Usage
Choline theophyllinate is prescribed for the symptomatic relief of reversible bronchoconstriction associated with conditions like bronchial asthma, chronic obstructive pulmonary disease (COPD), which includes chronic bronchitis and emphysema, and other related bronchospastic disorders. It is also used when expectoration is needed.
It is pharmacologically classified as a bronchodilator and expectorant (when combined with guaifenesin).
Choline theophyllinate’s mechanism of action involves inhibiting phosphodiesterase, leading to increased intracellular cyclic adenosine monophosphate (cAMP), which results in bronchodilation. It also exhibits some anti-inflammatory effects.
Alternate Names
Choline theophyllinate is also known as oxtriphylline. Brand names include Choledyl and Choledyl SA.
How It Works
Pharmacodynamics: Choline theophyllinate relaxes the bronchial smooth muscles, leading to bronchodilation. It also demonstrates mild anti-inflammatory effects and can stimulate the central nervous system and respiratory drive. It passes freely into breast milk, reaching similar concentrations as in plasma.
Pharmacokinetics: Choline theophyllinate is readily absorbed after oral administration. Theophylline, the active component, is metabolized primarily in the liver via CYP450 enzymes, including CYP1A2 and CYP3A4. Elimination occurs mainly through renal excretion.
Mode of Action: Theophylline, released from choline theophyllinate, inhibits phosphodiesterase enzymes, leading to an increase in cAMP levels within cells. This rise in cAMP causes relaxation of bronchial smooth muscles and produces anti-inflammatory effects. Theophylline is also believed to act as an adenosine receptor antagonist, enhancing respiratory drive.
Dosage
Standard Dosage
Adults:
Initial dose: 200-400 mg every 6-8 hours or 300-400 mg every 12 hours with extended-release formulations.
Maintenance: 0.8-1.2 g daily in 3-4 divided doses, not exceeding 600 mg/day for regular formulations or 400 mg/day for extended-release in older adults.
The dose should be titrated based on clinical response and serum theophylline levels (ideally within 8-20 mcg/mL).
Children:
10-14 years: 400-800 mg daily in 4 divided doses.
5-9 years: 200-400 mg daily in 4 divided doses.
<5 years: 24-36 mg/kg body weight daily in 3 divided doses.
Not generally recommended for children under 10.
Special Cases:
- Elderly Patients: Reduced dosages are recommended due to decreased clearance. Close monitoring is essential.
- Patients with Renal Impairment: Dose reduction is required depending on the severity of renal impairment.
- Patients with Hepatic Dysfunction: Lower doses and monitoring of liver function tests are recommended.
- Patients with Comorbid Conditions: Caution is advised in patients with cardiovascular disease, hyperthyroidism, peptic ulcer disease, and seizure disorders. Dosage adjustments may be necessary.
Clinical Use Cases
Dosing in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergencies is at the discretion of the attending physician and based on patient factors, clinical presentation, and serum theophylline levels.
Dosage Adjustments
Dosage adjustments are made based on patient-specific factors like renal or hepatic function, coexisting medical conditions, drug interactions, and response to therapy. Monitoring serum theophylline levels is crucial for optimizing dosage and minimizing toxicity.
Side Effects
Common Side Effects:
Nausea, vomiting, headache, insomnia, irritability, tachycardia, palpitations, tremor, diarrhea, abdominal discomfort, epigastric pain, restlessness, rash, flushing.
Rare but Serious Side Effects:
Seizures, cardiac arrhythmias, ventricular arrhythmias, peripheral vascular collapse.
Long-Term Effects:
Potential long-term complications from prolonged use are not well-documented but may include those related to underlying diseases and adverse effects on cardiovascular or nervous systems.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include seizures, arrhythmias, and other serious cardiac events that require immediate medical intervention.
Contraindications
Absolute contraindications include hypersensitivity to theophylline or its derivatives. Relative contraindications include peptic ulcer disease, severe coronary artery disease, uncontrolled seizure disorders, hyperthyroidism, and severe hypertension. Caution should be exercised in patients with liver or kidney disease.
Drug Interactions
Choline theophyllinate interacts with numerous medications, including:
- Xanthines: Additive effects.
- CYP450 inducers (e.g., rifampicin): Decreased theophylline levels.
- CYP450 inhibitors (e.g., cimetidine, macrolide antibiotics, fluvoxamine, quinolones): Increased theophylline levels.
- Beta-blockers: Possible antagonistic effects.
- Sympathomimetics: Enhanced CNS stimulation.
Alcohol, smoking, and certain foods like grapefruit juice may also affect theophylline levels.
Pregnancy and Breastfeeding
Choline theophyllinate crosses the placental barrier and is excreted in breast milk. It should be used during pregnancy and breastfeeding only if the potential benefit justifies the potential risk to the fetus or infant. It is recommended to consult with a doctor if you are pregnant or nursing before taking this medication.
Drug Profile Summary
- Mechanism of Action: Inhibits phosphodiesterase, increases cAMP, resulting in bronchodilation.
- Side Effects: Nausea, vomiting, headache, insomnia, irritability, seizures, arrhythmias.
- Contraindications: Hypersensitivity, peptic ulcer, severe coronary artery disease, uncontrolled seizures.
- Drug Interactions: Xanthines, CYP450 inducers/inhibitors, beta-blockers, sympathomimetics.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks. Consult doctor.
- Dosage: Adult: Start 200-400mg every 6-8 hrs, max 600mg/day. Child: Weight/age based dosing.
- Monitoring Parameters: Serum theophylline levels, ECG, respiratory function.
Popular Combinations
Choline theophyllinate is often combined with salbutamol or guaifenesin. Salbutamol provides synergistic bronchodilation through a different mechanism. Guaifenesin aids in expectoration.
Precautions
Assess renal and hepatic function, cardiovascular status, and history of seizures before starting treatment. Monitor serum theophylline levels, especially with concomitant illnesses or drug interactions. Monitor pregnant or nursing patients closely if the drug is deemed essential. Exercise caution in elderly patients and those with comorbid conditions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Choline Theophyllinate?
A: Adults: Initial dose is typically 200-400 mg every 6-8 hours, or 300-400 mg every 12 hours with extended-release versions. The dose should be adjusted based on clinical response and/or serum theophylline levels, which should ideally be between 8 and 20 mcg/mL. Maximum daily dosage is usually 600 mg.
Q2: How should Choline Theophyllinate be administered?
A: It can be administered orally as a tablet, capsule, syrup, or elixir. It is also available as a solution for nebulization.
Q3: What are the common side effects of Choline Theophyllinate?
A: Common side effects include nausea, vomiting, headache, insomnia, irritability, tachycardia, palpitations, and tremors.
Q4: When is Choline Theophyllinate contraindicated?
A: It is contraindicated in patients with hypersensitivity to the drug or other theophylline derivatives, and should be used with extreme caution in patients with active peptic ulcers. It is also contraindicated in patients with coronary artery disease where myocardial stimulation is not advisable, and in those with uncontrolled seizure disorders.
Q5: Does Choline Theophyllinate interact with other medications?
A: Yes, clinically significant drug interactions can occur with other xanthines, certain antibiotics (like macrolides and quinolones), cimetidine, and some antidepressants. Refer to the Drug Interactions section for a comprehensive list.
Q6: Can Choline Theophyllinate be used during pregnancy and breastfeeding?
A: Choline theophyllinate should be used during pregnancy and breastfeeding only if the potential benefit justifies the potential risk to the fetus or infant. Serum levels in breast milk can reach similar concentrations as plasma levels. Close monitoring of the mother and infant is necessary if the drug is used.
Q7: How should Choline Theophyllinate dosage be adjusted for elderly patients?
A: Elderly patients often require lower doses due to age-related decreases in drug clearance. Careful monitoring is essential.
A: It is metabolized primarily in the liver by CYP450 enzymes and eliminated mainly through renal excretion.
Q9: What are the symptoms of Choline Theophyllinate overdose?
A: Symptoms of overdose can include seizures, cardiac arrhythmias, and other serious cardiovascular events.
Q10: What are the monitoring parameters for patients on Choline Theophyllinate?
A: Serum theophylline levels, ECG, and respiratory function should be monitored regularly.
