HYDROCORTISONE Drug Interactions: What You Need to Know
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Drug Interactions (FDA Label)
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
12/2024
Contraindications
CONTRAINDICATIONS: Product should not be used in patients with a history of sensitivity to any of its ingredients or adverse reactions to lidocaine or amide anesthetics, which usually do not cross-react with “caine” ester type anesthetics. If excessive irritation and significant worsening occur, discontinue use and seek the advice of your physician. Product and topical lidocaine should be used cautiously in those with impaired liver function, as well as the very ill or very elderly and those with significant liver disease. Product should be used with caution on patients receiving antiarrhythmic drugs of Class I since the adverse effects are additive and generally synergistic. This product is contraindicated for tuberculous or fungal lesions or skin vaccinia, varicella and acute herpes simplex. Topical corticosteroids are contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation. structure structure2
Related 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. During periods of stress switch to another oral hydrocortisone product and increase the dose. Switch patients who are vomiting, severely ill or unable to take oral medications to parenteral corticosteroid formulations. ( 5.1 )
Systemic Adverse Reactions
Due to Inactive Ingredients : KHINDIVI contains the inactive ingredients polyethylene glycol 400, propylene and glycol, and glycerin, which may cause hyperosmolarity, metabolic acidosis, hypoglycemia, hepato-renal injury, central nervous toxicity, gastrointestinal adverse reactions. Discontinue KHINDIVI and switch to another hydrocortisone product if these adverse reactions occur. ( 5.2 ) 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. ( 5.3 )
Growth
Retardation : Long-term use in excessive doses may cause growth retardation. Use the minimum dosage of KHINDIVI to achieve desired clinical response and monitor the patient's growth. ( 5.4 ) 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. ( 5.5 ) 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. Use the minimum dosage of KHINDIVI to achieve desired clinical response.( 5.6 )
Psychiatric Adverse
Reactions : Use may be associated with severe psychiatric adverse reactions such as euphoria, mania, psychosis with hallucinations and delirium or depression. Symptoms typically emerge within a few days or weeks of starting the treatment. Most reactions resolve after either dose reduction or withdrawal, although specific treatment may be necessary. Monitor patients for behavioral and mood disturbances during treatment. Instruct caregivers and/or patients to seek medical advice if psychiatric symptoms develop. ( 5.7 )
Ophthalmic Adverse
Reactions : Cataracts, glaucoma and central serous chorioretinopathy have been reported with prolonged use of high doses. Monitor patients for blurred vision or other visual disturbances and if they occur, refer them to an ophthalmologist. ( 5.8 )
Gastrointestinal Adverse
Reactions : Increased risk in patients with certain gastrointestinal disorders. Signs and symptoms may be masked. ( 5.9 )
5.1 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 <span class="opacity-50 text-xs">[see Warnings and Precautions (5.2) ]</span> . 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.
5.2 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.
5.3 Immunosuppression and Increased Risk of Infection with Use of a Dosage Greater Than Replacement Use of the recommended dosage of KHINDIVI <span class="opacity-50 text-xs">[see Dosage and Administration (2.1 , 2.2) ]</span> 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 <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1) ]</span>.
5.4 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.
5.5 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.
5.6 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.
5.7 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 <span class="opacity-50 text-xs">[see Adverse Reactions (6) ]</span>. 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.
5.8 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.
5.9 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) ].