UNIPHYLLIN CONTINUS Prolonged release tablet Ref.[7752] Active ingredients: Theophylline

Posology

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.

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).

Clearance is increased in children compared to values observed in adult subjects. The rapid clearance observed in children decreases towards adult values in late teens. Therefore, lower dosages (based on usual adult dose) may be required for adolescents.

UNIPHYLLIN CONTINUS tablets should not be used in children below 6 years of age. Other dosage forms are available that are more suitable for children aged less than 6 years.

Theophylline distributes poorly into body fat, therefore mg/kg doses should be calculated on the basis of lean (ideal) bodyweight.

Plasma theophylline concentrations should ideally be maintained between 5 and 12 micrograms/ml. A plasma level of 5 micrograms/ml probably represents the lower level of clinical effectiveness. Significant adverse reactions are usually seen at plasma theophylline levels greater than 20 micrograms/ml. Monitoring of plasma theophylline concentrations may be required when:

• higher dosages are prescribed;
• patients have co-morbidities resulting in impaired clearance;
• theophylline is co-administered with medication that reduces theophylline clearance.

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 administer a larger evening or morning dose in some patients, in order to achieve optimum therapeutic effect when symptoms are most severe e.g. at the time of the ‘morning dip’ in lung function.

In patients whose night time or day time symptoms persist despite other therapy and who are not currently receiving theophylline, then the total daily requirement of UNIPHYLLIN CONTINUS tablets (as specified above) may be added to their treatment regimen as either a single evening or morning dose.

Method of administration

Oral.

These tablets must be swallowed whole and not broken, crushed or chewed as doing so may lead to a rapid release of theophylline with the potential for toxicity.

Missed dose

If a patient forgets to take a dose but remembers within 4 hours of the time the dose was due to be taken, the tablets can be taken straight away. The next dose should be taken at the normal time. Beyond 4 hours the prescriber may need to consider alternative treatment until the next dose is due.

Theophylline has a low therapeutic index. Theophylline toxicity is most likely to occur when serum concentrations exceed 20 micrograms/ml and becomes progressively more severe at higher serum concentrations.

Over 3 g could be serious in an adult (40 mg/kg in a child). The fatal dose may be as little as 4.5 g in an adult (60 mg/kg in a child), but is generally higher.

Symptoms

Warning: Serious symptoms may develop as long as 12 hours after overdosage with prolonged release formulations.

Alimentary symptoms: Nausea, vomiting (which is often severe), epigastric pain and haematemesis. Consider pancreatitis if abdominal pain persists.

Neurological symptoms: Restlessness, hypertonia, exaggerated limb reflexes, convulsions, seizures. Coma may develop in very severe cases.

Cardiovascular symptoms: Hypotension. Sinus tachycardia is common. Ectopic beats and supraventricular and ventricular tachycardia may follow.

Metabolic symptoms: Hypokalaemia due to shift of potassium from plasma into cells is common, can develop rapidly and may be severe. Hyperglycaemia, hypomagnesaemia and metabolic acidosis may also occur. Rhabdomyolysis may also occur.

Management

Activated charcoal or gastric lavage should be considered if a significant overdose has been ingested within 1-2 hours. Repeated doses of activated charcoal given by mouth can enhance theophylline elimination. Measure the plasma potassium concentration urgently, repeat frequently and correct hypokalaemia. BEWARE! If large amounts of potassium have been given, serious hyperkalaemia may develop during recovery. If plasma potassium is low, then the plasma magnesium concentration should be measured as soon as possible.

In the treatment of ventricular arrhythmias, proconvulsant antiarrhythmic agents such as lignocaine (lidocaine) should be avoided because of the risk of causing or exacerbating seizures.

Measure the plasma theophylline concentration regularly when severe poisoning is suspected, until concentrations are falling. Vomiting should be treated with an antiemetic such as metoclopramide or ondansetron.

Tachycardia with an adequate cardiac output is best left untreated. Beta-blockers may be given in extreme cases but not if the patient is asthmatic. Control isolated convulsions with intravenous diazepam. Exclude hypokalaemia as a cause.

Particularly in the setting of theophylline overdose induced convulsions, efficacy of some anticonvulsant drugs, such as benzodiazepines, may be reduced through suspected pharmacodynamic interactions.

Three years.

Do not store above 25°C.

Blister packs consisting of aluminium foil sealed to 250 µ m PVC with a PVdC coating of at least 40 gsm thickness, containing 8 or 56 tablets.

Polypropylene containers containing 60, 100, 250 or 1000 tablets.

Amber glass bottles containing 50 or 100 tablets.

Not all pack sizes may be marketed.

No special requirements.