4.1. Therapeutic indications

• Secondary prevention of ischaemic stroke and transient ischaemic attacks either alone or in conjunction with aspirin.

• An adjunct to oral anti-coagulation for prophylaxis of thromboembolism associated with prosthetic heart valves.

4.2. Posology and method of administration

For oral administration

Adults, including the elderly

The recommended dose is one capsule twice daily, usually one in the morning and one in the evening preferably with meals.

The capsules should be swallowed whole without chewing.

Children

Attia/Dipyridamole Dr. Reddy's Modified-Release Capsules is not recommended for children.

Alcohol

Attia/Dipyridamole Dr. Reddy's Modified-Release Capsules should not be taken at the same time as an alcoholic beverage (see section 4.5).

4.3. Contraindications

Hypersensitivity to any component of the product

4.4. Special warnings and precautions for use

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 Attia/Dipyridamole Dr. Reddy's Modified-Release Capsules 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 Interactions).

Attia/Dipyridamole Dr. Reddy's Modified-Release Capsules 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 (upto 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.

Attia/Dipyridamole Dr. Reddy's Modified-Release Capsules capsules contain ponceau 4R (E124), a colouring agent, which may cause allergic reactions.

4.5. Interaction with other medicinal products and other forms of interaction

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.

When dipyridamole is used in combination with any substance 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.

Attia/Dipyridamole Dr. Reddy's Modified-Release Capsules should not be taken at the same time as alcohol, as alcohol may increase the rate of release of dipyridamole from the modified-release preparation.

4.6. Fertility, pregnancy and lactation

Pregnancy

There is inadequate evidence of safety in human pregnancy, but dipyridamole has been used for many years without apparent ill-consequence. Animal studies have shown no hazard. 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

Attia/Dipyridamole Dr. Reddy's Modified-Release Capsules 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 dipyridamole. Non-clinical studies with dipyridamole did not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

4.7. Effects on ability to drive and use machines

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 Attia/Dipyridamole Dr. Reddy's Modified-Release Capsules. If patients experience dizziness they should avoid potentially hazardous tasks such as driving or operating machinery.

4.8. Undesirable effects

Adverse reactions at therapeutic doses are usually mild and transient. As a result of its vasodilating properties, Attia/Dipyridamole Dr. Reddy's Modified-Release Capsules may cause hypotension, hot flushes and tachycardia. Worsening of the symptoms of coronary heart disease such as angina and arrhythmias.

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

Frequencies

Very common

Common

Uncommon

Rare

Very rare

≥ 1/10

≥ 1/100 < 1/10

≥ 1/1,000< 1/100

≥ 1/10,000 < 1/1,000

< 1/10,000

Blood and lymphatic system disorders

Thrombocytopenia

not known

Immune system disorders

Hypersensitivity

not known

Angioedema

not known

Nervous system disorders

Headache

very common

Dizziness

very common

Cardiac disorders

Angina pectoris

common

Tachycardia

not known

Vascular disorders

Hypotension

not known

Hot flush

not known

Respiratory, thoracic and mediastinal disorders

Bronchospasm

not known

Gastrointestinal disorders

Diarrhoea

very common

Nausea

very common

Vomiting

common

Skin and subcutaneous tissue disorders

Rash

common

Urticaria

not known

Musculoskeletal, connective tissue and bone disorders

Myalgia

common

Injury, poisoning and procedural complications

post procedural haemorrhage

not known

operative haemorrhage

not known

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 products 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:

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Symptoms

Due to the low number of observations, experience with dipyridamole overdose is limited. Symptoms such as feeling warm, flushes, sweating, accelerated pulse, restlessness, feeling of weakness, dizziness, drop in blood pressure and anginal complaints can be expected.

Therapy

Symptomatic therapy is recommended. Administration of xanthine derivatives (e.g. aminophylline) may reverse the haemodynamic effects of dipyridamole overdose. ECG monitoring is advised in such a situation. Due to its wide distribution to tissues and its predominantly hepatic elimination, dipyridamole is not likely to be accessible to enhanced removal procedures.