="#footnote-20" name="footnote-reference-20">†</a> </span><span class="Bold"> <br/>(%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Grade 3-4<br/>(%)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Infections (pathogen not specified)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">55</p> </td><td align="center" class="Botrule Lrule Rrule Toprule">41</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Edema</td><td align="center" class="Botrule Lrule Rrule Toprule">51</td><td align="center" class="Botrule Lrule Rrule Toprule">13</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Hemorrhage</td><td align="center" class="Botrule Lrule Rrule Toprule">49</td><td align="center" class="Botrule Lrule Rrule Toprule">20</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Fatigue</td><td align="center" class="Botrule Lrule Rrule Toprule">37</td><td align="center" class="Botrule Lrule Rrule Toprule">14</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Bacterial infections</td><td align="center" class="Botrule Lrule Rrule Toprule">32</td><td align="center" class="Botrule Lrule Rrule Toprule">28</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Dyspnea</td><td align="center" class="Botrule Lrule Rrule Toprule">32</td><td align="center" class="Botrule Lrule Rrule Toprule">7</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Viral infections</td><td align="center" class="Botrule Lrule Rrule Toprule">31</td><td align="center" class="Botrule Lrule Rrule Toprule">14</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Thrombosis</td><td align="center" class="Botrule Lrule Rrule Toprule">25</td><td align="center" class="Botrule Lrule Rrule Toprule">11</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Diarrhea</td><td align="center" class="Botrule Lrule Rrule Toprule">24</td><td align="center" class="Botrule Lrule Rrule Toprule">7</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Rash</td><td align="center" class="Botrule Lrule Rrule Toprule">23</td><td align="center" class="Botrule Lrule Rrule Toprule">3</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Headache</td><td align="center" class="Botrule Lrule Rrule Toprule">21</td><td align="center" class="Botrule Lrule Rrule Toprule">4</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Hypertension</td><td align="center" class="Botrule Lrule Rrule Toprule">20</td><td align="center" class="Botrule Lrule Rrule Toprule">13</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Dizziness</td><td align="center" class="Botrule Lrule Rrule Toprule">16</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> </tbody> </table></div>

Selected laboratory abnormalities during treatment with Jakafi are shown in Table 17.

<div class="scrollingtable"><table width="471.54px"> <caption> <span>Table 17: Acute Graft-Versus-Host Disease: Selected Laboratory Abnormalities Worsening from Baseline in the Open-Label, Single Cohort Study</span> </caption> <col/> <col/> <col/> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-21" name="footnote-21">*</a> </dt> <dd>National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Jakafi (N=71)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Worst grade during treatment</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Laboratory Parameter</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">All Grades<a class="Sup" href="#footnote-21" name="footnote-reference-21">*</a> <br/> <span class="Bold"><span class="Sup">(%)</span></span></span></td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Grade 3-4<br/> <span class="Bold">(%)</span></span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="3"><span class="Bold">Hematology</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Anemia</td><td align="center" class="Botrule Lrule Rrule Toprule">75</td><td align="center" class="Botrule Lrule Rrule Toprule">45</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Thrombocytopenia</td><td align="center" class="Botrule Lrule Rrule Toprule">75</td><td align="center" class="Botrule Lrule Rrule Toprule">61</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Neutropenia</td><td align="center" class="Botrule Lrule Rrule Toprule">58</td><td align="center" class="Botrule Lrule Rrule Toprule">40</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="3"><span class="Bold">Chemistry</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Elevated ALT</td><td align="center" class="Botrule Lrule Rrule Toprule">48</td><td align="center" class="Botrule Lrule Rrule Toprule">8</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Elevated AST</td><td align="center" class="Botrule Lrule Rrule Toprule">48</td><td align="center" class="Botrule Lrule Rrule Toprule">6</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Hypertriglyceridemia</td><td align="center" class="Botrule Lrule Rrule Toprule">11</td><td align="center" class="Botrule Lrule Rrule Toprule">1</td> </tr> </tbody> </table></div>

Chronic Graft-Versus-Host Disease

In a Phase 3, randomized, open-label, multi-center study, 165 patients were treated with Jakafi and 158 patients were treated with best available therapy for cGVHD failing treatment with steroids with or without other immunosuppressive drugs [see Clinical Studies (14.4)]; sixty-five patients crossed over from best available therapy to treatment with Jakafi, for a total of 230 patients treated with Jakafi. The median duration of exposure to Jakafi for the study was 49.7 weeks (range, 0.7 to 144.9 weeks) in the Jakafi arm. One hundred and nine (47%) patients were on Jakafi for at least 1 year.

There were five fatal adverse reactions to Jakafi, including 1 from toxic epidermal necrolysis and 4 from neutropenia, anemia and/or thrombocytopenia. An adverse reaction resulting in treatment discontinuation occurred in 18% of patients treated with Jakafi. An adverse reaction resulting in dose modification occurred in 27%, and an adverse reaction resulting in treatment interruption occurred in 23%. The most common hematologic adverse reactions (incidence > 35%) are anemia and thrombocytopenia. The most common nonhematologic adverse reactions (incidence ≥ 20%) are infections (pathogen not specified) and viral infection.

Table 18 presents the most frequent nonlaboratory adverse reactions occurring up to Cycle 7 Day 1 of randomized treatment.

<div class="scrollingtable"><table> <caption> <span>Table 18: Chronic Graft-Versus-Host Disease: All-Grade (≥ 10%) and Grades 3-5 (≥ 3%) Nonlaboratory Adverse Reactions Occurring in Patients in the Open-Label, Active-controlled Study up to Cycle 7 Day 1 of Randomized Treatment</span> </caption> <col/> <col/> <col/> <col/> <col/> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-22" name="footnote-22">*</a> </dt> <dd>Grouped terms that are composites of applicable adverse reaction terms.</dd> <dt> <a href="#footnote-reference-23" name="footnote-23">†</a> </dt> <dd>National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.03</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" rowspan="2"><span class="Bold">Adverse Reaction<a class="Sup" href="#footnote-22" name="footnote-reference-22">*</a> </span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Jakafi<br/> (N = 165)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Best Available Therapy<br/> (N = 158)</span></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">  All Grades<a class="Sup" href="#footnote-23" name="footnote-reference-23">†</a>   <br/> </span><span class="Bold">(%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">  Grade ≥  3  <br/> </span><span class="Bold">(%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">  All Grades  <br/> </span><span class="Bold">(%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">  Grade </span><span class="Bold">≥ 3  <br/> </span><span class="Bold">(%)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">Infections and infestations</span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">   Infections (pathogen not specified)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 45</td><td align="center" class="Botrule Lrule Rrule Toprule">15</td><td align="center" class="Botrule Lrule Rrule Toprule">44</td><td align="center" class="Botrule Lrule Rrule Toprule">16</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">   Viral infections<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule"> 28</td><td align="center" class="Botrule Lrule Rrule Toprule">5</td><td align="center" class="Botrule Lrule Rrule Toprule">23</td><td align="center" class="Botrule Lrule Rrule Toprule">5</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">Musculoskeletal and connective tissue disorders</span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">   Musculoskeletal pain<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">18</td><td align="center" class="Botrule Lrule Rrule Toprule">1</td><td align="center" class="Botrule Lrule Rrule Toprule">13</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">General disorders and administration site conditions</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">   Pyrexia<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">16</td><td align="center" class="Botrule Lrule Rrule Toprule">2</td><td align="center" class="Botrule Lrule Rrule Toprule">9</td><td align="center" class="Botrule Lrule Rrule Toprule">1</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">   Fatigue<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">13</td><td align="center" class="Botrule Lrule Rrule Toprule">1</td><td align="center" class="Botrule Lrule Rrule Toprule">10</td><td align="center" class="Botrule Lrule Rrule Toprule">2</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">   Edema</td><td align="center" class="Botrule Lrule Rrule Toprule">10</td><td align="center" class="Botrule Lrule Rrule Toprule">1</td><td align="center" class="Botrule Lrule Rrule Toprule">12</td><td align="center" class="Botrule Lrule Rrule Toprule">1</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">Vascular disorders</span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">   Hypertension<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">16</td><td align="center" class="Botrule Lrule Rrule Toprule">5</td><td align="center" class="Botrule Lrule Rrule Toprule">13</td><td align="center" class="Botrule Lrule Rrule Toprule">7</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">   Hemorrhage<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">12</td><td align="center" class="Botrule Lrule Rrule Toprule">2</td><td align="center" class="Botrule Lrule Rrule Toprule">15</td><td align="center" class="Botrule Lrule Rrule Toprule">2</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">Respiratory, thoracic and mediastinal disorders</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">   Cough<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">13</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">8</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">   Dyspnea<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">11</td><td align="center" class="Botrule Lrule Rrule Toprule">1</td><td align="center" class="Botrule Lrule Rrule Toprule">8</td><td align="center" class="Botrule Lrule Rrule Toprule">1</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">Gastrointestinal disorders</span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">   Nausea<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">12</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td><td align="center" class="Botrule Lrule Rrule Toprule">13</td><td align="center" class="Botrule Lrule Rrule Toprule">2</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">   Diarrhea<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">10</td><td align="center" class="Botrule Lrule Rrule Toprule">1</td><td align="center" class="Botrule Lrule Rrule Toprule">13</td><td align="center" class="Botrule Lrule Rrule Toprule">1</td> </tr> </tbody> </table></div>

Clinically relevant laboratory abnormalities are shown in Table 19.

<div class="scrollingtable"><table> <caption> <span>Table 19: Chronic Graft-Versus-Host Disease: Selected Laboratory Abnormalities in the Open-Label, Active-controlled Study up to Cycle 7 Day 1 of Randomized Treatment<a class="Sup" href="#footnote-24" name="footnote-reference-24">*</a> </span> </caption> <col/> <col/> <col/> <col/> <col/> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-24" name="footnote-24">*</a> </dt> <dd>Presented values are worst Grade values regardless of baseline</dd> <dt> <a href="#footnote-reference-25" name="footnote-25">†</a> </dt> <dd>National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" rowspan="2"><span class="Bold"><span class="Bold">Laboratory Test</span></span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Jakafi<br/>(N = 165)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Best Available Therapy<br/>(N = 158)</span></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">  All Grades<a class="Sup" href="#footnote-25" name="footnote-reference-25">†</a>   <br/> </span><span class="Bold">(%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">  Grade ≥ 3  <br/> </span><span class="Bold">(%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">All Grades<br/> </span><span class="Bold">(%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Grade </span><span class="Bold">≥ 3<br/> </span><span class="Bold">(%)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold"><span class="Bold">Hematology</span></span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Anemia</td><td align="center" class="Botrule Lrule Rrule Toprule">82</td><td align="center" class="Botrule Lrule Rrule Toprule">13</td><td align="center" class="Botrule Lrule Rrule Toprule">75</td><td align="center" class="Botrule Lrule Rrule Toprule">8</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Neutropenia<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">27</td><td align="center" class="Botrule Lrule Rrule Toprule">12</td><td align="center" class="Botrule Lrule Rrule Toprule">23</td><td align="center" class="Botrule Lrule Rrule Toprule">9</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Thrombocytopenia</td><td align="center" class="Botrule Lrule Rrule Toprule">58</td><td align="center" class="Botrule Lrule Rrule Toprule">20</td><td align="center" class="Botrule Lrule Rrule Toprule">54</td><td align="center" class="Botrule Lrule Rrule Toprule">17</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold"><span class="Bold">Chemistry</span></span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Hypercholesterolemia<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">88</td><td align="center" class="Botrule Lrule Rrule Toprule">10</td><td align="center" class="Botrule Lrule Rrule Toprule">85</td><td align="center" class="Botrule Lrule Rrule Toprule">8</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Elevated AST<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">65</td><td align="center" class="Botrule Lrule Rrule Toprule">5</td><td align="center" class="Botrule Lrule Rrule Toprule">54</td><td align="center" class="Botrule Lrule Rrule Toprule">6</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Elevated ALT<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">73</td><td align="center" class="Botrule Lrule Rrule Toprule">11</td><td align="center" class="Botrule Lrule Rrule Toprule">71</td><td align="center" class="Botrule Lrule Rrule Toprule">16</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Gamma glutamyltransferase increased         <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">81</td><td align="center" class="Botrule Lrule Rrule Toprule">42</td><td align="center" class="Botrule Lrule Rrule Toprule">75</td><td align="center" class="Botrule Lrule Rrule Toprule">38</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Creatinine increased<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">47</td><td align="center" class="Botrule Lrule Rrule Toprule">1</td><td align="center" class="Botrule Lrule Rrule Toprule">40</td><td align="center" class="Botrule Lrule Rrule Toprule">2</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Elevated lipase<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">38</td><td align="center" class="Botrule Lrule Rrule Toprule">12</td><td align="center" class="Botrule Lrule Rrule Toprule">30</td><td align="center" class="Botrule Lrule Rrule Toprule">9</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Elevated amylase<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule">35</td><td align="center" class="Botrule Lrule Rrule Toprule">8</td><td align="center" class="Botrule Lrule Rrule Toprule">25</td><td align="center" class="Botrule Lrule Rrule Toprule">4</td> </tr> </tbody> </table></div>

The following adverse reactions have been identified during post-approval use of Jakafi. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: 

Fluconazole

Concomitant use of Jakafi with fluconazole increases ruxolitinib exposure [see Clinical Pharmacology (12.3)], which may increase the risk of exposure-related adverse reactions. Avoid concomitant use of Jakafi with fluconazole doses of greater than 200 mg daily. Reduce the Jakafi dosage when used concomitantly with fluconazole doses of less than or equal to 200 mg [see Dosage and Administration (2.6)].

Strong CYP3A4 Inhibitors

Concomitant use of Jakafi with strong CYP3A4 inhibitors increases ruxolitinib exposure [see Clinical Pharmacology (12.3)], which may increase the risk of exposure-related adverse reactions. Reduce the Jakafi dosage when used concomitantly with strong CYP3A4 inhibitors except in patients with aGVHD or cGVHD [see Dosage and Administration (2.6)].

Strong CYP3A4 Inducers

Concomitant use of Jakafi with strong CYP3A4 inducers may decrease ruxolitinib exposure [see Clinical Pharmacology (12.3)], which may reduce efficacy of Jakafi. Monitor patients frequently and adjust the Jakafi dose based on safety and efficacy [see Clinical Pharmacology (12.3)].

Risk Summary

When pregnant rats and rabbits were administered ruxolitinib during the period of organogenesis adverse developmental outcomes occurred at doses associated with maternal toxicity (see Data). There are no studies with the use of Jakafi in pregnant women to inform drug-associated risks.

The background risk of major birth defects and miscarriage for the indicated populations is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The background risk in the U.S. general population of major birth defects is 2% to 4% and miscarriage is 15% to 20% of clinically recognized pregnancies.

Data

Animal Data

Ruxolitinib was administered orally to pregnant rats or rabbits during the period of organogenesis, at doses of 15, 30 or 60 mg/kg/day in rats and 10, 30 or 60 mg/kg/day in rabbits. There were no treatment-related malformations. Adverse developmental outcomes, such as decreases of approximately 9% in fetal weights were noted in rats at the highest and maternally toxic dose of 60 mg/kg/day. This dose results in an exposure (AUC) that is approximately 2 times the clinical exposure at the maximum recommended dose of 25 mg twice daily. In rabbits, lower fetal weights of approximately 8% and increased late resorptions were noted at the highest and maternally toxic dose of 60 mg/kg/day. This dose is approximately 7% the clinical exposure at the maximum recommended dose.

In a pre- and post-natal development study in rats, pregnant animals were dosed with ruxolitinib from implantation through lactation at doses up to 30 mg/kg/day. There were no drug-related adverse findings in pups for fertility indices or for maternal or embryofetal survival, growth and development parameters at the highest dose evaluated (34% the clinical exposure at the maximum recommended dose of 25 mg twice daily).

Risk Summary

No data are available regarding the presence of ruxolitinib in human milk, the effects on the breast fed child, or the effects on milk production. Ruxolitinib and/or its metabolites were present in the milk of lactating rats (see Data). Because many drugs are present in human milk and because of the potential for thrombocytopenia and anemia shown for Jakafi in human studies, discontinue breastfeeding during treatment with Jakafi and for two weeks after the final dose.

Data

Animal Data

Lactating rats were administered a single dose of [14C]-labeled ruxolitinib (30 mg/kg) on postnatal Day 10, after which plasma and milk samples were collected for up to 24 hours. The AUC for total radioactivity in milk was approximately 13-fold the maternal plasma AUC. Additional analysis showed the presence of ruxolitinib and several of its metabolites in milk, all at levels higher than those in maternal plasma.

Myelofibrosis

The safety and effectiveness of Jakafi for treatment of myelofibrosis in pediatric patients have not been established.

Polycythemia Vera

The safety and effectiveness of Jakafi for treatment of polycythemia vera in pediatric patients have not been established.

Acute Graft-Versus-Host Disease

The safety and effectiveness of Jakafi for treatment of steroid-refractory aGVHD has been established for treatment of pediatric patients 12 years and older. Use of Jakafi in pediatric patients with steroid-refractory aGVHD is supported by evidence from adequate and well-controlled trials of Jakafi in adults [see Clinical Studies (14.3)] and additional pharmacokinetic and safety data in pediatric patients. The safety and effectiveness of Jakafi for treatment of steroid-refractory aGVHD has not been established in pediatric patients younger than 12 years old.

Chronic Graft-Versus-Host Disease

The safety and effectiveness of Jakafi for treatment of cGVHD after failure of one or two lines of systemic therapy has been established for treatment of pediatric patients 12 years and older. Use of Jakafi in pediatric patients with cGVHD after failure of one or two lines of systemic therapy is supported by evidence from adequate and well-controlled trials of Jakafi in adults and adolescents [see Clinical Studies (14.4)] and additional pharmacokinetic and safety data in pediatric patients. The safety and effectiveness of Jakafi for treatment of cGVHD has not been established in pediatric patients younger than 12 years old.

Other Myeloproliferative Neoplasms, Leukemias, and Solid Tumors

The safety and effectiveness of ruxolitinib were assessed but not established in a single-arm trial (NCT01164163) in patients with relapsed or refractory solid tumors, leukemias, or myeloproliferative neoplasms. The patients included 18 children (age 2 to < 12 years) and 14 adolescents (age 12 to < 17 years). Overall, 19% of patients received more than one cycle. No new safety signals were observed in pediatric patients in this trial.

The safety and effectiveness of ruxolitinib in combination with chemotherapy for treatment of high-risk, de novo CRLF2 rearranged or JAK pathway–mutant Ph-like acute lymphoblastic leukemia (ALL) were assessed but not established in a single-arm trial (NCT02723994). The patients included 2 infants (age < 2 years), 42 children (age 2 to < 12 years) and 62 adolescents (age 12 to < 17 years). No new safety signals were observed in pediatric patients in this trial.

Juvenile Animal Toxicity Data

Administration of ruxolitinib to juvenile rats resulted in effects on growth and bone measures. When administered starting at postnatal day 7 (the equivalent of a human newborn) at doses of 1.5 to 75 mg/kg/day, evidence of fractures occurred at doses ≥ 30 mg/kg/day, and effects on body weight and other bone measures [e.g., bone mineral content, peripheral quantitative computed tomography, and x-ray analysis] occurred at doses ≥ 5 mg/kg/day. When administered starting at postnatal day 21 (the equivalent of a human 2-3 years of age) at doses of 5 to 60 mg/kg/day, effects on body weight and bone occurred at doses ≥ 15 mg/kg/day, which were considered adverse at 60 mg/kg/day. Males were more severely affected than females in all age groups, and effects were generally more severe when administration was initiated earlier in the postnatal period. These findings were observed at exposures that are at least 27% the clinical exposure at the maximum recommended dose of 25 mg twice daily.

Of the total number of patients with MF in clinical studies with Jakafi, 52% were 65 years and older, while 15% were 75 years and older. No overall differences in safety or effectiveness of Jakafi were observed between these patients and younger patients.

Clinical studies of Jakafi in patients with aGVHD did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently from younger subjects.

Of the total number of patients with cGVHD treated with Jakafi in clinical trials, 11% were 65 years and older. No overall differences in safety or effectiveness of Jakafi were observed between these patients and younger patients.

Total exposure of ruxolitinib and its active metabolites increased with moderate (CLcr 30 to 59 mL/min) and severe (CLcr 15 to 29 mL/min) renal impairment, and ESRD (CLcr less than 15 mL/min) on dialysis [see Clinical Pharmacology (12.3)]. Modify Jakafi dosage as recommended [see Dosage and Administration (2.7)].

Exposure of ruxolitinib increased with mild (Child-Pugh A), moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment [see Clinical Pharmacology (12.3)].

Reduce Jakafi dosage as recommended in patients with MF or PV with hepatic impairment [see Dosage and Administration (2.7)]. Reduce Jakafi dosage as recommended for patients with Stage 4 liver aGVHD.

Monitor blood counts more frequently for toxicity and modify the Jakafi dosage for adverse reactions if they occur for patients with Score 3 liver cGVHD [see Dosage and Administration (2.7) and Clinical Pharmacology (12.3)].

There is no known antidote for overdoses with Jakafi. Single doses up to 200 mg have been given with acceptable acute tolerability. Higher than recommended repeat doses are associated with increased myelosuppression including leukopenia, anemia and thrombocytopenia. Appropriate supportive treatment should be given.

{ "type": "p", "children": [], "text": "There is no known antidote for overdoses with Jakafi. Single doses up to 200 mg have been given with acceptable acute tolerability. Higher than recommended repeat doses are associated with increased myelosuppression including leukopenia, anemia and thrombocytopenia. Appropriate supportive treatment should be given." }

Hemodialysis is not expected to enhance the elimination of Jakafi.

{ "type": "p", "children": [], "text": "Hemodialysis is not expected to enhance the elimination of Jakafi." }

Ruxolitinib phosphate is a kinase inhibitor with the chemical name (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate and a molecular weight of 404.36. Ruxolitinib phosphate has the following structural formula:

{ "type": "p", "children": [], "text": "Ruxolitinib phosphate is a kinase inhibitor with the chemical name (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate and a molecular weight of 404.36. Ruxolitinib phosphate has the following structural formula:" }

Ruxolitinib phosphate is a white to off-white to light pink powder and is soluble in aqueous buffers across a pH range of 1 to 8.

{ "type": "p", "children": [], "text": "Ruxolitinib phosphate is a white to off-white to light pink powder and is soluble in aqueous buffers across a pH range of 1 to 8. " }

Jakafi (ruxolitinib) Tablets are for oral administration. Each tablet contains 6.6 mg, 13.2 mg, 19.8 mg, 26.4 mg, or 33 mg of ruxolitinib phosphate equivalent to 5 mg, 10 mg, 15 mg, 20 mg, or 25 mg of ruxolitinib free base, respectively, together with microcrystalline cellulose, lactose monohydrate, magnesium stearate, colloidal silicon dioxide, sodium starch glycolate, povidone and hydroxypropyl cellulose.

{ "type": "p", "children": [], "text": "Jakafi (ruxolitinib) Tablets are for oral administration. Each tablet contains 6.6 mg, 13.2 mg, 19.8 mg, 26.4 mg, or 33 mg of ruxolitinib phosphate equivalent to 5 mg, 10 mg, 15 mg, 20 mg, or 25 mg of ruxolitinib free base, respectively, together with microcrystalline cellulose, lactose monohydrate, magnesium stearate, colloidal silicon dioxide, sodium starch glycolate, povidone and hydroxypropyl cellulose." }

Ruxolitinib, a kinase inhibitor, inhibits Janus Associated Kinases (JAKs) JAK1 and JAK2 which mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. JAK signaling involves recruitment of STATs (signal transducers and activators of transcription) to cytokine receptors, activation and subsequent localization of STATs to the nucleus leading to modulation of gene expression.

MF and PV are myeloproliferative neoplasms (MPN) known to be associated with dysregulated JAK1 and JAK2 signaling. In a mouse model of JAK2V617F-positive MPN, oral administration of ruxolitinib prevented splenomegaly, preferentially decreased JAK2V617F mutant cells in the spleen and decreased circulating inflammatory cytokines (e.g., TNF-α, IL-6).

JAK-STAT signaling pathways play a role in regulating the development, proliferation, and activation of several immune cell types important for GVHD pathogenesis. In a mouse model of aGVHD, oral administration of ruxolitinib was associated with decreased expression of inflammatory cytokines in colon homogenates and reduced immune-cell infiltration in the colon.

Jakafi inhibits cytokine induced STAT3 phosphorylation in whole blood from patients with MF and PV. STAT3 phosphorylation reached maximal inhibition 2 hours after Jakafi dosing and returned to near baseline by 10 hours in patients with MF and PV.

Cardiac Electrophysiology

At a dose of 1.25 to 10 times the highest recommended starting dosage, Jakafi does not prolong the QT interval to any clinically relevant extent.

Mean ruxolitinib maximal plasma concentration (Cmax) and AUC increased proportionally over a single dose range of 5 mg to 200 mg (4 times the approved highest recommended total daily dosage of 25 mg twice daily). Mean ruxolitinib Cmax ranged from 205 nM to 7100 nM and AUC ranged from 862 nM*hr to 30700 nM*hr over a single dose range of 5 mg to 200 mg.

Absorption

Ruxolitinib achieves Cmax within 1 hour to 2 hours post-dose. Oral absorption of ruxolitinib is estimated to be at least 95%.

Effect of Food

No clinically relevant changes in the pharmacokinetics of ruxolitinib were observed upon administration of Jakafi with a high-fat, high-calorie meal (approximately 800 to 1000 calories of which 50% were derived from fat).

Distribution

The mean ruxolitinib volume of distribution at steady-state is 72 L (coefficient of variation [CV] 29%) in patients with MF and 75 L (23%) in patients with PV.

Protein binding of ruxolitinib is approximately 97%, mostly to albumin.

Elimination

The mean elimination half-life of ruxolitinib is approximately 3 hours and the mean elimination half-life of ruxolitinib and its metabolites is approximately 5.8 hours in healthy volunteers.

Ruxolitinib clearance (%CV) was 17.7 L/h in women and 22.1 L/h in men with MF (39%).

Ruxolitinib clearance (%CV) was 12.7 L/h (42%) in patients with PV.

Ruxolitinib clearance (%CV) was 11.8 L/h (63%) in patients with aGVHD.

Ruxolitinib clearance (%CV) was 9.7 L/h (51%) in patients with cGVHD.

Metabolism

Ruxolitinib is metabolized by CYP3A4 and to a lesser extent by CYP2C9.

Excretion

Following a single oral dose of radiolabeled ruxolitinib, 74% of radioactivity was excreted in urine and 22% via feces. Unchanged drug accounted for less than 1% of the excreted total radioactivity.

Specific Populations

No clinically relevant differences in ruxolitinib pharmacokinetics were observed based on age (12-73 years), race (White, Asian), sex, or weight (29-139 kg).

Patients with Renal Impairment

Total AUC of ruxolitinib and its active metabolites increased by 1.3-, 1.5-, 1.9-, and 1.6-fold in subjects with mild, moderate, severe renal impairment, and with ESRD after dialysis, respectively, compared to subjects with normal renal function (CLcr ≥ 90 mL/min). The change in the pharmacodynamic marker, pSTAT3 inhibition, was consistent with the corresponding increase in metabolite exposure with renal impairment. Ruxolitinib is not removed by dialysis; however, the removal of some active metabolites by dialysis cannot be ruled out.

Patients with Hepatic Impairment

No clinically relevant effect on ruxolitinib pharmacokinetics was observed based on mild to severe hepatic impairment by NCI criteria (total bilirubin > ULN and any AST) in patients with aGVHD or cGVHD.

Ruxolitinib AUC increased in subjects with mild (Child-Pugh A) by 1.9-fold, moderate (Child-Pugh B) by 1.3-fold, and severe (Child-Pugh C) hepatic impairment by 1.7-fold compared to that in subjects with normal hepatic function.

The change in the pharmacodynamic marker, pSTAT3 inhibition, was consistent with the corresponding increase in ruxolitinib exposure except in the severe hepatic impairment cohort where the pharmacodynamic activity was more prolonged in some subjects than expected based on plasma concentrations of ruxolitinib.

Patients with Liver Involvement in Graft-Versus-Host Disease

No clinically relevant effect on ruxolitinib pharmacokinetics was observed based on Stage 1, 2 or 3 liver aGVHD, or Score 1, or 2 liver cGVHD.

A lower apparent clearance of ruxolitinib was observed in patients with Stage 4 liver aGVHD compared to patients with no liver aGVHD.

The effect of Score 3 liver cGVHD on the pharmacokinetics of ruxolitinib is unknown.

Drug Interaction Studies

Clinical Studies and Model-Informed Approaches

Fluconazole: Fluconazole 100 to 400 mg once daily (a moderate CYP3A4 and CYP2C9 inhibitor) increases steady state ruxolitinib AUC by approximately 100% to 300% [see Dosage and Administration (2.6) and Drug Interactions (7)].

Strong CYP3A4 inhibitors: Ketoconazole (strong CYP3A4 inhibitor) increased ruxolitinib Cmax by 33% and AUC by 91% and prolonged ruxolitinib half-life from 3.7 hours to 6 hours [see Dosage and Administration (2.6) and Drug Interactions (7)].

Moderate CYP3A4 inhibitors: Erythromycin (moderate CYP3A4 inhibitor) increased ruxolitinib Cmax by 8% and AUC by 27% [see Drug Interactions (7)].

Strong CYP3A4 inducers: Rifampin (strong CYP3A4 inducer) decreased ruxolitinib Cmax by 32% and AUC by 61%. The relative exposure to ruxolitinib’s active metabolites increased approximately 100% [see Drug Interactions (7)].

In Vitro Studies

Cytochrome P450 (CYP) Enzymes: Ruxolitinib and its M18 metabolite did not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4. Ruxolitinib did not induce CYP1A2, CYP2B6 or CYP3A4 at clinically relevant concentrations.

Transporter Systems: Ruxolitinib and its M18 metabolite did not inhibit the P-gp, BCRP, OATP1B1, OATP1B3, OCT1, OCT2, OAT1 or OAT3 at clinically relevant concentrations. Ruxolitinib was not a P-gp substrate.

Ruxolitinib was not carcinogenic in the 6-month Tg.rasH2 transgenic mouse model or in a 2-year carcinogenicity study in the rat.

Ruxolitinib was not mutagenic in a bacterial mutagenicity assay (Ames test) or clastogenic in in vitro chromosomal aberration assay (cultured human peripheral blood lymphocytes) or in vivo in a rat bone marrow micronucleus assay.

In a fertility study, ruxolitinib was administered to male rats prior to and throughout mating and to female rats prior to mating and up to the implantation day (gestation day 7). Ruxolitinib had no effect on fertility or reproductive function in male or female rats at doses of 10, 30 or 60 mg/kg/day. However, in female rats doses of greater than or equal to 30 mg/kg/day resulted in increased post-implantation loss. The exposure (AUC) at the dose of 30 mg/kg/day is approximately 34% the clinical exposure at the maximum recommended dose of 25 mg twice daily.

Two randomized Phase 3 studies (Studies 1 and 2) were conducted in patients with MF (either primary MF, post-polycythemia vera MF or post-essential thrombocythemia-MF). In both studies, patients had palpable splenomegaly at least 5 cm below the costal margin and risk category of intermediate 2 (2 prognostic factors) or high risk (3 or more prognostic factors) based on the International Working Group Consensus Criteria (IWG).

The starting dose of Jakafi was based on platelet count. Patients with a platelet count between 100 and 200 x 109/L were started on Jakafi 15 mg twice daily and patients with a platelet count greater than 200 x 109/L were started on Jakafi 20 mg twice daily. Doses were then individualized based upon tolerability and efficacy with maximum doses of 20 mg twice daily for patients with platelet counts between 100 to less than or equal to 125 x 109/L, of 10 mg twice daily for patients with platelet counts between 75 to less than or equal to 100 x 109/L, and of 5 mg twice daily for patients with platelet counts between 50 to less than or equal to 75 x 109/L.

Study 1

Study 1 (NCT00952289) was a double-blind, randomized, placebo-controlled study in 309 patients who were refractory to or were not candidates for available therapy. The median age was 68 years (range 40 to 91 years) with 61% of patients older than 65 years and 54% were male. Fifty percent (50%) of patients had primary MF, 31% had post-polycythemia vera MF and 18% had post-essential thrombocythemia MF. Twenty-one percent (21%) of patients had red blood cell transfusions within 8 weeks of enrollment in the study. The median hemoglobin count was 10.5 g/dL and the median platelet count was 251 x 109/L. Patients had a median palpable spleen length of 16 cm below the costal margin, with 81% having a spleen length 10 cm or greater below the costal margin. Patients had a median spleen volume as measured by magnetic resonance imaging (MRI) or computed tomography (CT) of 2595 cm3 (range 478 cm3 to 8881 cm3). (The upper limit of normal is approximately 300 cm3).

Patients were dosed with Jakafi or matching placebo. The primary efficacy endpoint was the proportion of patients achieving greater than or equal to a 35% reduction from baseline in spleen volume at Week 24 as measured by MRI or CT.

Secondary endpoints included duration of a 35% or greater reduction in spleen volume and proportion of patients with a 50% or greater reduction in Total Symptom Score from baseline to Week 24 as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 diary.

Study 2

Study 2 (NCT00934544) was an open-label, randomized study in 219 patients. Patients were randomized 2:1 to Jakafi versus best available therapy. Best available therapy was selected by the investigator on a patient-by-patient basis. In the best available therapy arm, the medications received by more than 10% of patients were hydroxyurea (47%) and glucocorticoids (16%). The median age was 66 years (range 35 to 85 years) with 52% of patients older than 65 years and 57% were male. Fifty-three percent (53%) of patients had primary MF, 31% had post-polycythemia vera MF and 16% had post-essential thrombocythemia MF. Twenty-one percent (21%) of patients had red blood cell transfusions within 8 weeks of enrollment in the study. The median hemoglobin count was 10.4 g/dL and the median platelet count was 236 x 109/L. Patients had a median palpable spleen length of 15 cm below the costal margin, with 70% having a spleen length 10 cm or greater below the costal margin. Patients had a median spleen volume as measured by MRI or CT of 2381 cm3 (range 451 cm3 to 7765 cm3).

The primary efficacy endpoint was the proportion of patients achieving 35% or greater reduction from baseline in spleen volume at Week 48 as measured by MRI or CT.

A secondary endpoint in Study 2 was the proportion of patients achieving a 35% or greater reduction of spleen volume as measured by MRI or CT from baseline to Week 24.

Study 1 and 2 Efficacy Results

Efficacy analyses of the primary endpoint in Studies 1 and 2 are presented in Table 20 below. A significantly larger proportion of patients in the Jakafi group achieved a 35% or greater reduction in spleen volume from baseline in both studies compared to placebo in Study 1 and best available therapy in Study 2. A similar proportion of patients in the Jakafi group achieved a 50% or greater reduction in palpable spleen length.

<div class="scrollingtable"><table> <caption> <span>Table 20: Percent of Patients with Myelofibrosis Achieving 35% or Greater Reduction from Baseline in Spleen Volume at Week 24 in Study 1 and at Week 48 in Study 2 (Intent to Treat)</span> </caption> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule">  </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> <span class="Bold">Study 1</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> <span class="Bold">Study 2</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">  </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <span class="Bold">Jakafi<br/>(N=155)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <span class="Bold">Placebo<br/>(N=154)</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <span class="Bold">Jakafi<br/>(N=146)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">Best Available<br/>Therapy<br/>(N=73)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Time Points</td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> Week 24</td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> Week 48</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Number (%) of Patients with <br/>Spleen Volume Reduction by <br/>35% or More</td><td align="center" class="Botrule Lrule Rrule Toprule">      65 (42)     </td><td align="center" class="Botrule Lrule Rrule Toprule">      1 (&lt; 1)     </td><td align="center" class="Botrule Lrule Rrule Toprule">      41 (29)     </td><td align="center" class="Botrule Lrule Rrule Toprule">      0     </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">P-value</td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> &lt; 0.0001</td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> &lt; 0.0001</td> </tr> </tbody> </table></div>

Figure 1 shows the percent change from baseline in spleen volume for each patient at Week 24 (Jakafi N=139, placebo N=106) or the last evaluation prior to Week 24 for patients who did not complete 24 weeks of randomized treatment (Jakafi N=16, placebo N=47). One (1) patient (placebo) with a missing baseline spleen volume is not included.

In Study 1, MF symptoms were a secondary endpoint and were measured using the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 diary. The modified MFSAF is a daily diary capturing the core symptoms of MF (abdominal discomfort, pain under left ribs, night sweats, itching, bone/muscle pain and early satiety). Symptom scores ranged from 0 to 10 with 0 representing symptoms "absent" and 10 representing "worst imaginable" symptoms. These scores were added to create the daily total score, which has a maximum of 60.

Table 21 presents assessments of Total Symptom Score from baseline to Week 24 in Study 1 including the proportion of patients with at least a 50% reduction (ie, improvement in symptoms). At baseline, the mean Total Symptom Score was 18.0 in the Jakafi group and 16.5 in the placebo group. A higher proportion of patients in the Jakafi group had a 50% or greater reduction in Total Symptom Score than in the placebo group, with a median time to response of less than 4 weeks.

<div class="scrollingtable"><table width="600px"> <caption> <span>Table 21: Improvement in Total Symptom Score in Patients with Myelofibrosis</span> </caption> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule">  </td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">Jakafi <br/>(N=148)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> <span class="Bold">Placebo <br/>(N=152)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Number (%) of Patients with 50% or Greater Reduction <br/>in Total Symptom Score by Week 24</td><td align="center" class="Botrule Lrule Rrule Toprule">        68 (46)       </td><td align="center" class="Botrule Lrule Rrule Toprule">        8 (5)       </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">P-value</td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> &lt; 0.0001</td> </tr> </tbody> </table></div>

Figure 2 shows the percent change from baseline in Total Symptom Score for each patient at Week 24 (Jakafi N=129, placebo N=103) or the last evaluation on randomized therapy prior to Week 24 for patients who did not complete 24 weeks of randomized treatment (Jakafi N=16, placebo N=42). Results are excluded for 5 patients with a baseline Total Symptom Score of zero, 8 patients with missing baseline and 6 patients with insufficient post-baseline data.

Figure 3 displays the proportion of patients with at least a 50% improvement in each of the individual symptoms that comprise the Total Symptom Score indicating that all 6 of the symptoms contributed to the higher Total Symptom Score response rate in the group treated with Jakafi.

An exploratory analysis of patients receiving Jakafi also showed improvement in fatigue-related symptoms (i.e., tiredness, exhaustion, mental tiredness, and lack of energy) and associated impacts on daily activities (i.e., activity limitations related to work, self-care, and exercise) as measured by the PROMIS® Fatigue 7-item short form total score at Week 24. Patients who achieved a reduction of 4.5 points or more from baseline to Week 24 in the PROMIS® Fatigue total score were considered to have achieved a fatigue response. Fatigue response was reported in 35% of patients in the Jakafi group versus 14% of the patients in the placebo group.

Overall survival was a secondary endpoint in both Study 1 and Study 2. Patients in the control groups were eligible for crossover in both studies, and the median times to crossover were 9 months in Study 1 and 17 months in Study 2.

Figure 4 and Figure 5 show Kaplan-Meier curves of overall survival at prospectively planned analyses after all patients remaining on study had completed 144 weeks on study.

Study 3 (NCT01243944) was a randomized, open-label, active-controlled Phase 3 study conducted in 222 patients with PV. Patients had been diagnosed with PV for at least 24 weeks, had an inadequate response to or were intolerant of hydroxyurea, required phlebotomy and exhibited splenomegaly. All patients were required to demonstrate hematocrit control between 40-45% prior to randomization. The age ranged from 33 to 90 years with 30% of patients over 65 years of age and 66% were male. Patients had a median spleen volume as measured by MRI or CT of 1272 cm3 (range 254 cm3 to 5147 cm3) and median palpable spleen length below the costal margin was 7 cm.

Patients were randomized to Jakafi or best available therapy. The starting dose of Jakafi was 10 mg twice daily. Doses were then individualized based upon tolerability and efficacy with a maximum dose of 25 mg twice daily. At Week 32, 98 patients were still on Jakafi with 8% receiving greater than 20 mg twice daily, 15% receiving 20 mg twice daily, 33% receiving 15 mg twice daily, 34% receiving 10 mg twice daily, and 10% receiving less than 10 mg twice daily. Best available therapy (BAT) was selected by the investigator on a patient-by-patient basis and included hydroxyurea (60%), interferon/pegylated interferon (12%), anagrelide (7%), pipobroman (2%), lenalidomide/thalidomide (5%), and observation (15%).

The primary endpoint was the proportion of subjects achieving a response at Week 32, with response defined as having achieved both hematocrit control (the absence of phlebotomy eligibility beginning at the Week 8 visit and continuing through Week 32) and spleen volume reduction (a greater than or equal to 35% reduction from baseline in spleen volume at Week 32). Phlebotomy eligibility was defined as a confirmed hematocrit greater than 45% that is at least 3 percentage points higher than the hematocrit obtained at baseline or a confirmed hematocrit greater than 48%, whichever was lower. Secondary endpoints included the proportion of all randomized subjects who achieved the primary endpoint and who maintained their response 48 weeks after randomization, and the proportion of subjects achieving complete hematological remission at Week 32 with complete hematological remission defined as achieving hematocrit control, platelet count less than or equal to 400 x 109/L, and white blood cell count less than or equal to 10 x 109/L.

Results of the primary and secondary endpoints are presented in Table 22. A significantly larger proportion of patients on the Jakafi arm achieved a response for the primary endpoint compared to best available therapy at Week 32 and maintained their response 48 weeks after randomization. A significantly larger proportion of patients on the Jakafi arm compared to best available therapy also achieved complete hematological remission at Week 32.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 22: Percent of Patients with Polycythemia Vera Achieving the Primary and Key Secondary Endpoints in Study 3 (Intent to Treat)</span> </caption> <col width="40%"/> <col width="30%"/> <col width="30%"/> <tfoot> <tr class="First Last"> <td colspan="3">Primary Response defined as having achieved both the absence of phlebotomy eligibility beginning at the Week 8 visit and continuing through Week 32 and a greater than or equal to 35% reduction from baseline in spleen volume at Week 32.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> </td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold"> Jakafi<br/>(N=110)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold"> Best Available<br/>Therapy<br/>(N=112)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Number (%) of Patients Achieving a Primary Response at Week 32 </td><td align="center" class="Botrule Lrule Rrule Toprule"> 25 (23%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 1 (&lt; 1%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">95% CI of the response rate (%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> (15%, 32%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> (0%, 5%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">P-value</td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> &lt; 0.0001</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Number (%) of Patients Achieving a Durable Primary Response at Week 48</td><td align="center" class="Botrule Lrule Rrule Toprule"> 22 (20%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 1 (&lt; 1%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">95% CI of the response rate (%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> (13%, 29%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> (0%, 5%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">P-value</td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> &lt; 0.0001</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Number (%) of Patients Achieving Complete Hematological Remission at Week 32</td><td align="center" class="Botrule Lrule Rrule Toprule"> 26 (24%)</td><td align="center" class="Botrule Lrule Rrule Toprule">9 (8%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">95% CI of the response rate (%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> (16%, 33%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> (4%, 15%)</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">P-value</td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> 0.0016</td> </tr> </tbody> </table></div>

Additional analyses for Study 3 to assess durability of response were conducted at Week 80 only in the Jakafi arm. On this arm, 91 (83%) patients were still on treatment at the time of the Week 80 data cut-off. Of the 25 patients who achieved a primary response at Week 32, 19 (76% of the responders) maintained their response through Week 80, and of the 26 patients who achieved complete hematological remission at Week 32, 15 (58% of the responders) maintained their response through Week 80. 

In an assessment of the individual components that make up the primary endpoint, there were 66 (60%) patients with hematocrit control on the Jakafi arm vs. 21 (19%) patients on best available therapy at Week 32; 51 (77% of hematocrit responders) patients on the Jakafi arm maintained hematocrit control through Week 80. There were 44 (40%) patients with spleen volume reduction from baseline greater than or equal to 35% on the Jakafi arm vs. 1 (< 1%) patient on best available therapy at Week 32; 43 (98% of spleen volume reduction responders) patients on the Jakafi arm maintained spleen volume reduction through Week 80.

Study 4 (NCT02953678) was an open-label, single-arm, multicenter study of Jakafi for treatment of patients with steroid-refractory aGVHD Grades 2 to 4 (Mount Sinai Acute GVHD International Consortium (MAGIC) criteria) occurring after allogeneic hematopoietic stem cell transplantation. Jakafi was administered at 5 mg twice daily, and the dose could be increased to 10 mg twice daily after 3 days in the absence of toxicity. 

There were 49 patients with aGVHD refractory to steroids alone. These patients had a median age of 57 years (range, 18-72 years), 47% were male, 92% were Caucasian, and 14% were Hispanic. At baseline, aGVHD was Grade 2 in 27%, Grade 3 in 55%, and Grade 4 in 18%; 84% had visceral GVHD; the median MAGIC biomarker score was 0.47 (range, 0.10‑0.92); and the median ST2 level was 334 mcg/L (range, 55-1286 mcg/L). The median duration of prior corticosteroid exposure at baseline was 15 days (range: 3 - 106 days). 

The efficacy of Jakafi was based on Day-28 overall response rate (ORR) (complete response, very good partial response or partial response by Center for International Blood and Marrow Transplant Research (CIBMTR) criteria) and the duration of response. The ORR results are presented in Table 23; Day-28 ORR was 100% for Grade 2 GVHD, 40.7% for Grade 3 GVHD, and 44.4% for Grade 4 GVHD.

The median duration of response, calculated from Day-28 response to progression, new salvage therapy for aGVHD or death from any cause (with progression being defined as worsening by one stage in any organ without improvement in other organs in comparison to prior response assessment) was 16 days (95% CI 9, 83). Also, for the Day-28 responders, the median time from Day-28 response to either death or need for new therapy for aGVHD (additional salvage therapy or increase in steroids) was 173 days (95% CI 66, NE).

<div class="scrollingtable"><table width="55%"> <caption> <span>Table 23: Day-28 Overall Response Rate for Patients with Steroid-Refractory Acute GVHD in Study 4</span> </caption> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> </td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Refractory to Steroids Alone<br/>(n=49)</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Overall Response (%) (95% CI)</span></td><td align="center" class="Botrule Lrule Rrule Toprule">28 (57.1%) (42.2, 71.2)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Complete Response</span></td><td align="center" class="Botrule Lrule Rrule Toprule">15 (30.6%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Very Good Partial Response</span></td><td align="center" class="Botrule Lrule Rrule Toprule">2 (4.1%)</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Partial Response</span></td><td align="center" class="Botrule Lrule Rrule Toprule">11 (22.4%)</td> </tr> </tbody> </table></div>

Study 5 (REACH-3; NCT03112603) was a randomized, open-label, multicenter study of Jakafi in comparison to best available therapy (BAT) for treatment of corticosteroid-refractory cGVHD after allogeneic stem cell transplantation. Eligible patients were ≥ 12 years old with moderate or severe cGVHD as defined by NIH Consensus Criteria requiring additional therapy after failure of corticosteroid therapy and no more than one additional salvage treatment. Patients were excluded if they had ANC < 1 Gi/L and platelet count < 25 Gi/L, estimated creatinine clearance < 30 ml/min, progressive onset cGVHD, oxygen saturation < 90%, total bilirubin > 2 mg/dL, or diarrhea due to GVHD.

A total of 329 patients were randomized 1:1 to receive either Jakafi 10 mg twice daily (n=165) or BAT (n=164). BAT was selected by the investigator prior to randomization and included the following treatments: extracorporeal photopheresis (ECP), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, or ibrutinib. Randomization was stratified by cGVHD severity (moderate versus severe). On Cycle 7 Day 1 and thereafter, patients randomized to BAT could cross over to Jakafi if they had disease progression, mixed response, unchanged response, cGVHD flare, or toxicity to BAT. All patients also received standard supportive care, including anti-infective medications. GVHD prophylaxis and cGVHD treatment medications initiated before randomization, including systemic corticosteroids, calcineurin inhibitors, and topical or inhaled corticosteroid therapy, were allowed to be continued per institutional guidelines. Table 24 shows the demographics and baseline disease characteristics of the randomized population.

<div class="scrollingtable"><table> <caption> <span>Table 24: REACH-3: Demographics and Baseline Chronic GVHD Characteristics</span> </caption> <col/> <col/> <col/> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-26" name="footnote-26">*</a> </dt> <dd>Prednisone equivalent milligrams/kilogram</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">       Jakafi       <br/> </span><span class="Bold">(N=165)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">    Best Available Therapy    <br/> </span><span class="Bold">(N=164)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Median Age, Years (range)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 49 (13, 73)</td><td align="center" class="Botrule Lrule Rrule Toprule">50 (12, 76)<br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">      Age 12 to &lt; 18 Year, n (%)<br/> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> 4 (2)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 8 (5)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">      Age &gt; 65 Years, n (%)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> 18 (11)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 22 (13)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Male, n (%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 109 (66)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 92 (56)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Race, n (%)</td><td class="Botrule Lrule Rrule Toprule"> </td><td class="Botrule Lrule Rrule Toprule"> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">      White</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> 116 (70)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 132 (81)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">      Black</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> 2 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">      Asian</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> 33 (20)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 21 (13)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">      American Indian or Alaska native</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> 2 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">      Other</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> 9 (6)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 4 (2)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">      Unknown</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> 3 (2)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 7 (4)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Median (range) time (days) from cGVHD diagnosis to randomization       </td><td align="center" class="Botrule Lrule Rrule Toprule"> 174 (7-2017)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 150 (10-1947)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Prior Therapy</td><td class="Botrule Lrule Rrule Toprule"> </td><td class="Botrule Lrule Rrule Toprule"> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">      No prior treatment for cGVHD</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> 2 (1)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 1 (1)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">      Failed first-line steroids alone</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> 115 (70)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 125 (76)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">      Failed first-line combination including steroids</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> 42 (25)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 30 (18)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">      Failed two lines of therapy</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> 6 (4)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 8 (5)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> ≥ 4 Organs involved, n (%) </td><td align="center" class="Botrule Lrule Rrule Toprule"> 67 (41)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 63 (38)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Severe cGVHD, n (%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 86 (52)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 79 (48)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> Median (range) cGVHD Total Symptom Score</td><td align="center" class="Botrule Lrule Rrule Toprule"> 19 (0-80)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 18 (1-54)</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> Median (range) corticosteroid dose at baseline (PE mg/kg)<a class="Sup" href="#footnote-26" name="footnote-reference-26">*</a> </td><td align="center" class="Botrule Lrule Rrule Toprule">   0.29 (0.01-1.81)   </td><td align="center" class="Botrule Lrule Rrule Toprule">   0.26 (0.06-1.21)</td> </tr> </tbody> </table></div>

The efficacy of Jakafi was based on overall response rate (ORR) through Cycle 7 Day 1, where overall response included complete response or partial response according to the 2014 NIH Response Criteria and durability of the response. The ORR results are presented in Table 25; the difference in ORR between Jakafi and BAT arms was 13% (95% CI 3%, 23%). The median time to first response in the responders was 3 weeks (range, 2 to 24) for the Jakafi arm and 4 weeks (range, 2 to 25) for the BAT arm. The median duration of response, calculated from first response to progression, death, or new systemic therapies for cGVHD, was 4.2 months (95% CI 3.2, 6.7) for the Jakafi arm and 2.1 months (95% CI 1.6, 3.2) for the BAT arm; and the median time from first response to death or new systemic therapies for cGVHD was 25 months (95% CI 16.8, NE) for the Jakafi arm and 5.6 months (95% CI 4.1, 7.8) for the BAT arm.

<div class="scrollingtable"><table> <caption> <span>Table 25: Overall Response Rate through Cycle 7 Day 1 for Patients with Chronic GVHD in Study 5</span> </caption> <col/> <col/> <col/> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-27" name="footnote-27">*</a> </dt> <dd>95% CI of Overall Response Rate is estimated using Clopper-Pearson method.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule"> </td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold"> Jakafi<br/> (N=165)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Best Available Therapy<br/> (N=164) </span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Overall Response (%) </span> <br/> <span class="Bold">(95% CI)<a class="Sup" href="#footnote-27" name="footnote-reference-27">*</a> </span></td><td class="Botrule Lrule Rrule Toprule">      116 (70%)<br/>     (63%, 77%)     </td><td align="center" class="Botrule Lrule Rrule Toprule"> 94 (57%)<br/> (49%, 65%)</td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">      <span class="Bold">Complete Response (%)       </span></td><td align="center" class="Botrule Lrule Rrule Toprule"> 14 (8%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 8 (5%)</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">      Partial Response (%)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> 102 (62%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> 86 (52%)</td> </tr> </tbody> </table></div>

ORR results were supported by exploratory analyses of patient-reported symptom severity which showed at least a 7-point decrease in the cGVHD Total Symptom Score at any time through Cycle 7 Day 1 in 66 (40%; 95% CI 32, 48) patients in the Jakafi arm and 47 (29%; 95% CI 22, 36) patients in the BAT arm.

Jakafi (ruxolitinib) Tablets are available as follows:

{ "type": "p", "children": [], "text": "Jakafi (ruxolitinib) Tablets are available as follows:" }

<div class="scrollingtable"><table width="650px"> <caption> <span>Jakafi Trade Presentations</span> </caption> <col width="120px"/> <col width="85px"/> <col width="250px"/> <col width="120px"/> <tfoot> <tr class="First Last"> <td colspan="4">Store at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">NDC Number</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Strength</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Description </span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Tablets per<br/>Bottle</span> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">50881-005-60</td><td class="Botrule Lrule Rrule Toprule">5 mg</td><td class="Botrule Lrule Rrule Toprule">Round tablet with “INCY” on one side and “5” on the other </td><td align="center" class="Botrule Lrule Rrule Toprule">60 </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">50881-010-60</td><td class="Botrule Lrule Rrule Toprule">10 mg</td><td class="Botrule Lrule Rrule Toprule">Round tablet with “INCY” on one side and “10” on the other</td><td align="center" class="Botrule Lrule Rrule Toprule">60 </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">50881-015-60</td><td class="Botrule Lrule Rrule Toprule">15 mg</td><td class="Botrule Lrule Rrule Toprule">Oval tablet with “INCY” on one side and “15” on the other</td><td align="center" class="Botrule Lrule Rrule Toprule">60 </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">50881-020-60</td><td class="Botrule Lrule Rrule Toprule">20 mg</td><td class="Botrule Lrule Rrule Toprule">Capsule-shaped tablet with “INCY” on one side and “20” on the other</td><td align="center" class="Botrule Lrule Rrule Toprule">60 </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">50881-025-60</td><td class="Botrule Lrule Rrule Toprule">25 mg</td><td class="Botrule Lrule Rrule Toprule">Oval tablet with “INCY” on one side and “25” on the other</td><td align="center" class="Botrule Lrule Rrule Toprule">60 </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"650px\">\n<caption>\n<span>Jakafi Trade Presentations</span>\n</caption>\n<col width=\"120px\"/>\n<col width=\"85px\"/>\n<col width=\"250px\"/>\n<col width=\"120px\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td colspan=\"4\">Store at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">NDC Number</span></td><td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Strength</span></td><td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Description </span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Tablets per<br/>Bottle</span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">50881-005-60</td><td class=\"Botrule Lrule Rrule Toprule\">5 mg</td><td class=\"Botrule Lrule Rrule Toprule\">Round tablet with “INCY” on one side and “5” on the other </td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">60 </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">50881-010-60</td><td class=\"Botrule Lrule Rrule Toprule\">10 mg</td><td class=\"Botrule Lrule Rrule Toprule\">Round tablet with “INCY” on one side and “10” on the other</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">60 </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">50881-015-60</td><td class=\"Botrule Lrule Rrule Toprule\">15 mg</td><td class=\"Botrule Lrule Rrule Toprule\">Oval tablet with “INCY” on one side and “15” on the other</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">60 </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">50881-020-60</td><td class=\"Botrule Lrule Rrule Toprule\">20 mg</td><td class=\"Botrule Lrule Rrule Toprule\">Capsule-shaped tablet with “INCY” on one side and “20” on the other</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">60 </td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">50881-025-60</td><td class=\"Botrule Lrule Rrule Toprule\">25 mg</td><td class=\"Botrule Lrule Rrule Toprule\">Oval tablet with “INCY” on one side and “25” on the other</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">60 </td>\n</tr>\n</tbody>\n</table></div>" }

Advise the patient to read the FDA-approved patient labeling (Patient Information).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Patient Information)." }

Thrombocytopenia, Anemia and Neutropenia

{ "type": "p", "children": [], "text": "\nThrombocytopenia, Anemia and Neutropenia\n" }

Inform patients that Jakafi is associated with thrombocytopenia, anemia and neutropenia, and of the need to monitor complete blood counts before and during treatment. Advise patients to observe for and report bleeding [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Inform patients that Jakafi is associated with thrombocytopenia, anemia and neutropenia, and of the need to monitor complete blood counts before and during treatment. Advise patients to observe for and report bleeding [see Warnings and Precautions (5.1)]." }

Infections

{ "type": "p", "children": [], "text": "\nInfections\n" }

Inform patients of the signs and symptoms of infection and to report any such signs and symptoms promptly.

{ "type": "p", "children": [], "text": "Inform patients of the signs and symptoms of infection and to report any such signs and symptoms promptly." }

Inform patients regarding the early signs and symptoms of herpes zoster and of progressive multifocal leukoencephalopathy, and advise patients to seek advice of a clinician if such symptoms are observed [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Inform patients regarding the early signs and symptoms of herpes zoster and of progressive multifocal leukoencephalopathy, and advise patients to seek advice of a clinician if such symptoms are observed [see Warnings and Precautions (5.2)]." }

Symptom Exacerbation Following Interruption or Discontinuation of Treatment with Jakafi

{ "type": "p", "children": [], "text": "\nSymptom Exacerbation Following Interruption or Discontinuation of Treatment with Jakafi\n" }

Inform patients that after discontinuation of treatment, signs and symptoms from myeloproliferative neoplasms are expected to return. Instruct patients not to interrupt or discontinue Jakafi therapy without consulting their physician [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Inform patients that after discontinuation of treatment, signs and symptoms from myeloproliferative neoplasms are expected to return. Instruct patients not to interrupt or discontinue Jakafi therapy without consulting their physician [see Warnings and Precautions (5.3)]. " }

Non-Melanoma Skin Cancer

{ "type": "p", "children": [], "text": "\nNon-Melanoma Skin Cancer\n" }

Inform patients that Jakafi may increase their risk of certain non-melanoma skin cancers. Advise patients to inform their healthcare provider if they have ever had any type of skin cancer or if they observe any new or changing skin lesions [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "Inform patients that Jakafi may increase their risk of certain non-melanoma skin cancers. Advise patients to inform their healthcare provider if they have ever had any type of skin cancer or if they observe any new or changing skin lesions [see Warnings and Precautions (5.4)]." }

Lipid Elevations

{ "type": "p", "children": [], "text": "\nLipid Elevations\n" }

Inform patients that Jakafi may increase blood cholesterol, and of the need to monitor blood cholesterol levels [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "Inform patients that Jakafi may increase blood cholesterol, and of the need to monitor blood cholesterol levels [see Warnings and Precautions (5.5)]." }

Major Adverse Cardiovascular Events (MACE)

{ "type": "p", "children": [], "text": "\nMajor Adverse Cardiovascular Events (MACE)\n" }

Advise patients that events of major adverse cardiovascular events (MACE) including myocardial infarction, stroke, and cardiovascular death, have been reported in clinical studies with another JAK-inhibitor used to treat rheumatoid arthritis, a condition for which Jakafi is not indicated. Advise patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions (5.6)].

{ "type": "p", "children": [], "text": "Advise patients that events of major adverse cardiovascular events (MACE) including myocardial infarction, stroke, and cardiovascular death, have been reported in clinical studies with another JAK-inhibitor used to treat rheumatoid arthritis, a condition for which Jakafi is not indicated. Advise patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions (5.6)]." }

Thrombosis

{ "type": "p", "children": [], "text": "\nThrombosis \n" }

Advise patients that events of DVT and PE have been reported in clinical studies with another JAK-inhibitor used to treat rheumatoid arthritis, a condition for which Jakafi is not indicated. Advise patients to tell their healthcare provider if they develop any signs or symptoms of a DVT or PE [see Warnings and Precautions (5.7)].

{ "type": "p", "children": [], "text": "Advise patients that events of DVT and PE have been reported in clinical studies with another JAK-inhibitor used to treat rheumatoid arthritis, a condition for which Jakafi is not indicated. Advise patients to tell their healthcare provider if they develop any signs or symptoms of a DVT or PE [see Warnings and Precautions (5.7)]." }

Secondary Malignancies

{ "type": "p", "children": [], "text": "\nSecondary Malignancies\n" }

Advise patients, especially current or past smokers and patients with a known secondary malignancy (other than a successfully treated NMSC), that lymphoma and other malignancies (excluding NMSC) have been reported in clinical studies with another JAK-inhibitor used to treat rheumatoid arthritis, a condition for which Jakafi is not indicated [see Warnings and Precautions (5.8)].

{ "type": "p", "children": [], "text": " Advise patients, especially current or past smokers and patients with a known secondary malignancy (other than a successfully treated NMSC), that lymphoma and other malignancies (excluding NMSC) have been reported in clinical studies with another JAK-inhibitor used to treat rheumatoid arthritis, a condition for which Jakafi is not indicated [see Warnings and Precautions (5.8)]." }

Drug-Drug Interactions

{ "type": "p", "children": [], "text": "\nDrug-Drug Interactions\n" }

Advise patients to inform their healthcare providers of all medications they are taking, including over-the-counter medications, herbal products and dietary supplements [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

{ "type": "p", "children": [], "text": "Advise patients to inform their healthcare providers of all medications they are taking, including over-the-counter medications, herbal products and dietary supplements [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]." }

Dialysis

{ "type": "p", "children": [], "text": "\nDialysis\n" }

Inform patients on dialysis that their dose should not be taken before dialysis but only following dialysis [see Dosage and Administration (2.7)].

{ "type": "p", "children": [], "text": "Inform patients on dialysis that their dose should not be taken before dialysis but only following dialysis [see Dosage and Administration (2.7)]." }

Lactation

{ "type": "p", "children": [], "text": "\nLactation\n" }

Inform women not to breastfeed during treatment with Jakafi and for two weeks after the final dose [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": " Inform women not to breastfeed during treatment with Jakafi and for two weeks after the final dose [see Use in Specific Populations (8.2)].\n" }

Compliance

{ "type": "p", "children": [], "text": "\nCompliance\n" }

Advise patients to continue taking Jakafi every day for as long as their physician tells them and that this is a long-term treatment. Patients should not change dose or stop taking Jakafi without first consulting their physician. Patients should be aware that after discontinuation of treatment, signs and symptoms from myeloproliferative neoplasms are expected to return.

{ "type": "p", "children": [], "text": "Advise patients to continue taking Jakafi every day for as long as their physician tells them and that this is a long-term treatment. Patients should not change dose or stop taking Jakafi without first consulting their physician. Patients should be aware that after discontinuation of treatment, signs and symptoms from myeloproliferative neoplasms are expected to return. " }

Manufactured for: Incyte Corporation1801 Augustine Cut-offWilmington, DE 19803      

{ "type": "p", "children": [], "text": "Manufactured for:\n\t\t\t\t\t\t\tIncyte Corporation1801 Augustine Cut-offWilmington, DE 19803\n     \t" }

Jakafi is a registered trademark of Incyte. All rights reserved.U.S. Patent Nos. 7598257; 8415362; 8722693; 8822481; 8829013; 9079912; 9814722; 10016429© 2011-2023 Incyte Corporation. All rights reserved.

{ "type": "p", "children": [], "text": "Jakafi is a registered trademark of Incyte. All rights reserved.U.S. Patent Nos. 7598257; 8415362; 8722693; 8822481; 8829013; 9079912; 9814722; 10016429© 2011-2023 Incyte Corporation. All rights reserved." }

<div class="scrollingtable"><table width="100%"> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Patient Information<br/>JAKAFI<span class="Sup">®</span> (JAK-ah-fye)</span> <br/>(ruxolitinib)<br/> <span class="Bold">tablets<br/> </span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">What is Jakafi?</span> </p> <p>Jakafi is a prescription medicine used to treat: </p> <ul class="Disk"> <li>adults with certain types of myelofibrosis (MF).</li> <li>adults with polycythemia vera (PV) who have already taken a medicine called hydroxyurea and it did not work well enough or they could not tolerate it.</li> <li>adults and children 12 years of age and older with acute graft-versus-host-disease (aGVHD) who have taken corticosteroids and they did not work well enough.</li> <li>adults and children 12 years of age and older with chronic graft-versus-host-disease (cGVHD) who have taken one or two types of treatments and they did not work well enough.</li> </ul> <p>It is not known if Jakafi is safe or effective in children for treatment of myelofibrosis or polycythemia vera.   </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Before taking Jakafi, tell your healthcare provider about of your medical conditions, including if you:</span> </p> <ul class="Disk"> <li>have an infection</li> <li>have or have had low white or red blood cell counts</li> <li>have or had tuberculosis (TB), or have been in close contact with someone who has TB</li> <li>have had shingles (herpes zoster)</li> <li>have or had hepatitis B</li> <li>have or have had liver problems</li> <li>have or have had kidney problems or are on dialysis. If you are on dialysis, Jakafi should be taken after your dialysis.</li> <li>have a high level of fat in your blood (high blood cholesterol or triglycerides) </li> <li>have had cancer in the past</li> <li>are a current or past smoker</li> <li>have had a blood clot, heart attack, other heart problems or stroke</li> <li>are pregnant or plan to become pregnant. It is not known if Jakafi will harm your unborn baby. </li> <li>are breastfeeding or plan to breastfeed. It is not known if Jakafi passes into your breast milk. Do not breastfeed during treatment with Jakafi and for 2 weeks after the final dose.</li> </ul> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take</span>, including prescription and over-the-counter medicines, vitamins and herbal supplements. Taking Jakafi with certain other medicines may affect how Jakafi works. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.    </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">How should I take Jakafi?</span> <ul class="Disk"> <li>Take Jakafi exactly as your healthcare provider tells you.</li> <li>Do not change your dose or stop taking Jakafi without first talking to your healthcare provider.</li> <li>You can take Jakafi with or without food.</li> <li>Jakafi may also be given through certain nasogastric tubes. <ul class="Circle"> <li>Tell your healthcare provider if you cannot take Jakafi by mouth. Your healthcare provider will decide if you can take Jakafi through a nasogastric tube.</li> <li>Ask your healthcare provider to give you specific instruction on how to properly take Jakafi through a nasogastric tube.</li> </ul> </li> <li>If you miss a dose of Jakafi, take your next dose at your regular time. Do not take 2 doses at the same time.</li> <li>If you take too much Jakafi call your healthcare provider or go to the nearest hospital emergency room right away. </li> <li>You will have regular blood tests during your treatment with Jakafi. Your healthcare provider may change your dose of Jakafi or stop your treatment based on the results of your blood tests.        </li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2"> <p class="First"> <span class="Bold">What are the possible side effects of Jakafi?<br/> <br/> </span><span class="Bold">Jakafi can cause serious side effects including:<br/> <br/> </span><span class="Bold">Low blood cell counts.</span> Jakafi may cause low platelet counts (thrombocytopenia), low red blood cell counts (anemia), and low white blood cell counts (neutropenia). If you develop bleeding, stop Jakafi and call your healthcare provider. Your healthcare provider will do a blood test to check your blood cell counts before you start Jakafi and regularly during your treatment with Jakafi. Tell your healthcare provider right away if you develop or have worsening of any of these symptoms:</p> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li>unusual bleeding</li> <li>bruising</li> <li>tiredness</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li>shortness of breath</li> <li>fever</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2"> <p class="First"> <span class="Bold">Infection.</span> You may be at risk for developing a serious infection during treatment with Jakafi. Tell your healthcare provider if you develop any of the following symptoms of infection:</p> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li>chills</li> <li>aches</li> <li>fever</li> <li>nausea</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li>vomiting</li> <li>weakness</li> <li>painful skin rash or blisters</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2"> <p class="First"> <span class="Bold">Cancer.</span> Some people have had certain types of non-melanoma skin cancers during treatment with Jakafi. Your healthcare provider will regularly check your skin during your treatment with Jakafi. Tell your healthcare provider if you develop any new or changing skin lesions during treatment with Jakafi<span class="Bold">.</span> </p> <p> <span class="Bold"> </span> </p> <p> <span class="Bold">Cholesterol increases.</span> You may have changes in your blood cholesterol levels during treatment with Jakafi. Your healthcare provider will do blood tests to check your cholesterol levels about every 8 to 12 weeks after you start taking Jakafi, and as needed.</p> <p> <span class="Bold"> </span> </p> <p> <span class="Bold">Increased risk of major cardiovascular events such as heart attack, stroke or death in people who have cardiovascular risk factors and who are current or past smokers while using another JAK inhibitor to treat rheumatoid arthritis.</span> </p> <p> <span class="Bold"> </span> </p> <p> <span class="Bold">  </span>Get emergency help right away if you have any symptoms of a heart attack or stroke while taking Jakafi, including:</p> <ul class="Disk"> <li>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</li> <li>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</li> <li>pain or discomfort in your arms, back, neck, jaw, or stomach</li> <li>shortness of breath with or without chest discomfort</li> <li>breaking out in a cold sweat</li> <li>nausea or vomiting</li> <li>feeling lightheaded</li> <li>weakness in one part or on one side of your body</li> <li>slurred speech</li> </ul> <p> <span class="Bold">Increased risk of blood clots. </span>Blood clots in the veins of your legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) have happened in people taking another JAK inhibitor for rheumatoid arthritis and may be life-threatening.<br/> <br/> </p> <ul class="Disk"> <li>Tell your healthcare provider right away if you have any signs and symptoms of blood clots during treatment with Jakafi, including:<br/> º  swelling, pain or tenderness in one or both legs<br/> º  sudden, unexplained chest or upper back pain<br/> º  shortness of breath or difficulty breathing</li> </ul> <p> <br/> <span class="Bold">Possible increased risk of new (secondary) cancers.</span> People who take another JAK inhibitor for rheumatoid arthritis have an increased risk of new (secondary) cancers, including lymphoma and other cancers. People who smoke or who smoked in the past have an added risk of new cancers.<br/> </p> <br/> <p> <span class="Bold">The most common side effects of Jakafi in adults with certain types of MF and PV include:</span> </p> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li>low platelet counts</li> <li>low red blood cell counts</li> <li>bruising</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li>dizziness</li> <li>headache</li> <li>diarrhea</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2"> <p class="First"> <span class="Bold">The most common side effects of Jakafi in people with aGVHD include:<br/> </span> </p> </td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li>low red blood cell counts</li> <li>low platelet counts</li> <li>low white blood cell counts</li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li>infections</li> <li>swelling</li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="2"> <br/> <span class="Bold">The most common side effects of Jakafi in people with cGVHD include:<br/> </span></td> </tr> <tr> <td class="Lrule"> <ul class="Disk"> <li>low red blood cell counts</li> <li>low platelet counts </li> </ul> </td><td class="Rrule"> <ul class="Disk"> <li> infections, including viral infections</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2">These are not all of the possible side effects of Jakafi. <br/>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. <br/>You may also report side effects to Incyte Corporation at 1-855-463-3463.</td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2"> <p class="First"> <span class="Bold">How should I store Jakafi?</span> </p> <ul class="Disk"> <li>Store Jakafi at room temperature 68°F to 77°F (20°C to 25°C).</li> </ul> <p> <span class="Bold">Keep Jakafi and all medicines out of the reach of children.<br/>    </span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2"><span class="Bold">General information about the safe and effective use of Jakafi.<br/> <br/> </span>Medicines are sometimes prescribed for purposes other than those listed in Patient Information. Do not use Jakafi for a condition for which it is not prescribed. Do not give Jakafi to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information that is written for healthcare professionals.<br/>   </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" colspan="2"> <p class="First"> <span class="Bold">What are the ingredients in Jakafi?<br/> </span><span class="Bold"> <br/>Active ingredient</span>: ruxolitinib phosphate<br/> <br/> <span class="Bold">Inactive ingredients</span>: microcrystalline cellulose, lactose monohydrate, magnesium stearate, colloidal silicon dioxide, sodium starch glycolate, povidone and hydroxypropyl cellulose<br/> <br/>Manufactured for: Incyte Corporation, 1801 Augustine Cut-off, Wilmington, DE 19803<br/> <br/>Jakafi is a registered trademark of Incyte. All rights reserved.<br/>U.S. Patent Nos. 7598257; 8415362; 8722693; 8822481; 8829013; 9079912; 9814722; 10016429<br/> <br/>© 2011-2021 Incyte Corporation. All rights reserved.<br/>For more information call 1-855-463-3463 or go to <a href="http://www.jakafi.com">www.jakafi.com</a>.</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Patient Information<br/>JAKAFI<span class=\"Sup\">®</span> (JAK-ah-fye)</span>\n<br/>(ruxolitinib)<br/>\n<span class=\"Bold\">tablets<br/>\n</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">What is Jakafi?</span>\n</p>\n<p>Jakafi is a prescription medicine used to treat: </p>\n<ul class=\"Disk\">\n<li>adults with certain types of myelofibrosis (MF).</li>\n<li>adults with polycythemia vera (PV) who have already taken a medicine called hydroxyurea and it did not work well enough or they could not tolerate it.</li>\n<li>adults and children 12 years of age and older with acute graft-versus-host-disease (aGVHD) who have taken corticosteroids and they did not work well enough.</li>\n<li>adults and children 12 years of age and older with chronic graft-versus-host-disease (cGVHD) who have taken one or two types of treatments and they did not work well enough.</li>\n</ul>\n<p>It is not known if Jakafi is safe or effective in children for treatment of myelofibrosis or polycythemia vera.   </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Before taking Jakafi, tell your healthcare provider about of your medical conditions, including if you:</span>\n</p>\n<ul class=\"Disk\">\n<li>have an infection</li>\n<li>have or have had low white or red blood cell counts</li>\n<li>have or had tuberculosis (TB), or have been in close contact with someone who has TB</li>\n<li>have had shingles (herpes zoster)</li>\n<li>have or had hepatitis B</li>\n<li>have or have had liver problems</li>\n<li>have or have had kidney problems or are on dialysis. If you are on dialysis, Jakafi should be taken after your dialysis.</li>\n<li>have a high level of fat in your blood (high blood cholesterol or triglycerides) </li>\n<li>have had cancer in the past</li>\n<li>are a current or past smoker</li>\n<li>have had a blood clot, heart attack, other heart problems or stroke</li>\n<li>are pregnant or plan to become pregnant. It is not known if Jakafi will harm your unborn baby. </li>\n<li>are breastfeeding or plan to breastfeed. It is not known if Jakafi passes into your breast milk. Do not breastfeed during treatment with Jakafi and for 2 weeks after the final dose.</li>\n</ul>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take</span>, including prescription and over-the-counter medicines, vitamins and herbal supplements. Taking Jakafi with certain other medicines may affect how Jakafi works. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.    </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">How should I take Jakafi?</span>\n<ul class=\"Disk\">\n<li>Take Jakafi exactly as your healthcare provider tells you.</li>\n<li>Do not change your dose or stop taking Jakafi without first talking to your healthcare provider.</li>\n<li>You can take Jakafi with or without food.</li>\n<li>Jakafi may also be given through certain nasogastric tubes. <ul class=\"Circle\">\n<li>Tell your healthcare provider if you cannot take Jakafi by mouth. Your healthcare provider will decide if you can take Jakafi through a nasogastric tube.</li>\n<li>Ask your healthcare provider to give you specific instruction on how to properly take Jakafi through a nasogastric tube.</li>\n</ul>\n</li>\n<li>If you miss a dose of Jakafi, take your next dose at your regular time. Do not take 2 doses at the same time.</li>\n<li>If you take too much Jakafi call your healthcare provider or go to the nearest hospital emergency room right away. </li>\n<li>You will have regular blood tests during your treatment with Jakafi. Your healthcare provider may change your dose of Jakafi or stop your treatment based on the results of your blood tests.        </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of Jakafi?<br/>\n<br/>\n</span><span class=\"Bold\">Jakafi can cause serious side effects including:<br/>\n<br/>\n</span><span class=\"Bold\">Low blood cell counts.</span> Jakafi may cause low platelet counts (thrombocytopenia), low red blood cell counts (anemia), and low white blood cell counts (neutropenia). If you develop bleeding, stop Jakafi and call your healthcare provider. Your healthcare provider will do a blood test to check your blood cell counts before you start Jakafi and regularly during your treatment with Jakafi. Tell your healthcare provider right away if you develop or have worsening of any of these symptoms:</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li>unusual bleeding</li>\n<li>bruising</li>\n<li>tiredness</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li>shortness of breath</li>\n<li>fever</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Infection.</span> You may be at risk for developing a serious infection during treatment with Jakafi. Tell your healthcare provider if you develop any of the following symptoms of infection:</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li>chills</li>\n<li>aches</li>\n<li>fever</li>\n<li>nausea</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li>vomiting</li>\n<li>weakness</li>\n<li>painful skin rash or blisters</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Cancer.</span> Some people have had certain types of non-melanoma skin cancers during treatment with Jakafi. Your healthcare provider will regularly check your skin during your treatment with Jakafi. Tell your healthcare provider if you develop any new or changing skin lesions during treatment with Jakafi<span class=\"Bold\">.</span>\n</p>\n<p>\n<span class=\"Bold\"> </span>\n</p>\n<p>\n<span class=\"Bold\">Cholesterol increases.</span> You may have changes in your blood cholesterol levels during treatment with Jakafi. Your healthcare provider will do blood tests to check your cholesterol levels about every 8 to 12 weeks after you start taking Jakafi, and as needed.</p>\n<p>\n<span class=\"Bold\"> </span>\n</p>\n<p>\n<span class=\"Bold\">Increased risk of major cardiovascular events such as heart attack, stroke or death in people who have cardiovascular risk factors and who are current or past smokers while using another JAK inhibitor to treat rheumatoid arthritis.</span>\n</p>\n<p>\n<span class=\"Bold\"> </span>\n</p>\n<p>\n<span class=\"Bold\">  </span>Get emergency help right away if you have any symptoms of a heart attack or stroke while taking Jakafi, including:</p>\n<ul class=\"Disk\">\n<li>discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back</li>\n<li>severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw</li>\n<li>pain or discomfort in your arms, back, neck, jaw, or stomach</li>\n<li>shortness of breath with or without chest discomfort</li>\n<li>breaking out in a cold sweat</li>\n<li>nausea or vomiting</li>\n<li>feeling lightheaded</li>\n<li>weakness in one part or on one side of your body</li>\n<li>slurred speech</li>\n</ul>\n<p>\n<span class=\"Bold\">Increased risk of blood clots. </span>Blood clots in the veins of your legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) have happened in people taking another JAK inhibitor for rheumatoid arthritis and may be life-threatening.<br/>\n<br/>\n</p>\n<ul class=\"Disk\">\n<li>Tell your healthcare provider right away if you have any signs and symptoms of blood clots during treatment with Jakafi, including:<br/> º  swelling, pain or tenderness in one or both legs<br/> º  sudden, unexplained chest or upper back pain<br/> º  shortness of breath or difficulty breathing</li>\n</ul>\n<p>\n<br/>\n<span class=\"Bold\">Possible increased risk of new (secondary) cancers.</span> People who take another JAK inhibitor for rheumatoid arthritis have an increased risk of new (secondary) cancers, including lymphoma and other cancers. People who smoke or who smoked in the past have an added risk of new cancers.<br/>\n</p>\n<br/>\n<p>\n<span class=\"Bold\">The most common side effects of Jakafi in adults with certain types of MF and PV include:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li>low platelet counts</li>\n<li>low red blood cell counts</li>\n<li>bruising</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li>dizziness</li>\n<li>headache</li>\n<li>diarrhea</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">The most common side effects of Jakafi in people with aGVHD include:<br/>\n</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li>low red blood cell counts</li>\n<li>low platelet counts</li>\n<li>low white blood cell counts</li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li>infections</li>\n<li>swelling</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"2\"> <br/>\n<span class=\"Bold\">The most common side effects of Jakafi in people with cGVHD include:<br/>\n</span></td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul class=\"Disk\">\n<li>low red blood cell counts</li>\n<li>low platelet counts </li>\n</ul>\n</td><td class=\"Rrule\">\n<ul class=\"Disk\">\n<li> infections, including viral infections</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\">These are not all of the possible side effects of Jakafi. <br/>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. <br/>You may also report side effects to Incyte Corporation at 1-855-463-3463.</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store Jakafi?</span>\n</p>\n<ul class=\"Disk\">\n<li>Store Jakafi at room temperature 68°F to 77°F (20°C to 25°C).</li>\n</ul>\n<p>\n<span class=\"Bold\">Keep Jakafi and all medicines out of the reach of children.<br/>    </span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">General information about the safe and effective use of Jakafi.<br/>\n<br/>\n</span>Medicines are sometimes prescribed for purposes other than those listed in Patient Information. Do not use Jakafi for a condition for which it is not prescribed. Do not give Jakafi to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information that is written for healthcare professionals.<br/>   </td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in Jakafi?<br/>\n</span><span class=\"Bold\">\n<br/>Active ingredient</span>: ruxolitinib phosphate<br/>\n<br/>\n<span class=\"Bold\">Inactive ingredients</span>: microcrystalline cellulose, lactose monohydrate, magnesium stearate, colloidal silicon dioxide, sodium starch glycolate, povidone and hydroxypropyl cellulose<br/>\n<br/>Manufactured for: Incyte Corporation, 1801 Augustine Cut-off, Wilmington, DE 19803<br/>\n<br/>Jakafi is a registered trademark of Incyte. All rights reserved.<br/>U.S. Patent Nos. 7598257; 8415362; 8722693; 8822481; 8829013; 9079912; 9814722; 10016429<br/>\n<br/>© 2011-2021 Incyte Corporation. All rights reserved.<br/>For more information call 1-855-463-3463 or go to <a href=\"http://www.jakafi.com\">www.jakafi.com</a>.</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: September 2021

{ "type": "p", "children": [], "text": "This Patient Information has been approved by the U.S. Food and Drug Administration.\t\t\t\tRevised: September 2021\n" }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

NDC 50881-005-60

{ "type": "p", "children": [], "text": "NDC 50881-005-60" }

Jakafi® (Ruxolitinib) Tablets

{ "type": "p", "children": [], "text": "Jakafi® (Ruxolitinib) Tablets" }

5 mg

{ "type": "p", "children": [], "text": "5 mg" }

60 tablets

{ "type": "p", "children": [], "text": "60 tablets" }

Each tablet contains 6.6 mg ruxolitinib phosphate equivalent to 5 mg ruxolitinib free base.

{ "type": "p", "children": [], "text": "Each tablet contains 6.6 mg ruxolitinib phosphate equivalent to 5 mg ruxolitinib free base." }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

NDC 50881-010-60

{ "type": "p", "children": [], "text": "NDC 50881-010-60" }

Jakafi® (Ruxolitinib) Tablets

{ "type": "p", "children": [], "text": "Jakafi® (Ruxolitinib) Tablets" }

10 mg

{ "type": "p", "children": [], "text": "10 mg" }

60 tablets

{ "type": "p", "children": [], "text": "60 tablets" }

Each tablet contains 13.2 mg ruxolitinib phosphate equivalent to 10 mg ruxolitinib free base.

{ "type": "p", "children": [], "text": "Each tablet contains 13.2 mg ruxolitinib phosphate equivalent to 10 mg ruxolitinib free base." }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

NDC 50881-015-60

{ "type": "p", "children": [], "text": "NDC 50881-015-60" }

Jakafi® (Ruxolitinib) Tablets

{ "type": "p", "children": [], "text": "Jakafi® (Ruxolitinib) Tablets" }

15 mg

{ "type": "p", "children": [], "text": "15 mg" }

60 tablets

{ "type": "p", "children": [], "text": "60 tablets" }

Each tablet contains 19.8 mg ruxolitinib phosphate equivalent to 15 mg ruxolitinib free base.

{ "type": "p", "children": [], "text": "Each tablet contains 19.8 mg ruxolitinib phosphate equivalent to 15 mg ruxolitinib free base." }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

NDC 50881-020-60

{ "type": "p", "children": [], "text": "NDC 50881-020-60" }

Jakafi® (Ruxolitinib) Tablets

{ "type": "p", "children": [], "text": "Jakafi® (Ruxolitinib) Tablets" }

20 mg

{ "type": "p", "children": [], "text": "20 mg" }

60 tablets

{ "type": "p", "children": [], "text": "60 tablets" }

Each tablet contains 26.4 mg ruxolitinib phosphate equivalent to 20 mg ruxolitinib free base.

{ "type": "p", "children": [], "text": "Each tablet contains 26.4 mg ruxolitinib phosphate equivalent to 20 mg ruxolitinib free base." }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

NDC 50881-025-60

{ "type": "p", "children": [], "text": "NDC 50881-025-60" }

Jakafi® (Ruxolitinib) Tablets

{ "type": "p", "children": [], "text": "Jakafi® (Ruxolitinib) Tablets" }

25 mg

{ "type": "p", "children": [], "text": "25 mg" }

60 tablets

{ "type": "p", "children": [], "text": "60 tablets" }

Each tablet contains 33 mg ruxolitinib phosphate equivalent to 25 mg ruxolitinib free base.

{ "type": "p", "children": [], "text": "Each tablet contains 33 mg ruxolitinib phosphate equivalent to 25 mg ruxolitinib free base." }