Dexamethasone

Registered South African indications:

• Anti-inflammatory or immunosuppressant in conditions where corticosteroid therapy is indicated

Contraindications

South African recommendations

• Hypersensitivity to corticosteroids, dexamethasone, or any of the excipients 
• Acute infections uncontrolled by appropriate antimicrobial chemotherapy 
• Acute psychosis and psychoneurosis 
• Ocular herpes simplex 
• Primary glaucoma 
• Osteoporosis 
• Peptic ulceration 

Recommendations in other jurisdictions

• Hypersensitivity to the active substance or to any of the excipients
• Unless considered to be life-saving systemic administration of corticosteroids are generally contraindicated in patients with systemic infections, (unless specific anti-infective therapy is employed)
• Local injection of a corticosteroid is contraindicated in
  - Bacteraemia
  - Systemic fungal infections
  - Unstable joints
  - Infection at the injection site e.g. septic arthritis resulting from gonorrhea or tuberculosis
• Known hypersensitivity to sulfites

Cautions

• Pregnancy
• Breastfeeding
• Males of reproductive potential
• Renal impairment
• Hepatic impairment
• Elderly
• Porphyria
• Children
• Preterm neonates with chronic lung disease
• Haematological malignancies
• High risk of tumour lysis syndrome
• High proliferation rates
• High tumour burden
• High sensitivity to cytotoxic agents
• High doses
• Non-specific ulcerative colitis
• Diverticulitis
• Fresh intestinal anastomoses
• Active or latent peptic ulcer
• Osteoporosis
• Previous steroid myopathy
• Hypertension
• Cardiac failure
• Existing or previous history of severe affective disorders
• Previous steroid psychosis
• Unusual stress (such as intercurrent illness, trauma or surgery)
• Abrupt withdrawal of therapy
• History of allergy to any medicine
• Recent myocardial infarction
• Diabetes mellitus or family history thereof
• Masking of signs and symptoms of infection
• Varicella-zoster or herpes zoster infection
• Ocular herpes simplex infection
• Measles
• Latent or active amoebiasis or strongyloidiasis
• Cerebral malaria
• Active tuberculosis (except fulminating or disseminated tuberculosis)
• Latent tuberculosis or tuberculin reactivity
• Glaucoma or family history thereof
• Myasthenia gravis
• Epilepsy
• Cirrhosis
• Sodium controlled diet
• Frequent intraarticular injections
• Over-use of joints despite symptomatic improvement
• Multiple myeloma patients treated with lenalidomide or thalidomide

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

Dosages below include:

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

South African registered indications and dosages

Anti-inflammatory or immunosuppressant in conditions where corticosteroid therapy is indicated
- Used parenterally in short term intensive therapy or in emergencies

• IM/IV: 0.5-20mg, dly, depending on severity of the disorder
• Soft tissue injection/Intra-articular/IM/Intralesional (inj): 0.8-4mg, depending on the size of the joint

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Dexamethasone solution for injection should not be administered intrathecally or subconjunctivally

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Rapid intravenous injection of massive doses may sometimes cause cardiovascular collapse and injections should therefore be given slowly or by infusion

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Withdrawal after high-dose or prolonged therapy should be gradual, depending on the individual patient’s response, the dose, the disease being treated, and the duration of therapy. During withdrawal the adrenal function should be monitored and symptoms attributable to over-rapid withdrawal should be countered by resuming a higher dose and continuing the reduction at a slower rate. Prolonged treatment with a high dose of dexamethasone injection is not recommended

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Indications and dosages registered in other jurisdictions

N.B. All doses are expressed as mg dexamethasone base

Short term management of acute self-limited allergic conditions such as
- Angioneurotic oedema
- Acute exacerbations of chronic allergic disorders such as bronchial asthma or serum sickness

• IM/IV: 0.4-20mg, dly, depending on severity of the disorder; Treatment duration: Dependent on the clinical response of the patient and as soon as improvement is indicated, adjust dose to the minimum required to maintain the desired clinical response 

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Withdrawal of dexamethasone on completion of therapy should be gradual

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Shock of haemorrhagic, traumatic, surgical or septic origin

• IV: Initial: 1.67-5mg/kg bodyweight as a single bolus dose; Repeat dose in 2-6hrs, if shock persists; High-dose therapy should be continued only until the patient's condition has stabilised and usually <48-72hrs; Then: Continuous IV infusion: 2.5mg/kg bodyweight, every 24hrs

Cerebral oedema associated with cerebral neoplasm

• IV: Initial: 8.3mg; Followed by: IM: 3.3mg, 6hrly until the symptoms of oedema subside (usually after 12-24hrs); After 2-4 days: Reduce dose and gradually stop over 5-7 days; In patients with recurrent or inoperable neoplasms: Maintenance: IM/IV: 1.7mg, 8-12hrly

Life-threatening cerebral oedema

High dose schedule (all doses are expressed as mg dexamethasone base)

Initial	IV: 41.6mg
1st day	IV: 6.6mg, 2hrly
2nd day	IV: 6.6mg, 2hrly
3rd day	IV: 6.6mg, 2hrly
4th day	IV: 3.3mg, 2hrly
5-8th day	IV: 3.3mg, 4hrly
After 8 days	Decrease by dly reduction of 3.3mg

Inflammatory diseases of joints and soft tissue such as rheumatoid arthritis

Site of injection	Dosage*
Large joint	1.7-3.3mg
Small joints	0.667-0.8mg
Bursae	1.6-2.5mg
Tendon sheaths	0.333-0.8mg
Soft tissue infiltration	1.7-5mg
Ganglia	0.8-1.7mg

*Dosage varies with the degree of inflammation and the size and location of the affected area. Injections may be repeated from once every 3-5 days (e.g. for bursae) to once every 2-3 weeks (for joints)

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The IV and IM routes of administration of dexamethasone should only be used where acute illness or life-threatening situations exist. Oral therapy should be substituted as soon as possible

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Dexamethasone solution for injection is indicated in acute conditions in which oral glucocorticoid therapy is not feasible

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The duration of therapy is dependent on the clinical response of the patient and as soon as improvement is indicated, the dosage should be adjusted to the minimum required to maintain the desired clinical response. Withdrawal of the drug on completion of therapy should be gradual

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High doses of dexamethasone are intended for the adjunctive treatment of shock where massive doses of corticosteroids are needed. There is a lack of evidence that use of corticosteroids in septic shock affects mortality in the long term. Use must be accompanied by the appropriate concomitant systemic antibiotic treatment and supportive measures which the patient's condition may require

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Not for intrathecal use – contains sulfites

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The lowest effective dose should be used for the minimum period and this should be reviewed frequently to appropriately titrate the dose against disease activity

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Dexamethasone solution for injection may be administered by intramuscular, intraarticular or direct intravenous injection, intravenous infusion or soft tissue infiltration

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Shock: Dexamethasone solution for injection can be diluted with sodium chloride injection BP or glucose injection BP

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Withdrawal of therapy: See additional prescribing points

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See link: General prescribing points for steroids

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

Dosages below include:

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

South African registered indications and dosages

Anti-inflammatory or immunosuppressant in conditions where corticosteroid therapy is indicated
- Used parenterally in short term intensive therapy or in emergencies

• No specific recommendations have been provided for paediatrics

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Hypertrophic cardiomyopathy may occur after systemic administration of corticosteroids, including dexamethasone injection, to prematurely born infants. In the majority of cases, this is reversible on withdrawal of treatment. In preterm infants treated with dexamethasone, diagnostic evaluation and monitoring of cardiac function and structure should be performed

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Dexamethasone causes growth retardation in infancy, childhood, and adolescence, which may be irreversible. Treatment should be limited to the minimum dosage for the shortest possible time, in order to minimise suppression of the hypothalamopituitary-adrenal axis and growth retardation

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Growth and development of infants and children on prolonged corticosteroid therapy should be carefully monitored. Children may require prophylaxis and immunoglobulin as they are at an increased risk of infection. Infections should be treated as an emergency

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Indications and dosages registered in other jurisdictions

Short term management of acute self-limited allergic conditions such as 
- Angioneurotic oedema
- Acute exacerbations of chronic allergic disorders such as bronchial asthma or serum sickness
Shock of haemorrhagic, traumatic, surgical or septic origin
Cerebral oedema associated with cerebral neoplasm
Life-threatening cerebral oedema
Inflammatory diseases of joints and soft tissue such as rheumatoid arthritis

• IV/IM: Individualised dosages

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Dosage requirements are variable and may have to be changed according to individual need. Usually 167-333μg/kg (0.05-0.1ml/kg) of body weight daily

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Dexamethasone solution for injection is indicated in acute conditions in which oral glucocorticoid therapy is not feasible

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Corticosteroids cause growth retardation in infancy, childhood and adolescence, which may be irreversible. Treatment should be limited to the minimum dosage for the shortest possible time. In order to minimise suppression of the hypothalamic-pituitary-adrenal axis and growth retardation, treatment should be limited, where possible, to a single dose on alternate days

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

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See link: General prescribing points for steroids

Pregnancy

• Caution
• The ability of corticosteroids to cross the placenta varies between individual agents, however, dexamethasone 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/lip in humans
• However, when administered for prolonged 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 medicines, 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 state

Breastfeeding

• Caution; not recommended
• Corticosteroids may pass into breast milk, although no data are available for dexamethasone. Infants of mothers taking high doses of systemic corticosteroids for prolonged periods may have a degree of adrenal suppression

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
  Consider lower end of dosing range

Porphyria Information

• Possibly porphyrinogenic (PSP)

Drugs in Sport

• Prohibited - In competition

Central Nervous System Disorders 

• Affective disorders
• Irritation
• Euphoria
• Depression
• Suicidal thoughts  
• Psychotic reactions
• Mania
• Labile mood
• Delusions
• Hallucinations
• Aggravation of schizophrenia
• Behavioural disturbances
• Anxiety
• Sleep disturbances
• Cognitive dysfunction
• Confusion
• Amnesia
• Increased intracranial pressure with papilloedema (pseudotumour cerebri) after treatment
• Convulsions
• Headache
• Cerebral palsy in pre-term infants
• Malaise

Cardiovascular Disorders 

• Hypertension
• Congestive heart failure
• Myocardial rupture following recent myocardial infarction
• Hypertrophic cardiomyopathy in low birth weight infants
• Hypotension

Gastrointestinal Disorders 

• Dyspepsia
• Peptic ulceration with perforation and haemorrhage
• Perforation of small and large intestine
• Pancreatitis
• Abdominal distention
• Ulcerative oesophagitis
• Nausea
• Hiccups
• Oesophageal candidiasis

Genitourinary Disorders 

• Menstrual irregularity and amenorrhoea

Endocrine and Metabolic Disorders 

• Sodium and fluid retention
• Potassium loss
• Hypokalaemic alkalosis
• Suppression of the hypothalamic-pituitary-adrenal axis
• Increased calcium excretion
• Growth suppression in infancy, childhood and adolescence
• Secondary adrenocortical and pituitary unresponsiveness
• Decreased carbohydrate tolerance
• Manifestation of latent diabetes mellitus
• Increased insulin or oral hypoglycaemic agents requirements
• Hirsutism
• Cushingoid state
• Weight gain
• Negative nitrogen balance
• Negative calcium balance
• Increased appetite
• Acute adrenal insufficiency

Musculoskeletal Disorders

• Osteoporosis
• Vertebral and compression fractures
• Pathological long bone fracture  
• Aseptic necrosis of femoral and humeral heads
• Pathological fracture of long bones
• Tendon rupture
• Muscle weakness
• Steroid myopathy
• Loss of muscle mass

Skin and Subcutaneous Tissue Disorders 

• Impaired wound healing
• Thin, fragile skin
• Petechiae and ecchymoses
• Erythema
• Striae
• Telangiectasia
• Acne
• Increased sweating
• Allergic dermatitis
• Urticaria
• Angioneurotic oedema
• Hypo- or hyperpigmentation

Immune, Blood and Lymphatic System Disorders 

• Increased susceptibility and severity of infection  
• Suppression of clinical symptoms and signs of infection
• Opportunistic infections
• Oesophageal candidiasis
• Recurrence of dormant tuberculosis 
• Decreased responsiveness to vaccination and skin tests
• Hypersensitivity
• Anaphylaxis
• Leucocytosis
• Thromboembolism

Sensory Disorders 

• Increased intraocular pressure
• Glaucoma exophthalmos
• Papilloedema
• Posterior subcapsular cataracts
• Corneal or scleral thinning
• Exacerbation of ophthalmic viral or fungal diseases
• Blindness associated with intralesional therapy around the face and head
• Retinopathy of prematurity
• Chorioretinopathy
• Vertigo

Others 

• Post-injection flare (intraarticular use)
• Sterile abscess
• Transient burning or tingling sensation mainly in the perineal area following intravenous injection
• Peritoneal irritation

• CYP3A inhibitors
• CYP3A4 substrates
• Rifampicin
• Rifabutin
• Ephedrine
• Carbamazepine
• Barbiturates
• Phenobarbital
• Phenytoin
• Indomethacin
• Aminoglutethimide
• Antimuscarinics
• Hypoglycaemic agents
• Insulin
• Antihypertensives
• Amphotericin B
• Hydrocortisone
• Potassium-depleting diuretics
• Thiazides
• Furosemide
• Xanthines
• Theophylline
• Beta-2 agonists
• Non-steroidal anti-inflammatory drugs (NSAIDS)
• Protease inhibitors
• Ritonavir
• Darunavir
• Indinavir
• Lopinavir
• Saquinavir
• Efavirenz
• Coumarin anticoagulants
• Salicylates
• Aspirin
• Live vaccines
• Oral contraceptives

None routine. Specific cases may require

• Weight and height (children)
• Blood pressure
• Serum potassium
• Blood glucose
• Bone mineral density
• Full blood count
• HPA axis suppression

Withdrawal of therapy

• In patients who have received more than physiological doses of systemic corticosteroids (approximately 1mg dexamethasone) for greater than 3 weeks, withdrawal should not be abrupt
• How dose reduction should be carried out depends largely on whether the disease is likely to relapse as the dose of systemic corticosteroids is reduced. Clinical assessment of disease activity may be needed during withdrawal
• If the disease is unlikely to relapse on withdrawal of systemic corticosteroids but there is uncertainty about HPA suppression, the dose of systemic corticosteroid may be reduced rapidly to physiological doses
• Once a daily dose of 1mg dexamethasone is reached, dose reduction should be slower to allow the HPA-axis to recover
• Abrupt withdrawal of systemic corticosteroid treatment, which has continued up to 3 weeks is appropriate if it is considered that the disease is unlikely to relapse
• Abrupt withdrawal of doses up to 6mg of dexamethasone for 3 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 3 weeks or less:
  - Patients who have had repeated courses of systemic corticosteroids, particularly if taken for greater than 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 corticosteroid greater than 6 mg daily of dexamethasone
  - Patients repeatedly taking doses in the evening
• Withdrawal symptoms and signs: 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 fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight

Suppression of inflammatory response

• Suppression of the inflammatory response and immune function increasing 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 reach an advanced stage before being recognised

Dexamethasone is an adrenocortical steroid that acts on the hypothalamic-pituitary axis and binds to specific receptors on the plasma membrane.It diffuses across cell membranes, enters the nucleus and stimulates protein synthesis; resulting in profound and varied metabolic effects that modify the body's immune responses to diverse stimuli.

Injection (per ml) 4mg

• Decasone (Pharmacare)
• Dexona (Zydus)
• Fresenius Dexamethasone (Fresenius)
• Mylan Dexamethasone (Xixia)
• Pharma-Q Dexamethasone Phosphate (Pharma-Q)
• Tagalon 4mg/ml (Trinity Pharma)

Also available in the following forms: Ear drop, eye drop and implant.