Dabigatran Sandoz

DVT & pulmonary embolism (PE), & prevention of recurrent DVT & PE in adults. Primary prevention of venous thromboembolic events in adults who have undergone elective total hip or knee replacement surgery. Prevention of stroke & systemic embolism in adults w/ non-valvular atrial fibrillation (NVAF), w/ ≥1 risk factors eg, prior stroke or transient ischemic attack; age ≥75 yr; heart failure (NYHA class ≥II); DM; HTN.

Primary prevention of VTE in orthopaedic surgery Treatment initiation on day of surgery 1-4 hr after completed surgery: Single 110 mg cap. Maintenance dose starting on 1st day after surgery: 220 mg taken as two 110 mg cap once daily. Duration of maintenance dose: Patient following elective knee replacement surgery 10 days. Patient following elective hip replacement surgery 28-35 days. Patient w/ moderate renal impairment (CrCl 30-50 mL/min), those who receive concomitant verapamil, amiodarone or quinidine, ≥75 yr Treatment initiation on day of surgery 1-4 hr after completed surgery: Single 75 mg cap. Maintenance dose starting on 1st day after surgery: 150 mg taken as two 75 mg cap once daily for 10 days in knee replacement surgery or 35 days in hip replacement surgery. Prevention of stroke & systemic embolism Adult w/ NVAF w/ ≥1 risk factors & those w/ moderate renal impairment (CrCl 30-50 mL/min) 300 mg taken as 150 mg cap bid. DVT & PE & prevention of recurrent DVT & PE Adult 300 mg taken as one 150 mg cap bid following treatment w/ parenteral anticoagulant for at least 5 days. Elderly ≥80 yr, patient who receive concomitant verapamil & those w/ high risk of bleeding 220 mg taken as one 110 mg cap bid.

May be taken with or without food: Swallow whole. Do not open cap.

Hypersensitivity. Active clinically significant bleeding. Lesion or condition, if considered significant risk factor for major bleeding including current or recent GI ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophth surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities. Prosthetic heart valves requiring anticoagulant treatment. Concomitant treatment w/ any other anticoagulants eg, unfractionated heparin (UFH), LMWH (enoxaparin, dalteparin), heparin derivatives (fondaparinux), oral anticoagulants (warfarin, rivaroxaban, apixaban) except under specific circumstances; strong P-gp inhibitors eg, systemic ketoconazole, cyclosporine, itraconazole, dronedarone & fixed-dose combination glecaprevir/pibrentasvir. Severe renal impairment (CrCl <30 mL/min). Hepatic impairment or liver disease expected to have any impact on survival.

Discontinue treatment in patients who develop acute renal failure; when severe bleedings occur & consider use of reversal agent (idarucizumab); 24 hr before invasive/surgical procedures. Temporarily discontinue treatment during emergency surgery or urgent procedures; subacute surgery/interventions. Consider stopping treatment 2-4 days before surgery in patients at higher risk of bleeding or in major surgery where complete haemostasis may be required. Delay surgery/intervention until at least 12 hr after last dose. Not recommended in patients undergoing hip fracture surgery; w/ elevated liver enzymes >2x ULN; w/ history of thrombosis who are diagnosed w/ antiphospholipid syndrome. Conditions w/ increased risk of bleeding; congenital or acquired coagulation disorders; thrombocytopenia or functional platelet defects; recent biopsy, major trauma; bacterial endocarditis; esophagitis, gastritis or gastroesophageal reflux. Higher rates of major GI bleeding. Consider PPI administration to prevent GI bleeding. Increased risk of spinal or epidural haematoma in cases of traumatic or repeated puncture & prolonged use of epidural catheters. Increased rates of recurrent thrombotic events compared w/ vit K antagonist therapy in patients that are triple +ve (for lupus anticoagulant, anticardiolipin, and anti-β-2-glycoprotein I Abs). Higher risk of MI. DVT/PE patients w/ active cancer. Low body wt (<50 kg). Patients undergoing catheter ablation for atrial fibrillation; at high surgical mortality risk & w/ intrinsic risk factors for thromboembolic events. Assess renal function prior to & during treatment. Closely observe for signs of bleeding or anaemia throughout treatment period; in patients concomitantly treated with NSAIDs. Measure dabigatran-related anticoagulation. Consider use of fibrinolytic medicinal products for acute ischemic stroke if patient presents w/ dTT, ECT or aPTT not exceeding ULN. Observe patients for neurological signs & symptoms of spinal or epidural haematoma. Not to perform INR tests due to false +ve INR elevations. Perform coagulation test to determine impaired haemostasis. Avoid concomitant use w/ P-gp inducers. Concomitant use w/ medicinal products affecting haemostasis by platelet aggregation inhibiton; P-gp inhibitors eg, verapamil, amiodarone, quinidine or clarithromycin. Contains Na 23 mg/cap. Moderate renal impairment (CrCl 30-50 mL/min). Avoid pregnancy during treatment in women of childbearing potential. Not to be used during pregnancy. Discontinue breastfeeding during treatment. Childn. Elderly ≥75 yr.

Anaemia; epistaxis; GI haemorrhage, abdominal pain, diarrhoea, dyspepsia, nausea, rectal haemorrhage; skin haemorrhage; genitourological haemorrhage including haematuria.

Increased AUC & C_max w/ ketoconazole, dronedarone, itraconazole, cyclosporine; verapamil; amiodarone; quinidine; clarithromycin; ticagrelor; clopidogrel. Increased exposure & risk of bleeding w/ glecaprevir/pibrentasvir. Decreased conc w/ rifampicin, St. John's wort (Hypericum perforatum), carbamazepine, phenytoin. Increased bleeding risk w/ SSRIs & SNRIs; NSAIDs; ASA; anticoagulants eg, UFH, LMWH, heparin derivatives (fondaparinux, desirudin), thrombolytic medicinal products, vit K antagonists, rivaroxaban or other oral anticoagulants & antiplatelet aggregation medicinal products eg, GPIIb/IIIa receptor antagonists, ticlopidine, prasugrel, ticagrelor, dextran & sulfinpyrazone. Decreased AUC w/ pantoprazole. Concomitant use w/ posaconazole. Not recommended for concomitant use w/ tacrolimus; ritonavir & its combinations w/ other PIs.

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

B01AE07 - dabigatran etexilate ; Belongs to the class of direct thrombin inhibitors. Used in the treatment of thrombosis.

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