Xanthines (bronchodilators).

Generic Aminophylline is a theophylline compound in combination with ethylenediamine. Theophylline has a narrow therapeutic window, to avoid toxicity and achieve optimum response a plasma theophylline level of 10 - 20mg/litre or 55-110 micromol/litre sho

Aminophylline hydrate 225 and 350 mg.

Prolonged release tablets PHYLLOCONTIN CONTINUS tablets 225 mg are pale yellow, film-coated tablets with the Napp logo on one side and SA on the other. PHYLLOCONTIN Forte CONTINUS tablets 350 mg are pale yellow, film-coated tablets with the Napp logo on one side and SA 350 on the other.

For the treatment and prophylaxis of bronchospasm associated with asthma, chronic obstructive pulmonary disease and chronic bronchitis. Also indicated in adults for the treatment of left ventricular and congestive cardiac failure.

Route of Administration

Oral.

The tablets should be swallowed whole and not chewed.

Children: The maintenance dose (expressed as mg aminophylline) is 12mg/kg twice daily adjusted to the nearest 225mg. It is recommended that half the maintenance dose be given for the first week of therapy if the patient has not previously been receiving xanthine preparations. PHYLLOCONTIN CONTINUS tablets 225mg are, therefore, not suitable as a starting dose for children weighing under 40 kg.

Some children with chronic asthma require and tolerate much higher doses (1320 mg/kg twice daily). Lower doses (based on the usual adult dose) may be required by adolescents.

Adults: The usual dose is two PHYLLOCONTIN CONTINUS tablets 225 mg, or one or two PHYLLOCONTIN Forte CONTINUS tablets 350mg twice-daily following an initial week of therapy on one tablet twice-daily.

The Elderly: The dose should be adjusted following the response to the initial week of therapy on one tablet twice-daily.

Dose Titration: Patients vary in their response to xanthines and it may be necessary to titrate dosage individually. Steady state theophylline levels are generally attained 3-4 days after dose adjustment. If a satisfactory clinical response is not achieved, serum theophylline should be measured 46 hours after the last dose. Based on serum theophylline assay results dosage should be titrated using the following as a guide:

Deteriorating acute severe asthma not previously treated with theophylline, 5 mg/kg, then as for acute severe asthma. Acute severe asthma, six months to nine years, 1 mg/kg/hour; 10- 16 years, 800 micrograms/kg/hour, adjusted according to plasma- theophylline concentration.

Should not be given concomitantly with ephedrine in children. Hypersensitivity to xanthines or any of the tablet constituents. Porphyria.

The patient's response to therapy should be carefully monitored – worsening of asthma symptoms requires medical attention.

Use with caution in patients with cardiac arrhythmias, peptic ulcer, hyperthyroidism, severe hypertension, hepatic dysfunction, chronic alcoholism or acute febrile illness.

The half-life of theophylline may be prolonged in the elderly and in patients with heart failure, hepatic impairment or viral infections. Toxic accumulation may occur.

A reduction of dosage may be necessary in the elderly patient.

Avoid concomitant use with other xanthine-containing products.

The hypokalaemia resulting from beta agonist therapy, steroids, diuretics and hypoxia may be potentiated by xanthines. Particular care is advised in patients suffering from severe asthma who require hospitalisation. It is recommended that serum potassium levels are monitored in such situations.

Alternative treatment is advised for patients with a history of seizure activity.

The following increase clearance and it may therefore be necessary to increase dosage to ensure a therapeutic effect: aminoglutethimide, carbamazepine, moracizine, phenytoin, rifampicin, sulphinpyrazone, barbiturates and Hypericum perforatum. Plasma concentrations of theophylline can be reduced by concomitant use of the herbal remedy St John's Wort (Hypericum perforatum). Smoking and alcohol consumption can also increase clearance of theophylline.

The following reduce clearance and a reduced dosage may therefore be necessary to avoid side-effects: allopurinol, carbimazole, cimetidine, ciprofloxacin, clarithromycin, diltiazem, disulfiram, erythromycin, fluconazole, interferon, isoniazid, isoprenaline, methotrexate, mexiletine, nizatidine, norfloxacin, oxpentifylline, propafenone, propranolol, ofloxacin, thiabendazole, verapamil, viloxazine hydrochloride and oral contraceptives. The concomitant use of theophylline and fluvoxamine should usually be avoided. Where this is not possible, patients should have their theophylline dose halved and plasma theophylline should be monitored closely.

Factors such as viral infections, liver disease and heart failure also reduce theophylline clearance. There are conflicting reports concerning the potentiation of theophylline by influenza vaccine and physicians should be aware that interaction may occur. A reduction of dosage may be necessary in elderly patients. Thyroid disease or associated treatment may alter theophylline plasma levels. There is also a pharmacological interaction with adenosine, benzodiazepines, halothane, lomustine and lithium and these drugs should be used with caution.

Theophylline may decrease steady state phenytoin levels

The side-effects usually associated with theophylline and xanthine derivatives such are nausea, gastric irritation, headache, CNS stimulation, tachycardia, palpitations, arrhythmias and convulsions.

Napp Pharmaceuticals Limited

P- Pharmacy

30 June 2009