Hydrocortisone

Hydrocortisone is a Glucocorticoid / Corticosteroid belonging to antihemorrhoidal / anti-inflammatory agent.

Hydrocortisone is a glucocorticoid used to treat corticosteroid-responsive dermatoses, endocrine disorders, immune conditions, and allergic disorders.

Hydrocortisone readily absorbed from the gastrointestinal tract; rapidly absorbed after IM injection (Na succinate, Na phosphate); slowly absorbed after intra-articular or soft tissue injection (acetate); partially absorbed after rectal administration; absorbed through the skin. The bioavailability is about 96 ± 20%. The time to peak plasma concentration is approximately 1 hour. Hydrocortisone rapidly distributed to body tissues. Hydrocortisone crosses the placenta and enters breast milk (small amounts). The volume of distribution is about 27 ± 7 L. the plasma protein binding is about >90%, to corticosteroid-binding globulin (CBG) and albumin. Hydrocortisone metabolized in the liver and most body tissues into hydrogenated and degraded forms (e.g. tetrahydrocortisone, tetrahydrocortisol). Hydrocortisone excreted via urine (mainly conjugated as glucuronides; small amounts as unchanged drug). Elimination half-life: 1.8 ± 0.5 hour (oral); 2 ± 0.3 hours (IV).

Hydrocortisone shows common side effects like Headache, dizziness, local pain or burning, muscle weakness, extreme changes in mood changes in personality, inappropriate happiness, difficulty falling asleep or staying asleep, slowed healing of cuts and bruises, irregular or absent menstrual periods, thin, fragile, or dry skin, acne, increased sweating, changes in the way fat is spread around the body.

Hydrocortisone is available in the form of Oral Tablet, Injectable solution, Suspension, Cream, Lotion, Form, Enema, Ointment and Rectal Suppositories.

Hydrocortisone is available in India, US, Canada, Spain, France, Italy, Malaysia, China, Russia, Singapore, and Australia.

Hydrocortisone belongs to the anti-inflammatory agent acts as a Glucocorticoid / Corticosteroid.

Hydrocortisone inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10. Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.

The onset and duration of action of Hydrocortisone is not clinically established.

The Tmax of Hydrocortisone is approximately 1 hours.

Hydrocortisone is available in the form of Oral Tablet, Injectable solution, Suspension, Cream, Lotion, Form, Enema, Ointment and Rectal Suppositories.

Hydrocortisone is like a natural hormone produced in the body which affects many functions in the body. It is used to relieve swelling and pain associated with conditions like arthritis, severe allergies, eczema, psoriasis, etc. It is also used to treat the deficiency of steroidal hormones in the body.

Hydrocortisone is a Glucocorticoid / Corticosteroid belonging to antihemorrhoidal / anti-inflammatory agent.

Hydrocortisone short-acting corticosteroid with minimal sodium-retaining potential; decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability.

Hydrocortisone is approved for use in the following clinical indications

Oral

• Anti-inflammatory or immunosuppressive
• Replacement therapy in adrenocortical insufficiency

Buccal

• Aphthous ulcer

Parenteral

• Anti-inflammatory or immunosuppressive
• Acute adrenocortical insufficiency
• Severe shock
• Adjunct in the emergency treatment of anaphylactic shock
• Status asthmaticus

Intravenous

• As supplement in adrenal insufficiency during minor surgery under general anaesthesia
• As supplement in adrenal insufficiency during moderate or major surgery
• Soft tissue inflammation
• Inflammatory joint diseases

Ophthalmic

• Inflammatory eye disorders

Rectal

• Ulcerative colitis
• Haemorrhoids

Topical/Cutaneous

• Corticosteroid-responsive dermatoses

Oral

• Anti-inflammatory or immunosuppressive

Adult: Usual range: Initially, 20-240 mg daily. Dosage is individualised and adjusted according to the disease being treated, the severity of the condition, and patient response. Refer to the disease-specific product guidelines for detailed dosage recommendations.

• Replacement therapy in adrenocortical insufficiency
• Adult: Dosage is individualised and adjusted according to patient response. As conventional tab: 20-30 mg daily in 2 divided doses, the larger dose to be given in the morning and the smaller in the evening; may be given together with NaCl or fludrocortisone. As modified-release tab: 20-30 mg once daily in the morning.
• Child: As conventional tab: 0.4-0.8 mg/kg daily in 2 or 3 divided doses; individualised and adjusted according to patient needs.

Buccal

• Aphthous ulcer

Adult: For previously diagnosed cases of the mouth whether simple or occurred as a complication in diseases: As hydrocortisone Na succinate buccal tab: Dissolve 1 tab (2.5 mg) slowly in the mouth (placed near the lesions) 4 times daily for 5 days. Do not suck the buccal tab.

Child: ≥12 years Same as adult dose.

Parenteral

• Anti-inflammatory or immunosuppressive

Adult: As hydrocortisone Na succinate: 100-500 mg via IV inj over 0.5-10 minutes, IV infusion over 20-30 minutes or IM inj; may be repeated at intervals of 2, 4, or 6 hours. Max duration: 48-72 hours. Dosage is individualised and adjusted according to the disease being treated, the severity of the condition, and patient response. Refer to the disease-specific product guidelines for detailed dosage recommendations.

Child: As hydrocortisone Na succinate: Initially, 0.5-8 mg/kg daily or 20-240 mg/m² daily in 3 or 4 divided doses. Alternatively, >25 mg daily. Dosage is individualised and adjusted according to the disease being treated, the severity of the condition, and patient response. Refer to the disease-specific product guidelines for detailed dosage recommendations.

• Acute adrenocortical insufficiency

Adult: Adjunct to adrenaline in anaphylactic shock: As hydrocortisone Na phosphate, or Na succinate: 100-500 mg via slow IV inj over 0.5-1 minute, may be repeated 3 or 4 times in 24 hours according to the disease being treated, the severity of the condition, and patient response. Alternatively, doses may be given via IV infusion, or IM inj (response is less rapid). Fluids and electrolytes must be given as needed to correct any metabolic disorder.

Child: As hydrocortisone Na phosphate: <1 year 25 mg; 1-5 years 50 mg; 6-12 years 100 mg. Doses are given intravenously; may be repeated 3 or 4 times in 24 hours according to the disease being treated, the severity of the condition, and patient response.

• Severe shock

Adult: Adjunct to adrenaline in anaphylactic shock: As hydrocortisone Na phosphate, or Na succinate: 100-500 mg via slow IV inj over 0.5-1 minute, may be repeated 3 or 4 times in 24 hours according to the disease being treated, the severity of the condition, and patient response. Alternatively, doses may be given via IV infusion, or IM inj (response is less rapid). Fluids and electrolytes must be given as needed to correct any metabolic disorder.

Child: As hydrocortisone Na phosphate: <1 year 25 mg; 1-5 years 50 mg; 6-12 years 100 mg. Doses are given intravenously; may be repeated 3 or 4 times in 24 hours according to the disease being treated, the severity of the condition, and patient response.

• Adjunct in the emergency treatment of anaphylactic shock

Adult: Adjunct to adrenaline in anaphylactic shock: As hydrocortisone Na phosphate, or Na succinate: 100-500 mg via slow IV inj over 0.5-1 minute, may be repeated 3 or 4 times in 24 hours according to the disease being treated, the severity of the condition, and patient response. Alternatively, doses may be given via IV infusion, or IM inj (response is less rapid). Fluids and electrolytes must be given as needed to correct any metabolic disorder.

Child: As hydrocortisone Na phosphate: <1 year 25 mg; 1-5 years 50 mg; 6-12 years 100 mg. Doses are given intravenously; may be repeated 3 or 4 times in 24 hours according to the disease being treated, the severity of the condition, and patient response.

• Status asthmaticus

Adult: Adjunct to adrenaline in anaphylactic shock: As hydrocortisone Na phosphate, or Na succinate: 100-500 mg via slow IV inj over 0.5-1 minute, may be repeated 3 or 4 times in 24 hours according to the disease being treated, the severity of the condition, and patient response. Alternatively, doses may be given via IV infusion, or IM inj (response is less rapid). Fluids and electrolytes must be given as needed to correct any metabolic disorder.

Child: As hydrocortisone Na phosphate: <1 year 25 mg; 1-5 years 50 mg; 6-12 years 100 mg. Doses are given intravenously; may be repeated 3 or 4 times in 24 hours according to the disease being treated, the severity of the condition, and patient response.

Intravenous

• As supplement in adrenal insufficiency during minor surgery under general anaesthesia
• Adult: In patients taking >10 mg daily of oral prednisolone or its equivalent: As hydrocortisone Na succinate: 25-50 mg at induction via inj or infusion. Resume the usual oral corticosteroid dose after surgery.
• As supplement in adrenal insufficiency during moderate or major surgery
• Adult: In patients taking >10 mg daily of oral prednisolone or its equivalent: As hydrocortisone Na succinate: Usual oral corticosteroid dose on the morning of surgery, followed by 25-50 mg at induction via inj or infusion, then 25-50 mg tid via inj for 24 hours after moderate surgery or 48-72 hours after major surgery. Resume the usual oral corticosteroid dose once the injections are stopped.
• Soft tissue inflammation

Adult: As hydrocortisone Na phosphate: 100-200 mg as local inj into soft tissue lesions; may be repeated on 2 or 3 occasions according to patient response.

• Inflammatory joint diseases

Adult: As hydrocortisone acetate: 5-50 mg depending on the size of the affected joint via intra-articular or periarticular inj; may be repeated at intervals of 3 weeks. Max: 3 joints treated per day.

Ophthalmic

• Inflammatory eye disorders

Adult: As 1% hydrocortisone acetate ointment: Apply 2-4 times daily. As 1% hydrocortisone acetate drops: Severe inflammation: Instil 1 or 2 drops every 30-60 minutes until satisfactory response occurs. Dosage and treatment duration may vary according to the severity of the condition and patient response.

Rectal

• Ulcerative colitis

Adult: Adjunctive treatment particularly in distal forms, including ulcerative proctitis, ulcerative proctosigmoiditis, and left-sided ulcerative colitis: As hydrocortisone base 100 mg/60 mL retention enema: 1 enema at night for 3 weeks or until the patient comes into clinical and proctological remission. In patients who cannot retain enemas: As 10% hydrocortisone acetate foam: 90 mg (1 applicatorful) 1 or 2 times daily for 2-3 weeks, then reduced to every other day. Dosage and treatment duration may vary according to the severity of the condition and patient response.

• Haemorrhoids

Adult: As hydrocortisone acetate supp: Insert 1 supp (25 mg) bid. Dosage and treatment duration may vary according to the severity of the condition and patient response.

Topical/Cutaneous

• Corticosteroid-responsive dermatoses

Adult: As 0.1% hydrocortisone base cream, 0.1% hydrocortisone butyrate cream/ointment/scalp lotion, 0.1% hydrocortisone probutate cream, 1% hydrocortisone acetate cream: Apply thinly to affected areas 1 or 2 times daily. As 1-2.5% hydrocortisone base ointment, 0.1% hydrocortisone butyrate solution, 0.2% hydrocortisone valerate cream/ointment: Apply thinly to affected areas 2 or 3 times daily. Dosage and treatment duration may vary according to the severity of the condition and patient response.

Child: As 0.1% hydrocortisone base cream: >10 years Same as adult dose. As 1-2.5% hydrocortisone base ointment, 0.1% hydrocortisone butyrate cream/ointment/scalp lotion: Same as adult dose; avoid prolonged treatment if possible. Max treatment duration in infants: 7 days.

Hydrocortisone is available in various strengths as 10 mg; 20 mg; 50 mg/mL; 1000 mg preservative-free; 100 mg preservative-free; 5 mg; 250 mg preservative-free; 500 mg preservative-free; 10 mg/5 mL; 100 mg; 250 mg; 500 mg; 1 g; 10%; 100 mg/60 mL; 25 mg/mL; 0.5 mg; 1 mg; 2 mg.

Hydrocortisone is available in the form of Oral Tablet, Injectable solution, Suspension, Cream, Lotion, Form, Enema, Ointment and Rectal Suppositories.

Follow a low-salt, high potassium, or high calcium diet.

Hydrocortisone is contraindicated in patients with

• Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Patients receiving >20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections.
• Anaphylactoid reactions: rare cases of anaphylactoid reactions have been observed in patients receiving corticosteroids.
• Dermal changes: Avoid injection or leakage into the dermis; dermal and/or subdermal skin depression may occur at the site of injection. Avoid deltoid muscle injection; subcutaneous atrophy may occur.
• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to killed or inactivated vaccines. Exposure to chickenpox or measles should be avoided. Corticosteroids should not be used for cerebral malaria, fungal infections, or viral hepatitis. Close observation is required in patients with latent tuberculosis (TB) and/or TB reactivity; restrict use in active TB (only fulminating or disseminated TB in conjunction with antituberculosis treatment). Latent or active amebiasis should be ruled out in any patient with recent travel to tropical climates or unexplained diarrhea prior to corticosteroid initiation. Use with extreme caution in patients with Strongyloides infections; hyperinfection, dissemination and fatalities have occurred.
• Kaposi sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi sarcoma (case reports); if noted, discontinuation of therapy should be considered.
• Myopathy: Acute myopathy has been reported with high dose corticosteroids, usually in patients with neuromuscular transmission disorders; may involve ocular and/or respiratory muscles; monitor creatine kinase; recovery may be delayed.
• Psychiatric disturbances: Corticosteroid use may cause psychiatric disturbances, including euphoria, insomnia, mood swings, personality changes, severe depression, or psychotic manifestations. Symptoms usually occur within a few days or weeks of initiation of treatment and usually resolve with dose reduction or discontinuation; monitor for signs and symptoms of behavioral or mood changes. Preexisting psychiatric conditions may be exacerbated by corticosteroid use.

Hydrocortisone is not recommended for use in breastfeeding women unless necessary. The risks and benefits should be discussed with the doctor before using Hydrocortisone.

Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Follow a low-salt, high potassium, or high calcium diet.

• Common

Bradycardia, cardiac arrhythmia, cardiac failure (especially in susceptible patients), cardiomegaly, circulatory shock, embolism (fat), hypertension, hypertrophic cardiomyopathy (premature infants), myocardial rupture (post-myocardial infarction), syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis, Acne vulgaris, allergic dermatitis, atrophic striae, burning sensation of skin (especially in the perineal area after IV injection), diaphoresis, ecchymoses, erythema of skin, facial erythema, hyperpigmentation, hypertrichosis, hypopigmentation, inadvertent suppression of skin test reaction, skin rash, thinning hair, urticaria, xeroderma, Adrenocortical insufficiency (secondary unresponsiveness, particularly during trauma, surgery, or illness), Cushing syndrome, decreased serum potassium, drug-induced Cushing’s syndrome, fluid retention, glycosuria, growth retardation, hirsutism, HPA-axis suppression, hyperglycemia (including increased requirements for insulin or oral hypoglycemic agents in diabetes mellitus), hypokalemic alkalosis, impaired glucose tolerance/prediabetes, lipodystrophy, manifestation of prediabetes, menstrual disease, moon face, negative nitrogen balance (due to protein catabolism), pituitary insufficiency (secondary unresponsiveness, particularly during trauma, surgery, or illness), protein catabolism, sodium retention, weight gain, Abdominal distention, gastrointestinal perforation (small and large intestine, particularly in patients with inflammatory bowel disease), hiccups, impaired intestinal carbohydrate absorption, increased appetite, nausea, pancreatitis, peptic ulcer (with possible perforation and hemorrhage), ulcerative esophagitis, Depression, emotional lability, euphoria, headache, increased intracranial pressure (with pseudotumor cerebri; usually following discontinuation), insomnia, malaise, myasthenia, neuritis, neuropathy, paresthesia, personality changes, psychic disorder, seizure, tingling of skin (especially in the perineal area after IV injection), vertigo, Amyotrophy, aseptic necrosis of femoral head, aseptic necrosis of humeral head, Charcot arthropathy, osteoporosis, pathological fracture (long bones), rupture of tendon (particularly rupture of Achilles tendon), steroid myopathy, vertebral compression fracture, Blindness (rare, periocular injection), exophthalmos, glaucoma, increased intraocular pressure, retinopathy (central serous chorioretinopathy), subcapsular posterior cataract, Pulmonary edema, Wound healing impairment.

● Abrocitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Abrocitinib. Management: The use of abrocitinib in combination with other immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive.

● Acetylcholinesterase Inhibitors: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur.

● Antacids: May decrease the bioavailability of Corticosteroids (Oral). Management: Consider separating doses by 2 or more hours. Budesonide enteric coated tablets could dissolve prematurely if given with drugs that lower gastric acid, with unknown impact on budesonide therapeutic effects.

● Baricitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Baricitinib. Management: The use of baricitinib in combination with potent immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive.

● BCG Products: Corticosteroids (Systemic) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of BCG Products.

● CAR-T Cell Immunotherapy: Corticosteroids (Systemic) may enhance the adverse/toxic effect of CAR-T Cell Immunotherapy. Specifically, the severity and duration of neurologic toxicities may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of CAR-T Cell Immunotherapy. Management: Avoid use of corticosteroids as premedication before treatment with CAR-T cell immunotherapy agents. Corticosteroids are indicated and may be required for treatment of toxicities such as cytokine release syndrome or neurologic toxicity.

● Corticorelin: Corticosteroids (Systemic) may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy.

● Cosyntropin: Hydrocortisone (Systemic) may diminish the diagnostic effect of Cosyntropin. Management: Patients receiving hydrocortisone should omit their pre-test dose on the day selected for cosyntropin testing.

● CYP3A4 Inducers (Moderate): May decrease the serum concentration of Hydrocortisone (Systemic).

● CYP3A4 Inducers (Strong): May decrease the serum concentration of Hydrocortisone (Systemic).

● CYP3A4 Inhibitors (Strong): May increase the serum concentration of Hydrocortisone (Systemic).

● Dengue Tetravalent Vaccine: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live).

● Denosumab: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and systemic corticosteroids. If combined, monitor patients for signs/symptoms of serious infections.

● Desirudin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Desirudin. More specifically, corticosteroids may increase hemorrhagic risk during desirudin treatment. Management: Discontinue treatment with systemic corticosteroids prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation.

● Deucravacitinib: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Management: The use of deucravacitinib in combination with potent immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive.

● Estrogen Derivatives: May increase the serum concentration of Hydrocortisone (Systemic). Estrogen Derivatives may decrease the serum concentration of Hydrocortisone (Systemic).

● Filgotinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Filgotinib. Management: Coadministration of filgotinib with systemic corticosteroids at doses equivalent to greater than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks is not recommended.

● Hyaluronidase: Corticosteroids (Systemic) may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required.

● Immune Checkpoint Inhibitors: Corticosteroids (Systemic) may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Management: Carefully consider the need for corticosteroids, at doses of a prednisone-equivalent of 10 mg or more per day, during the initiation of immune checkpoint inhibitor therapy. Use of corticosteroids to treat immune related adverse events is still recommended.

● Influenza Virus Vaccines: Corticosteroids (Systemic) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiation of systemic corticosteroids at immunosuppressive doses. Influenza vaccines administered less than 14 days prior to or during such therapy should be repeated 3 months after therapy.

● Leflunomide: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as systemic corticosteroids.

● Mifepristone: May diminish the therapeutic effect of Corticosteroids (Systemic). Mifepristone may increase the serum concentration of Corticosteroids (Systemic). Management: Avoid mifepristone in patients who require long-term corticosteroid treatment of serious illnesses or conditions (eg, for immunosuppression following transplantation). Corticosteroid effects may be reduced by mifepristone treatment.

● Neuromuscular-Blocking Agents (Nondepolarizing): May enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Management: If concomitant therapy is required, use the lowest dose for the shortest duration to limit the risk of myopathy or neuropathy. Monitor for new onset or worsening muscle weakness, reduction or loss of deep tendon reflexes, and peripheral sensory decriments.

● Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective).

● Nonsteroidal Anti-Inflammatory Agents (Nonselective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective).

● Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Corticosteroids (Systemic). Specifically, the risk of gastrointestinal bleeding, ulceration, and perforation may be increased.

● Pimecrolimus: May enhance the immunosuppressive effect of Corticosteroids (Systemic).

● Pneumococcal Vaccines: Corticosteroids (Systemic) may diminish the therapeutic effect of Pneumococcal Vaccines.

● Ruxolitinib (Topical): Corticosteroids (Systemic) may enhance the immunosuppressive effect of Ruxolitinib (Topical).

● Salicylates: May enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity.

● Sargramostim: Corticosteroids (Systemic) may enhance the therapeutic effect of Sargramostim. Specifically, corticosteroids may enhance the myeloproliferative effects of sargramostim.

● Succinylcholine: Corticosteroids (Systemic) may enhance the neuromuscular-blocking effect of Succinylcholine.

● Tacrolimus (Systemic): Corticosteroids (Systemic) may decrease the serum concentration of Tacrolimus (Systemic). Conversely, when discontinuing corticosteroid therapy, tacrolimus concentrations may increase. Ris

● Tacrolimus (Topical): Corticosteroids (Systemic) may enhance the immunosuppressive effect of Tacrolimus (Topical).

● Talimogene Laherparepvec: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased.

● Tertomotide: Corticosteroids (Systemic) may diminish the therapeutic effect of Tertomotide.

● Thiazide and Thiazide-Like Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics.

● Tofacitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive.

● Typhoid Vaccine: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Typhoid Vaccine.

● Upadacitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Upadacitinib. Management: Coadministration of upadacitinib with systemic corticosteroids at doses equivalent to greater than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks is not recommended.

● Urea Cycle Disorder Agents: Corticosteroids (Systemic) may diminish the therapeutic effect of Urea Cycle Disorder Agents. More specifically, Corticosteroids (Systemic) may increase protein catabolism and plasma ammonia concentrations, thereby increasing the doses of Urea Cycle Disorder Agents needed to maintain these concentrations in the target range.

● Vaccines (Inactivated/Non-Replicating): Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Administer vaccines at least 2 weeks prior to immunosuppressive corticosteroids if possible. If patients are vaccinated less than 14 days prior to or during such therapy, repeat vaccination at least 3 months after therapy if immunocompetence restored.

● Vitamin K Antagonists (eg, warfarin): Corticosteroids (Systemic) may enhance the anticoagulant effect of Vitamin K Antagonists.

The common side effects of Hydrocortisone include the following

• Common side effects

Headache, dizziness, local pain or burning, muscle weakness, extreme changes in mood changes in personality, inappropriate happiness, difficulty falling asleep or staying asleep, slowed healing of cuts and bruises, irregular or absent menstrual periods, thin, fragile, or dry skin, acne, increased sweating, changes in the way fat is spread around the body.

• Rare side effects

Bleeding, vision changes, depression, rash, itching, swelling of the eyes, face, lips, tongue, throat, hands, arms, feet, ankles, or lower legs, hives, difficulty breathing or swallowing.

• Pregnancy

Pregnancy Category C and D

Since adequate human reproduction studies have not been done with corticosteroids, the use of these drugs in pregnancy, nursing mothers or women of child-bearing potential requires that the possible benefits of the drug be weighed against the potential hazards to the mother and embryo or fetus. Neonates born of mothers who have received substantial doses of corticosteroid during pregnancy should be carefully observed for signs of hypoadrenalism.

• Nursing Mothers

Endogenous hydrocortisone (cortisol) is present in the breast milk. Corticosteroids (i.e. prednisone) have been detected in breast milk in low amounts, however, specific information on this drug in breast milk is not known. Theoretically, the presence of exogenous corticosteroids in breast milk could suppress growth, interfere with endogenous corticosteroid production, or cause other unwanted effects in breast fed babies. The use of this drug for replacement therapy is unlikely to have any clinically significant impact, however, it is presumed that breastfed infants of mothers taking high doses of systemic corticosteroids for prolonged periods of time may be at risk of adrenal suppression.

• Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Growth and development of pediatric patients on prolonged corticosteroid therapy should be carefully observed.

Symptoms: Nausea, vomiting, hyperglycemia, Na and water retention, gastrointestinal bleeding, hypokalemia, high blood pressure, excitement, mania or psychosis.

Management: Symptomatic and supportive treatment. May administer slow IV inj of cimetidine or ranitidine for gastrointestinal bleeding.

Pharmacodynamic

Hydrocortisone binds to the glucocorticoid receptor leading to downstream effects such as inhibition of phospholipase A2, NF-kappa B, other inflammatory transcription factors, and the promotion of anti-inflammatory genes. Hydrocortisone has a wide therapeutic index and a moderate duration of action. Patients should stop taking the medication if irritation or sensitization occurs.

Pharmacokinetics

• Absorption

Hydrocortisone readily absorbed from the gastrointestinal tract; rapidly absorbed after IM injection (Na succinate, Na phosphate); slowly absorbed after intra-articular or soft tissue injection (acetate); partially absorbed after rectal administration; absorbed through the skin. The bioavailability is about 96 ± 20%. The time to peak plasma concentration is approximately 1 hour.

• Distribution

Hydrocortisone rapidly distributed to body tissues. Hydrocortisone crosses the placenta and enters breast milk (small amounts). The volume of distribution is about 27 ± 7 L. the plasma protein binding is about >90%, to corticosteroid-binding globulin (CBG) and albumin.

• Metabolism

Hydrocortisone metabolized in the liver and most body tissues into hydrogenated and degraded forms (e.g. tetrahydrocortisone, tetrahydrocortisol).

• Excretion

Hydrocortisone excreted via urine (mainly conjugated as glucuronides; small amounts as unchanged drug). Elimination half-life: 1.8 ± 0.5 hour (oral); 2 ± 0.3 hours (IV).

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