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

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

Due to potential decreased theophylline 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
• fever
• viral infections

Due to potential increased theophylline 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.

Theophylline 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.

Use with caution in patients with severe hypertension or chronic alcoholism.

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 theophylline administration. It is recommended that serum theophylline concentrations are monitored in such situations.

In case of insufficient effect of the recommended dose and in case of adverse events, theophylline plasma concentration should be monitored.

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

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: aciclovir, allopurinol, carbimazole, cimetidine, clarithromycin, diltiazem, disulfiram, erythromycin, fluconazole, interferon, isoniazid, methotrexate, mexiletine, nizatidine, pentoxifylline, propafenone, propranolol, thiabendazole, verapamil and oral contraceptives (see section 4.9).

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 theophylline dose reduced and plasma theophylline should be monitored closely.

Factors such as viral infections, liver disease and heart failure also reduce theophylline clearance (see section 4.9). 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 theophylline 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.

Theophylline may decrease steady state phenytoin levels.

Hypokalaemia resulting from beta2 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.

Care should be taken in its concomitant use with β-adrenergic agonists, glucagon and other xanthines drugs, as these will potentiate the effects of theophylline.

Co-administration with ketamine may cause reduced convulsive threshold; with doxapram may cause increased CNS stimulation.

The incidence of toxic effects may be enhanced by the concomitant use of ephedrine.

Pregnancy

There are no adequate data from well controlled studies of the use of theophylline 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 clearly necessary.

Breastfeeding

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

UNIPHYLLIN 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 theophylline. Frequencies of “not known” have been assigned as accurate frequencies cannot be estimated from the available clinical trial data.

Immune system disorders: Anaphylactic reaction, Anaphylactoid reaction, Hypersensitivity

Metabolism and nutrition disorders: Hyperuricaemia

Psychiatric disorders: Agitation, Anxiety, Insomnia, Sleep disorder

Nervous system disorders: Convulsions, Dizziness, Headache, Tremor

Cardiac disorders: Atrial tachycardia, Palpitations, Sinus tachycardia

Gastrointestinal disorders: Abdominal pain, Diarrhoea, Gastric irritation, Gastro-oesophageal reflux, Nausea, Vomiting

Skin and subcutaneous tissue disorders: Pruritus, Rash

Renal and urinary disorders: Diuresis, Urinary retention*

* Please refer to section 4.4 as theophylline 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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

Not applicable.