Dipyridamole Tablets 25mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Dipyridamole Tablets 25mg
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Dipyridamole 25 mg
Also contains lactose and sucrose. For a full list of excipients see 6.1.
3. Pharmaceutical Form
Sugar-coated tablet
Orange biconvex sugar-coated tablet
Clinical Particulars
4.1. Therapeutic Indications
1. As an adjunct to oral anti-coagulation for prophylaxis of thromboembolism associated with prosthetic heart valves.
2. In combination with aspirin for:
a. Prophylaxis of deep venous thrombosis as an alternative to subcutaneous heparin, other than in hip surgery.
b. Prophylaxis of recurrent venous thrombosis resistant to oral anticoagulation.
c. Prophylaxis of occlusion following prosthetic arterial grafts and coronary artery bypass grafts.
4.2 Posology and method of administration
Adults: 300-600 mg daily in three or four doses.
Children: Dipyridamole is not recommended for children.
Elderly: As for adults.
Dipyridamole is taken by mouth, and should usually be taken before meals.
Contra-indications
4.3.
Patients with a known hypersensitivity to Dipyridamole. Patients with known cardiac conduction difficulties or dysrhythmias.
4.4. Special Warnings and Precautions for Use
Dipyridamole is a potent vasodilator and should be used with caution in patients with rapidly worsening angina, sub-valvular aortic stenosis or haemodynamic instability (e.g. decompensated heart failure) associated with a recently sustained myocardial infarction.
Dipyridamole should be used with caution in patients with coagulation disorders and hypotension. It may also exacerbate migraine.
In patients with myasthenia gravis, readjustment of therapy may be necessary after changes in dipyridamole dosage.
Patients with rare hereditary problems of fructose intolerance, galactose intolerance, the Lapp lactase deficiency, glucose/galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Adenosine: Dipyridamole enhances and extends the effects of adenosine (increased plasma levels; important risk of cardiovascular toxicity). Adjustment of adenosine dosage should be considered if use with dipyridamole is unavoidable.
Antacids: Absorption of Dipyridamole possibly decreased by antacids.
Anticoagulants & antiplatelet drugs: Dipyridamole enhances the antiplatelet effect of oral anticoagulants (e.g. coumarins and phenindione), and the anticoagulant effect of heparins. If it is considered necessary to use in combination, the current product information on intolerance and risk for these preparations must be taken into account (e.g. increased clinical and laboratory monitoring).
Dipyridamole and concurrent acetylsalicyclic acid has an additive effect on platelet function.
There is an increased risk of bleeding when Dipyridamole is given with Clopidogrel.
Antihypertensives: Dipyridamole is a coronary vasodilator and so may increase the hypotensive effects of drugs which reduce blood pressure
Cholinesterase inhibitors: Dipyridamole and may counteract the anticholinesterase effect of cholinesterase inhibitors thereby potentially aggravating myasthenia gravis.
Cytotoxic drugs: Dipyridamole possibly reduces effects of Fludarabine.
4.6 Pregnancy and lactation
Dipyridamole should not be used in pregnancy, especially for the first trimester, unless the expected benefit is thought to outweigh any possible risk to the foetus.
Low levels (6% of the plasma concentration) of Dipyridamole are excreted in breast milk; therefore it should only be used during lactation if considered essential by the physician.
4.7. Effects on Ability to Drive and Use Machines
Not applicable.
4.8 Undesirable effects
The following undesired events, listed by body system, have been reported [frequencies: very common 10%), common (1-9.9%), uncommon (0.1-0.9%), rare (0.01-0.09%), very rare (<0.01%) including isolated reports, not known (cannot be estimated from the available data)].
If these occur it is usually during the early part of treatment and they are often dose-related.
Blood and lymphatic system disorders
Rare: Isolated cases of thrombocytopenia have been reported in conjunction with treatment of dipyridamole.
Immune system disorders
Frequency not known: Hypersensitivity reactions such as rash, urticaria, severe bronchospasm and angio-oedema have been reported.
Nervous system disorders
Frequency not known: Dizziness, faintness
Cardiac disorders
Frequency not known: tachycardia
Worsening of symptoms of coronary heart disease such as angina and arrhythmias.
Vascular disorders
The vasodilating properties may occasionally produce a vascular headache which normally disappears with long-term use.
As a result of its vasodilator properties, dipyradimole may cause hypotension, hot flushes and tachycardia.
Gastrointestinal disorders
Frequency not known: Vomiting, diarrhoea, nausea, dyspepsia
Hepato-biliary disorders
Frequency not known: Dipyridamole has been shown to be incorporated into gallstones.
Musculoskeletal and connective tissue disorders:
Frequency not known: Myalgia Surgical and medical procedures:
In very rare cases, increased bleeding during or after surgery has been reported.
4.9 Overdose
Experience with dipyridamole in overdose is limited. The fatal dose is unknown but acute ingestion of more than 200mg may result in symptoms. The mean elimination half-life in therapeutic use is 11.6 hours (range 9.4 to 13.8 hours)
Symptoms
The following have been reported; headache, weakness, gastro-intestinal symptoms, facial flushing drowsiness, coma, severe chest pain, tachycardia, hypotension, left bundle branch block, deep S-T inversion, T-wave inversion and myocardial infarction.
The following may occur - shortness of breath, respiratory distress, apnoea and metabolic acidosis.
Management
• The benefits of gastric lavage are uncertain but consider activated charcoal if an adult presents within 1 hour of ingestion of more than 600mg, a child more than 10mg/kg
• Observe for a minimum of 4 hours after ingestion or 12 hours if sustained release preparation taken
• Monitor blood pressure and ECG
• Correct hypotension by raising the foot of the bed and/or expanding the intravascular volume. If severe hypotension persists consider inotropes (e.g. dopamine or dobutamine)
• Other measures as indicated by the patient’s condition
• Aminophylline has been used to reverse dipyridamole induced coronary vasodilatation and bronchospasm
• Because of its wide tissue distribution and predominantly hepatic elimination, dipyridamole is not likely to be eliminated by enhanced removal procedures.
Pharmacological Properties
5.1. Pharmacodynamic Properties
The antithrombotic activity of phosphodiesterase inhibitors, such as dipyridamole, depend upon the activation of platelet adenylcyclase by potentiation of endogenous prostacyclin.
Dipyridamole inhibits platelet function through its effect on prostacyclin metabolism in platelets.
5.2. Pharmacokinetic Properties
Dipyridamole is readily absorbed from the gastro-intestinal tract. It is concentrated in the liver and is mainly excreted in the faeces. Excretion may be delayed by reabsorption. A small amount is excreted in the urine as glucuronide.
5.3. Preclinical Safety Data
No relevant information additional to that contained elsewhere in the SPC.
Pharmaceutical Particulars
6.1. List of Excipients
Lactose Maize starch Povidone
Pregelatinised starch Magnesium stearate Bleached shellac Sucrose Talc
Titanium dioxide E171 Beeswax Carnauba wax Orange colour
6.2. Incompatibilities
Sensitivity to Dipyridamole or any of the other ingredients of Dipyridamole. The concurrent use of antacids may reduce the efficacy of Dipyridamole.
6.3. Shelf Life
Containers: 36 months Blister packs: 36 months
6.4. Special Precautions for Storage
Containers: Do not store above 25°C. Keep the container tightly closed. Blister packs: Do not store above 25°C. Store in the original package.
6.5. Nature and Contents of Container
Polypropylene or high density polystyrene with polythene closure and polyurethane wads or polythene inserts.
Packs of 28, 30, 50, 56, 60, 84, 100, 250, 500 and 1000.
PVC/Aluminium foil blister packs 250 micron PVC glass-clear bluish rigid PVC (Pharmaceutical grade). 20 micron hard-tempered aluminium foil coated on the dull side with 6-7 gsm heat-seal lacquer and printed on the bright side.
Packs of 28, 30, 50, 56, 60, 84, 100, 250, 500 and 1000.
6.6. Instruction for Use/Handling Not applicable.
Administrative Data
7. Marketing Authorisation Holder
Metwest Pharmaceuticals Limited 15 Runnelfield Harrow on the Hill Middlesex HA1 3NY United Kingdom
8. Marketing Authorisation Number
PL 17521/0005
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
08/12/2005
10 DATE OF REVISION OF THE TEXT
21/03/2012