Usage
- This combination medication is primarily prescribed for the treatment of reversible bronchospasm associated with respiratory conditions like asthma, chronic bronchitis, and emphysema, especially chronic obstructive pulmonary disease (COPD).
- Pharmacological Classification: Bronchodilator (combining a xanthine derivative and a beta-2 adrenergic agonist).
- Mechanism of Action: Choline theophyllinate inhibits phosphodiesterase, leading to increased intracellular cAMP, resulting in bronchodilation. Terbutaline, a beta-2 agonist, directly stimulates beta-2 receptors in the lungs, also causing bronchodilation. The combined effect results in synergistic bronchodilation.
Alternate Names
- Oxtriphylline (for choline theophyllinate).
- Brand Names: Numerous brand names exist, varying regionally. Examples include Ainavent PD, Asthelite PD, Caprivent PD, Covent, Corvent PD, Domvent ST, and Kidivent-PD.
How It Works
- Pharmacodynamics: Both components work synergistically to relax bronchial smooth muscle, leading to bronchodilation and improved airflow. Terbutaline also inhibits mast cell degranulation, reducing the release of inflammatory mediators.
- Pharmacokinetics:
- Absorption: Both drugs are absorbed orally. Choline theophyllinate is metabolized to theophylline.
- Metabolism: Primarily hepatic metabolism for both drugs, though the specific CYP enzymes involved vary. Theophylline metabolism is particularly susceptible to variations due to factors like smoking, age, and concomitant medications.
- Elimination: Renal excretion for both drugs, with theophylline clearance being significantly reduced in renal impairment.
- Mode of Action:
- Choline Theophyllinate: Inhibits phosphodiesterase, increasing intracellular cAMP levels, leading to smooth muscle relaxation in the airways.
- Terbutaline: Stimulates beta-2 adrenergic receptors, activating adenylate cyclase, which also increases cAMP, resulting in bronchodilation.
- Receptor Binding: Terbutaline selectively binds to beta-2 adrenergic receptors.
- Elimination Pathways: Primarily renal excretion for both drugs.
Dosage
Standard Dosage
Adults:
- A common formulation contains 1.25 mg of terbutaline and 50 mg of choline theophyllinate per 5 ml of syrup. The usual dose is 5 ml, three to four times a day.
Children:
- Pediatric dosing should be based on weight or age and individualized according to the child’s response and tolerance to the medication.
Special Cases:
- Elderly Patients: Start with lower doses due to potential age-related decline in renal and hepatic function.
- Patients with Renal Impairment: Dose reduction is necessary due to decreased theophylline clearance.
- Patients with Hepatic Dysfunction: Careful monitoring and dose adjustment may be required.
- Patients with Comorbid Conditions: Particular caution is advised in patients with heart disease, hyperthyroidism, hypertension, diabetes, or seizure disorders.
Clinical Use Cases
- The primary use is in the management of chronic respiratory conditions like COPD, rather than acute situations like intubation, surgery, mechanical ventilation, ICU care, or emergency scenarios. In these acute settings, other bronchodilators are typically preferred.
Dosage Adjustments
- Dose adjustments are made based on patient-specific factors such as age, weight, renal function, hepatic function, and concomitant medications, especially those affecting theophylline metabolism.
Side Effects
Common Side Effects
- Nausea
- Vomiting
- Stomach upset
- Restlessness
- Tremor
- Palpitations
- Increased heart rate
- Dizziness
- Headache
Rare but Serious Side Effects
- Cardiac arrhythmias
- Seizures
- Paradoxical bronchospasm
- Severe hypokalemia
- Allergic reactions
Long-Term Effects
- Potential for tolerance to the bronchodilator effects with prolonged use.
Adverse Drug Reactions (ADR)
- Severe allergic reactions (anaphylaxis) requiring immediate medical attention.
- Cardiac arrhythmias requiring prompt intervention.
Contraindications
- Hypersensitivity to theophylline, terbutaline, or any component of the formulation.
- Severe heart disease, especially tachyarrhythmias.
Drug Interactions
- Other xanthines (e.g., caffeine, theophylline) - additive effects.
- Beta-2 agonists - additive effects.
- Some antibiotics (e.g., erythromycin, ciprofloxacin) - may increase theophylline levels.
- Cimetidine - may increase theophylline levels.
- Alcohol - may worsen dizziness and other side effects.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Considered potentially harmful, particularly in the first trimester. Use only when clearly needed and under close medical supervision. Terbutaline has been used to suppress preterm labor but with significant risks.
- Breastfeeding: Terbutaline is excreted in breast milk; monitor infants for potential side effects.
Drug Profile Summary
- Mechanism of Action: Bronchodilation via phosphodiesterase inhibition (theophylline) and beta-2 receptor stimulation (terbutaline).
- Side Effects: Nausea, vomiting, tremor, palpitations, tachycardia, dizziness.
- Contraindications: Hypersensitivity, severe heart disease, tachyarrhythmias.
- Drug Interactions: Xanthines, beta-2 agonists, caffeine, some antibiotics.
- Pregnancy & Breastfeeding: Use with caution; potential fetal/neonatal effects.
- Dosage: Adults: commonly 5 ml syrup (containing 1.25mg terbutaline + 50mg choline theophyllinate), 3-4 times/day. Pediatric: Adjust by weight and age.
- Monitoring Parameters: Pulmonary function tests (PEFR, FEV1), heart rate, blood pressure, potassium levels.
Popular Combinations
- Formulated as a single product containing both drugs.
- May be co-administered with inhaled corticosteroids in some cases.
Precautions
- Monitor potassium levels.
- Caution in patients with cardiac, renal, hepatic, or thyroid disease.
- Caution in patients with diabetes or seizure disorders.
- Avoid alcohol.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Choline Theophyllinate + Terbutaline?
A: Adults commonly take 5 ml of syrup (containing 1.25 mg terbutaline + 50 mg choline theophyllinate), three to four times daily. Pediatric dosage is weight- and age-based, requiring individualization.
Q2: What are the common side effects?
A: Nausea, vomiting, tremors, palpitations, tachycardia, dizziness, headache.
Q3: What are the serious side effects?
A: Cardiac arrhythmias, seizures, paradoxical bronchospasm, severe hypokalemia, allergic reactions.
Q4: What conditions are contraindicated with this medication?
A: Hypersensitivity, severe heart disease, tachyarrhythmias.
Q5: What drugs interact with Choline Theophyllinate + Terbutaline?
A: Other beta-2 agonists, xanthines (including caffeine), some antibiotics (macrolides, quinolones), cimetidine.
Q6: Can this medication be used during pregnancy and breastfeeding?
A: Use with caution; potential for fetal/neonatal tachycardia and other adverse effects. Consult a specialist. Not generally recommended during pregnancy.
Q7: How should the dosage be adjusted in elderly patients or patients with renal/hepatic impairment?
A: Start with lower doses and titrate carefully based on clinical response and monitoring.
Q8: What are the long-term effects of using this combination?
A: Potential for tolerance to bronchodilator effects; regular monitoring of lung function is necessary.
Q9: Can this combination be used for acute bronchospasm?
A: While it can provide bronchodilation, other medications are generally preferred for acute attacks due to faster onset of action.
Q10: What lifestyle advice should be given to patients taking this medication?
A: Avoid smoking, minimize exposure to allergens and respiratory irritants, maintain good hydration. Limit caffeine intake. Do not consume alcohol while on this medication.
