Alkindi

Description

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, with a chemical formula of C21H30O5 and a molecular weight of 362 g·mol−1. Hydrocortisone appears as a white or almost white powder and is soluble in the pH range of 1-7. ALKINDI SPRINKLE is formulated as oral granules contained within hard capsules. The inactive ingredients in the granules include microcrystalline cellulose, hypromellose, magnesium stearate, and ethyl cellulose. The capsule shell is composed of hypromellose. The printing ink used on the capsules contains shellac, propylene glycol, and concentrated ammonia solution, along with colorants such as red iron oxide, potassium hydroxide for 0.5 mg (red), indigotine for 1 mg (blue), indigotine, yellow iron oxide, and titanium dioxide for 2 mg (green), and titanium dioxide, black iron oxide, and potassium hydroxide for 5 mg (gray).

Uses and Indications

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

There are no teratogenic or nonteratogenic effects associated with this medication.

Dosage and Administration

The dose should be individualized, utilizing the lowest effective dosage. The recommended starting replacement dosage is 8 to 10 mg/m² daily; however, higher doses may be necessary depending on the patient's age and the severity of disease symptoms. In cases where patients exhibit residual but decreased endogenous cortisol production, lower starting doses may be adequate.

Doses should be rounded to the nearest 0.5 mg or 1 mg, and it may be necessary to use more than one capsule to achieve the required dosage. The total daily dose should be divided into three separate doses, administered three times daily. For older patients, the total daily dose may be divided into two doses, administered twice daily.

When transitioning from other oral hydrocortisone formulations, it is essential to maintain the same total daily hydrocortisone dosage. Should symptoms of adrenal insufficiency arise, the total daily dosage should be increased accordingly.

ALKINDI SPRINKLE consists of oral granules contained within capsules. It is important to note that the capsule should not be swallowed, chewed, or crushed; the granules must be administered as directed.

Contraindications

Use of ALKINDI SPRINKLE is contraindicated in patients with a known hypersensitivity to hydrocortisone or any of the ingredients contained in the formulation.

Warnings and Precautions

Adrenal crisis may occur due to undertreatment, abrupt discontinuation of therapy, or switching from another oral hydrocortisone formulation, potentially leading to adrenocortical insufficiency, adrenal crisis, and death. Stress events such as infections or surgery can also precipitate an adrenal crisis. It is essential to increase the dosage during periods of stress. For patients who are vomiting, severely ill, or unable to take oral medications, a transition to parenteral corticosteroid formulations is recommended.

The use of dosages greater than replacement can result in immunosuppression, increasing the risk of new infections or exacerbation of latent infections from various pathogens, including viral, bacterial, fungal, protozoan, or helminthic sources. Healthcare professionals should monitor patients closely for signs and symptoms of infections.

Long-term use of excessive doses may lead to growth retardation. It is advisable to utilize the minimum dosage of ALKINDI SPRINKLE necessary to achieve the desired clinical response and to monitor the patient’s growth regularly.

Prolonged use of supraphysiologic doses of corticosteroids may result in Cushing’s syndrome. Patients should be monitored for signs and symptoms of this condition every six months, with pediatric patients under one year of age requiring more frequent assessments.

Corticosteroids can decrease bone mineral density by inhibiting bone formation and increasing bone resorption, potentially leading to osteoporosis. The minimum effective dosage of ALKINDI SPRINKLE should be employed to achieve the desired clinical outcome.

Severe psychiatric adverse reactions, including euphoria, mania, psychosis with hallucinations and delirium, or depression, may occur. Symptoms typically manifest within days to weeks of initiating treatment. Most reactions resolve following dose reduction or withdrawal, although specific treatment may be necessary. Patients should be monitored for behavioral and mood disturbances, and caregivers should be instructed to seek medical advice if psychiatric symptoms develop.

Prolonged use of high doses of corticosteroids has been associated with ophthalmic adverse reactions, including cataracts, glaucoma, and central serous chorioretinopathy. Patients should be monitored for blurred vision or other visual disturbances, and referrals to an ophthalmologist should be made if such symptoms arise.

Increased gastrointestinal adverse reactions may occur in patients with certain gastrointestinal disorders, and signs and symptoms may be masked. Monitoring for these reactions is advised.

Regular monitoring for signs and symptoms of infections, Cushing’s syndrome, behavioral and mood disturbances, and visual disturbances is essential to ensure patient safety and effective management during treatment.

Side Effects

Patients receiving ALKINDI SPRINKLE may experience a range of adverse reactions, which can be categorized into common and serious reactions.

Common adverse reactions observed in clinical trials include fluid retention, alterations in glucose tolerance, elevation in blood pressure, behavioral and mood changes, as well as increased appetite and weight gain.

Serious adverse reactions necessitate careful monitoring and management. An adrenal crisis may occur due to undertreatment, sudden discontinuation of therapy, or switching from another oral hydrocortisone formulation, potentially leading to adrenocortical insufficiency and death. Stress events, such as infections or surgery, may also precipitate an adrenal crisis.

The use of dosages greater than replacement can result in immunosuppression, increasing the risk of new infections or exacerbation of latent infections from various pathogens, including viral, bacterial, fungal, protozoan, or helminthic sources. Patients should be monitored for signs and symptoms of infections.

Long-term use of excessive doses may lead to growth retardation, necessitating the use of the minimum effective dosage to achieve the desired clinical response while monitoring the patient’s growth. Additionally, prolonged use of supraphysiologic doses may result in Cushing’s syndrome, with patients requiring monitoring for signs and symptoms every six months; pediatric patients under one year of age may need more frequent assessments.

Corticosteroids can also decrease bone mineral density by inhibiting bone formation and increasing resorption, which may lead to osteoporosis. Therefore, it is essential to use the minimum dosage necessary for the desired clinical effect.

Psychiatric adverse reactions, including euphoria, mania, psychosis with hallucinations and delirium, or depression, may occur, typically emerging within days or weeks of initiating treatment. Most psychiatric reactions resolve following dose reduction or withdrawal, although some may require specific treatment. Patients should be monitored for behavioral and mood disturbances throughout the treatment period.

Ophthalmic adverse reactions, such as cataracts, glaucoma, and central serous chorioretinopathy, have been reported with prolonged use of high doses. Patients should be monitored for blurred vision or other visual disturbances and referred to an ophthalmologist if such symptoms arise.

Gastrointestinal adverse reactions may also occur, particularly in patients with pre-existing gastrointestinal disorders, where signs and symptoms may be masked.

Lastly, hypersensitivity reactions to hydrocortisone or any of the ingredients in ALKINDI SPRINKLE have been noted and should be considered when evaluating patient responses to treatment.

Drug Interactions

Concomitant administration of ALKINDI SPRINKLE with CYP3A4 inhibitors may necessitate a reduction in the ALKINDI SPRINKLE dose due to the potential for increased plasma concentrations. Conversely, when ALKINDI SPRINKLE is administered alongside CYP3A4 inducers, an increase in the ALKINDI SPRINKLE dose may be required to maintain therapeutic efficacy.

The use of estrogen and estrogen-containing products in conjunction with ALKINDI SPRINKLE may also warrant an increase in the ALKINDI SPRINKLE dose, as these agents can influence the pharmacokinetics of the drug.

In patients receiving antidiabetic agents, caution is advised, as excessive doses of ALKINDI SPRINKLE may elevate blood glucose levels. Therefore, monitoring and potential dose adjustments of antidiabetic medications may be necessary to achieve optimal glycemic control.

The concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) with ALKINDI SPRINKLE is associated with an increased risk of gastrointestinal adverse reactions, necessitating careful consideration of the benefits and risks of such combinations.

No specific drug interactions or laboratory test interactions have been identified for ALKINDI SPRINKLE beyond those mentioned.

Packaging & NDC

The table below lists all NDC Code configurations of Alkindi (hydrocortisone), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of ALKINDI SPRINKLE have been established in pediatric patients for the replacement therapy of adrenocortical insufficiency. The use of ALKINDI SPRINKLE in this population is supported by data from pediatric patients treated with another hydrocortisone product for the same condition.

Supportive pharmacokinetic and safety data are available from a study involving 24 pediatric patients with adrenocortical insufficiency, and no new adverse reactions were identified in this group.

ALKINDI SPRINKLE is formulated as oral granules contained within capsules, which must be opened for administration; the granules should not be swallowed whole. It is important to note that ALKINDI SPRINKLE granules should not be administered via nasogastric or gastric tubes, as this may lead to tube blockage.

Geriatric Use

Elderly patients may require dose adjustments due to age-related physiological changes. Specifically, for patients aged 65 years and older, it is recommended that the daily dose be divided by 2 and administered twice daily. This modification aims to enhance safety and tolerability in the geriatric population, who may be more susceptible to adverse effects.

Healthcare providers should closely monitor elderly patients for any signs of increased sensitivity to the medication, as well as for potential interactions with other therapies commonly used in this age group. Regular assessment of the patient's response to treatment is advised to ensure optimal therapeutic outcomes while minimizing risks.

Pregnancy

Untreated adrenocortical insufficiency during pregnancy can lead to significant complications, including maternal mortality. The use of physiologic doses of hydrocortisone is not anticipated to result in major birth defects, miscarriage, or adverse maternal and fetal outcomes. Observational studies assessing hydrocortisone use in pregnant patients have not established a clear drug-associated risk for major birth defects or miscarriage.

The estimated background risk of major birth defects and miscarriage in the general U.S. population is reported to be 2–4% and 15–20%, respectively; however, the specific background risk for the indicated population remains unknown. Evidence from epidemiologic studies indicates a potential small increased risk of cleft lip with or without cleft palate associated with systemic corticosteroid use during the first trimester. It is important to note that these studies have significant methodological limitations, including non-randomized designs, retrospective data collection, and a lack of dose-response data, which may affect the reliability of the findings.

Unlike other corticosteroids, hydrocortisone is enzymatically deactivated by the placenta, which may limit fetal exposure. While corticosteroids have demonstrated teratogenic effects in various animal species at doses comparable to human doses, animal studies involving pregnant mice, rats, and rabbits without adrenocortical insufficiency have shown an increased incidence of cleft palate in the offspring. Given these considerations, healthcare professionals should carefully evaluate the risks and benefits of hydrocortisone use in pregnant patients, particularly in those with adrenocortical insufficiency.

Lactation

Cortisol is present in human milk. The use of hydrocortisone at a physiologic dose for adrenocortical insufficiency is not expected to adversely affect lactating mothers, breastfed infants, or milk production. However, there are no data available regarding the presence of hydrocortisone in breast milk, its effects on breastfed infants, or its impact on milk production.

When considering the use of ALKINDI SPRINKLE in lactating mothers, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for the medication and any potential adverse effects on the breastfed infant from ALKINDI SPRINKLE or from the underlying maternal condition.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In cases of acute overdosage, the primary approach involves supportive and symptomatic therapy. Healthcare professionals should closely monitor the patient for any adverse effects and provide appropriate interventions based on the symptoms presented.

It is essential to assess the patient's clinical status and initiate measures to stabilize vital signs. Supportive care may include intravenous fluids, oxygen supplementation, and other necessary interventions to maintain hemodynamic stability. Symptomatic treatment should be tailored to the specific symptoms exhibited by the patient, ensuring that any complications are promptly addressed.

Healthcare providers are advised to remain vigilant and prepared to manage potential complications that may arise during the course of treatment. Continuous monitoring and reassessment of the patient's condition are crucial to ensure optimal outcomes in cases of overdosage.

Nonclinical Toxicology

No adequate studies in animals have been conducted with hydrocortisone to evaluate its carcinogenic or mutagenic potential.

Corticosteroids have been shown to impair fertility in male rats.

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of corticosteroids, particularly with prolonged or high-dose administration. Ophthalmic effects, including cataract, glaucoma, and central serous chorioretinopathy, have been reported. Psychiatric reactions such as euphoria, mania, psychosis with hallucinations, and depression may also occur.

There is an increased risk of gastrointestinal perforation in patients with certain gastrointestinal disorders when corticosteroids are used. Long-term use of excessive doses in pediatric patients may lead to growth retardation. Additionally, prolonged use of corticosteroids in supraphysiologic doses has been associated with Cushing’s syndrome, characterized by symptoms such as weight gain, decreased height velocity, hyperglycemia, hypertension, edema, easy bruising, muscle weakness, and mood changes.

Corticosteroids have been shown to decrease bone formation and increase bone resorption, potentially leading to osteoporosis. Furthermore, excessive intake of ALKINDI SPRINKLE may compromise the immune system, increasing the risk of infections. The administration of live vaccines may be acceptable during treatment with ALKINDI SPRINKLE.

Patient Counseling

Advise patients and caregivers to read the FDA-approved patient labeling (Medication Guide) thoroughly to understand the proper use and potential risks associated with ALKINDI SPRINKLE. It is important to inform them that undertreatment or sudden discontinuation of ALKINDI SPRINKLE may lead to symptoms of adrenocortical insufficiency, adrenal crisis, and even death.

Healthcare providers should discuss the potential dosing inaccuracies associated with manipulated oral hydrocortisone preparations, such as split or crushed tablets or compounded suspensions, which may result in differences in dosing. When transitioning from conventional oral hydrocortisone to ALKINDI SPRINKLE, advise patients and caregivers that this switch could lead to unintended clinical consequences, necessitating close monitoring during this period.

Patients and caregivers should be instructed to contact their healthcare provider if they experience prolonged vomiting, severe illness, or an inability to take oral medications. It is essential to inform them that exceeding the replacement dosage of corticosteroids can suppress the immune system, increasing the risk of infections. They should also be advised to reach out to their healthcare provider if any infections develop.

Clarify that ALKINDI SPRINKLE is a granule formulation contained within a capsule, and it should not be swallowed whole, chewed, or crushed. Instruct caregivers to open the capsule and administer the granules directly into the patient’s mouth or sprinkle them onto soft food for immediate consumption, as the taste-masking cover can dissolve in as little as five minutes. Caution against wetting the capsule, as this may cause some granules to stick to it. Following administration, patients should take a sip of fluids to ensure all granules have been swallowed.

Discuss the potential long-term effects of corticosteroid use, particularly in pediatric patients, including the risk of growth retardation. Inform patients and caregivers that prolonged use of corticosteroids in supraphysiologic doses may lead to Cushing’s syndrome, with symptoms such as weight gain, decreased height velocity, hyperglycemia, hypertension, edema, easy bruising, muscle weakness, a red round face, depression, or mood swings.

Additionally, inform them that corticosteroids can decrease bone formation and increase bone resorption, potentially leading to osteoporosis. It is crucial to highlight that corticosteroid use may be associated with severe psychiatric adverse reactions, including euphoria, mania, psychosis with hallucinations, or depression. Caregivers and patients should be instructed to seek medical advice if any psychiatric symptoms develop.

Ophthalmic effects such as cataracts, glaucoma, or central serous chorioretinopathy have been reported with prolonged use of high-dose corticosteroids. Patients and caregivers should be advised to report any instances of blurred vision or visual disturbances to their healthcare provider. Furthermore, discuss the increased risk of gastrointestinal perforation associated with corticosteroid use in certain gastrointestinal disorders.

Finally, inform patients and caregivers that ALKINDI SPRINKLE granules may sometimes be visible in stools, as the center of the granule is not absorbed in the gut after the active substance has been released. This occurrence does not indicate that the product is ineffective, and they should not take an additional dose in such cases.

Storage and Handling

The product is supplied in its original bottle to ensure protection from light. It should be stored at a controlled room temperature of 20°C to 25°C (68°F to 77°F). Temporary excursions in temperature are permissible between 15°C to 30°C (59°F to 86°F).

Once the bottle has been opened, it is recommended that the capsules be used within 60 days to maintain optimal efficacy.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Alkindi as submitted by Eton Pharmaceuticals, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)