ARX-DABIGATRAN

What it is

ARX-Dabigatran 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. ARX-Dabigatran capsules can be taken with or without food and should be swallowed whole with a full glass of water to facilitate delivery to the stomach.

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

Patients with moderate renal impairment (30–50 mL/min creatinine clearance) have an increased risk for bleeding and should receive a reduced dose of 150 mg given as two 75 mg capsules once daily for VTE prevention following orthopaedic surgery. Patients aged 75 years and above should be treated with a daily dose of 220 mg taken orally as one 110 mg capsule twice daily for stroke prevention in atrial fibrillation. Treatment duration for VTE prevention is 10 days following knee replacement surgery and 28–35 days following hip replacement surgery.

Key safety warnings

Dabigatran etexilate increases the risk of bleeding and can cause significant and sometimes fatal bleeding. As with all anticoagulants, dabigatran etexilate should be used with caution in conditions with an increased risk of bleeding. Bleeding can occur at any site during therapy. An unexplained fall in haemoglobin and/or haematocrit or blood pressure should lead to a search for a bleeding site. For situations of life-threatening or uncontrolled bleeding, when rapid reversal of the anticoagulation effects of dabigatran is required, the specific reversal agent idarucizumab is available. Pharmacokinetic studies demonstrated an increase in drug exposure in patients with reduced renal function including age-related decline of renal function. 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 inhibitor co-medication are associated with increased dabigatran plasma levels. The presence of one or more of these factors may increase the risk of bleeding, especially if combined. Specifically, with concomitant intake of antiplatelets or strong P-gp inhibitors in patients aged ≥75 years, the risk of major bleeding, including gastrointestinal bleeding, increases.

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. Hepatic impairment or liver disease expected to have any impact on survival. History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding. Simultaneous initiation of treatment with dabigatran etexilate and oral verapamil, or treatment initiation with oral verapamil in patients following major orthopaedic surgery who are already treated with dabigatran etexilate. Prosthetic heart valve replacement. Concomitant treatment with systemic ketoconazole, ciclosporin, itraconazole, dronedarone or the fixed-dose combination glecaprevir/pibrentasvir.

Regulatory history

ARX-Dabigatran was registered on the Australian Register of Therapeutic Goods on 10 October 2023, with three strengths listed: 75 mg (ARTG 414770), 110 mg (ARTG 414771), and 150 mg (ARTG 414772) capsules.