Corticosteroid

Alkindi Sprinkle

Approved 29 Sept 2020OralGranule

The FDA lists this product in 4 strengths and forms.

Indications

ALKINDI SPRINKLE is indicated as replacement therapy in pediatric patients with adrenocortical insufficiency. ALKINDI SPRINKLE is a corticosteroid indicated as replacement therapy in pediatric patients with adrenocortical insufficiency. (1)

Contraindications

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 )] . Hypersensitivity to hydrocortisone or to any of the ingredients in ALKINDI SPRINKLE. ( 4 )

Warnings and precautions

Adrenal Crisis: Undertreatment, sudden discontinuation of therapy, or switching from another oral hydrocortisone formulation may lead to adrenocortical insufficiency, adrenal crisis and death. Adrenal crisis may also be induced by stress events such as infections or surgery. Increase the dose during periods of stress. Switch patients who are vomiting, severely ill or unable to take oral medications to parenteral corticosteroid formulations.

(5.1) Immunosuppression and Increased Risk of Infection with Use of a Dosage Greater Than Replacement : Use of a greater than replacement dosage can suppress the immune system and increase the risks of new infections or exacerbation of latent infections with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic infections. Monitor patients for signs and symptoms of infections. (5.2) Growth Retardation: Long-term use in excessive doses may cause growth retardation.

Use the minimum dosage of ALKINDI SPRINKLE to achieve desired clinical response and monitor the patient’s growth. (5.3) Cushing’s Syndrome Due to Use of Excessive Doses of Corticosteroids: Prolonged use with supraphysiologic doses may cause Cushing’s syndrome. 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. (5.4) Decrease in Bone Mineral Density: Corticosteroids decrease bone formation and increase bone resorption which may lead to inhibition of bone growth and development of osteoporosis.

Interactions

Table 2 Drug Interactions with ALKINDI SPRINKLE CYP3A4 Inhibitors Clinical Impact: 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. Intervention: Concomitant use of CYP3A4 inhibitors may require a decrease in the ALKINDI SPRINKLE dose.

Examples: Anti-fungals: itraconazole, posaconazole, voriconazole Antibiotics: erythromycin and clarithromycin Antiretrovirals: ritonavir Grapefruit juice CYP3A4 Inducers Clinical Impact: 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.

Intervention: Concomitant use of CYP3A4 inducers may require an increase in the ALKINDI SPRINKLE dose. Examples: Anticonvulsants: phenytoin, carbamazepine and oxcarbazepine Antibiotics: rifampicin and rifabutin Barbiturates: phenobarbital and primidone Antiretrovirals: efavirenz and nevirapine Estrogen and Estrogen Containing Products Clinical Impact: 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. Intervention: Concomitant use of estrogen/estrogen containing products may require an increase in the ALKINDI SPRINKLE dose. Antidiabetic Agents Clinical Impact: Corticosteroids in supraphysiologic doses may increase blood glucose concentrations. Intervention: Use of ALKINDI SPRINKLE in supraphysiologic doses may require a dose adjustment of antidiabetic agents.

Anticoagulant Agents Clinical Impact: Concomitant use of warfarin and corticosteroids usually results in inhibition of response to warfarin, although there have been some conflicting reports. Intervention: Monitor coagulation indices in patients receiving ALKINDI SPRINKLE and concomitant warfarin to maintain the desired anticoagulant effect. Cyclosporine Clinical Impact: Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently.

Convulsions have been reported with concurrent use. Intervention: Monitor patients receiving ALKINDI SPRINKLE and concomitant cyclosporine. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Clinical Impact: 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.

Intervention: Monitor patients receiving ALKINDI SPRINKLE and concomitant NSAIDs. CYP3A4 Inhibitors : concomitant administration may require a decrease in the ALKINDI SPRINKLE dose. ( 7 ) CYP3A4 Inducers : concomitant administration may require an increase in the ALKINDI SPRINKLE dose. ( 7 ) Estrogen and Estrogen Containing Products : concomitant administration may require an increase in the ALKINDI SPRINKLE dose. ( 7 ) Antidiabetic agents: excessive doses may increase blood glucose concentrations.

Dose adjustment of antidiabetic agents may be required. ( 7 ) NSAIDs: concomitant administration increases risk of gastrointestinal adverse reactions. ( 7 ) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling (Medication Guide). Revised 04/2026

Pregnancy and breastfeeding

8.1Pregnancy 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.

Adverse reactions

The following serious adverse reactions are described here and elsewhere in the label: Adrenal Crisis [see Warnings and Precautions ( 5.1 )] Immunosuppression and Increased Risk of Infection with Use of a Dosage Greater Than Replacement [see Warnings and Precautions ( 5.2 )] Growth Retardation [see Warnings and Precautions ( 5.3 )] Cushing’s Syndrome Due to Use of Excessive Doses of Corticosteroids [see Warnings and Precautions ( 5.4 )] Decrease in Bone Mineral Density [see Warnings and Precautions ( 5.5 )] Psychiatric Adverse Reactions [see Warnings and Precautions ( 5.6 )] Ophthalmic Adverse Reactions [see Warnings and Precautions ( 5.7 )] Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.8 )] Risk of Kaposi's Sarcoma with Use of Dosage Greater Than Replacement [see Warnings and Precautions (5.9)] Vaccinations [see Warnings and Precautions (5.10)] 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.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Eton Pharmaceuticals, Inc. at 1-855-224-0233 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical 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. Table 1 Adverse Reactions Occurring in >11% of Pediatric Patients with Adrenocortical Insufficiency Treated with ALKINDI SPRINKLE for up to 29 Months Adverse Reactions N=18 (%) Pyrexia 10 (56) Gastroenteritis 9 (50) Viral upper respiratory tract infection 8 (44) Vomiting 7 (39) Viral infection 6 (33) Conjunctivitis 5 (28) Otitis media viral 3 (17) Tonsillitis 3 (17) Body temperature increased 2 (11) Bronchitis 2 (11) Dental caries 2 (11) Diarrhea 2 (11) Genitourinary operation 2 (11) Pharyngitis 2 (11) Respiratory tract infection 2 (11) Rhinitis 2 (11)

6.2Postmarketing 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

Alkindi Sprinkle

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

5.1Adrenal Crisis Undertreatment with

5.3Growth Retardation

5.4Cushing’s Syndrome Due to Use of Excessive Doses of Corticosteroids

5.5Decrease in Bone Mineral Density

5.6Psychiatric Adverse Reactions

5.7Ophthalmic Adverse Reactions

5.8Gastrointestinal Adverse Reactions

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information

At a glance

Guidelines