Hydrocortisone

Registered South African indications:

• Acute adrenocortical insufficiency
• Bilateral adrenalectomy
• Severe shock
• Acute hypersensitivity reactions

Contraindications

South African recommendations

• Systemic fungal infections
• Known hypersensitivity to hydrocortisone sodium succinate or any of the excipients
• Traumatic brain injury
• Absolutely contraindicated in patients with (except when used for short-term or emergency therapy as in acute sensitivity reactions)
  - Herpes simplex keratitis
  - Acute psychoses
  - Latent, healed or arrested tuberculosis (however, concurrent administration of corticoids with antituberculous medicines may be lifesaving in certain cases of meningeal tuberculosis)
• Relatively contraindicated in
  - Active or latent peptic ulcer
  - Cushing’s syndrome
  - Diverticulitis
  - Recent intestinal anastomoses
  - Osteoporosis
  - Renal insufficiency
  - Thromboembolic tendencies
  - Psychotic tendencies
  - Diabetes mellitus
  - Hypertension
  - Local or systemic infections including vaccinia and varicella, as well as fungal diseases and other exanthematous diseases
  - First trimester of pregnancy
• Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids

Recommendations in other jurisdictions

• Known hypersensitivity to the active substance or any of the excipients
• Systemic fungal infection unless specific anti-infective therapy is employed
• Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids

Cautions

• Second and third trimester of pregnancy (South African recommendations)
• Pregnancy (Recommendations in other jurisdictions)
• Breastfeeding
• Renal impairment (Recommendations in other jurisdictions)
• Hepatic impairment
• Elderly
• Cerebral oedema associated with acute head injury or cerebrovascular accident
• Abrupt withdrawal in patients:
  - Who have received more than physiological doses of systemic corticosteroids for >3 weeks
  - Where a short course is prescribed within one year of cessation of long-term therapy (months or years)
  - With reasons for adrenocortical insufficiency other than exogenous corticosteroid therapy  
  - Receiving doses of systemic corticosteroids greater than 160mg hydrocortisone  
  - Repeatedly taking doses in the evening
• Masking of serious infections
• Patients without a definite history of chickenpox
• Exposure to measles
• Prolonged therapy
• Congestive cardiac failure
• Diabetes mellitus, or family history thereof
• Osteoporosis, or family history thereof
• Hypertension, or family history thereof
• Glaucoma, or family history thereof
• Epilepsy, or family history thereof
• Existing, personal or family history of history of severe affective disorders
• Previous steroid psychosis
• Previous steroid myopathy
• Peptic ulceration
• History of tuberculosis
• Pre-eclampsia or fluid retention

Forms avail. in SA and covered in this monograph: inj, poi

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Acute adrenocortical insufficiency
Bilateral adrenalectomy
- Prior to and immediately after
Severe shock
- Septic shock
Acute hypersensitivity reactions
- Status asthmaticus and allergic medicine anaphylactic reactions (Additional agent required)

• IV: Initial: Administer intravenously, over a period of 1 to several minutes; Treatment duration: 48-72hrs

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In general, high dose corticosteroid therapy should be continued only until the patient’s condition has stabilised, usually not beyond 48-72 hours

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- Other situations in which adequate preparations with intramuscularly administered cortisone or hydrocortisone cannot be accomplished

• IV: Initial: 100-500mg, depending on the severity of the condition, given over ≥30secs; Repeat at intervals of 1, 3, 6 and 10hrs according to patient response and clinical condition

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Hydrocortisone is indicated corticosteroid-responsive conditions when the oral route of corticosteroid administration is not suitable

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Hydrocortisone may be administered by intravenous injection, by intravenous infusion, or by intramuscular injection. The preferred method for initial emergency use is intravenous injection. Following the initial period, consideration should be given to employing a longer acting injectable preparation or an oral preparation

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In severe shock adjunctive use of intravenous hydrocortisone may aid in achieving haemodynamic restoration. Corticoid therapy should not replace standard methods of combating shock

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In general, high dose corticosteroid therapy should be continued only until the patient’s condition has stabilised, usually not beyond 48-72 hours. Although adverse effects associated with high dose, shortterm corticoid therapy are uncommon, peptic ulceration may occur. Prophylactic antacid therapy may be
indicated

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When massive hydrocortisone therapy must be continued beyond 48-72 hours, hypernatraemia may occur. Under such circumstances it may be desirable to replace hydrocortisone with a corticoid such as methylprednisolone sodium succinate which causes little or no sodium retention

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Hydrocortisone therapy is an adjunct to, and not a replacement for, conventional therapy

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Indications and dosages registered in other jurisdictions

Primary or secondary adrenocortical insufficiency
Systemic lupus erythematosus
Severe erythema multiforme (Stevens-Johnson syndrome)
Bronchial asthma, anaphylactic reactions
Ulcerative colitis
Crohn's disease
Aspiration of gastric contents
Treatment of shock secondary to adrenocortical insufficiency
Shock unresponsive to conventional therapy when adrenocortical insufficiency may be present

• IV: Initial: 100-500mg, depending on the severity of the condition as slow injection over a period of 1-10min; Repeat at intervals of 2, 4, or 6hrs according to patient response and clinical condition; Treatment duration: 48-72hrs OR until patient's condition has stabilised

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Intravenous hydrocortisone is indicated for any condition in which rapid and intense corticosteroid effect

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Dosage requirements are variable and must be individualized on the basis of the disease under treatment, its severity and the response of the patient over the entire duration of treatment. A risk/benefit decision must be made in each individual case on an ongoing basis

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The lowest possible dose of corticosteroid should be used to control the condition under treatment for the minimum period. The proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage, which will maintain an adequate clinical response, is reached

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In general, high-dose corticosteroid therapy should be continued only until the patient's condition has stabilised - usually not beyond 48-72 hours. If hydrocortisone therapy must be continued beyond 48-72 hours hypernatraemia may occur, therefore it may be preferable to replace hydrocortisone with a corticosteroid such as methylprednisolone sodium succinate as little or no sodium retention occurs14

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Although adverse effects associated with high dose, short-term corticoid therapy are uncommon, peptic ulceration may occur. Prophylactic antacid therapy may be indicated

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If after long-term therapy the drug is to be stopped, it needs to be withdrawn gradually rather than abruptly. Corticosteroid therapy is an adjunct to, and not a replacement for, conventional therapy

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This medicine may be administered by intravenous injection, by intravenous infusion, or by intramuscular injection, the preferred method for initial emergency use being intravenous injection. Following the initial emergency period, consideration should be given to employing a longer-acting injectable preparation or an oral preparation

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See link: General prescribing points for steroids

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See link: Choice of steroids for endocrine indications

Paed. forms avail. in SA and covered in this monograph: inj, poi

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Acute adrenocortical insufficiency
Bilateral adrenalectomy
- Prior to and immediately after
Severe shock
- Septic shock
Acute hypersensitivity reactions
- Status asthmaticus and allergic medicine anaphylactic reactions (Additional agent required)

• IV/IM: Individualised dosages

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While the dose may be reduced for infants and children, it is governed more by the severity of the condition and response of the patient, than by age or body mass, but should not be less than 25mg daily

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Indications and dosages registered in other jurisdictions

Primary or secondary adrenocortical insufficiency
Systemic lupus erythematosus
Severe erythema multiforme (Stevens-Johnson syndrome)
Bronchial asthma, anaphylactic reactions
Ulcerative colitis
Crohn's disease
Aspiration of gastric contents
Treatment of shock secondary to adrenocortical insufficiency
Shock unresponsive to conventional therapy when adrenocortical insufficiency may be present

• IV/IM: Individualised dosages

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While the dose may be reduced for infants and children, it is governed more by the severity of the condition and response of the patient than by age or body weight but should not be less than 25mg daily

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Treatment should be limited to the minimum dosage for the shortest possible time and restricted to the most serious indications. Growth and development should be carefully observed and high doses of corticosteroids should be avoided as they can produce pancreatitis

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See link: General prescribing points for steroids

Pregnancy

South African recommendations

• First trimester: Contraindicated
• Second and third trimester: Caution; positive evidence of risk
• Safety in pregnancy has not been demonstrated
• Some animal studies have shown that corticosteroids when administered to the mother at high doses, may cause foetal malformations
• Hydrocortisone is teratogenic in animals
• Corticosteroids readily cross the placenta. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy must be carefully observed and evaluated for signs of adrenal insufficiency
• Benzyl alcohol (contained in some formulations) can cross the placenta
• Pregnancy is a relative contraindication to corticoid therapy particularly during the first trimester because of the observation of foetal abnormalities in experimental animals. If it is necessary to give corticosteroids during pregnancy, the newborn infant should be observed closely for signs of hypoadrenalism and appropriate therapy instituted if such signs are present

Recommendations in other jurisdictions

• Caution; positive evidence of risk in animal studies
• The ability of corticosteroids to cross the placenta varies between individual agents, 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 effects on brain growth and development. There is no evidence that corticosteroids result in an increased incidence of congenital abnormalities, such as cleft palate in humans; however, when administered for long periods or repeatedly during pregnancy, corticosteroids may increase the risk of intrauterine growth retardation. Hypoadrenalism may, in theory, occur in the neonate following prenatal exposure to corticosteroids but usually resolves spontaneously following birth and is rarely clinically important. As with all agents, hydrocortisone should only be prescribed when the benefits to the mother and child outweigh the risks. When hydrocortisone is essential, however, patients with normal pregnancies may be treated as though they were in the non-gravid state
• Some corticosteroids readily cross the placenta. Some retrospective studies have found an increased incidence of low-birth weights in infants born of mothers receiving corticosteroids. In humans, the risk of low birth weight appears to be dose related and may be minimized by administering lower corticosteroid doses
• Cataracts have been observed in infants born to mothers treated with long-term corticosteroids during pregnancy

Breastfeeding

• Caution
• Corticosteroids are excreted in breast milk, although no data are available for hydrocortisone. Doses up to 160mg daily of hydrocortisone 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 breastfeeding are likely to outweigh any theoretical risk

Renal Impairment

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• Caution; no dose adjustment recommended
  Corticosteroids should be used with caution in patients with renal insufficiency

Hepatic Impairment

• Caution; no information available

Elderly

• Caution; no dose adjustment recommended
  The common adverse effects of systemic corticosteroids may be associated with more serious consequences in old age
  Close clinical supervision is required to avoid life-threatening reactions

Porphyria Information

• Possibly porphyrinogenic (PSP)

Drugs in Sport

• Prohibited - In-Competition

Central Nervous System Disorders 

• Euphoria
• Psychological dependence
• Depression
• Insomnia
• Aggravation of schizophrenia   
• Increased intracranial pressure with papilloedema in children (pseudotumour cerebri)
• Aggravation of epilepsy
• Psychotic reactions
  - Mania
  - Delusions
  - Hallucinations
• Behavioural disturbances
• Irritability
• Anxiety
• Cognitive dysfunction
  - Confusion
  - Amnesia
• Paraesthesia
• Labile mood
• Suicidal thoughts

Cardiovascular Disorders

• Hypotension (on abrupt withdrawal)
• Hypertension

Gastrointestinal Disorders 

• Dyspepsia
• Peptic ulceration with perforation and haemorrhage
• Acute pancreatitis
• Candidiasis

Genitourinary Disorders

• Menstrual irregularity
• Amenorrhoea

Endocrine and Metabolic Disorders 

• Suppression of the hypothalamic-pituitary-adrenal axis
• Adrenal insufficiency (on abrupt withdrawal)
• Growth suppression (in infancy, childhood and adolescence)
• Cushingoid faces
• Hirsutism
• Weight gain
• Weight loss
• Impaired carbohydrate tolerance
• Negative protein and calcium balance
• Increased appetite
• Fluid disturbance
• Electrolyte disturbance
• Sodium and water retention
• Potassium loss
• Hypokalaemic alkalosis
• Diabetes

Musculoskeletal Disorders 

• Osteoporosis
• Vertebral fractures
• Long bone fractures
• Avascular osteonecrosis
• Tendon rupture
• Proximal myopathy

Skin and Subcutaneous Tissue Disorders 

• Impaired healing
• Skin atrophy
• Bruising
• Telangiectasia
• Striae
• Acne
• Pruritus

Immune, Blood and Lymphatic System Disorders 

• Increased susceptibility and severity of infections
• Opportunistic infections
• Reoccurrence of dormant tuberculosis
• Hypersensitivity
• Anaphylaxis
• Leucocytosis
• Thromboembolism
• Flushing

Sensory Disorders 

• Increased intraocular pressure
• Glaucoma
• Papilloedema
• Posterior subcapsular cataracts
• Corneal or scleral thinning
• Exacerbation of ophthalmic viral or fungal diseases
• Blurred vision

Others

• 'Withdrawal syndrome'
  - Fever
  - Myalgia
  - Arthralgia
  - Rhinitis
  - Conjunctivitis
  - Painful itchy skin nodules
  - Weight loss
• Death (Too rapid a reduction of corticosteroid dosage following prolonged treatment)

• Live or live, attenuated vaccines
• CYP3A inhibitors
• Cobicistat
• Rifampicin
• Rifabutin
• Carbamazepine
• Phenobarbital
• Phenytoin
• Primidone
• Ephedrine
• Aminoglutethimide
• Antihypertensives
• Hypoglycaemic agents
• Insulin
• Diuretics
• Hypokalaemic agents
• Acetazolamide
• Loop diuretics
• Thiazide diuretics
• Carbenoxolone
• Coumarin anticoagulants
• Anticholinesterases
• Oestrogens
• Salicylates

Other interactions

• Cholecystographic x-ray media

Specific cases may require

• Blood pressure
• Blood glucose
• Electrolytes
• Intraocular pressure
• Bone mineral density
• INR or prothrombin time
• HPA axis suppression
• Renal function

Additional observations

• Mental status
• Weight
• Growth (children)
• Signs and symptoms of infection

Abrupt withdrawal

• Abrupt withdrawal of systemic corticosteroid treatment which has continued for up to three weeks is appropriate if it is considered that the disease is unlikely to relapse. Abrupt withdrawal of doses of up to 160mg hydrocortisone for three weeks is unlikely to lead to clinically relevant HPA-axis suppression, in the majority of patients
• In the following patient groups, gradual withdrawal of systemic corticosteroid therapy should be considered even after courses lasting three weeks or less
  - Patients who have had repeated courses of systemic corticosteroids, particularly if taken for >3 weeks
  - When a short course has been prescribed within one year of cessation of long-term therapy (months or years)
  - Patients who may have reasons for adrenocortical insufficiency other than exogenous corticosteroid therapy
  - Patients receiving doses of systemic corticosteroids >160mg hydrocortisone
  - Patients repeatedly taking doses in the evening
• Adrenal cortical atrophy develops during prolonged therapy and may persist for years after stopping treatment. Withdrawal of corticosteroids after prolonged therapy must therefore always be gradual to avoid acute adrenal insufficiency, being tapered off over weeks or months according to the dose and duration of treatment
• During prolonged therapy any intercurrent illness, trauma or surgical procedure will require a temporary increase in dosage; if corticosteroids have been stopped following prolonged therapy they may need to be temporarily re-introduced

Suppression of the immune and inflammatory response

• Suppression of the inflammatory response and immune function increases the susceptibility to infections and their
  severity. The clinical presentation may often be atypical and serious infections such as septicaemia and tuberculosis may be masked and may reach an advanced stage before being recognised
• Chickenpox is of particular concern since this normally minor illness may be fatal in immunosuppressed patients.
  Patients without a definite history of chickenpox should be advised to avoid close personal contact with chickenpox or
  herpes zoster and if exposed they should seek urgent medical attention. If the patient is a child, parents must be given the above advice. Passive immunisation with varicella zoster immunoglobulin (VZIG) is needed by exposed non-immune patients who are receiving systemic corticosteroids or who have used them within the previous three months; this should be given within 10 days of exposure to chickenpox. If a diagnosis of chickenpox is confirmed, the illness warrants specialist care and urgent treatment. Corticosteroids should not be stopped and the dose may need to be increased
• Patients should be advised to take particular care to avoid exposure to measles and to seek immediate medical advice if exposure occurs. Prophylaxis with intramuscular normal immunoglobulins may be needed
• Live vaccines should not be given to individuals with impaired immune responsiveness. The antibody response to other vaccines may be diminished

Psychiatric adverse reactions

• Patients and/or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids. Symptoms typically emerge within a few days or weeks of starting the treatment. Risks may be higher with high doses/ systemic exposure, although dose levels do not allow prediction of the onset, type, severity or duration of reactions

Hydrocortisone is a short-acting glucocorticoid with anti-inflammatory properties. It acts to decrease inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability

Injection (per vial) 100mg

• Solu-Cortef (Pfizer) originator

Injection (per 2ml) 100mg

• Macleods Hydrocortisone (Macleods)
• Solu-Cortef (Pfizer) originator

Injection (per 5ml) 100mg

• Cortaject (Strides SA)

Injection (per 4ml) 500mg

• Solu-Cortef (Pfizer) originator

Also available in the following forms: Tablet, cream, ointment and lotion.