PRADAXA

What it is

PRADAXA is a hard capsule for oral administration containing dabigatran etexilate (as dabigatran etexilate mesilate). It is available in three strengths: 75 mg, 110 mg, and 150 mg.

Approved indications

— Prevention of venous thromboembolic events in adult patients who have undergone major orthopaedic surgery of the lower limb (elective total hip or knee replacement). — Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and at least one additional risk factor for stroke. — Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and for the prevention of recurrent DVT and PE in adults.

Dosing overview

PRADAXA capsules can be taken with or without food and should be swallowed whole with a full glass of water. The capsule should not be chewed, broken, or opened as this may increase the risk of bleeding.

Key safety warnings

Dabigatran etexilate increases the risk of bleeding and can cause significant and sometimes fatal bleeding. Bleeding can occur at any site during therapy, and an unexplained fall in haemoglobin and/or haematocrit or blood pressure should lead to a search for a bleeding site. For life-threatening or uncontrolled bleeding when rapid reversal of the anticoagulation effects of dabigatran is required, the specific reversal agent PRAXBIND (idarucizumab) is available. Pharmacokinetic studies demonstrated an increase in drug exposure in patients with reduced renal function including age-related decline of renal function, and dabigatran etexilate is contraindicated in cases of severe renal impairment (CrCL <30 mL/min). Factors such as decreased renal function (30–50 mL/min CrCL), age ≥75 years or P-glycoprotein (P-gp) inhibitor co-medication are associated with increased dabigatran plasma levels, and the presence of one or more of these factors may increase the risk of bleeding, especially if combined. Gastrointestinal haemorrhage occurred at a higher frequency with dabigatran etexilate compared to warfarin, and the underlying mechanism of the increased rate of gastrointestinal bleeding has not been established. There have been post-marketing reports of anticoagulant-related nephropathy following anticoagulant use, presenting as acute kidney injury; in patients with altered glomerular integrity or with a history of kidney disease, acute kidney injury may occur, possibly in relation to episodes of excessive anticoagulation and haematuria.

Contraindications

Known hypersensitivity to dabigatran or dabigatran etexilate or to one of the excipients of the product. Severe renal impairment (CrCL <30 mL/min). Haemorrhagic manifestations, patients with a bleeding diathesis, or patients with spontaneous or pharmacological impairment of haemostasis. Current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities. Hepatic impairment or liver disease expected to have any impact on survival. History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding. Gastrointestinal haemorrhage within the past year unless the cause has been permanently eliminated, for example by surgery. Concomitant treatment with systemic ketoconazole, ciclosporin, itraconazole, dronedarone or the fixed-dose combination glecaprevir/pibrentasvir. Prosthetic heart valve replacement.

PBS listing

PRADAXA 150 mg capsules (2 PBS items) and 110 mg capsules (2 PBS items) are listed on the PBS with streamlined restriction status, with ex-manufacturer prices of A$34.07 and A$4.57 respectively.

Regulatory history

PRADAXA was first registered on the ARTG on 24 November 2008 for the 75 mg and 110 mg strengths, with the 150 mg strength registered on 29 April 2011. In November 2014 the PBAC recommended a change to the current PBS listing to allow use in patients with non-valvular atrial fibrillation who are at high risk of stroke or systemic embolism. An AusPAR was published on 24 August 2015 for the treatment of deep vein thrombosis and pulmonary embolism, and for the prevention of recurrent DVT and PE in adults. In November 2017 the PBAC recommended an amendment to the current PBS listing to allow dabigatran etexilate to be used for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation who are unsuitable for warfarin.