Prasugrel

Prasugrel is an oral P2Y12 receptor antagonist prodrug with faster and more consistent platelet inhibition than clopidogrel. It reduces stent thrombosis and recurrent myocardial infarction in patients undergoing percutaneous coronary intervention for acute coronary syndrome, but it raises major bleeding and is harmful in patients with prior stroke. It is expensive and rarely available in East Africa.

Classification. Antiplatelet; thienopyridine P2Y12 inhibitor (irreversible).

Mechanism. Converted in the liver (by CYP3A4 and CYP2B6, after intestinal hydrolysis) to an active metabolite that binds the P2Y12 receptor irreversibly, blocking ADP induced platelet aggregation.

Pharmacodynamics. Onset within 30 minutes of 60 mg loading; peak inhibition in 2 hours. Platelet function recovers over 7 to 10 days after stopping. Little variability between patients.

Pharmacokinetics. Absorbed rapidly; at least 79% bioavailability. Active metabolite half life about 7 hours. Excreted in urine (68%) and faeces (27%) as inactive metabolites. Not significantly affected by CYP2C19.

Acute coronary syndrome managed with percutaneous coronary intervention (with aspirin), adult.

• Loading 60 mg as a single dose at or just before the intervention (once the coronary anatomy is known).

• Then 10 mg once daily; use 5 mg once daily for body weight under 60 kg.

• Duration up to 12 months, and then a single antiplatelet drug.

• Not advised from 75 years of age (use 5 mg in a high risk case where treatment is judged necessary, such as diabetes or prior myocardial infarction).

Children. Not established.

Contraindications. Active pathological bleeding; previous stroke or transient ischaemic attack (higher intracranial bleeding); severe hepatic impairment; hypersensitivity. Pre treatment before angiography in non ST elevation acute coronary syndrome is not advised.

Warnings. Major bleeding including fatal bleeding; risk is higher with weight under 60 kg and age 75 years or older; stop 7 days before surgery; thrombotic thrombocytopenic purpura (rare); hypersensitivity; premature stopping increases thrombotic risk.

Adverse effects. Bleeding, bruising, anaemia, epistaxis, haematuria, gastrointestinal bleeding, rash, rarely thrombotic thrombocytopenic purpura.

Interactions. Warfarin, direct oral anticoagulants, non steroidal anti-inflammatory drugs and aspirin above 100 mg: bleeding. Selective serotonin reuptake inhibitors: bleeding. Morphine delays absorption. No significant effect from omeprazole or CYP2C19 inhibitors.

Special groups.

• Pregnancy: avoid unless essential; limited data.

• Breastfeeding: no data; avoid.

• Patients of African ancestry: no dose change.

• Older adults: avoid at 75 years and over unless high risk; use 5 mg if used.

• Kidney impairment: no adjustment; limited data in end stage kidney disease.

• Liver impairment: mild to moderate: no change; severe: contraindicated.

Formulations. Tablets 5 and 10 mg.

Administration. Oral once daily with or without food. Loading 60 mg may be swallowed whole; crushed tablets are acceptable in an emergency.

Baseline. Haemoglobin, platelet count, creatinine, liver function, body weight, history of stroke or transient ischaemic attack.

Monitoring. Bleeding signs; haemoglobin and platelets at 1 month and with symptoms; adherence.

Stopping. Do not stop in the first 6 to 12 months after a stent without cardiology advice. Stop 7 days before elective surgery when safe.

Common prescribing errors. Giving to a patient with prior stroke; starting 10 mg under 60 kg; using in older adults without dose reduction; pre treating before angiography in non ST elevation events; using it with oral anticoagulants without review.