Aminophylline is a classic bronchodilator used in asthma and bronchitis attacks that do not respond well to inhalers. It is administered in hospital by injection or drip in severe situations.
Also known as: Teofilina etilenodiamina, Cardophylin
Clarithromycin reduces the elimination of aminophylline (theophylline), potentially causing xanthine toxicity: tachycardia, arrhythmias, nausea, vomiting and seizures.
Macrolides (clarithromycin) inhibit CYP1A2/3A4, reducing theophylline/aminophylline clearance (Prontuário, Xanthines 5.1.4 and Annex 7).
Theophylline level (10–20 µg/ml), heart rate, nausea, tremor.
Palpitations, persistent vomiting, coarse tremor, seizures.
Reduce the aminophylline dose by about half and monitor serum theophylline levels where possible.
INFARMED Prontuário Terapêutico (11th ed., 2012), Xanthines 5.1.4 — macrolides and Annex 7 (Theophylline: drugs decreasing metabolism); DailyMed — Clarithromycin Tablet label, Drug Interactions: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Ciprofloxacin inhibits theophylline metabolism (aminophylline), raising serum levels and toxicity risk (arrhythmias, seizures).
Ciprofloxacin is a potent CYP1A2 inhibitor, the main metabolic pathway of theophylline (Prontuário, Annex 7 Quinolones).
Theophylline level, heart rate, neurological status.
Tachycardia, tremor, insomnia, seizures.
Reduce the aminophylline dose and monitor serum levels; consider an alternative antibiotic if possible.
INFARMED Prontuário Terapêutico (11th ed., 2012), Annex 7 — Quinolones: "Theophylline: ciprofloxacin... inhibit theophylline metabolism"; DailyMed — Ciprofloxacin Tablet label [Bayer, RLD Cipro]: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c47250c2-bece-46b5-8b3b-b7c97d9005d8
Cimetidine reduces theophylline (aminophylline) clearance, potentially raising serum levels and the risk of xanthine toxicity.
Cimetidine inhibits hepatic CYP enzymes (including CYP1A2), decreasing theophylline metabolism (Prontuário, Xanthines 5.1.4: "anti-ulcer drugs: cimetidine").
Theophylline level, heart rate, nausea, tremor.
Palpitations, vomiting, tremor, seizures.
Consider aminophylline dose reduction or switching cimetidine to an antacid/PPI.
INFARMED Prontuário Terapêutico (11th ed., 2012), Xanthines 5.1.4 (p. 281) — "anti-ulcer drugs: cimetidine" influence theophylline/aminophylline clearance; DailyMed — Cimetidine Tablet label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=496e258d-a5fd-42da-9a86-73afc8be359b
Aminophylline (theophylline) increases renal lithium excretion, potentially reducing its therapeutic effect and precipitating manic relapse.
Theophylline increases renal lithium clearance (Annex 7: "Theophylline: increased renal lithium excretion with reduced lithium effect").
Serum lithium, relapse symptoms (mood, sleep, agitation).
Manic symptom relapse, serum lithium below therapeutic range.
Monitor serum lithium after starting/stopping aminophylline; adjust the lithium dose if needed.
INFARMED Prontuário Terapêutico (11th ed., 2012), Annex 7 — Lithium: "Theophylline: increased renal lithium excretion with reduced lithium effect"; DailyMed — Lithium Carbonate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b839ff4b-f62d-41ab-a823-550a756d58ec
Salbutamol plus aminophylline adds bronchodilator effect but also additive tachycardia, arrhythmias and hypokalaemia.
Prontuário Xanthines 5.1.4: "Xanthines can potentiate the hypokalaemia associated with beta-2 sympathomimetics"; both increase myocardial O2 consumption.
Serum potassium, ECG, heart rate, tremor.
Tachycardia, coarse tremor, vomiting, symptomatic hypokalaemia.
Commonly used in severe acute asthma, but requires monitoring: potassium, ECG and heart rate; limit individual doses.
INFARMED Prontuário Terapêutico (11th ed., 2012), Xanthines 5.1.4 (p. 281) — hypokalaemia with beta-2 sympathomimetics; DailyMed — Aminophylline Injection label [RLD]: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=819207a2-0c37-b275-e053-2a91aa0afb36
Caffeine is also a xanthine — it adds CNS and cardiac stimulation effects (tremor, tachycardia, insomnia) to those of aminophylline.
Limit coffee, tea, energy drinks and chocolate during treatment.
Prontuário Terapêutico INFARMED, 5.1.4 Xanthines (additive xanthine effects; ADRs tremor, tachycardia, insomnia).
Food slows oral theophylline/aminophylline absorption without reducing total amount absorbed; sustained-release schedules require consistent timing relative to meals.
Always take at the same time and consistently relative to meals; do not change habits without informing the doctor (it alters serum levels).
Prontuário Terapêutico INFARMED, 5.1.4 Xanthines: "The clearance of theophylline and aminophylline is influenced by food…" (l. 20209).
Aminophylline/theophylline lowers the seizure threshold — seizures are the most serious toxicity sign.
Monitor serum levels in treatments > 24 h; reduced dose in elderly.
Site monograph (aminophylline — monitor serum levels, seizures as toxicity).
Aminophylline clearance is reduced in HF and liver disease — accumulation and toxicity.
Reduce dose; measure serum levels.
Site monograph (aminophylline — caution in hepatic, cardiac failure and elderly — reduced clearance).
No specific Annex 1 entry (See Xanthines); IV aminophylline is used in severe maternal asthma attacks with favourable experience, but may cause fetal tachycardia and, at maternal toxic doses, arrhythmias and seizures. Xanthines have also been used as tocolytics (positive neonatal effect: apnoea), but the preferred regimen in pregnancy asthma is inhaled corticosteroid + beta-2 agonist; aminophylline is reserved for refractory cases.
Use only in refractory severe crises, at adjusted dose (monitor plasma levels: 10–20 µg/ml); avoid high doses near term (neonatal tachycardia/irritability).
Passes into milk and may cause infant irritability and insomnia (theophylline is the documented prototype); monitor the infant if the mother keeps treatment.
Prontuário Terapêutico INFARMED — 5.1.4 (Xanthines); EMC-UK (MHRA) — Aminophylline SmPC (section 4.6).
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Bronchodilation within 30–60 min IV; ↑ diaphragmatic strength; mild diuresis.
Non-selective phosphodiesterase inhibition (↑ cAMP and cGMP → bronchial smooth muscle relaxation); adenosine receptor antagonism (pro-convulsant and diuretic effect).
Oral: good absorption (~ 90%); IV: 100% bioavailability; IV form preferred in emergency.
Extensive hepatic metabolism (CYP1A2 → 1-methylxanthine, CYP3A4, CYP2E1); ~ 10% excreted unchanged in urine.
~ 6–8 h (non-smoking adult); ~ 4–5 h (smoker); prolonged in neonates, elderly and liver/heart failure.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
