Theophylline tablets: uses, blood levels and cautions

Theophylline relaxes the muscle around the airways and has mild anti-inflammatory effects. The product information licenses it for the treatment and prevention of bronchospasm linked with asthma, chronic obstructive pulmonary disease (COPD) and chronic bronchitis, and also for left ventricular and congestive heart failure. It is not the first drug of choice for asthma in children.

Today it is usually an add-on rather than a starting treatment, tried when inhalers have not fully controlled symptoms. The entry notes it may be inappropriate as the only treatment for COPD in older people because of its narrow safety margin.

The usual maintenance dose for adults and older people in the entry is 200 mg every 12 hours, which may be raised to 300 mg or 400 mg according to response. For children from 6 years the figure is weight-based, calculated on lean body weight, and the tablets are not used under 6. Your prescriber and the leaflet for your brand govern your own regimen.

Some people are given a larger evening or morning dose to cover the early-morning dip in lung function. For people with symptoms despite other treatment who are not already on theophylline, the daily total may be added as a single evening or morning dose. Dose changes may be needed if smoking starts or stops.

The entry says blood theophylline concentrations should ideally be kept between 10 and 20 micrograms per ml, although 5 to 15 may be effective, and that significant adverse reactions are usually seen above 20. Levels may be checked when higher doses are used, when other illnesses slow clearance, or when other medicines reduce clearance.

Several conditions slow clearance and may call for a lower dose: heart disease and arrhythmias, liver disease, a flare of lung disease, an underactive thyroid, fever, viral infections and a tendency to low potassium. Clearance may be faster, and the dose higher, in overactive thyroid and cystic fibrosis. Anyone whose symptoms worsen should be reviewed.

Swallow prolonged-release tablets whole. Breaking, crushing or chewing them can release theophylline rapidly and risk toxicity. If a dose is forgotten but remembered within 4 hours of when it was due, take it straight away and keep the next dose at the normal time; after 4 hours, the prescriber may need to consider other cover until the next dose.

The entry lists effects reported after marketing, including agitation, anxiety, insomnia, dizziness, headache, tremor, palpitations, a fast heartbeat and arrhythmias, nausea, vomiting, abdominal pain, reflux, diarrhoea, rash, itching, low potassium, increased urine output and difficulty passing urine in older men with prostate enlargement. Seizures and anaphylaxis have also been reported, and the drug may worsen epilepsy.

Overdose is dangerous. Serious symptoms from a prolonged-release product can appear as long as 12 hours later and include severe vomiting, restlessness, a racing or irregular heartbeat, convulsions and a dangerous drop in potassium. Anyone who has taken too much, or has persistent vomiting, a pounding heartbeat or a fit, needs urgent help: call 999 or go to A&E. Suspected side effects can be reported through the Yellow Card scheme.

The entry lists medicines that may raise theophylline levels, including cimetidine, ciprofloxacin, macrolide antibiotics such as erythromycin and clarithromycin, propranolol, isoniazid, oral contraceptives, fluvoxamine, diltiazem, verapamil, fluconazole and allopurinol. Use with fluvoxamine should usually be avoided.

Others speed up clearance and may mean a higher dose is needed: carbamazepine, phenytoin, rifampicin, ritonavir, barbiturates and St John's wort, as well as smoking and alcohol. Theophylline can also add to low potassium caused by beta-2 agonist inhalers, steroids and diuretics, and may reduce the effect of benzodiazepines. Always check before starting or stopping any medicine, including herbal products.

It must not be used by anyone allergic to theophylline or other xanthines, or by people with porphyria, and it is contraindicated in infants under 6 months. Extra care is advised with peptic ulcers, heart disorders, epilepsy or past seizures, severe high blood pressure, chronic heavy alcohol use and, in older men, prostate enlargement.

For pregnancy, the entry reports neonatal irritability and apnoea and says theophylline should not be given in pregnancy unless clearly necessary. It passes into breast milk and may cause irritability in the infant, so it is given to breastfeeding women only when the expected benefit outweighs the risk. It has no known effect on driving.