Slo-Phyllin 60mg Capsules

Slo-Phyllin 125mg Capsules

Slo-Phyllin 250mg Capsules

Slo-Phyllin 60mg capsules each contain theophylline (anhydrous) EP 60mg

Slo-Phyllin 125mg capsules each contain theophylline (anhydrous) EP 125mg

Slo-Phyllin 250mg capsules each contain theophylline (anhydrous) EP 250mg

Prolonged release capsule

Slo-Phyllin 60mg

Hard gelatin capsules with opaque white body and clear colourless cap, printed radially in black with Slo-phyllin 60 on one half and Lipha on the other, and containing white-grey to light yellow pellets.

Slo-Phyllin 125mg

Hard gelatin capsules with opaque brown body and clear colourless cap, printed radially in black with Slo-phyllin 125 on one half and Lipha on the other, and containing white-grey to light yellow pellets.

Slo-Phyllin 250mg

Hard gelatin capsules with opaque purple body and clear colourless cap, printed radially in black with Slo-phyllin 250 on one half and Lipha on the other, and containing white-grey to light yellow pellets.

As a bronchodilator in the symptomatic and prophylactic treatment of asthma and for reversible bronchoconstriction associated with chronic bronchitis and bronchial asthma.

Each patient should be titrated to a suitable dosage regimen by clinical assessment. It may also be necessary to measure plasma theophylline levels.

Initially the lowest dosage for each group is recommended. This may be increased gradually if optimal bronchodilator effects are not achieved. The total dosage should not normally exceed 24 mg/kg body weight for children and 13 mg/kg for adults. However the plasma theophylline level measured 4-8 hours after dosing and at least three days after any dosage adjustment, provides a more accurate assessment of the patients' dosage need, especially as significant variations in the rate of drug elimination can occur between individuals. The following table provides a guide:

It is advisable to recheck the plasma level after dose adjustment and every 6-12 months.

It is not possible to ensure bioequivalence between different sustained release theophylline products. Once titrated to an effective dose, patients should not be changed from Slo-Phyllin to another sustained release xanthine preparation without re-titration and clinical assessment.

Hypersensitivity to theophylline or other xanthines. Concomitant use of theophylline and ephedrine in children.

Smoking and alcohol consumption can increase the clearance of theophylline and a higher dose may be necessary.

Careful monitoring is recommended for patients with congestive heart failure, chronic alcoholism, hepatic dysfunction, or viral infections, as they may have a lower clearance of theophylline, which could lead to higher than normal plasma levels.

Caution should be exercised in patients with peptic ulcers, cardiac arrhythmias, other cardiovascular diseases, hyperthyroidism or hypertension. Slo-Phyllin should not be used concurrently with other preparations containing xanthines derivatives. If it is necessary to administer aminophylline to a patient who is already receiving Slo-Phyllin, plasma theophylline concentration should be monitored.

The use of alternative treatments is advised in patients with a history of seizures, as these may be exacerbated by theophylline.

Theophylline has been reported to interact with a number of drugs. The following increase clearance and it may therefore be necessary to increase dosage to ensure therapeutic effect: barbiturates, carbamazepine, lithium, phenytoin, rifampicin and sulphinpyrazone.

The following reduce clearance and a reduced dosage may therefore be necessary to avoid side-effects: allopurinol, cimetidine, ciprofloxacin, corticosteroids, diltiazem, erythromycin, frusemide, isoprenaline, oral contraceptives, thiabendazole and verapamil. There is some evidence of an interaction between theophylline and influenza vaccine.

Xanthines can potentiate hypokalaemia resulting from beta₂ agonist therapy, steroids, diuretics and hypoxia. Particular caution is advised in severe asthma. It is recommended that serum potassium levels are monitored in such situations.

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.

Plasma concentrations of theophylline can be reduced by concomitant use of the herbal remedy St John's wort (Hypericum perforatum).

Slo-Phyllin is not recommended since theophylline is known to cross the placenta and its safety in pregnancy has not been established.

Theophylline is distributed in breast milk and therefore Slo-Phyllin should be used with caution in nursing mothers.

None known

Side effects usually occur when theophylline blood levels exceed 20 micrograms/ml and include gastric irritation, nausea, vomiting, abdominal discomfort, palpitations, a fall in blood pressure, headache, occasional diarrhoea and insomnia. CNS stimulation and diuresis may also occur, especially in children.

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 features may develop as long as 12 hours after overdosage with sustained release formulations.

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

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

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

Metabolic features: 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.

The mechanism of action of theophylline is unclear although a number of pharmacological actions have been implicated. The principal of these are: -

1) Inhibition of the enzyme phosphodiesterase leading to raised cyclic AMP levels.

2) Antagonism of adenosine receptors.

3) Inhibition of the intracellular release of calcium.

4) Stimulation of catecholamine release

5) Anti-inflammatory action possible involving the inhibition of submucosal action.

Following administration of Slo-Phyllin capsules at an appropriate twice-daily dosage, peak levels occur 4-8 hours after dosing, and steady state is achieved in three days.

No adverse effects can be predicted from animal toxicology studies other than those documented from human use of theophylline.

The inactive ingredients are sucrose, maize starch, refined bleached lac, talc and ethanol. The gelatine capsules contain the following shell colours: Slo-Phyllin 60mg E171; Slo-Phyllin 125mg E171 and E172; Slo-Phyllin 250mg E171, E127 and E132.

Printing ink: black iron oxide (E172), shellac glaze, propylene glycol.

None stated.

Three years.

Do not store above 25 degree C. Store in the original package.

PVC/Foil blister packs of 56 tablets

Sample PVC/Foil blister packs of 8 tablets

Plastic container of 100 tablets.

Patients should be instructed not to chew or suck the capsules or pellets as this destroys the time-release properties. However, for those who experience difficulty in swallowing capsules, the contents of a capsule may be sprinkled on to a spoonful of soft food, e.g. yoghurt.

Merck Serono Ltd, Bedfont Cross, Stanwell Road, Feltham, Middlesex, TW14 8NX, UK

Slo-Phyllin 60mg capsules PL 11648/0079

Slo-Phyllin 125mg capsules PL 11648/0080

Slo-Phyllin 250mg capsules PL 11648/0081

Year granted - 1977

31 January 2012