Hydrocortisone

Uses and Indications

This drug is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.

Hydrocortisone tablets are indicated in the following conditions:

Endocrine Disorders

• Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the first choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy, mineralocorticoid supplementation is of particular importance).

• Congenital adrenal hyperplasia.

• Non-suppurative thyroiditis.

• Hypercalcemia associated with cancer.

Rheumatic Disorders

• As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in:

  • Psoriatic arthritis.

  • Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy).

  • Ankylosing spondylitis.

  • Acute and subacute bursitis.

  • Acute nonspecific tenosynovitis.

  • Acute gouty arthritis.

  • Post-traumatic osteoarthritis.

  • Synovitis of osteoarthritis.

  • Epicondylitis.

Collagen Diseases

• During an exacerbation or as maintenance therapy in selected cases of:

  • Systemic lupus erythematosus.

  • Systemic dermatomyositis (polymyositis).

  • Acute rheumatic carditis.

Dermatologic Diseases

• Pemphigus.

• Bullous dermatitis herpetiformis.

• Severe erythema multiforme (Stevens-Johnson syndrome).

• Exfoliative dermatitis.

• Mycosis fungoides.

• Severe psoriasis.

• Severe seborrheic dermatitis.

Allergic States

• Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment:

  • Seasonal or perennial allergic rhinitis.

  • Serum sickness.

  • Bronchial asthma.

  • Contact dermatitis.

  • Atopic dermatitis.

  • Drug hypersensitivity reactions.

Ophthalmic Diseases

• Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as:

  • Allergic conjunctivitis.

  • Keratitis.

  • Allergic corneal marginal ulcers.

  • Herpes zoster ophthalmicus.

  • Iritis and iridocyclitis.

  • Chorioretinitis.

  • Anterior segment inflammation.

  • Diffuse posterior uveitis and choroiditis.

  • Optic neuritis.

  • Sympathetic ophthalmia.

Respiratory Diseases

• Symptomatic sarcoidosis.

• Loeffler's syndrome not manageable by other means.

• Berylliosis.

• Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy.

• Aspiration pneumonitis.

Hematologic Disorders

• Idiopathic thrombocytopenic purpura in adults.

• Secondary thrombocytopenia in adults.

• Acquired (autoimmune) hemolytic anemia.

• Erythroblastopenia (RBC anemia).

• Congenital (erythroid) hypoplastic anemia.

Neoplastic Diseases

• For palliative management of:

  • Leukemias and lymphomas in adults.

  • Acute leukemia of childhood.

Edematous States

• To induce a diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus.

Gastrointestinal Diseases

• To tide the patient over a critical period of the disease in:

  • Ulcerative colitis.

  • Regional enteritis.

Miscellaneous

• Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy.

• Trichinosis with neurologic or myocardial involvement.

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.

No teratogenic or nonteratogenic effects are mentioned in the provided text.

Dosage and Administration

Topical corticosteroids, including hydrocortisone formulations, are generally applied to the affected area as a thin film from two to four times daily, depending on the severity of the condition. Occlusive dressings may be utilized for the management of psoriasis or other recalcitrant conditions; however, if an infection develops, the use of occlusive dressings should be discontinued, and appropriate antimicrobial therapy should be instituted.

For oral hydrocortisone tablets, the initial dosage may vary from 20 mg to 240 mg per day, tailored to the specific disease entity being treated. In less severe situations, lower doses may suffice, while higher initial doses may be required for selected patients. The initial dosage should be maintained or adjusted until a satisfactory clinical response is noted. If there is a lack of satisfactory response after a reasonable period, hydrocortisone should be discontinued, and the patient should be transitioned to other appropriate therapy.

Dosage requirements for oral hydrocortisone are variable and must be individualized based on the disease under treatment and the patient's response. After achieving a favorable response, the maintenance dosage should be determined by gradually decreasing the initial dosage in small increments until the lowest effective dose is reached. Continuous monitoring of the dosage is essential, particularly in response to changes in clinical status, individual drug responsiveness, and exposure to stressful situations. In such cases, it may be necessary to temporarily increase the dosage.

For hydrocortisone rectal suspension, the usual course of therapy is one suspension administered nightly for 21 days or until the patient achieves clinical and proctological remission. Clinical symptoms typically subside within 3 to 5 days, although mucosal improvement may lag. In difficult cases, treatment may extend to 2 or 3 months. If therapy exceeds 21 days, the rectal suspension should be gradually discontinued by reducing administration to every other night for 2 to 3 weeks. Patients should be instructed to lie on their left side during administration and for 30 minutes thereafter to facilitate distribution throughout the left colon, and efforts should be made to retain the enema for at least an hour, preferably overnight.

In all cases, it is recommended that hydrocortisone be withdrawn gradually after long-term therapy rather than abruptly.

Contraindications

Topical corticosteroids are contraindicated in patients with a history of hypersensitivity to any of the components of the preparation. Additionally, systemic fungal infections are a contraindication for the use of hydrocortisone in tablet, enema, and suspension forms. The use of hydrocortisone is also contraindicated in patients with ileocolostomy during the immediate or early post-operative period.

Warnings and Precautions

Serious Warnings

• In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated.

• Immunosuppression and Increased Risk of Infection: Corticosteroids, including hydrocortisone, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. This can lead to reduced resistance to new infections, exacerbation of existing infections, increased risk of disseminated infections, and reactivation or exacerbation of latent infections. Corticosteroid-associated infections can be mild but can also be severe and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages. Monitor for the development of infection and consider hydrocortisone withdrawal or dosage reduction as needed.

• Tuberculosis: If hydrocortisone is used to treat a condition in patients with latent tuberculosis or tuberculin reactivity, reactivation of tuberculosis may occur. Closely monitor such patients for reactivation. During prolonged hydrocortisone therapy, patients with latent tuberculosis or tuberculin reactivity should receive chemoprophylaxis.

• Varicella Zoster and Measles Viral Infections: Varicella and measles can have a serious or even fatal course in non-immune patients taking corticosteroids. Particular care should be taken to avoid exposure to these infections in corticosteroid-treated patients who have not had these diseases or are non-immune. Prophylaxis with varicella zoster immune globulin may be indicated if exposed to varicella, and immunoglobulin may be indicated if exposed to measles.

• Hepatitis B Virus Reactivation: Reactivation can occur in patients who are hepatitis B carriers treated with immunosuppressive dosages of corticosteroids. Screen patients for hepatitis B infection before initiating immunosuppressive treatment with hydrocortisone.

• Fungal Infections: Corticosteroids may exacerbate systemic fungal infections; therefore, avoid hydrocortisone use in the presence of such infections unless necessary to control drug reactions.

• Amebiasis: Corticosteroids may activate latent amebiasis; it is recommended to rule out latent or active amebiasis before initiating treatment in patients who have spent time in the tropics or have unexplained diarrhea.

• Strongyloides Infestation: Use with caution in patients with known or suspected Strongyloides infestation, as corticosteroid-induced immunosuppression may lead to hyperinfection and severe complications.

• Cerebral Malaria: Avoid corticosteroids in patients with cerebral malaria.

• Ophthalmic Effects: Prolonged use may produce posterior subcapsular cataracts, glaucoma, and enhance the establishment of secondary ocular infections due to fungi or viruses.

• Kaposi’s Sarcoma: Has been reported in patients receiving corticosteroid therapy; discontinuation may result in clinical improvement.

• Hypertension, Volume Overload, and Hypokalemia: Average and large doses can cause elevation of blood pressure, salt and water retention, and increased potassium excretion. Dietary salt restriction and potassium supplementation may be necessary.

• Vaccinations: Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.

General Precautions

• Drug-induced secondary adrenocortical insufficiency may occur with prolonged therapy and may persist for months after discontinuation. Gradual reduction of dosage is recommended.

• There is an enhanced effect of corticosteroids on patients with hypothyroidism and cirrhosis.

• Use cautiously in patients with ocular herpes simplex due to the risk of corneal perforation.

• The lowest possible dose should be used to control the condition, and reductions should be gradual when possible.

• Psychiatric adverse reactions may occur, ranging from euphoria to severe depression and psychotic manifestations. Monitor for behavioral and mood disturbances.

• Caution is advised in patients with conditions such as ulcerative colitis, diverticulitis, renal insufficiency, hypertension, osteoporosis, and myasthenia gravis.

• Growth and development of infants and children on prolonged therapy should be carefully observed.

• Pheochromocytoma crisis has been reported after systemic corticosteroid administration; consider this risk prior to treatment.

• Tumor lysis syndrome (TLS) has been reported in patients with malignancies following corticosteroid use; monitor high-risk patients closely.

Monitoring Requirements

• Laboratory tests such as the urinary free cortisol test and ACTH stimulation test may be helpful in evaluating HPA axis suppression, especially in patients receiving large doses of potent topical steroids or those under occlusive dressings.

• Screen patients for hepatitis B infection before initiating immunosuppressive treatment with hydrocortisone.

Emergency Medical Help Instructions

• Specific instructions for emergency medical help are not explicitly stated in the provided text.

Stop Taking and Call Your Doctor Instructions

• If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted. If a favorable response does not occur promptly in the presence of dermatological infections, the corticosteroid should be discontinued until the infection has been adequately controlled.

Side Effects

Local adverse reactions commonly associated with hydrocortisone and related corticosteroids include:

• Burning

• Itching

• Irritation

• Dryness

• Folliculitis

• Hypertrichosis

• Acneiform eruptions

• Hypopigmentation

• Perioral dermatitis

• Allergic contact dermatitis

• Maceration of the skin

• Secondary infection

• Skin atrophy

• Striae

• Miliaria

Systemic adverse reactions may include:

• Reversible hypothalamic-pituitary-adrenal (HPA) axis suppression

• Manifestations of Cushing's syndrome

• Hyperglycemia

• Glucosuria

Pediatric Use

In pediatric patients, there is a greater susceptibility to topical corticosteroid-induced HPA axis suppression and Cushing's syndrome. Manifestations of adrenal suppression may include:

• Linear growth retardation

• Delayed weight gain

• Low plasma cortisol levels

• Absence of response to ACTH stimulation

Manifestations of intracranial hypertension may include:

• Bulging fontanelles

• Headaches

• Bilateral papilledema

Additional Adverse Reactions or Important Notes

• Signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids.

• Children may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity.

• If irritation develops, topical corticosteroids should be discontinued, and appropriate therapy instituted. In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, the corticosteroid should be discontinued until the infection has been adequately controlled.

Serious Adverse Reactions

Serious adverse reactions may include:

• Fluid and Electrolyte Disturbances: Sodium retention, fluid retention, congestive heart failure in susceptible patients, potassium loss, hypokalemic alkalosis, and hypertension.

• Musculoskeletal Effects: Muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, tendon rupture (particularly of the Achilles tendon), vertebral compression fractures, aseptic necrosis of femoral and humeral heads, and pathologic fractures of long bones.

• Gastrointestinal Effects: Peptic ulcer with possible perforation and hemorrhage, pancreatitis, abdominal distention, and ulcerative esophagitis.

• Neurological Effects: Increased intracranial pressure with papilledema (pseudotumor cerebri), convulsions, vertigo, and headache.

• Endocrine Effects: Development of Cushingoid state, suppression of growth in children, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress), menstrual irregularities, decreased carbohydrate tolerance, and increased requirements for insulin or oral hypoglycemic agents in diabetics.

• Ophthalmic Effects: Central serous chorioretinopathy, posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and exophthalmos.

• Metabolic Effects: Negative nitrogen balance due to protein catabolism.

• Blood and Lymphatic System Disorders: Leukocytosis.

Warnings

Corticosteroids may mask some signs of infection, and new infections may appear during their use. There may be decreased resistance and inability to localize infection when corticosteroids are used. Corticosteroid-associated infections can be mild but can be severe and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages.

In patients with latent tuberculosis or tuberculin reactivity, reactivation of tuberculosis may occur. Particular care should be taken to avoid exposure to varicella and measles in non-immune patients taking corticosteroids, as these infections can have a serious or even fatal course.

Corticosteroids may exacerbate systemic fungal infections and should be used with caution in patients with known or suspected Strongyloides infestation.

Psychiatric adverse reactions may occur, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations. Existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.

Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement of Kaposi’s sarcoma.

Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic corticosteroids. In patients with suspected pheochromocytoma, consider the risk of pheochromocytoma crisis prior to administering corticosteroids.

Drug Interactions

Drugs that induce hepatic enzymes, such as phenobarbital, phenytoin, and rifampin, may increase the clearance of corticosteroids, potentially necessitating dose increases to achieve the desired therapeutic response. Conversely, drugs like troleandomycin and ketoconazole may inhibit the metabolism of corticosteroids, leading to decreased clearance and requiring careful titration of corticosteroid doses to avoid toxicity.

Corticosteroids can also affect the pharmacokinetics of other medications. For instance, they may increase the clearance of chronic high-dose aspirin, which could result in decreased salicylate serum levels or an increased risk of salicylate toxicity upon withdrawal of corticosteroids. Therefore, caution is advised when using aspirin in conjunction with corticosteroids, particularly in patients with hypoprothrombinemia.

The interaction of corticosteroids with oral anticoagulants is variable, with reports indicating both enhanced and diminished effects. Consequently, it is essential to monitor coagulation indices closely to maintain the desired anticoagulant effect.

Additionally, for medications such as KHINDIVI and ALKINDI SPRINKLE, concomitant administration with CYP3A4 inhibitors may necessitate a decrease in their doses, while CYP3A4 inducers may require an increase in their doses. The use of estrogen and estrogen-containing products may also necessitate an increase in the doses of these medications. Furthermore, excessive doses of antidiabetic agents may lead to increased blood glucose concentrations, warranting dose adjustments. The concomitant use of NSAIDs with these medications may elevate the risk of gastrointestinal adverse reactions.

Overall, careful consideration and monitoring are required when managing patients on corticosteroids and other interacting medications to ensure safety and efficacy.

Pediatric Use

Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced hypothalamic-pituitary-adrenal (HPA) axis suppression and Cushing’s syndrome than mature patients due to a larger skin surface area to body weight ratio. Reports indicate that HPA axis suppression, Cushing’s syndrome, and intracranial hypertension have been observed in pediatric patients receiving topical corticosteroids.

Efficacy and Safety:

• Manifestations of adrenal suppression in pediatric patients include linear growth retardation, delayed weight gain, low plasma cortisol levels, and absence of response to ACTH stimulation.

• Symptoms of intracranial hypertension may present as bulging fontanelles, headaches, and bilateral papilledema.

• Chronic corticosteroid therapy may interfere with the growth and development of pediatric patients.

Dosing Considerations:

• Administration of topical corticosteroids should be limited to the least amount compatible with an effective therapeutic regimen to minimize risks.

• In pediatric patients receiving hydrocortisone for juvenile rheumatoid arthritis, low-dose maintenance therapy may be required in selected cases.

Cautions:

• Growth and development of infants and children on prolonged corticosteroid therapy should be carefully monitored.

• Infants born to mothers who received substantial doses of corticosteroids during pregnancy should be observed for signs of hypoadrenalism.

• Caution is advised in patients with known or suspected Strongyloides infestation, as corticosteroid-induced immunosuppression may lead to severe complications.

Overall, careful consideration and monitoring are essential when prescribing corticosteroids to pediatric patients to mitigate potential adverse effects on growth and development.

Geriatric Use

Elderly patients may exhibit increased sensitivity to the side effects of corticosteroids, including hydrocortisone. While no specific dosage adjustments are universally recommended for geriatric patients, caution is advised due to potential age-related physiological changes, such as reduced kidney function.

For those receiving hydrocortisone therapy, particularly in the form of tablets, solutions, or enemas, the lowest effective dose should be utilized to minimize the risk of adverse effects. Close monitoring for side effects and therapeutic response is essential, especially in patients with comorbid conditions such as hypertension, osteoporosis, or renal insufficiency.

In cases where older patients are prescribed hydrocortisone, periodic evaluation for evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression is recommended, particularly for those on high doses or using occlusive dressings. Additionally, caution is warranted in patients with existing emotional instability or psychotic tendencies, as corticosteroids may exacerbate these conditions.

For older patients receiving medications like Khindivi or Alkindi, it may be appropriate to divide the daily dose by two and administer it twice daily. Overall, careful monitoring and individualized treatment plans are crucial for managing geriatric patients on corticosteroid therapy.

Pregnancy

Pregnant patients should be aware that corticosteroids are classified as Pregnancy Category C, indicating potential teratogenic effects. Animal studies have demonstrated that corticosteroids can be teratogenic when administered systemically at relatively low dosage levels, and more potent corticosteroids have shown teratogenicity following dermal application. However, there are no adequate and well-controlled studies in pregnant women to assess the teratogenic effects of topically applied corticosteroids.

Topical corticosteroids should only be used during pregnancy if the potential benefits justify the potential risks to the fetus. It is advised that these medications not be used extensively, in large amounts, or for prolonged periods in pregnant patients.

Observational studies regarding the use of hydrocortisone during pregnancy have not identified a clear drug-associated risk of major birth defects, miscarriage, or adverse maternal and fetal outcomes. However, there is some evidence suggesting a small increased risk of cleft lip with or without cleft palate associated with first trimester systemic corticosteroid use, although the data are limited and inconsistent.

Untreated adrenocortical insufficiency during pregnancy can lead to significant complications, including maternal mortality. The use of physiologic doses of hydrocortisone is not expected to cause major birth defects or adverse outcomes. Nevertheless, infants born to mothers who received substantial doses of corticosteroids during pregnancy should be monitored for signs of hypoadrenalism.

In summary, the use of corticosteroids in pregnant patients requires careful consideration of the potential benefits and risks, and close monitoring of both maternal and fetal health is essential.

Lactation

It is not known whether topical administration of corticosteroids can lead to sufficient systemic absorption to produce detectable quantities in breast milk. However, systemically administered corticosteroids are secreted into breast milk in amounts that are not likely to have a deleterious effect on breastfed infants.

Caution should be exercised when administering topical corticosteroids to lactating mothers. The use of hydrocortisone at physiologic doses for conditions such as adrenocortical insufficiency is not expected to adversely affect breastfed infants or milk production. Nonetheless, there is a lack of data regarding the presence of hydrocortisone in breast milk and its effects on breastfed infants.

The developmental and health benefits of breastfeeding should be carefully weighed against the mother's clinical need for corticosteroids and any potential adverse effects on the infant from either the medication or the underlying maternal condition. Additionally, infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be closely monitored for signs of hypoadrenalism.

Renal Impairment

Patients with renal impairment may require careful consideration when using corticosteroids, particularly topical formulations. Corticosteroids are primarily metabolized in the liver and excreted by the kidneys, which raises concerns regarding systemic absorption and potential effects in this patient population.

Systemic absorption of topical corticosteroids can lead to reversible hypothalamic-pituitary-adrenal (HPA) axis suppression. Therefore, it is recommended that patients with renal impairment who are receiving large doses of potent topical steroids, especially when applied to extensive areas of skin or under occlusive dressings, be monitored periodically for signs of HPA axis suppression. This monitoring can be conducted using urinary free cortisol and ACTH stimulation tests.

If HPA axis suppression is detected, it is advisable to consider withdrawing the corticosteroid, reducing the frequency of application, or substituting a less potent steroid. Recovery of HPA axis function is typically prompt and complete upon discontinuation of the corticosteroid. However, in some cases, patients may experience signs and symptoms of steroid withdrawal, which could necessitate the administration of supplemental systemic corticosteroids.

While specific dosage adjustments or safety considerations for patients with renal impairment are not universally provided across all corticosteroid formulations, caution should be exercised due to the potential for systemic effects.

Hepatic Impairment

Patients with hepatic impairment may experience altered metabolism and excretion of corticosteroids, which are primarily metabolized in the liver and excreted by the kidneys. Systemic absorption of topical corticosteroids can lead to reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, necessitating careful monitoring in this population.

For patients receiving a large dose of a potent topical steroid applied to a large surface area or under an occlusive dressing, periodic evaluation for evidence of HPA axis suppression is recommended. This can be assessed using urinary free cortisol and ACTH stimulation tests. If HPA axis suppression is detected, it is advisable to withdraw the drug, reduce the frequency of application, or substitute a less potent steroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the corticosteroid.

Additionally, patients with a history of hepatitis B infection should be screened prior to initiating immunosuppressive treatment with corticosteroids, as reactivation of the virus can occur. Consultation with specialists in hepatitis B management may be warranted for those with evidence of infection, including consideration for antiviral therapy.

Caution is also advised in patients with known or suspected Strongyloides infestation, as corticosteroid-induced immunosuppression may lead to severe complications. Furthermore, systemic fungal infections may be exacerbated by corticosteroid use; therefore, hydrocortisone should be avoided in such cases unless necessary to manage drug reactions.

Overall, careful monitoring and dosage adjustments may be required for patients with hepatic impairment to mitigate potential risks associated with corticosteroid therapy.

Overdosage

In cases of overdosage, management primarily involves supportive and symptomatic therapy. Symptoms associated with hydrocortisone overdosage may include hypertension, volume overload, edema, and hypokalemia. Average and large doses of hydrocortisone or cortisone can lead to elevated blood pressure, salt and water retention, and increased potassium excretion. These effects are less likely with synthetic derivatives unless administered in large doses.

Long-term overdosage of corticosteroids, including hydrocortisone, can result in Cushing's syndrome, characterized by obesity, moon facies, hypertension, diabetes, and other metabolic disturbances. Patients should be monitored for signs of overdosage, and dosage adjustments should be made as necessary. Dietary salt restriction and potassium supplementation may be required to manage electrolyte imbalances.

There is no specific antidote for hydrocortisone overdosage; therefore, in cases of suspected overdosage, appropriate medical intervention should be sought. Additionally, drug-induced secondary adrenocortical insufficiency may occur and can persist for months after discontinuation of therapy, necessitating the reinstitution of hormone therapy during periods of stress.

Nonclinical Toxicology

Teratogenic Effects

Corticosteroids are generally considered teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have demonstrated teratogenic effects following dermal application in laboratory animals. There are no adequate and well-controlled studies in pregnant women regarding the teratogenic effects of topically applied corticosteroids. Consequently, the use of topical corticosteroids during pregnancy should be limited to situations where the potential benefits justify the risks to the fetus. It is advised that these drugs not be used extensively, in large amounts, or for prolonged periods in pregnant patients.

Impairment of Fertility

Corticosteroids have been shown to impair fertility in male rats. However, long-term animal studies have not been conducted to evaluate the effects of topical corticosteroids on fertility in other species.

Carcinogenesis and Mutagenesis

Long-term animal studies have not been performed to assess the carcinogenic potential of topical corticosteroids. Studies aimed at determining mutagenicity with prednisolone and hydrocortisone have yielded negative results, indicating no mutagenic effects associated with these compounds.

Summary of Nonclinical Toxicology

In summary, while corticosteroids exhibit teratogenic effects in animal models and have been associated with fertility impairment in male rats, the lack of long-term studies limits the understanding of their carcinogenic potential. Furthermore, available mutagenicity studies have not indicated any adverse effects.

Storage and Handling

Procto-Med Hc is supplied as a cream and should be stored at 20-25°C (68-77°F) see USP Controlled Room Temperature. It must be kept out of the reach of children.

Hydrocortisone is available in various forms including tablets, lotion, ointment, solution, cream, suspension, and enema. The storage conditions for these forms generally require a controlled room temperature of 20° to 25°C (68° to 77°F), with some forms allowing excursions to 15° to 30°C (59° to 86°F) see USP Controlled Room Temperature. Specific handling instructions include keeping the products out of the reach of children and ensuring that the lotion is shaken well before use.

Khindivi, supplied as a solution, should be stored at 2°C to 25°C (36°F to 77°F), with excursions permitted to 30°C (86°F). It must be protected from light and heat, and any unused portion should be discarded if not used within 120 days of first opening.

Texacort, also a solution, should be stored at controlled room temperature of 15° to 30°C (59° to 86°F).

Alkindi, supplied as granules, should be stored in the original bottle to protect from light, at a controlled room temperature of 20°C to 25°C (68°F to 77°F), with excursions permitted to 15°C to 30°C (59°F to 86°F). The capsules must be used within 60 days after opening the bottle.

For Hydrocortisone rectal suspension and enema, storage at controlled room temperature of 20° to 25°C (68° to 77°F) is required.

Proctosol-Hc and Anusol, both creams, should be stored at 20° to 25°C (68° to 77°F) see USP Controlled Room Temperature and must be protected from freezing.

Hydrocortisone creams, ointments, and lotions have similar storage requirements, generally at 20° to 25°C (68° to 77°F) with some allowing excursions to 15° to 30°C (59° to 86°F). It is important to keep these products tightly closed and out of the reach of children.

Cortef tablets should be stored at controlled room temperature of 20° to 25°C (68° to 77°F) see USP.

Proctozone-Hc cream must be kept tightly closed and stored at 20° to 25°C (68° to 77°F), with excursions permitted to 15° to 30°C (59° to 86°F) see USP Controlled Room Temperature.