Introduction
Dyphylline is a xanthine derivative bronchodilator used primarily in the management of reversible airway obstruction associated with asthma, chronic bronchitis, and emphysema. Unlike other methylxanthines, dyphylline is a neutral compound that differs structurally from theophylline by having a hydroxyethyl group at the N-7 position. This monograph provides comprehensive information about dyphylline for healthcare professionals.
Mechanism of Action
Dyphylline exerts its bronchodilatory effects through multiple mechanisms. Primarily, it acts as a phosphodiesterase inhibitor, increasing intracellular cyclic AMP levels by inhibiting its breakdown. This leads to relaxation of bronchial smooth muscle. Additionally, dyphylline may antagonize adenosine receptors and promote catecholamine release, contributing to its bronchodilatory effects. Unlike theophylline, dyphylline is not metabolized to active xanthine metabolites.
Indications
- Treatment and prevention of bronchospasm associated with asthma
- Management of reversible bronchospasm in chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema
- Adjuvant therapy in the management of acute exacerbations of asthma and COPD
Dosage and Administration
Adults: 15 mg/kg orally every 6 hours, not to exceed 400 mg per dose Maximum daily dose: 1600 mg (4 divided doses) Special Populations:- Renal impairment: Reduce dose by 25-50% for CrCl <50 mL/min
- Hepatic impairment: Use with caution; consider dose reduction
- Geriatric patients: Start with lower end of dosing range
- Pediatric patients: Safety and efficacy not established in children
- Oral administration with water
- May be taken with food to minimize gastrointestinal upset
- Do not crush or chew extended-release formulations
Pharmacokinetics
Absorption: Rapidly and completely absorbed from GI tract; bioavailability approximately 80-85% Distribution: Volume of distribution: 0.6-0.8 L/kg; minimal protein binding (5-10%) Metabolism: Undergoes minimal hepatic metabolism; not converted to theophylline Elimination: Primarily excreted unchanged in urine (80-90%); elimination half-life: 2-3 hours in normal renal function Special Considerations: Renal excretion is pH-dependent; alkaline urine may decrease eliminationContraindications
- Hypersensitivity to dyphylline, xanthine derivatives, or any component of the formulation
- Active peptic ulcer disease
- Uncontrolled seizure disorders
- Concurrent use with other xanthine derivatives
Warnings and Precautions
- Use with caution in patients with cardiac arrhythmias, hypertension, or heart failure
- May exacerbate gastroesophageal reflux disease (GERD)
- Caution in patients with hyperthyroidism
- Risk of seizures, particularly in patients with underlying seizure disorders
- May cause central nervous system stimulation
- Use cautiously in patients with renal impairment (requires dose adjustment)
Drug Interactions
Major Interactions:- Cimetidine: May decrease dyphylline clearance
- Macrolide antibiotics (erythromycin, clarithromycin): May increase dyphylline levels
- Fluoroquinolones: May increase dyphylline concentrations
- Beta-blockers: May antagonize bronchodilator effects
- Lithium: Dyphylline may increase lithium excretion
- Oral contraceptives: May decrease dyphylline clearance
- Phenytoin, carbamazepine: May increase dyphylline metabolism
- Smoking: May increase dyphylline clearance
Adverse Effects
Common (≥1%):- Gastrointestinal: Nausea, vomiting, epigastric pain, diarrhea
- Central nervous system: Headache, insomnia, nervousness, dizziness
- Cardiovascular: Palpitations, tachycardia
- Cardiac arrhythmias
- Seizures
- Hypersensitivity reactions
- Severe gastrointestinal bleeding
Monitoring Parameters
- Therapeutic drug monitoring: Not routinely required (unlike theophylline)
- Pulmonary function tests (FEV1, peak flow)
- Heart rate and rhythm
- Signs and symptoms of toxicity (nausea, vomiting, tachycardia, seizures)
- Renal function (serum creatinine, BUN)
- Clinical response and symptom control
Patient Education
- Take medication exactly as prescribed; do not exceed recommended dose
- Report any persistent nausea, vomiting, palpitations, or nervousness
- Avoid excessive caffeine consumption
- Inform all healthcare providers about dyphylline use
- Do not stop medication abruptly without medical supervision
- Seek immediate medical attention for difficulty breathing, chest pain, or severe side effects
- Store at room temperature away from moisture and heat
References
1. American Society of Health-System Pharmacists. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2023. 2. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2023. 3. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2023. 4. McEvoy GK, ed. AHFS Drug Information. American Society of Health-System Pharmacists; 2023. 5. Lexicomp Online. Dyphylline monograph. Wolters Kluwer Clinical Drug Information; 2023. 6. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th ed. McGraw-Hill Education; 2017. 7. Drugdex Evaluations. Micromedex Solutions. Truven Health Analytics; 2023.