OFCRAM Prolonged release capsules, hard Ref.[7998] Active ingredients: Dipyridamole

Among other properties, dipyridamole acts as a potent vasodilator. It should therefore 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 dipyridamole 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 adjustment of therapy may be necessary after changes in dipyridamole dosage (see section 4.5 Interactions).

Dipyridamole 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.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

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

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

It is possible that dipyridamole may enhance the effects of oral anti-coagulants.

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 blood pressure lowering drugs and may counteract the anticholinesterase effect of cholinesterase inhibitors thereby potentially aggravating myasthenia gravis.

Co-administration of alcohol may increase the rate of absorption of Ofcram PR 200mg Prolonged Release Capsules. It is recommended that patients are advised to avoid alcohol.

Pregnancy

There is inadequate evidence of safety in human pregnancy, but Ofcram PR 200mg Prolonged Release Capsules has been used for many years without apparent ill-consequence. Ofcram PR 200mg Prolonged Release Capsules, Hard should only be administrated if clearly needed. Data from the use of dipyridamole in pregnancy are inadequate. Animal studies have shown no hazard of fetal harm. Nevertheless, 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 (see section 5.3).

Breast-feeding

Dipyridamole is excreted in breast milk (at levels about 6% of plasma concentration), and therefore there is a risk of affecting the breast-feeding infant. Dipyridamole should only be used during breast-feeding if considered essential by the physician.

Fertility

No studies on the effect on human fertility have been conducted with Ofcram PR 200 mg prolonged-release capsules, hard. Non-clinical studies with dipyridamole did not indicate direct or indirect harmful effects with respect to fertility (see 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 dipyridamole. If patients experience dizziness they should avoid potentially hazardous tasks such as driving or operating machinery.

Adverse reactions at therapeutic doses are usually mild and transient.

The following side effects have been reported, frequencies have been assigned based on a clinical trial (ESPS-2) in which 1654 patients received dipyridamole alone.

Adverse reactions are listed according to MedDRA system organ class and frequency category. Frequency categories are defined using the following convention: 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).

Table 1:

Blood and lymphatic system disorders

Not known: Thrombocytopenia

Immune system disorders

Not known: Hypersensitivity, angioedema

Nervous system disorders

Very common: Headache, dizziness

Cardiac disorders

Common: Angina pectoris

Not known: Tachycardia

Vascular disorders

Not known: Hypotension, hot flush

Respiratory, thoracic and mediastinal disorders

Not known: Bronchospasm

Gastrointestinal disorders

Very common: Diarrhoea, nausea

Common: Vomiting

Skin and subcutaneous tissue disorders

Common: Rash

Not known: Urticaria

Musculoskeletal, connective tissue and bone disorders

Common: Myalgia

Injury, poisoning and procedural complications

Not known: Post procedural haemorrhage, operative haemorrhage

Dipyridamole has been shown to be incorporated into gallstones (please refer to section 4.4 Special warnings and precautions for use).

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 professionals 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.

Not applicable.