1-active ingredient... المادة الفعالة
apixaban
2-dosage form
oral tablets 2. 5 mg & 5mg
3-pharmacological action
-Inhibits platelet activation and fibrin clot formation via direct, selective and reversible inhibition of free and clot-bound factor Xa (FXa).
-FXa, as part of the prothrombinase complex consisting also of factor Va, calcium ions, and phospholipid, catalyzes the conversion of prothrombin to thrombin.
-Thrombin both activates platelets and catalyzes the conversion of fibrinogen to fibrin.
Onset of Action
-3 to 4 hours
Time to Peak
3 to 4 hours
Half-Life Elimination
~12 hours
Protein Binding
~87%
4- Administration
-Administer without regard to meals.
-After hip/knee replacement, initial dose should be administered 12 to 24 hours postoperatively.
-If patient unable to swallow whole tablets, may crush 5 mg or 2.5 mg tablets and suspend in 60 mL of water, D5W, or apple juice or mix with applesauce; administer immediately.
- For delivery through a nasogastric tube, crushed tablets may be suspended in 60 mL of water or D5W followed by immediate delivery.
-Crushed tablets are stable in water, D5W, apple juice, and applesauce for up to 4 hours.
5- Indications
Deep vein thrombosis:
-Treatment of deep vein thrombosis;
- to reduce the risk of recurrent deep vein thrombosis following initial therapy
Nonvalvular atrial fibrillation:
- To reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF)
Note: The 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society guidelines for the management of AF recommend oral anticoagulation for patients with nonvalvular AF or atrial flutter with prior stroke, TIA, or a CHA2DS2-VASc score ≥2.
-As an alternative to warfarin, apixaban may also be used for 3 weeks prior and 4 weeks after cardioversion in patients with AF or atrial flutter of ≥48 hours duration or when the duration is unknown
Postoperative venous thromboprophylaxis following hip or knee replacement surgery:Prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism, in patients who have undergone hip or knee replacement surgery
Pulmonary embolism: Treatment of pulmonary embolism; to reduce the risk of recurrent pulmonary embolism following initial therapy
6-Dosing:
***Adult
-Deep venous thrombosis: Oral:
*Treatment: 10 mg twice daily for 7 days followed by 5 mg twice daily
*Reduction in the risk of recurrence: 2.5 mg twice daily after at least 6 months of treatment for DVT
-Nonvalvular atrial fibrillation (to prevent stroke and systemic embolism): Oral:
5 mg twice daily unless patient has any 2 of the following: Age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL, then reduce dose to 2.5 mg twice daily.
-Postoperative venous thromboprophylaxis:Oral:
*Hip replacement surgery: 2.5 mg twice daily beginning 12 to 24 hours postoperatively; duration: 35 days
*Knee replacement surgery: 2.5 mg twice daily beginning 12 to 24 hours postoperatively; duration: 12 days
-Pulmonary embolism (PE): Oral:
*Treatment: 10 mg twice daily for 7 days followed by 5 mg twice daily
*Reduction in the risk of recurrence: 2.5 mg twice daily after at least 6 months.
Dosing: Geriatric
-Refer to adult dosing. Nonvalvular atrial fibrillation
(to prevent stroke and systemic embolism): If patient is ≥80 years of age andeither weighs ≤60 kg or has a serum creatinine ≥1.5 mg/dL, then reduce dose to 2.5 mg twice daily.
7-Drug Interactions
-Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the adverse/toxic effect of Apixaban.
-Specifically, the risk for bleeding may be increased.
-Management: Carefully consider risks and benefits of this combination and monitor closely. Monitor therapy
-Anticoagulants: Apixaban may enhance the anticoagulant effect of Anticoagulants.
-Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods.
-Exceptions: Acenocoumarol; Warfarin.
Avoid combination
-Antiplatelet Agents (P2Y12 Inhibitors): May enhance the adverse/toxic effect of Apixaban.
-Specifically, the risk for bleeding may be increased.
-Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Consider therapy modification
-Aspirin: May enhance the adverse/toxic effect of Apixaban.
-Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Consider therapy modification
-Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
-Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy
-CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
-CYP3A4 Inducers (Strong): May decrease the serum concentration of Apixaban. Avoid combination
-CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Apixaban. Monitor therapy
-CYP3A4 Inhibitors (Strong): May increase the serum concentration of Apixaban.
-Exceptions: Clarithromycin; Cobicistat; Darunavir; Itraconazole; Ketoconazole (Systemic); Lopinavir; Ombitasvir, Paritaprevir, and Ritonavir; Ritonavir; Saquinavir; Telaprevir. Monitor therapy
-Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination
-Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible.
-If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).Consider therapy modification
-Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy
Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy
-Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Avoid combination
-Estrogen Derivatives: May diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of estrogens against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations.Exceptions: Tibolone. Consider therapy modification
-Factor X (Human): Anticoagulants (Inhibitors of Factor Xa) may diminish the therapeutic effect of Factor X (Human). Monitor therapy
-Fusidic Acid (Systemic): May increase the serum concentration of Apixaban. Management: Consider alternatives to this combination when possible. Apixaban dose adjustments may be required when used with systemic fusidic acid. Patients using this combination should be monitored extra closely. Consider therapy modification
-Hemin: May enhance the anticoagulant effect of Anticoagulants. Avoid combination
-Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Consider therapy modification
-Ibritumomab: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to an increased risk of bleeding. Monitor therapy
-Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy
-Inhibitors of CYP3A4 (Strong) and P-glycoprotein: May increase the serum concentration of Apixaban. Management: US labeling recommends a 50% apixaban dose reduction in patients who would otherwise receive 5 or 10 mg twice daily, and avoiding in patients who would otherwise receive 2.5 mg twice daily. Canadian labeling lists any combined use as contraindicated. Consider therapy modification
-Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Monitor therapy
-Naproxen: May enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Naproxen may increase the serum concentration of Apixaban. Consider therapy modification
-Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Monitor therapy
-Nonsteroidal Anti-Inflammatory Agents: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
-NSAID (Nonselective): May enhance the adverse/toxic effect of Apixaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of apixaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Consider therapy modification
-Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy
-Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Avoid combination
-Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants.Monitor therapy
-Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants.Monitor therapy
Progestins: May diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of progestins against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification
-Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Monitor therapy
-Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods.Avoid combination
-Salicylates: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
-Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
-St John's Wort: May decrease the serum concentration of Apixaban. Avoid combination
-Sugammadex: May enhance the anticoagulant effect of Anticoagulants.Monitor therapy
-Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: See full drug monograph for guidelines for the use of alteplase for acute ischemic stroke during treatment with oral anticoagulants. Monitor therapy
-Tibolone: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
-Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy
-Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Anticoagulants may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse effects may be increased. Monitor therapy
-Urokinase: May enhance the anticoagulant effect of Anticoagulants. Avoid combination
-Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants.Monitor therapy
-Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
-Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Avoid combination
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