CAMPATH is indicated as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL).

{ "type": "p", "children": [], "text": "CAMPATH is indicated as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL)." }

Continue PCP and herpes viral prophylaxis for a minimum of 2 months after completion of CAMPATH or until the CD4+ count is ≥200 cells/µL, whichever occurs later [see Warnings and Precautions (5.3)].

<div class="scrollingtable"><table width="75%"> <caption> <span>Dose Modification for Neutropenia or Thrombocytopenia [see <a href="#S5.1">Warnings and Precautions (5.1)</a>]</span> </caption> <col align="left" valign="top" width="50%"/> <col align="left" valign="top" width="50%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule">Hematologic Values</th><th align="center" class="Rrule">Dosage Modification<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>If the delay between dosing is ≥7 days, initiate therapy at CAMPATH 3 mg and escalate to 10 mg and then to 30 mg as tolerated <span class="Italics">[see <a href="#S2.1">Dosage and Administration (2.1)</a>]</span>.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="2">ANC &lt;250/μL and/or platelet count ≤25,000/μL </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  For first occurrence:</td><td align="left" class="Rrule">Withhold CAMPATH therapy. Resume CAMPATH at 30 mg when ANC ≥500/μL and platelet count ≥50,000/μL.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  For second occurrence:</td><td align="left" class="Rrule">Withhold CAMPATH therapy. Resume CAMPATH at 10 mg when ANC ≥500/μL and platelet count ≥50,000/μL.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  For third occurrence:</td><td align="left" class="Rrule">Discontinue CAMPATH therapy.</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" colspan="2">≥50% decrease from baseline in patients initiating therapy with a baseline ANC ≤250/μL and/or a baseline platelet count ≤25,000/μL</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  For first occurrence:</td><td align="left" class="Rrule">Withhold CAMPATH therapy. Resume CAMPATH at 30 mg upon return to baseline value(s).</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  For second occurrence:</td><td align="left" class="Rrule">Withhold CAMPATH therapy. Resume CAMPATH at 10 mg upon return to baseline value(s).</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">  For third occurrence:</td><td align="left" class="Rrule">Discontinue CAMPATH therapy.</td> </tr> </tbody> </table></div>

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. If particulate matter is present or the solution is discolored, discard the vial. DO NOT SHAKE VIAL.

Use aseptic technique during the preparation and administration of CAMPATH. Withdraw the necessary amount of CAMPATH from the vial into a syringe.

Inject syringe contents into 100 mL sterile 0.9% Sodium Chloride USP or 5% Dextrose in Water USP. Gently invert the bag to mix the solution. Discard syringe.

The vial contains no preservatives and is intended for single use only. DISCARD VIAL including any unused portion after withdrawal of dose.

Use within 8 hours after dilution. Store diluted CAMPATH at room temperature between 15°C to 30°C (59°F to 86°F) or refrigerated at 2°C to 8°C (36°F to 46°F). Protect from light.

CAMPATH is compatible with polyvinylchloride (PVC) bags and PVC or polyethylene-lined PVC administration sets. Do not add or simultaneously infuse other drug substances through the same intravenous line.

Injection: 30 mg/1 mL as a clear, colorless solution in single-dose vial

{ "type": "p", "children": [], "text": "Injection: 30 mg/1 mL as a clear, colorless solution in single-dose vial" }

None.

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

Severe, including fatal, autoimmune anemia and thrombocytopenia, and prolonged myelosuppression have been reported in patients receiving CAMPATH.

In addition, hemolytic anemia, pure red cell aplasia, bone marrow aplasia, and hypoplasia have been reported after treatment with CAMPATH at the recommended dose. Single doses of CAMPATH greater than 30 mg or cumulative doses greater than 90 mg per week increase the incidence of pancytopenia.

Withhold CAMPATH for severe cytopenias (except lymphopenia). Discontinue for autoimmune cytopenias or recurrent/persistent severe cytopenias (except lymphopenia) [see Dosage and Administration (2.3)]. No data exist on the safety of CAMPATH resumption in patients with autoimmune cytopenias or marrow aplasia [see Adverse Reactions (6.1)].

Obtain complete blood counts (CBC) at weekly intervals during CAMPATH therapy and more frequently if worsening anemia, neutropenia, or thrombocytopenia occurs. Assess CD4+ counts after treatment until recovery to ≥200 cells/µL [see Dosage and Administration (2.3) and Adverse Reactions (6)].

Adverse reactions occurring during or shortly after CAMPATH infusion include pyrexia, chills/rigors, nausea, hypotension, urticaria, dyspnea, rash, emesis, and bronchospasm [see Adverse Reactions (6.1)]. In clinical trials, the frequency of infusion-related reactions was highest in the first week of treatment. Monitor for the signs and symptoms listed above and withhold infusion for Grade 3 or 4 infusion-related reactions.

The following serious, including fatal, infusion-related reactions have been identified in postmarketing reports: syncope, pulmonary infiltrates, acute respiratory distress syndrome (ARDS), respiratory arrest, cardiac arrhythmias, myocardial infarction, acute cardiac insufficiency, cardiac arrest, angioedema, and anaphylactoid shock.

Initiate CAMPATH according to the recommended dose-escalation scheme [see Dosage and Administration (2.1)]. Premedicate patients with an antihistamine and acetaminophen prior to each dose. Institute appropriate medical management (e.g., glucocorticoids, epinephrine, meperidine) for infusion-related reactions as needed [see Dosage and Administration (2.2)]. If therapy is interrupted for 7 or more days, reinstitute CAMPATH with gradual dose escalation [see Dosage and Administration (2.1)].

CAMPATH treatment results in severe and prolonged lymphopenia with a concomitant increased incidence of opportunistic infections [see Adverse Reactions (6.1)]. Administer PCP and herpes viral prophylaxis during treatment with CAMPATH and for a minimum of 2 months after completion of CAMPATH or until the CD4+ count is ≥200 cells/µL, whichever occurs later [see Dosage and Administration (2.2)]. Prophylaxis does not eliminate these infections.

Routinely monitor patients for CMV infection during treatment with CAMPATH and for at least 2 months following completion of CAMPATH. Withhold CAMPATH for serious infections and during antiviral treatment for CMV infection or confirmed CMV viremia (defined as polymerase chain reaction [PCR] positive CMV in ≥2 consecutive samples obtained 1 week apart). Initiate therapeutic ganciclovir (or equivalent) for CMV infection or confirmed CMV viremia.

Epstein-Barr virus (EBV) infection, including severe and fatal EBV-associated hepatitis, has been reported in patients who received CAMPATH.

Monitor for sign and symptoms of EBV infections. Withhold CAMPATH for EBV reactivation or severe infection.

Administer only irradiated blood products to avoid transfusion associated Graft versus Host Disease (TAGVHD), unless emergent circumstances dictate immediate transfusion.

In patients who received CAMPATH as initial therapy, recovery of CD4+ counts to ≥200 cells/µL occurred by 6 months following completion of CAMPATH; however, at 2 months post treatment, the median was 183 cells/µL. In previously treated patients who received CAMPATH, the median time to recovery of CD4+ counts to ≥200 cells/µL was 2 months; however, full recovery (to baseline) of CD4+ and CD8+ counts may take more than 12 months [see Adverse Reactions (6)].

The safety of immunization with live viral vaccines following CAMPATH therapy has not been studied. Do not administer live viral vaccines to patients or infants born to patients receiving CAMPATH. The ability to generate an immune response to any vaccine following CAMPATH therapy has not been studied.

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.

The data below reflect exposure to CAMPATH in 296 patients with CLL of whom 147 were previously untreated and 149 received at least 2 prior chemotherapy regimens. The median duration of exposure was 11.7 weeks for previously untreated patients and 8 weeks for previously treated patients.

The most common adverse reactions with CAMPATH are: infusion-related reactions (pyrexia, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia), infections (CMV viremia, CMV infection, other infections), gastrointestinal symptoms (nausea, emesis, abdominal pain), and neurological symptoms (insomnia, anxiety). The most common serious adverse reactions are cytopenias, infusion-related reactions, and immunosuppression/infections.

Lymphopenia

Severe lymphopenia and a rapid and sustained decrease in lymphocyte subsets occurred in previously untreated and previously treated patients following administration of CAMPATH. In previously untreated patients, the median CD4+ was 0 cells/μL at one month after treatment and 238 cells/μL [25%–75% interquartile range 115 to 418 cells/μL at 6 months post treatment [see Warnings and Precautions (5.3)].

Neutropenia

In previously untreated patients, the incidence of Grade 3 or 4 neutropenia was 42% with a median time to onset of 31 days and a median duration of 37 days. In previously treated patients, the incidence of Grade 3 or 4 neutropenia was 64% with a median duration of 28 days. Ten percent of previously untreated patients and 17% of previously treated patients received granulocyte colony stimulating factors.

Anemia

In previously untreated patients, the incidence of Grade 3 or 4 anemia was 12% with a median time to onset of 31 days and a median duration of 8 days. In previously treated patients, the incidence of Grade 3 or 4 anemia was 38%. Seventeen percent of previously untreated patients and 66% of previously treated patients received either erythropoiesis stimulating agents, transfusions or both.

Thrombocytopenia

In previously untreated patients, the incidence of Grade 3 or 4 thrombocytopenia was 14% with a median time to onset of 9 days and a median duration of 14 days. In previously treated patients, the incidence of Grade 3 or 4 thrombocytopenia was 52% with a median duration of 21 days. Autoimmune thrombocytopenia was reported in 2% of previously treated patients with one fatality.

Infusion-Related Reactions

Infusion-related reactions, which included pyrexia, chills, hypotension, urticaria, and dyspnea, were common. Grade 3 and 4 pyrexia and/or chills occurred in approximately 10% of previously untreated patients and in approximately 35% of previously treated patients. The occurrence of infusion-related reactions was greatest during the initial week of treatment and decreased with subsequent doses of CAMPATH. All patients were pretreated with antipyretics and antihistamines; additionally, 43% of previously untreated patients received glucocorticoid pre-treatment.

Infections

In the study of previously untreated patients, patients were tested weekly for CMV using a PCR assay from initiation through completion of therapy, and every 2 weeks for the first 2 months following therapy. CMV infection occurred in 16% (23/147) of previously untreated patients; approximately one-third of these infections were serious or life threatening. In studies of previously treated patients in which routine CMV surveillance was not required, CMV infection was documented in 6% (9/149) of patients; nearly all of these infections were serious or life threatening.

Other infections were reported in approximately 50% of patients across all studies. Grade 3 to 5 sepsis ranged from 3% to 10% across studies and was higher in previously treated patients. Grade 3 to 4 febrile neutropenia ranged from 5% to 10% across studies and was higher in previously treated patients. Infection-related fatalities occurred in 2% of previously untreated patients and 16% of previously treated patients. There were 198 episodes of other infection in 109 previously untreated patients; 16% were bacterial, 7% were fungal, 4% were other viral, and in 73% the organism was not identified.

Cardiac

Cardiac dysrhythmias occurred in approximately 14% of previously untreated patients. The majority were tachycardias and were temporally associated with infusion; dysrhythmias were Grade 3 or 4 in 1% of patients.

Previously Untreated Patients

Table 1 contains selected adverse reactions observed in 294 patients randomized (1:1) to receive CAMPATH or chlorambucil as first line therapy for B-CLL. CAMPATH was administered at a dose of 30 mg intravenously three times weekly for up to 12 weeks. The median duration of therapy was 11.7 weeks with a median weekly dose of 82 mg (25%–75% interquartile range: 69–90 mg).

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 1: Per Patient Incidence of Selected<a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a> Adverse Reactions in Treatment Naive B-CLL Patients</span> </caption> <col align="left" valign="top" width="25%"/> <col align="left" valign="middle" width="25%"/> <col align="center" valign="middle" width="12%"/> <col align="center" valign="middle" width="13%"/> <col align="center" valign="middle" width="12%"/> <col align="center" valign="middle" width="13%"/> <thead> <tr class="First"> <th align="left" class="Lrule"></th><th align="left" class="Rrule"></th><th align="center" class="Botrule Rrule" colspan="2">CAMPATH (n=147)</th><th align="center" class="Botrule Rrule" colspan="2">Chlorambucil (n=147)</th> </tr> <tr class="Last"> <th align="left" class="Lrule"></th><th align="left" class="Rrule"></th><th align="center" class="Rrule">All Grades<a class="Sup" href="#footnote-3" name="footnote-reference-3">†</a> <br/>%</th><th align="center" class="Rrule">Grades 3–4<br/>%</th><th align="center" class="Rrule">All Grades<br/>%</th><th align="center" class="Rrule">Grades 3–4<br/>%</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>Adverse reactions occurring at a higher relative frequency in the CAMPATH arm</dd> <dt> <a href="#footnote-reference-3" name="footnote-3">†</a> </dt> <dd>NCI CTC version 2.0 for adverse reactions; NCI CTCAE version 3.0 for laboratory values</dd> <dt> <a href="#footnote-reference-4" name="footnote-4">‡</a> </dt> <dd>CMV viremia (without evidence of symptoms) includes both cases of single PCR positive test results and of confirmed CMV viremia (≥2 occasions in consecutive samples 1 week apart). For the latter, ganciclovir (or equivalent) was initiated per protocol.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" rowspan="4">Blood and Lymphatic System Disorders</td><td align="left" class="Rrule">Lymphopenia</td><td align="center" class="Rrule">97</td><td align="center" class="Rrule">97</td><td align="center" class="Rrule">9</td><td align="center" class="Rrule">1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Neutropenia</td><td align="center" class="Rrule">77</td><td align="center" class="Rrule">42</td><td align="center" class="Rrule">51</td><td align="center" class="Rrule">26</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Anemia</td><td align="center" class="Rrule">76</td><td align="center" class="Rrule">13</td><td align="center" class="Rrule">54</td><td align="center" class="Rrule">18</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Thrombocytopenia</td><td align="center" class="Rrule">71</td><td align="center" class="Rrule">13</td><td align="center" class="Rrule">70</td><td align="center" class="Rrule">14</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="2">General Disorders and Administration Site Conditions</td><td align="left" class="Rrule">Pyrexia</td><td align="center" class="Rrule">69</td><td align="center" class="Rrule">10</td><td align="center" class="Rrule">11</td><td align="center" class="Rrule">1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Chills</td><td align="center" class="Rrule">53</td><td align="center" class="Rrule">3</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="3">Infections and Infestations</td><td align="left" class="Rrule">CMV viremia<a class="Sup" href="#footnote-4" name="footnote-reference-4">‡</a></td><td align="center" class="Rrule">55</td><td align="center" class="Rrule">4</td><td align="center" class="Rrule">8</td><td align="center" class="Rrule">0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">CMV infection</td><td align="center" class="Rrule">16</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule">0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Other infections</td><td align="center" class="Rrule">74</td><td align="center" class="Rrule">21</td><td align="center" class="Rrule">65</td><td align="center" class="Rrule">10</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="3">Skin and Subcutaneous Tissue Disorders</td><td align="left" class="Rrule">Urticaria</td><td align="center" class="Rrule">16</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Rash</td><td align="center" class="Rrule">13</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">4</td><td align="center" class="Rrule">0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Erythema</td><td align="center" class="Rrule">4</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="2">Vascular Disorders</td><td align="left" class="Rrule">Hypotension</td><td align="center" class="Rrule">16</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule">0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Hypertension</td><td align="center" class="Rrule">14</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">2</td><td align="center" class="Rrule">1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="2">Nervous System Disorders </td><td align="left" class="Rrule">Headache</td><td align="center" class="Rrule">14</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">8</td><td align="center" class="Rrule">0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Tremor</td><td align="center" class="Rrule">3</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Respiratory, Thoracic and Mediastinal Disorders</td><td align="left" class="Rrule">Dyspnea</td><td align="center" class="Rrule">14</td><td align="center" class="Rrule">4</td><td align="center" class="Rrule">7</td><td align="center" class="Rrule">3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Gastrointestinal Disorders</td><td align="left" class="Rrule">Diarrhea</td><td align="center" class="Rrule">10</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">4</td><td align="center" class="Rrule">0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="2">Psychiatric Disorders</td><td align="left" class="Rrule">Insomnia</td><td align="center" class="Rrule">10</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule">3</td><td align="center" class="Rrule">0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Anxiety</td><td align="center" class="Rrule">8</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">0</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Cardiac Disorders</td><td align="left" class="Rrule">Tachycardia</td><td align="center" class="Rrule">10</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">0</td> </tr> </tbody> </table></div>

Previously Treated Patients

Additional safety information was obtained from 3 single arm studies of 149 previously treated patients with CLL administered 30 mg CAMPATH intravenously three times weekly for 4 to 12 weeks (median cumulative dose 673 mg [range 2–1106 mg]; median duration of therapy 8.0 weeks). Adverse reactions in these studies not listed in Table 1 that occurred at an incidence rate of >5% were fatigue, nausea, emesis, musculoskeletal pain, anorexia, dysesthesia, mucositis, and bronchospasm.

As with all therapeutic proteins, there is potential for immunogenicity. The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies with the incidence of antibodies to other alemtuzumab products may be misleading.

Using an ELISA assay, anti-human antibodies (HAHA) were detected in 11 of 133 (8.3%) previously untreated patients. In addition, two patients were weakly positive for neutralizing activity. Limited data suggest that the anti-CAMPATH antibodies did not adversely affect tumor response. Four of 211 (1.9%) previously treated patients were found to have antibodies to CAMPATH following treatment.

CAMPATH

The following adverse reactions have been identified during postapproval use of CAMPATH. 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.

General Disorders and Administration Site Conditions: Fatal infusion-related reactions.

Cardiovascular Disorders: Congestive heart failure, cardiomyopathy, decreased ejection fraction (some patients had been previously treated with cardiotoxic agents).

Cerebrovascular Disorders: Cervicocephalic arterial dissection, stroke, including hemorrhagic and ischemic stroke.

Gastrointestinal Disorders: Acute acalculous cholecystitis.

Immune System Disorders: Goodpasture's syndrome, Graves' disease, aplastic anemia, Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, serum sickness, fatal transfusion associated graft versus host disease, hemophagocytic lymphohistiocytosis (HLH).

Infections: Epstein-Barr virus (EBV) infection, progressive multifocal leukoencephalopathy (PML), reactivation of latent viruses.

Metabolism and Nutrition Disorders: Tumor lysis syndrome.

Neoplasms: EBV-associated lymphoproliferative disorder.

Nervous System Disorders: Optic neuropathy.

Renal and Urinary Disorders: Glomerular nephropathies.

Other Alemtuzumab Products

The following adverse reactions have been identified during postapproval use of another alemtuzumab product. 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.

Endocrine Disorders: Hypothyroidism, hyperthyroidism, and thyroiditis.

Nervous System Disorders: Autoimmune encephalitis.

No formal drug interaction studies have been performed with CAMPATH.

{ "type": "p", "children": [], "text": "No formal drug interaction studies have been performed with CAMPATH." }

Risk Summary

Based on findings from animal studies, CAMPATH may cause fetal harm when administered to a pregnant woman. Available data from published cohort studies in pregnant women are insufficient to establish a CAMPATH-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Alemtuzumab was embryolethal in pregnant huCD52 transgenic mice when administered during organogenesis (see Data). Human IgG antibodies are known to cross the placental barrier; therefore, CAMPATH may be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus. Infants born to pregnant women treated with CAMPATH may be at increased risk of infection (see Clinical Considerations).

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Fetal/Neonatal adverse reactions

Monoclonal antibodies are transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Consider the risks and benefits of administering live or live-attenuated vaccines to infants exposed to CAMPATH in utero [see Warnings and Precautions (5.3, 5.4)].

Data

Animal data

When alemtuzumab was administered to pregnant huCD52 transgenic mice during organogenesis (gestation days [GD] 6–10 or GD 11–15) at intravenous doses of 3 or 10 mg/kg, no teratogenic effects were observed. However, there was an increase in embryolethality (increased postimplantation loss and the number of dams with all fetuses dead or resorbed) in pregnant animals dosed during GD 11–15. In a separate study in pregnant huCD52 transgenic mice, administration of alemtuzumab during organogenesis (GD 6–10 or GD 11–15) at intravenous doses of 3 or 10 mg/kg, decreases in B-lymphocyte and T-lymphocyte populations were observed in the offspring at both doses tested.

In pregnant huCD52 transgenic mice administered alemtuzumab at intravenous doses of 3 or 10 mg/kg/day throughout gestation and lactation, there was an increase in pup deaths during the lactation period at 10 mg/kg. Decreases in T-lymphocyte and B-lymphocyte populations and in antibody response were observed in offspring at both doses tested.

Risk Summary

There are no data on the presence of alemtuzumab in human milk, effects on milk production, or the breastfed child. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to alemtuzumab are unknown. Alemtuzumab was detected in the milk of lactating huCD52 transgenic mice administered alemtuzumab (see Data). Maternal IgG is known to be present in human milk and when a drug is present in animal milk, it is likely that the drug will be present in human milk.

Because of the potential for serious adverse reactions from CAMPATH in a breastfed child, including reduced lymphocyte counts, advise lactating women not to breastfeed during treatment with CAMPATH and for at least 3 months following the last dose.

Data

Alemtuzumab was detected in the milk of lactating huCD52 transgenic mice following intravenous administration of alemtuzumab at a dose of 10 mg/kg on postpartum days 8–12. Serum levels of alemtuzumab were similar in lactating mice and offspring on postpartum day 13 and were associated with evidence of pharmacological activity (decrease in lymphocyte counts) in the offspring.

CAMPATH may cause embryo-fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)].

Pregnancy Testing

Pregnancy testing is recommended for females of reproductive potential prior to initiating CAMPATH therapy.

Contraception

Females

Advise female patients of reproductive potential to use effective contraception during treatment with CAMPATH and for at least 3 months after the last dose.

Infertility

Based on findings from animal studies, alemtuzumab may impair fertility in females and males of reproductive potential [see Nonclinical Toxicology (13.1)]. The reversibility of the effect on fertility is unknown.

Safety and effectiveness of CAMPATH have not been established in pediatric patients.

Of 147 previously untreated B-CLL patients treated with CAMPATH, 35% were ≥ age 65 and 4% were ≥ age 75. Of 149 previously treated patients with B-CLL, 44% were ≥65 years of age and 10% were ≥75 years of age. Clinical studies of CAMPATH did not include sufficient number of subjects age 65 and over to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Across all clinical experience, the reported maximum single dose received was 90 mg. Bone marrow aplasia, infections, or severe infusion-related reactions occurred in patients who received a dose higher than recommended.

{ "type": "p", "children": [], "text": "Across all clinical experience, the reported maximum single dose received was 90 mg. Bone marrow aplasia, infections, or severe infusion-related reactions occurred in patients who received a dose higher than recommended." }

One patient who received an 80 mg dose intravenously experienced acute bronchospasm, cough, and dyspnea, followed by anuria and death. Another patient received two 90 mg doses intravenously one day apart during the second week of treatment and experienced a rapid onset of bone marrow aplasia.

{ "type": "p", "children": [], "text": "One patient who received an 80 mg dose intravenously experienced acute bronchospasm, cough, and dyspnea, followed by anuria and death. Another patient received two 90 mg doses intravenously one day apart during the second week of treatment and experienced a rapid onset of bone marrow aplasia." }

There is no known specific antidote for CAMPATH overdosage. Discontinue CAMPATH and provide supportive therapy.

{ "type": "p", "children": [], "text": "There is no known specific antidote for CAMPATH overdosage. Discontinue CAMPATH and provide supportive therapy." }

Alemtuzumab, a CD52-directed cytolytic antibody, is a recombinant DNA-derived humanized monoclonal antibody (CAMPATH-1H). CAMPATH-1H is an IgG1 kappa antibody with human variable framework and constant regions, and complementarity-determining regions from a murine (rat) monoclonal antibody (CAMPATH-1G). The CAMPATH-1H antibody has an approximate molecular weight of 150 kD. CAMPATH is produced in mammalian cell (Chinese hamster ovary) suspension culture in a medium containing neomycin. Neomycin is not detectable in the final product.

{ "type": "p", "children": [], "text": "Alemtuzumab, a CD52-directed cytolytic antibody, is a recombinant DNA-derived humanized monoclonal antibody (CAMPATH-1H). CAMPATH-1H is an IgG1 kappa antibody with human variable framework and constant regions, and complementarity-determining regions from a murine (rat) monoclonal antibody (CAMPATH-1G). The CAMPATH-1H antibody has an approximate molecular weight of 150 kD. CAMPATH is produced in mammalian cell (Chinese hamster ovary) suspension culture in a medium containing neomycin. Neomycin is not detectable in the final product." }

CAMPATH (alemtuzumab) injection is a sterile, clear, colorless, isotonic solution (pH 6.8–7.4) in a single-dose vial for intravenous use. Each single-dose vial of CAMPATH contains 30 mg alemtuzumab, 8.0 mg sodium chloride, 1.44 mg dibasic sodium phosphate, 0.2 mg potassium chloride, 0.2 mg monobasic potassium phosphate, 0.1 mg polysorbate 80, and 0.0187 mg disodium edetate dihydrate. No preservatives are added.

{ "type": "p", "children": [], "text": "CAMPATH (alemtuzumab) injection is a sterile, clear, colorless, isotonic solution (pH 6.8–7.4) in a single-dose vial for intravenous use. Each single-dose vial of CAMPATH contains 30 mg alemtuzumab, 8.0 mg sodium chloride, 1.44 mg dibasic sodium phosphate, 0.2 mg potassium chloride, 0.2 mg monobasic potassium phosphate, 0.1 mg polysorbate 80, and 0.0187 mg disodium edetate dihydrate. No preservatives are added." }

CAMPATH binds to CD52, an antigen present on the surface of B and T lymphocytes, a majority of monocytes, macrophages, NK cells, and a subpopulation of granulocytes. A proportion of bone marrow cells, including some CD34+ cells, express variable levels of CD52. The proposed mechanism of action is antibody-dependent cellular-mediated lysis following cell surface binding of CAMPATH to the leukemic cells.

Cardiac Electrophysiology

The effect of multiple doses of alemtuzumab (12 mg/day for 5 days) on the QTc interval was evaluated in a single-arm study in 53 patients without malignancy. No large changes in the mean QTc interval (i.e., >20 ms) were detected in the study. A mean increase in heart rate of 22 to 26 beats/min was observed for at least 2 hours following the initial infusion of alemtuzumab. This increase in heart rate was not observed with subsequent doses.

CAMPATH pharmacokinetics were characterized in a study of 30 previously treated B-CLL patients in whom CAMPATH was administered at the recommended dose and schedule. After 12 weeks of dosing, patients exhibited a 7-fold increase in mean AUC.

Distribution

After the last 30 mg dose, the mean volume of distribution at steady-state was 0.18 L/kg (range 0.1 to 0.4 L/kg).

Elimination

CAMPATH pharmacokinetics displayed nonlinear elimination kinetics. Systemic clearance decreased with repeated administration due to decreased receptor-mediated clearance (i.e., loss of CD52 receptors in the periphery). Mean half-life was 11 hours (range 2 to 32 hours) after the first 30 mg dose and was 6 days (range 1 to 14 days) after the last 30 mg dose.

Specific Populations

The effects of renal or hepatic impairment on the pharmacokinetics of CAMPATH have not been studied.

Studies to assess the carcinogenic or genotoxic potential of CAMPATH have not been conducted.

In fertility studies, alemtuzumab (3 or 10 mg/kg intravenously) was administered to huCD52 transgenic male mice on 5 consecutive days prior to cohabitation with untreated wild-type females. No effect on fertility or reproductive performance was observed. However, adverse effects on sperm parameters (including abnormal morphology [detached/no head] and reduced total count and motility) were observed at both doses tested.

When alemtuzumab (3 or 10 mg/kg intravenously) was administered to huCD52 transgenic female mice for 5 consecutive days prior to cohabitation with untreated wild-type males, there was a decrease in the average number of corpora lutea and implantation sites and an increase in postimplantation loss, resulting in fewer viable embryos at the higher dose tested.

CAMPATH was evaluated in an open-label, randomized (1:1) active-controlled study in previously untreated patients with B-CLL, Rai Stage I–IV, with evidence of progressive disease requiring therapy. Patients received either CAMPATH 30 mg intravenously 3 times per week for a maximum of 12 weeks or chlorambucil 40 mg/m2 orally once every 28 days for a maximum of 12 cycles.

Of the 297 patients randomized, the median age was 60 years, 72% were male, 99% were Caucasian, 96% had a WHO performance status 0–1, 23% had maximum lymph node diameter ≥5 cm, 34% were Rai Stage III/IV, and 8% were treated in the U.S.

Patients randomized to receive CAMPATH experienced longer progression free survival (PFS) compared to those randomized to receive chlorambucil (median PFS 14.6 months vs. 11.7 months, respectively). The overall response rates were 83% and 55% (p <0.0001) and the complete response rates were 24% and 2% (p <0.0001) for CAMPATH and chlorambucil arms, respectively. The Kaplan-Meier curve for PFS is shown in Figure 1.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="top" width="100%"/> <thead> <tr> <th align="left">Figure 1: Progression Free Survival in Previously Untreated B-CLL Patients<a class="Sup" href="#footnote-5" name="footnote-reference-5">*</a></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="1"> <dl class="Footnote"> <dt> <a href="#footnote-reference-5" name="footnote-5">*</a> </dt> <dd>Log-rank test adjusted for Rai Stage (I–II vs. III–IV).</dd> </dl> </td> </tr> </tfoot> <tbody> <tr> <td align="left"> <p class="First"> <img alt="Figure 1" src="/dailymed/image.cfm?name=campath-01.jpg&amp;setid=4f5f7255-7abc-4328-bd1a-ceaf139ef3e0"/></p> </td> </tr> </tbody> </table></div>

CAMPATH was evaluated in three multicenter, open-label, single-arm studies of 149 patients with B-CLL previously treated with alkylating agents, fludarabine, or other chemotherapies. Patients were treated with the recommended dose of CAMPATH 30 mg intravenously 3 times per week for up to 12 weeks. Partial response rates of 21% to 31% and complete response rates of 0% to 2% were observed.

Store CAMPATH at 2°C to 8°C (36°F to 46°F). Do not freeze. If accidentally frozen, thaw at 2°C to 8°C before administration. Protect from direct sunlight.

Cytopenias

Advise patients to report any signs or symptoms such as bleeding, easy bruising, petechiae or purpura, pallor, weakness or fatigue [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].

Infusion-Related Reactions

Advise patients of the signs and symptoms of infusion-related reactions and of the need to take premedications as prescribed [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)].

Immunosuppression/Infections

Advise patients to immediately report symptoms of infection (e.g., pyrexia) and to take prophylactic anti-infectives for PCP (trimethoprim/sulfamethoxazole DS or equivalent) and for herpes virus (famciclovir or equivalent) as prescribed [see Warnings and Precautions (5.3) and Adverse Reactions (6.1)].

Advise patients that irradiation of blood products is required [see Warnings and Precautions (5.3)].

Immunization

Advise patients that they should not be immunized with live viral vaccines if they have recently been treated with CAMPATH. Advise females with infants exposed to CAMPATH in utero to inform the pediatrician of the exposure [see Warnings and Precautions (5.4)].

Embryo-Fetal Toxicity

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1, 8.3)].

Advise female patients of reproductive potential to use effective contraception during treatment with CAMPATH and for 3 months after the final dose [see Use in Specific Populations (8.1, 8.3)].

Lactation

Advise females not to breastfeed during treatment with CAMPATH and for 3 months after the final dose [see Use in Specific Populations (8.2)].

Infertility

Advise females and males of reproductive potential that CAMPATH may impair fertility [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1)].

Glomerular Nephropathies

Advise patients on signs and symptoms of glomerular nephropathies that may occur months to years after receiving CAMPATH [see Adverse Reactions (6.2)].

Manufactured and distributed by:Genzyme Corporation, Cambridge, MA 02141A SANOFI COMPANY US License Number: 1596

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CAMPATH is a registered trademark of Genzyme Corporation.

{ "type": "p", "children": [], "text": "CAMPATH is a registered trademark of Genzyme Corporation." }

©2023 Genzyme Corporation.

{ "type": "p", "children": [], "text": "©2023 Genzyme Corporation." }

NDC 58468-0357-1 Rx only

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Campath® alemtuzumab Injection

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30 mg/mL

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For Intravenous Infusion After Dilution

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Sterile – No U.S. Standard of Potency

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One single-dose vial Discard unused portion

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sanofi

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NDC 58468-0357-3Rx only

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Campath® alemtuzumab Injection

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30 mg/mL

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For Intravenous Infusion After Dilution

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Sterile – No U.S. Standard of Potency

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Three single-dose vials Discard unused portion

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sanofi

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Limitations of Use

LEMTRADA is not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile [see Warnings and Precautions (5)].

Baseline laboratory tests are required prior to treatment with LEMTRADA [see Dosage and Administration (2.6)]. In addition, prior to starting treatment with LEMTRADA [see Warnings and Precautions (5.15)]:

Corticosteroids

Premedicate patients with high dose corticosteroids (1,000 mg methylprednisolone or equivalent) immediately prior to LEMTRADA infusion and for the first 3 days of each treatment course [see Warnings and Precautions (5.2)].

Herpes Prophylaxis

Administer antiviral prophylaxis for herpetic viral infections starting on the first day of each treatment course and continue for a minimum of two months following treatment with LEMTRADA or until the CD4+ lymphocyte count is at least 200 cells per microliter, whichever occurs later [see Warnings and Precautions (5.15)].

Following the second treatment course, subsequent treatment courses of 12 mg per day on 3 consecutive days (36 mg total dose) may be administered, as needed, at least 12 months after the last dose of any prior treatment courses.

Follow the steps below to prepare the diluted solution of LEMTRADA for intravenous infusion:

Prior to administration, protect diluted LEMTRADA solution from light and store for as long as 8 hours either at room temperature 15°C to 25°C (59°F to 77°F) or keep refrigerated at conditions 2°C to 8°C (36°F to 46°F).

Infuse LEMTRADA over 4 hours starting within 8 hours after dilution. Extend the duration of the infusion if clinically indicated.

Administer LEMTRADA in a setting in which equipment and personnel to appropriately manage anaphylaxis, serious infusion reactions, myocardial ischemia, myocardial infarction, and cerebrovascular and respiratory adverse reactions are available [see Warnings and Precautions (5.2)].

Do not add or simultaneously infuse other drug substances through the same intravenous line. Do not administer as an intravenous push or bolus.

Obtain a baseline ECG. Monitor vital signs before the infusion and periodically during the infusion. Provide appropriate symptomatic treatment for infusion reactions as needed. Consider immediate discontinuation of the intravenous infusion if severe infusion reactions occur.

Observe patients for infusion reactions during and for at least 2 hours after each LEMTRADA infusion. Consider longer periods of observation if clinically indicated. Inform patients that they should report symptoms that occur during and after each infusion because they may indicate a need for prompt medical intervention [see Warnings and Precautions (5.2)].

Measure the urine protein to creatinine ratio prior to initiation of treatment. Conduct the following laboratory tests at baseline and at periodic intervals until 48 months after the last treatment course of LEMTRADA in order to monitor for early signs of potentially serious adverse effects:

Conduct baseline and yearly skin exams to monitor for melanoma [see Warnings and Precautions (5.4)].

Injection: 12 mg/1.2 mL (10 mg/mL) in a single-dose vial. LEMTRADA is a clear and colorless to slightly yellow solution that requires dilution prior to intravenous infusion.

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LEMTRADA is contraindicated in patients:

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Treatment with LEMTRADA can result in the formation of autoantibodies and increase the risk of serious autoimmune conditions, which may be life threatening.

In clinical studies (controlled and open-label extension), the following serious autoimmune conditions were reported in LEMTRADA-treated patients, which are described in separate warnings:

In clinical studies (controlled and open-label extension), vitiligo (0.3%), undifferentiated connective tissue disorders (0.2%), type 1 diabetes (0.2%), rheumatoid arthritis (0.1%), and retinal pigment epitheliopathy (0.1%) were also reported in LEMTRADA-treated patients.

In the postmarketing setting, cases of autoimmune hepatitis [see Warnings and Precautions (5.10)], hemophagocytic lymphohistiocytosis [see Warnings and Precautions (5.11)], Adult Onset Still's Disease [see Warnings and Precautions (5.12)], thrombotic thrombocytopenic purpura [see Warnings and Precautions (5.13)], autoimmune encephalitis [see Warnings and Precautions (5.14)], immune-mediated colitis [see Warnings and Precautions (5.16)], Guillain-Barré syndrome, and vasculitis have been reported.

Chronic inflammatory demyelinating polyradiculoneuropathy has been reported in the treatment of patients with B-cell chronic lymphocytic leukemia (B-CLL), as well as other autoimmune disorders, generally at higher and more frequent doses than recommended in MS.

Autoantibodies may be transferred from the mother to the fetus during pregnancy. A case of transplacental transfer of anti-thyrotropin receptor antibodies resulting in neonatal Graves' disease occurred after alemtuzumab treatment in the mother [see Use in Specific Populations (8.1)].

LEMTRADA may increase the risk of other autoimmune conditions because of the broad range of autoantibody formation with LEMTRADA.

Measure the urine protein to creatinine ratio prior to initiation of treatment. Monitor complete blood counts with differential, serum creatinine levels, and urinalysis with urine cell counts before starting treatment and then at monthly intervals until 48 months after the last dose of LEMTRADA to allow for early detection and treatment of autoimmune adverse reactions [see Dosage and Administration (2.6)]. After 48 months, testing should be performed based on clinical findings suggestive of autoimmunity.

LEMTRADA is available only through a restricted program under a REMS [see Warnings and Precautions (5.5)].

LEMTRADA causes cytokine release syndrome resulting in infusion reactions, some of which may be serious and life threatening. In clinical studies, 92% of LEMTRADA-treated patients experienced infusion reactions. In some patients, infusion reactions were reported more than 24 hours after LEMTRADA infusion. Serious reactions occurred in 3% of patients and included anaphylaxis in 2 patients (including anaphylactic shock), angioedema, bronchospasm, hypotension, chest pain, bradycardia, tachycardia (including atrial fibrillation), transient neurologic symptoms, hypertension, headache, pyrexia, and rash. Other infusion reactions included nausea, urticaria, pruritus, insomnia, chills, flushing, fatigue, dyspnea, pulmonary infiltrates, dysgeusia, dyspepsia, dizziness, and pain. In clinical studies, 0.6% of patients with infusion reactions received epinephrine or atropine.

During postmarketing use, cases of pulmonary alveolar hemorrhage, myocardial ischemia, myocardial infarction, stroke (including ischemic and hemorrhagic stroke), and cervicocephalic (e.g., vertebral, carotid) arterial dissection have been reported. Reactions may occur following any of the doses during the treatment course. In the majority of cases, time to onset was within 1 to 3 days of LEMTRADA infusion. Patients should be informed about the signs and symptoms and advised to seek immediate medical attention if any of these symptoms occur. Cases of severe (including fatal) neutropenia have been reported within 2 months of LEMTRADA infusion; some cases resolved with receiving granulocyte-colony stimulating factor treatment. Mild to moderate decreases in platelet counts, starting at the time of alemtuzumab infusion and often resolving without treatment, have been reported. Other serious and sometimes fatal infusion reactions (e.g., hypoxia, syncope, acute respiratory distress syndrome, respiratory arrest, myocardial infarction, acute cardiac insufficiency, cardiac arrest) have been reported in the treatment of patients with B-CLL, as well as other disorders, generally at higher and more frequent doses than recommended in MS.

Premedicate patients with corticosteroids immediately prior to LEMTRADA infusion for the first 3 days of each treatment course. In clinical studies, patients received 1,000 mg of methylprednisolone for the first 3 days of each LEMTRADA treatment course. Consider pretreatment with antihistamines and/or antipyretics prior to LEMTRADA administration. Infusion reactions may occur despite pretreatment.

Consider additional monitoring in patients with medical conditions which predispose them to cardiovascular or pulmonary compromise. Physicians should alert patients that an infusion reaction could occur within 48 hours of infusion.

LEMTRADA can only be administered in certified healthcare settings that have on-site access to equipment and personnel trained to manage infusion reactions (including anaphylaxis, cerebrovascular, cardiac and respiratory emergencies) [see Dosage and Administration (2.5)].

LEMTRADA is available only through a restricted program under a REMS [see Warnings and Precautions (5.5)].

Stroke

In the postmarketing setting, serious and life-threatening stroke (including ischemic and hemorrhagic stroke) has been reported within 3 days of LEMTRADA administration, with most cases occurring within 1 day.

Cervicocephalic Arterial Dissection

In the postmarketing setting, cases of cervicocephalic (e.g., vertebral, carotid) arterial dissection involving multiple arteries have been reported within 3 days of LEMTRADA administration. Ischemic stroke was reported in one of these cases.

Educate patients on the symptoms of stroke and cervicocephalic (e.g., carotid, vertebral) arterial dissection. Instruct patients to seek immediate medical attention if symptoms of stroke or cervicocephalic arterial dissection occur.

Thyroid Cancer

LEMTRADA may increase the risk of thyroid cancer. In controlled clinical studies, 3 of 919 (0.3%) LEMTRADA-treated patients developed thyroid cancer, compared to none in the interferon beta-1a–treated group. However, screening for thyroid cancer was performed more frequently in the LEMTRADA-treated group, because of the higher incidence of autoimmune thyroid disorders in those patients. Two additional cases of thyroid cancer in LEMTRADA-treated patients occurred in uncontrolled studies.

Patients and healthcare providers should monitor for symptoms of thyroid cancer including a new lump or swelling in the neck, pain in the front of the neck, persistent hoarseness or other voice changes, trouble swallowing or breathing, or a constant cough not due to an upper respiratory tract infection.

Melanoma

LEMTRADA may increase the risk of melanoma. In MS clinical studies (controlled and open-label extension), 5 of 1486 (0.3%) LEMTRADA-treated patients developed melanoma or melanoma in situ. One of those patients had evidence of locally advanced disease.

Perform baseline and yearly skin examinations to monitor for melanoma in patients receiving LEMTRADA.

Lymphoproliferative Disorders and Lymphoma

Cases of lymphoproliferative disorders and lymphoma have occurred in LEMTRADA-treated patients with MS, including a MALT lymphoma, Castleman's Disease, and a fatality following treatment of non-Epstein Barr Virus–associated Burkitt's lymphoma. There are postmarketing reports of Epstein Barr Virus–associated lymphoproliferative disorders in non-MS patients.

Because LEMTRADA is an immunomodulatory therapy, caution should also be exercised in initiating LEMTRADA in patients with preexisting or ongoing malignancies.

LEMTRADA is available only through a restricted program under a REMS [see Warnings and Precautions (5.5)].

LEMTRADA is available only through a restricted program under a REMS called the LEMTRADA REMS Program because of the risks of autoimmunity, infusion reactions, and malignancies [see Warnings and Precautions (5.1, 5.2, 5.4)].

Notable requirements of the LEMTRADA REMS Program include the following:

Further information, including a list of qualified healthcare facilities, is available at 1-855-676-6326.

Immune thrombocytopenia (ITP) occurred in 2% of LEMTRADA-treated patients in MS clinical studies (controlled and open-label extension).

In a controlled clinical study in patients with MS, one LEMTRADA-treated patient developed ITP that went unrecognized prior to the implementation of monthly blood monitoring requirements, and died from intracerebral hemorrhage. Nadir platelet counts ≤20,000 cells per microliter as a result of ITP occurred in 2% of all LEMTRADA-treated patients in clinical studies in MS. Anti-platelet antibodies did not precede ITP onset. ITP has been diagnosed more than 3 years after the last LEMTRADA dose.

Symptoms of ITP include easy bruising, petechiae, spontaneous mucocutaneous bleeding (e.g., epistaxis, hemoptysis), and heavier than normal or irregular menstrual bleeding. Hemoptysis may also be indicative of anti-glomerular basement membrane (GBM) disease [see Warnings and Precautions (5.7)], and an appropriate differential diagnosis has to be undertaken. Remind the patient to remain vigilant for symptoms they may experience and to seek immediate medical help if they have any concerns.

Obtain complete blood counts (CBCs) with differential prior to initiation of treatment and at monthly intervals thereafter until 48 months after the last infusion [see Dosage and Administration (2.6)]. After this period of time, testing should be performed based on clinical findings suggestive of ITP. If ITP is suspected, a complete blood count should be obtained immediately. If ITP onset is confirmed, promptly initiate appropriate medical intervention.

Glomerular nephropathies occurred in 0.3% of LEMTRADA-treated patients in MS clinical studies. There were 3 cases of membranous glomerulonephritis and 2 cases of anti-glomerular basement membrane (anti-GBM) disease.

In postmarketing cases, some LEMTRADA-treated patients with anti-GBM disease developed end-stage renal disease requiring dialysis or renal transplantation. Urgent evaluation and treatment are required because early treatment can improve the preservation of renal function. Anti-GBM disease can be life-threatening if left untreated. Alveolar hemorrhage, manifested as hemoptysis, is a common component of anti-GBM disease and has been reported in postmarketing cases. Cases of anti-GBM disease have been diagnosed up to 40 months after the last dose of LEMTRADA.

Symptoms of nephropathy may include edema, hematuria, change in urine color, decreased urine output, fatigue, dyspnea, and hemoptysis. Patients and caregivers should be instructed to seek medical advice if they have concerns.

Obtain serum creatinine levels, urinalysis with cell counts, and urine protein to creatinine ratio prior to initiation of treatment. Obtain serum creatinine levels and urinalysis with cell counts at monthly intervals thereafter until 48 months after the last infusion. After this period of time, testing should be performed based on clinical findings suggestive of nephropathies.

For urine dipstick results of 1+ protein or greater, measure the urine protein to creatinine ratio. For urine protein to creatinine ratio greater than 200 mg/g, increase in serum creatinine greater than 30%, or unexplained hematuria, perform further evaluation for nephropathies. Increased serum creatinine with hematuria or signs of pulmonary involvement of anti-GBM disease (e.g., hemoptysis, exertional dyspnea) warrant immediate evaluation. Early detection and treatment of nephropathies may decrease the risk of poor outcomes.

Thyroid endocrine disorders, including autoimmune thyroid disorders, occurred in 36.8% of LEMTRADA-treated patients in MS clinical studies (controlled and open-label extension). Newly diagnosed thyroid disorders occurred throughout the uncontrolled clinical study follow-up period, more than 7 years after the first LEMTRADA dose. Autoimmune thyroid disorders included Graves' disease, hyperthyroidism, hypothyroidism, autoimmune thyroiditis, and goiter. Graves' ophthalmopathy with decreased vision, eye pain, and exophthalmos occurred in 2% of LEMTRADA-treated patients. Seven patients required surgical orbital decompression. Serious thyroid events occurred in about 5.2% of LEMTRADA-treated patients in clinical studies and included cardiac and psychiatric events associated with thyroid disease. Of all LEMTRADA-treated patients, 3.8% underwent thyroidectomy.

Thyroid disease poses special risks in women who are pregnant [see Use in Specific Populations (8.1)].

Obtain thyroid function tests, such as TSH levels, prior to initiation of treatment and every 3 months thereafter until 48 months after the last infusion. Continue to test thyroid function after 48 months if clinically indicated or in case of pregnancy.

In patients with ongoing thyroid disorder, LEMTRADA should be administered only if the potential benefit justifies the potential risks.

Autoimmune cytopenias such as neutropenia (0.1%), hemolytic anemia (0.3%), and pancytopenia (0.2%) occurred in LEMTRADA-treated patients in MS clinical studies (controlled and open-label extension). In cases of autoimmune hemolytic anemia, patients tested positive for direct antiglobulin antibodies, and nadir hemoglobin levels ranged from 2.9–8.6 g/dL. Symptoms of autoimmune hemolytic anemia include weakness, chest pain, jaundice, dark urine, and tachycardia. One LEMTRADA-treated patient with autoimmune pancytopenia died from sepsis.

During postmarketing use, additional autoimmune cytopenias, including fatal autoimmune hemolytic anemia and aplastic anemia, have been reported in the treatment of patients with B-CLL, as well as other disorders, generally at higher and more frequent doses of alemtuzumab than recommended in MS.

Use CBC results to monitor for cytopenias. Prompt medical intervention is indicated if a cytopenia is confirmed.

Autoimmune hepatitis causing clinically significant liver injury, including acute liver failure requiring transplant, has been reported in patients treated with LEMTRADA in the postmarketing setting. If a patient develops clinical signs, including unexplained liver enzyme elevations or symptoms suggestive of hepatic dysfunction (e.g., unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine), promptly measure serum transaminases and total bilirubin and interrupt or discontinue treatment with LEMTRADA, as appropriate.

Prior to starting treatment with LEMTRADA, obtain serum transaminases (ALT and AST) and total bilirubin levels. Obtain transaminase levels and total bilirubin levels at periodic intervals until 48 months after the last dose.

Hemophagocytic lymphohistiocytosis (HLH) has occurred in patients taking LEMTRADA. HLH is a life-threatening syndrome of pathologic immune activation characterized by clinical signs and symptoms of extreme systemic inflammation. It is associated with high mortality rates if not recognized early and treated. Common findings include fever, hepatosplenomegaly, rash, lymphadenopathy, neurologic symptoms (e.g., mental status changes, ataxia, or seizures), cytopenias, high serum ferritin, hypertriglyceridemia, and liver function and coagulation abnormalities. Hemophagocytosis may be seen on histologic examination of bone marrow, spleen, or lymph nodes. In cases of HLH reported with LEMTRADA, most patients presented with fever, elevated ferritin, transaminitis, hypertriglyceridemia, and all patients required hospitalization. Although the small number of cases limits the ability to draw conclusions pertaining to mean or range of latency for HLH, symptoms have been reported to occur within approximately thirteen months to thirty-three months following the initiation of treatment. Patients who develop early manifestations of pathologic immune activation should be evaluated immediately, and a diagnosis of HLH should be considered. LEMTRADA should be discontinued if an alternate etiology for the signs or symptoms cannot be established.

During postmarketing use, Adult Onset Still's Disease (AOSD) has been reported in patients treated with LEMTRADA. AOSD is a rare inflammatory condition that requires urgent evaluation and treatment. Patients with AOSD may have a combination of the following signs and symptoms: fever, arthritis, rash, and leukocytosis in the absence of infections, malignancies, and other rheumatic conditions. Patients with manifestations of AOSD should be evaluated immediately and LEMTRADA should be discontinued if an alternate etiology for the signs or symptoms cannot be established.

TTP has been reported in patients treated with LEMTRADA. TTP is characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurological sequelae, fever, and renal impairment. TTP is associated with high morbidity and mortality rates if not recognized and treated early. LEMTRADA should be discontinued if TTP is confirmed or an alternate etiology for the signs or symptoms cannot be established.

During postmarketing use, cases of AIE have been reported in patients treated with LEMTRADA. AIE can present with a variety of clinical manifestations, including subacute onset of memory impairment, altered mental status, psychiatric symptoms, neurological findings, and seizures. LEMTRADA should be discontinued if AIE is confirmed by the presence of neural autoantibodies or an alternate etiology cannot be established.

Cases of acquired hemophilia A (anti-Factor VIII antibodies) have been reported in both the clinical trial and postmarketing settings. Patients typically present with spontaneous subcutaneous hematomas and extensive bruising, although hematuria, epistaxis, gastrointestinal, or other types of bleeding may occur. Obtain a coagulopathy panel including aPTT in patients who present with such symptoms. Patients should be informed about the signs and symptoms of acquired hemophilia A and advised to seek immediate medical attention if any of these symptoms occur.

Immune-mediated colitis, which can present as a severe and acute-onset form of colitis, has been reported in patients receiving LEMTRADA in the postmarketing setting. Some cases of colitis were serious, requiring hospitalization. Systemic corticosteroids were required in some of these patients. The time from treatment initiation to onset of symptoms in these cases ranged from a few months to years.

Monitor patients for immune-mediated colitis during and after LEMTRADA treatment, and evaluate promptly if signs and symptoms that may indicate immune-mediated colitis, such as new or persistent diarrhea or other gastrointestinal signs and symptoms, occur.

It is unknown whether immune-mediated colitis in patients treated with LEMTRADA is a monophasic disorder, or whether recurrent flares (as are seen in patients with inflammatory bowel disease) will occur.

Infections occurred in 71% of LEMTRADA-treated patients compared to 53% of patients treated with interferon beta-1a in controlled clinical studies in MS up to 2 years in duration. Infections that occurred more often in LEMTRADA-treated patients than interferon beta-1a patients included nasopharyngitis, urinary tract infection, upper respiratory tract infection, sinusitis, herpetic infections, influenza, and bronchitis. Serious infections occurred in 3% of patients treated with LEMTRADA as compared to 1% of patients treated with interferon beta-1a. Serious infections in the LEMTRADA group included: appendicitis, gastroenteritis, pneumonia, herpes zoster, and tooth infection.

Do not administer live viral vaccines following a course of LEMTRADA. Patients treated with LEMTRADA have altered immunity and may be at increased risk of infection following administration of live viral vaccines.

LEMTRADA administration is contraindicated in patients with active infection [see Contraindications (4)].

Concomitant use of LEMTRADA with antineoplastic or immunosuppressive therapies could increase the risk of immunosuppression.

Opportunistic Infections

In the postmarketing setting, serious, sometimes fatal, opportunistic infections have been reported in patients taking LEMTRADA, including aspergillosis, coccidioidomycosis, histoplasmosis, Pneumocystis jirovecii pneumonia, nocardiosis, Epstein-Barr virus, and cytomegalovirus infections.

Listeria Monocytogenes Infections

Listeria monocytogenes infections (e.g., meningitis, encephalitis, sepsis, and gastroenteritis), including fatal cases of Listeria meningoencephalitis, have occurred in LEMTRADA-treated patients. Listeria infections have occurred as early as 3 days after treatment and up to 8 months after the last LEMTRADA dose. The duration of increased risk for Listeria infection after LEMTRADA treatment is unknown.

Advise patients to avoid or adequately heat foods that are potential sources of Listeria monocytogenes (e.g., deli meat, dairy products made with unpasteurized milk, soft cheeses, or undercooked meat, seafood, or poultry). Initiate these Listeria precautions prior to starting LEMTRADA treatment. The incubation period for Listeria monocytogenes ranges from 3 to 70 days. In most cases, signs and symptoms of invasive listeriosis start within 1 month of exposure to Listeria monocytogenes. Symptoms of Listeria infection include fever, chills, diarrhea, nausea, vomiting, headache, pains in joints and muscles, neck stiffness, difficulty walking, mental status changes, coma, and other neurologic changes. As is the case with many infections, treatment cannot always prevent mortality and morbidity related to Listeria infections. Therefore, advise patients to watch for symptoms of Listeria infection and seek prompt medical help if symptoms occur.

Herpes Viral Infections

In controlled clinical studies, 16% of LEMTRADA-treated patients developed a herpes viral infection compared to 3% of interferon beta-1a patients. These events included oral herpes (8.8%), herpes zoster (4.2%), herpes simplex (1.8%), and genital herpes (1.3%). Serious herpetic infections in LEMTRADA-treated patients included primary varicella (0.1%), herpes zoster (0.2%), and herpes meningitis (0.1%). Administer antiviral agents for herpetic prophylaxis at appropriate suppressive dosing regimens. Administer antiviral prophylaxis for herpetic viral infections starting on the first day of each treatment course and continue for a minimum of two months following treatment with LEMTRADA or until the CD4+ lymphocyte count is ≥200 cells per microliter, whichever occurs later [see Dosage and Administration (2.2)].

Human Papilloma Virus

Cervical human papilloma virus (HPV) infection, including cervical dysplasia, occurred in 2% of LEMTRADA-treated patients. Annual HPV screening is recommended for female patients.

Tuberculosis

Tuberculosis occurred in patients treated with LEMTRADA and interferon beta-1a in controlled clinical studies. Active and latent tuberculosis cases occurred in 0.3% of LEMTRADA-treated patients, most often in endemic regions. Perform tuberculosis screening according to local guidelines prior to initiation of LEMTRADA. For patients testing positive in tuberculosis screening, treat by standard medical practice prior to therapy with LEMTRADA.

Fungal Infections

Fungal infections, especially oral and vaginal candidiasis, occurred more commonly in LEMTRADA-treated patients (12%) than in patients treated with interferon beta-1a (3%) in controlled clinical studies in MS.

Infections in Non-MS Patients

During postmarketing use, serious and sometimes fatal viral, bacterial, protozoan, and fungal infections, including some due to reactivation of latent infections, have been reported in the treatment of patients with B-CLL, as well as other disorders, generally at higher and more frequent doses than recommended in MS.

Hepatitis

No data are available on the association of LEMTRADA with Hepatitis B virus (HBV) or Hepatitis C virus (HCV) reactivation because patients with evidence of active or chronic infections were excluded from the clinical studies. Consider screening patients at high risk of HBV and/or HCV infection before initiation of LEMTRADA and exercise caution in prescribing LEMTRADA to patients identified as carriers of HBV and/or HCV as these patients may be at risk of irreversible liver damage relative to a potential virus reactivation as a consequence of their pre-existing status.

Progressive multifocal leukoencephalopathy (PML) has occurred in a patient with MS treated with LEMTRADA. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. PML was diagnosed two months after the second course of LEMTRADA. The patient had previously received multiple MS therapies, but had not received other drugs for treatment of MS for more than one year. The patient had no other identified systemic medical conditions resulting in compromised immune system function and had not previously been treated with natalizumab, which has a known association with PML. The patient was not taking any immunosuppressive or immunomodulatory medications concomitantly. After the diagnosis of PML, the patient developed immune reconstitution inflammatory syndrome (IRIS). The patient's condition improved, but mild residual neurologic sequelae remained at last follow-up.

At the first sign or symptom suggestive of PML, withhold LEMTRADA and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.

MRI findings may be apparent before clinical signs or symptoms. Cases of PML, diagnosed based on MRI findings and the detection of JCV DNA in the cerebrospinal fluid in the absence of clinical signs or symptoms specific to PML, have been reported in patients treated with other MS medications associated with PML. Many of these patients subsequently became symptomatic with PML. Therefore, monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. Following discontinuation of another MS medication associated with PML, lower PML-related mortality and morbidity have been reported in patients who were initially asymptomatic at diagnosis compared to patients who had characteristic clinical signs and symptoms at diagnosis. It is not known whether these differences are due to early detection and discontinuation of MS treatment or due to differences in disease in these patients.

LEMTRADA may increase the risk of acute acalculous cholecystitis. In controlled clinical studies, 0.2% of LEMTRADA-treated MS patients developed acute acalculous cholecystitis, compared to 0% of patients treated with interferon beta-1a. During postmarketing use, additional cases of acute acalculous cholecystitis have been reported in LEMTRADA-treated patients. Time to onset of symptoms ranged from less than 24 hours to 2 months after LEMTRADA infusion. Typical risk or predisposing factors such as concurrent critical illness was often not reported. Abnormal ultrasound or computed tomography was used to support the diagnosis of acute acalculous cholecystitis in some cases. Some patients were treated conservatively with antibiotics and recovered without surgical intervention, whereas others underwent cholecystectomy.

Symptoms of acute acalculous cholecystitis include abdominal pain, abdominal tenderness, fever, nausea, and vomiting. Leukocytosis and abnormal liver enzymes are also commonly observed. Acute acalculous cholecystitis is a condition that is associated with high morbidity and mortality rates if not diagnosed early and treated. If acute acalculous cholecystitis is suspected, evaluate and treat promptly.

In clinical studies, 6 of 1217 (0.5%) LEMTRADA-treated patients had pneumonitis of varying severity. Cases of hypersensitivity pneumonitis and pneumonitis with fibrosis occurred in clinical studies. Patients should be advised to report symptoms of pneumonitis, which may include shortness of breath, cough, wheezing, chest pain or tightness, and hemoptysis.

LEMTRADA contains the same active ingredient (alemtuzumab) found in CAMPATH®. If LEMTRADA is considered for use in a patient who has previously received CAMPATH, exercise increased vigilance for additive and long-lasting effects on the immune system.

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.

In controlled clinical trials (Study 1 and Study 2), a total of 811 patients with relapsing forms of MS received LEMTRADA. The population was 18 to 55 years of age, 65% were female, and 92% were Caucasian. A total of 811 patients received 1 course of therapy, and 789 patients received a second course of therapy at 12 months. The overall follow-up in the controlled trials was equivalent to 1622 patient years.

In MS clinical studies (controlled and open-label extension), overall, a total of 1217 patients received LEMTRADA. Approximately 60% of patients received a total of 2 treatment courses and approximately 24% of patients received a total of 3 treatment courses; others received a total of 4 or more treatment courses, although data beyond 3 treatment courses are limited. The overall follow-up was 6858 person-years. Patients had a median of 6 years of follow-up from the first LEMTRADA dose, with approximately 14% having at least 7 years of follow-up.

Most Common Adverse Reactions

In controlled clinical trials, the most common adverse reactions with LEMTRADA (in at least 10% of patients and more frequently than in interferon beta-1a) were rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infection, urticaria, pruritus, thyroid gland disorders, fungal infection, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting.

Table 1 lists adverse reactions occurring in ≥5% of LEMTRADA-treated patients in Study 1 and 2 and at the same or at a higher rate than interferon beta-1a.

<div class="scrollingtable"><table width="80%"> <caption> <span>Table 1: Adverse Reactions in the Pooled 2-Year Active-Controlled Studies in Patients with Relapsing-Remitting Multiple Sclerosis</span> </caption> <col align="left" valign="top" width="37%"/> <col align="center" valign="bottom" width="30%"/> <col align="center" valign="bottom" width="33%"/> <thead> <tr class="Botrule First Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule" valign="top">LEMTRADA<br/>(N=811) <br/>%</th><th align="center" class="Rrule" valign="top">interferon beta-1a 44 mcg<br/>(N=389)<br/>%</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Rash</td><td align="center" class="Rrule">53</td><td align="center" class="Rrule">6</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Headache</td><td align="center" class="Rrule">52</td><td align="center" class="Rrule">23</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pyrexia</td><td align="center" class="Rrule">29</td><td align="center" class="Rrule">9</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Nasopharyngitis</td><td align="center" class="Rrule">25</td><td align="center" class="Rrule">19</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Nausea</td><td align="center" class="Rrule">21</td><td align="center" class="Rrule">9</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Urinary tract infection</td><td align="center" class="Rrule">19</td><td align="center" class="Rrule">8</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Fatigue</td><td align="center" class="Rrule">18</td><td align="center" class="Rrule">13</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Insomnia</td><td align="center" class="Rrule">16</td><td align="center" class="Rrule">15</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Upper respiratory tract infection</td><td align="center" class="Rrule">16</td><td align="center" class="Rrule">13</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Herpes viral infection</td><td align="center" class="Rrule">16</td><td align="center" class="Rrule">3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Urticaria</td><td align="center" class="Rrule">16</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pruritus</td><td align="center" class="Rrule">14</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Thyroid gland disorders</td><td align="center" class="Rrule">13</td><td align="center" class="Rrule">3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Fungal infection</td><td align="center" class="Rrule">13</td><td align="center" class="Rrule">4</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Arthralgia</td><td align="center" class="Rrule">12</td><td align="center" class="Rrule">9</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pain in extremity</td><td align="center" class="Rrule">12</td><td align="center" class="Rrule">9</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Back pain</td><td align="center" class="Rrule">12</td><td align="center" class="Rrule">8</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Diarrhea</td><td align="center" class="Rrule">12</td><td align="center" class="Rrule">6</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Sinusitis</td><td align="center" class="Rrule">11</td><td align="center" class="Rrule">8</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Oropharyngeal pain</td><td align="center" class="Rrule">11</td><td align="center" class="Rrule">5</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Paresthesia</td><td align="center" class="Rrule">10</td><td align="center" class="Rrule">8</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Dizziness</td><td align="center" class="Rrule">10</td><td align="center" class="Rrule">5</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Abdominal pain</td><td align="center" class="Rrule">10</td><td align="center" class="Rrule">5</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Flushing</td><td align="center" class="Rrule">10</td><td align="center" class="Rrule">4</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Vomiting</td><td align="center" class="Rrule">10</td><td align="center" class="Rrule">3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Cough</td><td align="center" class="Rrule">9</td><td align="center" class="Rrule">4</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Chills</td><td align="center" class="Rrule">9</td><td align="center" class="Rrule">3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Dysgeusia</td><td align="center" class="Rrule">8</td><td align="center" class="Rrule">7</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Influenza</td><td align="center" class="Rrule">8</td><td align="center" class="Rrule">6</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Dermatitis</td><td align="center" class="Rrule">8</td><td align="center" class="Rrule">5</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Dyspepsia</td><td align="center" class="Rrule">8</td><td align="center" class="Rrule">4</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Blood in urine</td><td align="center" class="Rrule">8</td><td align="center" class="Rrule">3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Dyspnea</td><td align="center" class="Rrule">8</td><td align="center" class="Rrule">1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Tachycardia</td><td align="center" class="Rrule">8</td><td align="center" class="Rrule">1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Anxiety</td><td align="center" class="Rrule">7</td><td align="center" class="Rrule">6</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Muscular weakness</td><td align="center" class="Rrule">7</td><td align="center" class="Rrule">6</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Bronchitis</td><td align="center" class="Rrule">7</td><td align="center" class="Rrule">4</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Chest discomfort</td><td align="center" class="Rrule">7</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Muscle spasms</td><td align="center" class="Rrule">6</td><td align="center" class="Rrule">5</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Myalgia</td><td align="center" class="Rrule">6</td><td align="center" class="Rrule">5</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Decrease in CD4 lymphocytes</td><td align="center" class="Rrule">6</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Decrease in CD8 lymphocytes</td><td align="center" class="Rrule">6</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Asthenia</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">4</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Decrease in T-lymphocyte count</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">3</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Erythema</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Peripheral edema</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Epistaxis</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Neck pain</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">2</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Abnormal uterine bleeding</td><td align="center" class="Rrule">5</td><td align="center" class="Rrule">1</td> </tr> </tbody> </table></div>

Nearly all (99.9%) patients treated with LEMTRADA in MS clinical trials experienced lymphopenia. The lowest lymphocyte counts occurred approximately by 1 month after each course of treatment. The mean lymphocyte count at 1 month after LEMTRADA treatment was 0.25 × 109 L (range 0.02–2.30 × 109 L) and 0.32 (0.02–1.81 × 109 L) for treatment courses 1 and 2, respectively. Total lymphocyte counts increased to reach the lower limit of normal in approximately 40% of patients by 6 months after each LEMTRADA treatment course and approximately 80% of patients by 12 months after each course [see Clinical Pharmacology (12.2)].

In clinical studies, 0.6% of patients in both the LEMTRADA and interferon beta-1a groups had events of attempted suicide or suicidal ideation. There were no completed suicides in either clinical study treatment group. Suicidal behavior or ideation occurred in patients with or without a history of a psychiatric or thyroid disorder. Advise patients to report immediately any symptoms of depression or suicidal ideation to the prescribing physician.

As with all therapeutic proteins, there is potential for immunogenicity. The incidence of antibodies is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including inhibitory antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to LEMTRADA with the incidence of antibodies to other products may be misleading.

Using an enzyme-linked immunosorbent assay (ELISA) and a competitive binding assay, anti-alemtuzumab binding antibodies were detected in 62%, 67%, and 29% of LEMTRADA-treated patients, at months 1, 3, and 12 (Course 1) as well as 83%, 83%, and 75% of LEMTRADA-treated patients at months 13, 15, and 24 (Course 2). Samples that tested positive for binding antibodies were further evaluated for evidence of in vitro inhibition using a flow cytometry assay. Neutralizing antibodies were detected in 87%, 46%, and 5% of positive binding antibody patients at months 1, 3, and 12 (Course 1) as well as 94%, 88%, and 42% of positive binding antibody patients at months 13, 15, and 24 (Course 2). Anti-alemtuzumab antibodies were associated with decreased alemtuzumab concentration during Course 2, but not Course 1. Through 2 treatment courses, there was no evidence from clinical trials that the presence of binding or inhibitory anti-alemtuzumab antibodies had a significant effect on clinical outcomes, total lymphocyte count, or adverse events. High titer anti-alemtuzumab antibodies, which were observed in 13 patients, were associated with incomplete lymphocyte depletion following a third or fourth treatment course, but there was no clear effect of anti-alemtuzumab antibodies on the clinical efficacy or safety profile of LEMTRADA.

The following adverse reactions have been identified during post approval use of alemtuzumab. 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.

Postmarketing Experience with LEMTRADA

Blood and Lymphatic System Disorders: Acquired hemophilia A [see Warnings and Precautions (5.15)], neutropenia, thrombocytopenia [see Warnings and Precautions (5.2)], thrombotic thrombocytopenic purpura [see Warnings and Precautions (5.13)]

Cerebrovascular Disorders: Stroke, including hemorrhagic and ischemic stroke and cervicocephalic arterial dissection [see Warnings and Precautions (5.3)]

Gastrointestinal System Disorders: Cholecystitis, including acalculous cholecystitis and acute acalculous cholecystitis [see Warnings and Precautions (5.19)], immune-mediated colitis [see Warnings and Precautions (5.16)]

Hepatobiliary Disorders: Autoimmune hepatitis [see Warnings and Precautions (5.10)], viral hepatitis [see Warnings and Precautions (5.17)]

Infections and Infestations: Opportunistic infections [see Warnings and Precautions (5.17)], Progressive multifocal leukoencephalopathy [see Warnings and Precautions (5.18)]

Immune System Disorders: Autoimmune hepatitis, vasculitis, Guillain-Barré syndrome [see Warnings and Precautions (5.1)], hemophagocytic lymphohistiocytosis [see Warnings and Precautions (5.11)], sarcoidosis

Musculoskeletal and Connective Tissue Disorders: Adult Onset Still's Disease [see Warnings and Precautions (5.12)]

Nervous System Disorders: Autoimmune encephalitis [see Warnings and Precautions (5.14)], myasthenia gravis, Lambert-Eaton myasthenic syndrome

Pulmonary System Disorders: Pulmonary alveolar hemorrhage [see Warnings and Precautions (5.2)]

Skin and Subcutaneous Tissue Disorders: Alopecia

Postmarketing Experience with CAMPATH

CAMPATH is approved for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) and is generally administered at higher and more frequent doses (e.g., 30 mg) than recommended in the treatment of MS.

Cardiac Disorders: Congestive heart failure, cardiomyopathy, and decreased ejection fraction in non-MS patients previously treated with potentially cardiotoxic agents.

Risk Summary

There are no adequate data on the developmental risk associated with the use of LEMTRADA in pregnant women. LEMTRADA was embryolethal in pregnant huCD52 transgenic mice when administered during organogenesis [see Animal data]. Auto-antibodies may develop after administration of LEMTRADA. Placental transfer of anti-thyroid antibodies resulting in neonatal Graves' disease has been reported.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

There is a pregnancy surveillance program for LEMTRADA. If LEMTRADA exposure occurs during pregnancy, healthcare providers and patients are encouraged to report pregnancies by calling 1-800-745-4447, option 2.

Clinical Considerations

LEMTRADA induces persistent thyroid disorders [see Warnings and Precautions (5.8)]. Untreated hypothyroidism in pregnant women increases the risk for miscarriage and may have effects on the fetus including mental retardation and dwarfism. In mothers with Graves' disease, maternal thyroid stimulating hormone receptor antibodies can be transferred to a developing fetus and can cause neonatal Graves' disease. In a patient who developed Graves' disease after treatment with alemtuzumab, placental transfer of anti-thyrotropin receptor antibodies resulted in neonatal Graves' disease with thyroid storm in her infant who was born 1 year after alemtuzumab dosing [see Warnings and Precautions (5.1)].

Data

Animal data

When LEMTRADA was administered to pregnant huCD52 transgenic mice during organogenesis (gestation days [GD] 6–10 or GD 11–15) at doses of 3 or 10 mg/kg IV, no teratogenic effects were observed. However, there was an increase in embryolethality (increased postimplantation loss and the number of dams with all fetuses dead or resorbed) in pregnant animals dosed during GD 11–15. In a separate study in pregnant huCD52 transgenic mice, administration of LEMTRADA during organogenesis (GD 6–10 or GD 11–15) at doses of 3 or 10 mg/kg IV, decreases in B- and T-lymphocyte populations were observed in the offspring at both doses tested.

In pregnant huCD52 transgenic mice administered LEMTRADA at doses of 3 or 10 mg/kg/day IV throughout gestation and lactation, there was an increase in pup deaths during the lactation period at 10 mg/kg. Decreases in T- and B-lymphocyte populations and in antibody response were observed in offspring at both doses tested.

Risk Summary

There are no data on the presence of alemtuzumab in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Alemtuzumab was detected in the milk of lactating huCD52 transgenic mice administered LEMTRADA [see Animal data].

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LEMTRADA and any potential adverse effects on the breastfed child from LEMTRADA or from the underlying maternal conditions.

Data

Animal data

Alemtuzumab was detected in the milk of lactating huCD52 transgenic mice following intravenous administration of LEMTRADA at a dose of 10 mg/kg on postpartum days 8–12. Serum levels of alemtuzumab were similar in lactating mice and offspring on postpartum Day 13 and were associated with evidence of pharmacological activity (decrease in lymphocyte counts) in the offspring.

Contraception

Before initiation of LEMTRADA treatment, women of childbearing potential should be counselled on the potential for a serious risk to the fetus. To avoid in utero exposure to LEMTRADA, women of childbearing potential should use effective contraceptive measures when receiving a course of treatment with LEMTRADA and for 4 months following that course of treatment [see Use in Specific Populations (8.1)].

Infertility

In huCD52 transgenic mice, administration of LEMTRADA prior to and during the mating period resulted in adverse effects on sperm parameters in males and reduced number of corpora lutea and implantations in females [see Nonclinical Toxicology (13.1)].

Safety and effectiveness in pediatric patients less than 17 years of age have not been established. Use of LEMTRADA is not recommended in pediatric patients due to the risks of autoimmunity, infusion reactions, and stroke, and because it may increase the risk of malignancies (thyroid, melanoma, lymphoproliferative disorders, and lymphoma) [see Warnings and Precautions (5.1, 5.2, 5.3, 5.4)].

Clinical studies of LEMTRADA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.

Two MS patients experienced serious reactions (headache, rash, and either hypotension or sinus tachycardia) after a single accidental infusion up to 60 mg of LEMTRADA. Doses of LEMTRADA greater than those recommended may increase the intensity and/or duration of infusion reactions or its immune effects. There is no known antidote for alemtuzumab overdosage.

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Alemtuzumab is a recombinant humanized IgG1 kappa monoclonal antibody directed against the cell surface glycoprotein, CD52. Alemtuzumab has an approximate molecular weight of 150 kD. Alemtuzumab is produced in mammalian cell (Chinese hamster ovary) suspension culture in a nutrient medium containing neomycin. Neomycin is not detectable in the final product.

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LEMTRADA (alemtuzumab) injection is a sterile, clear and colorless to slightly yellow, solution (pH 7.2 ± 0.2) for intravenous infusion.

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Each 1 mL of solution contains 10 mg alemtuzumab, dibasic sodium phosphate (1.15 mg), disodium edetate dihydrate (0.0187 mg), polysorbate 80 (0.1 mg), potassium chloride (0.2 mg), potassium dihydrogen phosphate (0.2 mg), sodium chloride (8 mg), and Water for Injection, USP.

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The precise mechanism by which alemtuzumab exerts its therapeutic effects in multiple sclerosis is unknown but is presumed to involve binding to CD52, a cell surface antigen present on T and B lymphocytes, and on natural killer cells, monocytes, and macrophages. Following cell surface binding to T and B lymphocytes, alemtuzumab results in antibody-dependent cellular cytolysis and complement-mediated lysis.

Effects of LEMTRADA on the Lymphocyte Population

LEMTRADA depletes circulating T and B lymphocytes after each treatment course. In clinical trials, the lowest cell counts occurred 1 month after a course of treatment at the time of the first post-treatment blood count. Lymphocyte counts then increased over time: B cell counts usually recovered within 6 months; T cell counts increased more slowly and usually remained below baseline 12 months after treatment. Approximately 60% of patients had total lymphocyte counts below the lower limit of normal 6 months after each treatment course and 20% had counts below the lower limit of normal after 12 months.

Reconstitution of the lymphocyte population varies for the different lymphocyte subtypes. At Month 1 in clinical trials, the mean CD4+ lymphocyte count was 40 cells per microliter, and, at Month 12, 270 cells per microliter. At 30 months, approximately half of patients had CD4+ lymphocyte counts that remained below the lower limit of normal.

Cardiac Electrophysiology

In a study of 53 MS patients, alemtuzumab 12 mg per day for 5 days caused no changes in the QTc interval greater than 20 ms. An average 22 to 26 beats-per-minute increase in heart rate was observed for at least 2 hours after the first but not subsequent infusions.

The pharmacokinetics of LEMTRADA were evaluated in a total of 148 patients with relapsing forms of MS who received 12 mg/day on 5 consecutive days, followed by 12 mg/day on 3 consecutive days 12 months following the first treatment course.

Absorption

Serum concentrations increased with each consecutive dose within a treatment course, with the highest observed concentrations occurring following the last infusion of a treatment course. The mean maximum concentration was 3014 ng/mL on Day 5 of the first treatment course, and 2276 ng/mL on Day 3 of the second treatment course.

Distribution

LEMTRADA is largely confined to the blood and interstitial space with a central volume of distribution of 14.1 L.

Elimination

The elimination half-life was approximately 2 weeks and was comparable between courses. The serum concentrations were generally undetectable (<60 ng/mL) within approximately 30 days following each treatment course.

Specific Populations

Age, race, or gender had no effect on the pharmacokinetics of LEMTRADA.

Studies to assess the carcinogenic or genotoxic potential of LEMTRADA have not been conducted.

When LEMTRADA (3 or 10 mg/kg IV) was administered to huCD52 transgenic male mice on 5 consecutive days prior to cohabitation with untreated wild-type females, no effect on fertility or reproductive performance was observed. However, adverse effects on sperm parameters (including abnormal morphology [detached/no head] and reduced total count and motility) were observed at both doses tested.

When LEMTRADA (3 or 10 mg/kg IV) was administered to huCD52 transgenic female mice for 5 consecutive days prior to cohabitation with untreated wild-type males, there was a decrease in the average number of corpora lutea and implantation sites and an increase in postimplantation loss, resulting in fewer viable embryos at the higher dose tested.

Study 1

Study 1 was a 2-year randomized, open-label, rater-blinded, active comparator (interferon beta-1a 44 micrograms administered subcutaneously three times a week) controlled study in patients with RRMS. Patients entering Study 1 had Expanded Disability Status Scale (EDSS) scores of 5 or less and had to have experienced at least one relapse while on interferon beta or glatiramer acetate therapy.

Patients were randomized to receive LEMTRADA (n=426) or interferon beta-1a (n=202). At baseline, the mean age was 35 years, the mean disease duration was 4.5 years, and the mean EDSS score was 2.7.

The clinical outcome measures were the annualized relapse rate (ARR) over 2 years and the time to confirmed disability progression. Confirmed disability progression was defined as at least a 1 point increase above baseline EDSS (1.5 point increase for patients with baseline EDSS of 0) sustained for 6 months. The MRI outcome measure was the change in T2 lesion volume.

The annualized relapse rate was significantly lower in patients treated with LEMTRADA than in patients who received interferon beta-1a. Time to onset of 6-month confirmed disability progression was significantly delayed with LEMTRADA treatment compared to interferon beta-1a. There was no significant difference between the treatment groups for the change in T2 lesion volume. The results of Study 1 are shown in Table 2 and Figure 1.

<div class="scrollingtable"><table width="85%"> <caption> <span>Table 2: Clinical and MRI Results of Study 1</span> </caption> <col align="left" valign="middle" width="45%"/> <col align="center" valign="middle" width="20%"/> <col align="center" valign="middle" width="20%"/> <col align="center" valign="middle" width="15%"/> <thead> <tr class="First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule" valign="top">LEMTRADA</th><th align="center" class="Rrule" valign="top">interferon beta-1a<br/> 44 mcg</th><th align="center" class="Rrule" valign="top">p-value</th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">(N=426)</th><th align="center" class="Rrule">(N=202)</th><th align="center" class="Rrule"></th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">Clinical Outcomes</span></td><td align="center" class="Botrule Rrule"></td> </tr> <tr> <td align="left" class="Lrule Rrule">Annualized relapse rate</td><td align="center" class="Rrule">0.26</td><td align="center" class="Rrule">0.52</td><td align="center" class="Rrule">&lt;0.0001</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Relative reduction</td><td align="center" class="Rrule">49%</td><td align="center" class="Rrule"></td><td align="center" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule Rrule">Proportion of patients with disability progression at Year 2</td><td align="center" class="Rrule">13%</td><td align="center" class="Rrule">21%</td><td align="center" class="Rrule">0.0084</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Relative risk reduction</td><td align="center" class="Rrule">42%</td><td align="center" class="Rrule"></td><td align="center" class="Rrule"></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Percent of patients remaining relapse-free at Year 2</td><td align="center" class="Botrule Rrule">65%</td><td align="center" class="Botrule Rrule">47%</td><td align="center" class="Botrule Rrule">&lt;0.0001</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">MRI Outcomes</span></td><td align="center" class="Botrule Rrule"> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule">Percent change in T2 lesion volume from baseline</td><td align="center" class="Botrule Rrule">-1.3</td><td align="center" class="Botrule Rrule">-1.2</td><td align="center" class="Botrule Rrule">0.14</td> </tr> </tbody> </table></div>

Figure 1: Time to 6-month Confirmed Disability Progression (Study 1)

Study 2

Study 2 was a 2-year randomized, open-label, rater-blinded, active comparator (interferon beta-1a 44 micrograms administered subcutaneously three times a week) controlled study in patients with RRMS. Patients entering Study 2 had EDSS scores of 3 or less and no prior treatment for multiple sclerosis.

Patients were randomized to receive LEMTRADA (n=376) or interferon beta-1a (n=187). At baseline, the mean age was 33 years, the mean disease duration was 2 years, and the mean EDSS score was 2.

The clinical outcome measures were the annualized relapse rate (ARR) over 2 years and the time to confirmed disability progression, as defined in Study 1. The MRI outcome measure was the change in T2 lesion volume.

The annualized relapse rate was significantly lower in patients treated with LEMTRADA than in patients who received interferon beta-1a. There was no significant difference between the treatment groups for the time to confirmed disability progression and for the primary MRI endpoint (change in T2 lesion volume). The results for Study 2 are shown in Table 3.

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 3: Clinical and MRI Results of Study 2</span> </caption> <col align="left" valign="top" width="45%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="15%"/> <thead> <tr class="First"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">LEMTRADA</th><th align="center" class="Rrule">interferon beta-1a<br/> 44 mcg</th><th align="center" class="Rrule">p-value</th> </tr> <tr class="Botrule Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule" valign="bottom">(N=376)</th><th align="center" class="Rrule">(N=187)</th><th align="center" class="Rrule"></th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Clinical Outcomes</span></td><td align="center" class="Botrule Rrule"> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Annualized relapse rate<br/>  Relative reduction</td><td align="center" class="Rrule">0.18<br/>55%</td><td align="center" class="Rrule">0.39</td><td align="center" class="Rrule">&lt;0.0001</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Proportion of patients with disability progression at Year 2<br/>  Relative risk reduction</td><td align="center" class="Rrule">8%<br/>30%</td><td align="center" class="Rrule">11%</td><td align="center" class="Rrule">0.22</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Percent of patients remaining relapse-free at Year 2</td><td align="center" class="Rrule">78%</td><td align="center" class="Rrule">59%</td><td align="center" class="Rrule">&lt;0.0001</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">MRI Outcomes</span></td><td align="center" class="Botrule Rrule"> </td> </tr> <tr class="Botrule Last"> <td align="left" class="Lrule Rrule">Percent change in T2 lesion volume from baseline</td><td align="center" class="Rrule">-9.3</td><td align="center" class="Rrule">-6.5</td><td align="center" class="Rrule">0.31</td> </tr> </tbody> </table></div>

LEMTRADA (alemtuzumab) injection is a sterile, clear and colorless to slightly yellow solution for intravenous infusion, containing no antimicrobial preservatives.

Each LEMTRADA carton (NDC: 58468-0200-1) contains one single-dose vial that delivers 12 mg/1.2 mL (10 mg/mL). The vial stopper is not made with natural rubber latex.

Store LEMTRADA vials at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Store in original carton to protect from light.

Autoimmunity

Infusion Reactions

Stroke and Cervicocephalic Arterial Dissection

Malignancies

LEMTRADA REMS Program

Hemophagocytic Lymphohistiocytosis

Adult Onset Still's Disease (AOSD)

Thrombotic Thrombocytopenic Purpura

Immune-Mediated Colitis

Infections

Progressive Multifocal Leukoencephalopathy

Acute Acalculous Cholecystitis

Pneumonitis

Concomitant Use of CAMPATH

Fetal Risk

Manufactured and distributed by:Genzyme Corporation Cambridge, MA 02141A SANOFI COMPANYUS License Number: 1596

{ "type": "p", "children": [], "text": "Manufactured and distributed by:Genzyme Corporation Cambridge, MA 02141A SANOFI COMPANYUS License Number: 1596" }

LEMTRADA and CAMPATH are registered trademarks of Genzyme Corporation. ©2024 Genzyme Corporation.

{ "type": "p", "children": [], "text": "LEMTRADA and CAMPATH are registered trademarks of Genzyme Corporation. ©2024 Genzyme Corporation." }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="2%"/> <col align="left" valign="top" width="2%"/> <col align="left" valign="top" width="46%"/> <col align="left" valign="top" width="50%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="3">This Medication Guide has been approved by the U.S. Food and Drug Administration</td><td align="right">Revised: May 2024</td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="4"> <p class="First"> <span class="Bold">MEDICATION GUIDE</span> <br/>LEMTRADA<span class="Sup">®</span> (lem-TRA-da)<br/>(alemtuzumab), injection for intravenous infusion</p> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First">Read this Medication Guide before you start receiving LEMTRADA and before you begin each treatment course. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.</p> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First"> <a name="important"></a><span class="Bold">What is the most important information I should know about LEMTRADA?</span> </p> <p> <span class="Bold">LEMTRADA can cause serious side effects, including:</span> </p> <dl> <dt class="Bold">1.</dt> <dd> <span class="Bold">Serious autoimmune problems.</span> Some people receiving LEMTRADA develop a condition where the immune cells in your body attack other cells or organs in the body (autoimmunity) which can be serious and may cause death. Serious autoimmune problems may include:</dd> </dl> <ul class="Disc"> <li> <span class="Bold">immune thrombocytopenic purpura (ITP).</span> LEMTRADA may cause the number of platelets in your blood to be reduced (ITP). ITP can cause severe bleeding that may cause life-threatening problems. Call your healthcare provider right away if you have any of the following symptoms:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Circle"> <li>easy bruising</li> <li>bleeding from a cut that is hard to stop</li> <li>coughing up blood</li> <li>heavier menstrual periods than normal</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>bleeding from your gums or nose that is new or takes longer than usual to stop</li> <li>small, scattered spots on your skin that are red, pink, or purple</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li> <span class="Bold">kidney problems.</span> LEMTRADA may cause a serious kidney problem called anti-glomerular basement membrane disease. If this happens and you do not get treated, anti-glomerular basement membrane disease can lead to severe kidney damage, kidney failure that needs dialysis, a kidney transplant, or death. Call your healthcare provider right away if you have any of the following symptoms:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Circle"> <li>swelling of your legs or feet</li> <li>blood in the urine (red or tea-colored urine)</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>decrease in urine</li> <li>fatigue</li> <li>coughing up blood</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First">Side effects may happen while you receive LEMTRADA and for 4 years after you stop receiving LEMTRADA. Your healthcare provider will order blood and urine tests before you receive, while you are receiving, and every month for 4 years after you receive your last LEMTRADA infusion. You may need to continue these blood and urine tests after 4 years if you have any autoimmune signs or symptoms. The blood and urine tests will help your healthcare provider watch for signs and symptoms of serious autoimmune problems.</p> <p>It is important to have your blood and urine tested, even if you are feeling well and do not have any symptoms from LEMTRADA and your multiple sclerosis. This may help your healthcare provider find any problems early.</p> <dl class="Disc"> <dt class="Bold">2.</dt> <dd> <span class="Bold">Serious infusion reactions.</span> LEMTRADA can cause serious infusion reactions that may cause death. Serious infusion reactions may happen while you receive, or up to 24 hours or longer after you receive LEMTRADA.<br/>You will receive your infusion at a healthcare facility with equipment and staff trained to manage infusion reactions. You will be watched while you receive and for at least <span class="Bold">2</span> hours after you receive LEMTRADA. <span class="Bold">It is important</span> that you stay at the infusion center for at least <span class="Bold">2</span> hours after your infusion is finished or longer if your healthcare provider decides you need to stay longer. If a serious infusion reaction happens while you are receiving LEMTRADA, your infusion may be stopped.<br/>Tell your healthcare provider right away if you have any of the following symptoms of a serious infusion reaction during the infusion, and after you have left the healthcare facility:</dd> </dl> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Circle"> <li>swelling in your mouth or throat</li> <li>trouble breathing</li> <li>weakness</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>fast, slow, or irregular heartbeat</li> <li>chest pain</li> <li>rash</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First">To lower your chances of getting a serious infusion reaction, your healthcare provider will give you a medicine called corticosteroids before your first 3 infusions of a treatment course. You may also be given other medicines before or after the infusion to try to reduce your chances of these reactions or to treat them after they happen.</p> <dl> <dt class="Bold">3.</dt> <dd> <span class="Bold">Stroke and tears in your arteries that supply blood to your brain (carotid and vertebral arteries).</span> Some people have had serious and sometimes deadly strokes and tears in their carotid or vertebral arteries within 3 days of receiving LEMTRADA. Get help right away if you have any of the following symptoms that may be signs of a stroke or tears in your carotid or vertebral arteries:</dd> </dl> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>drooping of parts of your face</li> <li>sudden severe headache</li> <li>neck pain</li> </ul> </td><td align="left" class="Rrule"> <ul class="Disc"> <li>weakness on one side</li> <li>difficulty with speech</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <dl> <dt class="Bold">4.</dt> <dd> <span class="Bold">Certain cancers.</span> Receiving LEMTRADA may increase your chance of getting some kinds of cancers, including thyroid cancer, skin cancer (melanoma), and blood cancers called lymphoproliferative disorders and lymphoma. Call your healthcare provider if you have the following symptoms that may be a sign of thyroid cancer:</dd> </dl> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>new lump</li> <li>swelling in your neck</li> <li>pain in the front of your neck</li> <li>hoarseness or other voice changes that do not go away</li> </ul> </td><td align="left" class="Rrule"> <ul class="Disc"> <li>trouble swallowing or breathing</li> <li>cough that is not caused by a cold</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First">You should have your skin checked before you start receiving LEMTRADA and each year while you are receiving treatment to monitor symptoms of skin cancer.</p> <p> <span class="Bold">Because of your risk of autoimmunity, infusion reactions, and the risk of some kinds of cancers, LEMTRADA is only available through a restricted program called the LEMTRADA Risk Evaluation and Mitigation Strategy (REMS) Program.</span> Call 1-855-676-6326 to enroll in the LEMTRADA REMS Program.</p> <ul class="Disc"> <li>You and your healthcare provider must be enrolled in the LEMTRADA REMS Program.</li> <li>LEMTRADA can only be given at a certified healthcare facility that participates in the LEMTRADA REMS Program. Your healthcare provider can give you information on how to find a certified healthcare facility.</li> <li>Read the LEMTRADA REMS "LEMTRADA Treatment and Infusion Reactions Patient Guide" after you are enrolled in the program.</li> <li>Carry your LEMTRADA REMS Patient Safety Information Card with you in case of an emergency.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First"> <span class="Bold">What is LEMTRADA?</span> </p> <p>LEMTRADA is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults. Since treatment with LEMTRADA can increase your risk of getting certain conditions and diseases, LEMTRADA is generally prescribed for people who have tried 2 or more MS medicines that have not worked well enough. LEMTRADA is not recommended for use in patients with clinically isolated syndrome (CIS).</p> <p>It is not known if LEMTRADA is safe and effective for use in children under 17 years of age.</p> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First"> <span class="Bold">Who should not receive LEMTRADA?</span> </p> <p> <span class="Bold">Do not receive LEMTRADA if you:</span> </p> <ul class="Disc"> <li>are allergic to alemtuzumab or to any of the inactive ingredients in LEMTRADA. See the end of this Medication Guide for a complete list of ingredients in LEMTRADA.</li> <li>are infected with human immunodeficiency virus (HIV).</li> <li>have an active infection.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First"> <span class="Bold">What should I tell my healthcare provider before receiving LEMTRADA?</span> </p> <p>Before receiving LEMTRADA, tell your healthcare provider if you:</p> <ul class="Disc"> <li>have bleeding problems.</li> <li>have thyroid problems.</li> <li>have kidney problems.</li> <li>have a recent history of infection.</li> <li>are taking a medicine called CAMPATH<span class="Sup">®</span>. Alemtuzumab, the active ingredient in LEMTRADA, is the same drug as CAMPATH.</li> <li>have received a live vaccine in the past 6 weeks before receiving LEMTRADA or plan to receive any live vaccines. Ask your healthcare provider if you are not sure if your vaccine is a live vaccine.</li> <li>are pregnant or plan to become pregnant. LEMTRADA may harm your unborn baby.<ul class="Circle"> <li>There is a pregnancy surveillance program for people who are exposed to LEMTRADA during pregnancy. The purpose of the program is to collect information about the health of pregnant people exposed to LEMTRADA and their babies. If you become pregnant, inform your healthcare provider.</li> </ul> </li> <li>you should use birth control while receiving LEMTRADA and for 4 months after your course of treatment.</li> <li>are breastfeeding or plan to breastfeed. It is not known if LEMTRADA passes into your breast milk. You and your healthcare provider should decide if you should receive LEMTRADA or breastfeed.</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>LEMTRADA and other medicines may affect each other causing side effects. Especially tell your healthcare provider if you take medicines that increase your chance of getting infections, including medicines used to treat cancer or to control your immune system.</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 class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First"> <span class="Bold">How will I receive LEMTRADA?</span> </p> <ul class="Disc"> <li>LEMTRADA is given through a needle placed in your vein (IV infusion).</li> <li>It takes about 4 hours to receive a full dose of LEMTRADA each day.</li> <li>You will receive LEMTRADA over 2 or more treatment courses.</li> <li>You will receive LEMTRADA for 5 days in a row (consecutive) for the first treatment course and then for 3 days in a row (consecutive) about 1 year later for your second treatment course.</li> <li>Additional LEMTRADA treatment courses, if needed, may be given for 3 days in a row (consecutive) at least 1 year after the prior treatment course.</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First"> <span class="Bold">What are the possible side effects of LEMTRADA?</span> </p> <p> <span class="Bold">LEMTRADA may cause serious side effects including:</span> </p> <ul class="Disc"> <li>see <span class="Bold">"<a href="#important">What is the most important information I should know about LEMTRADA?</a>"</span> </li> <li> <span class="Bold">thyroid problems.</span> Some people who receive LEMTRADA may get thyroid problems including an overactive thyroid (hyperthyroidism) or an underactive thyroid (hypothyroidism). Your healthcare provider will do blood tests to check how your thyroid is working. Call your healthcare provider if you have any of the symptoms of thyroid problems.<ul class="Circle"> <li>Symptoms of <span class="Bold">hyperthyroidism</span> may include:</li> </ul> </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule" colspan="2"></td><td align="left"> <dl> <dt>–</dt> <dd>excessive sweating</dd> <dt>–</dt> <dd>unexplained weight loss</dd> <dt>–</dt> <dd>fast heartbeat</dd> </dl> </td><td align="left" class="Rrule"> <dl> <dt>–</dt> <dd>eye swelling</dd> <dt>–</dt> <dd>nervousness</dd> </dl> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" class="Rrule" colspan="3"> <ul class="Circle"> <li>Symptoms of <span class="Bold">hypothyroidism</span> may include:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule" colspan="2"></td><td align="left"> <dl> <dt>–</dt> <dd>unexplained weight gain</dd> <dt>–</dt> <dd>feeling cold</dd> </dl> </td><td align="left" class="Rrule"> <dl> <dt>–</dt> <dd>worsening tiredness</dd> <dt>–</dt> <dd>constipation</dd> </dl> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li> <span class="Bold">low blood counts (cytopenias).</span> LEMTRADA may cause a decrease in some types of blood cells. Some people with these low blood counts have increased infections. Symptoms of cytopenias may include:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Circle"> <li>weakness</li> <li>chest pain</li> <li>yellowing of the skin or whites of eyes (jaundice)</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>dark urine</li> <li>fast heartbeat</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First">Your healthcare provider will do blood tests to check for cytopenias. Call your healthcare provider right away if you have symptoms listed above.</p> <ul class="Disc"> <li> <span class="Bold">inflammation of the liver.</span> Call your healthcare provider right away if you have symptoms such as unexplained nausea, stomach pain, tiredness, loss of appetite, yellowing of skin or whites of eyes, or bleeding or bruising more easily than normal.</li> <li> <span class="Bold">hemophagocytic lymphohistiocytosis (HLH).</span> LEMTRADA may increase the risk of a type of overactivity of the immune system (hemophagocytic lymphohistiocytosis) that can be fatal, especially if not diagnosed and treated early. Call your healthcare provider right away if you have symptoms such as fever, swollen glands, skin rash, or new nervous system problems, such as seizures, changes in your thinking or level of alertness, or new or worsening unsteadiness or trouble walking. These symptoms have happened in people taking LEMTRADA about 13 months to 33 months after they started taking LEMTRADA.</li> <li> <span class="Bold">adult onset still's disease (AOSD).</span> Adult onset still's disease (AOSD) is a rare condition that can cause a high fever lasting more than 1 week, pain, stiffness with or without swelling in multiple joints, and/or a skin rash. If you experience a combination of these symptoms, contact your healthcare provider immediately.</li> <li> <span class="Bold">thrombotic thrombocytopenic purpura (TTP).</span> Thrombotic thrombocytopenic purpura (TTP) can occur with LEMTRADA. TTP is a blood clotting problem where blood clots can form in blood vessels anywhere in the body. TTP needs to be treated in a hospital right away, because it can cause death. Get medical help right away if you have any of these symptoms: </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Circle"> <li>purplish spots (called purpura) on the skin or in the mouth (mucous membranes) due to bleeding under the skin</li> <li>your skin or the whites of your eyes are yellow (jaundice)</li> <li>you feel tired or weak</li> <li>your skin looks very pale</li> <li>fever</li> <li>fast heart rate or feeling short of breath</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>headache</li> <li>speech changes</li> <li>confusion</li> <li>vision changes</li> <li>seizure</li> <li>low amount of urine or dark urine, or urine that has blood in it</li> <li>stomach area (abdominal) pain</li> <li>nausea, vomiting, or diarrhea</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li> <span class="Bold">autoimmune encephalitis (AIE).</span> Autoimmune encephalitis (AIE), a brain disorder, can occur after receiving LEMTRADA and may include symptoms that may seem like an MS relapse. Call your healthcare provider right away if you have any of the following symptoms:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Circle"> <li>personality changes</li> <li>mood changes</li> <li>agitation</li> <li>seeing things that are not there (hallucinations)</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>short term memory loss</li> <li>confusion</li> <li>movement disorders</li> <li>seizure</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li> <span class="Bold">bleeding disorder (acquired hemophilia A).</span> LEMTRADA may cause a bleeding disorder called acquired hemophilia A. Call your healthcare provider right away if you have any of the following symptoms:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Circle"> <li>bruising</li> <li>nose bleeds</li> <li>painful or swollen joints</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>blood in urine</li> <li>dark or bloody stools</li> <li>bleeding from a cut that may take longer than usual to stop</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li> <span class="Bold">inflammation of the colon (colitis):</span> <br/>Tell your healthcare provider if you have any symptoms of colitis, such as<span class="Bold">:</span> <ul class="Circle"> <li>diarrhea (loose stools) or more frequent bowel movements than usual</li> <li>stools that are black, tarry, sticky or have blood or mucous</li> <li>severe stomach-area (abdomen) pain or tenderness</li> </ul> </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li> <span class="Bold">serious infections.</span> LEMTRADA may cause you to have serious infections while you receive and after receiving a treatment course. Serious infections may include:<ul class="Circle"> <li> <span class="Bold">listeria.</span> People who receive LEMTRADA have an increased chance of getting an infection caused by the bacteria, listeria, which can lead to significant complications or death. Avoid foods that may be a source for listeria (for example, deli meat, unpasteurized milk and cheese products, soft cheeses, or undercooked meat, seafood or poultry) or make sure that the food you eat which may contain listeria is heated well if you receive treatment with LEMTRADA.</li> <li> <span class="Bold">herpes viral infections.</span> Some people taking LEMTRADA have an increased chance of getting herpes viral infections. Your healthcare provider will prescribe medicines to reduce your chances of getting these infections. Take these medicines exactly as your healthcare provider tells you to.</li> <li> <span class="Bold">human papilloma virus (HPV).</span> Females have an increased chance of getting a cervical HPV infection. If you are a female, you should have an HPV screening each year.</li> <li> <span class="Bold">tuberculosis.</span> Your healthcare provider should check you for tuberculosis before you receive LEMTRADA.</li> <li> <span class="Bold">fungal infections.</span> </li> </ul> </li> </ul> <p class="First">Call your healthcare provider right away if you have symptoms of a serious infection, such as fever or swollen glands. You may need to go to the hospital for treatment if you get a serious infection. It is important to tell the healthcare providers that you have received LEMTRADA.</p> <p>Talk to your healthcare provider before you get vaccinations after receiving LEMTRADA. Certain vaccinations may increase your chances of getting infections.</p> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li> <span class="Bold">Progressive multifocal leukoencephalopathy (PML).</span> A rare brain infection that usually leads to death or severe disability has been reported with LEMTRADA. Symptoms of PML get worse over days to weeks. It is important that you call your doctor right away if you have any new or worsening medical problems that have lasted several days, including problems with: </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Circle"> <li>thinking</li> <li>eyesight</li> <li>strength</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>balance</li> <li>weakness on 1 side of your body</li> <li>using your arms or legs</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li> <span class="Bold">Inflammation of the gallbladder without gallstones (acalculous cholecystitis).</span> LEMTRADA may increase your chance of getting inflammation of the gallbladder without gallstones, a serious medical condition that can be life-threatening. Call your healthcare provider right away if you have any of the following symptoms of acalculous cholecystitis, which may include: </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Circle"> <li>stomach pain or discomfort</li> <li>fever</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>nausea or vomiting</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <ul class="Disc"> <li> <span class="Bold">swelling of lung tissue (pneumonitis).</span> Some people have had swelling of the lung tissue while receiving LEMTRADA. Call your healthcare provider right away if you have the following symptoms:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Circle"> <li>shortness of breath</li> <li>cough</li> <li>wheezing</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>chest pain or tightness</li> <li>coughing up blood</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First">The most common side effects of LEMTRADA include:</p> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Disc"> <li>rash</li> <li>headache</li> <li>thyroid problems</li> <li>fever</li> <li>swelling of your nose and throat (nasopharyngitis)</li> <li>nausea </li> <li>urinary tract infection</li> <li>feeling tired</li> <li>trouble sleeping</li> <li>upper respiratory tract infection</li> <li>herpes viral infection</li> <li>hives</li> <li>itching</li> </ul> </td><td align="left" class="Rrule"> <ul class="Disc"> <li>fungal infection</li> <li>joint pain</li> <li>pain in your arms or legs</li> <li>back pain</li> <li>diarrhea</li> <li>sinus infection</li> <li>mouth pain or sore throat</li> <li>tingling sensation</li> <li>dizziness</li> <li>stomach pain</li> <li>sudden redness in face, neck, or chest</li> <li>vomiting</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First">Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</p> <p>These are not all the possible side effects of LEMTRADA. For more information, ask your healthcare provider or pharmacist.</p> <p>Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.</p> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First"> <span class="Bold">General information about the safe and effective use of LEMTRADA.</span> </p> <p>This Medication Guide summarizes the most important information about LEMTRADA. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about LEMTRADA that is written for health professionals.</p> <p>For more information, go to www.LemtradaREMS.com or call Genzyme at 1-855-676-6326.</p> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First"> <span class="Bold">What are the ingredients in LEMTRADA?</span> </p> <p> <span class="Bold">Active ingredient:</span> alemtuzumab</p> <p> <span class="Bold">Inactive ingredients:</span> dibasic sodium phosphate, disodium edetate dihydrate, polysorbate 80, potassium chloride, potassium dihydrogen phosphate, sodium chloride, and Water for Injection, USP.</p> </td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="4"> <p class="First">Manufactured and distributed by:<br/>Genzyme Corporation<br/>Cambridge, MA 02141<br/>A SANOFI COMPANY<br/>US License Number: 1596</p> <p>LEMTRADA and CAMPATH are registered trademarks of Genzyme Corporation.<br/>©2024 Genzyme Corporation. All rights reserved.</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"2%\"/>\n<col align=\"left\" valign=\"top\" width=\"2%\"/>\n<col align=\"left\" valign=\"top\" width=\"46%\"/>\n<col align=\"left\" valign=\"top\" width=\"50%\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"3\">This Medication Guide has been approved by the U.S. Food and Drug Administration</td><td align=\"right\">Revised: May 2024</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">MEDICATION GUIDE</span>\n<br/>LEMTRADA<span class=\"Sup\">®</span> (lem-TRA-da)<br/>(alemtuzumab), injection for intravenous infusion</p>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">Read this Medication Guide before you start receiving LEMTRADA and before you begin each treatment course. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">\n<a name=\"important\"></a><span class=\"Bold\">What is the most important information I should know about LEMTRADA?</span>\n</p>\n<p>\n<span class=\"Bold\">LEMTRADA can cause serious side effects, including:</span>\n</p>\n<dl>\n<dt class=\"Bold\">1.</dt>\n<dd>\n<span class=\"Bold\">Serious autoimmune problems.</span> Some people receiving LEMTRADA develop a condition where the immune cells in your body attack other cells or organs in the body (autoimmunity) which can be serious and may cause death. Serious autoimmune problems may include:</dd>\n</dl>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">immune thrombocytopenic purpura (ITP).</span> LEMTRADA may cause the number of platelets in your blood to be reduced (ITP). ITP can cause severe bleeding that may cause life-threatening problems. Call your healthcare provider right away if you have any of the following symptoms:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>easy bruising</li>\n<li>bleeding from a cut that is hard to stop</li>\n<li>coughing up blood</li>\n<li>heavier menstrual periods than normal</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>bleeding from your gums or nose that is new or takes longer than usual to stop</li>\n<li>small, scattered spots on your skin that are red, pink, or purple</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">kidney problems.</span> LEMTRADA may cause a serious kidney problem called anti-glomerular basement membrane disease. If this happens and you do not get treated, anti-glomerular basement membrane disease can lead to severe kidney damage, kidney failure that needs dialysis, a kidney transplant, or death. Call your healthcare provider right away if you have any of the following symptoms:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>swelling of your legs or feet</li>\n<li>blood in the urine (red or tea-colored urine)</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>decrease in urine</li>\n<li>fatigue</li>\n<li>coughing up blood</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">Side effects may happen while you receive LEMTRADA and for 4 years after you stop receiving LEMTRADA. Your healthcare provider will order blood and urine tests before you receive, while you are receiving, and every month for 4 years after you receive your last LEMTRADA infusion. You may need to continue these blood and urine tests after 4 years if you have any autoimmune signs or symptoms. The blood and urine tests will help your healthcare provider watch for signs and symptoms of serious autoimmune problems.</p>\n<p>It is important to have your blood and urine tested, even if you are feeling well and do not have any symptoms from LEMTRADA and your multiple sclerosis. This may help your healthcare provider find any problems early.</p>\n<dl class=\"Disc\">\n<dt class=\"Bold\">2.</dt>\n<dd>\n<span class=\"Bold\">Serious infusion reactions.</span> LEMTRADA can cause serious infusion reactions that may cause death. Serious infusion reactions may happen while you receive, or up to 24 hours or longer after you receive LEMTRADA.<br/>You will receive your infusion at a healthcare facility with equipment and staff trained to manage infusion reactions. You will be watched while you receive and for at least <span class=\"Bold\">2</span> hours after you receive LEMTRADA. <span class=\"Bold\">It is important</span> that you stay at the infusion center for at least <span class=\"Bold\">2</span> hours after your infusion is finished or longer if your healthcare provider decides you need to stay longer. If a serious infusion reaction happens while you are receiving LEMTRADA, your infusion may be stopped.<br/>Tell your healthcare provider right away if you have any of the following symptoms of a serious infusion reaction during the infusion, and after you have left the healthcare facility:</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>swelling in your mouth or throat</li>\n<li>trouble breathing</li>\n<li>weakness</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>fast, slow, or irregular heartbeat</li>\n<li>chest pain</li>\n<li>rash</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">To lower your chances of getting a serious infusion reaction, your healthcare provider will give you a medicine called corticosteroids before your first 3 infusions of a treatment course. You may also be given other medicines before or after the infusion to try to reduce your chances of these reactions or to treat them after they happen.</p>\n<dl>\n<dt class=\"Bold\">3.</dt>\n<dd>\n<span class=\"Bold\">Stroke and tears in your arteries that supply blood to your brain (carotid and vertebral arteries).</span> Some people have had serious and sometimes deadly strokes and tears in their carotid or vertebral arteries within 3 days of receiving LEMTRADA. Get help right away if you have any of the following symptoms that may be signs of a stroke or tears in your carotid or vertebral arteries:</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>drooping of parts of your face</li>\n<li>sudden severe headache</li>\n<li>neck pain</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Disc\">\n<li>weakness on one side</li>\n<li>difficulty with speech</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<dl>\n<dt class=\"Bold\">4.</dt>\n<dd>\n<span class=\"Bold\">Certain cancers.</span> Receiving LEMTRADA may increase your chance of getting some kinds of cancers, including thyroid cancer, skin cancer (melanoma), and blood cancers called lymphoproliferative disorders and lymphoma. Call your healthcare provider if you have the following symptoms that may be a sign of thyroid cancer:</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>new lump</li>\n<li>swelling in your neck</li>\n<li>pain in the front of your neck</li>\n<li>hoarseness or other voice changes that do not go away</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Disc\">\n<li>trouble swallowing or breathing</li>\n<li>cough that is not caused by a cold</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">You should have your skin checked before you start receiving LEMTRADA and each year while you are receiving treatment to monitor symptoms of skin cancer.</p>\n<p>\n<span class=\"Bold\">Because of your risk of autoimmunity, infusion reactions, and the risk of some kinds of cancers, LEMTRADA is only available through a restricted program called the LEMTRADA Risk Evaluation and Mitigation Strategy (REMS) Program.</span> Call 1-855-676-6326 to enroll in the LEMTRADA REMS Program.</p>\n<ul class=\"Disc\">\n<li>You and your healthcare provider must be enrolled in the LEMTRADA REMS Program.</li>\n<li>LEMTRADA can only be given at a certified healthcare facility that participates in the LEMTRADA REMS Program. Your healthcare provider can give you information on how to find a certified healthcare facility.</li>\n<li>Read the LEMTRADA REMS \"LEMTRADA Treatment and Infusion Reactions Patient Guide\" after you are enrolled in the program.</li>\n<li>Carry your LEMTRADA REMS Patient Safety Information Card with you in case of an emergency.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">What is LEMTRADA?</span>\n</p>\n<p>LEMTRADA is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults. Since treatment with LEMTRADA can increase your risk of getting certain conditions and diseases, LEMTRADA is generally prescribed for people who have tried 2 or more MS medicines that have not worked well enough. LEMTRADA is not recommended for use in patients with clinically isolated syndrome (CIS).</p>\n<p>It is not known if LEMTRADA is safe and effective for use in children under 17 years of age.</p>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">Who should not receive LEMTRADA?</span>\n</p>\n<p>\n<span class=\"Bold\">Do not receive LEMTRADA if you:</span>\n</p>\n<ul class=\"Disc\">\n<li>are allergic to alemtuzumab or to any of the inactive ingredients in LEMTRADA. See the end of this Medication Guide for a complete list of ingredients in LEMTRADA.</li>\n<li>are infected with human immunodeficiency virus (HIV).</li>\n<li>have an active infection.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">What should I tell my healthcare provider before receiving LEMTRADA?</span>\n</p>\n<p>Before receiving LEMTRADA, tell your healthcare provider if you:</p>\n<ul class=\"Disc\">\n<li>have bleeding problems.</li>\n<li>have thyroid problems.</li>\n<li>have kidney problems.</li>\n<li>have a recent history of infection.</li>\n<li>are taking a medicine called CAMPATH<span class=\"Sup\">®</span>. Alemtuzumab, the active ingredient in LEMTRADA, is the same drug as CAMPATH.</li>\n<li>have received a live vaccine in the past 6 weeks before receiving LEMTRADA or plan to receive any live vaccines. Ask your healthcare provider if you are not sure if your vaccine is a live vaccine.</li>\n<li>are pregnant or plan to become pregnant. LEMTRADA may harm your unborn baby.<ul class=\"Circle\">\n<li>There is a pregnancy surveillance program for people who are exposed to LEMTRADA during pregnancy. The purpose of the program is to collect information about the health of pregnant people exposed to LEMTRADA and their babies. If you become pregnant, inform your healthcare provider.</li>\n</ul>\n</li>\n<li>you should use birth control while receiving LEMTRADA and for 4 months after your course of treatment.</li>\n<li>are breastfeeding or plan to breastfeed. It is not known if LEMTRADA passes into your breast milk. You and your healthcare provider should decide if you should receive LEMTRADA or breastfeed.</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>LEMTRADA and other medicines may affect each other causing side effects. Especially tell your healthcare provider if you take medicines that increase your chance of getting infections, including medicines used to treat cancer or to control your immune system.</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 class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">How will I receive LEMTRADA?</span>\n</p>\n<ul class=\"Disc\">\n<li>LEMTRADA is given through a needle placed in your vein (IV infusion).</li>\n<li>It takes about 4 hours to receive a full dose of LEMTRADA each day.</li>\n<li>You will receive LEMTRADA over 2 or more treatment courses.</li>\n<li>You will receive LEMTRADA for 5 days in a row (consecutive) for the first treatment course and then for 3 days in a row (consecutive) about 1 year later for your second treatment course.</li>\n<li>Additional LEMTRADA treatment courses, if needed, may be given for 3 days in a row (consecutive) at least 1 year after the prior treatment course.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of LEMTRADA?</span>\n</p>\n<p>\n<span class=\"Bold\">LEMTRADA may cause serious side effects including:</span>\n</p>\n<ul class=\"Disc\">\n<li>see <span class=\"Bold\">\"<a href=\"#important\">What is the most important information I should know about LEMTRADA?</a>\"</span>\n</li>\n<li>\n<span class=\"Bold\">thyroid problems.</span> Some people who receive LEMTRADA may get thyroid problems including an overactive thyroid (hyperthyroidism) or an underactive thyroid (hypothyroidism). Your healthcare provider will do blood tests to check how your thyroid is working. Call your healthcare provider if you have any of the symptoms of thyroid problems.<ul class=\"Circle\">\n<li>Symptoms of <span class=\"Bold\">hyperthyroidism</span> may include:</li>\n</ul>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" colspan=\"2\"></td><td align=\"left\">\n<dl>\n<dt>–</dt>\n<dd>excessive sweating</dd>\n<dt>–</dt>\n<dd>unexplained weight loss</dd>\n<dt>–</dt>\n<dd>fast heartbeat</dd>\n</dl>\n</td><td align=\"left\" class=\"Rrule\">\n<dl>\n<dt>–</dt>\n<dd>eye swelling</dd>\n<dt>–</dt>\n<dd>nervousness</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" class=\"Rrule\" colspan=\"3\">\n<ul class=\"Circle\">\n<li>Symptoms of <span class=\"Bold\">hypothyroidism</span> may include:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" colspan=\"2\"></td><td align=\"left\">\n<dl>\n<dt>–</dt>\n<dd>unexplained weight gain</dd>\n<dt>–</dt>\n<dd>feeling cold</dd>\n</dl>\n</td><td align=\"left\" class=\"Rrule\">\n<dl>\n<dt>–</dt>\n<dd>worsening tiredness</dd>\n<dt>–</dt>\n<dd>constipation</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">low blood counts (cytopenias).</span> LEMTRADA may cause a decrease in some types of blood cells. Some people with these low blood counts have increased infections. Symptoms of cytopenias may include:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>weakness</li>\n<li>chest pain</li>\n<li>yellowing of the skin or whites of eyes (jaundice)</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>dark urine</li>\n<li>fast heartbeat</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">Your healthcare provider will do blood tests to check for cytopenias. Call your healthcare provider right away if you have symptoms listed above.</p>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">inflammation of the liver.</span> Call your healthcare provider right away if you have symptoms such as unexplained nausea, stomach pain, tiredness, loss of appetite, yellowing of skin or whites of eyes, or bleeding or bruising more easily than normal.</li>\n<li>\n<span class=\"Bold\">hemophagocytic lymphohistiocytosis (HLH).</span> LEMTRADA may increase the risk of a type of overactivity of the immune system (hemophagocytic lymphohistiocytosis) that can be fatal, especially if not diagnosed and treated early. Call your healthcare provider right away if you have symptoms such as fever, swollen glands, skin rash, or new nervous system problems, such as seizures, changes in your thinking or level of alertness, or new or worsening unsteadiness or trouble walking. These symptoms have happened in people taking LEMTRADA about 13 months to 33 months after they started taking LEMTRADA.</li>\n<li>\n<span class=\"Bold\">adult onset still's disease (AOSD).</span> Adult onset still's disease (AOSD) is a rare condition that can cause a high fever lasting more than 1 week, pain, stiffness with or without swelling in multiple joints, and/or a skin rash. If you experience a combination of these symptoms, contact your healthcare provider immediately.</li>\n<li>\n<span class=\"Bold\">thrombotic thrombocytopenic purpura (TTP).</span> Thrombotic thrombocytopenic purpura (TTP) can occur with LEMTRADA. TTP is a blood clotting problem where blood clots can form in blood vessels anywhere in the body. TTP needs to be treated in a hospital right away, because it can cause death. Get medical help right away if you have any of these symptoms: </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>purplish spots (called purpura) on the skin or in the mouth (mucous membranes) due to bleeding under the skin</li>\n<li>your skin or the whites of your eyes are yellow (jaundice)</li>\n<li>you feel tired or weak</li>\n<li>your skin looks very pale</li>\n<li>fever</li>\n<li>fast heart rate or feeling short of breath</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>headache</li>\n<li>speech changes</li>\n<li>confusion</li>\n<li>vision changes</li>\n<li>seizure</li>\n<li>low amount of urine or dark urine, or urine that has blood in it</li>\n<li>stomach area (abdominal) pain</li>\n<li>nausea, vomiting, or diarrhea</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">autoimmune encephalitis (AIE).</span> Autoimmune encephalitis (AIE), a brain disorder, can occur after receiving LEMTRADA and may include symptoms that may seem like an MS relapse. Call your healthcare provider right away if you have any of the following symptoms:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>personality changes</li>\n<li>mood changes</li>\n<li>agitation</li>\n<li>seeing things that are not there (hallucinations)</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>short term memory loss</li>\n<li>confusion</li>\n<li>movement disorders</li>\n<li>seizure</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">bleeding disorder (acquired hemophilia A).</span> LEMTRADA may cause a bleeding disorder called acquired hemophilia A. Call your healthcare provider right away if you have any of the following symptoms:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>bruising</li>\n<li>nose bleeds</li>\n<li>painful or swollen joints</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>blood in urine</li>\n<li>dark or bloody stools</li>\n<li>bleeding from a cut that may take longer than usual to stop</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">inflammation of the colon (colitis):</span>\n<br/>Tell your healthcare provider if you have any symptoms of colitis, such as<span class=\"Bold\">:</span>\n<ul class=\"Circle\">\n<li>diarrhea (loose stools) or more frequent bowel movements than usual</li>\n<li>stools that are black, tarry, sticky or have blood or mucous</li>\n<li>severe stomach-area (abdomen) pain or tenderness</li>\n</ul>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">serious infections.</span> LEMTRADA may cause you to have serious infections while you receive and after receiving a treatment course. Serious infections may include:<ul class=\"Circle\">\n<li>\n<span class=\"Bold\">listeria.</span> People who receive LEMTRADA have an increased chance of getting an infection caused by the bacteria, listeria, which can lead to significant complications or death. Avoid foods that may be a source for listeria (for example, deli meat, unpasteurized milk and cheese products, soft cheeses, or undercooked meat, seafood or poultry) or make sure that the food you eat which may contain listeria is heated well if you receive treatment with LEMTRADA.</li>\n<li>\n<span class=\"Bold\">herpes viral infections.</span> Some people taking LEMTRADA have an increased chance of getting herpes viral infections. Your healthcare provider will prescribe medicines to reduce your chances of getting these infections. Take these medicines exactly as your healthcare provider tells you to.</li>\n<li>\n<span class=\"Bold\">human papilloma virus (HPV).</span> Females have an increased chance of getting a cervical HPV infection. If you are a female, you should have an HPV screening each year.</li>\n<li>\n<span class=\"Bold\">tuberculosis.</span> Your healthcare provider should check you for tuberculosis before you receive LEMTRADA.</li>\n<li>\n<span class=\"Bold\">fungal infections.</span>\n</li>\n</ul>\n</li>\n</ul>\n<p class=\"First\">Call your healthcare provider right away if you have symptoms of a serious infection, such as fever or swollen glands. You may need to go to the hospital for treatment if you get a serious infection. It is important to tell the healthcare providers that you have received LEMTRADA.</p>\n<p>Talk to your healthcare provider before you get vaccinations after receiving LEMTRADA. Certain vaccinations may increase your chances of getting infections.</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Progressive multifocal leukoencephalopathy (PML).</span> A rare brain infection that usually leads to death or severe disability has been reported with LEMTRADA. Symptoms of PML get worse over days to weeks. It is important that you call your doctor right away if you have any new or worsening medical problems that have lasted several days, including problems with: </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>thinking</li>\n<li>eyesight</li>\n<li>strength</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>balance</li>\n<li>weakness on 1 side of your body</li>\n<li>using your arms or legs</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Inflammation of the gallbladder without gallstones (acalculous cholecystitis).</span> LEMTRADA may increase your chance of getting inflammation of the gallbladder without gallstones, a serious medical condition that can be life-threatening. Call your healthcare provider right away if you have any of the following symptoms of acalculous cholecystitis, which may include: </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>stomach pain or discomfort</li>\n<li>fever</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>nausea or vomiting</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">swelling of lung tissue (pneumonitis).</span> Some people have had swelling of the lung tissue while receiving LEMTRADA. Call your healthcare provider right away if you have the following symptoms:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>shortness of breath</li>\n<li>cough</li>\n<li>wheezing</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>chest pain or tightness</li>\n<li>coughing up blood</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">The most common side effects of LEMTRADA include:</p>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>rash</li>\n<li>headache</li>\n<li>thyroid problems</li>\n<li>fever</li>\n<li>swelling of your nose and throat (nasopharyngitis)</li>\n<li>nausea </li>\n<li>urinary tract infection</li>\n<li>feeling tired</li>\n<li>trouble sleeping</li>\n<li>upper respiratory tract infection</li>\n<li>herpes viral infection</li>\n<li>hives</li>\n<li>itching</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Disc\">\n<li>fungal infection</li>\n<li>joint pain</li>\n<li>pain in your arms or legs</li>\n<li>back pain</li>\n<li>diarrhea</li>\n<li>sinus infection</li>\n<li>mouth pain or sore throat</li>\n<li>tingling sensation</li>\n<li>dizziness</li>\n<li>stomach pain</li>\n<li>sudden redness in face, neck, or chest</li>\n<li>vomiting</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</p>\n<p>These are not all the possible side effects of LEMTRADA. For more information, ask your healthcare provider or pharmacist.</p>\n<p>Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.</p>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of LEMTRADA.</span>\n</p>\n<p>This Medication Guide summarizes the most important information about LEMTRADA. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about LEMTRADA that is written for health professionals.</p>\n<p>For more information, go to www.LemtradaREMS.com or call Genzyme at 1-855-676-6326.</p>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in LEMTRADA?</span>\n</p>\n<p>\n<span class=\"Bold\">Active ingredient:</span> alemtuzumab</p>\n<p>\n<span class=\"Bold\">Inactive ingredients:</span> dibasic sodium phosphate, disodium edetate dihydrate, polysorbate 80, potassium chloride, potassium dihydrogen phosphate, sodium chloride, and Water for Injection, USP.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">\n<p class=\"First\">Manufactured and distributed by:<br/>Genzyme Corporation<br/>Cambridge, MA 02141<br/>A SANOFI COMPANY<br/>US License Number: 1596</p>\n<p>LEMTRADA and CAMPATH are registered trademarks of Genzyme Corporation.<br/>©2024 Genzyme Corporation. All rights reserved.</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

NDC 58468-0200-1

{ "type": "p", "children": [], "text": "NDC 58468-0200-1" }

LEMTRADA® (alemtuzumab)injection

{ "type": "p", "children": [], "text": "LEMTRADA®\n(alemtuzumab)injection" }

12 mg/1.2 mL(10 mg/mL)

{ "type": "p", "children": [], "text": "12 mg/1.2 mL(10 mg/mL)" }

For Intravenous Infusion Only

{ "type": "p", "children": [], "text": "For Intravenous Infusion Only" }

Dilute before Intravenous Infusion

{ "type": "p", "children": [], "text": "Dilute before Intravenous Infusion" }

Single-Dose Vial, Discard Unused Portion

{ "type": "p", "children": [], "text": "Single-Dose Vial, Discard Unused Portion" }

Rx only

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

Dispense the enclosed Medication Guide to each patient.

{ "type": "p", "children": [], "text": "Dispense the enclosed Medication Guide to each patient." }