TRENTAL 400 Modified release tablet Ref.[7993] Active ingredients: Pentoxifylline

At the first signs of an anaphylactic/anaphylactoid reaction, Trental 400 must be discontinued immediately, and a physician must be informed.

Particular careful monitoring is required:

In patients with hypotension or severe coronary artery disease, Trental 400 should be used with caution, as a transient hypotensive effect is possible and, in isolated cases, might result in a reduction in coronary artery perfusion.

Particularly careful monitoring is required in patients with impaired renal function. In patients with a creatinine clearance of less than 30 ml/min it may be necessary to reduce the daily dose of Trental 400 to one or two tablets to avoid accumulation. In patients with severely impaired liver function the dosage may need to be reduced.

In patients treated concomitantly with pentoxifylline and anti-vitamin K or platelet aggregation inhibitors (see also section 4.5).

In patients treated concomitantly with pentoxifylline and antidiabetic agents (see also section 4.5).

In patients treated concomitantly with pentoxifylline and ciprofloxacin (see also section 4.5).

In patients treated concomitantly with pentoxifylline and theophylline (see also section 4.5).

High doses of Trental injection have been shown, in rare cases, to intensify the hypoglycaemic action of insulin and oral hypoglycaemic agents. However, no effect on insulin release has been observed with Trental following oral administration. It is recommended that patients under medication for diabetes mellitus be carefully monitored.

Post-marketing cases of increased anti-coagulant activity have been reported in patients concomitantly treated with pentoxifylline and anti-vitamin K. Monitoring of anti-coagulant activity in these patients is recommended when pentoxifylline is introduced or the dose is changed.

Trental 400 may potentiate the effect of anti-hypertensive agents and the dosage of the latter may need to be reduced.

Trental 400 should not be given concomitantly with ketorolac as there is increased risk of bleeding and/or prolongation of prothrombin time.

Concomitant administration of pentoxifylline and theophylline may increase theophylline levels in some patients. Therefore there may be an increase in and intensification of adverse effects of theophylline.

Concomitant administration with ciprofloxacin may increase the serum concentration of pentoxifylline in some patients. Therefore, there may be an increase in and intensification of adverse reactions associated with co-administration.

Potential additive effect with platelet aggregation inhibitors: Because of the increased risk of bleeding, the concomitant administration of a platelet aggregation inhibitor (such as clopidogrel, eptifibatide, tirofiban, epoprostenol, iloprost, abciximab, anagrelide, NSAIDs other than selective COX-2 inhibitors, acetylsalicylates (ASA/LAS), ticlopidine, dipyridamole) with pentoxifylline should be undertaken with caution.

Concomitant administration with cimetidine may increase the plasma concentration of pentoxifylline and the active metabolite, lisofylline.

There is no information on the use of Trental in pregnancy but no untoward effects have been found in animal studies. Trental 400 should not be administered during pregnancy.

Pentoxifylline passes into breast milk in minute quantities. Because insufficient experience has been gained, the possible risks and benefits must be weighed before administration of Trental 400 to breast feeding mothers.

No effect known.

These adverse reactions have been reported in clinical trials or post-marketing. Frequencies are unknown.

Investigations: Transaminases increased

Cardiac disorders: Arrhythmia, Tachycardia, Angina Pectoris

Blood and lymphatic system disorders: Thrombocytopenia, Leukopenia/neutropenia

Nervous system disorders: Dizziness, headache, meningitis aseptic*

Gastrointestinal disorders: Gastrointestinal disorder, Epigastric discomfort, Abdominal distension, Nausea, Vomiting, Diarrhoea, Constipation, Hypersalivation

Skin and subcutaneous tissue disorders: Pruritus, Erythema, Urticaria, Hot flush, Rash

Vascular disorders: Haemorrhage**, Hypotension

Immune system disorders: Anaphylactic reactions, Anaphylactoid reaction, Angioedema

Hepatobiliary disorders: Cholestasis

Psychiatric disorders: Agitation, Sleep disorder

Respiratory disorders: Bronchospasm

Description of selected adverse reactions

* Reports of aseptic meningitis were predominantly in patients with underlying connective tissue disorders

** A few very rare events of bleeding (e.g. skin, mucosa) have been reported in patients treated with Trental with and without anticoagulants or platelet aggregation inhibitors. The serious cases are predominantly concentrated in the gastrointestinal, genitourinary, multiple site and surgical wound areas and are associated with bleeding risk factors. A causal relationship between Trental therapy and bleeding has not been established. Thrombocytopenia has occurred in isolated cases.

Reporting of suspected 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 professional are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

None known.