PROCARDIN Film-coated tablet Ref.[28220] Active ingredients: Dipyridamole

Among other properties, dipyridamole acts as a vasodilator. It should be used with caution in patients with severe coronary artery disease, including unstable angina and/or recent myocardial infarction, left ventricular outflow obstruction or haemodynamic instability (e.g. decompensated heart failure).

Patients being treated with regular oral doses of Procardin should not receive additional intravenous dipyridamole. Clinical experience suggests that patients being treated with oral dipyridamole who also require pharmacological stress testing with intravenous dipyridamole, should discontinue drugs containing oral dipyridamole for twenty-four hours prior to stress testing.

In patients with myasthenia gravis, readjustment of therapy may be necessary after changes in dipyridamole dosage (see section 4.5).

Procardin should be used with caution in patients with coagulation disorders.

A small number of cases have been reported in which unconjugated dipyridamole was shown to be incorporated into gallstones to a variable extent (up to 70% by dry weight of stone). These patients were all elderly, had evidence of ascending cholangitis and had been treated with oral dipyridamole for a number of years. There is no evidence that dipyridamole was the initiating factor in causing gallstones to form in these patients. It is possible that bacterial deglucuronidation of conjugated dipyridamole in the bile may be the mechanism responsible for the presence of dipyridamole in gallstones.

Dipyridamole increases plasma levels and cardiovascular effects of adenosine. Adjustment of adenosine dosage should be considered if use with dipyridamole is unavoidable.

There is evidence that the effects of aspirin and dipyridamole on platelet behaviour are additive.

The administration of antacids may reduce the efficacy of dipyridamole.

It is possible that dipyridamole may enhance the effects of oral anticoagulants.

When dipyridamole is used in combination with any substances impacting coagulation such as anticoagulants and antiplatelets, the safety profile for these medications must be observed.. Addition of dipyridamole to acetylsalicylic acid does not increase the incidence of bleeding events. When dipyridamole was administered concomitantly with warfarin, bleeding was no greater in frequency or severity than that observed when warfarin was administered alone.

Dipyridamole may increase the hypotensive effect of drugs, which reduce blood pressure and may counteract the anticholinesterase effect of cholinesterase inhibitors thereby potentially aggravating myasthenia gravis.

Pregnancy

There is inadequate evidence of safety in human pregnancy, but dipyridamol has been used for many years without apparent ill-consequence. Animal studies have shown no hazard. Medicines should not be used in pregnancy, especially the first trimester unless the expected benefit is thought to outweigh the possible risk to the foetus (please refer to section 5.3).

Breast-feeding

Dipyridamole is excreted in breast milk at levels approximately 6% of the plasma concentration. Therefore dipyridamol should only be used during lactation if considered essential by the physician.

Fertility

No studies on the effect on human fertility have been conducted with dipyridamol. Non-clinical studies with dipyridamole did not indicate direct or indirect harmful effects with respect to fertility (please refer to section 5.3).

No studies on the effects on the ability to drive and use machines have been performed.

However, patients should be advised that they may experience undesirable effects such as dizziness during treatment with PROCARDIN. If patients experience dizziness they should avoid potentially hazardous tasks such as driving or operating machinery.

Adverse effects at therapeutic doses are usually mild and transient. The following side effects have been reported, frequencies have been assigned based on aclinical trial (ESPS-2) in which 1654 patients received dipyridamole alone.

Frequencies: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).

Dipyridamole has been shown to be incorporated into gallstones (please refer to section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be reported to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.

None.