Hydrocortisone

Registered South African indications:

• Addison's disease
• Chronic adrenocortical insufficiency secondary to hypopituitarism

Contraindication

• Hypersensitivity to the active ingredient or any of its excipients
• Infections, including systemic infections where anti-infective therapy has not been started
• Porphyria
• Coadministration with live vaccines

Caution

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Existing or previous history of severe affective disorders or in first-degree relatives
• Depressive or manic-depressive illness
• Previous steroid psychosis
• Immunocompromised patients
• Patients without a definite history of chickenpox
• Personal contact with chickenpox or herpes zoster
• Exposure to measles
• Systemic fungal infections
• Recent myocardial infarction
• Cerebral malaria
• Latent tuberculosis or tuberculin reactivity
• Active tuberculosis (other than fulminating or disseminated tuberculosis)
• Hypertension
• Diabetes mellitus, including latent diabetes
• Family history of diabetes
• Congestive cardiac failure
• Thrombophlebitis
• Exanthematous disease
• Chronic nephritis
• Acute glomerulonephritis
• Metastatic carcinoma
• Osteoporosis, especially postmenopausal women
• Epilepsy
• Previous steroid-induced myopathy
• Glaucoma
• Family history of glaucoma
• Myasthenia gravis
• Non-specific ulcerative colitis (if there is a probability of impending perforation)
• Diverticulitis
• Fresh intestinal anastamoses
• Active or latent peptic ulcer
• Signs of peritoneal irritation following gastrointestinal perforation (large doses)
• Hypothyroidism
• Cirrhosis
• Atypical presentation of infections
• Latent or active amoebiasis or strongyloidiasis
• Secondary ocular infections
• Ocular herpes simplex
• Hypoprothrombinaemia (when coadministered with aspirin)
• History of drug allergies
• Abrupt withdrawal
• Prolonged therapy in infants, children and adolescents
• Premature infants
• Galactose intolerance
• Total lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: tab

Pre-operatively, and during serious trauma or illness in patients with known adrenal insufficiency or doubtful
adrenocortical reserve
Chronic adrenocortical insufficiency
- Primary (Addisons' disease)
- Secondary

• Oral (tab): 20-30mg, dly in the morning OR 48hrly in the morning

Acute adrenocortical insufficiency

• Oral (tab): 10-30mg, dly in the morning OR 48hrly in the morning

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Dosage must be individualised according to the response of the individual patient. The lowest possible dosage should be used

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Doses should be multiples of 10 (i.e. 10mg, 20mg, 30mg)

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Undesirable effects may be minimised by using the lowest effective dose for the minimum period and by administering
the daily requirement as a single morning dose or whenever possible, as a single morning dose on alternate days

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Frequent patient review is required to titrate the dose against disease activity

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To avoid hypoadrenalism and/or a relapse of the underlying disease, it may be necessary to withdraw the drug gradually

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Hydrocortisone may be used with 4-6g sodium chloride or 50-300 micrograms of fludrocortisone daily in chronic adrenocortical insufficiency

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When immediate support is mandatory, one of the soluble adrenocortical hormone preparations (e.g. dexamethasone
sodium phosphate), which may be effective within minutes after parenteral administration, can be life-saving

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In serious trauma or illness with known adrenal insufficiency or doubtful adrenocortical reserve, patients should be observed closely for signs that might require dosage adjustment, including changes in clinical status resulting from remissions or exacerbations of the disease, individual drug responsiveness, and the effect of stress (e.g. surgery, infection, trauma)

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Patients should be observed closely for signs that might require dosage adjustment, including changes in clinical status
resulting from remissions or exacerbations of the disease, individual drug responsiveness, and the effect of stress (e.g.
surgery, infection, trauma). During stress it may be necessary to increase the dosage temporarily

---

During stress it may be necessary to increase the dosage temporarily

---

For pre-operative use, anaesthetists must be informed if the patient is taking corticosteroids or has previously taken corticosteroids

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When long term treatment is to be discontinued, the dose should be gradually reduced over a period of weeks or
months, depending on dosage and duration of therapy

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See link: General prescribing points for steroids

See link: Choice of steroids for endocrine indications

Paed. forms avail. in SA and covered in this monograph: tab

Pre-operatively, and during serious trauma or illness in patients with known adrenal insufficiency or doubtful adrenocortical reserve 
Chronic adrenocortical insufficiency
- Primary (Addison's disease)
- Secondary

• Oral (tab): 0.4-0.8mg/kg/day, in 2-3 divided doses

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Dosage must be individualised according to the response of the individual patient. The lowest possible dosage should be used

---

Doses should be multiples of 10 (i.e. 10mg, 20mg, 30mg, etc)

---

In serious trauma or illness with known adrenal insufficiency or doubtful adrenocortical reserve, doses are generally higher than that used for chronic adrenocortical insufficiency and should be selected as appropriate for the clinical situation

---

Undesirable effects may be minimised by using the lowest effective dose for the minimum period and by administering
the daily requirement as a single morning dose or whenever possible, as a single morning dose on alternate days

---

Frequent patient review is required to titrate the dose against disease activity

---

To avoid hypoadrenalism and/or a relapse of the underlying disease, it may be necessary to withdraw the drug gradually

---

Hydrocortisone may be used with 4-6 g of sodium chloride or 50-300 micrograms of fludrocortisone daily in chronic adrenocortical insufficiency

---

When immediate support is mandatory, one of the soluble adrenocortical hormone preparations (e.g. dexamethasone
sodium phosphate), which may be effective within minutes after parenteral administration, can be life-saving

---

Patients should be observed closely for signs that might require dosage adjustment, including changes in clinical status
resulting from remissions or exacerbations of the disease, individual drug responsiveness, and the effect of stress (e.g.
surgery, infection, trauma). During stress it may be necessary to increase the dosage temporarily

---

During stress it may be necessary to increase the dosage temporarily

---

For pre-operative use, anaesthetists must be informed if the patient is taking corticosteroids or has previously taken corticosteroids

---

When long term treatment is to be discontinued, the dose should be gradually reduced over a period of weeks or months, depending on dosage and duration of therapy

---

See link: General prescribing points for steroids

See link: Choice of steroids for endocrine indications

Pregnancy

• Caution  
• 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

Breastfeeding

• Caution
• Corticosteroids are excreted in breast milk, although no data are available for hydrocortisone. Infants of mothers taking high doses of systemic corticosteroids for prolonged periods may have a degree of adrenal suppression. Mothers taking pharmacological doses of corticosteroids should be advised not to breastfeed. Maternal treatment should be carefully documented in the infant's medical records to assist in follow up

Fertility

• 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
• Corticosteroids may increase or decrease motility and number of spermatozoa

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended
  Treatment of elderly patients, particularly if long term, should be planned bearing in mind the more serious consequences of the common side effects of corticosteroids
  For replacement therapy, the daily dose should be given when practicable, in two doses. The first dose in the morning should be larger than the second dose in the evening, thus simulating the normal diurnal rhythm of cortisol secretion

Porphyria Information

• Possibly porphyrinogenic (PSP)

Drugs in Sport

• Prohibited - In competition

Central Nervous System Disorders 

• Psychic disturbances
• Psychological dependence
• Depression
• Insomnia
• Psychiatric reactions
• Affective disorders
  - Irritable mood
  - Euphoric mood
  - Depressed mood
  - Labile mood
  - Suicidal thoughts
• Psychotic reactions
  - Mania
  - Delusions
  - Hallucinations
  - Aggravation of schizophrenia
• Aggravation of epilepsy
• Behavioural disturbances
• Irritability
• Anxiety
• Sleep disturbances
• Cognitive dysfunction
  - Confusion
  - Amnesia
• Seizures
• Increased intracranial pressure with papilloedema (pseudotumour cerebri)
• Headache
• Malaise

Cardiovascular Disorders 

• Myocardial rupture following recent myocardial infarction
• Congestive heart failure
• Hypertrophic cardiomyopathy (premature infants)
• Thromboembolism
• Hypertension

Respiratory Disorders

• Hiccups

Gastrointestinal Disorders 

• Peptic ulcer with possible perforation and haemorrhage
• Perforation of the small and large bowel particularly in patients with inflammatory bowel disease
• Pancreatitis
• Abdominal distension
• Ulcerative oesophagitis 
• Dyspepsia
• Oesophageal candidiasis
• Nausea

Genitourinary Disorders

• Acute renal insufficiency
• Increased or decreased motility of spermatozoa
• Menstrual irregularities
• Amenorrhoea

Endocrine and Metabolic Disorders 

• Development of Cushingoid state
• Secondary adrenocortical and pituitary unresponsiveness
• Decreased carbohydrate tolerance
• Manifestations of latent diabetes mellitus
• Hyperglycemia
• Increased requirements for insulin or oral hypoglycaemic agents in diabetes
• Hirsutism
• Sodium retention
• Fluid retention
• Hypokalaemia
• Hypokalaemic alkalosis
• Increased calcium excretion
• Negative nitrogen balance due to protein catabolism
• Weight gain
• Increased appetite
• Growth suppression (infants, childhood and adolescents)

Musculoskeletal Disorders 

• Muscle weakness
• Steroid myopathy
• Loss of muscle mass
• Osteoporosis (especially in post-menopausal females)
• Vertebral compression fractures
• Aseptic necrosis of femoral and humeral heads
• Pathological fracture of long bones
• Avascular osteonecrosis
• Tendon rupture

Skin and Subcutaneous Tissue Disorders 

• Impaired wound healing
• Thin fragile skin
• Petechiae
• Ecchymoses
• Erythema
• Striae
• Telangiectasia
• Acne
• Increased sweating
• Suppressed reactions to skin tests
• Cutaneous reactions
  - Allergic dermatitis
  - Urticaria
  - Angioneurotic oedema

Immune, Blood and Lymphatic Disorders 

• Leucocytosis
• Hypersensitivity
• Anaphylaxis
• Increased susceptibility and severity of infection
• Opportunistic infections
• Recurrence of dormant tuberculosis

Sensory Disorders 

• Posterior subcapsular cataracts
• Increased intra-ocular pressure
• Papilloedema
• Corneal or scleral thinning
• Exacerbation of ophthalmic viral or fungal disease
• Glaucoma
• Exophthalmos
• Blurred vision
• Vertigo

Others

• Withdrawal syndrome
  - Fever
  - Myalgia
  - Arthralgia
  - Rhinitis
  - Conjunctivitis
  - Painful itchy skin nodules
  - Weight loss

• Aspirin
• Non-steroidal anti-inflammatory drugs
• Salicylates 
• Phenytoin
• Ephedrine
• Rifabutin
• Carbamazepine
• Barbiturates
• Rifampicin
• Primidone
• Sympathomimetics
• Aminoglutethimide
• Coumarin anticoagulants
• Ketoconazole
• Potassium-depleting diuretics
• Acetazolamide
• Loop diuretics
• Thiazides
• Carbenoxolone
• Beta-blockers
• Alpha- blockers
• Calcium channel blockers
• Clonidine
• Diazoxide
• Methyldopa
• Moxonidine
• Nitrates
• Nitroprusside
• Hydralazine
• Minoxidil
• Adrenergic neurone blockers
• ACE inhibitors
• Angiotensin II receptor antagonists
• Cardiac glycosides
• Digoxin
• Theophylline
• Beta sympathomimetics
• Bambuterol
• Fenoterol
• Formoterol
• Ritodrine
• Salbutamol
• Salmeterol
• Terbutaline
• Amphotericin
• Mifepristone
• Oral contraceptives
• Oestrogen
• Ritonavir
• Calcium salts
• Erythromycin
• Antidiabetic agents
• Methotrexate
• Somatropin
• Live vaccines
• Sodium benzoate
• Sodium phenyl butyrate
• CYP3A inhibitors
• Cobicistat containing products

Others

• Nitroblue tetrazolium test

None routine. Specific cases may require

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

Additional observations

• Growth and development (children) 
• Signs and symptoms of
  - Pre-eclampsia and fluid retention (pregnancy)
  - 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
• Drug-induced secondary adrenocortical insufficiency may result from too rapid a withdrawal of corticosteroids and may be minimised by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, corticosteroid therapy should be reinstated. If the patient is receiving steroids already, the dosage may have to be increased. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently

Suppression of the immune and inflammatory response

• Caution should be exercised in immunocompromised patients
• Chickenpox is of particular concern since this normally minor illness may be fatal in immunosuppressed patients. Patients (or parents of children receiving hydrocortisone) without a definite history of chickenpox should be advised to avoid close personal contact with chickenpox or herpes zoster. If exposed, they should seek urgent medical attention. 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 3 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
• 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 immunoglobulin may be needed
• Live vaccines should not be given to individuals with impaired immune responsiveness caused by high doses of corticosteroids. Killed vaccines or toxoids may be given though their effects may be attenuated
• Corticosteroids may exacerbate systemic fungal infections and therefore should not be used in the presence of such infections unless they are needed to control life-threatening drug reactions due to amphotericin

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 glucocorticoid. Glucocorticoids are adrenocortical steroids, both naturally-occurring and synthetic, which are readily absorbed from the gastrointestinal tract. Hydrocortisone is believed to be the principal corticosteroid secreted by the adrenal cortex. Naturally-occurring glucocorticosteroids (hydrocortisone and cortisone), which also have salt retaining properties, are used as replacement therapy in adrenocortical deficiency states. They are also used for their potent anti-inflammatory effects in disorders of many organ systems. Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli.

Tablet 10mg

• Covocort (Adcock Ingram) originator

Also available in the following forms: Cream, ointment, lotion and injection.