PRASUGREL

What it is

Prasugrel Lupin is a film-coated tablet available in two strengths: 5 mg and 10 mg. Prasugrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y 12 class of ADP receptors on platelets.

Approved indications

— Prevention of atherothrombotic events (myocardial infarction, stroke and cardiovascular death) in patients with acute coronary syndromes (moderate to high risk unstable angina, non ST-segment elevation myocardial infarction or ST-segment elevation myocardial infarction) who are to undergo percutaneous coronary intervention.

Dosing overview

Prasugrel Lupin should be initiated with a single 60 mg loading dose and then continued at a 10 mg once daily maintenance dose. Patients taking Prasugrel Lupin should also take aspirin (75 mg to 325 mg) daily. Prasugrel Lupin is generally not recommended in patients aged 75 years or over; if used, a single 60 mg loading dose should be given and consideration may be given to a 5 mg once daily maintenance dose, as the 10 mg maintenance dose is not recommended. For patients weighing less than 60 kg, Prasugrel Lupin should be given as a single 60 mg loading dose and then continued at a 5 mg once daily maintenance dose; the 10 mg maintenance dose is not recommended.

Key safety warnings

In the Phase 3 clinical trial, prasugrel-treated patients with a history of transient ischaemic attack or ischaemic stroke more than 3 months prior to drug therapy had a higher rate of the primary composite endpoint including ischaemic or haemorrhagic stroke compared to clopidogrel, and the rate of major or minor bleeding was also increased in these patients compared to patients without such a history; patients with ischaemic stroke within 3 months of drug therapy or haemorrhagic stroke were excluded from the trial. Patients with acute coronary syndromes undergoing percutaneous coronary intervention treated with prasugrel showed an increased risk of major and minor bleeding; therefore use of prasugrel in patients at increased risk of bleeding should only be considered when the benefits in terms of prevention of ischaemic events are deemed to outweigh the risk of serious bleeding. Patients aged 75 years or older taking prasugrel were at a greater risk of bleeding, including fatal bleeding, compared to patients under 75 years of age. In patients with body weight less than 60 kg, a 5 mg maintenance dose is recommended. Caution is necessary with concomitant administration of medications that may increase the risk of bleeding, including oral anticoagulants, non-steroidal anti-inflammatory drugs, and fibrinolytics. In a clinical trial of NSTEMI patients, patients given a 30 mg loading dose approximately 4 hours prior to coronary angiography followed by 30 mg at the time of percutaneous coronary intervention had an increased risk of major and minor peri-procedural bleeding and no additional benefit compared to patients receiving a 60 mg loading dose at the time of percutaneous coronary intervention; therefore in NSTEMI patients, the 60 mg loading dose should generally be given at the time of percutaneous coronary intervention. Thrombotic thrombocytopenic purpura has been reported with the use of prasugrel and is a serious condition requiring prompt treatment. Hypersensitivity reactions including angioedema and anaphylaxis have been reported in patients receiving prasugrel, including in patients with a history of hypersensitivity reaction to clopidogrel; monitoring for signs of hypersensitivity in patients with a known allergy to thienopyridines is advised.

Contraindications

Prasugrel Lupin is contraindicated in patients with active pathological bleeding; a known history of transient ischaemic attack or stroke; severe hepatic impairment (Child Pugh Class C); or a known hypersensitivity or allergy to any ingredient of the product.

PBS listing

Prasugrel Lupin 5 mg tablets are listed on the PBS with streamlined restriction at an ex-manufacturer price of A$47.25, and the 10 mg tablets are listed with streamlined restriction at an ex-manufacturer price of A$52.50.

Regulatory history

Prasugrel Lupin 5 mg and 10 mg film-coated tablets were first registered on the Australian Register of Therapeutic Goods on 26 June 2020.