SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

DIPYRIDAMOLE TABLETS BP 100mg

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 100mg Dipyridamole Ph.Eur.

3.    PHARMACEUTICAL FORM

White film-coated tablets.

4.    CLINICAL PARTICULARS

4.1.    Therapeutic Indications

1) As an adjunct to oral anticoagulation for prophylaxis of thromboembolism associated with prosthetic heart valves.

4.2.    Posology and Method of Administration

Dipyridamole should usually be taken before meals.

Adults: 300-600mg daily in three or four divided doses.

Children: The normal total oral daily dose is 5mg/kg bodyweight daily in divided doses.

Elderly: No specific information is available.

Route of administration For oral administration.

4.3 Contra-Indications

Hypersensitivity to dipyridamole or any other ingredients in the formulation.

4.4.    Special Warnings and Special Precautions for Use

Dipyridamole is a potent vasodilator. It should be used with caution in patients with sub-valvular aortic stenosis, hypotension, severe coronary artery disease including unstable angina or haemodynamic instability associated with recent myocardial infarction, left ventricular outflow obstruction such as aortic stenosis, and in patients with decompensated heart failure.

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

Oral dipyridamole should be stopped 24 hours before intravenous use for stress testing.

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

This product contains lactose and sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.

4.5.    Interaction with other Medicinal Products and other Forms of Interaction

The absorption of dipyridamole may be reduced by drugs such as antacids that increase gastric pH.

Dipyridamole Tablets may enhance the effects of oral anticoagulants due to its antiplatelet effect. When dipyridamole is used in combination with anticoagulants and aspirin the statements on intolerance and risks for these preparations must be observed.

Addition of dipyridamole to aspirin does not appear to increase the incidence of bleeding. The combination of dipyridamole and coumarin anticoagulants does not alter the prothrombin time, but might cause an increased risk of serious bleeding when compared with anticoagulants alone

There is an increased risk of bleeding when Clopidogrel is given with dipyridamole.

Dipyridamole inhibits the reuptake of adenosine and may enhance its effects; the dose of adenosine must be reduced if both drugs are given concomitantly.

Dipyridamole may also inhibit the uptake of fludarabine and may reduce its efficacy.

Dipyridamole has some antimuscarinic effects. Additive antimuscarinic effects, both peripheral and central, can develop if two or more drugs with antimuscarinic properties are used together.

Dipyridamole may cause a minor increase in the absorption of digoxin.

Dipyridamole may increase the hypotensive effects of drugs which reduce blood pressure.

Dipyridamole may counteract the anticholinesterase effects of cholinesterase inhibitors thereby potentially aggravating myasthenia gravis.

4.6. Pregnancy and Lactation

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 hazards. Medicines should not be used in pregnancy, especially the first trimester, unless the expected benefit is thought to outweigh any possible risk to the foetus.

4.7. Effects on Ability to Drive and Use Machines

None known.

4.8 Undesirable effects

Adverse reactions at therapeutic doses are usually mild. If these occur it is usually in the beginning of treatment and they are often dose-related. Hypersensitivity reactions such as rash, urticaria, severe bronchospasm and angio-odema have been reported.

The vasodilating properties of Dipyridamole Tablets may occasionally produce a throbbing headache which normally disappears with dosage reduction.

ADVERSE REACTIONS REPORTED IN PATIENTS TAKING DIPYRIDAMOLE

The following adverse reactions have been reported in patients taking dipyridamole. The adverse reactions are classified according to frequencies determined from postmarketing experience and reference literature.

Very common >1/10 (>10%)

Common >1/100 and <1/10 (>1% and <10%)

Uncommon >1/1000 and <1/100 (>0.1% and <1%)

Rare >1/10,000 and <1/1000 (>0.01% and 0.1%)

Very rare < 1/10,000 (<0.1%)

Immune System Disorders

Uncommon: Hypersensitivity reaction

Nervous System Disorders

Common: Headache, dizziness Uncommon: Fainting

Cardiac Disorders

Uncommon: Angina pectoris aggravated, cardiac arrhythmia

Vascular Disorders

Common: Hypotension, facial flushing

Gastrointestinal Disorders

Common: Nausea, diarrhoea Uncommon: Vomiting

Skin and Subcutaneous Tissue Disorders

Uncommon: rash

General Disorders and Administration Site Conditions

Uncommon: Chest pain

In very rare cases, increased bleeding during or after surgery has been observed. Isolated cases of thrombocytopenia have been reported in conjunction with treatment with dipyridamole.

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; website: www.mhra.gov.uk/yellowcard

4.9. Overdose

Due to the low number of observations, experience with dipyridamole overdose is limited.

Symptoms such as a headache, gastrointestinal disturbances, warm feeling, flushes, sweating, restlessness, feeling of weakness, dizziness, hypotension and angina complaints can be expected. Coronary vasodilation may cause chest pain in patients with ischaemic heart disease.

General supportive measures should be employed. Coronary vasodilation may be reversed by administering of xanthine derivatives (e.g. aminophylline) by slow iv injection, whilst monitoring the ECG.

Due to its wide distribution to tissues and its predominantly hepatic elimination, dipyridamole is not likely to be accessible to enhanced removal procedures.

PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

Dipyridamole is an antithrombotic agent with antiplatelet activity.

Dipyridamole has an antithrombotic action based on its ability to modify various aspects of platelet function, such as platelet aggregation, adhesion and survival, which are factors associated with the initiation of thrombus formation.

5.2. Pharmacokinetic Properties

Dipyridamole is rapidly absorbed from the gastro-intestinal tract. Peak plasma concentrations occur about 75 minutes after oral administration. Dipyridamole is highly bound to plasma proteins. A terminal half-life of 1012 hours has been reported. It is conjugated in the liver and is mainly excreted in the faeces as glucuronides. Excretion may be delayed by reabsorption. A small amount is excreted in the urine.

Dipyridamole is detectable in breast milk, but at only approximately one seventeenth the concentration present in plasma.

5.3. Pre-clinical Safety Data

Not applicable.

6. PHARMACEUTICAL PARTICULARS

6.1. List of Excipients

Also contains: lactose, magnesium stearate, maize starch, polyvidone, propylene glycol, E171, E464, E553.

6.2. Incompatibilities

None known.

6.3. Shelf Life

Shelf-life

We propose a shelf-life of two years from the date of manufacture, to be extended when further stability testing becomes available.

Shelf-life after dilution/reconstitution Not applicable.

Shelf-life after first opening Not applicable.

6.4. Special Precautions for Storage

Store below 25°C in a dry place. Protect from light.

6.5. Nature and Contents of Container

The product containers are rigid injection moulded polypropylene or injection blow-moulded polyethylene containers with polyfoam wad or polyethylene ullage filler and snap-on polyethylene lids; in case any supply difficulties should arise the alternative is amber glass containers with screw caps and polyfoam wad or cotton wool. An alternative closure for polyethylene containers is a polypropylene, twist on, push down and twist off child-resistant, tamper-evident lid.

The product may also be supplied in blister packs in cartons:

a)    Carton: Printed carton manufactured from white folding box board.

b) Blister pack: (i) 25Opm white rigid PVC. (ii) Surface printed 20pm hard

temper aluminium foil with 5-8g/M² PVC and PVdC compatible heat seal lacquer on the reverse side.

Pack sizes: 28s, 30s, 56s, 60s, 84s, 90s, l00s, 112s, l20s, l68s, l80s, 250s, 500s, l000s.

Product may also be supplied in bulk packs, for reassembly purposes only, in polybags contained in tins, skillets or polybuckets filled with suitable cushioning material. Bulk packs are included for temporary storage of the finished product before final packaging into the proposed marketing containers.

Maximum size of bulk packs: 50,000.

Instructions for Use/Handling

Not applicable.

7    MARKETING AUTHORISATION HOLDER

Actavis UK Limited (Trading style: Actavis) Whiddon Valley BARNSTAPLE N Devon EX32 8NS

8. MARKETING AUTHORISATION NUMBER(S)

PL 0142/0309

9.    DATE OF FIRST AUTHORISATION/RENEWAL OF

AUTHORISATION

24.8.90

10 DATE OF REVISION OF THE TEXT

20/04/2015