Introduction
Betamethasone is a potent synthetic glucocorticoid with significant anti-inflammatory, immunosuppressive, and vasoconstrictive properties. As a corticosteroid, it is approximately 25-30 times more potent than hydrocortisone. Betamethasone is available in various formulations including oral tablets, injectable solutions, topical creams/ointments, lotions, and aerosol preparations for diverse clinical applications.
Mechanism of Action
Betamethasone exerts its effects through binding to intracellular glucocorticoid receptors, forming a complex that translocates to the cell nucleus. This complex binds to glucocorticoid response elements on DNA, modulating gene transcription. The drug inhibits the expression of pro-inflammatory genes (including cytokines, chemokines, adhesion molecules, and inflammatory enzymes) while promoting the transcription of anti-inflammatory proteins. This results in:
- Suppression of inflammatory cell migration
- Inhibition of phospholipase A2 activity
- Reduction of capillary permeability and edema
- Stabilization of lysosomal membranes
- Suppression of immune responses
Indications
FDA-Approved Indications:- Inflammatory dermatoses (topical formulations)
- Rheumatologic disorders (rheumatoid arthritis, osteoarthritis)
- Allergic conditions (severe allergic reactions, angioedema)
- Endocrine disorders (adrenal insufficiency, congenital adrenal hyperplasia)
- Hematologic disorders (autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura)
- Ophthalmic inflammatory conditions
- Respiratory diseases (asthma, COPD exacerbations)
- Palliative management of leukemias and lymphomas
- Acute spinal cord injury
- Prevention of neonatal respiratory distress syndrome (antenatal use)
- Nausea and vomiting associated with chemotherapy
- Thyroid storm
- Cerebral edema
Dosage and Administration
General Principles:- Use the lowest effective dose for the shortest duration
- Taper gradually when discontinuing chronic therapy
- Oral: 0.6-7.2 mg daily in divided doses
- IM/IV: 0.5-9 mg daily (varies by indication)
- Topical: Apply thinly to affected area 1-4 times daily
- Intra-articular: 0.25-2.0 mL depending on joint size
- Hepatic impairment: Dose reduction recommended
- Renal impairment: No specific adjustment needed
- Elderly: Increased risk of adverse effects; use lowest effective dose
- Pediatrics: Dose based on severity of condition and response (typically 0.0175-0.25 mg/kg/day)
Pharmacokinetics
Absorption: Well absorbed from GI tract; topical absorption depends on skin integrity and formulation Distribution: Widely distributed throughout body tissues; crosses placenta and appears in breast milk; 64% protein-bound Metabolism: Hepatic via CYP3A4 to inactive metabolites Elimination: Primarily renal excretion (mostly as metabolites); elimination half-life 36-54 hours Onset of Action: Variable depending on formulation and route: oral (1-2 hours), IV (rapid), topical (variable)Contraindications
- Systemic fungal infections (unless concurrent antifungal therapy)
- Hypersensitivity to betamethasone or components
- Live virus vaccinations during immunosuppressive therapy
- Idiopathic thrombocytopenic purpura (IM route)
- Intrathecal administration
Warnings and Precautions
Black Box Warnings:- Corticosteroids may cause serious and fatal infections due to immunosuppression
- Avoid use in patients with cerebral malaria
- Serious adverse reactions可能 occur with epidural injection
- Adrenal suppression with chronic use
- Increased infection risk
- Hyperglycemia and diabetes mellitus
- Cardiovascular effects (hypertension, fluid retention)
- Psychiatric effects (euphoria, insomnia, mood swings, depression)
- Ophthalmic effects (cataracts, glaucoma)
- Gastrointestinal effects (peptic ulcer, pancreatitis)
- Musculoskeletal effects (osteoporosis, myopathy)
- Dermatologic effects (impaired wound healing, skin atrophy)
Drug Interactions
Significant Interactions:- Anticoagulants: Altered anticoagulant effect
- Antidiabetic agents: Reduced hypoglycemic effect
- CYP3A4 inducers (phenytoin, rifampin): Reduced betamethasone efficacy
- CYP3A4 inhibitors (ketoconazole): Increased betamethasone toxicity
- Diuretics: Enhanced potassium wasting
- NSAIDs: Increased GI ulcer risk
- Vaccines: Reduced immune response to vaccines
- Live vaccines: Risk of disseminated infection
Adverse Effects
Common (≥1%):- Fluid retention
- Weight gain
- Hypertension
- Glucose intolerance
- Mood changes
- Insomnia
- Increased appetite
- Skin thinning (topical)
- Acneiform eruptions
- Adrenal insufficiency
- Severe infections
- Osteoporosis with fractures
- Avascular necrosis
- Peptic ulcer disease
- Pancreatitis
- Anaphylaxis
- Psychiatric disorders
- Vision changes
- Thromboembolic events
Monitoring Parameters
Baseline:- Blood pressure
- Weight
- Glucose tolerance test
- Electrolytes
- Bone density scan (if long-term use anticipated)
- Ophthalmologic exam
- Blood pressure regularly
- Weight weekly
- Serum glucose regularly
- Electrolytes (especially potassium)
- Signs of infection
- Growth parameters in children
- Bone density annually with chronic use
- Ophthalmologic exams annually with chronic use
- Assess for adrenal insufficiency symptoms
- Monitor for disease flare
Patient Education
Key Points:- Do not stop medication abruptly; taper as directed
- Take with food to reduce GI upset
- Report signs of infection (fever, sore throat)
- Monitor for weight gain, swelling, or mood changes
- Inform all healthcare providers of betamethasone use
- Carry medical identification indicating steroid use
- Avoid exposure to infections when possible
- For topical use: Apply thinly, avoid occlusive dressings unless directed
- Report vision changes or eye pain
- Discuss bone health strategies with provider
- Notify provider if pregnancy is suspected or planned
- Maintain low-sodium diet to reduce fluid retention
- Ensure adequate calcium and vitamin D intake
- Regular weight-bearing exercise
- Glucose monitoring if predisposed to diabetes
- Avoid alcohol and NSAIDs to reduce GI risk
References
1. Lexicomp Online. Betamethasone monograph. Wolters Kluwer Clinical Drug Information, Inc. 2023. 2. Joint Formulary Committee. British National Formulary. London: BMJ Group and Pharmaceutical Press; 2023. 3. corticosteroids: Betamethasone. In: Drugs.com [Internet]. Auckland (NZ): Drugsite Trust; 2023. 4. Liu D, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9(1):30. 5. Bethametasone. In: Micromedex Solutions. Truven Health Analytics, Inc. 2023. 6. Hodgens A, Sharman T. Corticosteroids. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. 7. FDA prescribing information: Celestone (betamethasone) tablets. Merck & Co., Inc. 2022. 8. Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci (Lond). 1998;94(6):557-72.