Theophylline

Source: UK SPC (eMC) §4.2 for UNIPHYLLIN 200mg prolonged release tablets (https://www.medicines.org.uk/emc/product/100850/smpc). Verbatim: 'Adults and the elderly: The usual maintenance dose is 200 mg 12 hourly. This may be titrated to either 300 mg or 400 mg dependent on the therapeutic response.' No absolute maximum adult dose is stated in §4.2. PLASMA LEVELS: plasma theophylline concentrations should ideally be maintained between 10 and 20 micrograms/ml, although 5 to 15 micrograms/ml may be effective; adverse effects can occur within the 10-20 micrograms/ml range, and significant adverse reactions are usually seen above 20 micrograms/ml. Monitoring may be required when higher dosages are prescribed, when patients have co-morbidities impairing clearance, or when co-administered with medication that reduces theophylline clearance. Dose adjustment may be necessary if smoking is started or stopped during treatment. Patients vary in their response to xanthines and it may be necessary to titrate the dose on an individual basis; it may be appropriate to give a larger evening or morning dose to cover the time symptoms are most severe (e.g. the 'morning dip'). In patients whose night-time or day-time symptoms persist despite other therapy and who are not currently receiving theophylline, the total daily requirement may be added as either a single evening or morning dose. MISSED DOSE: if remembered within 4 hours of the time due, the tablets can be taken straight away and the next dose taken at the normal time; beyond 4 hours the prescriber may need to consider alternative treatment until the next dose is due. §4.4 (dose reduction / monitoring): decreased clearance is expected in elderly patients and in cardiac arrhythmias or other cardiac disease, hepatic disease, exacerbations of lung disease, hypothyroidism, fever, viral infections and risk of hypokalaemia; increased clearance (dose increase may be needed) in hyperthyroidism and cystic fibrosis. The retrieved eMC §4.2 states no renal dose adjustment.

eMC §4.2 verbatim: 'Paediatric population aged 6 years and above: The usual paediatric maintenance dose is 9 mg/kg twice daily. Some children with chronic asthma require and tolerate much higher doses (10-16 mg/kg twice daily).' No numeric paediatric maximum is stated in this SPC. Clearance is increased in children compared with adults and the rapid clearance decreases towards adult values in the late teens, so lower dosages (based on the usual adult dose) may be required for adolescents. Theophylline distributes poorly into body fat, therefore mg/kg doses should be calculated on the basis of lean (ideal) bodyweight. UNIPHYLLIN tablets should not be used in children below 6 years of age — other dosage forms are available that are more suitable. Theophylline is contraindicated in children under 6 months of age, and concomitant administration with ephedrine is contraindicated in children less than 6 years of age (or less than 22 kg). Target plasma theophylline 10-20 micrograms/ml. Verify against a children's formulary before prescribing.