Usage
Doxofylline + Salbutamol is prescribed for the treatment of reversible obstructive airway diseases, primarily asthma and chronic obstructive pulmonary disease (COPD). This combination therapy is indicated for the relief of bronchospasm and improvement of lung function in these conditions. It is not intended for the management of acute asthma attacks.
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Pharmacological Classification: Bronchodilator (a combination of a xanthine derivative and a beta-2 agonist).
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Mechanism of Action: Doxofylline inhibits phosphodiesterase enzymes, increasing intracellular cyclic AMP and relaxing bronchial smooth muscle. It also exhibits some anti-inflammatory activity. Salbutamol, a beta-2 adrenergic receptor agonist, directly relaxes bronchial smooth muscle. The combination results in synergistic bronchodilation.
Alternate Names
While “Doxofylline + Salbutamol” represents the generic name, various brand names exist depending on the manufacturer and geographical location. Salbutamol is also referred to as Albuterol, especially in the United States. Some examples of brand names include Carbasma S, Doxoril Plus, and Gazodox S.
How It Works
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Pharmacodynamics: Doxofylline acts as a bronchodilator and exhibits mild anti-inflammatory properties. It relaxes the smooth muscles of the airways, reducing bronchospasm and improving airflow. Salbutamol, by stimulating beta-2 adrenergic receptors, also relaxes bronchial smooth muscle and promotes bronchodilation.
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Pharmacokinetics: Doxofylline is metabolized in the liver and primarily excreted via the kidneys. It reaches peak serum concentration in approximately 2 hours when administered orally. Salbutamol is also metabolized in the liver and excreted through the kidneys and in feces.
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Mode of Action: Doxofylline inhibits phosphodiesterase enzymes, leading to an increase in intracellular cyclic AMP. This, in turn, relaxes the bronchial smooth muscles. Salbutamol directly activates beta-2 adrenergic receptors, also leading to bronchial smooth muscle relaxation.
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Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Doxofylline primarily acts through phosphodiesterase enzyme inhibition. It demonstrates a significantly lower affinity for adenosine receptors compared to theophylline. Salbutamol directly binds to and activates beta-2 adrenergic receptors.
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Elimination Pathways: Both Doxofylline and Salbutamol are metabolized in the liver and excreted by the kidneys.
Dosage
Standard Dosage
Adults:
Doxofylline: 400 mg twice or three times daily (BID or TID), with a maximum daily dose of 1200 mg.
Salbutamol: Dosage depends on the administration route (inhalation, nebulization, oral) and the severity of symptoms. Common inhaled doses are 100-200 mcg per puff via metered-dose inhaler (MDI) or dry powder inhaler (DPI), up to four times daily. Oral doses range from 2mg to 8mg three to four times a day.
Children:
Doxofylline: Limited safety and efficacy data are available for children under 18. Doxofylline use in children is generally not recommended. If necessary, use with caution under specialist supervision. Doses may range from 6-9 mg/kg BID for children under 12, up to 200 mg BID or TID for children over 12. Salbutamol dosage is also dependent on age and the severity of symptoms and is usually 1-2 puffs via MDI or 2.5-5 mg by nebulizer up to four times per day.
Special Cases:
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Elderly Patients: Reduce Doxofylline dose to 200 mg BID or TID. Salbutamol: Start with a lower dose, such as 2mg three times a day.
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Patients with Renal Impairment: Doxofylline dose reduction is recommended. Salbutamol is mostly excreted through urine and should be used with caution and possibly dose reduction.
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Patients with Hepatic Dysfunction: Doxofylline and Salbutamol dose reduction might be necessary.
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Patients with Comorbid Conditions: Consider dose adjustments for cardiovascular disease, hyperthyroidism, peptic ulcer disease, etc.
Clinical Use Cases
The Doxofylline + Salbutamol combination is typically not specifically indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is generally intended for maintenance therapy of chronic airway diseases.
Dosage Adjustments
Dose modifications should be considered based on individual patient factors such as renal/hepatic impairment, metabolic disorders, concomitant medications, and other relevant clinical conditions.
Side Effects
Common Side Effects:
Headache, nausea, vomiting, stomach pain, irritability, insomnia, palpitations, tachycardia, throat irritation, dysphagia, difficulty urinating.
Rare but Serious Side Effects:
Severe allergic reactions, seizures, arrhythmias, hypokalemia.
Long-Term Effects:
Chronic complications from long-term use are rare but may include cardiovascular effects.
Adverse Drug Reactions (ADR):
Severe allergic reactions, paradoxical bronchospasm, QT interval prolongation.
Contraindications
- Hypersensitivity to Doxofylline, Salbutamol, or any component of the formulation.
- Acute myocardial infarction.
- Hypotension.
- Lactation.
Drug Interactions
- Xanthine derivatives (including caffeine), ephedrine, erythromycin, troleandomycin, lincomycin, clindamycin, allopurinol, cimetidine, propranolol, influenza vaccine, phenytoin, beta-blockers, diuretics.
Pregnancy and Breastfeeding
- Pregnancy: Doxofylline use during pregnancy should be avoided unless clearly necessary and the potential benefits outweigh the risks.
- Breastfeeding: Doxofylline is contraindicated during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Doxofylline: Phosphodiesterase inhibitor, increases cAMP, bronchodilation. Salbutamol: Beta-2 agonist, bronchodilation.
- Side Effects: Headache, nausea, vomiting, insomnia, palpitations, tachycardia, irritability.
- Contraindications: Hypersensitivity, acute MI, hypotension, lactation.
- Drug Interactions: Xanthines, ephedrine, some antibiotics, cimetidine, propranolol.
- Pregnancy & Breastfeeding: Pregnancy: Use with caution. Breastfeeding: Contraindicated.
- Dosage: Adults: Doxofylline 400 mg BID-TID, Salbutamol varies based on route and condition. Children: Not generally recommended.
- Monitoring Parameters: Lung function tests (FEV1, FVC), heart rate, blood pressure, electrolyte levels (potassium).
Popular Combinations
Doxofylline is sometimes combined with other bronchodilators, corticosteroids, or mucolytics for enhanced therapeutic effects in managing COPD or asthma.
Precautions
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General Precautions: Evaluate patients for pre-existing medical conditions such as cardiovascular disease, hyperthyroidism, hepatic or renal dysfunction, and peptic ulcer disease.
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Specific Populations: Use with caution in pregnant women and avoid use during breastfeeding. Use cautiously in children and the elderly, adjusting dosage as needed.
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Lifestyle Considerations: Advise patients to avoid smoking and excessive caffeine intake.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Doxofylline + Salbutamol?
A: Doxofylline: Adults: 400 mg BID-TID (max 1200mg/day). Salbutamol dosage varies depending on age, route of administration, and indication. It is typically used via MDI (100-200mcg/puff up to 4 times daily), nebulizer (2.5-10 mg up to 4 times daily) or oral (2-8mg TID or QID). Pediatric dosing is complex and should be guided by clinical experience and best practices. Doxofylline use in children is generally avoided.
Q2: What are the common side effects of Doxofylline + Salbutamol?
A: Common side effects include headache, nausea, vomiting, stomach pain, irritability, insomnia, palpitations, and tachycardia.
Q3: What are the contraindications for Doxofylline + Salbutamol?
A: This combination is contraindicated in patients with hypersensitivity to the components, acute myocardial infarction, hypotension, and during breastfeeding.
Q4: What are the key drug interactions to be aware of with Doxofylline + Salbutamol?
A: Important drug interactions include those with other xanthine derivatives (including caffeine), ephedrine, certain antibiotics (erythromycin, lincomycin, etc.), cimetidine, propranolol, and phenytoin.
Q5: Can Doxofylline + Salbutamol be used during pregnancy?
A: Doxofylline use during pregnancy should be avoided unless the potential benefits outweigh the risks. Consult a specialist for guidance.
Q6: Can Doxofylline + Salbutamol be used during breastfeeding?
A: Doxofylline is contraindicated during breastfeeding.
Q7: What are the monitoring parameters for Doxofylline + Salbutamol?
A: Monitor lung function (FEV1, FVC), heart rate, blood pressure, and electrolyte levels (especially potassium).
Q8: What is the mechanism of action of Doxofylline?
A: Doxofylline acts by inhibiting phosphodiesterase enzymes, increasing intracellular cAMP and promoting bronchodilation. It also shows mild anti-inflammatory activity.
Q9: How does Salbutamol work?
A: Salbutamol is a beta-2 adrenergic agonist, directly relaxing bronchial smooth muscle and promoting bronchodilation.
Q10: What should be considered when prescribing this combination to elderly patients?
A: Lower doses of Doxofylline and Salbutamol are usually recommended for elderly patients due to age-related changes in metabolism and organ function.
