Aminophylline

Aminophylline is the soluble salt of theophylline with ethylenediamine, given intravenously for severe acute asthma not responding to nebulised bronchodilators and corticosteroids, and orally as modified release. It contains about 79% theophylline by weight.

Classification. Methylxanthine, phosphodiesterase inhibitor and adenosine antagonist.

Mechanism. Releases theophylline, which relaxes airway smooth muscle by phosphodiesterase inhibition and adenosine antagonism.

Pharmacokinetics. Intravenous bioavailability is complete. Metabolised by CYP1A2 with saturable kinetics. Half-life 7 to 9 hours in non-smoking adults, 4 to 5 hours in smokers and over 24 hours in severe heart failure or cirrhosis.

Emergency, severe or life-threatening asthma not responding to nebulised bronchodilators and corticosteroids. Specialist or senior decision, in a monitored setting. Evidence of benefit is weak, so it is reserved for patients failing other treatment.

• Loading: 5 mg/kg (by ideal body weight) intravenously over 20 to 30 minutes, at a rate not above 25 mg/minute. Omit the loading dose if the patient has taken theophylline or aminophylline in the past 24 hours, unless a level is available.

• Maintenance infusion: 0.5 mg/kg/hour. Use 0.3 mg/kg/hour in older adults, heart failure, cirrhosis or when interacting drugs are given. Smoking adults may need up to 0.7 mg/kg/hour.

• Children 6 months to 11 years: loading 5 mg/kg over 20 to 30 minutes, then 1 mg/kg/hour. Children 12 years and over: adult doses.

Target serum level. 10 to 20 mg/L (55 to 110 micromol/L). Take a level 4 to 6 hours after the loading dose and then every 24 hours during the infusion.

COPD exacerbation. Not routine. Considered only when the response to nebulised bronchodilators is inadequate, with level monitoring.

Oral modified-release. 225 to 450 mg twice daily, adjusted to level. Aminophylline 225 mg contains about 180 mg theophylline.

First-line, alternative, specialist. No first-line use. Intravenous use is an emergency or specialist option. Oral use is an alternative add-on controller.

Titration. Adjust the infusion rate to the level and clinical response.

Contraindications. Hypersensitivity to xanthines or ethylenediamine, uncontrolled arrhythmia, untreated epilepsy, porphyria.

Serious adverse effects. Arrhythmia and hypotension with fast injection, seizures, severe hypokalaemia, hyperglycaemia, lactic acidosis, vomiting.

Common adverse effects. Nausea, tachycardia, tremor, headache, agitation.

Interactions. Levels rise with ciprofloxacin, macrolides, fluvoxamine, cimetidine and oral contraceptives. Levels fall with rifampicin, phenytoin, carbamazepine and phenobarbital. Additive hypokalaemia and tachycardia with beta-2 agonists, corticosteroids and diuretics.

Common prescribing errors. Loading in a patient already on theophylline. Dosing by actual weight in obesity. Giving the loading dose as a fast bolus. Continuing the infusion without levels.

Special groups.

• Pregnancy: used in severe asthma if needed; check levels in the third trimester. Breastfeeding: small amounts in milk; compatible with monitoring.

• Older adults: lower maintenance rate.

• Kidney impairment: no adjustment. Liver impairment: reduce the infusion rate to 0.3 mg/kg/hour and monitor levels.

• East Africa: aminophylline is widely stocked and used in severe asthma where other options are limited. Where levels are unavailable, use the lowest effective dose, avoid loading after recent theophylline and watch closely for toxicity.

Formulations. Injection 25 mg/mL (250 mg in 10 mL). Modified-release tablets 225 mg and 350 mg in some regions.

Preparation. Dilute in sodium chloride 0.9% or glucose 5%. A usual loading dilution is the dose in 100 mL given over 20 to 30 minutes. A usual maintenance bag is 500 mg in 500 mL (1 mg/mL), run through an infusion pump.

Baseline. ECG, potassium, heart rate, recent theophylline use, ideal body weight.

Monitoring. Continuous ECG and SpO2 during loading. Level 4 to 6 hours after loading and every 24 hours. Potassium, glucose and lactate during prolonged infusion. Respiratory rate and peak flow.

Stop and reduce rules. Stop for arrhythmia, seizure or level over 20 mg/L with symptoms. Omit and reduce when the level is 20 to 25 mg/L. Level over 30 mg/L or any seizure: this is an emergency needing poisoning care.

Referral and escalation. Escalate to critical care for failure to improve, exhaustion, rising carbon dioxide or any arrhythmia.