16th May 2025

Theophylline

Theophylline is a medication used in the treatment and prophylaxis of bronchospasm associated with asthma, chronic obstructive pulmonary disease, and chronic bronchitis. It works to relax smooth muscle located in the bronchial airways and pulmonary vessels. This works in two ways: (1) it competitively inhibits type III and IV phosphodiesterase, reducing the breakdown of cyclic AMP, leading to bronchodilation, (2) it binds to adenosine A2B receptors preventing adenosine mediated bronchoconstriction.

Monitoring of theophylline is required 5 days after initiation or 3 days after any dose change and a level should be taken 4-6 hours post dose in the case of oral modified release theophylline. Therapeutic bronchodilation occurs at levels between 10-20 mg/L, although lower levels of 5-15mg/L may be used. The frequency and severity of side effects increase at concentrations >20mg/L. Signs of theophylline toxicity include vomiting, agitation, restlessness, dilated pupils, sinus bradycardia, and hyperglycaemia. More severe signs can include haematemesis, convulsions, arrhythmias (supraventricular and ventricular). Alongside this severe hypokalaemia may develop rapidly. The ‘Poisoning, emergency treatment’ summary in the BNF includes information on the management of theophylline overdose.

It is worth noting that theophylline is a substrate for cytochrome P450 enzymes, therefore there are several medications that can affect the concentration of theophylline in the blood. CYP P450 inhibitors such as amiodarone, fluconazole, and sodium valproate can cause an increase in theophylline levels. Inducers of CYP450 enzymes such as carbamazepine, rifampicin, St John’s Wort can cause a decrease in theophylline levels. Concomitant use of these medications should be avoided, if this is not possible close monitoring of theophylline levels is advised. Other notable interactions include beta-agonists, diuretics, and corticosteroids which can potentiate hypokalaemia. A significant reaction between lithium and theophylline can result in a potentiation of lithium therapy.