Beclometasone
1. Drug Name
Generic Name: Beclometasone
Brand Names: Beconase, Qvar, Clenil, Becotide, and others.
2. Drug Classification
Class: Corticosteroid
Subclass: Inhaled Glucocorticoid (for asthma), Nasal Corticosteroid (for rhinitis)
Other Classifications: Anti-inflammatory, Immunosuppressant
3. Mechanism of Action
Glucocorticoid Receptor Activation: Beclometasone works by binding to the glucocorticoid receptor inside cells. This complex then translocates to the nucleus, where it binds to glucocorticoid response elements (GREs) in DNA, altering the transcription of genes that control the inflammatory response.
Anti-inflammatory Effects: It reduces the production of pro-inflammatory cytokines (such as IL-1, IL-2, TNF-α), thereby inhibiting the migration of inflammatory cells like eosinophils, neutrophils, and lymphocytes to the site of inflammation.
Reduction of Mucus Secretion: Beclometasone decreases mucus production and mucus gland hyperplasia in the airways, reducing bronchoconstriction in asthma and controlling nasal inflammation in rhinitis.
Immunosuppressive Effects: It suppresses the activity of the immune system by reducing the formation of antibodies and the release of histamine, contributing to reduced allergic reactions and immune responses.
4. Pharmacokinetics
Absorption:
Inhaled Beclometasone: When inhaled, the bioavailability is low (~20%) due to extensive first-pass metabolism in the lungs and liver. Only about 1-2% of the inhaled dose reaches the systemic circulation.
Nasal Beclometasone: Nasal bioavailability is also low, and systemic absorption is minimal, which helps reduce the risk of systemic side effects.
Distribution:
Volume of Distribution (Vd): Beclometasone is highly protein-bound in the plasma (over 90% bound to corticosteroid-binding globulin and albumin).
Half-life (t½): The terminal half-life of inhaled beclometasone is approximately 15 hours, allowing for once- or twice-daily dosing.
Metabolism:
Liver Metabolism: Beclometasone is extensively metabolized in the liver. It is converted to its active metabolite, beclometasone-17-monopropionate, by the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD).
Excretion:
Excretion: The metabolites are excreted in the urine, with a smaller amount excreted in the feces.
Renal Considerations: No significant renal dosing adjustments are necessary for beclometasone, as the excretion of the active drug is minimal.
5. Indications
Primary Indications:
Asthma: Beclometasone is primarily used as a maintenance therapy for asthma. It helps prevent asthma attacks and reduces inflammation in the airways, improving airflow and lung function.
Chronic Obstructive Pulmonary Disease (COPD): Beclometasone may be used in combination with long-acting bronchodilators for managing chronic symptoms and exacerbations of COPD.
Allergic Rhinitis: Beclometasone is used intranasally to treat symptoms of allergic rhinitis, including nasal congestion, sneezing, and runny nose.
Off-label Uses:
Eosinophilic Esophagitis: Beclometasone has been used off-label to treat eosinophilic esophagitis by reducing esophageal inflammation.
Sinusitis: In some cases, beclometasone nasal spray is used to alleviate symptoms of acute and chronic sinusitis.
6. Dosage and Administration
Adult Dosing:
Asthma (Inhaled): The typical starting dose is 200–400 mcg twice daily (maximum dose: 800 mcg twice daily).
COPD (Inhaled): 200–400 mcg twice daily, typically as part of a combination therapy with a long-acting bronchodilator.
Allergic Rhinitis (Nasal): 1–2 sprays per nostril once or twice daily, depending on the severity of symptoms (maximum 4 sprays per nostril per day).
Pediatric Dosing:
Asthma (Inhaled): In children aged 5–12 years, the dose typically ranges from 100–200 mcg twice daily.
Allergic Rhinitis (Nasal): Children aged 6-12 years may use 1–2 sprays per nostril once daily (max 4 sprays per nostril per day).
Renal and Hepatic Adjustments:
No specific dosing adjustments are required for renal or hepatic impairment in the case of inhaled formulations.
For oral doses (if prescribed for severe cases), caution should be used, and lower doses may be warranted in hepatic dysfunction.
7. Contraindications
Absolute Contraindications:
Hypersensitivity: Known hypersensitivity to beclometasone or any of the components of the formulation.
Relative Contraindications:
Untreated Fungal, Bacterial, or Viral Infections: Active infections of the respiratory tract should be treated before starting beclometasone.
Tuberculosis: Should be used with caution in individuals with active or latent tuberculosis, as it may suppress the immune response and worsen the infection.
8. Warnings and Precautions
Systemic Effects: Though inhaled, beclometasone can still cause systemic corticosteroid side effects with long-term use, such as adrenal suppression, osteoporosis, and cataracts.
Growth Suppression: Long-term use in children may lead to growth retardation. Regular monitoring of growth is recommended.
Respiratory Infections: Beclometasone can increase the risk of respiratory infections, including fungal infections such as oropharyngeal candidiasis. Rinsing the mouth after inhalation can reduce this risk.
Hyperglycemia: Corticosteroids, including beclometasone, can increase blood sugar levels. Diabetic patients should monitor blood glucose levels closely.
9. Adverse Effects
Common Adverse Effects:
Oral Candidiasis: Inhaled corticosteroids like beclometasone can cause fungal infections in the mouth and throat (thrush).
Hoarseness: Dysphonia, or hoarseness, is common due to local irritation in the throat.
Cough: Some patients may experience a cough after inhalation.
Less Common but Clinically Significant:
Osteoporosis: Long-term use may increase the risk of osteoporosis and fractures.
Cataracts and Glaucoma: Chronic use of corticosteroids can increase the risk of cataracts and glaucoma.
Adrenal Suppression: Prolonged use can suppress the hypothalamic-pituitary-adrenal (HPA) axis, leading to adrenal insufficiency.
Rare/Serious Adverse Reactions:
Growth Suppression in Children: Corticosteroids may slow growth in children with long-term use.
Psychiatric Effects: Rarely, corticosteroids can cause mood swings, depression, or psychosis.
10. Drug Interactions
Cytochrome P450 Interactions: Beclometasone has a low potential for significant interactions via the CYP450 system, but caution should be exercised when co-administered with strong CYP3A4 inhibitors (e.g., ketoconazole) as these may increase the systemic concentration of beclometasone.
Other Inhaled Corticosteroids: Concomitant use of multiple inhaled corticosteroids should be avoided to prevent overdose.
Beta-Blockers: Beta-adrenergic blockers can reduce the effectiveness of beclometasone in asthma patients by blocking beta-receptors in the lungs.
11. Clinical Pharmacology
Pharmacodynamics: Beclometasone acts by reducing airway inflammation, bronchial hyperresponsiveness, and mucus production. It also inhibits the late-phase response to allergens, contributing to better asthma control.
Efficacy in Asthma: Studies show that inhaled beclometasone significantly reduces the frequency of asthma exacerbations and improves lung function.
12. Special Populations
Pregnancy: Category C. Use during pregnancy should be limited to situations where the benefit clearly outweighs the risk. Corticosteroids may increase the risk of cleft palate in the fetus with oral or systemic use.
Lactation: It is excreted in breast milk, but the systemic exposure from inhalation is minimal, making it likely safe during breastfeeding.
Pediatrics: Beclometasone is used in children, though careful monitoring of growth and development is recommended.
Geriatrics: Older adults are more susceptible to the systemic side effects of corticosteroids, including osteoporosis and cataracts.
13. Therapeutic Uses
Primary: Beclometasone is used for the long-term management of asthma and COPD, reducing inflammation and preventing bronchospasm.
Secondary: It is used as a part of combination therapy in asthma and COPD with long-acting bronchodilators.
Off-label: In some cases, it is used for nasal polyps and other inflammatory respiratory conditions.
14. Monitoring and Follow-Up
Inhaler Technique: Regularly review the patient's inhaler technique to ensure optimal drug delivery.
Growth Monitoring in Children: Growth velocity should be monitored in pediatric patients using inhaled corticosteroids long-term.
Bone Health: Consider bone mineral density testing for long-term users, especially if risk factors for osteoporosis are present.
15. Overdose Management
Symptoms of Overdose: Acute overdose is unlikely with inhaled forms due to low systemic absorption. However, chronic overdose can lead to symptoms of corticosteroid toxicity, such as weight gain, fluid retention, and hyperglycemia.
Management: No specific antidote. Overdose management involves supportive care, such as electrolyte monitoring, glucose control, and blood pressure management.
16. Patient Counseling Information
Administration: Inhaled beclometasone should be taken as prescribed, with proper inhaler technique. Rinse the mouth after each use to avoid oral candidiasis.
Possible Side Effects: Patients should be informed about the risk of throat irritation, hoarseness, and oral thrush. If these symptoms occur, seek medical advice.
Avoid Triggers: Advise patients with asthma to avoid known triggers and use their inhalers regularly as prescribed.