Usage
Etofylline + Theophylline is prescribed for the symptomatic relief and prevention of reversible bronchospasm associated with asthma and chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. It belongs to the pharmacological classification of bronchodilators, specifically xanthines. The combination works by relaxing the smooth muscles of the airways, leading to bronchodilation and improved airflow to the lungs.
Alternate Names
While “Etofylline + Theophylline” is the generic name, it is marketed under various brand names, including Deriphyllin. There may be international or regional variations of these names.
How It Works
Pharmacodynamics: Etofylline and Theophylline are bronchodilators. They relax the smooth muscles in the airways, primarily by inhibiting phosphodiesterase enzymes, leading to increased intracellular cyclic adenosine monophosphate (cAMP). This increase in cAMP results in bronchodilation. Theophylline also exhibits some anti-inflammatory properties and can stimulate the respiratory drive.
Pharmacokinetics: Both drugs are absorbed orally. Theophylline’s metabolism is complex and subject to numerous drug interactions. It undergoes hepatic metabolism, primarily via the cytochrome P450 (CYP) enzyme system, particularly CYP1A2 and CYP3A4. Individual variations in CYP enzyme activity can significantly affect theophylline levels. Etofylline is thought to enhance the bronchodilatory effects of theophylline, but its specific pharmacokinetic profile in combination therapy is less well-defined. Both drugs are primarily eliminated through renal excretion.
Mode of Action: The primary mechanism is phosphodiesterase inhibition, leading to increased cAMP, which causes bronchodilation. Theophylline may also act as an adenosine receptor antagonist and have effects on intracellular calcium.
Elimination Pathways: Primarily renal excretion, with hepatic metabolism playing a significant role, especially for theophylline.
Dosage
Standard Dosage
Adults:
- Immediate-release: 300 mg per day, divided every 6-8 hours. This may be adjusted based on serum theophylline levels, with a target therapeutic range of 10-20 mcg/mL. Maximum dose generally not to exceed 400 mg per day for patients at risk for impaired clearance, including elderly patients.
- Extended-release: 300-400 mg once or twice daily. This can be adjusted based on individual patient needs and serum levels. Maximum daily dose generally not exceeding 600 mg. Patients stabilized on immediate-release theophylline can be switched to extended-release on a mg-for-mg basis.
Children:
- Dosing is weight-based, starting at 12-14 mg/kg/day divided every 4-6 hours and titrated based on serum levels, not exceeding 20 mg/kg/day or 600 mg/day total. Use ideal body weight for calculations. Specific dosing regimens vary based on age and formulation.
Special Cases:
- Elderly Patients: Initiate therapy at lower doses and titrate cautiously due to potential for age-related decline in renal and hepatic function.
- Patients with Renal Impairment: Dosage adjustments are crucial based on the degree of impairment. Consult current guidelines for specific recommendations.
- Patients with Hepatic Dysfunction: Reduced dosages are necessary. Careful monitoring of serum theophylline levels is essential.
- Patients with Comorbid Conditions: Conditions like congestive heart failure, liver disease, and certain infections can affect theophylline clearance and necessitate dosage adjustments.
Clinical Use Cases
Dosage in clinical situations like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations should be individualized based on the patient’s specific needs and monitored via serum theophylline levels.
Dosage Adjustments
Dosage must be individualized based on patient-specific factors including renal/hepatic function, age, smoking status, concomitant medications, and other comorbid conditions. Serum theophylline monitoring is essential for optimizing therapy and minimizing toxicity.
Side Effects
Common Side Effects:
Nausea, vomiting, headache, stomach upset, diarrhea, dizziness, insomnia, restlessness, irritability, and increased heart rate.
Rare but Serious Side Effects:
Seizures, cardiac arrhythmias, and severe allergic reactions.
Long-Term Effects:
Potential for chronic complications with prolonged use is not well-established, but monitoring for organ dysfunction is advisable.
Adverse Drug Reactions (ADR):
Severe adverse reactions such as seizures and cardiac arrhythmias require immediate medical intervention.
Contraindications
Hypersensitivity to etofylline, theophylline, or other xanthines; acute myocardial infarction; unstable angina; and severe cardiac arrhythmias. Use with caution in patients with peptic ulcer disease, seizure disorders, hyperthyroidism, and severe liver or kidney disease.
Drug Interactions
Numerous drug interactions can occur. CYP1A2 and CYP3A4 inducers (e.g., rifampin, phenytoin, smoking) can decrease theophylline levels. CYP inhibitors (e.g., cimetidine, erythromycin, fluconazole) can increase levels. Other clinically relevant interactions include those with certain antibiotics, antifungals, antiviral medications, lithium, and caffeine.
Pregnancy and Breastfeeding
Theophylline is categorized as Pregnancy Category C. It crosses the placenta and is excreted in breast milk. Use only if the potential benefit outweighs the risk to the fetus or nursing infant.
Drug Profile Summary
- Mechanism of Action: Bronchodilation via phosphodiesterase inhibition and possibly adenosine antagonism.
- Side Effects: Nausea, vomiting, headache, insomnia, seizures, arrhythmias.
- Contraindications: Hypersensitivity, acute MI, unstable angina, severe arrhythmias.
- Drug Interactions: Numerous, especially with CYP inducers and inhibitors.
- Pregnancy & Breastfeeding: Use with caution; weigh risks and benefits.
- Dosage: Individualized based on age, weight, and clinical status; serum monitoring is essential.
- Monitoring Parameters: Serum theophylline levels, ECG, renal and liver function tests.
Popular Combinations
Often used in combination with other bronchodilators or inhaled corticosteroids in the management of asthma and COPD.
Precautions
Careful monitoring of serum levels, particularly in patients with renal or hepatic impairment, the elderly, and those on interacting medications. Patient education on proper administration and recognizing signs of toxicity is crucial.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Etofylline + Theophylline?
A: Dosage is highly individualized based on patient factors and clinical context. See detailed dosage guidelines above.
Q2: What are the common side effects?
A: Common side effects include nausea, vomiting, headache, insomnia, dizziness, and gastrointestinal upset.
Q3: What are the serious side effects I should watch for?
A: Seizures and cardiac arrhythmias are rare but serious side effects requiring immediate medical attention.
Q4: What are the contraindications for this medication?
A: Contraindications include hypersensitivity, recent myocardial infarction, unstable angina, and severe cardiac arrhythmias.
Q5: How does smoking affect theophylline levels?
A: Smoking induces CYP1A2, which can decrease theophylline levels, potentially requiring dosage adjustments.
Q6: What are the key drug interactions I need to be aware of?
A: Many drugs interact with theophylline, especially those affecting CYP1A2 and CYP3A4 enzymes. See detailed drug interactions section.
Q7: Can this medication be used during pregnancy or breastfeeding?
A: Use with caution. Weigh potential benefits against the risks to the fetus or infant. Consult current guidelines for detailed recommendations.
Q8: How is Etofylline thought to affect Theophylline?
A: Etofylline is thought to enhance the bronchodilatory effects of Theophylline.
Q9: What are the key monitoring parameters for patients on this medication?
A: Serum theophylline levels, ECG, renal and liver function tests are important monitoring parameters.
Q10: What patient education is essential for this medication?
A: Educate patients on proper administration, potential side effects, and the importance of regular serum level monitoring. Advise patients to avoid caffeine and other interacting substances.
