Aminophylline
Synonym :
Theophylline
Mechanism :
It is a soluble salt of theophylline with ethylenediamine. Theophylline is structurally classified as a methylxanthine. It causes two distinct actions in the airways of patients with reversible obstruction - smooth muscle relaxation (i.e., bronchodilation) and non-bronchodilator prophylactic effects. Bronchodilatation is mediated by the inhibition of two isozymes of phosphodiesterase (PDE III and to a lesser extent, PDE IV) while non-bronchodilator prophylactic actions are probably mediated through different molecular mechanisms.
Indication :
- Asthma
- Neonatal apnea
- Diuretic
Contraindications :
Contraindicated in individuals who have shown hypersensitivity to its components. It is also contraindicated in patients with active peptic ulcer disease, and in underlying seizure disorders. Clearance can decrease with impaired hepatic or cardiac function.
Dosing :
Bronchospasm:
Loading dose: 5 to 7 mg/kg IV over 20-30 mins or oral.
Maintenance dose:
1.5 to 6 months: 0.5 mg/kg/hour or 10 mg/kg/day orally in divided doses.
6-12 months: 0.6-0.7 mg/kg/hour IV or 12-18 mg/kg/day orally in divided doses.
1-9 years: 1 mg/kg/hour or 8 mg/kg orally every 8 hours.
9-12 years: 0.8-0.9 mg/kg/hour IV or 6.4 mg/kg orally every 8 hours.
12-16 years: 0.7 mg/kg/hour IV or 5.6 mg/kg orally every 8 hours.
Neonatal apnea:
Loading dose: 4-5 mg/kg oral/IV as a single dose.
Maintenance: 3-6 mg/kg/day oral/IV every 8 hours in divided doses.
Adverse Effect :
Nausea, vomiting, headache, irritability, insomnia. On high doses can cause myocardial infarction, urinary retention, seizures that is resistant to anticonvulsants, persistent vomiting.
Interaction :
Ciprofloxacin, Cimetidine, Thiabendazole, Erythromycin, Isoniazid, Verapamil, Diltiazem: Increased theophylline levels.
Phenobarbitone, Rifampicin, Carbamazepine, Phenytoin, Sulfinpyrazone: Reduces levels of theophylline.
Salbutamol, Salmeterol, Terbutaline: Increased risk of hypokalemia.
Halothane: Increased risk of arrythmia.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Oral: Dose as in normal renal function and adjust in accordance with blood levels IV: Dose as in normal renal function and adjust in accordance with blood levels |
| 10-20 | Oral: Dose as in normal renal function and adjust in accordance with blood levels IV: Dose as in normal renal function and adjust in accordance with blood levels |
| <10 | Oral: Dose as in normal renal function and adjust in accordance with blood levels IV: Dose as in normal renal function and adjust in accordance with blood levels |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in GFR<10 mL/min Monitor blood levels. |
| HD | Not dialysed. Dose as in GFR<10 mL/min. |
| HDF/High flux | Unknown dialysability. Dose as in GFR<10 mL/min Monitor blood levels. |
| CAV/VVHD | Not dialysed. Dose as in GFR=10– 20 mL/min Monitor blood levels. |
Hepatic Dose :
Use with caution as aminophylline clearance is reduced. Decrease the dose in patients with liver disease. Maximum initial dose = 0.2 mg/kg/day IV (theophylline) in patients > 1 year. Do not exceed 400 mg/day IV or PO in patients > 16 years, or 16 mg/kg/day up to 400 mg/day PO in patients < 16 years. Adjust dose as per serum theophylline concentrations and clinical needs.