Chemical formula: C₂₁H₃₀O₅ Molecular mass: 362.46 g/mol PubChem compound: 5754
Hydrocortisone interacts in the following cases:
The renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication.
Potent CYP 3A4 inducers such as phenytoin, rifabutin, primidone, carbamazepine, aminoglutethimide, barbiturates (e.g. phenobarbital), rifampicin, St John’s wort and less potent inducers such as the antiretroviral medicinal products efavirenz and nevirapine can enhance the metabolic clearance of cortisol, decrease terminal half-life and thus reduce circulating levels and increase fluctuations of cortisol (due to shorter terminal half-life). This may require dose adjustment of hydrocortisone.
Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.
Potent CYP 3A4 inhibitors such as ketoconazole, itraconazole, posaconazole, voriconazole, erythromycin, telithromycin, clarithromycin, ritonavir and grapefruit juice can inhibit the metabolism of hydrocortisone and thus increase blood levels. During long-term prophylactic treatment with any of the antibiotics, adjustment of the hydrocortisone dosage should be considered.
The desired effects of hypoglycaemic agents (including insulin) are antagonised by corticosteroids.
The efficacy of coumarin anticoagulants may be enhanced by concurrent corticosteroid therapy and close monitoring of the INR or prothrombin time is required to avoid spontaneous bleeding.
The desired effects of anti-hypertensives and diuretics are antagonised by corticosteroids.
Oestrogens and other oral contraceptives increase the plasma concentration of corticosteroids and dosage adjustments may be required if oral contraceptives are added to or withdrawn from a stable dosage regimen.
Steroids may reduce the effects of anticholinesterases in myasthenia gravis and cholecystographic x-ray media.
Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) with corticosteroids increases the risk of gastrointestinal bleeding and ulceration.
The hypokalaemic effects of acetazolamide, loop diuretics, thiazide diuretics and carbenoxolone are enhanced by corticosteroids.
The risk of hypokalaemia also increases if high doses of corticosteroids are given with high doses of sympathomimetics e.g. bambuterol, fenoterol, formoterol, ritodrine, salbutamol, salmeterol and terbutaline.
Concomitant use with methotrexate may increase the risk of haematological toxicity.
Mifepristone may reduce the effect of corticosteroids for 3-4 days.
Rifampicin, rifabutin, carbamazepine, phenobarbital, phenytoin, primidone, ephedrine and aminoglutethimide enhance the metabolism of corticosteroids and their therapeutic effects may be reduced.
The growth promoting effect of somatropin may be inhibited by the concomitant use of corticosteroids.
The risk of hypokalaemia is increased with theophylline and amphotericin. Corticosteroids should not be given concomitantly with amphotericin, unless required to control reactions.
Corticosteroids should NOT be used in the treatment of cerebral oedema associated with acute head injury or cerebrovascular accident, as they are unlikely to be of benefit and may even be harmful.
Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.
The ability of corticosteroids to cross the placenta varies between individual drugs; however, hydrocortisone readily crosses the placenta.
Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate, intra-uterine growth retardation and affects on brain growth and development.
There is no evidence that corticosteroids result in an increased incidence of congenital abnormalities, such as cleft palate/lip in man. However, when administered for prolonged periods or repeatedly during pregnancy, corticosteroids may increase the risk of intra-uterine growth retardation. Hypoadrenalism may, in theory, occur in the neonate following prenatal exposure to corticosteroids but it is usually resolved spontaneously following birth and is rarely clinically important. As with all drugs, corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks. When corticosteroids are essential however, patients with normal pregnancies may be treated as though they were in the non-gravid states.
Patients with pre-eclampsia or fluid retention require close monitoring.
Depression of hormone levels has been described in pregnancy but the significance of this finding is not clear.
Hydrocortisone is excreted in breast milk. Doses of up to 200 mg daily of cortisone are unlikely to cause systemic effects in the infant.
Infants of mothers taking higher doses than this may have a degree of adrenal suppression but the benefits of breast feeding are likely to outweigh any theoretical risk.
There is no evidence against topical use in lactating women. However, caution should be exercised when hydrocortisone cream is administered to nursing mothers. In this event, the product should not be applied to the chest area. There is theoretical risk of infant adrenal function impairment if maternal systemic absorption occurs.
Patients with adrenal insufficiency have been shown to have reduced parity, which is most likely due to the underlying disease, but there is no indication that hydrocortisone in doses for replacement therapy will affect fertility.
Hydrocortisone may cause changes in vision and/or muscle weakness. If you have any of these symptoms you should not drive or operate machinery.
Hydrocortisone after topical application does not affect the ability to drive and use machines.
The incidence of predictable undesirable effects, including hypothalamic-pituitary-adrenal suppression correlates with the relative potency of the drug, dosage, timing of administration and the duration of treatment.
Adverse events are which have been associated with hydrocortisone are given below, listed by system organ class and frequency.
Undesirable effects are especially likely to occur at treatment onset or at dose increase.
The undesirable effects are listed below by organ class and the following frequency convention: Very common: (≥1/10), Common: (≥1/100 to <1/10), Uncommon: (≥1/1,000 to <1/100), Rare: (≥1/10,000 to <1/1,000), Very rare: (<1/10,000), Not known – cannot be estimated from the available data.
The following side effects may be associated with the long-term systemic use of corticosteroids.
Not known: Gastroenteritis. Upper respiratory tract infection. Viral infection. Increased susceptibility and severity of infections with suppression of clinical symptoms and signs, opportunistic infections, recurrence of dormant tuberculosis, activation of fungal and viral infections including herpes
Not known: Leukocytosis.
Not known: Hypersensitivity, anaphylaxis.
Not known: Negative protein and calcium balance. Sodium and fluid retention. Oedema tendency. Alkalosis hypokalaemic. Hypokalaemia. Increased appetite.
Common: A wide range of psychiatric reactions including affective disorders (such as irritable, euphoric, depressed and labile mood and suicidal thoughts), psychotic reactions (including mania, delusions, hallucinations and aggravation of schizophrenia), behavioural disturbance, irritability, anxiety, sleep disturbances and cognitive dysfunction including confusion and amnesia have been reported.
Not known: Psychosis with hallucinations and delirium. Mania. Euphoria
Not known: Aggravation of epilepsy. Sedation. Increased intracranial pressure with papilloedema in children (pseudotumour cerebri), usually after treatment withdrawal.
Not known: Increased intraocular pressure. Glaucoma. Papilloedema. Posterior subcapsular cataracts. Corneal or scleral thinning. Dry eye. Exacerbation of ophthalmic viral or fungal diseases, vision, blurred.
Not known: Vertigo.
Not known: Myocardial rupture following recent myocardial infarction.
Not known: Hypertension. Thromboembolism.
Not known: Dyspepsia. Peptic ulceration with perforation and haemorrhage. Deterioration of existing gastric ulcer. Abdominal distension. Oesophageal ulcer. Oesophagitis. Upper abdominal pain. Tooth erosion. Candidiasis. Acute pancreatitis. Gastritis. Nausea.
Not known: Impaired healing. Skin atrophy. Contusion. Ecchymosis. Skin striae. Rash pruritic. Cushing-like symptoms. Acne. Telangiectasia. Hirsutism.
Not known: Proximal myopathy. Osteoporosis and spontaneous fractures. Vertebral and long bone fractures. Avascular osteonecrosis. Tendon rupture. Joint swelling.
Not known: Malaise. Fatigue.
Not known: Suppression of the hypothalamo-pituitary-adrenal axis. Growth retardation in infancy, childhood and adolescence. Cushingoid facies. Induction of glucose intolerance or diabetes mellitus.
Not known: Menstruation irregular and amenorrhoea.
Not known: Hypokalaemic alkalosis
Not known: Weight increased. High density lipoprotein decreased. Blood potassium decreased.
a Reactions are common and may occur in both adults and children. In adults, the frequency of severe reactions have been estimated to be 5-6%. Psychological effects have been reported on withdrawal of corticosteroids and psychological dependence has occurred; the frequency is not known.
Too rapid a reduction of corticosteroid dosage following prolonged treatment can lead to acute adrenal insufficiency, hypotension and death. A withdrawal syndrome may also occur including pyrexia, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin modules and weight loss.
Paraesthesia may occur following intravenous administration and is probably related to the rate of injection. It is often localised to the genital area but in some cases may radiate over the entire body. The unpleasant and sometimes painful sensation usually passes off within a few minutes and no sequelae have been reported. The effect seems to be related to the sodium phosphate salt of hydrocortisone.
The incidence of predictable undesirable effects, including hypothalamic-pituitary-adrenal suppression correlates with the relative potency of the drug, dosage, timing of administration and the duration of treatment.
Endocrine/metabolic: Suppression of the hypothalamic-pituitary-adrenal axis, growth suppression in infancy, childhood and adolescence, menstrual irregularity and amenorrhoea, cushingoid faces, hirsutism, weight gain, impaired carbohydrate tolerance with increased requirement for anti-diabetic therapy. Negative protein and calcium balance. Increased appetite.
Anti-inflammatory and immunosuppressive effects: Increased susceptibility and severity of infections with suppression of clinical symptoms and signs, opportunistic infections, recurrence of dormant tuberculosis.
Musculoskeletal: Osteoporosis, vertebral and long bone fractures, avascular osteonecrosis, tendon rupture. Proximal myopathy.
Fluid and electrolyte disturbance: Sodium and water retention, hypertension, potassium loss, hypokalaemic alkalosis.
Neuropsychiatric: Euphoria, psychological dependence, depression, insomnia, aggravation of schizophrenia and increased intra-cranial pressure with papilloedema in children (pseudotumour cerebri), usually after treatment withdrawal. Aggravation of epilepsy.
Ophthalmic: Increased intra-ocular pressure, glaucoma, papilloedema, posterior subcapsular cataracts, corneal or scleral thinning, exacerbation of ophthalmic viral or fungal diseases.
Not known: Vision, blurred.
Gastrointestinal: Dyspepsia, peptic ulceration with perforation and haemorrhage, acute pancreatitis, candidiasis.
Dermatological: Impaired healing, skin atrophy, bruising, telangiectasia, striae, acne.
General: Hypersensitivity, including anaphylaxis, has been reported. Leucocytosis. Thrombo-embolism. Flushing and pruritus.
Too rapid a reduction of corticosteroid dosage following prolonged treatment can lead to adrenal insufficiency, hypotension and death.
A ‘withdrawal syndrome’ may also occur including, fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight.
Corticosteroids cause dose-related growth retardation in infancy, childhood and adolescence, which may be irreversible.
The common adverse effects of systemic corticosteroids may be associated with more serious consequences in old age, especially osteoporosis, hypertension, hypokalaemia, diabetes, susceptibility to infections and thinning of the skin. Close clinical supervision is required to avoid life-threatening reactions.
A wide range of psychiatric reactions including affective disorders (such as irritable, euphoric, depressed and labile mood, and suicidal thoughts), psychotic reactions (including mania, delusions, hallucinations, and aggravation of schizophrenia), behavioural disturbances, irritability, anxiety, sleep disturbances, and cognitive dysfunction including confusion and amnesia have been reported. Reactions are common and may occur in both adults and children. In adults, the frequency of severe reactions has been estimated to be 5-6%. Psychological effects have been reported on withdrawal of corticosteroids; the frequency is unknown.
Hydrocortisone preparations are usually well tolerated but if signs of hypersensitivity appear, application should be stopped immediately.
Epidermal thinning, telangectasia and striae may occur in areas of high absorption such as skin folds, the face and where occlusive dressings are used.
Local atrophic changes may occur where skin folds are involved, or in areas such as the nappy area in small children, where constant moist conditions favour the absorption of hydrocortisone.
Sufficient systemic absorption may also occur in such sites to produce the features of hypercorticism and suppression of the HPA axis after prolonged treatment. This effect is more likely to occur in infants and children and if occlusive dressings are used or large areas of skin are treated.
Frequency Not known: Vision, blurred.
There are reports of pigmentation changes and hypertrichosis with topical steroids. Contact dermatitis may also occur.
Exacerbation of symptoms may occur.
Hydrocortisone preparations are usually well tolerated, but if any signs of hypersensitivity appear, application should stop immediately.
Striae may occur especially in intertriginous areas.
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