ALKINDI SPRINKLE is indicated as replacement therapy in pediatric patients with adrenocortical insufficiency.

{ "type": "p", "children": [], "text": "ALKINDI SPRINKLE is indicated as replacement therapy in pediatric patients with adrenocortical insufficiency." }

When switching patients from other oral hydrocortisone formulations to ALKINDI SPRINKLE, use the same total daily hydrocortisone dosage. Closely monitor patients after switching to ALKINDI SPRINKLE for symptoms of adrenocortical insufficiency. If symptoms of adrenal insufficiency occur after switching, increase the total daily dosage of ALKINDI SPRINKLE [see Warnings and Precautions (5.1)].

cause tube blockage.

the granules are in the lower half of the capsule.

patient’s tongue, pouring the granules onto a spoon and placing in the patient’s mouth, or sprinkling onto a spoonful of cold or room temperature soft food (such as yogurt or fruit puree). The granules should be given and swallowed within 5 minutes to avoid a bitter taste as the outer taste masking cover can dissolve.

on the tongue or soft food as this may result in granules remaining in the capsule.

milk or formula to ensure all granules are swallowed.

may result in a bitter taste.

administered (e.g., regurgitating, vomiting of granules). A repeat dose may be required to avoid adrenal insufficiency [see Warnings and Precautions (5.1)].

ALKINDI SPRINKLE oral granules are white to off-white granules contained within transparent capsules and are available as follows:

{ "type": "p", "children": [], "text": "ALKINDI SPRINKLE oral granules are white to off-white granules contained within transparent capsules and are available as follows:" }

<div class="scrollingtable"><table width="30%"> <col align="left" width="15%"/> <col align="left" width="20%"/> <tbody class="Headless"> <tr class="Botrule First"> <th align="left" class="Lrule Rrule">Strength</th><th align="left" class="Rrule">Imprint on Capsules</th> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">0.5 mg</td><td align="left" class="Rrule">“INF-0.5” in red ink</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">1 mg</td><td align="left" class="Rrule">“INF-1.0” in blue ink</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">2 mg</td><td align="left" class="Rrule">“INF-2.0” in green ink</td> </tr> <tr class="Botrule Last"> <td align="left" class="Lrule Rrule">5 mg</td><td align="left" class="Rrule">“INF-5.0” in gray ink</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"30%\">\n<col align=\"left\" width=\"15%\"/>\n<col align=\"left\" width=\"20%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<th align=\"left\" class=\"Lrule Rrule\">Strength</th><th align=\"left\" class=\"Rrule\">Imprint on Capsules</th>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">0.5 mg</td><td align=\"left\" class=\"Rrule\">“INF-0.5” in red ink</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">1 mg</td><td align=\"left\" class=\"Rrule\">“INF-1.0” in blue ink</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">2 mg</td><td align=\"left\" class=\"Rrule\">“INF-2.0” in green ink</td>\n</tr>\n<tr class=\"Botrule Last\">\n<td align=\"left\" class=\"Lrule Rrule\">5 mg</td><td align=\"left\" class=\"Rrule\">“INF-5.0” in gray ink</td>\n</tr>\n</tbody>\n</table></div>" }

ALKINDI SPRINKLE is contraindicated in patients with hypersensitivity to hydrocortisone or to any of the ingredients in ALKINDI SPRINKLE. Anaphylactic reactions have occurred in patients receiving corticosteroids [see Adverse Reactions ( 6.2)] .

{ "type": "p", "children": [], "text": "ALKINDI SPRINKLE is contraindicated in patients with hypersensitivity to hydrocortisone or to any of the ingredients in ALKINDI SPRINKLE. Anaphylactic reactions have occurred in patients receiving corticosteroids\n \n [see Adverse Reactions (\n \n 6.2)]\n \n .\n\n " }

Undertreatment with ALKINDI SPRINKLE or sudden discontinuation of therapy with ALKINDI SPRINKLE may lead to adrenocortical insufficiency, adrenal crisis, and death. Adrenal crisis may also be induced by stress events such as infections or surgery when patients require higher doses of corticosteroids. Symptoms of adrenocortical insufficiency include poor feeding, fatigue, low muscle tone, joint pain, nausea, vomiting, hypoglycemia, low blood pressure and electrolyte disturbances.

Increase the dosage of ALKINDI SPRINKLE during periods of stress (infections, surgery). Switch patients who are vomiting, severely ill or unable to take oral medications to parenteral corticosteroid formulations without delay. Once the patient recovers, gradually reduce the steroid dosage used during the acute event.

When switching patients to ALKINDI SPRINKLE from another oral hydrocortisone formulation, consider the potential for dosing inaccuracy if the other oral hydrocortisone formulation has been manipulated (e.g., split or crushed tablets, compounded formulations). Manipulation of oral hydrocortisone formulations may result in a relative difference in hydrocortisone exposure when using the same dosage to initiate ALKINDI SPRINKLE treatment. Closely monitor patients after switching to ALKINDI SPRINKLE to ensure ALKINDI SPRINKLE is providing the same level of hydrocortisone exposure as the previously used oral hydrocortisone formulation. If symptoms of adrenal insufficiency occur, increase the total daily dosage of ALKINDI SPRINKLE.

Use of the recommended dosage of ALKINDI SPRINKLE [see Dosage and Administration (2.1, 2.2)] as a replacement therapy in pediatric patients with adrenocortical insufficiency is not expected to cause immunosuppression or increase the risk of infection. The use of a greater than replacement dosage can suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. The use of ALKINDI SPRINKLE at greater than replacement dosage can:

• Reduce resistance to new infections

• Exacerbate existing infections

• Increase the risk of disseminated infections

• Increase the risk of reactivation or exacerbation of latent infections

• Mask some signs of infection

Infections associated with the use of corticosteroids at a greater than replacement dosage range

from mild to severe or fatal, and the rate of infectious complications increases with increasing

corticosteroid dosages.

Monitor for the development of infection and consider ALKINDI SPRINKLE dosage reduction as

needed.

Long-term use of corticosteroids in excessive doses may cause growth retardation in pediatric patients. Historical cohorts of adults treated from childhood for congenital adrenal hyperplasia have been found to have growth retardation. Effects on linear growth are less likely when using corticosteroids as replacement therapy. Use the minimum dosage of ALKINDI SPRINKLE to achieve desired clinical response and monitor the patient’s growth.

Prolonged use of corticosteroids in supraphysiologic doses may cause Cushing’s syndrome. Symptoms and signs of Cushing’s syndrome include weight gain, decreased height velocity, hyperglycemia, hypertension, edema, easy bruising, muscle weakness, red round face, depression or mood swings. Monitor patients for signs and symptoms of Cushing’s syndrome every 6 months; pediatric patients under one year of age may require more frequent monitoring, e.g., every 3 to 4 months.

Corticosteroids decrease bone formation and increase bone resorption which may lead to development of osteoporosis. Historical cohorts of adults treated from childhood for congenital adrenal hyperplasia have been found to have reduced bone mineral density and increased fracture rates. Use the minimum dosage of ALKINDI SPRINKLE to achieve desired clinical response.

Corticosteroid use may be associated with severe psychiatric adverse reactions. Euphoria, mania, psychosis with hallucinations and delirium or depression have been seen in patients at replacement doses of hydrocortisone [see Adverse Reactions ( 6)] . Symptoms typically emerge within a few days or weeks of starting the treatment. Risks may be higher with high doses, although dose levels do not allow prediction of the onset, type, severity or duration of reactions. Most reactions resolve after either dose reduction or withdrawal, although specific treatment may be necessary. Monitor patients for behavioral and mood disturbances during treatment with ALKINDI SPRINKLE. Instruct caregivers and/or patients to seek medical advice if psychiatric symptoms develop.

Ophthalmic effects, such as cataract, glaucoma or central serous chorioretinopathy have been reported with prolonged use of corticosteroids in high doses. Monitor patients for blurred vision or other visual disturbances. If patients develop ophthalmic adverse reactions, refer them to an ophthalmologist for further evaluation.

There is an increased risk of gastrointestinal perforation in patients with certain gastrointestinal disorders. Signs of gastrointestinal perforation, such as peritoneal irritation may be masked in patients receiving corticosteroids. Corticosteroids should be used with caution if there is a probability of impending perforation, abscess, or other pyogenic infections; diverticulitis; fresh intestinal anastomoses; and active or latent peptic ulcer.

Concurrent administration of corticosteroids with non-steroidal anti-inflammatory drugs (NSAIDS) may increase the risk of gastrointestinal adverse reactions. Monitor patients receiving corticosteroids and concomitant NSAIDS for gastrointestinal adverse reactions [see Drug Interactions ( 7)] .

Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often

for chronic conditions at a dosage greater than replacement (supraphysiologic dosage). If patients

take a supraphysiologic chronic dosage of ALKINDI SPRINKLE, they are at increased risk of

developing Kaposi’s sarcoma.

Administration of live vaccines may be acceptable in ALKINDI SPRINKLE-treated pediatric patients

with adrenocortical insufficiency who receive replacement corticosteroids.

6.1 Clinical Trials Experience

Because clinical studies 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.

ALKINDI SPRINKLE was evaluated in an uncontrolled, open-label, single-arm clinical study in 18 pediatric patients with adrenocortical insufficiency. Adrenocortical insufficiency was due to congenital adrenal hyperplasia in 17 patients and to hypopituitarism in one patient. All patients received at least one dose of ALKINDI SPRINKLE. The age ranged from 36 days to 5.7 years at start of treatment; 8 patients were female and 10 were male; 100% were White. Adverse reactions that were reported in two or more patients (≥ 11%) are shown in Table 1.

<div class="scrollingtable"><table width="55%"> <caption> <span>Table 1 Adverse Reactions Occurring in &gt;11% of Pediatric Patients with Adrenocortical Insufficiency Treated with ALKINDI SPRINKLE for up to 29 Months</span> </caption> <col align="left" width="20%"/> <col align="left" width="20%"/> <tbody class="Headless"> <tr class="Botrule First"> <th align="left" class="Lrule Rrule">Adverse Reactions</th><th align="left" class="Rrule">N=18 <br/> <br/> (%) </th> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pyrexia</td><td align="left" class="Rrule">10 (56)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Gastroenteritis</td><td align="left" class="Rrule">9 (50)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Viral upper respiratory tract infection</td><td align="left" class="Rrule">8 (44)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Vomiting</td><td align="left" class="Rrule">7 (39)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Viral infection</td><td align="left" class="Rrule">6 (33)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Conjunctivitis</td><td align="left" class="Rrule">5 (28)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Otitis media viral</td><td align="left" class="Rrule">3 (17)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Tonsillitis</td><td align="left" class="Rrule">3 (17)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Body temperature increased</td><td align="left" class="Rrule">2 (11)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Bronchitis</td><td align="left" class="Rrule">2 (11)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Dental caries</td><td align="left" class="Rrule">2 (11)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Diarrhea</td><td align="left" class="Rrule">2 (11)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Genitourinary operation</td><td align="left" class="Rrule">2 (11)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pharyngitis</td><td align="left" class="Rrule">2 (11)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Respiratory tract infection</td><td align="left" class="Rrule">2 (11)</td> </tr> <tr class="Botrule Last"> <td align="left" class="Lrule Rrule">Rhinitis</td><td align="left" class="Rrule">2 (11)</td> </tr> </tbody> </table></div>

6.2 Postmarketing Experience

The following adverse reactions seen in pediatric and adult patients associated with the use of corticosteroids were identified in the literature and from postmarketing reports. Because some of 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.

Common adverse reactions for corticosteroids include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain.

Allergic Reactions:Anaphylaxis, angioedema

Cardiovascular:Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction, pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis

Dermatologic:Acne, allergic dermatitis, cutaneous and subcutaneous atrophy, dry scalp, edema, facial erythema, hyper or hypo-pigmentation, impaired wound healing, increased sweating, petechiae and ecchymoses, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria

Endocrine:Abnormal fat deposits, decreased carbohydrate tolerance, development of Cushingoid state, hirsutism, manifestations of latent diabetes mellitus and increased requirements for insulin or oral hypoglycemic agents in diabetics, menstrual irregularities, moon faces, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery or illness), suppression of growth in pediatric patients

Fluid and Electrolyte Disturbances:Fluid retention, potassium loss, hypertension, hypokalemic alkalosis, sodium retention

Gastrointestinal:Abdominal distention, elevation in serum liver enzymes levels (usually reversible upon discontinuation), hepatomegaly, hiccups, malaise, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, ulcerative esophagitis

General:Increased appetite and weight gain

Metabolic:Negative nitrogen balance due to protein catabolism

Musculoskeletal:Osteonecrosis of femoral and humeral heads, Charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, steroid myopathy, tendon rupture, vertebral compression fractures

Neurological:Arachnoiditis, convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudo-tumor cerebri) usually following discontinuation of treatment, insomnia, meningitis, mood swings, neuritis, neuropathy, paraparesis/paraplegia, paresthesia, personality changes, sensory disturbances, vertigo

Ophthalmic:Exophthalmos, glaucoma, increased intraocular pressure, posterior subcapsular cataracts, and central serous chorioretinopathy

Reproductive:Alteration in motility and number of spermatozoa

<div class="scrollingtable"><table width="68%"> <caption> <span>Table 2 Drug Interactions with ALKINDI SPRINKLE</span> </caption> <col width="17%"/> <col width="25%"/> <tbody class="Headless"> <tr class="Botrule First Lrule"> <td class="Lrule"><span class="Bold">CYP3A4 Inhibitors</span></td><td class="Rrule"></td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Clinical Impact:</span></td><td class="Lrule Rrule">Hydrocortisone is metabolized by cytochrome P450 3A4 (CYP3A4). Concomitant administration of inhibitors of CYP3A4 may lead to increases in serum concentrations of ALKINDI SPRINKLE and increase the risk of adverse reactions associated with the use of excessive doses.</td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Intervention:</span></td><td class="Lrule Rrule">Concomitant use of CYP3A4 inhibitors may require a decrease in the ALKINDI SPRINKLE dose.</td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Examples:</span></td><td class="Lrule Rrule"><span class="Italics">Anti-fungals:</span>itraconazole, posaconazole, voriconazole <br/> <br/> <span class="Italics">Antibiotics:</span>erythromycin and clarithromycin <br/> <br/> <span class="Italics">Antiretrovirals:</span>ritonavir <br/> <br/> Grapefruit juice </td> </tr> <tr class="Botrule Lrule"> <td class="Lrule"><span class="Bold">CYP3A4 Inducers</span></td><td class="Rrule"></td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Clinical Impact:</span></td><td class="Lrule Rrule">Hydrocortisone is metabolized by cytochrome P450 3A4 (CYP3A4). Concomitant administration of inducers of CYP3A4 may lead to decreases in serum concentrations of ALKINDI SPRINKLE and increase the risk of adverse reactions, including adrenal crisis.</td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Intervention:</span></td><td class="Lrule Rrule">Concomitant use of CYP3A4 inducers may require an increase in the ALKINDI SPRINKLE dose.</td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Examples:</span></td><td class="Lrule Rrule"><span class="Italics">Anticonvulsants:</span>phenytoin, carbamazepine and oxcarbazepine <br/> <br/> <span class="Italics">Antibiotics:</span>rifampicin and rifabutin <br/> <br/> <span class="Italics">Barbiturates:</span>phenobarbital and primidone <br/> <br/> <span class="Italics">Antiretrovirals:</span>efavirenz and nevirapine </td> </tr> <tr class="Botrule Lrule"> <td class="Lrule"><span class="Bold">Estrogen and Estrogen Containing Products</span></td><td class="Rrule"></td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Clinical Impact:</span></td><td class="Lrule Rrule">Oral estrogen and estrogen-containing oral contraceptives may interact with hydrocortisone by increasing serum cortisol-binding globulin (CBG) concentration. Concomitant use may reduce the efficacy of ALKINDI SPRINKLE by binding and delaying or preventing absorption.</td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Intervention:</span></td><td class="Lrule Rrule">Concomitant use of estrogen/estrogen containing products may require an increase in the ALKINDI SPRINKLE dose.</td> </tr> <tr class="Botrule Lrule"> <td class="Lrule"><span class="Bold">Antidiabetic Agents</span></td><td class="Rrule"></td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Clinical Impact:</span></td><td class="Lrule Rrule">Corticosteroids in supraphysiologic doses may increase blood glucose concentrations.</td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Intervention:</span></td><td class="Lrule Rrule">Use of ALKINDI SPRINKLE in supraphysiologic doses may require a dose adjustment of antidiabetic agents.</td> </tr> <tr class="Botrule Lrule"> <td class="Lrule"><span class="Bold">Anticoagulant Agents</span></td><td class="Rrule"></td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Clinical Impact:</span></td><td class="Lrule Rrule">Concomitant use of warfarin and corticosteroids usually results in inhibition of response to warfarin, although there have been some conflicting reports.</td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Intervention:</span></td><td class="Lrule Rrule">Monitor coagulation indices in patients receiving ALKINDI SPRINKLE and concomitant warfarin to maintain the desired anticoagulant effect.</td> </tr> <tr class="Botrule Lrule"> <td class="Lrule"><span class="Bold">Cyclosporine</span></td><td class="Rrule"></td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Clinical Impact:</span></td><td class="Lrule Rrule">Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with concurrent use.</td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Intervention:</span></td><td class="Lrule Rrule">Monitor patients receiving ALKINDI SPRINKLE and concomitant cyclosporine.</td> </tr> <tr class="Botrule Lrule"> <td class="Lrule"><span class="Bold">Nonsteroidal Anti-inflammatory Drugs (NSAIDs)</span></td><td class="Rrule"></td> </tr> <tr class="Botrule Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Clinical Impact:</span></td><td class="Lrule Rrule">Concomitant use of NSAIDs and corticosteroids increases the risk of gastrointestinal adverse reactions. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids; this could lead to decreased salicylate serum levels or increase the risk of salicylate toxicity when corticosteroid is withdrawn.</td> </tr> <tr class="Botrule Last Lrule Rrule"> <td class="Lrule Rrule"><span class="Italics">Intervention:</span></td><td class="Lrule Rrule">Monitor patients receiving ALKINDI SPRINKLE and concomitant NSAIDs.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"68%\">\n<caption>\n<span>Table 2 Drug Interactions with ALKINDI SPRINKLE</span>\n</caption>\n<col width=\"17%\"/>\n<col width=\"25%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First Lrule\">\n<td class=\"Lrule\"><span class=\"Bold\">CYP3A4 Inhibitors</span></td><td class=\"Rrule\"></td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Clinical Impact:</span></td><td class=\"Lrule Rrule\">Hydrocortisone is metabolized by cytochrome P450 3A4 (CYP3A4). Concomitant administration of inhibitors of CYP3A4 may lead to increases in serum concentrations of ALKINDI SPRINKLE and increase the risk of adverse reactions associated with the use of excessive doses.</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Intervention:</span></td><td class=\"Lrule Rrule\">Concomitant use of CYP3A4 inhibitors may require a decrease in the ALKINDI SPRINKLE dose.</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Examples:</span></td><td class=\"Lrule Rrule\"><span class=\"Italics\">Anti-fungals:</span>itraconazole, posaconazole, voriconazole \n <br/>\n<br/>\n<span class=\"Italics\">Antibiotics:</span>erythromycin and clarithromycin \n <br/>\n<br/>\n<span class=\"Italics\">Antiretrovirals:</span>ritonavir \n <br/>\n<br/> Grapefruit juice\n \n </td>\n</tr>\n<tr class=\"Botrule Lrule\">\n<td class=\"Lrule\"><span class=\"Bold\">CYP3A4 Inducers</span></td><td class=\"Rrule\"></td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Clinical Impact:</span></td><td class=\"Lrule Rrule\">Hydrocortisone is metabolized by cytochrome P450 3A4 (CYP3A4). Concomitant administration of inducers of CYP3A4 may lead to decreases in serum concentrations of ALKINDI SPRINKLE and increase the risk of adverse reactions, including adrenal crisis.</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Intervention:</span></td><td class=\"Lrule Rrule\">Concomitant use of CYP3A4 inducers may require an increase in the ALKINDI SPRINKLE dose.</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Examples:</span></td><td class=\"Lrule Rrule\"><span class=\"Italics\">Anticonvulsants:</span>phenytoin, carbamazepine and oxcarbazepine \n <br/>\n<br/>\n<span class=\"Italics\">Antibiotics:</span>rifampicin and rifabutin \n <br/>\n<br/>\n<span class=\"Italics\">Barbiturates:</span>phenobarbital and primidone \n <br/>\n<br/>\n<span class=\"Italics\">Antiretrovirals:</span>efavirenz and nevirapine\n \n </td>\n</tr>\n<tr class=\"Botrule Lrule\">\n<td class=\"Lrule\"><span class=\"Bold\">Estrogen and Estrogen Containing Products</span></td><td class=\"Rrule\"></td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Clinical Impact:</span></td><td class=\"Lrule Rrule\">Oral estrogen and estrogen-containing oral contraceptives may interact with hydrocortisone by increasing serum cortisol-binding globulin (CBG) concentration. Concomitant use may reduce the efficacy of ALKINDI SPRINKLE by binding and delaying or preventing absorption.</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Intervention:</span></td><td class=\"Lrule Rrule\">Concomitant use of estrogen/estrogen containing products may require an increase in the ALKINDI SPRINKLE dose.</td>\n</tr>\n<tr class=\"Botrule Lrule\">\n<td class=\"Lrule\"><span class=\"Bold\">Antidiabetic Agents</span></td><td class=\"Rrule\"></td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Clinical Impact:</span></td><td class=\"Lrule Rrule\">Corticosteroids in supraphysiologic doses may increase blood glucose concentrations.</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Intervention:</span></td><td class=\"Lrule Rrule\">Use of ALKINDI SPRINKLE in supraphysiologic doses may require a dose adjustment of antidiabetic agents.</td>\n</tr>\n<tr class=\"Botrule Lrule\">\n<td class=\"Lrule\"><span class=\"Bold\">Anticoagulant Agents</span></td><td class=\"Rrule\"></td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Clinical Impact:</span></td><td class=\"Lrule Rrule\">Concomitant use of warfarin and corticosteroids usually results in inhibition of response to warfarin, although there have been some conflicting reports.</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Intervention:</span></td><td class=\"Lrule Rrule\">Monitor coagulation indices in patients receiving ALKINDI SPRINKLE and concomitant warfarin to maintain the desired anticoagulant effect.</td>\n</tr>\n<tr class=\"Botrule Lrule\">\n<td class=\"Lrule\"><span class=\"Bold\">Cyclosporine</span></td><td class=\"Rrule\"></td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Clinical Impact:</span></td><td class=\"Lrule Rrule\">Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with concurrent use.</td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Intervention:</span></td><td class=\"Lrule Rrule\">Monitor patients receiving ALKINDI SPRINKLE and concomitant cyclosporine.</td>\n</tr>\n<tr class=\"Botrule Lrule\">\n<td class=\"Lrule\"><span class=\"Bold\">Nonsteroidal Anti-inflammatory Drugs (NSAIDs)</span></td><td class=\"Rrule\"></td>\n</tr>\n<tr class=\"Botrule Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Clinical Impact:</span></td><td class=\"Lrule Rrule\">Concomitant use of NSAIDs and corticosteroids increases the risk of gastrointestinal adverse reactions. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids; this could lead to decreased salicylate serum levels or increase the risk of salicylate toxicity when corticosteroid is withdrawn.</td>\n</tr>\n<tr class=\"Botrule Last Lrule Rrule\">\n<td class=\"Lrule Rrule\"><span class=\"Italics\">Intervention:</span></td><td class=\"Lrule Rrule\">Monitor patients receiving ALKINDI SPRINKLE and concomitant NSAIDs.</td>\n</tr>\n</tbody>\n</table></div>" }

Risk Summary

Untreated adrenocortical insufficiency in pregnancy can result in a high rate of complications, including maternal mortality. The use of physiologic doses of hydrocortisone is not expected to cause major birth defects, miscarriage and adverse maternal and fetal outcomes. Available data from observational studies with hydrocortisone use in pregnancy have not identified a clear drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes (see Data ).

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

Data

Human Data

Available data from observational studies with hydrocortisone use in pregnant women have not identified a clear drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Evidence from published epidemiologic studies suggest that there may be a small increased risk of cleft lip with or without cleft palate associated with first trimester systemic corticosteroid use in pregnant patients. However, the data are limited and report inconsistent findings, and studies have important methodological limitations, including non-randomized design, retrospective data collection, lack of dose-response data and the inability to control for confounders,such as underlying maternal disease and use of concomitant medications. In addition, unlike other corticosteroids, hydrocortisone is enzymatically deactivated by the placenta and therefore, limits fetal exposure.

Animal Data

Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose. Animal studies in which corticosteroids have been given to pregnant mice, rats and rabbits without adrenocortical insufficiency have yielded an increased incidence of cleft palate in the offspring.

Risk Summary

Cortisol is present in human milk. The use of hydrocortisone at a physiologic dose for adrenocortical insufficiency is not expected to adversely affect the breastfed infant or milk production. There are no data on the presence of hydrocortisone in breast milk, the effect on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ALKINDI SPRINKLE and any potential adverse effects on the breastfed infant from ALKINDI SPRINKLE or from the underlying maternal condition.

The safety and effectiveness of ALKINDI SPRINKLE have been established in pediatric patients for replacement therapy of adrenocortical insufficiency and the information on this use is discussed throughout the labeling. Use of ALKINDI SPRINKLE in pediatric patients is supported by use in pediatric patients for adrenocortical insufficiency with another hydrocortisone product, along with supportive pharmacokinetic and safety data in 24 pediatric patients with adrenocortical insufficiency. No new adverse reactions were identified [see Adverse Reactions (6) and Clinical Pharmacology (12.3)]. ALKINDI SPRINKLE are oral granules contained within capsules that must be opened and not swallowed whole to administer the granules. Additionally, ALKINDI SPRINKLE granules should not be administered via nasogastric or gastric tubes as they may cause tube blockage [see Dosage and Administration (2.2)].

Treatment of acute overdosage is by supportive and symptomatic therapy.

{ "type": "p", "children": [], "text": "Treatment of acute overdosage is by supportive and symptomatic therapy." }

ALKINDI SPRINKLE contains hydrocortisone, a corticosteroid, also known as cortisol. The chemical name of hydrocortisone is 11β,17α,21-trihydroxy-pregn-4-ene-3,20-dione and it has the chemical formula of C 21H 30O 5, and molecular weight of 362 g·mol −1. Hydrocortisone is a white or almost white powder soluble in the pH range of 1-7.

{ "type": "p", "children": [], "text": "ALKINDI SPRINKLE contains hydrocortisone, a corticosteroid, also known as cortisol. The chemical name of hydrocortisone is 11β,17α,21-trihydroxy-pregn-4-ene-3,20-dione and it has the chemical formula of C\n \n 21H\n \n 30O\n \n 5, and molecular weight of 362 g·mol\n \n −1. Hydrocortisone is a white or almost white powder soluble in the pH range of 1-7.\n\n " }

Structural formula of hydrocortisone:

{ "type": "p", "children": [], "text": "\nStructural formula of hydrocortisone:\n" }

ALKINDI SPRINKLE are oral granules contained within hard capsules. The inactive ingredients in the granules are microcrystalline cellulose, hypromellose, magnesium stearate and ethyl cellulose and the capsule shell contains hypromellose. The printing ink contains shellac, propylene glycol and concentrated ammonia solution. The printing ink also contains red iron oxide, potassium hydroxide for 0.5 mg (red), indigotine for 1 mg (blue), indigotine, yellow iron oxide, titanium dioxide for 2 mg (green) and titanium dioxide, black iron oxide, potassium hydroxide for 5 mg (gray).

{ "type": "p", "children": [], "text": "ALKINDI SPRINKLE are oral granules contained within hard capsules. The inactive ingredients in the granules are microcrystalline cellulose, hypromellose, magnesium stearate and ethyl cellulose and the capsule shell contains hypromellose. The printing ink contains shellac, propylene glycol and concentrated ammonia solution. The printing ink also contains red iron oxide, potassium hydroxide for 0.5 mg (red), indigotine for 1 mg (blue), indigotine, yellow iron oxide, titanium dioxide for 2 mg (green) and titanium dioxide, black iron oxide, potassium hydroxide for 5 mg (gray)." }

Hydrocortisone is a glucocorticoid. Glucocorticoids, adrenocortical steroids, cause varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli..

Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states.

Absorption Following oral administration, a dose of ALKINDI SPRINKLE 4x5 mg was approximately 87% bioavailable when compared to intravenous hydrocortisone in dexamethasone-suppressed healthy adult male volunteers. The median time to peak serum concentration (Tmax) was 0.75 hours post-dose following oral administration.

In an open label, single dose study in 24 pediatric patients with adrenocortical insufficiency, ALKINDI SPRINKLE (1-4 mg based on body surface area) increased cortisol levels from baseline to median cortisol level 19.4 mcg/dL (range 12.5 – 52.4 mcg/dL) at Cmax (60 minutes post-dose).

Effect of Food The coadministration of ALKINDI SPRINKLE with soft food (yogurt and fruit puree) has been studied in healthy adult male volunteers, where it was shown to be bioequivalent to administration of dry granules directly to the back of the tongue.

Distribution 90% or more of circulating hydrocortisone is reversibly bound to protein.

The binding is accounted for by two protein fractions. One, corticosteroid-binding globulin is a glycoprotein; the other is albumin.

Elimination Hydrocortisone is metabolized in the liver and most body tissues to hydrogenated and degraded forms such as tetrahydrocortisone and tetrahydrocortisol which are excreted in the urine, mainly conjugated as glucuronides, together with a very small proportion of unchanged hydrocortisone.

The terminal half-life of hydrocortisone is about 1.5 hours following intravenous and oral dosing of hydrocortisone tablets and ALKINDI SPRINKLE in dexamethasone-suppressed healthy adult male volunteers.

No adequate studies in animals have been conducted with hydrocortisone to evaluate carcinogenic or mutagenic potential. Corticosteroids have been shown to impair fertility in male rats.

ALKINDI SPRINKLE oral granules are supplied as white to off-white granules in transparent capsules as follows:

{ "type": "p", "children": [], "text": "ALKINDI SPRINKLE oral granules are supplied as white to off-white granules in transparent capsules as follows:" }

<div class="scrollingtable"><table width="60%"> <col align="left" width="15%"/> <col align="left" width="20%"/> <col align="left" width="20%"/> <col align="left" width="20%"/> <tbody class="Headless"> <tr class="Botrule First"> <th align="left" class="Lrule Rrule">Strength</th><th align="left" class="Rrule">Imprint on Capsules</th><th align="left" class="Rrule">Amount in Bottle</th><th align="left" class="Rrule">NDC</th> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">0.5 mg</td><td align="left" class="Rrule">“INF-0.5” in red ink</td><td align="left" class="Rrule">50 capsules</td><td align="left" class="Rrule">71863-109-50</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">1 mg</td><td align="left" class="Rrule">“INF-1.0” in blue ink</td><td align="left" class="Rrule">50 capsules</td><td align="left" class="Rrule">71863-110-50</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">2 mg</td><td align="left" class="Rrule">“INF-2.0” in green ink</td><td align="left" class="Rrule">50 capsules</td><td align="left" class="Rrule">71863-111-50</td> </tr> <tr class="Botrule Last"> <td align="left" class="Lrule Rrule">5 mg</td><td align="left" class="Rrule">“INF-5.0” in gray ink</td><td align="left" class="Rrule">50 capsules</td><td align="left" class="Rrule">71863-112-50</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"60%\">\n<col align=\"left\" width=\"15%\"/>\n<col align=\"left\" width=\"20%\"/>\n<col align=\"left\" width=\"20%\"/>\n<col align=\"left\" width=\"20%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<th align=\"left\" class=\"Lrule Rrule\">Strength</th><th align=\"left\" class=\"Rrule\">Imprint on Capsules</th><th align=\"left\" class=\"Rrule\">Amount in Bottle</th><th align=\"left\" class=\"Rrule\">NDC</th>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">0.5 mg</td><td align=\"left\" class=\"Rrule\">“INF-0.5” in red ink</td><td align=\"left\" class=\"Rrule\">50 capsules</td><td align=\"left\" class=\"Rrule\">71863-109-50</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">1 mg</td><td align=\"left\" class=\"Rrule\">“INF-1.0” in blue ink</td><td align=\"left\" class=\"Rrule\">50 capsules</td><td align=\"left\" class=\"Rrule\">71863-110-50</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">2 mg</td><td align=\"left\" class=\"Rrule\">“INF-2.0” in green ink</td><td align=\"left\" class=\"Rrule\">50 capsules</td><td align=\"left\" class=\"Rrule\">71863-111-50</td>\n</tr>\n<tr class=\"Botrule Last\">\n<td align=\"left\" class=\"Lrule Rrule\">5 mg</td><td align=\"left\" class=\"Rrule\">“INF-5.0” in gray ink</td><td align=\"left\" class=\"Rrule\">50 capsules</td><td align=\"left\" class=\"Rrule\">71863-112-50</td>\n</tr>\n</tbody>\n</table></div>" }

Store at controlled room temperature (USP) 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30 °C (59°F to 86°F). Store in the original bottle in order to protect from light.

{ "type": "p", "children": [], "text": "Store at controlled room temperature (USP) 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30 °C (59°F to 86°F). Store in the original bottle in order to protect from light." }

Once the bottle has been opened, use the capsules within 60 days.

{ "type": "p", "children": [], "text": "Once the bottle has been opened, use the capsules within 60 days." }

Adrenal Crisis

Inform the patient or caregiver that undertreatment or sudden discontinuation of ALKINDI SPRINKLE may lead to symptoms of adrenocortical insufficiency, adrenal crisis, and death. Advise the caregiver that the potential dosing inaccuracy of manipulated oral hydrocortisone preparations (e.g., split or crushed tablets or compounded suspension) may result in differences. When switching treatment from conventional oral hydrocortisone to ALKINDI SPRINKLE, advise the patient or caregiver that this could lead to unintended clinical consequences and recommend close monitoring of patients after the switch. Inform the patient or caregiver to contact their healthcare provider if they have prolonged vomiting, are severely ill or are unable to take oral medications. [see Warnings and Precautions ( 5.1)]

Immunosuppression and Increased Risk of Infections

Advise patients and/or caregivers that greater than replacement dosage of corticosteroids can

suppress the immune system and increase the risk of infections. Instruct patients and/or

caregivers to contact their healthcare provider if they develop any infections [see Warnings and

Precautions ( 5.2)]

Administration Information

Advise the patient or caregiver that ALKINDI SPRINKLE is a granule formulation contained in a capsule. Do not swallow the capsule. Do not chew or crush the granules. Open the capsule and give the granules directly into the patient’s mouth. Alternatively, sprinkle the granules onto soft food and give immediately as the taste masking cover can dissolve in as little as 5 minutes. Avoid wetting the capsule as this may cause some granules to stick to the capsule. Immediately following administration, take a sip of fluids to ensure all granules have been swallowed. [see Dosage and Administration ( 2.3)].

Growth Retardation

Discuss with the caregiver that long-term use of corticosteroids in excessive doses may cause growth retardation in pediatric patients. [see Warnings and Precautions ( 5.3)]

Cushing’s Syndrome

Inform patients and caregivers that prolonged use of corticosteroids in supraphysiologic doses may cause Cushing’s syndrome and that symptoms and signs include weight gain, decreased height velocity, hyperglycemia, hypertension, edema, easy bruising, muscle weakness, red round face, depression or mood swings. [see Warnings and Precautions ( 5.4)]

Decrease in Bone Mineral Density

Inform the patient or caregiver that corticosteroids decrease bone formation and increase bone resorption that may lead to osteoporosis. [see Warnings and Precautions ( 5.5)]

Psychiatric Adverse Reactions

Advise the patient or caregiver that corticosteroid use may be associated with severe psychiatric adverse reactions such as euphoria, mania, psychosis with hallucinations or depression. Instruct caregivers and/or patients to seek medical advice if psychiatric symptoms develop. [see Warnings and Precautions ( 5.6)]

Ophthalmic Adverse Reactions

Inform patients or caregivers that ophthalmic effects such as cataract, glaucoma or central serous chorioretinopathy have been reported with prolonged use of high-dose corticosteroids. Instruct patients or caregivers to report any blurred vision or visual disturbances to their healthcare provider. [see Warnings and Precautions ( 5.7)]

Gastrointestinal Adverse Reactions

Discuss with patients or caregivers that use of corticosteroids may increase risk of gastrointestinal perforation in certain gastrointestinal disorders [see Warnings and Precautions ( 5.8)].

Excretion of Granules

ALKINDI SPRINKLE granules may sometimes be seen in stools since the center of the granule is not absorbed in the gut after the active substance has been released. Inform patients or caregivers that this does not mean the product is ineffective and they should not take another dose.

ALKINDI SPRINKLE is manufactured for Eton Pharmaceuticals, Inc. by Glatt Pharmaceutical Services GmbH & Co. KG Werner-Glatt-Strasse 1, Binzen, Baden-Wuerttemberg, 79589, Germany.

ALKINDI SPRINKLE ®is a registered trademark of Neurocrine UK Limited.

ALKINDI is covered by the following US patents: 9,649,280; 9,675,559; 9,717,740; and other patents in other countries internationally.

ALKINDI SPRINKLE is distributed in the USA by Eton Pharmaceuticals, Inc. under license from Neurocrine UK Limited.

Medication Guide

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

ALKINDI SPRINKLE® (ælˈkɪndi spr-en-kle)

{ "type": "p", "children": [], "text": "ALKINDI SPRINKLE® (ælˈkɪndi spr-en-kle)" }

(hydrocortisone) oral granules

{ "type": "p", "children": [], "text": "(hydrocortisone) oral granules" }

Read this Medication Guide before you start giving ALKINDI SPRINKLE to your child, and each time your child gets a

{ "type": "p", "children": [], "text": "Read this Medication Guide before you start giving ALKINDI SPRINKLE to your child, and each time your child gets a" }

refill. There may be new information. This information does not take the place of talking to your healthcare provider about your child’s medical condition or treatment.

{ "type": "p", "children": [], "text": "refill. There may be new information. This information does not take the place of talking to your healthcare provider about your child’s medical condition or treatment." }

What is the most important information I should know about ALKINDI SPRINKLE?

{ "type": "p", "children": [], "text": "\nWhat is the most important information I should know about ALKINDI SPRINKLE?\n" }

ALKINDI SPRINKLE may cause serious side effects, including:

{ "type": "p", "children": [], "text": "\nALKINDI SPRINKLE may cause serious side effects, including:\n" }

Adrenal gland problems.Not giving enough ALKINDI SPRINKLE, stopping ALKINDI SPRINKLE, or switching to ALKINDI SPRINKLE after taking another hydrocortisone medicine (the same class of medicines as ALKINDI SPRINKLE) by mouth, can cause serious and life-threatening adrenal gland problems including death. Do not stop giving ALKINDI SPRINKLE without talking to your healthcare provider. Tell your healthcare provider if your child has any of these symptoms:

{ "type": "p", "children": [], "text": "\nAdrenal gland problems.Not giving enough ALKINDI SPRINKLE, stopping ALKINDI SPRINKLE, or switching to ALKINDI SPRINKLE after taking another hydrocortisone medicine (the same class of medicines as ALKINDI SPRINKLE) by mouth, can cause serious and life-threatening adrenal gland problems including death. Do not stop giving ALKINDI SPRINKLE without talking to your healthcare provider. Tell your healthcare provider if your child has any of these symptoms:\n\n " }

{ "type": "", "children": [], "text": "" }

Your healthcare provider will change the dose of ALKINDI SPRINKLE depending on your child’s size. Tell your healthcare provider if your child cannot swallow medicines by mouth. During episodes of acute infections, surgery, major trauma or if your child cannot take medicines by mouth, your healthcare provider may recommend increased doses of ALKINDI SPRINKLE or use of corticosteroid medicines given directly into the bloodstream instead.

{ "type": "p", "children": [], "text": "Your healthcare provider will change the dose of ALKINDI SPRINKLE depending on your child’s size. Tell your healthcare provider if your child cannot swallow medicines by mouth. During episodes of acute infections, surgery, major trauma or if your child cannot take medicines by mouth, your healthcare provider may recommend increased doses of ALKINDI SPRINKLE or use of corticosteroid medicines given directly into the bloodstream instead." }

The amount of hydrocortisone in a dose of ALKINDI SPRINKLE may not be the same as in previous hydrocortisone medicines that your child takes by mouth if these oral hydrocortisone medicines have been changed (for example, crushed or compounded). When switching to ALKINDI SPRINKLE, your healthcare provider may need to prescribe a starting dose of ALKINDI SPRINKLE that is different from previous hydrocortisone medicines that your child may have been taking by mouth. Watch your child closely after being switched to ALKINDI SPRINKLE and contact your healthcare provider if your child has any symptoms of adrenal gland problems. Your healthcare provider may need to change the dose of ALKINDI SPRINKLE.

{ "type": "p", "children": [], "text": "The amount of hydrocortisone in a dose of ALKINDI SPRINKLE may not be the same as in previous hydrocortisone medicines that your child takes by mouth if these oral hydrocortisone medicines have been changed (for example, crushed or compounded). When switching to ALKINDI SPRINKLE, your healthcare provider may need to prescribe a starting dose of ALKINDI SPRINKLE that is different from previous hydrocortisone medicines that your child may have been taking by mouth. Watch your child closely after being switched to ALKINDI SPRINKLE and contact your healthcare provider if your child has any symptoms of adrenal gland problems. Your healthcare provider may need to change the dose of ALKINDI SPRINKLE." }

See “What are the possible side effects of ALKINDI SPRINKLE?” for more information about side effects.

{ "type": "p", "children": [], "text": "\nSee “What are the possible side effects of ALKINDI SPRINKLE?” for more information about side effects.\n" }

What is ALKINDI SPRINKLE?

{ "type": "p", "children": [], "text": "\nWhat is ALKINDI SPRINKLE?\n" }

ALKINDI SPRINKLE is a prescription medicine that contains a medicine hydrocortisone. Hydrocortisone belongs to a group of medicines known as corticosteroids. Hydrocortisone is a synthetic version of the hormone cortisol. Cortisol is made naturally by the adrenal glands in the body. ALKINDI SPRINKLE (hydrocortisone) is a man-made (synthetic) corticosteroid used to replace the body’s cortisol when the adrenal glands do not make enough (adrenal insufficiency) in

{ "type": "p", "children": [], "text": "ALKINDI SPRINKLE is a prescription medicine that contains a medicine hydrocortisone. Hydrocortisone belongs to a group of medicines known as corticosteroids. Hydrocortisone is a synthetic version of the hormone cortisol. Cortisol is made naturally by the adrenal glands in the body. ALKINDI SPRINKLE (hydrocortisone) is a man-made (synthetic) corticosteroid used to replace the body’s cortisol when the adrenal glands do not make enough (adrenal insufficiency) in" }

children from birth to 17 years of age.

{ "type": "p", "children": [], "text": "children from birth to 17 years of age." }

Who should not take or be given ALKINDI SPRINKLE?

{ "type": "p", "children": [], "text": "\nWho should not take or be given ALKINDI SPRINKLE?\n" }

Do not give your child ALKINDI SPRINKLE if they:

{ "type": "p", "children": [], "text": "\nDo not give your child ALKINDI SPRINKLE if they:\n" }

{ "type": "ul", "children": [ "are allergic to hydrocortisone or any of the ingredients in ALKINDI SPRINKLE. See the end of this Medication Guide for a complete list of ingredients in ALKINDI SPRINKLE.", "have any reaction like swelling or shortness of breath after being given ALKINDI SPRINKLE. Get medical help right away and tell your healthcare provider as soon as possible as these can be signs of an allergic reaction." ], "text": "" }

What should I tell my healthcare provider before giving ALKINDI SPRINKLE?

{ "type": "p", "children": [], "text": "\nWhat should I tell my healthcare provider before giving ALKINDI SPRINKLE?\n" }

Before you give your child ALKINDI SPRINKLE, tell your healthcare provider about all of your child’s medical conditions, including if they:

{ "type": "p", "children": [], "text": "\nBefore you give your child ALKINDI SPRINKLE, tell your healthcare provider about all of your child’s medical conditions, including if they:\n" }

{ "type": "ul", "children": [ "are feeling unwell, or their body is under stress because of surgery or trauma. Your healthcare provider may need to increase the dose of ALKINDI SPRINKLE for a short period of time.", "have a fever or infection.", "have nausea, vomiting, or diarrhea.", "are due for vaccinations. Taking ALKINDI SPRINKLE should not stop your child from being vaccinated. Tell your healthcare provider when your child is due for vaccinations.", "are scheduled for surgery.", "cannot swallow medicines by mouth or are fed through a nasogastric or gastric tube.", "are pregnant or plan to become pregnant. It is not known if ALKINDI SPRINKLE will harm your child’s unborn baby. Talk to your child’s healthcare provider if your child is pregnant or plans to become pregnant.", "are breastfeeding or plan to breastfeed. It is not known if ALKINDI SPRINKLE passes into the breast milk. You and your child’s healthcare provider should decide if your child will receive ALKINDI SPRINKLE while your child breastfeeds." ], "text": "" }

Tell your healthcare provider about all the medicines your child takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

{ "type": "p", "children": [], "text": "\nTell your healthcare provider about all the medicines your child takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements.\n\n " }

Some medicines, food and drink can affect the way that ALKINDI SPRINKLE works and may mean that your healthcare

{ "type": "p", "children": [], "text": "Some medicines, food and drink can affect the way that ALKINDI SPRINKLE works and may mean that your healthcare" }

provider needs to change your child’s dose of ALKINDI SPRINKLE.

{ "type": "p", "children": [], "text": "provider needs to change your child’s dose of ALKINDI SPRINKLE." }

Especially tell your healthcare provider if your child:

{ "type": "p", "children": [], "text": "\nEspecially tell your healthcare provider if your child:\n" }

{ "type": "ul", "children": [ "takes medicines used to treat fungal infections such as itraconazole, posaconazole, and voriconazole.", "takes medicines used to treat bacterial infections such as rifampicin, rifabutin, erythromycin, andclarithromycin.", "takes medicines used to treat human immunodeficiency virus (HIV) infection and AIDS such as ritonavir, efavirenz, and nevirapine.", "takes seizure medicines such as phenytoin, carbamazepine, oxcarbazepine, phenobarbital, and primidone.", "takes estrogen.", "takes warfarin.", "takes nonsteroidal anti-inflammatory medicines such as aspirin, ibuprofen.", "takes cyclosporine.", "takes diabetes medicines.", "drinks grapefruit juice." ], "text": "" }

Know the medicines your child takes. Keep a list of them to show your healthcare provider and pharmacist when your child gets a new medicine.

{ "type": "p", "children": [], "text": "Know the medicines your child takes. Keep a list of them to show your healthcare provider and pharmacist when your child gets a new medicine." }

How should I give ALKINDI SPRINKLE?

{ "type": "p", "children": [], "text": "\nHow should I give ALKINDI SPRINKLE?\n" }

{ "type": "ul", "children": [ "See the detailed Instructions for Use that comes with your ALKINDI SPRINKLE for information on how to give a dose of ALKINDI SPRINKLE the right way.", "Give ALKINDI SPRINKLE exactly as prescribed by your healthcare provider.", "\nDo notstop giving ALKINDI SPRINKLE without talking to your healthcare provider. See “\n \n What is the most important information I should know about ALKINDI SPRINKLE?”\n \n ", "\nDo notlet your child chew or crush the granules. Do not let your child swallow the capsule.\n \n ", "\nDo notlet the capsules get wet as this may make some of the granules stick to the capsule.\n \n ", "Call your healthcare provider if granules come back up into your child’s mouth (regurgitation) or your child has vomiting after swallowing ALKINDI SPRINKLE. Your child may not have received the full dose of ALKINDI SPRINKLE and another dose of ALKINDI SPRINKLE may be needed.", "Your child may sometimes pass the ALKINDI SPRINKLE granules in their stools (bowel movement). It does not mean that ALKINDI SPRINKLE is not working.\n \n Do notgive your child another dose of ALKINDI SPRINKLE.\n \n ", "ALKINDI SPRINKLE granules should not be given through a nasogastric tube because the granules may block the tube.", "If your child takes too much ALKINDI SPRINKLE, call your healthcare provider right away or go to the nearest emergency room." ], "text": "" }

What are the possible side effects of ALKINDI SPRINKLE?

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects of ALKINDI SPRINKLE?\n" }

ALKINDI SPRINKLE may cause serious side effects, including:

{ "type": "p", "children": [], "text": "\nALKINDI SPRINKLE may cause serious side effects, including:\n" }

{ "type": "ul", "children": [ "\nSee “What is the most important information I should know about ALKINDI SPRINKLE?”\n", "\nWeakened immune system and increased risk of Infections.Taking too much ALKINDI SPRINKLE can weaken your body's immune system and increase your change of getting infections. Tell your healthcare provider if your child has any infection or has any of these symptoms:\n \n " ], "text": "" }

{ "type": "", "children": [], "text": "" }

{ "type": "ul", "children": [ "\nSlowed growth in children.Taking too much ALKINDI SPRINKLE and taking it for long periods of time can affect your child’s growth. Tell your healthcare provider if you are worried about your child’s growth. Your healthcare provider will change the dose depending on your child’s size.\n \n ", "\nCushing’s syndrome.Taking too much ALKINDI SPRINKLE and taking it for long periods of time can cause Cushing’s syndrome. Tell your healthcare provider if your child has any of these symptoms:\n \n " ], "text": "" }

{ "type": "", "children": [], "text": "" }

{ "type": "ul", "children": [ "\nWeak, brittle, or soft bones.ALKINDI SPRINKLE can affect your child’s bones. Your healthcare provider will change the dose depending on your child’s size and will monitor your child’s growth and bones.\n \n ", "\nChanges in behavior.Your child’s behavior may change after starting or during treatment with ALKINDI\n \n " ], "text": "" }

SPRINKLE. Tell your healthcare provider right away if your child develops any changes inbehavior including:

{ "type": "p", "children": [], "text": "SPRINKLE. Tell your healthcare provider right away if your child develops any changes inbehavior including:" }

strong feelings of happiness and excitement overexcited and overactivity loss of contact with reality, with feelings that are not real, and mental confusion depression

{ "type": "p", "children": [], "text": "strong feelings of happiness and excitement \n overexcited and overactivity \n loss of contact with reality, with feelings that are not real, and mental confusion \n depression\n " }

{ "type": "ul", "children": [ "\nVision problems.Tell your healthcare provider if your child develops blurred vision or other vision problems during treatment with ALKINDI SPRINKLE. Your healthcare provider may have your child see an eye doctor.\n \n ", "\nGastrointestinal problems.ALKINDI SPRINKLE can affect your child’s stomach or intestine. Tell your healthcare provider if your child has gastrointestinal illnesses such as stomach or intestinal ulcers, infections, or gastrointestinal surgery.\n \n ", "\nVaccinations.Administration of live vaccine may be acceptable while taking ALKINDI SPRINKLE.\n \n " ], "text": "" }

The most common side effects of ALKINDI SPRINKLE include:

{ "type": "p", "children": [], "text": "\nThe most common side effects of ALKINDI SPRINKLE include:\n" }

{ "type": "", "children": [], "text": "" }

These are not all the possible side effects of ALKINDI SPRINKLE. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

{ "type": "p", "children": [], "text": "These are not all the possible side effects of ALKINDI SPRINKLE. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088." }

How should I store ALKINDI SPRINKLE?

{ "type": "p", "children": [], "text": "\nHow should I store ALKINDI SPRINKLE?\n" }

{ "type": "ul", "children": [ "Store ALKINDI SPRINKLE at room temperature between 68°F to 77°F (20°C to 25°C).", "Store in the original bottle to protect from light.", "After the bottle has been opened, use the ALKINDI SPRINKLE capsules within 60 days." ], "text": "" }

Keep ALKINDI SPRINKLE and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep ALKINDI SPRINKLE and all medicines out of the reach of children.\n" }

General information about the safe and effective use of ALKINDI SPRINKLE.

{ "type": "p", "children": [], "text": "\nGeneral information about the safe and effective use of ALKINDI SPRINKLE.\n" }

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ALKINDI SPRINKLE for a condition for which it was not prescribed. Do not give ALKINDI SPRINKLE to other people, even if they

{ "type": "p", "children": [], "text": "Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ALKINDI SPRINKLE for a condition for which it was not prescribed. Do not give ALKINDI SPRINKLE to other people, even if they" }

have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about ALKINDI SPRINKLE that is written for health professionals.

{ "type": "p", "children": [], "text": "have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about ALKINDI SPRINKLE that is written for health professionals." }

What are the ingredients in ALKINDI SPRINKLE?

{ "type": "p", "children": [], "text": "\nWhat are the ingredients in ALKINDI SPRINKLE?\n" }

Active ingredient:hydrocortisone

{ "type": "p", "children": [], "text": "\nActive ingredient:hydrocortisone\n\n " }

Inactive ingredients:

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

granules: microcrystalline cellulose, hypromellose, magnesium stearate, ethyl cellulose.

{ "type": "p", "children": [], "text": "granules: microcrystalline cellulose, hypromellose, magnesium stearate, ethyl cellulose." }

capsule: hypromellose

{ "type": "p", "children": [], "text": "capsule: hypromellose" }

printing ink: shellac, propylene glycol, concentrated ammonia solution.

{ "type": "p", "children": [], "text": "printing ink: shellac, propylene glycol, concentrated ammonia solution." }

ALKINDI SPRINKLE is manufactured for Eton Pharmaceuticals, Inc. by Glatt Pharmaceutical Services GmbH & Co. KG Werner-Glatt-Strasse 1, Binzen, Baden- Wuerttemberg, 79589, Germany

{ "type": "p", "children": [], "text": "ALKINDI SPRINKLE is manufactured for Eton Pharmaceuticals, Inc. by Glatt Pharmaceutical Services GmbH & Co. KG Werner-Glatt-Strasse 1, Binzen, Baden- Wuerttemberg, 79589, Germany" }

ALKINDI SPRINKLE® is a registered trademark of Neurocrine UK Limited.

{ "type": "p", "children": [], "text": "ALKINDI SPRINKLE® is a registered trademark of Neurocrine UK Limited." }

ALKINDI is covered by the following US patents: 9,649,280; 9,675,559; 9,717,740; and other patents in other countries internationally. For more information, go to www.alkindisprinkle.com or call 1-833-343-2500.

{ "type": "p", "children": [], "text": "ALKINDI is covered by the following US patents: 9,649,280; 9,675,559; 9,717,740; and other patents in other countries internationally. For more information, go to www.alkindisprinkle.com or call\n \n 1-833-343-2500.\n\n " }

This Medication Guide has been approved by the U.S. Food and Drug Administration

{ "type": "p", "children": [], "text": "This Medication Guide has been approved by the U.S. Food and Drug Administration" }

Revised 12/2024

{ "type": "p", "children": [], "text": "Revised 12/2024" }

Instructions for Use

{ "type": "p", "children": [], "text": "\nInstructions for Use\n" }

ALKINDI SPRINKLE®(ælˈkɪndi spr-en-kle) (hydrocortisone) oral granules

{ "type": "p", "children": [], "text": "\nALKINDI SPRINKLE®(ælˈkɪndi spr-en-kle)\n\n\n(hydrocortisone) oral granules\n" }

Read this Instructions for Use before you start using ALKINDI SPRINKLE, and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your child’s medical condition or treatment.

{ "type": "p", "children": [], "text": "Read this Instructions for Use before you start using ALKINDI SPRINKLE, and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your child’s medical condition or treatment." }

Important information you need to know before giving ALKINDI SPRINKLE

{ "type": "p", "children": [], "text": "\nImportant information you need to know before giving ALKINDI SPRINKLE\n" }

{ "type": "ul", "children": [ "ALKINDI SPRINKLE comes in a capsule that must be opened before use.", "\nDo notlet your child swallow the capsule. Small children may choke.\n \n ", "\nDo notlet your child chew or crush the granules in the capsule.\n \n ", "\nDo notlet the capsules get wet as this may make some of the granules stick to the capsule.\n \n ", "Your healthcare provider will decide the right dose of ALKINDI SPRINKLE for your child. Follow your healthcare provider’s instructions for the dose of ALKINDI SPRINKLE to give your child.", "Ask your healthcare provider or pharmacist if you are not sure how to prepare or give the prescribed dose of ALKINDI SPRINKLE to your child.", "Call your healthcare provider if granules come back up into your child’s mouth (regurgitation) or your child has vomiting after swallowing ALKINDI SPRINKLE. Your child may not have received the full dose of ALKINDI SPRINKLE and another dose of ALKINDI SPRINKLE may be needed.", "Your child may sometimes pass the ALKINDI SPRINKLE granules in their stools (bowel movement). It does not mean that ALKINDI SPRINKLE is not working. Do not give your child another dose of ALKINDI SPRINKLE." ], "text": "" }

Supplies needed to give ALKINDI SPRINKLE:

{ "type": "p", "children": [], "text": "\nSupplies needed to give ALKINDI SPRINKLE:\n" }

{ "type": "ul", "children": [ "ALKINDI SPRINKLE capsule(s) for prescribed dose", "1 spoon", "soft food such as yogurt or pureed fruit or sip of fluids such as water, milk, breastmilk or formula" ], "text": "" }

Preparing and giving ALKINDI SPRINKLE:

{ "type": "p", "children": [], "text": "\nPreparing and giving ALKINDI SPRINKLE:\n" }

Step 1:Check the expiration date on the ALKINDI SPRINKLE bottle. Do not use ALKINDI SPRINKLE after the expiration date on the bottle has passed.

{ "type": "p", "children": [], "text": "\nStep 1:Check the expiration date on the ALKINDI SPRINKLE bottle. Do not use ALKINDI SPRINKLE after the expiration date on the bottle has passed.\n\n " }

Step 2:Remove the prescribed dose of ALKINDI SPRINKLE capsules from the bottle.

{ "type": "p", "children": [], "text": "\nStep 2:Remove the prescribed dose of ALKINDI SPRINKLE capsules from the bottle.\n\n " }

<div class="scrollingtable"><table class="Noautorules" width="60%"> <col align="left" valign="top" width="16%"/> <col align="left" valign="top" width="14%"/> <col align="left" valign="top" width="14%"/> <tbody class="Headless"> <tr> <td align="left"><span class="Bold">Step 3:</span>Hold and Tap <br/> <br/> <img alt="IMAGE-1" src="/dailymed/image.cfm?name=image-1.jpg&amp;setid=26c13a5f-7119-4c6a-bf10-fda4e07d7682"/><br/> <br/> Hold the capsule with the writing at the top. Tap the capsule to make sure the granules fall to the bottom. </td><td align="left"><span class="Bold">Step 4:</span>Squeeze <br/> <br/> <img alt="IMAGE-2" src="/dailymed/image.cfm?name=image-2.jpg&amp;setid=26c13a5f-7119-4c6a-bf10-fda4e07d7682"/><br/> <br/> Gently squeeze the bottom of the capsule to loosen the top of the capsule from the bottom. </td><td align="left"><span class="Bold">Step 5:</span>Twist <br/> <br/> <img alt="IMAGE-3" src="/dailymed/image.cfm?name=image-3.jpg&amp;setid=26c13a5f-7119-4c6a-bf10-fda4e07d7682"/>Carefully twist off the top of the capsule. </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"60%\">\n<col align=\"left\" valign=\"top\" width=\"16%\"/>\n<col align=\"left\" valign=\"top\" width=\"14%\"/>\n<col align=\"left\" valign=\"top\" width=\"14%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\"><span class=\"Bold\">Step 3:</span>Hold and Tap \n <br/>\n<br/>\n<img alt=\"IMAGE-1\" src=\"/dailymed/image.cfm?name=image-1.jpg&amp;setid=26c13a5f-7119-4c6a-bf10-fda4e07d7682\"/><br/>\n<br/> Hold the capsule with the writing at the top. Tap the capsule to make sure the granules fall to the bottom.\n \n </td><td align=\"left\"><span class=\"Bold\">Step 4:</span>Squeeze \n <br/>\n<br/>\n<img alt=\"IMAGE-2\" src=\"/dailymed/image.cfm?name=image-2.jpg&amp;setid=26c13a5f-7119-4c6a-bf10-fda4e07d7682\"/><br/>\n<br/> Gently squeeze the bottom of the capsule to loosen the top of the capsule from the bottom.\n \n </td><td align=\"left\"><span class=\"Bold\">Step 5:</span>Twist \n <br/>\n<br/>\n<img alt=\"IMAGE-3\" src=\"/dailymed/image.cfm?name=image-3.jpg&amp;setid=26c13a5f-7119-4c6a-bf10-fda4e07d7682\"/>Carefully twist off the top of the capsule.\n \n </td>\n</tr>\n</tbody>\n</table></div>" }

Step 6: Giving ALKINDI SPRINKLE

{ "type": "p", "children": [], "text": "\nStep 6: Giving ALKINDI SPRINKLE\n" }

ALKINDI SPRINKLE can be given (a) with food onto a spoon, (b) without food onto a spoon, or (c) directly into the child’s mouth.

{ "type": "p", "children": [], "text": "ALKINDI SPRINKLE can be given (a) with food onto a spoon, (b) without food onto a spoon, or (c) directly into the child’s mouth." }

Do notadd the granules to a fluid before giving ALKINDI SPRINKLE because it can result in less than the full dose given and it may leave a bitter taste in the mouth.

{ "type": "p", "children": [], "text": "\nDo notadd the granules to a fluid before giving ALKINDI SPRINKLE because it can result in less than the full dose given and it may leave a bitter taste in the mouth.\n\n " }

<div class="scrollingtable"><table class="Noautorules" width="65%"> <col align="left" valign="top" width="15%"/> <col align="left" valign="top" width="13%"/> <col align="left" valign="top" width="15%"/> <tbody class="Headless"> <tr> <td align="left">(a) With food onto a spoon <br/> <br/> <img alt="IMAGE-4" src="/dailymed/image.cfm?name=image-4.jpg&amp;setid=26c13a5f-7119-4c6a-bf10-fda4e07d7682"/><br/> <br/> Pour <span class="Bold">all</span>granules from each capsule directly onto a spoonful of cold or room temperature soft food (such as yogurt or fruit puree) and give right away. </td><td align="left">(b) Without food onto a spoon <br/> <br/> <img alt="IMAGE-5" src="/dailymed/image.cfm?name=image-5.jpg&amp;setid=26c13a5f-7119-4c6a-bf10-fda4e07d7682"/><br/> <br/> <br/> <br/> Pour <span class="Bold">all</span>granules directly onto a spoon and place them in the child’s mouth. </td><td align="left"> <p class="First">(c) Directly onto the child’s tongue. <br/> <br/> <img alt="IMAGE-6" src="/dailymed/image.cfm?name=image-6.jpg&amp;setid=26c13a5f-7119-4c6a-bf10-fda4e07d7682"/></p> <p>Pour <span class="Bold">all</span>granules that make up the prescribed dose directly onto the child’s tongue. </p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"65%\">\n<col align=\"left\" valign=\"top\" width=\"15%\"/>\n<col align=\"left\" valign=\"top\" width=\"13%\"/>\n<col align=\"left\" valign=\"top\" width=\"15%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\">(a) With food onto a spoon \n <br/>\n<br/>\n<img alt=\"IMAGE-4\" src=\"/dailymed/image.cfm?name=image-4.jpg&amp;setid=26c13a5f-7119-4c6a-bf10-fda4e07d7682\"/><br/>\n<br/> Pour\n \n <span class=\"Bold\">all</span>granules from each capsule directly onto a spoonful of cold or room temperature soft food (such as yogurt or fruit puree) and give right away.\n \n </td><td align=\"left\">(b) Without food onto a spoon \n <br/>\n<br/>\n<img alt=\"IMAGE-5\" src=\"/dailymed/image.cfm?name=image-5.jpg&amp;setid=26c13a5f-7119-4c6a-bf10-fda4e07d7682\"/><br/>\n<br/>\n<br/>\n<br/> Pour\n \n <span class=\"Bold\">all</span>granules directly onto a spoon and place them in the child’s mouth.\n \n </td><td align=\"left\">\n<p class=\"First\">(c) Directly onto the child’s tongue. \n <br/>\n<br/>\n<img alt=\"IMAGE-6\" src=\"/dailymed/image.cfm?name=image-6.jpg&amp;setid=26c13a5f-7119-4c6a-bf10-fda4e07d7682\"/></p>\n<p>Pour\n \n <span class=\"Bold\">all</span>granules that make up the prescribed dose directly onto the child’s tongue.\n \n </p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Tap the capsule to make sure all granules are removed.

{ "type": "p", "children": [], "text": "Tap the capsule to make sure all granules are removed." }

The ALKINDI SPRINKLE granules should be given and swallowed within 5 minutes to avoid a bitter taste.

{ "type": "p", "children": [], "text": "The ALKINDI SPRINKLE granules should be given and swallowed within 5 minutes to avoid a bitter taste." }

Step 7: Give Fluids

{ "type": "p", "children": [], "text": "\nStep 7: Give Fluids\n" }

After giving ALKINDI SPRINKLE, give a sip of fluids such as water, milk, breastmilk or formula right away to make sure all granules are swallowed.

{ "type": "p", "children": [], "text": "After giving ALKINDI SPRINKLE, give a sip of fluids such as water, milk, breastmilk or formula right away to make sure all granules are swallowed." }

Throwing Away (disposal of) ALKINDI SPRINKLE:

{ "type": "p", "children": [], "text": "\nThrowing Away (disposal of) ALKINDI SPRINKLE:\n" }

Ask your pharmacist how to throw away medicines you no longer use.

{ "type": "p", "children": [], "text": "Ask your pharmacist how to throw away medicines you no longer use." }

How should I store ALKINDI SPRINKLE?

{ "type": "p", "children": [], "text": "\nHow should I store ALKINDI SPRINKLE?\n" }

{ "type": "ul", "children": [ "Store ALKINDI SPRINKLE at room temperature between 68°F to 77°F (20°C to 25°C).", "Store in the original bottle to protect from light.", "After the bottle has been opened, use the ALKINDI SPRINKLE capsules within 60 days." ], "text": "" }

Keep ALKINDI SPRINKLE and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep ALKINDI SPRINKLE and all medicines out of the reach of children.\n" }

ALKINDI SPRINKLE is manufactured for Eton Pharmaceuticals, Inc. by Glatt Pharmaceutical Services GmbH & Co. KG Werner-Glatt-Strasse 1, Binzen, Baden-Wuerttemberg, 79589, Germany

{ "type": "p", "children": [], "text": "ALKINDI SPRINKLE is manufactured for Eton Pharmaceuticals, Inc. by Glatt Pharmaceutical Services GmbH & Co. KG Werner-Glatt-Strasse 1, Binzen, Baden-Wuerttemberg, 79589, Germany" }

ALKINDI SPRINKLE® is a registered trademark of Neurocrine UK Limited.

{ "type": "p", "children": [], "text": "ALKINDI SPRINKLE® is a registered trademark of Neurocrine UK Limited." }

ALKINDI is covered by the following US patents: 9,649,280; 9,675,559; 9,717,740; and other patents in other countries internationally.

{ "type": "p", "children": [], "text": "ALKINDI is covered by the following US patents: 9,649,280; 9,675,559; 9,717,740; and other patents in other countries internationally." }

For more information, go to www.alkindisprinkle.comor call 1-833-343-2500.

{ "type": "p", "children": [], "text": "For more information, go to\n \n www.alkindisprinkle.comor call\n \n 1-833-343-2500.\n" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "\nThis Instructions for Use has been approved by the U.S. Food and Drug Administration.\n" }

Revised: 12/2024

{ "type": "p", "children": [], "text": "\nRevised: 12/2024\n" }

Alkindi Sprinkle (hydrocortisone) oral granules 0.5 mg - NDC 71863-109-50 - 50 Tablets Carton Label

{ "type": "p", "children": [], "text": "\nAlkindi Sprinkle (hydrocortisone) oral granules 0.5 mg - NDC 71863-109-50 - 50 Tablets Carton Label\n" }

Alkindi Sprinkle (hydrocortisone) oral granules 0.5 mg - NDC 71863-109-50 - 50 Tablets Container Label

{ "type": "p", "children": [], "text": "\nAlkindi Sprinkle (hydrocortisone) oral granules 0.5 mg - NDC 71863-109-50 - 50 Tablets Container Label\n" }

Alkindi Sprinkle (hydrocortisone) oral granules 1 mg - NDC 71863-110-50 - 50 Tablets Carton Label

{ "type": "p", "children": [], "text": "\nAlkindi Sprinkle (hydrocortisone) oral granules 1 mg - NDC 71863-110-50 - 50 Tablets Carton Label\n" }

Alkindi Sprinkle (hydrocortisone) oral granules 1 mg - NDC 71863-110-50 - 50 Tablets Container Label

{ "type": "p", "children": [], "text": "\nAlkindi Sprinkle (hydrocortisone) oral granules 1 mg - NDC 71863-110-50 - 50 Tablets Container Label\n" }

Alkindi Sprinkle (hydrocortisone) oral granules 2 mg - NDC 71863-111-50 - 50 Tablets Carton Label

{ "type": "p", "children": [], "text": "\nAlkindi Sprinkle (hydrocortisone) oral granules 2 mg - NDC 71863-111-50 - 50 Tablets Carton Label\n" }

Alkindi Sprinkle (hydrocortisone) oral granules 2 mg - NDC 71863-111-50 - 50 Tablets Container Label

{ "type": "p", "children": [], "text": "\nAlkindi Sprinkle (hydrocortisone) oral granules 2 mg - NDC 71863-111-50 - 50 Tablets Container Label\n" }

Alkindi Sprinkle (hydrocortisone) oral granules 5 mg - NDC 71863-112-50 - 50 Tablets Carton Label

{ "type": "p", "children": [], "text": "\nAlkindi Sprinkle (hydrocortisone) oral granules 5 mg - NDC 71863-112-50 - 50 Tablets Carton Label\n" }

Alkindi Sprinkle (hydrocortisone) oral granules 5 mg - NDC 71863-112-50 - 50 Tablets Container Label

{ "type": "p", "children": [], "text": "\nAlkindi Sprinkle (hydrocortisone) oral granules 5 mg - NDC 71863-112-50 - 50 Tablets Container Label\n" }

Alkindi Sprinkle (hydrocortisone) oral granules 0.5 mg Samples - NDC 71863-117-50 - 50 Tablets Container Label

{ "type": "p", "children": [], "text": "\nAlkindi Sprinkle (hydrocortisone) oral granules 0.5 mg Samples - NDC 71863-117-50 - 50 Tablets Container Label\n" }

Alkindi Sprinkle (hydrocortisone) oral granules 1 mg Samples - NDC 71863-118-50 - 50 Tablets Container Label

{ "type": "p", "children": [], "text": "\nAlkindi Sprinkle (hydrocortisone) oral granules 1 mg Samples - NDC 71863-118-50 - 50 Tablets Container Label\n" }

Hydrocortisone Butyrate Lotion is indicated for the topical treatment of mild to moderate atopic dermatitis in patients 3 months of age and older.

{ "type": "p", "children": [], "text": "Hydrocortisone Butyrate Lotion is indicated for the topical treatment of mild to moderate atopic dermatitis in patients 3 months of age and older." }

{ "type": "ul", "children": [ "Apply Hydrocortisone Butyrate Lotion for up to 2 weeks as a thin layer to the affected skin two times daily and rub in gently.", "Discontinue Hydrocortisone Butyrate Lotion when control is achieved.", "If no improvement is seen within 2 weeks, consider reassessment of the diagnosis. Before prescribing for more than 2 weeks, the additional benefits of extending treatment up to 4 weeks should be weighed against the risk of endocrine system adverse reactions and local adverse reactions\n \n [see\n \n Warnings and Precautions (5.1),\n \n Adverse Reactions (6.1,\n \n 6.2)].\n \n \n", "Hydrocortisone Butyrate Lotion is not for oral, ophthalmic, or intravaginal use.", "Do not use Hydrocortisone Butyrate Lotion\n \n [see\n \n Warnings and Precautions (5.1)]\n \n .\n \n ", "With occlusive dressings unless directed by a healthcare provider. Avoid use in the diaper area, as diapers or plastic pants may constitute occlusive dressings.", "On the face, underarms, or groin areas unless directed by a healthcare provider." ], "text": "" }

Lotion: Each gram contains 1 mg of hydrocortisone butyrate (0.1%) in a white to off-white lotion base.

{ "type": "p", "children": [], "text": "Lotion: Each gram contains 1 mg of hydrocortisone butyrate (0.1%) in a white to off-white lotion base." }

None.

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

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression

Use of topical corticosteroids, including Hydrocortisone Butyrate Lotion, can cause systemic adverse reactions including reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for clinical glucocorticosteroid insufficiency. Factors that predispose a patient to HPA axis suppression include the use of high-potency steroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure, and young age. Such patients should be considered for periodic evaluation of the HPA axis. This may be done by using cosyntropin (ACTH 1-24) stimulation testing (CST). If HPA axis suppression is noted, reduce the frequency of application or discontinue Hydrocortisone Butyrate Lotion, or substitute with a less potent corticosteroid. Signs and symptoms of glucocorticosteroid insufficiency may occur, requiring supplemental systemic corticosteroids [see Adverse Reactions (6)].

Studies conducted in pediatric subjects demonstrated reversible HPA axis suppression after use of Hydrocortisone Butyrate Lotion. Pediatric patients may be more susceptible than adults to systemic toxicity from equivalent doses of Hydrocortisone Butyrate Lotion due to their larger skin-surface-to-body-mass ratios [see Use in Specific Populations (8.4)].

Cushing’s Syndrome, Hyperglycemia, and Glucosuria

Systemic adverse reactions of topical corticosteroids, including Hydrocortisone Butyrate Lotion, may also include manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria.

Additional Considerations for Endocrine Adverse Reactions

Use of more than one corticosteroid-containing product at the same time may increase total systemic corticosteroid exposure.

Minimize systemic corticosteroid adverse reactions by mitigating the risk factors for increased systemic absorption and using Hydrocortisone Butyrate Lotion as recommended [ see Dosage and Administration (2)].

Use of topical corticosteroids, including Hydrocortisone Butyrate Lotion, may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported in post-marketing experience with the use of topical corticosteroid products [see Adverse Reactions (6.2)] .

Avoid contact of Hydrocortisone Butyrate Lotion with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.

Use of topical corticosteroids, including Hydrocortisone Butyrate Lotion, may delay healing or worsen concomitant skin infections. If skin infections are present or develop, an appropriate antimicrobial agent should be used. If a favorable response does not occur promptly, use of Hydrocortisone Butyrate Lotion should be discontinued until the infection has been adequately controlled [see Adverse Reactions (6)].

Use of topical corticosteroids, including Hydrocortisone Butyrate Lotion, can cause allergic contact dermatitis [see Adverse Reactions (6)] . Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noticing a clinical exacerbation. Such an observation should be corroborated with appropriate patch testing. Discontinue Hydrocortisone Butyrate Lotion if the diagnosis is established .

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 safety data described below reflect exposure to Hydrocortisone Butyrate Lotion applied topically twice daily for up to 4 weeks in vehicle-controlled clinical trials of 284 pediatric subjects 3 months to 18 years of age and 301 adult subjects with mild to moderate atopic dermatitis [see Clinical Studies (14)] .

The incidence of selected adverse reactions reported by ≥1% of subjects during the studies is presented in Table 1 and Table 2. 

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1. Adverse Reactions in ≥1% of Hydrocortisone Butyrate Lotion-treated Pediatric Subjects 3 Months to 18 Years of Age with Mild to Moderate Atopic Dermatitis</span> </caption> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Hydrocortisone Butyrate Lotion</span> </p> <p> <span class="Bold">(n=139) n (%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Vehicle</span> </p> <p> <span class="Bold">(n=145) n (%)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Application site reactions, including application site burning, pruritus, dermatitis, erythema, eczema, inflammation, or irritation</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2 (1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">20 (14)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Infantile acne</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1 (1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0 (0)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Skin depigmentation</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1 (1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0 (0)</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 2. Adverse Reactions in ≥1% of Hydrocortisone Butyrate Lotion-treated Adult Subjects with Mild to Moderate Atopic Dermatitis</span> </caption> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Hydrocortisone Butyrate Lotion</span> </p> <p> <span class="Bold">(n=151) n (%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Vehicle</span> </p> <p> <span class="Bold">(n=150) n (%)</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Application site reactions, including application site burning, dermatitis, eczema, erythema, or pruritus</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">5 (3)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">7 (5)</p> </td> </tr> </tbody> </table></div>

The following adverse reactions have been identified during postapproval use of topical corticosteroids, including Hydrocortisone Butyrate Lotion. 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.

Local Adverse Reactions: folliculitis, acneiform eruptions, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, miliaria, and telangiectasia.

Ophthalmic Adverse Reactions:blurred vision, cataracts, glaucoma, and increased intraocular pressure.

Risk Summary

There are no controlled or large-scale epidemiologic studies with Hydrocortisone Butyrate Lotion in pregnant women, and available data on hydrocortisone butyrate use in pregnant women have not identified a drug associated risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes.

In animal reproduction studies, when administered subcutaneously or topically to pregnant rats, rabbits, and mice, hydrocortisone butyrate induced adverse reproductive and developmental outcomes, including abortion, fetal death, malformation, delayed ossification, decrease in fetal weight, and delay in sexual maturation ( see Data). The available data do not allow the calculation of relevant comparisons between the systemic exposure of hydrocortisone butyrate observed in animal studies and the systemic exposure that would be expected in humans after topical use of Hydrocortisone Butyrate Lotion.

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 2-4% and 15-20%, respectively.

Data

Animal Data

Systemic embryofetal development studies were conducted in rats and rabbits. Subcutaneous doses of 0.6, 1.8, and 5.4 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats during gestation days 6 – 17. In the presence of maternal toxicity, fetal effects noted at 5.4 mg/kg/day included increased ossification variations and unossified sternebra. No treatment-related embryofetal toxicity or malformation were noted at 5.4 and 1.8 mg/kg/day, respectively.

Subcutaneous doses of 0.1, 0.2 and 0.3 mg/kg/day hydrocortisone butyrate were administered to pregnant female rabbits during gestation days 7 – 20. Increased abortion was noted at 0.3 mg/kg/day. In the absence of maternal toxicity, a dose-dependent decrease in fetal body weight was noted at doses ≥0.1 mg/kg/day. Embryofetal toxicities (reduction in litter size, decreased number of viable fetuses, and increased post-implantation loss) were noted at doses ≥0.2 mg/kg/day. Additional fetal effects included delayed ossification noted at doses ≥0.1 mg/kg/day and increased fetal malformations (primarily skeletal malformations) noted at doses ≥0.2 mg/kg/day. A dose at which no embryofetal toxicity or malformation was observed was not established in this study.

Additional systemic embryofetal development studies were conducted in rats and mice. Subcutaneous doses of 0.1 and 9 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats during gestation days 9 – 15. In the presence of maternal toxicity, an increase in fetal death and fetal resorption and an increase in ossification of caudal vertebrae were noted at 9 mg/kg/day. No treatment-related embryofetal toxicity or malformation was noted at 0.1 mg/kg/day.

Subcutaneous doses of 0.2 and 1 mg/kg/day hydrocortisone butyrate were administered to pregnant female mice during gestation days 7 – 13. In the absence of maternal toxicity, an increased number of cervical ribs and one fetus with clubbed legs were noted at 1 mg/kg/day. No treatment-related embryofetal toxicity or malformation was noted at 1 and 0.2 mg/kg/day.

No topical embryofetal development studies were conducted with hydrocortisone butyrate lotion. However, topical embryofetal development studies were conducted in rats and rabbits with a hydrocortisone butyrate ointment formulation. Topical doses of 1% and 10% hydrocortisone butyrate ointment were administered to pregnant female rats during gestation days 6 – 15 or pregnant female rabbits during gestation days 6 – 18. A dose-dependent increase in fetal resorption was noted in rabbits and fetal resorptions were noted in rats at the 10% hydrocortisone butyrate ointment dose. No treatment-related embryofetal toxicity was noted at the 1% hydrocortisone butyrate ointment dose in rats. A dose at which no embryofetal toxicity was observed in rabbits after topical administration of hydrocortisone butyrate ointment was not established. No treatment-related malformation was noted at a dose of 10% hydrocortisone butyrate ointment in rats or rabbits.

A peri- and post-natal development study was conducted in rats. Subcutaneous doses of 0.6, 1.8 and 5.4 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats from gestation day 6 to lactation day 20. In the presence of maternal toxicity, a dose-dependent decrease in fetal weight was noted at doses ≥1.8 mg/kg/day. No treatment-related fetal toxicity was noted at 0.6 mg/kg/day. A delay in sexual maturation was noted at 5.4 mg/kg/day. No treatment-related effects on sexual maturation were noted at 1.8 mg/kg/day. No treatment-related effects on behavioral development or subsequent reproductive performance were noted at 5.4 mg/kg/day.

Risk Summary

There are no data on the presence of hydrocortisone butyrate in human or animal milk, effects on the breastfed infant, or effects on milk production.

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of Hydrocortisone Butyrate Lotion could result in sufficient systemic absorption to produce detectable quantities in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Hydrocortisone Butyrate Lotion and any potential adverse effects on the breastfed infant from Hydrocortisone Butyrate Lotion or from the underlying maternal condition.

Clinical Considerations

To minimize potential exposure to the breastfed infant via breast milk, use Hydrocortisone Butyrate Lotion on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women to wash off prior to breastfeeding any Hydrocortisone Butyrate Lotion that has been applied to the areas at risk for direct infant contact.

The safety and effectiveness of Hydrocortisone Butyrate Lotion for the topical treatment of mild to moderate atopic dermatitis have been established in pediatric patients 3 months of age and older. Use of Hydrocortisone Butyrate Lotion for this indication is supported by evidence from an adequate and well-controlled trial in 284 pediatric patients 3 months to 18 years of age with mild to moderate atopic dermatitis.

The safety and effectiveness of Hydrocortisone Butyrate Lotion have not been established in pediatric patients younger than 3 months of age.

Endocrine Adverse Reactions

Eighty-four (84) pediatric subjects (3 months to less than 18 years of age) with moderate to severe atopic dermatitis affecting at least 25% of body surface area (BSA) treated with Hydrocortisone Butyrate Lotion three times daily for up to 4 weeks were assessed for HPA axis suppression. The disease severity (moderate to severe atopic dermatitis) and the dosing regimen (three times daily) in this HPA axis trial were different from the subject population (mild to moderate atopic dermatitis) and the dosing regimen (twice daily) for which Hydrocortisone Butyrate Lotion is indicated. Seven of the 82 evaluable subjects (8.5%) demonstrated laboratory evidence of HPA axis suppression, where the criterion for defining HPA axis suppression was a serum cortisol level of less than or equal to 18 mcg/dL after cosyntropin stimulation. Subjects with HPA axis suppression ranged from 1 to 12 years of age and, at the time of enrollment, had 35% to 90% BSA involvement. These subjects did not develop any other signs or symptoms of HPA axis suppression. At the first follow-up visit, approximately 1 month after the conclusion of treatment, cosyntropin stimulation results of all subjects had returned to normal, with the exception of one subject. This last subject recovered adrenal function by the second post-treatment visit, 55 days post-treatment [see Clinical Pharmacology (12.2)] .

Because of higher skin-surface-to-body-mass ratios, pediatric patients are at a greater risk than adults of HPA axis suppression when they are treated with topical corticosteroids [see Warnings and Precautions (5.1)] . They are therefore also at a greater risk of glucocorticosteroid insufficiency after withdrawal of treatment and of Cushing’s syndrome while on treatment.

Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients include low plasma cortisol levels to an absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

Clinical trials of Hydrocortisone Butyrate Lotion did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger adult subjects.

Hydrocortisone Butyrate Lotion, 0.1% contains hydrocortisone butyrate, a non-fluorinated hydrocortisone ester, for topical use.

{ "type": "p", "children": [], "text": "Hydrocortisone Butyrate Lotion, 0.1% contains hydrocortisone butyrate, a non-fluorinated hydrocortisone ester, for topical use." }

Hydrocortisone butyrate is a corticosteroid.

{ "type": "p", "children": [], "text": "Hydrocortisone butyrate is a corticosteroid." }

The chemical name of hydrocortisone butyrate is Pregn-4-ene-3,20-dione, 11,21-dihydroxy-17-[(1-oxobutyl)oxy(11β)-]. It has the following structural formula:

{ "type": "p", "children": [], "text": "The chemical name of hydrocortisone butyrate is Pregn-4-ene-3,20-dione, 11,21-dihydroxy-17-[(1-oxobutyl)oxy(11β)-]. It has the following structural formula:" }

Hydrocortisone butyrate is a white to off-white powder with a molecular weight of 432.56, and a molecular formula of C 25H 36O 6. It is practically insoluble in water, slightly soluble in ether, soluble in methanol, alcohol, and acetone, and freely soluble in chloroform.

{ "type": "p", "children": [], "text": "Hydrocortisone butyrate is a white to off-white powder with a molecular weight of 432.56, and a molecular formula of C\n \n 25H\n \n 36O\n \n 6. It is practically insoluble in water, slightly soluble in ether, soluble in methanol, alcohol, and acetone, and freely soluble in chloroform.\n\n " }

Each gram of Hydrocortisone Butyrate Lotion contains 1 mg of hydrocortisone butyrate in a white to off-white lotion base consisting of anhydrous citric acid, ceteth-20, cetostearyl alcohol, butylated hydroxytoluene (BHT), butylparaben, light mineral oil, propylparaben, purified water, safflower oil, sodium citrate, and white petrolatum.

{ "type": "p", "children": [], "text": "Each gram of Hydrocortisone Butyrate Lotion contains 1 mg of hydrocortisone butyrate in a white to off-white lotion base consisting of anhydrous citric acid, ceteth-20, cetostearyl alcohol, butylated hydroxytoluene (BHT), butylparaben, light mineral oil, propylparaben, purified water, safflower oil, sodium citrate, and white petrolatum." }

Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action in atopic dermatitis is unknown.

Pharmacodynamics of Hydrocortisone Butyrate Lotion is unknown.

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression

Eighty-four (84) pediatric subjects (3 months to less than 18 years of age) with moderate to severe atopic dermatitis affecting at least 25% of body surface area (BSA) treated with Hydrocortisone Butyrate Lotion three times daily for up to 4 weeks were assessed for HPA axis suppression. The disease severity (moderate to severe atopic dermatitis) and the dosing regimen (three times daily) in this HPA axis trial were different from the subject population (mild to moderate atopic dermatitis) and the dosing regimen (twice daily) for which Hydrocortisone Butyrate Lotion is indicated. Seven of the 82 evaluable subjects (8.5%) demonstrated laboratory evidence of HPA axis suppression, where the criterion for defining HPA axis suppression was a serum cortisol level of less than or equal to 18 mcg/dL after cosyntropin stimulation. Subjects with HPA axis suppression ranged from 1 to 12 years of age and, at the time of enrollment, had 35% to 90% BSA involvement. These subjects did not develop any other signs or symptoms of HPA axis suppression. At the first follow-up visit, approximately 1 month after the conclusion of treatment, cosyntropin stimulation results of all subjects had returned to normal, with the exception of one subject. This last subject recovered adrenal function by the second post-treatment visit, 55 days post-treatment [see Warnings and Precautions (5.1),Use in Specific Populations (8.4)].

No studies were conducted to determine the pharmacokinetics of Hydrocortisone Butyrate Lotion.

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings.

Topical corticosteroids can be absorbed through normal intact skin. Inflammation and/or other disease processes in the skin, occlusive dressings, or widespread application may increase percutaneous absorption.

Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids.

In a 2-year dermal rat carcinogenicity study with Hydrocortisone Butyrate Lotion, hydrocortisone butyrate was administered to Sprague-Dawley rats at topical doses of 0.05, 0.15, and 0.3 mg/kg/day in males and 0.1, 0.25, and 0.5 mg/kg/day in females (0.1% lotion). No drug-related tumors were noted in this study up to the highest doses evaluated in this study of 0.3 mg/kg/day in males and 0.5 mg/kg/day in females.

Hydrocortisone butyrate revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames test and L5178Y/TK +/-mouse lymphoma assay) and one in vivo genotoxicity test (mouse micronucleus assay).

No evidence of impairment of fertility or effect on mating performance was observed in a fertility and general reproductive performance study conducted in male and female rats at subcutaneous doses up to 1.8 mg/kg/day. Mild effects on maternal animals, such as reduced food consumption and a subsequent reduction in body weight gain, were seen at doses ≥0.6 mg/kg/day.

In a multicenter, randomized, vehicle-controlled trial of 284 pediatric subjects 3 months to 18 years of age with mild to moderate atopic dermatitis, Hydrocortisone Butyrate Lotion or vehicle was applied topically twice daily for up to 4 weeks. Treatment success was assessed at day 29 (after 28 days of treatment) and was defined as the proportion of subjects who achieved both “clear” or “almost clear” and at least a 2-grade improvement from baseline on a 5-point Physician’s Global Assessment (PGA) scale. The trial results are shown in Table 3.

{ "type": "p", "children": [], "text": "In a multicenter, randomized, vehicle-controlled trial of 284 pediatric subjects 3 months to 18 years of age with mild to moderate atopic dermatitis, Hydrocortisone Butyrate Lotion or vehicle was applied topically twice daily for up to 4 weeks. Treatment success was assessed at day 29 (after 28 days of treatment) and was defined as the proportion of subjects who achieved both “clear” or “almost clear” and at least a 2-grade improvement from baseline on a 5-point Physician’s Global Assessment (PGA) scale. The trial results are shown in Table 3." }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 3. Efficacy Results at Day 29 in Pediatric Subjects 3 Months to 18 Years of Age with Mild to Moderate Atopic Dermatitis</span> </caption> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Hydrocortisone Butyrate Lotion</span> </p> <p> <span class="Bold">(n=139)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Vehicle</span> </p> <p> <span class="Bold">(n=145)</span> </p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Number (%) successes</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">68 (49%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">35 (24%)</p> </td> </tr> </tbody> </table></div>

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How Supplied

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

Hydrocortisone Butyrate Lotion, 0.1% is white to off-white in color and supplied in:

{ "type": "p", "children": [], "text": "Hydrocortisone Butyrate Lotion, 0.1% is white to off-white in color and supplied in:" }

{ "type": "ul", "children": [ "2 fl. oz. bottle: NDC 68682-392-02", "4 fl. oz. bottle: NDC 68682-392-04" ], "text": "" }

Storage and Handling

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

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from freezing.

{ "type": "p", "children": [], "text": "Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from freezing." }

Patients using Hydrocortisone Butyrate Lotion should receive the following information and instructions:

{ "type": "p", "children": [], "text": "Patients using Hydrocortisone Butyrate Lotion should receive the following information and instructions:" }

Administration Instructions

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

Instruct patients to apply a thin layer to the affected skin two times daily and rub in gently [see Dosage and Administration (2)] .

{ "type": "p", "children": [], "text": "Instruct patients to apply a thin layer to the affected skin two times daily and rub in gently\n \n [see\n \n Dosage and Administration (2)]\n \n .\n\n " }

Advise patients to discontinue Hydrocortisone Butyrate Lotion when control is achieved [see Dosage and Administration (2)] .

{ "type": "p", "children": [], "text": "Advise patients to discontinue Hydrocortisone Butyrate Lotion when control is achieved\n \n [see\n \n Dosage and Administration (2)]\n \n .\n\n " }

Advise patients to avoid use for longer than 2 weeks. Instruct patients to contact their healthcare provider if no improvement is seen within 2 weeks [see Dosage and Administration (2)] .

{ "type": "p", "children": [], "text": "Advise patients to avoid use for longer than 2 weeks. Instruct patients to contact their healthcare provider if no improvement is seen within 2 weeks\n \n [see\n \n Dosage and Administration (2)]\n \n .\n\n " }

Advise patients to NOT[see Dosage and Administration (2)and Warnings and Precautions (5.1)] :

{ "type": "p", "children": [], "text": "Advise patients to\n \n NOT[see\n \n Dosage and Administration (2)and\n \n Warnings and Precautions (5.1)]\n \n :\n\n " }

{ "type": "ul", "children": [ "Bandage, otherwise cover, or wrap the affected skin area unless directed by their healthcare provider.", "Use Hydrocortisone Butyrate Lotion in the diaper area, as diapers or plastic pants may constitute occlusive dressings.", "Use Hydrocortisone Butyrate Lotion on the face, underarms, or groin areas unless directed by their healthcare provider." ], "text": "" }

Endocrine System Adverse Reactions

{ "type": "p", "children": [], "text": "\nEndocrine System Adverse Reactions\n" }

Instruct patients not to use other corticosteroid-containing products while using Hydrocortisone Butyrate Lotion without first consulting their healthcare provider [see Warnings and Precautions (5.1)] .

{ "type": "p", "children": [], "text": "Instruct patients not to use other corticosteroid-containing products while using Hydrocortisone Butyrate Lotion without first consulting their healthcare provider\n \n [see\n \n Warnings and Precautions (5.1)]\n \n .\n\n " }

Ophthalmic Adverse Reactions

{ "type": "p", "children": [], "text": "\nOphthalmic Adverse Reactions\n" }

Advise patients to avoid contact with the eyes. Instruct patients to report any visual symptoms to their healthcare providers [see Warnings and Precautions (5.4)] .

{ "type": "p", "children": [], "text": "Advise patients to avoid contact with the eyes. Instruct patients to report any visual symptoms to their healthcare providers\n \n [see\n \n Warnings and Precautions (5.4)]\n \n .\n\n " }

Lactation

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

Advise breastfeeding women to use Hydrocortisone Butyrate Lotion on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise to wash off prior to breastfeeding any Hydrocortisone Butyrate Lotion that has been applied to the areas at risk for direct infant contact. [see Use in Specific Populations (8.2)] .

{ "type": "p", "children": [], "text": "Advise breastfeeding women to use Hydrocortisone Butyrate Lotion on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise to wash off prior to breastfeeding any Hydrocortisone Butyrate Lotion that has been applied to the areas at risk for direct infant contact.\n \n [see\n \n Use in Specific Populations (8.2)]\n \n .\n\n " }

Distributed by: Oceanside Pharmaceuticals, a division of Bausch Health US, LLC Bridgewater, NJ 08807 USA

{ "type": "p", "children": [], "text": "\nDistributed by:\n Oceanside Pharmaceuticals, a division of \n Bausch Health US, LLC \n Bridgewater, NJ 08807 USA\n\n " }

Manufactured by: Ferndale Laboratories, Inc. Ferndale, MI 48220 USA

{ "type": "p", "children": [], "text": "\nManufactured by:\n Ferndale Laboratories, Inc. \n Ferndale, MI 48220 USA\n\n " }

U.S. Patent Number: 7,981,877

{ "type": "p", "children": [], "text": "U.S. Patent Number: 7,981,877" }

© 2023 Bausch Health Companies Inc. or its affiliates

{ "type": "p", "children": [], "text": "© 2023 Bausch Health Companies Inc. or its affiliates" }

9625202

{ "type": "p", "children": [], "text": "9625202" }

PRINCIPAL DISPLAY PANEL – Hydrocortisone Butyrate Lotion 4 fl. oz. Carton

{ "type": "p", "children": [], "text": "\nPRINCIPAL DISPLAY PANEL – Hydrocortisone Butyrate Lotion 4 fl. oz. Carton\n" }

NDC 68682-392-04

{ "type": "p", "children": [], "text": "\nNDC 68682-392-04\n" }

Rx only

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

Hydrocortisone Butyrate Lotion, 0.1%

{ "type": "p", "children": [], "text": "\nHydrocortisone\n\nButyrate\n\nLotion, 0.1%\n" }

For topical use only Not for eye use

{ "type": "p", "children": [], "text": "\nFor topical use only\n\nNot for eye use\n" }

4 fl. oz. (118 mL)

{ "type": "p", "children": [], "text": "\n4 fl. oz. (118 mL)\n" }

OCEANSIDE PHARMACEUTICALS

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

Hydrocortisone Butyrate Cream (lipid), 0.1% is indicated for:

{ "type": "p", "children": [], "text": "Hydrocortisone Butyrate Cream (lipid), 0.1% is indicated for:" }

{ "type": "ul", "children": [ "Relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in adults.", "The topical treatment of mild to moderate atopic dermatitis in pediatric patients 3 months of age and older." ], "text": "" }

Recommended Dosage for Corticosteroid-Responsive Dermatoses

{ "type": "p", "children": [], "text": "\nRecommended Dosage for Corticosteroid-Responsive Dermatoses\n" }

For corticosteroid-responsive dermatoses in adults, apply a thin layer to the affected skin areas 2 or 3 times daily, depending on the severity of the condition, and rub in gently.

{ "type": "p", "children": [], "text": "For corticosteroid-responsive dermatoses in adults, apply a thin layer to the affected skin areas 2 or 3 times daily, depending on the severity of the condition, and rub in gently." }

Recommended Dosage for Atopic Dermatitis

{ "type": "p", "children": [], "text": "\nRecommended Dosage for Atopic Dermatitis\n" }

For atopic dermatitis in patients 3 months of age and older, apply a thin layer to the affected skin areas 2 times daily and rub in gently.

{ "type": "p", "children": [], "text": "For atopic dermatitis in patients 3 months of age and older, apply a thin layer to the affected skin areas 2 times daily and rub in gently." }

Administration Instructions

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

{ "type": "ul", "children": [ "Discontinue therapy when control is achieved.", "If no improvement is seen within 2 weeks, reassessment of the diagnosis may be necessary. Before prescribing for more than 2 weeks, weigh any additional benefits of extending treatment to 4 weeks against the risk of HPA-axis suppression and local adverse events\n \n [see\n \n Warnings and Precautions(\n \n 5.1)]\n \n .\n \n ", "Hydrocortisone Butyrate Cream (lipid), 0.1% is not for oral, ophthalmic, or intravaginal use.", "Do not use Hydrocortisone Butyrate Cream (lipid), 0.1%:", "With occlusive dressings unless directed by a healthcare provider. Avoid use in the diaper area, as diapers or plastic pants may constitute occlusive dressings.", "On the face, underarms, or groin areas unless directed by a healthcare provider." ], "text": "" }

Cream: Each gram contains 1 mg of hydrocortisone butyrate (0.1%) in a white to off-white hydrophilic cream base.

{ "type": "p", "children": [], "text": "Cream: Each gram contains 1 mg of hydrocortisone butyrate (0.1%) in a white to off-white hydrophilic cream base." }

None.

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

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression

Use of topical corticosteroids, including Hydrocortisone Butyrate Cream (lipid), 0.1%, can cause systemic adverse reactions including HPA-axis suppression with the potential for clinical glucocorticosteroid insufficiency. Factors that predispose a patient to HPA axis suppression include the use of high-potency steroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure, and young age. Consider patients for periodic evaluation of the HPA axis. This may be done by using cosyntropin (ACTH1-24) stimulation testing (CST). If HPA-axis suppression is noted, reduce the frequency of application or withdraw Hydrocortisone Butyrate Cream (lipid), 0.1%, or substitute a less potent corticosteroid. Signs and symptoms of glucocorticosteroid insufficiency may occur, requiring supplemental systemic corticosteroids.

Studies conducted in pediatric subjects demonstrated reversible HPA-axis suppression after use of Hydrocortisone Butyrate Cream (lipid), 0.1%. Pediatric patients may be more susceptible than adults to systemic toxicity from equivalent doses of Hydrocortisone Butyrate Cream (lipid), 0.1% due to their larger skin-surface-to-body-mass ratios [ seeUse in Specific Populations( 8.4) , Clinical Pharmacology( 12.2) ].

Cushing’s Syndrome, Hyperglycemia, and Glucosuria

Systemic adverse reactions of topical corticosteroids, including Hydrocortisone Butyrate Cream (lipid), 0.1%, may also include manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria.

Additional Considerations for Endocrine Adverse Reactions

Use of more than one corticosteroid-containing product at the same time may increase total systemic corticosteroid exposure.

Minimize systemic corticosteroid effects by mitigating the risk factors for increased systemic absorption and using Hydrocortisone Butyrate Cream (lipid), 0.1% as recommended [ seeDosage and Administration( 2) ].

Use of topical corticosteroids, including Hydrocortisone Butyrate Cream (lipid), 0.1%, may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported in postmarketing experience with the use of topical corticosteroid products [ seeAdverse Reactions( 6.2) ].

Avoid contact of Hydrocortisone Butyrate Cream (lipid), 0.1% with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.

Use of topical corticosteroids, including Hydrocortisone Butyrate Cream (lipid), 0.1%, may delay healing or worsen concomitant skin infections. If skin infections are present or develop, use an appropriate antifungal, antibacterial or antiviral agent. If a favorable response does not occur promptly, discontinue use of Hydrocortisone Butyrate Cream (lipid), 0.1% until the infection has been adequately controlled.

Use of topical corticosteroids, including Hydrocortisone Butyrate Cream (lipid), 0.1%, can cause allergic contact dermatitis Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noticing a clinical exacerbation. Such an observation should be corroborated with appropriate patch testing. Discontinue Hydrocortisone Butyrate Cream (lipid), 0.1% if the diagnosis is established.

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 clinical practice.

The safety data derived from Hydrocortisone Butyrate Cream (lipid), 0.1% clinical trials reflect exposure to Hydrocortisone Butyrate Cream (lipid), 0.1% twice daily for up to 4 weeks in pediatric subjects 3 months of age and older with mild to moderate atopic dermatitis.

<div class="scrollingtable"><table width="96.08%"> <caption> <span>Table 1. Frequency of Adverse Reactions in Pediatric Subjects 3 Months of Age and Older with Mild to Moderate Atopic Dermatitis</span> </caption> <col width="40%"/> <col width="26%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Hydrocortisone Butyrate Cream (lipid), 0.1%</span> <br/> <span class="Bold">(n=131)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Vehicle</span> <br/> <span class="Bold">(n=133)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Application site folliculitis</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0.0%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Application site irritation</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0.0%</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Acne</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.0%</p> </td> </tr> </tbody> </table></div>

The following adverse reactions have been reported during post approval use of topical corticosteroids, including Hydrocortisone Butyrate Cream (lipid), 0.1%. 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.

Local Adverse Reactions:burning, itching, drying, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria.

Ophthalmic Adverse Reactions: blurred vision, cataracts, glaucoma, and increased intraocular pressure.

Risk Summary

There are no controlled or large-scale epidemiologic studies with Hydrocortisone Butyrate Cream (lipid), 0.1% use in pregnant women, and available data on hydrocortisone butyrate use in pregnant women have not identified a drug-associated risk for major birth defects, miscarriages or adverse maternal or fetal outcomes.

In animal reproduction studies, when administered subcutaneously or topically to pregnant rats, rabbits, and mice, hydrocortisone butyrate induced adverse reproductive and developmental outcomes, including abortion, fetal death, malformation, delayed ossification, decrease in fetal weight, and delay in sexual maturation (see Data). The available data do not allow the calculation of relevant comparisons between the systemic exposure of hydrocortisone butyrate observed in animal studies and the systemic exposure that would be expected in humans after topical use of Hydrocortisone Butyrate Cream (lipid), 0.1%.

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.

Data

Animal Data

Systemic embryofetal development studies were conducted in rats and rabbits. Subcutaneous doses of 0.6, 1.8, and 5.4 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats during gestation days 6 - 17. In the presence of maternal toxicity, fetal effects noted at 5.4 mg/kg/day included increased ossification variations and unossified sternebra. No treatment-related embryofetal toxicity or malformation were noted at doses of 5.4 and 1.8 mg/kg/day, respectively.

Subcutaneous doses of 0.1, 0.2, and 0.3 mg/kg/day hydrocortisone butyrate were administered to pregnant female rabbits during gestation days 7 - 20. Increased abortion was noted at 0.3 mg/kg/day. In the absence of maternal toxicity, a dose-dependent decrease in fetal body weight was noted at doses ≥0.1 mg/kg/day. Embryofetal toxicities (reduction in litter size, decreased number of viable fetuses, and increased post-implantation loss) were noted at doses ≥0.2 mg/kg/day. Additional fetal effects included delayed ossification noted at doses ≥0.1 mg/kg/day and increased fetal malformations (primarily skeletal malformations) noted at doses ≥0.2 mg/kg/day. A dose at which no embryofetal toxicity or malformation was observed was not established in this study.

Additional systemic embryofetal development studies were conducted in rats and mice. Subcutaneous doses of 0.1 and 9 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats during gestation days 9 – 15. In the presence of maternal toxicity, an increase in fetal death and fetal resorption and an increase in ossification of caudal vertebrae were noted at 9 mg/kg/day. No treatment-related embryofetal toxicity or malformation was noted at 0.1 mg/kg/day.

Subcutaneous doses of 0.2 and 1 mg/kg/day hydrocortisone butyrate were administered to pregnant female mice during gestation days 7 – 13. In the absence of maternal toxicity, an increased number of cervical ribs and one fetus with clubbed legs were noted at 1 mg/kg/day. No treatment-related embryofetal toxicity or malformation was noted at 1 and 0.2 mg/kg/day.

No topical embryofetal development studies were conducted with hydrocortisone butyrate cream. However, topical embryofetal development studies were conducted in rats and rabbits with a hydrocortisone butyrate ointment formulation. Topical doses of 1% and 10% hydrocortisone butyrate ointment were administered to pregnant female rats during gestation days 6 – 15 or pregnant female rabbits during gestation days 6 -18. A dose-dependent increase in fetal resorption was noted in rabbits and fetal resorptions were noted in rats at the 10% hydrocortisone butyrate ointment dose. No treatment-related embryofetal toxicity was noted at the 1% hydrocortisone butyrate ointment dose in rats. A dose at which no embryofetal toxicity was observed in rabbits after topical administration of hydrocortisone butyrate ointment was not established. No treatment-related malformation was noted at a dose of 10% hydrocortisone butyrate ointment in rats or rabbits.

A peri- and postnatal development study was conducted in rats. Subcutaneous doses of 0.6, 1.8, and 5.4 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats from gestation day 6 to lactation day 20. In the presence of maternal toxicity, a dose-dependent decrease in fetal weight was noted at doses ≥1.8 mg/kg/day). No treatment-related fetal toxicity was noted at 0.6 mg/kg/day. A delay in sexual maturation was noted at 5.4 mg/kg/day. No treatment-related effects on sexual maturation were noted at 1.8 mg/kg/day. No treatment-related effects on behavioral development or subsequent reproductive performance were noted at 5.4 mg/kg/day.

Risk Summary

There are no data on the presence of hydrocortisone in human or animal milk, the effects on the breastfed infant, or the effects on milk production after treatment with Hydrocortisone Butyrate Cream (lipid), 0.1%.

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of Hydrocortisone Butyrate Cream (lipid), 0.1% could result in sufficient systemic absorption to produce detectable quantities in human milk. 

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Hydrocortisone Butyrate Cream (lipid), 0.1% and any potential adverse effects on the breastfed infant from Hydrocortisone Butyrate Cream (lipid), 0.1% or from the underlying maternal condition.

Corticosteroid-Responsive Dermatoses

The safety and efficacy of Hydrocortisone Butyrate Cream (lipid), 0.1% for relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses have not been established in pediatric patients.

Atopic Dermatitis

The safety and effectiveness of Hydrocortisone Butyrate Cream (lipid), 0.1% for the topical treatment of mild to moderate atopic dermatitis have been established in pediatric patients 3 months of age and older. Use of Hydrocortisone Butyrate Cream (lipid), 0.1% for this indication is supported by evidence from a multicenter, randomized, vehicle-controlled trial of 264 pediatric subjects 3 months of age and older [see Clinical Studies( 14)] .

The safety and efficacy of Hydrocortisone Butyrate Cream (lipid), 0.1% for the topical treatment of mild to moderate atopic dermatitis have not been established in pediatric patients younger than 3 months of age.

Endocrine Adverse Reactions

Eighty-six (86) subjects (between 5 months and 18 years of age) with moderate to severe atopic dermatitis affecting at least 25% of body surface area (BSA) treated with Hydrocortisone Butyrate Cream (lipid), 0.1% 3 times daily for up to 4 weeks were assessed for HPA-axis suppression in two separate studies. Five of the 82 evaluable subjects (6.1%) demonstrated evidence of suppression, where the criterion for defining HPA-axis suppression was a serum cortisol level of ≤18 mcg/dL after cosyntropin stimulation.  At the first follow-up visit, approximately 1 month after the conclusion of treatment, cosyntropin stimulation results of all subjects had returned to normal, with the exception of one subject. This last subject recovered adrenal function by 65 days post-treatment [see Clinical Pharmacology( 12.2)] .

Because of higher skin-surface-to-body-mass ratios, pediatric patients are at a greater risk than adults of HPA-axis suppression when they are treated with topical corticosteroids [see Warnings and Precautions( 5.1)] . They are therefore also at a greater risk of glucocorticosteroid insufficiency after withdrawal of treatment and of Cushing’s syndrome while on treatment. Manifestations of adrenal suppression in pediatric patients include low plasma cortisol levels in response to ACTH stimulation. 

Linear growth retardation, delayed weight gain, and intracranial hypertension have also been reported in pediatric patients receiving topical corticosteroids. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

Clinical trials of Hydrocortisone Butyrate Cream (lipid), 0.1% did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger adult subjects.

Hydrocortisone Butyrate Cream (lipid), 0.1% contains hydrocortisone butyrate, a non-fluorinated hydrocortisone ester, for topical use. Hydrocortisone butyrate is a corticosteroid.

{ "type": "p", "children": [], "text": "Hydrocortisone Butyrate Cream (lipid), 0.1% contains hydrocortisone butyrate, a non-fluorinated hydrocortisone ester, for topical use. Hydrocortisone butyrate is a corticosteroid." }

The chemical name of hydrocortisone butyrate is 11β,17,21-Trihydroxypregn-4-ene-3,20-dione 17-butyrate. It has the following structural formula:

{ "type": "p", "children": [], "text": "The chemical name of hydrocortisone butyrate is 11β,17,21-Trihydroxypregn-4-ene-3,20-dione 17-butyrate. It has the following structural formula:" }

Hydrocortisone butyrate is a white to off-white powder with a molecular weight of 432.56, and a molecular formula of C 25H 36O 6. It is practically insoluble in water, slightly soluble in ether, soluble in methanol, in alcohol, and in acetone, and freely soluble in chloroform.

{ "type": "p", "children": [], "text": "Hydrocortisone butyrate is a white to off-white powder with a molecular weight of 432.56, and a molecular formula of C\n \n 25H\n \n 36O\n \n 6. It is practically insoluble in water, slightly soluble in ether, soluble in methanol, in alcohol, and in acetone, and freely soluble in chloroform.\n\n " }

Each gram of Hydrocortisone Butyrate Cream (lipid), 0.1% contains 1 mg of hydrocortisone butyrate in a white to off-white hydrophilic cream base consisting of anhydrous citric acid, butylparaben, ceteth-20, cetostearyl alcohol, mineral oil, propylparaben, purified water, sodium citrate, and white petrolatum.

{ "type": "p", "children": [], "text": "Each gram of Hydrocortisone Butyrate Cream (lipid), 0.1% contains 1 mg of hydrocortisone butyrate in a white to off-white hydrophilic cream base consisting of anhydrous citric acid, butylparaben, ceteth-20, cetostearyl alcohol, mineral oil, propylparaben, purified water, sodium citrate, and white petrolatum." }

Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action in atopic dermatitis is unknown.

Pharmacodynamics of Hydrocortisone Butyrate Cream (lipid), 0.1% is unknown.

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression

Eighty-six (86) subjects (between 5 months and 18 years of age) with moderate to severe atopic dermatitis affecting at least 25% of body surface area (BSA) treated with Hydrocortisone Butyrate Cream (lipid), 0.1% 3 times daily for up to 4 weeks were assessed for HPA-axis suppression in two separate studies. The disease severity (moderate to severe atopic dermatitis) and the dosing regimen (3 times daily) in these HPA-axis trials were different from the subject population (mild to moderate atopic dermatitis) and the dosing regimen (2 times daily) for which Hydrocortisone Butyrate Cream (lipid), 0.1% is indicated. Five of the 82 evaluable subjects (6.1%) demonstrated evidence of suppression, where the criterion for defining HPA-axis suppression was a serum cortisol level of ≤18 mcg/dL after cosyntropin stimulation. Suppressed subjects ranged in age from 5 months to 16 years and, at the time of enrollment, had 25% to 95% BSA involvement. These subjects did not demonstrate any clinical signs or symptoms despite evidence of HPA-axis suppression. At the first follow-up visit, approximately 1 month after the conclusion of treatment, cosyntropin stimulation results of all subjects had returned to normal, with the exception of one subject. This last subject recovered adrenal function by 65 days post-treatment [see Warnings and Precautions( 5.1), Use in Specific Populations( 8.4)] .

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings.

Topical corticosteroids can be absorbed through normal intact skin. Inflammation and/or other disease processes in the skin, occlusive dressings, or widespread application may increase percutaneous absorption and increase the risk of HPA-axis suppression.

The vasoconstrictor assay showed that Hydrocortisone Butyrate Cream (lipid), 0.1% had a more pronounced skin blanching effect than Hydrocortisone Butyrate Cream, 0.1%, suggesting greater percutaneous absorption from the former.

Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids.

In a 2-year dermal rat carcinogenicity study with a hydrocortisone butyrate lotion formulation, hydrocortisone butyrate was administered to Sprague-Dawley rats at topical doses of 0.05, 0.15, and 0.3 mg/kg/day in males and 0.1, 0.25, and 0.5 mg/kg/day in females (0.1% lotion). No drug-related tumors were noted in this study up to the highest doses evaluated in this study of 0.3 mg/kg/day in males and 0.5 mg/kg/day in females.

Hydrocortisone butyrate revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames test and L5178Y/TK +/-mouse lymphoma assay) and one in vivo genotoxicity test (mouse micronucleus assay).

No evidence of impairment of fertility or effect on mating performance was observed in a fertility and general reproductive performance study conducted in male and female rats at subcutaneous doses up to 1.8 mg/kg/day. Mild effects on maternal animals, such as reduced food consumption and a subsequent reduction in body weight gain, were seen at doses ≥0.6 mg/kg/day.

In a multicenter, randomized, vehicle-controlled trial of 264 pediatric subjects 3 months age and older with mild to moderate atopic dermatitis, Hydrocortisone Butyrate Cream (lipid), 0.1% or vehicle was applied twice daily for up to 4 weeks. Treatment success was assessed at Day 29 (after 28 days of treatment) and was defined as the proportion of subjects who achieved both “clear” or “almost clear” and at least a 2-grade improvement from baseline on a 5-point Physician’s Global Assessment (PGA) scale. The trial results are shown in Table 2.

{ "type": "p", "children": [], "text": "In a multicenter, randomized, vehicle-controlled trial of 264 pediatric subjects 3 months age and older with mild to moderate atopic dermatitis, Hydrocortisone Butyrate Cream (lipid), 0.1% or vehicle was applied twice daily for up to 4 weeks. Treatment success was assessed at Day 29 (after 28 days of treatment) and was defined as the proportion of subjects who achieved both “clear” or “almost clear” and at least a 2-grade improvement from baseline on a 5-point Physician’s Global Assessment (PGA) scale. The trial results are shown in Table 2." }

<div class="scrollingtable"><table width="96.08%"> <caption> <span>Table 2. Efficacy Results at Day 29 in Pediatric Subjects 3 Months of Age and Older with Mild to Moderate Atopic Dermatitis</span> </caption> <col width="23%"/> <col width="23%"/> <col width="28%"/> <col width="26%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Hydrocortisone Butyrate Cream (lipid), 0.1%</span> <br/> <span class="Bold">(n=131) </span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Vehicle</span> <br/> <span class="Bold">(n=133) </span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Number (%) of successes </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">82 (63%) </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> 37 (28%)</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"96.08%\">\n<caption>\n<span>Table 2. Efficacy Results at Day 29 in Pediatric Subjects 3 Months of Age and Older with Mild to Moderate Atopic Dermatitis</span>\n</caption>\n<col width=\"23%\"/>\n<col width=\"23%\"/>\n<col width=\"28%\"/>\n<col width=\"26%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\"> </p>\n</td><td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Hydrocortisone Butyrate Cream (lipid), 0.1%</span>\n<br/>\n<span class=\"Bold\">(n=131) </span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"bottom\">\n<p class=\"First\">\n<span class=\"Bold\">Vehicle</span>\n<br/>\n<span class=\"Bold\">(n=133) </span>\n</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Number (%) of successes </p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">82 (63%) </p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\"> 37 (28%)</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

How Supplied

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

Hydrocortisone Butyrate Cream (lipid), 0.1% is white to off-white in color, and supplied in:

{ "type": "p", "children": [], "text": "Hydrocortisone Butyrate Cream (lipid), 0.1% is white to off-white in color, and supplied in:" }

{ "type": "ul", "children": [ "tubes of 45 g: NDC 68682-384-45", "tubes of 60 g: NDC 68682-384-60" ], "text": "" }

Storage and Handling

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

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from freezing.

{ "type": "p", "children": [], "text": "Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from freezing." }

Patients using Hydrocortisone Butyrate Cream (lipid), 0.1% should receive the following information and instructions:

{ "type": "p", "children": [], "text": "Patients using Hydrocortisone Butyrate Cream (lipid), 0.1% should receive the following information and instructions:" }

Administration Instructions [seeDosage and Administration(2)]

{ "type": "p", "children": [], "text": "\nAdministration Instructions\n \n [seeDosage and Administration(2)]\n" }

{ "type": "ul", "children": [ "\nCorticosteroid-Responsive Dermatoses:\n", "Instruct patients to apply a thin layer to the affected skin areas 2 or 3 times daily for corticosteroid-responsive dermatoses in adults and rub in gently. ", "\nAtopic Dermatitis:\n", "Instruct patients to apply a thin layer to the affected skin areas 2 times daily for atopic dermatitis in patients 3 months of age or older and rub in gently.", "Advise patients to discontinue Hydrocortisone Butyrate Cream (lipid), 0.1% when control is achieved.", "Instruct patients to contact their healthcare provider if no improvement is seen within 2 weeks.", "Advise patients to not\n \n [see\n \n Warnings and Precautions(\n \n 5.1)]:\n \n \n", "Bandage, otherwise cover, or wrap the affected skin area so as to be occlusive unless directed by their healthcare provider.", "Use Hydrocortisone Butyrate Cream (lipid), 0.1% in the diaper area, as diapers or plastic pants may constitute occlusive dressings.", "Use Hydrocortisone Butyrate Cream (lipid), 0.1% on the face, underarms, or groin areas unless directed by their healthcare provider." ], "text": "" }

Endocrine System Adverse Reactions

{ "type": "p", "children": [], "text": "\nEndocrine System Adverse Reactions\n" }

Advise patients to not use other corticosteroid-containing products while using Hydrocortisone Butyrate Cream (lipid), 0.1% without first consulting their healthcare provider [see Warnings and Precautions( 5.1)] .

{ "type": "p", "children": [], "text": "Advise patients to not use other corticosteroid-containing products while using Hydrocortisone Butyrate Cream (lipid), 0.1% without first consulting their healthcare provider\n \n [see\n \n Warnings and Precautions(\n \n 5.1)]\n \n .\n\n " }

Ophthalmic Adverse Reactions

{ "type": "p", "children": [], "text": "\nOphthalmic Adverse Reactions\n" }

Advise patients to avoid contact with the eyes. Instruct patients to report any visual symptoms to their healthcare providers [see Warnings and Precautions( 5.2)] .

{ "type": "p", "children": [], "text": "Advise patients to avoid contact with the eyes. Instruct patients to report any visual symptoms to their healthcare providers\n \n [see\n \n Warnings and Precautions(\n \n 5.2)]\n \n .\n\n " }

Lactation

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

Advise patients that are breastfeeding to use Hydrocortisone Butyrate Cream (lipid), 0.1% on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise patients to wash off prior to breastfeeding any Hydrocortisone Butyrate Cream (lipid), 0.1% that has been applied to the areas at risk for direct infant contact [see  Use in Specific Populations( 8.2)] .

{ "type": "p", "children": [], "text": "Advise patients that are breastfeeding to use Hydrocortisone Butyrate Cream (lipid), 0.1% on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise patients to wash off prior to breastfeeding any Hydrocortisone Butyrate Cream (lipid), 0.1% that has been applied to the areas at risk for direct infant contact\n \n [see \n \n Use in Specific Populations(\n \n 8.2)]\n \n .\n\n " }

Distributed by:

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

Oceanside Pharmaceuticals, a division of

{ "type": "p", "children": [], "text": "Oceanside Pharmaceuticals, a division of" }

Bausch Health US, LLC

{ "type": "p", "children": [], "text": "Bausch Health US, LLC" }

Bridgewater, NJ 08807 USA

{ "type": "p", "children": [], "text": "Bridgewater, NJ 08807 USA" }

Manufactured by:

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

Ferndale Laboratories, Inc.

{ "type": "p", "children": [], "text": "Ferndale Laboratories, Inc." }

Ferndale, MI 48220 USA

{ "type": "p", "children": [], "text": "Ferndale, MI 48220 USA" }

© 2024 Bausch Health Companies Inc. or its affiliates

{ "type": "p", "children": [], "text": "© 2024 Bausch Health Companies Inc. or its affiliates" }

9438002

{ "type": "p", "children": [], "text": "9438002" }

NDC68682-384-60

{ "type": "p", "children": [], "text": "\nNDC68682-384-60\n\n " }

Rx only

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

HYDROCORTISONE BUTYRATE CREAM (lipid) 0.1%

{ "type": "p", "children": [], "text": "\nHYDROCORTISONE BUTYRATE CREAM (lipid)\n\n0.1%\n" }

For topical use only Net Wt. 60 g

{ "type": "p", "children": [], "text": "\nFor topical use only\n\nNet Wt. 60 g\n" }

OCEANSIDE PHARMACEUTICALS

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

Limitations of Use

KHINDIVI is not approved for increased dosing during periods of stress or acute events. Use a different hydrocortisone-containing drug product for stress dosing [(see Warnings and Precautions (5.1)].

KHINDIVI oral solution, 1 mg/mL is a clear, colorless to slightly yellow colored viscous oral solution.

{ "type": "p", "children": [], "text": "KHINDIVI oral solution, 1 mg/mL is a clear, colorless to slightly yellow colored viscous oral solution." }

KHINDIVI is contraindicated in patients with hypersensitivity to hydrocortisone or to any component of KHINDIVI. Reactions have included anaphylaxis in patients receiving corticosteroids [see Adverse Reactions (6.2)].

{ "type": "p", "children": [], "text": "KHINDIVI is contraindicated in patients with hypersensitivity to hydrocortisone or to any component of KHINDIVI. Reactions have included anaphylaxis in patients receiving corticosteroids [see Adverse Reactions (6.2)]." }

Undertreatment with KHINDIVI or sudden discontinuation of therapy with KHINDIVI may lead to adrenocortical insufficiency, adrenal crisis, and death. Adrenal crisis may also be induced by stress events such as infections or surgery when patients require higher doses of corticosteroids. Symptoms of adrenocortical insufficiency include poor feeding, fatigue, low muscle tone, joint pain, nausea, vomiting, hypoglycemia, low blood pressure and electrolyte disturbances.

During periods of stress (e.g., infections, surgery), switch to another oral hydrocortisone product and increase the dose, if oral medications are tolerated. Switch patients who are vomiting, severely ill, or unable to take oral medications to parenteral corticosteroid formulations without delay. Once the patient recovers, gradually reduce the steroid dosage used during the acute event and do not switch back to KHINDIVI until the maintenance dosage can be resumed.

KHINDIVI is not approved for stress dosing. KHINDIVI contains inactive ingredients polyethylene glycol 400, propylene glycol, and glycerin at levels that individually or in combination may result in hyperosmolarity, metabolic acidosis, hypoglycemia, hepato-renal injury, central nervous system toxicity (e.g., seizure and coma) and/or gastrointestinal adverse reactions [see Warnings and Precautions (5.2)]. Use of KHINDIVI for stress dosing will result in a greater exposure to inactive ingredients and may increase the risk of these adverse reactions.

When switching patients to KHINDIVI from other oral hydrocortisone formulations, consider the potential for dosing inaccuracy if other oral hydrocortisone formulations have been manipulated (e.g., split or crushed tablets, compounded formulations). Manipulation of oral hydrocortisone formulations may result in a relative difference in hydrocortisone exposure when using the same dosage to initiate KHINDIVI treatment. Monitor patients after switching to KHINDIVI to ensure KHINDIVI is providing the same level of hydrocortisone exposure as the previously used oral hydrocortisone formulation. If symptoms of adrenal insufficiency occur, increase the total daily dosage of KHINDIVI.

Hyperosmolarity

KHINDIVI is not approved in pediatric patients less than 5 years of age. KHINDIVI contains the inactive ingredients polyethylene glycol 400, propylene glycol, and glycerin, which undergo substantial systemic absorption. These inactive ingredients, individually or in combination may increase plasma osmolarity in all pediatric patients, especially in pediatric patients less than 5 years of age due to incomplete maturity of the alcohol dehydrogenase enzyme that metabolizes propylene glycol and polyethylene glycol 400.

Monitor pediatric patients using KHINDIVI for signs and symptoms consistent with hyperosmolarity. Discontinue KHINDIVI and switch to another hydrocortisone formulation if this occurs.

Metabolic Acidosis and Other Adverse Reactions

KHINDIVI contains the inactive ingredient polyethylene glycol 400 and propylene glycol that may result in metabolic acidosis, hypoglycemia, hepato-renal injury, and central nervous system toxicity (e.g., seizure and coma). These adverse reactions may increase the risk of adrenal crisis [see Warnings and Precautions (5.1)]. Monitor laboratory values and for physical signs and symptoms of these adverse reactions. Discontinue KHINDIVI and switch to another hydrocortisone formulation if these adverse reactions occur.

Laxative Effects Due to Inactive Ingredients

KHINDIVI contains the inactive ingredients polyethylene glycol 400 and glycerin, which alone or in combination, may cause gastrointestinal irritation resulting in vomiting and/or diarrhea. These gastrointestinal reactions may increase the risk of adrenal crisis in patients with adrenal insufficiency [see Warnings and Precautions (5.1)]. Monitor for signs or symptoms of gastrointestinal irritation and associated fluid and electrolyte abnormalities. Discontinue KHINDIVI and switch to another hydrocortisone formulation if these adverse reactions occur.

Use of the recommended dosage of KHINDIVI [see Dosage and Administration (2.1, 2.2)] as a replacement therapy in pediatric patients with adrenocortical insufficiency is not expected to cause immunosuppression or increase the risk of infection. The use of a greater than replacement dosage can suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. The use of KHINDIVI at greater than replacement dosage can:

Infections associated with the use of corticosteroids at a greater than replacement dosage range from mild to severe or fatal, and the rate of infectious complications increases with increasing corticosteroid dosages.

Monitor for the development of infection and consider KHINDIVI dosage reduction as needed [see Warnings and Precautions (5.1)].

Long-term use of corticosteroids in excessive doses may cause growth retardation in pediatric patients. Historical cohorts of adults treated from childhood for congenital adrenal hyperplasia have been found to have growth retardation. Effects on linear growth are less likely when using corticosteroids as replacement therapy. Use the minimum dosage of KHINDIVI to achieve desired clinical response and monitor the patient's growth.

Prolonged use of corticosteroids in supraphysiologic doses may cause Cushing's syndrome. Symptoms and signs of Cushing's syndrome include weight gain, decreased height velocity, hyperglycemia, hypertension, edema, easy bruising, muscle weakness, red round face, depression, or mood swings. Monitor patients for signs and symptoms of Cushing's syndrome every 6 months.

Corticosteroids decrease bone formation and increase bone resorption which may lead to development of osteoporosis. Historical cohorts of adults treated from childhood for congenital adrenal hyperplasia have been found to have reduced bone mineral density and increased fracture rates. Use the minimum dosage of KHINDIVI to achieve desired clinical response.

Corticosteroid use may be associated with severe psychiatric adverse reactions. Euphoria, mania, psychosis with hallucinations and delirium or depression have been seen in patients at replacement doses of hydrocortisone [see Adverse Reactions (6)]. Symptoms typically emerge within a few days or weeks of starting the treatment. Risks may be higher with high doses, although dose levels do not allow prediction of the onset, type, severity, or duration of reactions. Most reactions resolve after either dose reduction or withdrawal, although specific treatment may be necessary. Monitor patients for behavioral and mood disturbances during treatment with KHINDIVI. Instruct caregivers and/or patients to seek medical advice if psychiatric symptoms develop.

Ophthalmic effects, such as cataract, glaucoma or central serous chorioretinopathy have been reported with prolonged use of corticosteroids in high doses. Monitor patients for blurred vision or other visual disturbances. If patients develop ophthalmic adverse reactions, refer them to an ophthalmologist for further evaluation.

Gastrointestinal Perforation

There is an increased risk of gastrointestinal perforation in patients with certain gastrointestinal disorders. Signs of gastrointestinal perforation, such as peritoneal irritation may be masked in patients receiving corticosteroids. Corticosteroids should be used with caution if there is a probability of impending perforation, abscess, or other pyogenic infections, diverticulitis, fresh intestinal anastomoses, and active or latent peptic ulcer.

Concomitant Use with Non-Steroidal Anti-Inflammatory Drugs

Concurrent administration of corticosteroids with non-steroidal anti-inflammatory drugs (NSAIDS) may increase the risk of gastrointestinal adverse reactions. Monitor patients receiving corticosteroids and concomitant NSAIDS for gastrointestinal adverse reactions [see Drug Interactions (7)].

Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions at a dosage greater than replacement (supraphysiologic dosage). If patients take a supraphysiologic chronic dosage of KHINDIVI, they are at increased risk of developing Kaposi's sarcoma.

Administration of live vaccines may be acceptable in KHINDIVI-treated pediatric patients with adrenocortical insufficiency who receive replacement corticosteroids.

Because clinical studies 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 safety of oral hydrocortisone was evaluated in an uncontrolled, open-label, single-arm clinical study in 18 pediatric patients with adrenocortical insufficiency treated with oral hydrocortisone granules. Adrenocortical insufficiency was due to congenital adrenal hyperplasia in 17 patients and to hypopituitarism in one patient. All patients received at least one dose of hydrocortisone granules. The age ranged from 36 days to 5.7 years at start of treatment; 8 patients were female and 10 were male; 100% were White. Adverse reactions that were reported in two or more patients (≥ 11%) are shown in Table 1.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 1: Adverse Reactions Occurring in ≥11% of Pediatric Patients with Adrenocortical Insufficiency Treated with Hydrocortisone Granules for up to 29 Months</span> </caption> <col align="left" valign="top" width="70%"/> <col align="center" valign="top" width="30%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">Adverse Reactions</th><th align="center" class="Rrule">N=18<br/> n (%)</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Pyrexia</td><td align="center" class="Rrule">10 (56)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Gastroenteritis</td><td align="center" class="Rrule">9 (50)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Viral upper respiratory tract infection</td><td align="center" class="Rrule">8 (44)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Vomiting</td><td align="center" class="Rrule">7 (39)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Viral infection</td><td align="center" class="Rrule">6 (33)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Conjunctivitis</td><td align="center" class="Rrule">5 (28)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Otitis media viral</td><td align="center" class="Rrule">3 (17)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Tonsillitis</td><td align="center" class="Rrule">3 (17)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Body temperature increased</td><td align="center" class="Rrule">2 (11)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Bronchitis</td><td align="center" class="Rrule">2 (11)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Dental caries</td><td align="center" class="Rrule">2 (11)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Diarrhea</td><td align="center" class="Rrule">2 (11)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Genitourinary operation</td><td align="center" class="Rrule">2 (11)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pharyngitis</td><td align="center" class="Rrule">2 (11)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Respiratory tract infection</td><td align="center" class="Rrule">2 (11)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Rhinitis</td><td align="center" class="Rrule">2 (11)</td> </tr> </tbody> </table></div>

The following adverse reactions seen in pediatric and adult patients associated with the use of corticosteroids were identified in the literature and from postmarketing reports. Because some of 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.

Common adverse reactions for corticosteroids include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain.

Allergic Reactions: Anaphylaxis, angioedema

Cardiovascular: Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction, pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis

Dermatologic: Acne, allergic dermatitis, cutaneous and subcutaneous atrophy, dry scalp, edema, facial erythema, hyper or hypo-pigmentation, impaired wound healing, increased sweating, petechiae and ecchymoses, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria

Endocrine: Abnormal fat deposits, decreased carbohydrate tolerance, development of Cushingoid state, hirsutism, manifestations of latent diabetes mellitus and increased requirements for insulin or oral hypoglycemic agents in diabetics, menstrual irregularities, moon faces, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery or illness), suppression of growth in pediatric patients

Fluid and Electrolyte Disturbances: Fluid retention, potassium loss, hypertension, hypokalemic alkalosis, sodium retention

Gastrointestinal: Abdominal distention, elevation in serum liver enzymes levels (usually reversible upon discontinuation), hepatomegaly, hiccups, malaise, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, ulcerative esophagitis

General: Increased appetite and weight gain

Metabolic: Negative nitrogen balance due to protein catabolism

Musculoskeletal: Osteonecrosis of femoral and humeral heads, Charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, steroid myopathy, tendon rupture, vertebral compression fractures

Neurological: Arachnoiditis, convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudo-tumor cerebri) usually following discontinuation of treatment, insomnia, meningitis, mood swings, neuritis, neuropathy, paraparesis/paraplegia, paresthesia, personality changes, sensory disturbances, vertigo

Ophthalmic: Exophthalmos, glaucoma, increased intraocular pressure, posterior subcapsular cataracts, and central serous chorioretinopathy

Reproductive: Alteration in motility and number of spermatozoa

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 2: Drug Interactions with KHINDIVI</span> </caption> <col align="left" valign="middle" width="20%"/> <col align="left" valign="middle" width="80%"/> <tbody class="Headless"> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">CYP3A4 Inhibitors</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Clinical Impact:</span></td><td align="left" class="Rrule">Hydrocortisone is metabolized by cytochrome P450 3A4 (CYP3A4). Concomitant administration of inhibitors of CYP3A4 may lead to increases in serum concentrations of KHINDIVI and increase the risk of adverse reactions associated with the use of excessive doses.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Intervention:</span></td><td align="left" class="Rrule">Concomitant use of CYP3A4 inhibitors may require a decrease in the KHINDIVI dose.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Examples:</span></td><td align="left" class="Rrule"><span class="Italics">Anti-fungals:</span> itraconazole, posaconazole, voriconazole <br/> <span class="Italics">Antibiotics:</span> erythromycin and clarithromycin <br/> <span class="Italics">Antiretrovirals:</span> ritonavir <br/>Grapefruit juice</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">CYP3A4 Inducers</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Clinical Impact:</span></td><td align="left" class="Rrule">Hydrocortisone is metabolized by cytochrome P450 3A4 (CYP3A4). Concomitant administration of inducers of CYP3A4 may lead to decreases in serum concentrations of KHINDIVI and increase the risk of adverse reactions, including adrenal crisis.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Intervention:</span></td><td align="left" class="Rrule">Concomitant use of CYP3A4 inducers may require an increase in the KHINDIVI dose.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Examples:</span></td><td align="left" class="Rrule"><span class="Italics">Anticonvulsants</span>: phenytoin, carbamazepine and oxcarbazepine<br/> <span class="Italics">Antibiotics</span>: rifampicin and rifabutin <br/> <span class="Italics">Barbiturates:</span> phenobarbital and primidone <br/> <span class="Italics">Antiretrovirals</span>: efavirenz and nevirapine</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Estrogen and Estrogen-Containing Products</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Clinical Impact:</span></td><td align="left" class="Rrule">Oral estrogen and estrogen-containing oral contraceptives may interact with hydrocortisone by increasing serum cortisol-binding globulin (CBG) concentration. Concomitant use may reduce the efficacy of KHINDIVI by binding and delaying or preventing absorption.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Intervention:</span></td><td align="left" class="Rrule">Concomitant use of estrogen/estrogen containing products may require an increase in the KHINDIVI dose.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Antidiabetic Agents</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Clinical Impact:</span></td><td align="left" class="Rrule">Corticosteroids in supraphysiologic doses may increase blood glucose concentrations.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Intervention:</span></td><td align="left" class="Rrule">Use of KHINDIVI in supraphysiologic doses may require a dose adjustment of antidiabetic agents.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Anticoagulant Agents</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Clinical Impact:</span></td><td align="left" class="Rrule">Concomitant use of warfarin and corticosteroids usually results in inhibition of response to warfarin, although there have been some conflicting reports.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Intervention:</span></td><td align="left" class="Rrule">Monitor coagulation indices in patients receiving KHINDIVI and concomitant warfarin to maintain the desired anticoagulant effect.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Cyclosporine</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Clinical Impact:</span></td><td align="left" class="Rrule">Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with concurrent use.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Intervention:</span></td><td align="left" class="Rrule" valign="top">Monitor patients receiving KHINDIVI and concomitant cyclosporine.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Nonsteroidal Anti-inflammatory Drugs (NSAIDs)</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">Clinical Impact:</span></td><td align="left" class="Rrule">Concomitant use of NSAIDs and corticosteroids increases the risk of gastrointestinal adverse reactions. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids; this could lead to decreased salicylate serum levels or increase the risk of salicylate toxicity when corticosteroid is withdrawn.</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule"><span class="Italics">Intervention:</span></td><td align="left" class="Rrule">Monitor patients receiving KHINDIVI and concomitant NSAIDs.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"90%\">\n<caption>\n<span>Table 2: Drug Interactions with KHINDIVI</span>\n</caption>\n<col align=\"left\" valign=\"middle\" width=\"20%\"/>\n<col align=\"left\" valign=\"middle\" width=\"80%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">CYP3A4 Inhibitors</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Clinical Impact:</span></td><td align=\"left\" class=\"Rrule\">Hydrocortisone is metabolized by cytochrome P450 3A4 (CYP3A4). Concomitant administration of inhibitors of CYP3A4 may lead to increases in serum concentrations of KHINDIVI and increase the risk of adverse reactions associated with the use of excessive doses.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Intervention:</span></td><td align=\"left\" class=\"Rrule\">Concomitant use of CYP3A4 inhibitors may require a decrease in the KHINDIVI dose.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Examples:</span></td><td align=\"left\" class=\"Rrule\"><span class=\"Italics\">Anti-fungals:</span> itraconazole, posaconazole, voriconazole <br/>\n<span class=\"Italics\">Antibiotics:</span> erythromycin and clarithromycin <br/>\n<span class=\"Italics\">Antiretrovirals:</span> ritonavir <br/>Grapefruit juice</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">CYP3A4 Inducers</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Clinical Impact:</span></td><td align=\"left\" class=\"Rrule\">Hydrocortisone is metabolized by cytochrome P450 3A4 (CYP3A4). Concomitant administration of inducers of CYP3A4 may lead to decreases in serum concentrations of KHINDIVI and increase the risk of adverse reactions, including adrenal crisis.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Intervention:</span></td><td align=\"left\" class=\"Rrule\">Concomitant use of CYP3A4 inducers may require an increase in the KHINDIVI dose.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Examples:</span></td><td align=\"left\" class=\"Rrule\"><span class=\"Italics\">Anticonvulsants</span>: phenytoin, carbamazepine and oxcarbazepine<br/>\n<span class=\"Italics\">Antibiotics</span>: rifampicin and rifabutin <br/>\n<span class=\"Italics\">Barbiturates:</span> phenobarbital and primidone <br/>\n<span class=\"Italics\">Antiretrovirals</span>: efavirenz and nevirapine</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Estrogen and Estrogen-Containing Products</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Clinical Impact:</span></td><td align=\"left\" class=\"Rrule\">Oral estrogen and estrogen-containing oral contraceptives may interact with hydrocortisone by increasing serum cortisol-binding globulin (CBG) concentration. Concomitant use may reduce the efficacy of KHINDIVI by binding and delaying or preventing absorption.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Intervention:</span></td><td align=\"left\" class=\"Rrule\">Concomitant use of estrogen/estrogen containing products may require an increase in the KHINDIVI dose.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Antidiabetic Agents</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Clinical Impact:</span></td><td align=\"left\" class=\"Rrule\">Corticosteroids in supraphysiologic doses may increase blood glucose concentrations.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Intervention:</span></td><td align=\"left\" class=\"Rrule\">Use of KHINDIVI in supraphysiologic doses may require a dose adjustment of antidiabetic agents.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Anticoagulant Agents</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Clinical Impact:</span></td><td align=\"left\" class=\"Rrule\">Concomitant use of warfarin and corticosteroids usually results in inhibition of response to warfarin, although there have been some conflicting reports.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Intervention:</span></td><td align=\"left\" class=\"Rrule\">Monitor coagulation indices in patients receiving KHINDIVI and concomitant warfarin to maintain the desired anticoagulant effect.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Cyclosporine</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Clinical Impact:</span></td><td align=\"left\" class=\"Rrule\">Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with concurrent use.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Intervention:</span></td><td align=\"left\" class=\"Rrule\" valign=\"top\">Monitor patients receiving KHINDIVI and concomitant cyclosporine.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Nonsteroidal Anti-inflammatory Drugs (NSAIDs)</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Clinical Impact:</span></td><td align=\"left\" class=\"Rrule\">Concomitant use of NSAIDs and corticosteroids increases the risk of gastrointestinal adverse reactions. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids; this could lead to decreased salicylate serum levels or increase the risk of salicylate toxicity when corticosteroid is withdrawn.</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Italics\">Intervention:</span></td><td align=\"left\" class=\"Rrule\">Monitor patients receiving KHINDIVI and concomitant NSAIDs.</td>\n</tr>\n</tbody>\n</table></div>" }

Risk Summary

Untreated adrenocortical insufficiency in pregnancy can result in a high rate of complications, including maternal mortality. The use of physiologic doses of hydrocortisone is not expected to cause major birth defects, miscarriage and adverse maternal and fetal outcomes. Available data from observational studies with hydrocortisone use in pregnancy have not identified a clear drug- associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes (see Data).

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

Data

Human Data

Available data from observational studies with hydrocortisone use in pregnant women have not identified a clear drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Evidence from published epidemiologic studies suggest that there may be a small increased risk of cleft lip with or without cleft palate associated with first trimester systemic corticosteroid use in pregnant patients. However, the data are limited and report inconsistent findings, and studies have important methodological limitations, including non-randomized design, retrospective data collection, lack of dose-response data and the inability to control for confounders, such as underlying maternal disease and use of concomitant medications. In addition, unlike other corticosteroids, hydrocortisone is enzymatically deactivated by the placenta and therefore limits fetal exposure.

Animal Data

Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose. Animal studies in which corticosteroids have been given to pregnant mice, rats and rabbits without adrenocortical insufficiency have yielded an increased incidence of cleft palate in the offspring.

Risk Summary

Cortisol is present in human milk. The use of hydrocortisone at a physiologic dose for adrenocortical insufficiency is not expected to adversely affect the breastfed infant or milk production. There are no data on the presence of hydrocortisone in breast milk, the effect on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for KHINDIVI and any potential adverse effects on the breastfed infant from KHINDIVI or from the underlying maternal condition.

The safety and effectiveness of KHINDIVI have been established in pediatric patients 5 years of age and older for replacement therapy of adrenocortical insufficiency and the information on this use is discussed throughout the labeling. Use of KHINDIVI for this indication is supported by findings of safety and efficacy in other approved hydrocortisone products, including supportive pharmacokinetic and safety data in pediatric patients with adrenocortical insufficiency.

KHINDIVI is not approved in pediatric patients less than 5 years of age. KHINDIVI contains the inactive ingredients polyethylene glycol 400, propylene glycol, and glycerin, which undergo substantial systemic absorption. These inactive ingredients, individually or in combination, may increase plasma osmolarity in all pediatric patients, especially in pediatric patients less than 5 years of age due to incomplete alcohol dehydrogenase maturity [see Warnings and Precautions (5.2)].

When prescribing KHINDIVI in pediatric patients 5 years of age and older, consider the combined daily amount of polyethylene glycol 400, propylene glycol, and glycerin from all sources including KHINDIVI and other drugs with inactive ingredients utilizing the same metabolic pathways as these inactive ingredients, which may increase exposure and lead to an increased risk of systemic toxicity [see Warnings and Precautions (5.2)].

Treatment of acute overdosage is by supportive and symptomatic therapy.

{ "type": "p", "children": [], "text": "Treatment of acute overdosage is by supportive and symptomatic therapy." }

KHINDIVI contains hydrocortisone, a corticosteroid, also known as cortisol. The chemical name of hydrocortisone is 11β,17α,21-trihydroxy-pregn-4-ene-3,20-dione and it has the chemical formula of C21H30O5, and molecular weight of 362 g∙mol–1. Hydrocortisone is a white or almost white powder soluble in the pH range of 1-7.

{ "type": "p", "children": [], "text": "KHINDIVI contains hydrocortisone, a corticosteroid, also known as cortisol. The chemical name of hydrocortisone is 11β,17α,21-trihydroxy-pregn-4-ene-3,20-dione and it has the chemical formula of C21H30O5, and molecular weight of 362 g∙mol–1. Hydrocortisone is a white or almost white powder soluble in the pH range of 1-7." }

Structural formula of hydrocortisone:

{ "type": "p", "children": [], "text": "\nStructural formula of hydrocortisone:\n" }

KHINDIVI is a clear, colorless to slightly yellow colored viscous solution of hydrocortisone available for oral administration in a concentration of 1 mg/mL. The inactive ingredients are berry flavor, butylated hydroxyanisole, ethyl maltol, glycerin (623 mg/mL), methylparaben, propylparaben, polyethylene glycol 400 (500 mg/mL), propylene glycol (50 mg/mL), and sucralose.

{ "type": "p", "children": [], "text": "KHINDIVI is a clear, colorless to slightly yellow colored viscous solution of hydrocortisone available for oral administration in a concentration of 1 mg/mL. The inactive ingredients are berry flavor, butylated hydroxyanisole, ethyl maltol, glycerin (623 mg/mL), methylparaben, propylparaben, polyethylene glycol 400 (500 mg/mL), propylene glycol (50 mg/mL), and sucralose." }

Hydrocortisone is a glucocorticoid. Glucocorticoids, adrenocortical steroids, cause varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli.

Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states.

Absorption

Following oral administration of KHINDIVI (5 mg) in dexamethasone-suppressed healthy adult volunteers under fasted conditions, mean (range) maximum plasma concentration (Cmax) of hydrocortisone is 152 (98-210) ng/mL. Mean (range) time to reach maximum concentration (Tmax) is 0.5 (0.25-0.75) hours.

Effect of Food

No clinically significant differences in KHINDIVI pharmacokinetics were observed following administration of a high-fat meal.

Distribution

90% or more of circulating hydrocortisone is reversibly bound to protein.

The binding is accounted for by two protein fractions. One, corticosteroid-binding globulin is a glycoprotein; the other is albumin.

Following administration of 5 mg Hydrocortisone oral solution in dexamethasone-suppressed healthy adult volunteers under fasted conditions, mean (range) apparent (oral) volume of distribution (Vd/F) of hydrocortisone is 23 (5-59) L.

Elimination

Hydrocortisone is metabolized in the liver and most body tissues to hydrogenated and degraded forms such as tetrahydrocortisone and tetrahydrocortisol which are excreted in the urine, mainly conjugated as glucuronides, together with a very small proportion of unchanged hydrocortisone.

Following administration of 5 mg Hydrocortisone oral solution in dexamethasone-suppressed healthy adult volunteers under fasted conditions, mean (range) terminal half-life of hydrocortisone is about 0.95 (0.3-2.3) hours.

No adequate studies in animals have been conducted with hydrocortisone to evaluate carcinogenic or mutagenic potential. Corticosteroids have been shown to impair fertility in male rats.

Store at 2°C to 25°C (36°F to 77°F). Excursions permitted to 30°C (86°F) [see USP refrigerated and controlled room temperature]. Protect from light and heat.

Product must be used within 120 days of first opening. If not used within 120 days, the unused portion must be discarded.

Administration Information

Instruct patients and/or caregivers to use an oral dosing syringe to correctly measure the prescribed amount of medication. Inform patients and/or caregivers that oral dosing syringes may be obtained from their pharmacy.

Advise patients and/or caregivers to take a sip of water immediately following administration to ensure all the solution has been swallowed.

For administration through a gastric tube, flush with 20 mL of water to ensure that the entire dose is delivered [see Dosage and Administration (2.2)].

Adrenal Crisis

Inform patients and/or caregivers that undertreatment or sudden discontinuation of KHINDIVI or switching to KHINDIVI from another oral hydrocortisone formulation, may lead to adrenocortical insufficiency, adrenal crisis, and death.

Inform patients and/or caregivers to switch to another oral hydrocortisone product and increase the dose during periods of stress, and not to use KHINDIVI for increased dosing during period of stress or acute events due to increased risk of systemic and gastrointestinal adverse reactions.

Inform the caregiver that potential dosing inaccuracy of the manipulated oral hydrocortisone formulation (e.g., split or crushed tablets, compounded formulations) may result in dosing differences when switching to KHINDIVI which may require dose adjustments. Advise caregivers to watch the patient for symptoms of adrenocortical insufficiency during the days after switching to KHINDIVI. Inform patient and/or caregiver to contact their healthcare provider if they have symptoms of adrenocortical insufficiency, prolonged vomiting, are severely ill or are unable to take oral medications [see Warnings and Precautions (5.1)].

Systemic Adverse Reactions Due to Inactive Ingredients

Inform patients and/or caregivers that some inactive ingredients in KHINDIVI may increase the risk for hyperosmolarity, metabolic acidosis, loose stools, diarrhea, and other systemic adverse reactions, which may increase the risk of adrenal crisis. Patients and/or caregivers should contact the healthcare provider if patients have altered mental status, abnormal urine output, or are severely ill [see Warnings and Precautions (5.2)].

Immunosuppression and Increased Risk of Infections

Advise patients and/or caregivers that greater than replacement dosage of corticosteroids can suppress the immune system and increase the risk of infections. Instruct patients and/or caregivers to contact their healthcare provider if they develop any infections [see Warnings and Precautions (5.3)].

Growth Retardation

Discuss with caregivers that long-term use of corticosteroids in excessive doses may cause growth retardation in pediatric patients [see Warnings and Precautions (5.4)].

Cushing's Syndrome

Inform patients and/or caregivers that prolonged use of corticosteroids in supraphysiologic doses may cause Cushing's syndrome and that symptoms and signs include weight gain, decreased height velocity, hyperglycemia, hypertension, edema, easy bruising, muscle weakness, red round face, depression, or mood swings [see Warnings and Precautions (5.5)].

Decrease in Bone Mineral Density

Inform patients and/or caregivers that corticosteroids decrease bone formation and increase bone resorption that may lead to osteoporosis [see Warnings and Precautions (5.6)].

Psychiatric Adverse Reactions

Advise patients and/or caregivers that corticosteroid use may be associated with severe psychiatric adverse reactions such as euphoria, mania, psychosis with hallucinations or depression. Instruct caregivers and/or patients to seek medical advice if psychiatric symptoms develop [see Warnings and Precautions (5.7)].

Ophthalmic Adverse Reactions

Inform patients and/or caregivers that ophthalmic effects such as cataract, glaucoma or central serous chorioretinopathy have been reported with prolonged use of high-dose corticosteroids. Instruct patients or caregivers to report any blurred vision or visual disturbances to their healthcare provider [see Warnings and Precautions (5.8)].

Gastrointestinal Adverse Reactions

Discuss with patients and/or healthcare providers that use of corticosteroids may increase risk of gastrointestinal perforation in certain gastrointestinal disorders [see Warnings and Precautions (5.9)].

Risk of Kaposi's Sarcoma

Inform patients that they are at risk of developing Kaposi's sarcoma [see Warnings and Precautions (5.10)].

Vaccination

Inform patients and/or caregivers that administration of live vaccine may be acceptable [see Warnings and Precautions (5.11)].

KHINDIVI is manufactured for Eton Pharmaceuticals, Inc. by Tulex Pharmaceuticals, Inc., 5 Cedarbrook Dr., Cranbury, NJ 08512, USA.

{ "type": "p", "children": [], "text": "KHINDIVI is manufactured for Eton Pharmaceuticals, Inc. by Tulex Pharmaceuticals, Inc., 5 Cedarbrook Dr., Cranbury, NJ 08512, USA." }

KHINDIVI® is a registered trademark of Eton Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "KHINDIVI® is a registered trademark of Eton Pharmaceuticals, Inc." }

KHINDIVI is covered by the following US patents: 11,904,046, and 12,133, 914.

{ "type": "p", "children": [], "text": "KHINDIVI is covered by the following US patents: 11,904,046, and 12,133, 914." }

PL-1-1.0

{ "type": "p", "children": [], "text": "PL-1-1.0" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="2%"/> <col align="left" valign="top" width="1%"/> <col align="left" valign="top" width="18%"/> <col align="left" valign="top" width="17%"/> <col align="left" valign="top" width="3%"/> <col align="left" valign="top" width="18%"/> <col align="left" valign="top" width="19%"/> <col align="left" valign="top" width="2%"/> <col align="left" valign="top" width="20%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="6">This Medication Guide has been approved by the U.S. Food and Drug Administration.</td><td align="right" colspan="3">Issued: 06/2025      </td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="9"><span class="Bold">Medication Guide</span> <br/> KHINDIVI® (kɪn-dɪv-i)<br/> (hydrocortisone) oral solution</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="9">Read this Medication Guide before you start giving KHINDIVI to your child, and each time your child gets a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your child's medical condition or treatment.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold"><a name="important"></a>What is the most important information I should know about KHINDIVI?</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">KHINDIVI may cause serious side effects, including</span>:</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">Adrenal gland problems</span>. Not giving enough KHINDIVI, stopping KHINDIVI, or switching to KHINDIVI after taking another hydrocortisone medicine (the same class of medicines as KHINDIVI) by mouth, can cause serious and life-threatening adrenal gland problems including death. Do not stop giving KHINDIVI without talking to your healthcare provider. Tell your healthcare provider if your child has any of these symptoms:</td> </tr> <tr> <td align="left" class="Lrule" colspan="2"></td><td align="left" colspan="2"> <ul class="Disc"> <li>loss of appetite</li> <li>fatigue</li> <li>weakness</li> </ul> </td><td align="left" colspan="2"> <ul class="Disc"> <li>joint pain</li> <li>nausea</li> <li>vomiting</li> </ul> </td><td align="left" class="Rrule" colspan="3"> <ul class="Disc"> <li>low blood sugar</li> <li>feeling lightheaded or dizzy</li> <li>problems with body salt (electrolyte) levels</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9">Your healthcare provider will change the dose of KHINDIVI depending on your child's size. During episodes of acute infections, surgery, or major trauma, your healthcare provider may prescribe your child a different hydrocortisone medicine and increase the dose. If your child is vomiting, severely ill, or unable to take medicines by mouth, your healthcare provider may use corticosteroid medicines that are given directly into the bloodstream instead.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9">The amount of hydrocortisone in a dose of KHINDIVI may not be the same as in previous hydrocortisone medicines that your child takes by mouth if these oral hydrocortisone medicines have been changed (for example, crushed or compounded). When switching to KHINDIVI, your healthcare provider may need to prescribe a starting dose of KHINDIVI that is different from previous hydrocortisone medicines that your child may have been taking by mouth. Watch your child closely after being switched to KHINDIVI and contact your healthcare provider if your child has any symptoms of adrenal gland problems. Your healthcare provider may need to change the dose of KHINDIVI.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">See "<a href="#side">What are the possible side effects of KHINDIVI?</a>" for more information about side effects.</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">What is KHINDIVI?</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="9">KHINDIVI is a prescription medicine that contains a medicine hydrocortisone. Hydrocortisone belongs to a group of medicines known as corticosteroids. Hydrocortisone is a synthetic version of the hormone cortisol. Cortisol is made naturally by the adrenal glands in the body. KHINDIVI (hydrocortisone) is a man-made (synthetic) corticosteroid used to replace the body's cortisol when the adrenal glands do not make enough (adrenal insufficiency) in children from 5 to 17 years of age.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">Who should not take or be given KHINDIVI?</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">Do not give your child KHINDIVI if they:</span> <ul class="Disc"> <li>are allergic to hydrocortisone or any of the ingredients in KHINDIVI. See the end of this Medication Guide for a complete list of ingredients in KHINDIVI.</li> <li>have any reaction like swelling or shortness of breath after being given KHINDIVI. Get medical help right away and tell your healthcare provider as soon as possible as these can be signs of an allergic reaction.</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">What should I tell my healthcare provider before giving KHINDIVI?</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">Before you give your child KHINDIVI, tell your healthcare provider about all of your child's medical conditions, including if they:</span> <ul class="Disc"> <li>are feeling unwell, or their body is under stress because of surgery or trauma. Your healthcare provider may prescribe your child a different hydrocortisone medicine for a short period of time.</li> <li>have a fever or infection.</li> <li>have nausea, vomiting, or diarrhea.</li> <li>are due for vaccinations. Taking KHINDIVI should not stop your child from being vaccinated. Tell your healthcare provider when your child is due for vaccinations.</li> <li>are scheduled for surgery.</li> <li>cannot swallow medicines by mouth or are fed through a gastric tube.</li> <li>are pregnant or plan to become pregnant. It is not known if KHINDIVI will harm your child's unborn baby. Talk to your child's healthcare provider if your child is pregnant or plans to become pregnant.</li> <li>are breastfeeding or plan to breastfeed. It is not known if KHINDIVI passes into the breast milk. You and your child's healthcare provider should decide if your child will receive KHINDIVI while your child breastfeeds.</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">Tell your healthcare provider about all the medicines your child takes,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9">Some medicines, food and drink can affect the way that KHINDIVI works and may mean that your healthcare provider needs to change your child's dose of KHINDIVI.<br/> <span class="Bold">Especially tell your healthcare provider if your child:</span> <ul class="Disc"> <li>takes medicines used to treat fungal infections such as itraconazole, posaconazole, and voriconazole.</li> <li>takes medicines used to treat bacterial infections such as rifampicin, rifabutin, erythromycin, and clarithromycin.</li> <li>takes medicines used to treat human immunodeficiency virus (HIV) infection and AIDS such as ritonavir, efavirenz, and nevirapine.</li> <li>takes seizure medicines such as phenytoin, carbamazepine, oxcarbazepine, phenobarbital, and primidone.</li> <li>takes estrogen.</li> <li>takes warfarin.</li> <li>takes nonsteroidal anti-inflammatory medicines such as aspirin and ibuprofen.</li> <li>takes cyclosporine.</li> <li>takes diabetes medicines.</li> <li>drinks grapefruit juice.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="9">Know the medicines your child takes. Keep a list of them to show your healthcare provider and pharmacist when your child gets a new medicine.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">How should I give KHINDIVI?</span> <ul class="Disc"> <li>Give KHINDIVI exactly as prescribed by your healthcare provider.</li> <li>Give KHINDIVI by mouth with or without food.</li> <li>Give a sip of water right away after giving KHINDIVI to make sure that all of the medicine has been swallowed.</li> <li>Give KHINDIVI using the oral syringe provided by the pharmacy.</li> <li> <span class="Bold">Do not</span> stop giving KHINDIVI without talking to your healthcare provider. See <span class="Bold">"<a href="#important">What is the most important information I should know about KHINDIVI?</a>"</span> </li> <li>KHINDIVI can be given through a gastric tube. After KHINDIVI is given through the gastric tube, flush the gastric tube with 20 mL of water right away to make sure all the medicine has been given.</li> <li>If your child takes too much KHINDIVI, call your healthcare provider right away or go to the nearest emergency room.</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold"><a name="side"></a>What are the possible side effects of KHINDIVI?</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">KHINDIVI may cause serious side effects, including:</span> <ul class="Disc"> <li> <span class="Bold">See "<a href="#important">What is the most important information I should know about KHINDIVI?</a>"</span> </li> <li> <span class="Bold">Hyperosmolarity, metabolic acidosis, and stomach problems.</span> Some of the ingredients in KHINDIVI may increase the risk for imbalance of salts and other substances in your blood leading to fluid shifts (hyperosmolarity), too much acid in the blood (metabolic acidosis), vomiting, loose stools, diarrhea, and other side effects, which may increase the risk of adrenal gland problems. Tell your healthcare provider if your child has confusion (altered mental status), urine output that is not normal, or is severely ill. Your healthcare provider may prescribe your child a different hydrocortisone medicine.</li> <li> <span class="Bold">Weakened immune system and increased risk of infections.</span> Taking too much KHINDIVI can weaken your body's immune system and increase your chance of getting infections. Tell your healthcare provider if your child develops any infections or has any of these symptoms:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="4"> <ul class="Circle"> <li>fever</li> <li>cough</li> <li>flu-like symptoms</li> </ul> </td><td align="left" class="Rrule" colspan="4"> <ul class="Circle"> <li>stomach area (abdominal) pain</li> <li>diarrhea</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"> <ul class="Disc"> <li> <span class="Bold">Slowed growth in children</span>. Taking too much KHINDIVI and taking it for long periods of time can affect your child's growth. Tell your healthcare provider if you are worried about your child's growth. Your healthcare provider will change the dose depending on your child's size.</li> <li> <span class="Bold">Cushing's syndrome.</span> Taking too much KHINDIVI and taking it for long periods of time can cause Cushing's syndrome. Tell your healthcare provider if your child has any of these symptoms:</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="2"> <ul class="Circle"> <li>weight gain</li> <li>slowed growth in height</li> </ul> </td><td align="left"> <ul class="Circle"> <li>high blood sugar</li> <li>high blood pressure</li> </ul> </td><td align="left" colspan="2"> <ul class="Circle"> <li>swelling</li> <li>bruising easily</li> </ul> </td><td align="left" colspan="2"> <ul class="Circle"> <li>muscle weakness</li> <li>red, round face</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>feeling depressed</li> <li>mood swings</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"> <ul class="Disc"> <li> <span class="Bold">Weak, brittle, or soft bones.</span> KHINDIVI can affect your child's bones. Your healthcare provider will change the dose depending on your child's size and will monitor your child's growth and bones.</li> <li> <span class="Bold">Changes in behavior.</span> Your child's behavior may change after starting or during treatment with KHINDIVI. Tell your healthcare provider right away if your child develops any changes in behavior including:<ul class="Circle"> <li>strong feelings of happiness and excitement.</li> <li>overexcited and overactive.</li> <li>loss of contact with reality, with feelings that are not real, and mental confusion.</li> <li>depression.</li> </ul> </li> <li> <span class="Bold">Vision problems.</span> Tell your healthcare provider if your child develops blurred vision or other vision problems during treatment with KHINDIVI. Your healthcare provider may have your child see an eye doctor.</li> <li> <span class="Bold">Gastrointestinal problems.</span> KHINDIVI can affect your child's stomach or intestine. Tell your healthcare provider if your child has gastrointestinal illnesses such as stomach or intestinal ulcers, infections, or gastrointestinal surgery.</li> <li> <span class="Bold">Risk of Kaposi's Sarcoma if your child takes too much KHINDIVI.</span> Kaposi's Sarcoma has happened in people who receive corticosteroid therapy, most often for treatment of long-lasting (chronic) conditions. Taking too much KHINDIVI over a long period of time can increase your child's risk of developing Kaposi's Sarcoma.</li> <li> <span class="Bold">Vaccinations.</span> Administration of live vaccine may be acceptable while taking KHINDIVI.</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">The most common side effects of KHINDIVI include:</span></td> </tr> <tr> <td align="left" class="Lrule" colspan="4"> <ul class="Disc"> <li>fluid retention</li> <li>behavioral and mood changes</li> </ul> </td><td align="left" colspan="3"> <ul class="Disc"> <li>change in blood sugar (glucose) tolerance</li> <li>increased appetite and weight gain</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>increase in blood pressure</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="9">These are not all the possible side effects of KHINDIVI.<br/> Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">How should I store KHINDIVI?</span> <ul class="Disc"> <li>Store KHINDIVI in the refrigerator between 36°F to 46°F (2°C to 8°C) or at room temperature between 68°F to 77°F (20°C to 25°C).</li> <li>Protect from light and heat.</li> <li>After the bottle has been opened, use KHINDIVI within 120 days. Throw away any KHINDIVI that has not been used within 120 days after the bottle has been opened.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">Keep KHINDIVI and all medicines out of the reach of children.</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">General information about the safe and effective use of KHINDIVI.</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="9">Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use KHINDIVI for a condition for which it was not prescribed. Do not give KHINDIVI to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about KHINDIVI that is written for health professionals.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">What are the ingredients in KHINDIVI?</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">Active ingredient:</span> hydrocortisone</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="9"><span class="Bold">Inactive ingredients</span>: berry flavor, butylated hydroxyanisole, ethyl maltol, glycerin, methylparaben, propylparaben, polyethylene glycol, propylene glycol, and sucralose.</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="9">KHINDIVI is manufactured for Eton Pharmaceuticals, Inc. by Tulex Pharmaceuticals, Inc., 5 Cedarbrook Dr., Cranbury, NJ 08512, USA.<br/> KHINDIVI® is a registered trademark of Eton Pharmaceuticals, Inc.<br/> KHINDIVI is covered by the following US patent: 11,904,046.<br/> For more information, go to www.KHINDIVI.com or call <span class="Bold">1-833-343-2500.</span></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=\"1%\"/>\n<col align=\"left\" valign=\"top\" width=\"18%\"/>\n<col align=\"left\" valign=\"top\" width=\"17%\"/>\n<col align=\"left\" valign=\"top\" width=\"3%\"/>\n<col align=\"left\" valign=\"top\" width=\"18%\"/>\n<col align=\"left\" valign=\"top\" width=\"19%\"/>\n<col align=\"left\" valign=\"top\" width=\"2%\"/>\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"6\">This Medication Guide has been approved by the U.S. Food and Drug Administration.</td><td align=\"right\" colspan=\"3\">Issued: 06/2025      </td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">Medication Guide</span>\n<br/> KHINDIVI® (kɪn-dɪv-i)<br/> (hydrocortisone) oral solution</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\">Read this Medication Guide before you start giving KHINDIVI to your child, and each time your child gets a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your child's medical condition or treatment.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\"><a name=\"important\"></a>What is the most important information I should know about KHINDIVI?</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">KHINDIVI may cause serious side effects, including</span>:</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">Adrenal gland problems</span>. Not giving enough KHINDIVI, stopping KHINDIVI, or switching to KHINDIVI after taking another hydrocortisone medicine (the same class of medicines as KHINDIVI) by mouth, can cause serious and life-threatening adrenal gland problems including death. Do not stop giving KHINDIVI without talking to your healthcare provider. Tell your healthcare provider if your child has any of these symptoms:</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" colspan=\"2\"></td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>loss of appetite</li>\n<li>fatigue</li>\n<li>weakness</li>\n</ul>\n</td><td align=\"left\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>joint pain</li>\n<li>nausea</li>\n<li>vomiting</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"3\">\n<ul class=\"Disc\">\n<li>low blood sugar</li>\n<li>feeling lightheaded or dizzy</li>\n<li>problems with body salt (electrolyte) levels</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\">Your healthcare provider will change the dose of KHINDIVI depending on your child's size. During episodes of acute infections, surgery, or major trauma, your healthcare provider may prescribe your child a different hydrocortisone medicine and increase the dose. If your child is vomiting, severely ill, or unable to take medicines by mouth, your healthcare provider may use corticosteroid medicines that are given directly into the bloodstream instead.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\">The amount of hydrocortisone in a dose of KHINDIVI may not be the same as in previous hydrocortisone medicines that your child takes by mouth if these oral hydrocortisone medicines have been changed (for example, crushed or compounded). When switching to KHINDIVI, your healthcare provider may need to prescribe a starting dose of KHINDIVI that is different from previous hydrocortisone medicines that your child may have been taking by mouth. Watch your child closely after being switched to KHINDIVI and contact your healthcare provider if your child has any symptoms of adrenal gland problems. Your healthcare provider may need to change the dose of KHINDIVI.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">See \"<a href=\"#side\">What are the possible side effects of KHINDIVI?</a>\" for more information about side effects.</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">What is KHINDIVI?</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\">KHINDIVI is a prescription medicine that contains a medicine hydrocortisone. Hydrocortisone belongs to a group of medicines known as corticosteroids. Hydrocortisone is a synthetic version of the hormone cortisol. Cortisol is made naturally by the adrenal glands in the body. KHINDIVI (hydrocortisone) is a man-made (synthetic) corticosteroid used to replace the body's cortisol when the adrenal glands do not make enough (adrenal insufficiency) in children from 5 to 17 years of age.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">Who should not take or be given KHINDIVI?</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">Do not give your child KHINDIVI if they:</span>\n<ul class=\"Disc\">\n<li>are allergic to hydrocortisone or any of the ingredients in KHINDIVI. See the end of this Medication Guide for a complete list of ingredients in KHINDIVI.</li>\n<li>have any reaction like swelling or shortness of breath after being given KHINDIVI. Get medical help right away and tell your healthcare provider as soon as possible as these can be signs of an allergic reaction.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">What should I tell my healthcare provider before giving KHINDIVI?</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">Before you give your child KHINDIVI, tell your healthcare provider about all of your child's medical conditions, including if they:</span>\n<ul class=\"Disc\">\n<li>are feeling unwell, or their body is under stress because of surgery or trauma. Your healthcare provider may prescribe your child a different hydrocortisone medicine for a short period of time.</li>\n<li>have a fever or infection.</li>\n<li>have nausea, vomiting, or diarrhea.</li>\n<li>are due for vaccinations. Taking KHINDIVI should not stop your child from being vaccinated. Tell your healthcare provider when your child is due for vaccinations.</li>\n<li>are scheduled for surgery.</li>\n<li>cannot swallow medicines by mouth or are fed through a gastric tube.</li>\n<li>are pregnant or plan to become pregnant. It is not known if KHINDIVI will harm your child's unborn baby. Talk to your child's healthcare provider if your child is pregnant or plans to become pregnant.</li>\n<li>are breastfeeding or plan to breastfeed. It is not known if KHINDIVI passes into the breast milk. You and your child's healthcare provider should decide if your child will receive KHINDIVI while your child breastfeeds.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">Tell your healthcare provider about all the medicines your child takes,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\">Some medicines, food and drink can affect the way that KHINDIVI works and may mean that your healthcare provider needs to change your child's dose of KHINDIVI.<br/>\n<span class=\"Bold\">Especially tell your healthcare provider if your child:</span>\n<ul class=\"Disc\">\n<li>takes medicines used to treat fungal infections such as itraconazole, posaconazole, and voriconazole.</li>\n<li>takes medicines used to treat bacterial infections such as rifampicin, rifabutin, erythromycin, and clarithromycin.</li>\n<li>takes medicines used to treat human immunodeficiency virus (HIV) infection and AIDS such as ritonavir, efavirenz, and nevirapine.</li>\n<li>takes seizure medicines such as phenytoin, carbamazepine, oxcarbazepine, phenobarbital, and primidone.</li>\n<li>takes estrogen.</li>\n<li>takes warfarin.</li>\n<li>takes nonsteroidal anti-inflammatory medicines such as aspirin and ibuprofen.</li>\n<li>takes cyclosporine.</li>\n<li>takes diabetes medicines.</li>\n<li>drinks grapefruit juice.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\">Know the medicines your child takes. Keep a list of them to show your healthcare provider and pharmacist when your child gets a new medicine.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">How should I give KHINDIVI?</span>\n<ul class=\"Disc\">\n<li>Give KHINDIVI exactly as prescribed by your healthcare provider.</li>\n<li>Give KHINDIVI by mouth with or without food.</li>\n<li>Give a sip of water right away after giving KHINDIVI to make sure that all of the medicine has been swallowed.</li>\n<li>Give KHINDIVI using the oral syringe provided by the pharmacy.</li>\n<li>\n<span class=\"Bold\">Do not</span> stop giving KHINDIVI without talking to your healthcare provider. See <span class=\"Bold\">\"<a href=\"#important\">What is the most important information I should know about KHINDIVI?</a>\"</span>\n</li>\n<li>KHINDIVI can be given through a gastric tube. After KHINDIVI is given through the gastric tube, flush the gastric tube with 20 mL of water right away to make sure all the medicine has been given.</li>\n<li>If your child takes too much KHINDIVI, call your healthcare provider right away or go to the nearest emergency room.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\"><a name=\"side\"></a>What are the possible side effects of KHINDIVI?</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">KHINDIVI may cause serious side effects, including:</span>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">See \"<a href=\"#important\">What is the most important information I should know about KHINDIVI?</a>\"</span>\n</li>\n<li>\n<span class=\"Bold\">Hyperosmolarity, metabolic acidosis, and stomach problems.</span> Some of the ingredients in KHINDIVI may increase the risk for imbalance of salts and other substances in your blood leading to fluid shifts (hyperosmolarity), too much acid in the blood (metabolic acidosis), vomiting, loose stools, diarrhea, and other side effects, which may increase the risk of adrenal gland problems. Tell your healthcare provider if your child has confusion (altered mental status), urine output that is not normal, or is severely ill. Your healthcare provider may prescribe your child a different hydrocortisone medicine.</li>\n<li>\n<span class=\"Bold\">Weakened immune system and increased risk of infections.</span> Taking too much KHINDIVI can weaken your body's immune system and increase your chance of getting infections. Tell your healthcare provider if your child develops any infections or has any of these symptoms:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"4\">\n<ul class=\"Circle\">\n<li>fever</li>\n<li>cough</li>\n<li>flu-like symptoms</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"4\">\n<ul class=\"Circle\">\n<li>stomach area (abdominal) pain</li>\n<li>diarrhea</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Slowed growth in children</span>. Taking too much KHINDIVI and taking it for long periods of time can affect your child's growth. Tell your healthcare provider if you are worried about your child's growth. Your healthcare provider will change the dose depending on your child's size.</li>\n<li>\n<span class=\"Bold\">Cushing's syndrome.</span> Taking too much KHINDIVI and taking it for long periods of time can cause Cushing's syndrome. Tell your healthcare provider if your child has 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>weight gain</li>\n<li>slowed growth in height</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Circle\">\n<li>high blood sugar</li>\n<li>high blood pressure</li>\n</ul>\n</td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>swelling</li>\n<li>bruising easily</li>\n</ul>\n</td><td align=\"left\" colspan=\"2\">\n<ul class=\"Circle\">\n<li>muscle weakness</li>\n<li>red, round face</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>feeling depressed</li>\n<li>mood swings</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Weak, brittle, or soft bones.</span> KHINDIVI can affect your child's bones. Your healthcare provider will change the dose depending on your child's size and will monitor your child's growth and bones.</li>\n<li>\n<span class=\"Bold\">Changes in behavior.</span> Your child's behavior may change after starting or during treatment with KHINDIVI. Tell your healthcare provider right away if your child develops any changes in behavior including:<ul class=\"Circle\">\n<li>strong feelings of happiness and excitement.</li>\n<li>overexcited and overactive.</li>\n<li>loss of contact with reality, with feelings that are not real, and mental confusion.</li>\n<li>depression.</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Vision problems.</span> Tell your healthcare provider if your child develops blurred vision or other vision problems during treatment with KHINDIVI. Your healthcare provider may have your child see an eye doctor.</li>\n<li>\n<span class=\"Bold\">Gastrointestinal problems.</span> KHINDIVI can affect your child's stomach or intestine. Tell your healthcare provider if your child has gastrointestinal illnesses such as stomach or intestinal ulcers, infections, or gastrointestinal surgery.</li>\n<li>\n<span class=\"Bold\">Risk of Kaposi's Sarcoma if your child takes too much KHINDIVI.</span> Kaposi's Sarcoma has happened in people who receive corticosteroid therapy, most often for treatment of long-lasting (chronic) conditions. Taking too much KHINDIVI over a long period of time can increase your child's risk of developing Kaposi's Sarcoma.</li>\n<li>\n<span class=\"Bold\">Vaccinations.</span> Administration of live vaccine may be acceptable while taking KHINDIVI.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">The most common side effects of KHINDIVI include:</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" colspan=\"4\">\n<ul class=\"Disc\">\n<li>fluid retention</li>\n<li>behavioral and mood changes</li>\n</ul>\n</td><td align=\"left\" colspan=\"3\">\n<ul class=\"Disc\">\n<li>change in blood sugar (glucose) tolerance</li>\n<li>increased appetite and weight gain</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>increase in blood pressure</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\">These are not all the possible side effects of KHINDIVI.<br/> Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">How should I store KHINDIVI?</span>\n<ul class=\"Disc\">\n<li>Store KHINDIVI in the refrigerator between 36°F to 46°F (2°C to 8°C) or at room temperature between 68°F to 77°F (20°C to 25°C).</li>\n<li>Protect from light and heat.</li>\n<li>After the bottle has been opened, use KHINDIVI within 120 days. Throw away any KHINDIVI that has not been used within 120 days after the bottle has been opened.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">Keep KHINDIVI and all medicines out of the reach of children.</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">General information about the safe and effective use of KHINDIVI.</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\">Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use KHINDIVI for a condition for which it was not prescribed. Do not give KHINDIVI to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about KHINDIVI that is written for health professionals.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">What are the ingredients in KHINDIVI?</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">Active ingredient:</span> hydrocortisone</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\"><span class=\"Bold\">Inactive ingredients</span>: berry flavor, butylated hydroxyanisole, ethyl maltol, glycerin, methylparaben, propylparaben, polyethylene glycol, propylene glycol, and sucralose.</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"9\">KHINDIVI is manufactured for Eton Pharmaceuticals, Inc. by Tulex Pharmaceuticals, Inc., 5 Cedarbrook Dr., Cranbury, NJ 08512, USA.<br/> KHINDIVI® is a registered trademark of Eton Pharmaceuticals, Inc.<br/> KHINDIVI is covered by the following US patent: 11,904,046.<br/> For more information, go to www.KHINDIVI.com or call <span class=\"Bold\">1-833-343-2500.</span></td>\n</tr>\n</tbody>\n</table></div>" }

PL-2-1.0

{ "type": "p", "children": [], "text": "PL-2-1.0" }

NDC-71863-116-16 Rx Only

{ "type": "p", "children": [], "text": "NDC-71863-116-16 Rx Only" }

Khindivi (hydrocortisone) oral solution

{ "type": "p", "children": [], "text": "Khindivi (hydrocortisone) oral solution" }

1 mg/mL

{ "type": "p", "children": [], "text": "1 mg/mL" }

For Oral Use Only

{ "type": "p", "children": [], "text": "For Oral Use Only" }

ATTENTION PHARMACIST: Dispense the following to each patient:

{ "type": "p", "children": [], "text": "ATTENTION PHARMACIST: Dispense the following to each patient:" }

{ "type": "ul", "children": [ "Accompanying Medication Guide", "Oral Dosing Syringe" ], "text": "" }

16 oz (473 mL)

{ "type": "p", "children": [], "text": "16 oz (473 mL)" }

Manufactured for: eTon PHARMACEUTICALS Deer Park, IL 60010, USA

{ "type": "p", "children": [], "text": "Manufactured for: eTon PHARMACEUTICALS Deer Park, IL 60010, USA" }

LAB-1613-v3 Rev. 05/2025

{ "type": "p", "children": [], "text": "LAB-1613-v3 Rev. 05/2025" }