Khindivi
(hydrocortisone)Dosage & Administration
By using PrescriberAI, you agree to the AI Terms of Use.
Khindivi Prescribing Information
KHINDIVI is indicated as replacement therapy in pediatric patients 5 years of age and older with adrenocortical insufficiency.
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)].
Important Considerations for Dosing
- Individualize the dose for each patient, using the lowest possible dosage.
- Monitor patients for symptoms of under and/or overtreatment including signs and symptoms of adrenocortical insufficiency, linear growth, and weight gain. Adjust doses accordingly.
- When stress dosing is needed (during episodes of acute febrile illness, gastroenteritis, surgery or major trauma) use a different hydrocortisone-containing drug product. [see Warnings and Precautions (5.1)].
Recommended Dosage and Administration
- The recommended starting replacement dosage of KHINDIVI is 8 to 10 mg/m2 daily administered orally with or without food. Higher doses may be needed based on the patient's age and symptoms of the disease. Use of lower starting dose may be sufficient in patients with residual but decreased endogenous cortisol production.
- Round the dose to the nearest 0.5 mg or 1 mg.
- Divide the total daily dose into 3 doses and administer 3 times daily. Older pediatric patients may have their daily dose divided by 2 and administered twice daily.
- Administer KHINDIVI using the oral syringe provided by the pharmacy.
- KHINDIVI may be administered through a gastric tube. Flush gastric tube with 20 mL of water to ensure the entire dose is delivered.
Discontinue KHINDIVI Due to Adverse Reactions Associated with Inactive Ingredients
- KHINDIVI contains the inactive ingredients polyethylene glycol 400, propylene glycol, and glycerin, which have been associated with hyperosmolarity, metabolic acidosis, hypoglycemia, hepato-renal injury, central nervous system toxicity, and gastrointestinal adverse reactions. If patient presents with adverse reactions that could be related to these conditions, monitor the patient, and consider discontinuation of KHINDIVI and switching to another hydrocortisone product [see Warnings and Precautions (5.2)].
Switching to KHINDIVI from Other Oral Hydrocortisone Formulations
- When switching patients to KHINDIVI from other oral hydrocortisone formulations to KHINDIVI use the same total daily hydrocortisone dosage. After switching to KHINDIVI, monitor patients for symptoms of adrenocortical insufficiency. If symptoms of adrenal insufficiency occur after switching, increase the total daily dosage of KHINDIVI [see Dosage and Administration (2.2) and Warnings and Precautions (5.1, 5.2)].
KHINDIVI oral solution, 1 mg/mL is a clear, colorless to slightly yellow colored viscous oral solution.
Pregnancy
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.
Lactation
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.
Pediatric Use
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)].
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)].
Adrenal Crisis
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.
Systemic Adverse Reactions Due to Inactive Ingredients
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.
Immunosuppression and Increased Risk of Infection with Use of a Dosage Greater Than Replacement
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:
- 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 KHINDIVI dosage reduction as needed [see Warnings and Precautions (5.1)].
Growth Retardation
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.
Cushing's Syndrome Due to Use of Excessive Doses of Corticosteroids
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.
Decrease in Bone Mineral Density
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.
Psychiatric Adverse Reactions
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 Adverse Reactions
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 Adverse Reactions
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)].
Risk of Kaposi's Sarcoma with Use of a Dosage Greater Than Replacement
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.
Vaccination
Administration of live vaccines may be acceptable in KHINDIVI-treated pediatric patients with adrenocortical insufficiency who receive replacement corticosteroids.