What is theophylline used to treat?
- COPD (chronic bronchitis, ephysema)
- Premature apnea
What is the MOA of theophylline?
- Bronchodilation: antagonism of adenosine receptors, inhibition of phosphodiesterase (increase cAMP)
- Enhances contractile ability of the diaphragm (helps break up mucus in the lungs and gets mucus moving)
What is aminophylline?
derivative of theophylline
How is theophylline dosed?
- Use ABW for dosing unless the patient is obese, then use IBW
- For every 1 mg/kg of theophylline, blood concentrations will rise ~2 mg/L
What is the LD of theophylline?
- LD is optional for patients who have had previous doses in the past 24 hours
- Must use IV or rapid-release oral products
- 4-6 mg/kg
- 2-3 mg/kg (for patients who have received theophylline in the past 24 hours)
What is the maintenance dose for theophylline?
- Oral: 10 mg/kg/day (max 900mg daily)
- decreased to 5 mg/kg/day in patients w/ heart failure or liver dysfunction (max 400mg daily)
- SR = split dose in half
- IR = split into 4 doses
IV continuous infusion: 0.5 mg/kg/hr
What is the therapeutic range for theophylline?
- Adults: 5-15 mg/L
- serum concentrations up to 20mg/L may be acceptable in some patients
Neonates: 6-13 mg/L
What are the AE (within therapeutic range) of theophylline?
What AE can be experienced with theophylline serum concentrations of 20-30 mg/L?
What AE can be experienced with theophylline serum concentrations > 40 mg/L?
- Life threatening arrhythmias
- ventricular tachycardia, fibrillations, or PVCs
What is the absorption of theophylline?
- S = 1 for theophylline
- S = 0.8 for aminophylline
- Accelerated absorption and potentially toxic concentration of theophylline may occur if once-daily formulations are administered with food
- Absorption greatly increased when taken with food
- Take 1 hour before or 2 hours after eating
What is the distribution of theophylline?
- Vd = 0.4 - 0.6 L/kg
- Remains stable regardless of concomitant disease states
- 40% bound to plasma proteins (limited effect of clearance)
What is the metabolism of theophylline?
- >90% hepatic metabolism
- CYP450: 1A2, 2E1, 3A4
- Leads to hydroxylation, demethylation, or methylation of theophylline
- Half-life is variable and depends on clearance factors
How is theophylline excreted?
- 10% unchanged in the urine
- Dosage adjustment not necessary in patients with renal impairment
- Removed by hemodialysis (dosing should occur after dialysis)
What is the half-life of theophylline?
- rages from 5-24 hours
- longer in neonates and premature neonates
- accelerated in children 1-9 years
- may be prolonged in patients > 65 years
What drugs will increase the clearance of theophylline?
Inducers of 1A2 and 3A4: smoking, phenytoin, carbamazepine, phenobarbital, rifampin
Diet:charbroiled foods, low carbohydrates, high protein
What drugs decrease the clearance of theophylline?
- Inhibitors of 1A2 and 3A4:
- ciprofloxacin, azoles, clarithromycin, erythromycin, telitrhomycin, protease inhibitors, verapamil, oral contraceptives,
Others: cirrhosis, acute hepatitis, heart failure, hypothyroidism, diet (low protein, high carbs)