CopiXa Tablet

CopiXa Tablet is used for: Indicated to reduce risk of stroke and systemic embolism associated with nonvalvular atrial fibrillation, Postoperative Prophylaxis of DVT/PE following hip or knee replacement surgery, Deep venous thrombosis (DVT), Pulmonary embolism (PE),

Oral Adult Prevention of VTE: Elective hip or knee replacement surgery Tablet 2.5 mg twice daily. The initial dose should be taken 12-24 hr post-op. Recommended duration of treatment: Patient undergoing hip replacement surgery 32-38 days. Patient undergoing knee replacement surgery 10-14 days. Prevention of stroke and systemic embolism in non-valvular atrial fibrillation Adult: 5 mg bid. Deep vein thrombosis, Pulmonary embolism Adult: 10 mg bid for 7 days, followed by 5 mg bid. Prevention of recurrence: 2.5 mg bid after at least 6 months of treatment.

Renal impairment, including ESRD on dialysis Deep Vein Thrombosis: No dose adjustment recommended; clinical efficacy and safety studies did not enroll patients with ESRD on dialysis or patients with a CrCl <15 mL/min; dosing recommendations are based on pharmacokinetic and pharmacodynamic (anti-FXa activity) data in study subjects with ESRD maintained on dialysis Renal impairment (nonvalvular atrial fibrillation) Mild-to-moderate: No dosage adjustment required Serum creatinine >1.5 mg/dL: Decrease dose to 2.5 mg BID if the patient has 1 additional characteristic of age >80 years or weight <60 kg ESRD maintained on hemodialysis: 5 mg BID; decrease dose to 2.5 mg BID if 1 additional characteristic of age >80 years or weight <60 kg is present

May be taken with or without food.

Hypersensitivity. Clinically significant active bleeding. Hepatic disease associated w/ coagulopathy & clinically relevant bleeding risk. Lesion or condition at significant risk of major bleeding. Concomitant treatment w/ other anticoagulant agent.

Discontinuing in patients with nonvalvular atrial fibrillation Premature discontinuation of any oral anticoagulant, including, apixaban, increases risk of thrombotic events Consider using another anticoagulant if anticoagulation with apixaban is discontinued for a reason other than pathological bleeding or completion of a course of therapy An increased rate of stroke was observed following discontinuation of apixaban in clinical trials in patients with nonvalvular atrial fibrillation If anticoagulation with apixaban must be discontinued for a reason other than pathological bleeding, coverage with another anticoagulant should be strongly considered Spinal/epidural hematoma Increased risk of epidural or spinal hematoma when used with neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture (can result in long-term or permanent paralysis) Risk increased with indwelling epidural catheters for administration of analgesia or by the concomitant use of drugs affecting hemostasis (eg, NSAIDs, platelet aggregation inhibitors, other anticoagulants) Risk also increased by traumatic or repeated epidural or spinal puncture; if this occurs, delay apixaban administration for 48 hr Monitor patients for signs and symptoms of neurologic impairment; if neurologic compromise is noted, urgent treatment is necessary Indwelling epidural or intrathecal catheters should not be removed earlier than 24 hr after the last administration of apixaban; the next apixaban dose should not be administered earlier than 5 hr after the removal of the catheter Consider the potential benefit versus risk before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis Increased risk of hemorrhage eg, congenital or acquired bleeding disorders; active ulcerative GI disease; bacterial endocarditis; thrombocytopenia; platelet disorders; history of haemorrhagic stroke; severe uncontrolled HTN; recent brain, spinal or ophthalmological surgery. Discontinue use if severe haemorrhage occurs. Renal impairment (CrCl <15 mL/min). Contraindicated in patients w/ hepatic disease associated w/ coagulopathy & clinically relevant bleeding risk. Not recommended in patients w/ severe hepatic impairment. Patients w/ mild or moderate hepatic impairment (Child Pugh A or B). Low body wt (<60 kg). Patients receiving concomitant systemic treatment w/ strong inhibitors of both CYP3A4 & P-gp eg, azole antimycotics (eg, ketoconazole, itraconazole, voriconazole & posaconazole) & HIV-PIs (eg, ritonavir); strong CYP3A4 & P-gp inducers (eg, rifampin, phenytoin, carbamazepine, phenobarb or St. John's wort). Patients receiving concomitant systemic treatment w/ strong inducers of both CYP3A4 & P-gp for the prevention of VTE in elective hip or knee replacement surgery, stroke in patients w/ NVAF. Patients treated concomitantly w/ medicinal products affecting haemostasis eg, NSAIDs, acetylsalicylic acid, platelet aggregation inhibitors or other antithrombotic agents. Spinal/epidural anaesth or puncture. Hip fracture surgery. Patients w/ prosthetic heart valves w/ or w/o atrial fibrillation. Patients w/ rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption. Pregnancy & lactation. Childn <18 yr. Elderly. Monitoring Parameters Patients should be monitored for signs of bleeding or anaemia; treatment should be stopped if severe bleeding occurs. No routine anticoagulant monitoring is required (INR tests are unreliable). Monitor patients for signs and symptoms of neurologic impairment; if neurologic compromise is noted, urgent treatment is necessary.

Pregnancy There are no adequate and well-controlled studies in pregnant women Treatment is likely to increase the risk of hemorrhage during pregnancy and delivery Use of anticoagulants, during pregnancy, may increase risk of bleeding in fetus and neonate Pregnancy confers an increased risk of thromboembolism that is higher for women with underlying thromboembolic disease and certain high-risk pregnancy conditions Published data describe that women with a previous history of venous thrombosis are at high risk for recurrence during pregnancy Therapy should be administered during pregnancy only if the potential benefit outweighs the potential risk to the mother and fetus Animal studies Treatment of pregnant rats, rabbits, and mice after implantation until the end of gestation resulted in fetal exposure to apixaban, but was not associated with increased risk for fetal malformations or toxicity Labor and delivery All patients receiving anticoagulants, including pregnant women, are at risk for bleeding; use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas; consider use of a shorter acting anticoagulant as delivery approaches Consider the risks of bleeding and of stroke in this setting Females of reproductive potential Females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician The risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants should be assessed in females of reproductive potential and those with abnormal uterine bleeding Lactation There are no data on presence of drug metabolites in human milk, effects on breastfed child, or the effects on milk production; the drug and/or its metabolites were present in milk of rats Rats excrete apixaban in milk (12% of the maternal dose) Because human exposure through milk is unknown, instruct women to either discontinue breastfeeding or to discontinue apixaban therapy, taking into account the importance of the drug to the mother

Increased exposure w/ strong dual CYP3A4 and P-glycoprotein (P-gp) inhibitors (e.g. clarithromycin, itraconazole, ketoconazole, ritonavir). Increased risk of bleeding w/ drugs affecting hemostasis (e.g. aspirin, heparin, fibrinolytics, SSRIs, NSAIDs, serotonin norepinephrine reuptake inhibitors). Increased risk of stroke w/ strong dual CYP3A4 and P-gp inducers (e.g. rifampicin, phenytoin, carbamazepine). Contraindicated (14) betrixaban carbamazepine defibrotide dexamethasone fondaparinux fosphenytoin mifepristone omacetaxine phenytoin prothrombin complex concentrate, human rifabutin secobarbital St John's Wort vorapaxar

Side effects of Apixaban : Bleeding (Aristotle Study) Major (2.13%, warfarin 3.09%; P <0.0001) GI (0.83%, warfarin 0.93%) Intracranial (0.33%, warfarin 0.82%) Intraocular (0.06%, warfarin 0.14%) Fatal (0.06%, warfarin 0.24%) Clinically relevant nonmajor bleeding (2.08%, warfarin 3.0%; P <0.0001) Bleeding (Averroes Study) Major (1.41%, aspirin 0.92%; P = 0.07) Fatal (0.16%, aspirin 0.16%) Intracranial (0.34%, aspirin 0.35%) <1% Hypersensitivity reactions (including skin rash and anaphylactic reactions such as allergic edema) Syncope Potentially Fatal: Epidural or spinal haematoma, fatal bleeding.

Apixaban is an anticoagulant that inhibits platelet activation and fibrin clot formation via direct, selective and reversible inhibition of free and clot-bound factor Xa in both intrinsic and extrinsic coagulation pathways. Inhibition of coagulation factor Xa prevents conversion of thrombin and subsequent thrombus formation.

CopiXa 2.5 mg Tablet manufactured by Synovia Pharma PLC. Its generic name is Apixaban. CopiXa is availble in Bangladesh. Farmaco BD drug index information on CopiXa Tablet is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.