Why this drug is interesting

Aminophylline is theophylline complexed with ethylenediamine to make it soluble enough to inject. Roughly 80% of what you give is theophylline, which is what the assay measures and what causes the toxicity.

It is interesting for two opposite reasons. In asthma it is a drug in retreat — displaced by inhaled and nebulised beta agonists, ipratropium, magnesium and steroids, and carrying a narrow therapeutic index that makes it hard to give safely in a crowded resuscitation room. In the bradycardia algorithm it holds a small, specific and largely unknown place: the transplanted heart.

Dosing

Patients not currently on theophylline

Loading dose 5 mg/kg — 250–500 mg
Administer slowly, at a rate not exceeding 25 mg of aminophylline per minute
If acute adverse effects occur during the load, stop the infusion for 5–10 minutes or slow the rate

The two UK labels do not agree — check which one your department follows

The figures above and below are the hameln label's. The ADVANZ label differs materially: a loading dose of 6 mg/kg rather than 5, a therapeutic range of 5–20 µg/mL rather than 10–20, and a different maintenance table — "otherwise healthy non-smoking adults: 0.7 mg/kg/hour (reducing to 0.5 mg/kg/hour beyond 12 hours)", "older patients and those with cor pulmonale: 0.6 mg/kg/hour (reducing to 0.3 mg/kg/hour)", plus a row hameln does not carry, "patients with congestive cardiac failure or hepatic disease: 0.5 mg/kg/hour".³

Both are current UK labels for the same drug. The divergence matters most for the dose reduction beyond 12 hours and the heart failure and liver disease row, neither of which appears in the hameln table — and both describe patients whose clearance is reduced. Whichever label your stock carries, prescribe this from a local protocol and a serum level, not from memory.

Contraindications

Acute porphyria
Concomitant administration with other xanthine drugs
Hypersensitivity to aminophylline, theophylline or ethylenediamine

Approximate maintenance infusion rates

Group	Maintenance
Children 6 months to 9 years	1 mg/kg/hour
Children 10–16 years and young adult smokers	0.8 mg/kg/hour
Otherwise healthy non-smoking adults	0.5 mg/kg/hour
Elderly patients	0.3 mg/kg/hour

Aminophylline is not recommended in children under 6 months, in whom elimination is reduced.

Levels and the narrow therapeutic index

The SmPC states plainly that "Aminophylline has a narrow therapeutic index, therefore cautious dosage determination is essential."¹

Therapeutic range: 10–20 micrograms/mL of theophylline
Often adequate: 5–15 micrograms/mL, with fewer adverse effects
Toxic: Levels above 20 micrograms/mL are often associated with toxic effects

Toxic features include vomiting, agitation, tremor, tachyarrhythmia, hypokalaemia, hyperglycaemia, metabolic acidosis and seizures. The hypokalaemia is driven by intracellular shift and can be profound; it is a reason to check a potassium early rather than to replace aggressively, since the total body deficit is small. Management of significant toxicity is a discussion with the National Poisons Information Service and TOXBASE.

Where it is used

Reversible airways obstruction

The licensed indication covers "reversible airways obstruction including status asthmaticus and acute bronchospasm", and cardiovascular disease including pulmonary oedema or paroxysmal nocturnal dyspnoea from left ventricular failure.¹ In current UK practice, intravenous aminophylline in acute asthma is a decision for senior clinicians, after inhaled therapy, steroids and magnesium, and generally with critical care involvement. The evidence for added benefit over optimal inhaled therapy is weak, and the adverse effect burden is not.

Bradycardia after cardiac transplant

This is the use most likely to catch a clinician out. The transplanted heart is denervated, so it has no vagal supply for atropine to block. Atropine is therefore ineffective — and the Resuscitation Council states directly that it should not be given after cardiac transplant, recommending aminophylline instead.²

The dose for this indication is not the asthma dose. RCUK specifies "aminophylline (100–200 mg slow intravenous injection)" — considerably less than the 5 mg/kg loading dose used for airways disease, which would be 400 mg in an 80 kg adult.² Use the guideline figure, not the loading dose from the section above.

Aminophylline works here because it antagonises adenosine receptors, and adenosine-mediated depression of sinus and AV nodal conduction is a mechanism that survives denervation. The same reasoning explains why adenosine itself is hazardous in the transplanted heart: the adenosine SmPC records increased sensitivity within a year of transplant, and severe bradycardia has been reported in early post-transplant patients. Full resuscitation facilities are required.

Aminophylline has also been used for bradyasystolic arrest and for spinal-cord-injury bradycardia on the same adenosine-antagonist reasoning, though the evidence there is weaker still.

Pharmacology

Mechanism

Three actions are usually described, and their relative contributions at therapeutic concentrations remain debated:

Non-selective phosphodiesterase inhibition, raising intracellular cyclic AMP — bronchodilatation and positive inotropy
Adenosine receptor antagonism — the action most relevant to its chronotropic effect and to the transplant indication
Anti-inflammatory effects at low concentrations, through histone deacetylase activation — of more interest in chronic respiratory disease than in the resuscitation room

Kinetics

Metabolism: Hepatic, principally CYP1A2 — hence the interaction burden
Induced by: Smoking, phenytoin, carbamazepine, rifampicin
Inhibited by: Ciprofloxacin, erythromycin, clarithromycin, cimetidine, fluvoxamine, allopurinol
Reduced clearance in: Heart failure, liver disease, sepsis, viral infection, the elderly

Adverse effects and cautions

Tachyarrhythmia — supraventricular and ventricular
Seizures — may occur without preceding warning symptoms
Nausea and vomiting, common and dose-related
Tremor, agitation, insomnia, headache
Hypokalaemia, hyperglycaemia, metabolic acidosis in toxicity
Hypotension, arrhythmias and convulsions may follow intravenous injection, "particularly if the injection is too rapid, and sudden deaths have been reported" — hence the 25 mg/minute ceiling

Caution is required in cardiac arrhythmia, hypertension, hyperthyroidism, peptic ulcer disease, epilepsy and hepatic impairment, and in the elderly. The ethylenediamine component is a recognised, if uncommon, cause of hypersensitivity reactions.

Critical appraisal

Its decline in asthma is appropriate and should not be reversed by nostalgia. Intravenous aminophylline adds toxicity reliably and benefit inconsistently on top of optimal inhaled therapy. Where it is still used, it should be a considered senior decision with levels and monitoring, not a reflex when the nebulisers have not worked.
The narrow therapeutic index is a systems hazard, not just a pharmacological fact. A drug requiring a loading-dose decision based on a drug history, a weight-based rate, an infusion pump and serum levels is a drug with several places to go wrong, in exactly the setting — an acutely breathless patient — where attention is scarcest.
The transplant indication is genuinely useful and almost entirely unknown. It appears in the resuscitation guidance in a single line, and a clinician who has not read that line will give atropine to a denervated heart and watch nothing happen.
Levels are frequently sent and infrequently acted on. A theophylline concentration taken during an ongoing infusion, without a documented time relative to the loading dose, is close to uninterpretable. If you send one, record when the load finished.

References

1
Aminophylline 25 mg/ml solution for injection/infusion — Summary of Product Characteristics, hameln pharma ltd. electronic Medicines Compendium. Sections 4.1–4.5, 4.8. Verified 24 Aug 2026.
2
Aminophylline hydrate 25mg/ml Solution for injection — Summary of Product Characteristics, ADVANZ Pharma. electronic Medicines Compendium. §4.2 — gives a 6 mg/kg load, a 5–20 µg/mL therapeutic range and a different maintenance table from the hameln label. Verified 24 Aug 2026.
3
Resuscitation Council UK. Adult advanced life support guidelines, 2025 — bradycardia. resus.org.uk — local copies at lifesupport.resusdoc.uk. “For bradycardia in patients with cardiac transplant or spinal cord injury, consider giving aminophylline (100–200 mg slow intravenous injection).” Verified 24 Aug 2026.
4
TOXBASE — theophylline and aminophylline. National Poisons Information Service. toxbase.org (NHS login required. NPIS: 0344 892 0111.)
5
British Thoracic Society / SIGN. British guideline on the management of asthma. brit-thoracic.org.uk
6
Aminophylline — dosing and safety monograph. BNF, NICE. bnf.nice.org.uk

Aminophylline

At a glance