Usage
- Doxofylline + Terbutaline is prescribed for the treatment of Chronic Obstructive Pulmonary Disease (COPD), asthma, and chronic bronchitis.
- Pharmacological Classification: Bronchodilator, Anti-asthmatic
- Mechanism of Action: Doxofylline, a xanthine derivative, inhibits phosphodiesterase enzymes, leading to increased intracellular cyclic AMP levels, which relaxes airway smooth muscle. Terbutaline, a beta-2 adrenergic agonist, stimulates beta-2 receptors, further promoting bronchodilation and reducing airway resistance.
Alternate Names
- Doxinext-T, Doxofyn T
- Various brand names depending on the manufacturer (e.g., Doxinext-T, Doxofyn T, Fildox T, Glydil TS).
How It Works
- Pharmacodynamics: Doxofylline and terbutaline both work to relax the bronchial smooth muscles, leading to bronchodilation and improved airflow. Terbutaline, through its beta-2 agonist activity, may also inhibit mast cell degranulation, which contributes to the anti-asthmatic effect.
- Pharmacokinetics: Doxofylline is well-absorbed orally and is metabolized in the liver. Approximately 90% of the drug is cleared hepatically with a small amount excreted unchanged in urine. Terbutaline can be administered orally, subcutaneously, or via inhalation, but its oral bioavailability is low due to extensive first-pass metabolism. It’s metabolized by conjugation in the liver and excreted primarily in urine.
- Mode of Action: Doxofylline increases intracellular cyclic AMP (cAMP) by inhibiting phosphodiesterase enzymes. Terbutaline activates beta-2 adrenergic receptors on bronchial smooth muscle cells, leading to activation of adenylate cyclase and increased cAMP production. Elevated cAMP levels cause relaxation of the airway smooth muscle.
- Receptor Binding/Enzyme Inhibition: Doxofylline inhibits phosphodiesterase enzymes, particularly PDE4. Terbutaline is a beta-2 adrenergic receptor agonist.
- Elimination Pathways: Doxofylline is primarily metabolized in the liver and eliminated through hepatic excretion, while terbutaline is also metabolized in the liver and eliminated renally.
Dosage
Standard Dosage
Adults:
- Doxofylline: 400 mg twice or thrice daily, up to a maximum of 1200 mg daily.
- Terbutaline: 2.5-5 mg three times daily at eight-hour intervals, up to 15 mg per 24 hours (oral). Inhalation: 0.5 mg (one inhalation) as needed, repeated doses five minutes apart, up to 3 mg in 24 hours.
Children:
- Doxofylline: <12 years: 6-9 mg/kg twice daily as syrup; ≥12 years: 200 mg twice or thrice daily.
- Terbutaline: Not generally recommended for children under 12 for oral or subcutaneous administration. For children 12-15 years of age, the dose is 2.5 mg orally three times a day, not to exceed 7.5 mg in 24 hours. Inhalational use may be considered for children older than 6 years.
Special Cases:
- Elderly Patients: Doxofylline: Reduced dose (200 mg twice or thrice daily). Terbutaline: Dosage adjustments may be necessary.
- Patients with Renal Impairment: Dose reduction may be required for both drugs.
- Patients with Hepatic Dysfunction: Dose reduction may be required for both drugs.
- Patients with Comorbid Conditions: Caution in patients with cardiovascular disease, hyperthyroidism, diabetes mellitus, glaucoma, seizure disorders, and peptic ulcers.
Clinical Use Cases
- Specific dosage adjustments for clinical use cases like intubation, surgical procedures, mechanical ventilation, and ICU use are not universally standardized and should be determined based on the patient’s condition and in consultation with a pulmonologist or critical care specialist.
- Emergency Situations: Parenteral terbutaline may be used in acute exacerbations of asthma or COPD, but its use should be short-term.
Dosage Adjustments
- Adjust dosages based on patient-specific factors such as renal/hepatic function, age, and concomitant medications.
Side Effects
Common Side Effects
- Headache, nausea, tremors, restlessness, dizziness, palpitations, insomnia, vomiting, gastrointestinal upset.
Rare but Serious Side Effects
- Severe tremors, chest pain, rapid or irregular heartbeat, seizures, confusion, paradoxical bronchospasm, allergic reactions (rash, itching/swelling, severe dizziness, trouble breathing), hypokalemia.
Long-Term Effects
- Potential long-term effects are not well-established but may include worsening of underlying cardiovascular conditions.
Adverse Drug Reactions (ADR)
- Paradoxical bronchospasm, severe allergic reactions, cardiac arrhythmias, hypokalemia.
Contraindications
- Hypersensitivity to doxofylline or terbutaline, acute myocardial infarction, hypotension. Terbutaline injection is contraindicated for prolonged tocolysis.
Drug Interactions
- Beta-blockers, diuretics, digoxin, MAOIs, tricyclic antidepressants, theophylline, cimetidine, allopurinol, erythromycin, ciprofloxacin, caffeine, alcohol.
Pregnancy and Breastfeeding
- The safety of Doxofylline + Terbutaline during pregnancy and lactation has not been established. Terbutaline injection is contraindicated for the prevention or prolonged treatment of preterm labor. Oral terbutaline is not recommended for tocolysis. Doxofylline may be present in breast milk. Use only if clearly needed and under strict medical supervision.
Drug Profile Summary
(Refer to sections above)
Popular Combinations
- None specifically listed, however, it is often used in combination with inhaled corticosteroids for COPD management.
Precautions
(Refer to sections on side effects, contraindications, and drug interactions). Exercise caution in elderly patients, patients with renal/hepatic impairment, cardiovascular disease, diabetes, hyperthyroidism, glaucoma, seizure disorders, and peptic ulcers.
FAQs (Frequently Asked Questions)
(Please see specific answers below common FAQs. Remember that medical advice should be tailored to the individual patient. These FAQs and their answers are for informational purposes only and do not constitute medical advice. Always consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.)
Q1: What is the recommended dosage for Doxofylline + Terbutaline?
A: See the detailed dosage guidelines above. Standard adult dosages are doxofylline 400 mg and terbutaline 2.5-5 mg, each taken twice daily. Adjust based on individual patient needs and tolerability.
Q2: What are the common side effects?
A: Common side effects may include headache, nausea, tremors, palpitations, dizziness, and insomnia.
Q3: Is Doxofylline + Terbutaline safe in pregnancy?
A: No, the safety of Doxofylline + Terbutaline in pregnancy has not been established. Injectable terbutaline is contraindicated for tocolysis or preterm labor prevention. Oral terbutaline is also not recommended for this purpose. Use during pregnancy only if the potential benefits justify the potential risks and under close medical supervision.
Q4: How should I monitor a patient on this medication?
A: Monitor heart rate, respiratory rate, CNS effects (irritability, insomnia), and potassium levels.
Q5: Are there any contraindications to using this combination?
A: Yes. Contraindications include hypersensitivity to either component, acute myocardial infarction, and hypotension. Terbutaline injection should not be used for prolonged tocolysis.
Q6: What are the key drug interactions I should be aware of?
A: Important drug interactions exist with beta-blockers, diuretics, digoxin, MAOIs, tricyclic antidepressants, and theophylline, amongst others. See detailed section on drug interactions above.
Q7: Can this medication be used in children?
A: Doxofylline can be used in children. See dosage recommendations in the relevant section. Terbutaline is not routinely used in children under 12 except under specialized circumstances.
Q8: What should I do if my patient experiences side effects?
A: Evaluate the severity and nature of the side effects. Mild side effects may resolve on their own, while others may require dose adjustments or discontinuation of the medication. For severe side effects, prompt medical intervention is necessary.
Q9: How does Doxofylline + Terbutaline compare to other COPD treatments?
A: The choice of COPD treatment depends on the severity and individual characteristics of the patient. Doxofylline + Terbutaline offers a combined bronchodilatory effect, but other options like inhaled corticosteroids, long-acting beta-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), or combinations thereof may be more appropriate for some patients. Treatment should be personalized.
