Usage
Montelukast + Theophylline is prescribed for the treatment of asthma and to prevent exercise-induced bronchoconstriction (EIB). Theophylline belongs to the class of bronchodilators known as methylxanthines and Montelukast is a leukotriene receptor antagonist. Together, these medications work synergistically to manage asthma symptoms. Montelukast targets the inflammatory component of asthma by blocking leukotrienes, while theophylline acts as both a bronchodilator and anti-inflammatory agent.
Alternate Names
While “Montelukast + Theophylline” is the generic name, this combination is marketed under various brand names. One example is Monotair FX.
How It Works
Montelukast:
- Pharmacodynamics: Montelukast is a selective and competitive leukotriene receptor antagonist, primarily binding to the CysLT1 receptor. This action inhibits the effects of leukotrienes, which are potent bronchoconstrictors and mediators of inflammation in the airways.
- Pharmacokinetics: Montelukast is rapidly absorbed after oral administration, reaching peak plasma concentrations within 3-4 hours. It is highly bound to plasma proteins (greater than 99%) and extensively metabolized in the liver, primarily by CYP3A4, 2C8, and 2C9 enzymes. It is eliminated mainly through biliary excretion, with a half-life of 2.7-5.5 hours in adults.
Theophylline:
- Pharmacodynamics: Theophylline is a bronchodilator, believed to work primarily by inhibiting phosphodiesterase enzymes, leading to increased intracellular cyclic adenosine monophosphate (cAMP). This results in smooth muscle relaxation in the airways. Theophylline also has some anti-inflammatory properties.
- Pharmacokinetics: Theophylline is well absorbed after oral administration. It is metabolized in the liver, primarily by CYP1A2 and 3A4, and eliminated primarily through renal excretion, with a half-life varying widely (3-15 hours) depending on factors such as age, smoking status, and concurrent medications.
Dosage
Standard Dosage
Adults:
- Montelukast: 10 mg orally once daily, typically in the evening for asthma.
- Theophylline: Dosage is individualized based on serum theophylline levels, aiming for a therapeutic range of 5-15 mcg/mL. Extended-release formulations allow for once- or twice-daily dosing.
Children:
- Montelukast: Dosing varies by age: 4 mg chewable tablet once daily for ages 2-5 years, 5 mg chewable tablet once daily for ages 6-14 years.
- Theophylline: Dosing is individualized based on age and serum theophylline levels.
Special Cases:
- Elderly Patients: Theophylline clearance may be reduced, necessitating lower doses. Monitor serum levels closely.
- Patients with Renal Impairment: Theophylline dosage adjustments are required, with dose reduction and careful monitoring of serum levels.
- Patients with Hepatic Dysfunction: Both montelukast and theophylline dosage may need adjustment. Closely monitor serum theophylline levels.
- Patients with Comorbid Conditions: Consider drug interactions and the potential impact of comorbid conditions on drug metabolism.
Clinical Use Cases
Theophylline has specific clinical use cases, such as apnea of prematurity, while montelukast is primarily for asthma maintenance and prophylaxis of EIB. These medications are not typically adjusted for procedures like intubation, surgery, or use in ICU settings.
Dosage Adjustments
Dosage adjustments are patient-specific and may be based on:
- Renal function
- Hepatic function
- Age
- Concomitant medications known to interact with montelukast or theophylline
- Therapeutic drug monitoring, particularly for theophylline
Side Effects
Common Side Effects
- Montelukast: Headache, upper respiratory infection, abdominal pain, diarrhea.
- Theophylline: Nausea, vomiting, headache, insomnia, irritability, gastroesophageal reflux.
Rare but Serious Side Effects
- Montelukast: Neuropsychiatric events (e.g., agitation, aggression, hallucinations, depression, suicidal ideation).
- Theophylline: Seizures, cardiac arrhythmias.
Long-Term Effects
Long-term effects of combined use are not well-established, but monitoring for potential neuropsychiatric effects with montelukast remains essential.
Adverse Drug Reactions (ADR)
ADRs requiring immediate attention include severe neuropsychiatric symptoms (montelukast) and seizures or cardiac arrhythmias (theophylline).
Contraindications
- Montelukast: Hypersensitivity to montelukast.
- Theophylline: Hypersensitivity to theophylline or other xanthine derivatives; active peptic ulcer disease; uncontrolled seizure disorders.
Drug Interactions
Montelukast:
- Phenobarbital and rifampicin reduce the plasma concentration of montelukast.
- Montelukast is an inhibitor of CYP2C8 in vitro, but clinical interactions have not been observed.
Theophylline:
- Numerous drug interactions; some important ones include:
- Cimetidine, ciprofloxacin, erythromycin, and other macrolides: Increase theophylline levels.
- Phenytoin, phenobarbital, rifampin: Decrease theophylline levels.
- Lithium: Decreases theophylline levels.
- Beta-blockers: May interact with theophylline, altering its effects.
Pregnancy and Breastfeeding
- Montelukast: Pregnancy Category B. Generally considered safe to use during pregnancy if the benefits outweigh the risks.
- Theophylline: Use with caution during pregnancy. Monitor serum theophylline levels closely. Theophylline is excreted in breast milk.
Drug Profile Summary
Please refer to individual drug information for a complete summary.
Popular Combinations
Montelukast and theophylline are sometimes combined with inhaled corticosteroids for enhanced asthma control.
Precautions
- Assess liver and kidney function before initiating theophylline therapy.
- Closely monitor serum theophylline levels, especially when starting therapy, adjusting dosages, or adding/discontinuing interacting medications.
- Observe patients for neuropsychiatric events when taking montelukast.
- Advise patients not to abruptly discontinue medications.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Montelukast + Theophylline?
A: Montelukast is usually dosed at 10 mg once daily for adults. Theophylline dosing is individualized based on serum theophylline levels, typically targeting 5-15 mcg/mL.
Q2: How should Theophylline be monitored?
A: Serum theophylline levels should be measured regularly, particularly when initiating therapy or making dosage changes.
Q3: Are there any specific dietary restrictions when taking Theophylline?
A: A high-protein/low-carbohydrate diet or charcoal-broiled foods may decrease theophylline clearance. A low-protein/high-carbohydrate diet may increase clearance. Caffeine intake should be limited as caffeine and theophylline are both methylxanthines, with the potential to interact.
Q4: What are the signs of Theophylline toxicity?
A: Signs of toxicity include nausea, vomiting, abdominal pain, headache, insomnia, irritability, seizures, and cardiac arrhythmias.
Q5: Can Montelukast be used in children under 2 years of age?
A: The safety and efficacy of montelukast have not been established in children younger than 2 years. Other formulations are available for younger children.
Q6: How do I manage a patient who experiences neuropsychiatric events while taking Montelukast?
A: Discontinue Montelukast immediately and consider alternative therapies. Carefully evaluate the patient for underlying psychiatric conditions.
Q7: Can pregnant women take Montelukast and Theophylline?
A: Montelukast is generally considered safe during pregnancy. Theophylline should be used with caution and serum levels closely monitored. Consult a specialist.
Q8: What is the mechanism of action for this drug combination?
A: Montelukast works by blocking leukotrienes, thus reducing inflammation in the airways. Theophylline works by relaxing airway smooth muscle and also exhibits some anti-inflammatory properties.
Q9: What are the common side effects of Montelukast?
A: Common side effects include headache, upper respiratory tract infection, abdominal pain, and diarrhea.
Q10: Can Montelukast be used to treat an acute asthma attack?
A: No, Montelukast is not effective for relieving acute asthma symptoms. Patients should use a rescue inhaler (short-acting beta-agonist) for acute exacerbations.
