TRENTAL 400.

Pentoxifylline 400MG.

Modified release tablet.

Trental 400 is indicated in the treatment of peripheral vascular disease, including intermittent claudication and rest pain.

The recommended initial dose is 1 tablet (400 mg) three times daily; two tablets daily may prove sufficient in some patients, particularly for maintenance therapy. Tablets should be taken with or immediately after meals, and swallowed whole with plenty of water.

Special Cases: In patients with impairment of renal function (creatinine clearance below 30ml/min) a dose reduction by approximately 30% to 50% may be necessary guided by individual tolerance.

Trental 400 is contra-indicated in cases where there is known hypersensitivity to the active constituent, pentoxifylline other methyl xanthines or any of the excipients. Also in patients with cerebral haemorrhage, extensive retinal haemorrhage, acute myocardial infarction and severe cardiac arrhythmias.

At the first signs of an anaphylactic/anaphylactoid reaction, Trental 400 must be discontinued or the infusion must be halted 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 (see also section 4.5).

In patients treated concomitantly with pentoxifylline and antidiabetic agents (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.

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.

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.

The treatment of overdosage should be symptomatic with particular attention to supporting the cardiovascular system.

Leukocyte properties of haemorrheologic importance have been modified in animal and in vitro human studies. Pentoxifylline has been shown to increase leukocyte deformability and to inhibit neutrophil adhesion and activation.

The half life of absorption of Trental 400 is 4-6 hours. Pentoxifylline is extensively metabolised, mainly in the liver. Sixty percent of a single dose of Trental 400 is eliminated via the kidney over 24 hours.

Nothing of clinical relevance.

Hydroxyethyl cellulose, povidone, talc, magnesium stearate, hypromellose, macrogol 8000, erythrosine (E127). titanium dioxide (E171).

None known.

5 years.

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

Blister Pack (Alu/PVC): 90 tablets.

None.

Sanofi-aventis

One Onslow Street

Guildford

Surrey, GU1 4YS, UK

PL 04425/0213

15^th April 2002

13 June 2011

POM