Dipyridamole/ Aspirin

Registered South African indications:

• Secondary prevention of ischaemic stroke
• Secondary prevention of transient ischaemic attacks

Contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• Third trimester of pregnancy
• Active gastric or duodenal ulcers 
• Bleeding disorders
• Fructose intolerance
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• Sucrase-isomaltase insufficiency

Cautions

• First and second trimester of pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Increased bleeding risk 
• Severe coronary artery disease
• Unstable angina 
• Recent myocardial infarction
• Left ventricular outflow obstruction
• Haemodynamic instability 
• Myasthenia gravis
• History of ascending cholangitis
• Asthma
• Allergic rhinitis
• Nasal polyps
• Chronic or recurring gastric or duodenal complaints
• Glucose-6-phosphate dehydrogenase deficiency
• Children
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: cap

Secondary prevention of ischaemic stroke 
Secondary prevention of transient ischaemic attacks

Dipyridamole/ Aspirin
200/25 (mg) 

• Oral (cap): 1 cap, 12hrly with meals

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Swallow whole with water

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In the case of intolerable headaches: Switch to 1 cap at night and low dose aspirin in the morning for 3-5 days, then re-initiate treatment as normal

Not established for use in children

Pregnancy

• First and second trimester: Caution
• Third trimester: Contraindicated
• There is inadequate evidence of the safety in human pregnancy regarding dipyridamole and aspirin at low dose
• Animal studies performed with the drug combination revealed no increased teratogenic risk over the individual components alone. Studies covering the peripostnatal period have not been performed with the combination
• Dipyridamole and aspirin should only be used with caution in the first and second trimester if considered essential in terms of benefit and risk
• Dipyridamole and aspirin should be avoided completely in the third trimester

Breastfeeding

• Caution
• Dipyridamole and salicylates are excreted in breast milk. Therefore dipyridamole/aspirin should only be used in breast-feeding women when the potential benefits for the mother outweigh the possible risks for the newborn

Renal Impairment

• eGFR ≥30- 89 mL/min/1.73 m²: No dose adjustment is recommended
• eGFR ≥21- 29 mL/min/1.73 m²: Caution, dose adjustment recommended
• Limit use to 200mg/25mg, once per day. Closely monitor renal function (CrCl/eGFR)
• eGFR ≤20 mL/min/1.73 m²: Contraindicated

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended
• Severe: Contraindicated

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Intracranial haemorrhage
• Migrain-like headache
• Agitation
• Brain oedema
• Lethargy
• Convulsion
• Confusion

Cardiovascular Disorders

• Coronary artery disease exaccerbation
• Syncope
• Tachycardia
• Arrhythmia
• Hypertension
• Hot flush

Respiratory Disorders

• Epistaxis
• Dyspnoea
• Gingival bleeding
• Laryngeal oedema
• Hyperventilation
• Pulmonary oedema
• Tachypnoea

Gastrointestinal Disorders

• Dyspepsia
• Diarrhoea
• Nausea and vomiting
• Abdominal pain
• Gastrointestinal haemorrhage
• Gastric ulcer
• Duodenal ulcer
• Erosive gastritis
• Gastric ulcer perforation
• Duodenal ulcer perforation
• Melaena
• Haematemesis
• Pancreatitis

Hepatobiliary Disorders

• Gallstones
• Hepatitis
• Reye's syndrome
• Abnormal liver function tests

Genitourinary Disorders

• Renal failure
• Interstitial nephritis
• Renal papillary necrosis
• Proteinuria
• Increased blood uric acid
• Prolonged pregnancy
• Prolonged labour
• Small for dates baby
• Stillbirth
• Haemorrhage in pregnancy
• Postpartum haemorrhage

Endocrine and Metabolic Disorders

• Hypoglycaemia
• Hyperglycaemia
• Thirst
• Dehydration
• Hyperkalaemia
• Metabolic acidosis
• Respiratory alkalosis
• Hypothermia

Musculoskeletal Disorders

• Myalgia
• Rhabdomyolysis

Skin and Subcutaneous Tissue Disorders

• Skin haemorrhage
• Erythema exsudativum multiforme

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Anaphylactic reactions
• Pyrexia
• Anaemia
• Thrombocytopaenia
• Iron deficiency anaemia
• Disseminated intravascular coagulation
• Coagulopathy
• Prolonged bleeding time
• Prolonged prothrombin time

Sensory Disorders

• Tinnitis
• Deafness
• Eye haemorrhage

Others

• Post procedural haemorrhage
• Procedural haemorrhage

• Anticoagulants
• Antiplatelet agents
• Selective serotonin reuptake inhibitors
• Anagrelide
• Non-steroidal anti-inflammatory drugs
• Corticosteroids
• Chronic alcohol use
• Anticonvulsants
• Adenosine
• Antihypertensives
• Cholinesterase inhibitors 
• Hypoglycaemic agents
• Methotrexate
• Spironolactone
• Uricosuric agents

None routine. Specific cases may require

• Urine pH

Dipyridamole
Dipyridamole is a phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. 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.

Aspirin
Acetylsalicylic acid inhibits the cyclooxygenase enzyme, thereby preventing production of prostaglandins and thromboxanes. 

COMBINATION PREPARATIONS

Dipyridamole/ Aspirin

Capsule 200mg/25mg 

• Asasantin 200/25 Retard (Ingelheim) originator