PHYLLOCONTIN CONTINUS Prolonged release tablets Ref.[50284] Active ingredients: Aminophylline

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

Due to potential decreased clearance, dose reduction and monitoring of serum theophylline concentrations may be required in elderly patients and patients with:

• cardiac disease
• hepatic disease
• exacerbations of lung disease
• hypothyroidism (and when starting acute treatment)
• fever
• viral infections

Due to potential increased clearance, dose increase and monitoring of serum theophylline concentrations may be required in patients with hyperthyroidism (and when starting acute hyperthyroidism treatment) and cystic fibrosis.

Aminophylline may:

• act as a gastrointestinal tract irritant and increase gastric secretion, therefore caution should be exercised in patients with peptic ulcers.
• exacerbate cardiac arrhythmias and therefore caution should be exercised in patients with cardiac disorders
• exacerbate frequency and duration of seizures and therefore caution should be exercised in patients with history of seizures and alternative treatment considered.

Caution should be exercised in elderly males with pre-existing partial urinary tract obstruction, such as prostatic enlargement, due to risk of urinary retention.

Particular care is advised in patients suffering from severe asthma who require acute aminophylline administration. It is recommended that serum theophylline concentrations are monitored in such situations.

The following increase clearance of theophylline and it may therefore be necessary to increase dosage of aminophylline to ensure a therapeutic effect: aminoglutethimide, carbamazepine, isoprenaline, phenytoin, rifampicin, sulphinpyrazone, barbiturates, ritonavir and hypericum perforatum (St. John’s Wort).

Smoking and alcohol consumption can also increase clearance of theophylline.

The following reduce clearance of theophylline and a reduced dosage of aminophylline may therefore be necessary to avoid side-effects: aciclovir, allopurinol, carbimazole, cimetidine, clarithromycin, diltiazem, disulfiram, erythromycin, fluconazole, interferon, isoniazid, methotrexate, mexiletine, nizatidine, pentoxifylline, propafenone, propranolol, thiabendazole, verapamil and oral contraceptives. Theophylline has been shown to interact with some quinolone antibiotics including ciprofloxacin and enoxacin, which may result in elevated plasma theophylline levels.

The concomitant use of theophylline and fluvoxamine should usually be avoided. Where this is not possible, patients should have their aminophylline dose reduced 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 resulting in increased serum theophylline levels. A reduction of dosage may also be necessary in elderly patients. Thyroid disease or associated treatment may alter theophylline plasma levels.

Concurrent administration of aminophylline may:

• inhibit the effect of adenosine receptor agonists (adenosine, regadenoson, dipyridamol) and may reduce their toxicity when used for cardiac perfusion scanning;
• oppose the sedatory effect of benzodiazepines;
• result in the occurrence of arrhythmias with halothane;
• result in thrombocytopenia with lomustine
• increase urinary lithium clearance.

Therefore these drugs should be used with caution.

Care should be taken in its concomitant use with -adrenergic agonists, glucagon and other xanthine drugs, as these will potentiate the effects of theophylline. The incidence of toxic effects may be enhanced by the concomitant use of ephedrine.

Hypokalaemia resulting from 2 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 concentrations are monitored in such situations.

Theophylline may decrease steady state phenytoin levels.

Pregnancy

There are no adequate data from well controlled studies of the use of theophylline/aminophylline in pregnant women. Theophylline has been reported to give rise to teratogenic effects in mice, rats and rabbits (See section 5.3). The potential risk for humans is unknown.

Theophylline should not be administered during pregnancy unless the benefit is considered to outweigh the risk.

Breast-feeding

Theophylline is secreted in breast milk, and may be associated with irritability in the infant, therefore it should only be given to breast feeding women when the anticipated benefits outweigh the risk to the child.

PHYLLOCONTIN CONTINUS tablets have no or negligible influence on the ability to drive and use machines.

The following adverse drug reactions have been reported in the post-marketing setting for aminophylline. Frequencies of “not known” have been assigned as accurate frequencies cannot be estimated from the available clinical trial data.

^* Please refer to section 4.4 as aminophylline may induce urinary retention in elderly males with pre-existing partial urinary tract obstruction.

Reporting of adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; Email: medsafety@hpra.ie.

Not applicable.