Usage
Doxofylline + Montelukast is prescribed for the treatment and management of respiratory conditions, primarily asthma and chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. It is also used to alleviate symptoms of allergic rhinitis (hay fever) and exercise-induced bronchoconstriction (EIB).
This combination drug falls under the pharmacological classifications of bronchodilator (doxofylline) and leukotriene receptor antagonist (montelukast).
Doxofylline works by relaxing the airway muscles and widening the bronchi, facilitating easier breathing. Montelukast inhibits the action of leukotrienes, inflammatory mediators that contribute to bronchoconstriction, mucus production, and airway inflammation.
Alternate Names
While “Doxofylline + Montelukast” represents the generic name, various brand names exist depending on the manufacturer and region. Some common examples include Doxolin M, Doxiflo-M, Doxoford-M, ABIDOX-M, Kivodoxo-M, Ishdox-M and Monteluke DX.
How It Works
Pharmacodynamics: Doxofylline, a xanthine derivative, acts as a bronchodilator by inhibiting phosphodiesterases, enzymes that break down cyclic AMP. This leads to increased intracellular cAMP levels, promoting smooth muscle relaxation in the airways. It also exhibits some anti-inflammatory properties. Montelukast antagonizes leukotriene receptors, particularly LTD4 receptors, thereby reducing bronchoconstriction, mucus secretion, and airway edema associated with leukotriene activity.
Pharmacokinetics: Doxofylline is well-absorbed orally, reaching peak plasma concentration in 1-2 hours for immediate-release formulations, while sustained-release preparations have longer time to reach peak concentrations. Doxofylline is metabolized in the liver and primarily eliminated via renal excretion. The elimination half-life varies.
Montelukast is rapidly absorbed orally, reaching peak plasma concentration in 3-4 hours. Food doesn’t significantly affect its absorption. Montelukast is extensively metabolized in the liver, primarily by CYP2C8 and to a lesser extent by CYP3A4 and CYP2C9. It is excreted mainly in bile, with minimal renal elimination. The elimination half-life is typically 2.7 to 5.5 hours in adults.
Dosage
Standard Dosage
Adults:
The standard dose for adults and adolescents 15 years and older is one tablet containing Doxofylline 400 mg and Montelukast 10 mg, taken orally once daily, usually in the evening for asthma and morning or evening for allergic rhinitis. For patients with both asthma and allergic rhinitis, a single evening dose is recommended.
Children:
For children younger than 15 years, the dosage should be determined by a pediatrician based on age, weight, and the specific condition. Montelukast 10 mg tablets are generally not recommended for children under 15. Doxofylline dosage needs adjustment in pediatric population based on weight or body surface area.
Special Cases:
- Elderly Patients: No specific dosage adjustment is usually required for elderly patients unless significant renal or hepatic impairment is present.
- Patients with Renal Impairment: Caution is advised in patients with moderate to severe renal impairment. Dosage adjustment may be necessary.
- Patients with Hepatic Dysfunction: Dosage adjustment may be required in patients with moderate to severe hepatic impairment, particularly for doxofylline.
- Patients with Comorbid Conditions: Careful consideration is needed for patients with cardiovascular disease, hyperthyroidism, peptic ulcer disease, and seizure disorders.
Clinical Use Cases
Doxofylline + Montelukast is not recommended for acute exacerbations of asthma or COPD. It is intended for long-term management of these chronic respiratory conditions. In emergency situations like status asthmaticus or severe bronchospasm, short-acting bronchodilators and other appropriate interventions are necessary. Doxofylline + Montelukast is not indicated for specific clinical scenarios like intubation, surgical procedures, mechanical ventilation, or general ICU use, beyond its role in managing underlying chronic asthma or COPD within those settings.
Dosage Adjustments
Dosage adjustments might be needed depending on individual patient responses, the severity of the disease, and the presence of renal or hepatic impairment.
Side Effects
Common Side Effects:
Headache, nausea, vomiting, abdominal pain, diarrhea, dizziness, fatigue, insomnia, irritation, sore throat, increased heart rate, and flu-like symptoms.
Rare but Serious Side Effects:
Allergic reactions (rash, urticaria, angioedema), neuropsychiatric events (agitation, anxiety, depression, suicidal ideation), and cardiovascular effects (palpitations, tachycardia, arrhythmias).
Long-Term Effects:
The potential long-term adverse effects of Doxofylline + Montelukast require further investigation. Monitoring for neuropsychiatric effects is especially important with prolonged montelukast use.
Adverse Drug Reactions (ADR):
Severe allergic reactions, significant mood or behavioral changes (including suicidal thoughts or behavior), and severe cardiovascular effects are potentially serious ADRs requiring prompt medical intervention.
Contraindications
Hypersensitivity to doxofylline, montelukast, or any component of the formulation; acute myocardial infarction; severe hypotension; active peptic ulcer disease; Status epilepticus.
Drug Interactions
Doxofylline + Montelukast may interact with several medications, including:
- Xanthines (theophylline, aminophylline)
- CYP2C8 inhibitors and inducers (gemfibrozil, rifampicin)
- CYP3A4 inhibitors (itraconazole, ketoconazole, erythromycin, clarithromycin)
- H2 receptor antagonists (cimetidine, ranitidine)
- Phenytoin
- Allopurinol
Alcohol should be limited as it may enhance drowsiness and other side effects.
Pregnancy and Breastfeeding
The safety of Doxofylline + Montelukast during pregnancy and breastfeeding has not been fully established. It should be used only if the potential benefit outweighs the potential risk to the fetus or infant.
Drug Profile Summary
- Mechanism of Action: Doxofylline: Bronchodilation via phosphodiesterase inhibition. Montelukast: Leukotriene receptor antagonist.
- Side Effects: Headache, nausea, dizziness, neuropsychiatric events, allergic reactions.
- Contraindications: Hypersensitivity, acute MI, severe hypotension.
- Drug Interactions: Xanthines, CYP2C8 inhibitors/inducers, CYP3A4 inhibitors, H2 antagonists.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
- Dosage: Adults: Doxofylline 400 mg + Montelukast 10 mg once daily. Pediatric: Consult pediatrician.
- Monitoring Parameters: Pulmonary function tests, mood and behavior, cardiovascular status.
Popular Combinations
Doxofylline + Montelukast is itself a popular combination. Sometimes, it may be used in conjunction with inhaled corticosteroids for enhanced asthma control.
Precautions
- General Precautions: Assess for allergies, cardiac, hepatic, or renal dysfunction, and neuropsychiatric history.
- Specific Populations: Pregnancy and breastfeeding: Use with caution. Children: Consult pediatrician. Elderly: Monitor closely.
- Lifestyle Considerations: Limit alcohol, avoid driving if experiencing dizziness or drowsiness. Smoking cessation is strongly advised.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Doxofylline + Montelukast?
A: The usual adult dose is Doxofylline 400 mg + Montelukast 10 mg once daily. Pediatric dosing should be determined by a pediatrician.
Q2: Can this combination be used for acute asthma attacks?
A: No, it’s not recommended for acute asthma attacks. Use a rescue inhaler (short-acting beta-agonist) for acute episodes.
Q3: Are there any drug interactions I should be aware of?
A: Yes, several. Inform your doctor about all other medications you’re taking, including OTC drugs and supplements.
Q4: What are the common side effects?
A: Common side effects include headache, nausea, dizziness, and gastrointestinal upset.
Q5: Can pregnant or breastfeeding women take this medication?
A: Consult a doctor before use during pregnancy or breastfeeding as safety hasn’t been fully established.
Q6: How should this medication be stored?
A: Store in a cool, dry place away from direct sunlight and out of reach of children.
Q7: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember unless it’s close to your next scheduled dose. Don’t double the dose.
Q8: Can I drink alcohol while taking this medicine?
A: Alcohol should be limited, as it may exacerbate side effects like drowsiness.
Q9: Are there any specific monitoring requirements?
A: Pulmonary function tests, mood and behavior monitoring (especially for montelukast), and assessment of cardiovascular parameters may be necessary.
Q10: Does this medication interact with food?
A: Food does not significantly affect the absorption of montelukast. Doxofylline can be taken with or without food. However, taking it with food might decrease gastrointestinal discomfort in some individuals.
