Side Effects of Deriphylline
Deriphylline, a methylxanthine derivative, has numerous side effects primarily affecting the gastrointestinal, cardiovascular, and central nervous systems, with the most common being nausea, headache, and cardiac arrhythmias. 1
Mechanism and Classification
Deriphylline is a methylxanthine derivative related to theophylline, used primarily as a bronchodilator in respiratory conditions like COPD. It works through:
- Inhibition of phosphodiesterase (PDE) enzymes
- Bronchodilation (primarily through PDE3 inhibition)
- Anti-inflammatory effects (through PDE4 inhibition and histone deacetylase-2 activation) 2
Common Side Effects
Gastrointestinal Effects
- Gastric irritation and nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Dyspepsia 1
These GI side effects are dose-dependent and often the most common reason for discontinuation.
Cardiovascular Effects
- Tachycardia and palpitations
- Cardiac arrhythmias (at higher concentrations)
- Changes in blood pressure
- Increased heart rate 1, 3
Central Nervous System Effects
- Headache
- Dizziness
- Insomnia and sleep disturbances
- Irritability
- Anxiety
- Tremor
- Seizures (at higher concentrations) 1, 2
Other Effects
- Increased diuresis and urinary frequency
- Decreased appetite
- Weight loss
- Electrolyte disturbances 1
Factors Affecting Side Effects
The severity and frequency of side effects are influenced by:
Serum Concentration: Side effects increase considerably at levels >15 μg/mL 1
Drug Interactions: Medications that affect deriphylline metabolism:
- Increased levels: Cimetidine, ciprofloxacin, oral contraceptives
- Decreased levels: Smoking, alcohol, anticonvulsants, rifampicin 1
Patient Factors:
- Age (elderly patients more susceptible)
- Liver or heart failure
- Sustained fever 1
Monitoring Recommendations
To minimize adverse effects:
- Monitor blood levels regularly (therapeutic range: 5-15 μg/mL)
- Check levels after initiation, every 6-12 months during therapy, after dose changes, or when adding potentially interacting medications
- Start with low doses and titrate slowly
- Consider using with food to reduce GI side effects 1
Contraindications
Deriphylline should be avoided in patients with:
- Uncontrolled hypertension
- Underlying coronary artery disease
- Tachyarrhythmias
- Seizure disorders
- Severe hepatic impairment 1
Clinical Considerations
- In COPD patients, deriphylline may improve cardiovascular function by reducing pulmonary artery pressures and pulmonary vascular resistance while increasing ventricular ejection fraction 4, 3
- Despite potential benefits, the high frequency of side effects has led to decreased use as primary therapy, with deriphylline now typically used as add-on therapy when other treatments are insufficient 2
- Withdrawal rates of up to 27% have been reported in the first 3 months of therapy due to side effects 1
When prescribing deriphylline, always start with lower doses, monitor closely for side effects, and adjust based on therapeutic response and tolerability.