Betamethasone

Betamethasone is a long-acting, potent glucocorticoid with negligible mineralocorticoid activity. It is the most widely used steroid for antenatal lung maturation, and is also given topically for skin disease, by joint or soft tissue injection, and orally or intramuscularly for inflammatory conditions. It is chemically close to dexamethasone and has the same potency (0.75 mg equals hydrocortisone 20 mg).

Classification. Glucocorticoid. Oral tablets 0.5 mg; injection (sodium phosphate with acetate suspension, 6 mg/mL, and sodium phosphate 4 mg/mL); topical creams, ointments, lotions and scalp applications in potencies from moderate to very potent; eye and ear drops; enemas.

Mechanism. Binds the intracellular glucocorticoid receptor, altering gene transcription: reduced cytokines and capillary permeability, suppressed leukocyte migration and lymphocyte function, increased gluconeogenesis, and induced surfactant production in foetal lung.

Pharmacodynamics. Anti-inflammatory potency 25 to 30 times hydrocortisone; biological effect lasts 36 to 54 hours. The combined phosphate and acetate injection acts quickly from the soluble phosphate and persists from the acetate for 1 to 2 weeks.

Pharmacokinetics. Oral bioavailability about 70 to 90%; peak 1 to 2 hours; about 60% protein bound; half-life 5 to 6 hours (plasma) but the biological effect is much longer. Crosses the placenta mostly unchanged; metabolised by the liver; excreted in urine.

Antenatal lung maturation (women at risk of preterm birth).

• Betamethasone 12 mg intramuscularly (the combined phosphate and acetate preparation) every 24 hours for 2 doses, given when birth is expected within 7 days between 24 and 34 weeks (and 34 to 36 weeks plus 6 days in selected women where facilities and glucose monitoring allow). A single rescue course may be repeated if the first course was given 14 days or more before and birth remains likely within 7 days and before 34 weeks. Avoid more than two courses.
• Dexamethasone 6 mg every 12 hours for 4 doses is an equally effective alternative; do not give both.

Oral anti-inflammatory use. 0.5 to 5 mg daily (0.75 mg equals prednisolone 5 mg), in 1 to 4 divided doses, as a short course; rarely used long term.

Intramuscular or intra-articular and soft tissue injection (combined preparation).

• Intramuscular 1 to 2 mL (6 to 12 mg) as a single dose, repeated no more often than every 1 to 2 weeks. Intra-articular: large joints 1 to 2 mL (6 to 12 mg), medium joints 0.5 to 1 mL, small joints 0.25 to 0.5 mL, repeated no more often than every 3 months.

Topical use for inflammatory skin disease (eczema, psoriasis, lichen planus).

• Apply a thin layer once or twice daily for 1 to 2 weeks for potent and very potent preparations (up to 4 weeks on thick skin of the palms, soles and knees); use moderate potency or lower on the face, flexures and in children; avoid occlusion and use under specialist direction for very potent forms in children.
• Adult weekly maximum of a very potent topical about 50 g; children less.

Severe allergy and adrenal replacement. Not suited to adrenal replacement because of potency and lack of salt-retaining activity.

Adjustments.

• Kidney: no change.
• Liver: reduce the oral dose in cirrhosis.
• Older adults: use the lowest dose.
• Weight: dose by weight in children.

Contraindications. Systemic fungal infection; untreated sepsis; idiopathic thrombocytopenic purpura (for intramuscular injection); hypersensitivity; skin infection, rosacea, acne and perioral dermatitis (topical); live vaccines at immunosuppressive doses.

Serious adverse effects.

• Systemic: hyperglycaemia, hypertension, fluid retention, psychiatric effects, infection, gastrointestinal bleeding, adrenal suppression with prolonged use.
• Antenatal: transient maternal hyperglycaemia and leucocytosis; neonatal hypoglycaemia; foetal heart rate pattern changes that settle; avoid repeated or very early exposure because of possible effects on foetal growth and neurodevelopment.
• Injection: skin atrophy and depigmentation at the site, joint infection, tendon rupture, flushing.
• Topical: skin thinning, striae, telangiectasia, folliculitis, perioral dermatitis, adrenal suppression when large areas are treated for long periods, glaucoma around the eyes.

Major interactions.

• Reduced effect: rifampicin, phenytoin, carbamazepine, phenobarbital.
• Increased effect: ketoconazole, itraconazole, clarithromycin, ritonavir.
• NSAIDs and aspirin: gastrointestinal bleeding; diuretics: hypokalaemia; antidiabetic drugs: glucose rises.
• Live vaccines are avoided at immunosuppressive doses.

Special groups.

• Pregnancy: antenatal use is a core indication. In diabetic women, give insulin as needed and monitor glucose for 3 to 5 days after the course; in women with chorioamnionitis, give steroids with antibiotics.
• Breastfeeding: compatible.
• Children: topical use in low potencies only; growth suppression with oral courses.
• Older adults: thinning skin and bruising with topical use.
• Kidney impairment: no change; liver impairment: reduce oral dose.
• East Africa: give antenatal steroids only where gestational age is reliable, birth is likely within 7 days and newborn care (including resuscitation and thermal care) is available, since use without newborn care can raise harm for late preterm babies. Dexamethasone is often the supplied alternative. Many skin-lightening creams contain potent topical steroids such as betamethasone; counsel on thinning skin, stretch marks, acne and adrenal suppression.

Formulation and administration. Shake the injection suspension well before use; give deep intramuscular injection into a large muscle (gluteal or thigh), never intravenously. Intra-articular use is by sterile technique. Apply topical preparations to clean, dry skin; wash hands afterwards unless treating the hands.

Baseline. Gestational age confirmation, blood pressure and glucose (antenatal); infection screen and glucose for oral courses; skin assessment for topical use.

Monitoring.

• Antenatal: maternal glucose for 3 to 5 days in diabetic women, blood pressure, and neonatal glucose after birth.
• Oral and injected courses: blood pressure, glucose, potassium and signs of infection.
• Topical: skin thinning, striae, infection and signs of absorption; review every 2 to 4 weeks.

Dose reduction and stopping. Antenatal courses are complete after 2 doses. Short oral courses stop without a taper; courses over 3 weeks need a taper (reduce by 5 to 10 mg every 1 to 2 weeks to 10 mg, then by 1 mg every 2 to 4 weeks). Step down topical potency as the skin improves and stop after the planned course.

Referral and escalation. Admit suspected adrenal crisis, severe infection or uncontrolled hyperglycaemia. Refer topical steroid damage, uncontrolled skin disease and any need for repeated antenatal courses to the relevant specialist.