These Highlights Do Not Include All The Information Needed To Use Khindivi™ Safely And Effectively. See Full Prescribing Information For Khindivi™.

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)] .

PL-2-2.0

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.

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 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.

Structural formula of hydrocortisone:

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.

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

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)] .

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.

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)] .

The following serious adverse reactions are described here and elsewhere in the label:

• Adrenal Crisis [see Warnings and Precautions (5.1)]
• Systemic Adverse Reactions Due to Inactive Ingredients [see Warnings and Precautions (5.2)]
• Immunosuppression and Increased Risk of Infection with Use of a Dosage Greater Than Replacement [see Warnings and Precautions (5.3)]
• Growth Retardation [see Warnings and Precautions (5.4)]
• Cushing's Syndrome Due to Use of Excessive Doses of Corticosteroids [see Warnings and Precautions (5.5)]
• Decrease in Bone Mineral Density [see Warnings and Precautions (5.6)]
• Psychiatric Adverse Reactions [see Warnings and Precautions (5.7)]
• Ophthalmic Adverse Reactions [see Warnings and Precautions (5.8)]
• Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.9)]
• Risk of Kaposi's Sarcoma with Use of Dosage Greater than Replacement [see Warnings and Precautions (5.10)]
• Vaccinations [see Warnings and Precautions (5.11)]

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

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.

KHINDIVI is indicated as replacement therapy in pediatric patients 5 years of age and older with adrenocortical insufficiency.

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

• 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)

• Individualize the dose, using the lowest possible dosage. ( 2.1)
• When stress dosing is needed use a different hydrocortisone containing drug product. ( 2.1)
• The recommended starting replacement dosage of KHINDIVI is 8 to 10 mg/m ²daily. Higher doses may be needed based on the patient's age and symptoms of the disease. Use of lower starting doses may be sufficient in patients with residual but decreased endogenous cortisol production. ( 2.2)
• Divide the total daily dose into 3 doses and administer 3 times daily. Older patients may have their daily dose divided by 2 and administered twice daily. ( 2.2)
• KHINDIVI contains the inactive ingredients polyethylene glycol 400, propylene glycol, and glycerin. If patients experience adverse reactions (i.e., hyperosmolarity, metabolic acidosis, hypoglycemia, hepato-renal injury, central nervous system toxicity, and gastrointestinal adverse reactions), consider discontinuation of KHINDIVI and switch to another hydrocortisone product. ( 2.3)
• When switching from other oral hydrocortisone formulations, use the same total daily hydrocortisone dosage. If symptoms of adrenal insufficiency occur, increase total daily dosage. ( 2.4)
• See the Full Prescribing Information for detailed dosing and administration instructions. ( 2)

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

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

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.

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.

Advise patients and/or caregivers to read the FDA-approved patient labeling (Medication Guide).

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.

KHINDIVI is supplied as a colorless to slightly yellow colored, clear viscous solution:

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.

• 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)] .

• The recommended starting replacement dosage of KHINDIVI is 8 to 10 mg/m ²daily 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.

NDC-71863-116-16

Rx Only

Khindivi

(hydrocortisone)

oral solution

1 mg/mL

For Oral Use Only

ATTENTION PHARMACIST:

Dispense the following to each patient:

• Accompanying Medication Guide
• Oral Dosing Syringe

16 oz (473 mL)

Manufactured for:

eTon

PHARMACEUTICALS

Deer Park, IL 60010, USA

LAB-1613-v3

Rev. 05/2025

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.

• 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)].

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.

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.

• 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)] .

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)].

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)] .

PL-2-2.0

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.

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 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.

Structural formula of hydrocortisone:

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.

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

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)] .

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.

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)] .

The following serious adverse reactions are described here and elsewhere in the label:

• Adrenal Crisis [see Warnings and Precautions (5.1)]
• Systemic Adverse Reactions Due to Inactive Ingredients [see Warnings and Precautions (5.2)]
• Immunosuppression and Increased Risk of Infection with Use of a Dosage Greater Than Replacement [see Warnings and Precautions (5.3)]
• Growth Retardation [see Warnings and Precautions (5.4)]
• Cushing's Syndrome Due to Use of Excessive Doses of Corticosteroids [see Warnings and Precautions (5.5)]
• Decrease in Bone Mineral Density [see Warnings and Precautions (5.6)]
• Psychiatric Adverse Reactions [see Warnings and Precautions (5.7)]
• Ophthalmic Adverse Reactions [see Warnings and Precautions (5.8)]
• Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.9)]
• Risk of Kaposi's Sarcoma with Use of Dosage Greater than Replacement [see Warnings and Precautions (5.10)]
• Vaccinations [see Warnings and Precautions (5.11)]

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

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.

KHINDIVI is indicated as replacement therapy in pediatric patients 5 years of age and older with adrenocortical insufficiency.

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

• 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)

• Individualize the dose, using the lowest possible dosage. ( 2.1)
• When stress dosing is needed use a different hydrocortisone containing drug product. ( 2.1)
• The recommended starting replacement dosage of KHINDIVI is 8 to 10 mg/m ²daily. Higher doses may be needed based on the patient's age and symptoms of the disease. Use of lower starting doses may be sufficient in patients with residual but decreased endogenous cortisol production. ( 2.2)
• Divide the total daily dose into 3 doses and administer 3 times daily. Older patients may have their daily dose divided by 2 and administered twice daily. ( 2.2)
• KHINDIVI contains the inactive ingredients polyethylene glycol 400, propylene glycol, and glycerin. If patients experience adverse reactions (i.e., hyperosmolarity, metabolic acidosis, hypoglycemia, hepato-renal injury, central nervous system toxicity, and gastrointestinal adverse reactions), consider discontinuation of KHINDIVI and switch to another hydrocortisone product. ( 2.3)
• When switching from other oral hydrocortisone formulations, use the same total daily hydrocortisone dosage. If symptoms of adrenal insufficiency occur, increase total daily dosage. ( 2.4)
• See the Full Prescribing Information for detailed dosing and administration instructions. ( 2)

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

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

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.

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.

Advise patients and/or caregivers to read the FDA-approved patient labeling (Medication Guide).

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.

KHINDIVI is supplied as a colorless to slightly yellow colored, clear viscous solution:

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.

• 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)] .

• The recommended starting replacement dosage of KHINDIVI is 8 to 10 mg/m ²daily 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.

NDC-71863-116-16

Rx Only

Khindivi

(hydrocortisone)

oral solution

1 mg/mL

For Oral Use Only

ATTENTION PHARMACIST:

Dispense the following to each patient:

• Accompanying Medication Guide
• Oral Dosing Syringe

16 oz (473 mL)

Manufactured for:

eTon

PHARMACEUTICALS

Deer Park, IL 60010, USA

LAB-1613-v3

Rev. 05/2025

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.

• 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)].

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.

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.

• 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)] .

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)].