Acenocoumarol (United States: Not available): Drug information

(For additional information see "Acenocoumarol (United States: Not available): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: Canada

Sintrom [DSC]

Pharmacologic Category

Anticoagulant;
Anticoagulant, Vitamin K Antagonist

Dosing: Adult

Note: Dosage must be individualized. The following information is based on the manufacturer's labeling in Canada.

Prevention/treatment of thrombosis/embolism

Prevention/treatment of thrombosis/embolism: Oral: Initial: 8 to 12 mg on day 1, followed by 4 to 8 mg on day 2. Subsequent dosage should be based on INR measurements. Usual range of maintenance doses: 1 to 10 mg/day. Tapering of dosage is recommended prior to discontinuation.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Use with caution; the manufacturer's labeling does not provide specific dosing recommendations.

Dosing: Hepatic Impairment: Adult

Use with caution; the manufacturer's labeling does not provide specific dosing recommendations.

Dosing: Older Adult

Refer to adult dosing. Use with caution; lower dosages may be necessary.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

As with all anticoagulants, bleeding is the major adverse effect of acenocoumarol. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the intensity of anticoagulation and patient susceptibility. Frequency not defined.

Dermatologic: Skin necrosis (including hemorrhagic forms) (rare)

Genitourinary: Priapism

Hematologic & oncologic: Hemorrhage may occur at virtually any site that may be predisposed to bleeding. Includes cerebral hemorrhage, gallbladder hemorrhage, hematuria, hemophthalmos, hepatic hemorrhage, melena, menorrhagia, metrorrhagia

Hepatic: Hepatotoxicity

Contraindications

Hypersensitivity to acenocoumarol, related coumarin derivatives, or any component of the formulation; hemorrhagic tendencies and/or blood dyscrasias (eg, hemophilia, thrombocytopenic purpura, leukemia); recent or potential surgery of the eye or CNS; major regional lumbar block anesthesia or surgery resulting in large, open surfaces; bleeding from the GI, respiratory, or GU tract; aneurysm (cerebral or dissecting aortic); cerebrovascular hemorrhage; recent surgical procedures resulting in increased fibrinolytic activity (eg, surgery of the lung, prostate, uterus); polyarthritis; severe hypertension; severe parenchymal lesions of the liver and kidneys; pericarditis or pericardial effusion; subacute bacterial endocarditis; ascorbic acid deficiency; uncooperative patient (eg, patient with alcohol use disorder, unsupervised senile, or psychotic) intramuscular injections; inadequate laboratory facilities; threatened abortion; eclampsia/pre-eclampsia; pregnancy

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity: May cause hypersensitivity reactions, including anaphylaxis; use with caution in patients with anaphylactic disorders. Cross-reactivity among coumarin anticoagulants has been described.

• Bleeding: May cause major or fatal bleeding. Risk factors for bleeding include high intensity anticoagulation (INR >4), age (>65 years), variable INRs, history of GI bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, severe diabetes, malignancy, trauma, renal insufficiency, polycythemia vera, vasculitis, open wound, history of PUD, indwelling catheters, menstruating and postpartum women, and long duration of therapy or known genetic deficiency in CYP2C9 activity. Patient must be instructed to report bleeding, accidents, or falls as well as any new or discontinued medications, herbal or alternative products used, significant changes in smoking or dietary habits. Unrecognized bleeding sites (eg, colon cancer) may be uncovered by anticoagulation. Treatment should be withdrawn at the earliest signs of bleeding.

• Skin necrosis/gangrene: Necrosis or gangrene of the skin and other tissues can occur (rarely) due to early hypercoagulability; risk is increased in patients with protein C or S deficiency. Onset is usually within the first few days of therapy and is frequently localized to the limbs, breast, or penis.

• "Purple toe” syndrome: "Purple toe” syndrome, due to cholesterol microembolization, has been described with coumarin-type anticoagulants.

Disease-related concerns:

• Dietary insufficiency: Use with caution in patients with prolonged dietary insufficiencies (vitamin K deficiency).

• Infection: Use with caution in patients with acute infection or active TB; antibiotics and fever may alter response to acenocoumarol.

• Hepatic impairment: Use with caution in patients with hepatic impairment (undergoes hepatic metabolism).

• Renal impairment: Use with caution in patients with renal impairment.

• Thyroid disease: Use with caution in patients with thyroid disease.

Special populations:

• Older adult: The elderly may be more sensitive to anticoagulant therapy.

• Ovulating women: May be at risk of developing ovarian hemorrhage at the time of ovulation.

• Patients with genomic variants in CYP2C9 and/or VKORC1: Presence of the CYP2C9*3 allele and/or polymorphism of the vitamin K oxidoreductase (VKORC1) gene may increase the risk of bleeding. Lower doses may be required in these patients.

Other warnings/precautions:

• Patient selection: Use care in the selection of patients appropriate for this treatment; ensure patient cooperation.

Product Availability

Not available in the US

Generic Equivalent Available: US

May be product dependent

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Sintrom: 1 mg [DSC], 4 mg [DSC]

Administration: Adult

Administer at the same time each day.

Use: Labeled Indications

Note: Not approved in the US

Prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders; atrial fibrillation with risk of embolism; adjunct in the treatment of coronary occlusion and transient ischemic attacks

Medication Safety Issues

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Other safety concerns:

Interferes with hepatic synthesis of vitamin K-dependent coagulation factors (II, VII, IX, X)

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2C19 (minor), CYP2C9 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the anticoagulant effect of Vitamin K Antagonists. 5-Aminosalicylic Acid Derivatives may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Acalabrutinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Acetaminophen: May enhance the anticoagulant effect of Vitamin K Antagonists. This appears most likely with daily acetaminophen doses exceeding 1.3 or 2 g/day for multiple consecutive days. Risk C: Monitor therapy

Adalimumab: May decrease the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Alcohol (Ethyl): May decrease the serum concentration of Vitamin K Antagonists. More specifically, this effect has been described in heavy drinking alcoholic patients (over 250 g alcohol daily for over 3 months). The role of alcohol itself is unclear. Risk C: Monitor therapy

Aldesleukin: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Alemtuzumab: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Allopurinol: May enhance the anticoagulant effect of Vitamin K Antagonists. Management: Monitor for increased prothrombin times (PT)/therapeutic effects of oral anticoagulants if allopurinol is initiated/dose increased, or decreased effects if allopurinol is discontinued/dose decreased. Reductions in coumarin dosage will likely be needed. Risk D: Consider therapy modification

Alpelisib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: Monitor therapy

Amiodarone: May enhance the anticoagulant effect of Vitamin K Antagonists. Amiodarone may increase the serum concentration of Vitamin K Antagonists. Management: Monitor patients extra closely for evidence of increased anticoagulant effects if amiodarone is started. Consider empiric reduction of 30% to 50% in warfarin dose, though no specific guidelines on dose adjustment have been published. Risk D: Consider therapy modification

Amitriptyline: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Amorolfine: May enhance the anticoagulant effect of Acenocoumarol. Risk C: Monitor therapy

Anacaulase: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Anagrelide: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Androgens: May enhance the anticoagulant effect of Vitamin K Antagonists. Management: Monitor for increased effects of vitamin K antagonists if an androgen is initiated/dose increased, or decreased effects if androgen is discontinued/dose decreased. Significant reductions in vitamin K antagonist dose are likely required. Risk D: Consider therapy modification

Anticoagulants: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Antithyroid Agents: May diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Aprepitant: May decrease the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

AzaTHIOprine: May diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Barbiturates: May increase the metabolism of Vitamin K Antagonists. Management: Monitor INR more closely. Anticoagulant dose increases of 30% to 60% may be needed after a barbiturate is initiated or given at an increased dose. Anticoagulant dose decreases may be needed following barbiturate discontinuation or dose reduction. Risk D: Consider therapy modification

Bicalutamide: May increase the serum concentration of Vitamin K Antagonists. Specifically, free concentrations of the vitamin K antagonists may be increased. Risk C: Monitor therapy

Bimekizumab: May decrease the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

Bosentan: May decrease the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Bromperidol: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy

Caplacizumab: May enhance the anticoagulant effect of Anticoagulants. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification

CarBAMazepine: May decrease the serum concentration of Vitamin K Antagonists. Management: Monitor for decreased INR and effects of vitamin K antagonists if carbamazepine is initiated/dose increased, or increased INR and effects if carbamazepine is discontinued/dose decreased. Vitamin K antagonist dose adjustments will likely be required. Risk D: Consider therapy modification

Carbimazole: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Cephalosporins: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Chenodiol: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Chloral Betaine: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Chloral Hydrate: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Cholestyramine Resin: May decrease the serum concentration of Vitamin K Antagonists. Management: Separate the administration of vitamin K antagonists and cholestyramine by at least 3 to 4 hours. Monitor patients closely for reduced vitamin K antagonist effects (eg, decreased INR, thrombosis) when these agents are combined. Risk D: Consider therapy modification

Cimetidine: May enhance the anticoagulant effect of Vitamin K Antagonists. Management: Avoid coadministration of cimetidine and vitamin K antagonists. If unavoidable, monitor for increased effects of vitamin K antagonists when cimetidine is initiated/dose increased, or decreased effects if cimetidine is discontinued/dose decreased. Risk D: Consider therapy modification

Cloxacillin: May diminish the anticoagulant effect of Vitamin K Antagonists. Cloxacillin may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Coenzyme Q-10: May diminish the anticoagulant effect of Vitamin K Antagonists. Coenzyme Q-10 may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: 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. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Cranberry: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

CYP2C9 Inducers (Moderate): May decrease the serum concentration of Vitamin K Antagonists. Management: Monitor for decreased effects of vitamin K antagonists (eg, decreased INR, thrombosis) if combined with moderate CYP2C9 inducers. Vitamin K antagonist dose adjustments will likely be required. Risk D: Consider therapy modification

CYP2C9 Inducers (Weak): May decrease the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

CYP2C9 Inhibitors (Weak): May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: 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. Risk C: Monitor therapy

Defibrotide: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

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. Risk C: Monitor therapy

Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Management: Discontinue treatment with other anticoagulants prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Risk D: Consider therapy modification

Dexlansoprazole: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Dicloxacillin: May diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Direct Acting Antiviral Agents (HCV): May diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Disulfiram: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Dronedarone: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Econazole: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Efavirenz: May decrease the serum concentration of Vitamin K Antagonists. Efavirenz may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Elranatamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Epcoritamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Esomeprazole: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Ethacrynic Acid: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Ethotoin: May enhance the anticoagulant effect of Vitamin K Antagonists. Ethotoin may diminish the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may increase the serum concentration of Ethotoin. Risk C: Monitor therapy

Etoposide: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Etoposide Phosphate: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Fibric Acid Derivatives: May enhance the anticoagulant effect of Vitamin K Antagonists. Management: Consider reducing the oral anticoagulant dose by 25% to 33% when initiating a fibric acid derivative. Monitor for toxic or reduced anticoagulant effects if a fibric acid derivative is initiated/dose increased, or discontinued/dose decreased, respectively. Risk D: Consider therapy modification

Flucloxacillin: May diminish the anticoagulant effect of Vitamin K Antagonists. Flucloxacillin may decrease the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Fluconazole: May increase the serum concentration of Vitamin K Antagonists. Management: Consider alternatives when possible. If combined, consider reducing the vitamin K antagonist dose by 10% to 20% if combined with fluconazole. Monitor for increased anticoagulant effects (ie, increased INR, bleeding) to guide further dose adjustments. Risk D: Consider therapy modification

Fluorouracil Products: May increase the serum concentration of Vitamin K Antagonists. Management: Monitor INR and for signs/symptoms of bleeding closely when a fluorouracil product is combined with a vitamin K antagonist (eg, warfarin). Anticoagulant dose adjustment will likely be necessary. Risk D: Consider therapy modification

FluvoxaMINE: May increase the serum concentration of Acenocoumarol. Risk C: Monitor therapy

Fosaprepitant: May decrease the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: May enhance the anticoagulant effect of Vitamin K Antagonists. Fosphenytoin-Phenytoin may diminish the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of Vitamin K Antagonists. Management: Vitamin K antagonist dose adjustments may be required when used with systemic fusidic acid. Patients using this combination should be monitored extra closely for evidence of bleeding and to determine appropriate dose. Risk D: Consider therapy modification

Gefitinib: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Ginkgo Biloba: May enhance the adverse/toxic effect of Vitamin K Antagonists. Management: Consider avoiding the use of this combination of agents. Monitor for signs and symptoms of bleeding if vitamin K antagonists and Ginkgo biloba are used concomitantly. Risk D: Consider therapy modification

Glofitamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Glucagon and Glucagon Analogs: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Griseofulvin: May decrease the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Hemin: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Risk C: Monitor therapy

HMG-CoA Reductase Inhibitors (Statins): May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Hormonal Contraceptives: May increase the serum concentration of Vitamin K Antagonists. Hormonal Contraceptives may decrease the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy

Icosapent Ethyl: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Ifosfamide: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Inotersen: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Interferons (Alfa): May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Interleukin-6 (IL-6) Inhibiting Therapies: May decrease the serum concentration of CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

Itraconazole: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Ivermectin (Systemic): May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Management: Consider alternatives to this combination when possible. If combined, monitor for decreased effectiveness of these CYP2C9 substrates if combined with ivosidenib. Risk D: Consider therapy modification

Kanamycin: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Ketoconazole (Systemic): May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Lactulose: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Lansoprazole: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Lecanemab: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy

LevOCARNitine: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Risk C: Monitor therapy

Lipid Emulsion (Fish Oil and Plant Based): May diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Lipid Emulsion (Fish Oil Based): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Lornoxicam: May enhance the anticoagulant effect of Vitamin K Antagonists. Lornoxicam may increase the serum concentration of Vitamin K Antagonists. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor coagulation status closely and advise patients to promptly report any evidence of bleeding or bruising. Risk D: Consider therapy modification

Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor therapy

Macrolide Antibiotics: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Mavacamten: May decrease the serum concentration of CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

Megestrol: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Menadiol Diphosphate: May diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Menatetrenone: May diminish the anticoagulant effect of Vitamin K Antagonists. Management: Coadministration is not recommended. If concomitant use of menatetrenone and vitamin K antagonists cannot be avoided, monitor coagulation parameters, such as PT/INR. Risk D: Consider therapy modification

Mercaptopurine: May diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Mesoglycan: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

MetFORMIN: May diminish the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may enhance the hypoglycemic effect of MetFORMIN. Risk C: Monitor therapy

MetroNIDAZOLE (Systemic): May increase the serum concentration of Vitamin K Antagonists. Management: Consider alternatives to concomitant therapy with these agents. If concomitant therapy cannot be avoided, consider reducing the dose of the vitamin K antagonist and monitor for increased INR/bleeding. Risk D: Consider therapy modification

Miconazole (Topical): May increase the serum concentration of Vitamin K Antagonists. Management: Avoid using any miconazole-containing preparation in patients who are taking warfarin. If coadministration is unavoidable, consider reducing warfarin dose 10% to 20% and monitor for increased warfarin effects (eg, INR, bleeding). Risk D: Consider therapy modification

MiFEPRIStone: May enhance the adverse/toxic effect of Vitamin K Antagonists. Specifically, the risk of bleeding may be increased. MiFEPRIStone may increase the serum concentration of Vitamin K Antagonists. Risk X: Avoid combination

Mitapivat: May decrease the serum concentration of CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

Mosunetuzumab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Multivitamins/Fluoride (with ADE): May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the anticoagulant effect of Vitamin K Antagonists. Multivitamins/Minerals (with ADEK, Folate, Iron) may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Nafcillin: May diminish the anticoagulant effect of Vitamin K Antagonists. Management: Consider choosing an alternative antibiotic. Monitor for decreased therapeutic effects and need for dose adjustments of oral anticoagulants if nafcillin is initiated/dose increased, or increased effects if nafcillin is discontinued/dose decreased. Risk D: Consider therapy modification

Neomycin (Systemic): May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Nirmatrelvir and Ritonavir: May decrease the serum concentration of Vitamin K Antagonists. Nirmatrelvir and Ritonavir may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Nonselective): May enhance the anticoagulant effect of Vitamin K Antagonists. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor coagulation status closely and advise patients to promptly report any evidence of bleeding or bruising. Risk D: Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents (Ophthalmic): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: 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. Risk X: Avoid combination

Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Omeprazole: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Oritavancin: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Orlistat: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Ornidazole: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Oxatomide: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk X: Avoid combination

Penicillins: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Pentoxifylline: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Phytonadione: May diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Pirtobrutinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Posaconazole: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Propacetamol: May enhance the anticoagulant effect of Vitamin K Antagonists. This appears most likely with higher doses (equivalent to acetaminophen doses exceeding 1.3 to 2 g/day) for multiple consecutive days. Risk C: Monitor therapy

Propafenone: May increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

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. Risk C: Monitor therapy

Protein C Concentrate (Human): May enhance the adverse/toxic effect of Vitamin K Antagonists. Specifically, the risk of warfarin-induced skin necrosis may be increased. Protein C Concentrate (Human) may diminish the therapeutic effect of Vitamin K Antagonists. This is effect is transient and occurs at the initiation of vitamin K antagonist therapy. Risk C: Monitor therapy

QuiNIDine: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

QuiNINE: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Quinolones: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Raloxifene: May diminish the anticoagulant effect of Vitamin K Antagonists. Raloxifene may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Ribavirin (Systemic): May diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Rifamycin Derivatives: May decrease the serum concentration of Vitamin K Antagonists. Management: Consider alternatives if possible. If combined, monitor for reduced anticoagulant effects if a rifamycin derivative is initiated in a vitamin K antagonist treated patient. Vitamin K antagonist dose adjustments will likely be required. Risk D: Consider therapy modification

Ritonavir: May decrease the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Salicylates: May enhance the anticoagulant effect of Vitamin K Antagonists. Management: Avoid as needed use of salicylates in patients taking vitamin K antagonists. Aspirin (80 to 325 mg/day) may be used with warfarin for prevention of cardiovascular events. If coadministering salicylates and vitamin K antagonists, monitor for bledding. Risk D: Consider therapy modification

Salicylates: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Selumetinib: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the adverse/toxic effect of Vitamin K Antagonists. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Soybean: May diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Sparsentan: May decrease the serum concentration of CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

Spinach: May diminish the therapeutic effect of Vitamin K Antagonists. Risk C: Monitor therapy

St John's Wort: May increase the metabolism of Vitamin K Antagonists. Management: Consider avoiding coadministration of St John's Wort and vitamin K antagonists. If combined, monitor for decreased anticoagulant therapeutic effects (eg, decreased INR, thromboembolic events) if St John's Wort is initiated/dose increased. Risk D: Consider therapy modification

Streptokinase: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk X: Avoid combination

Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Sulfinpyrazone: May decrease the metabolism of Vitamin K Antagonists. Sulfinpyrazone may decrease the protein binding of Vitamin K Antagonists. Risk C: Monitor therapy

Sulfonamide Antibiotics: May enhance the anticoagulant effect of Vitamin K Antagonists. Management: Consider reducing the vitamin K antagonist dose by 10% to 20% prior to starting the sulfonamide antibiotic. Monitor INR closely to further guide dosing. Risk D: Consider therapy modification

Sulfonylureas: May enhance the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Talquetamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Tamoxifen: May increase the serum concentration of Vitamin K Antagonists. Management: Use of a vitamin K antagonist (VKA) is contraindicated when tamoxifen is used to reduce breast cancer incidence and for ductal carcinoma in situ. Monitor VKA closely when tamoxifen is used to treat metastatic breast cancer or as adjuvant therapy. Risk D: Consider therapy modification

Teclistamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Telavancin: May diminish the therapeutic effect of Anticoagulants. Specifically, telavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Risk C: Monitor therapy

Tetracyclines: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: Monitor for signs and symptoms of bleeding if these agents are combined. For the treatment of acute ischemic stroke, avoidance with anticoagulants is often recommended, see full drug interaction monograph for details. Risk C: Monitor therapy

Thyroid Products: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Tibolone: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Toremifene: May increase the serum concentration of CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

TraMADol: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Urokinase: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Ustekinumab: May decrease the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

Valproate Products: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Risk X: Avoid combination

Vorinostat: May enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Zanubrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy

Food Interactions

Ethanol: Acute ethanol ingestion (binge drinking) decreases the metabolism of oral anticoagulants and increases PT/INR. Chronic daily ethanol use increases the metabolism of oral anticoagulants and decreases PT/INR. Management: Limit alcohol consumption; monitor INR closely.

Food: Vitamin K can reverse the anticoagulation effects of acenocoumarol; large amounts of food high in vitamin K (such as beef liver, pork liver, green tea, and green leafy vegetables) may reverse acenocoumarol, decrease prothrombin time, and lead to therapeutic failure. Management: Patients should not change dietary habits once stabilized on acenocoumarol therapy. A balanced diet with a consistent intake of vitamin K is essential. High doses of vitamin A, E, or C may alter PT. Cranberry juice or other cranberry products may increase the INR in patients receiving a similar agent (warfarin) and cause severe bleeding (flavonoids found in cranberries may inhibit cytochrome P450 isoenzyme CYP2C9 which metabolize warfarin). Similar risks might be anticipated with acenocoumarol as it also undergoes CYP2C9 metabolism. Management: Use caution with fish oils or omega-3 fatty acids; cranberry juice or other cranberry products.

Reproductive Considerations

Women of childbearing potential are advised to use effective contraception during treatment.

Pregnancy Considerations

Acenocoumarol crosses the placenta.

Teratogenic effects have been reported with coumarin derivative anticoagulants following first trimester exposure and may include coumarin embryopathy (nasal hypoplasia and/or stippled epiphyses; limb hypoplasia may also be present). Adverse events to the fetus have also been observed following second and third trimester exposure with coumarin derivative anticoagulants and may include CNS abnormalities (including ventral midline dysplasia, dorsal midline dysplasia). Fatal hemorrhage in the fetus has been reported even when the mother’s acenocoumarol levels were in the therapeutic range. Acenocoumarol should not be used during pregnancy because of significant risks.

Breastfeeding Considerations

Very small quantities of acenocoumarol can be detected in breast milk and undesirable effects in nursing infants are not anticipated. The manufacturer recommends prophylaxis therapy with phytonadione (1 mg administered once weekly) and monitoring of the infant for signs of bleeding. The American College of Chest Physicians (ACCP) considers acenocoumarol to be safe to use in breast-feeding women (Guyatt, 2012).

Dietary Considerations

Foods high in vitamin K (eg, beef liver, pork liver, green tea, and leafy green vegetables) inhibit anticoagulant effect. Do not change dietary habits once stabilized on acenocoumarol therapy. A balanced diet with a consistent intake of vitamin K is essential. Avoid large amounts of alfalfa, asparagus, broccoli, Brussels sprouts, cabbage, cauliflower, green teas, kale, lettuce, spinach, turnip greens, watercress; these decrease efficacy of oral anticoagulants. It is recommended that an adult diet contain a consistent vitamin K content of 75-120 mcg/day. Check with healthcare provider before changing diet. Avoid using multivitamins that contain vitamin K.

Monitoring Parameters

PT/INR (Note: To obtain a valid PT in patients receiving heparin, allow 4 to 5 hours after last IV dose and 12 to 24 hours after last SubQ dose before blood is drawn); hepatic function, CBC

Mechanism of Action

Hepatic synthesis of coagulation factors II, VII, IX, and X, as well as proteins C and S, requires the presence of vitamin K. These clotting factors are biologically activated by the addition of carboxyl groups to key glutamic acid residues within the proteins’ structure. In the process, “active” vitamin K is oxidatively converted to an “inactive” form, which is then subsequently reactivated by vitamin K epoxide reductase complex 1 (VKORC1). Coumarins are thought to inhibit VKORC1, thus depleting functional vitamin K reserves and hence reduce synthesis of active clotting factors.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Peak anticoagulant effect: Oral: 36-48 hours

Absorption: Rapid

Distribution: V_d: 0.16-0.34 L/kg

Protein binding: 99%

Metabolism: Hepatic, via oxidation: R-enantiomer (by CYP2C9 [primary], 1A2, and 2C19; S-enantiomer primarily by CYP2C9) and via keto-reduction to inactive metabolites; also undergoes nitro-reduction via gut flora. (Thijssen, 2000)

Bioavailability: 60%

Half-life elimination: R-enantiomer: ~11 hours; S-enantiomer: <2 hours (Thijssen, 1986)

Time to peak, plasma: 1-3 hours

Excretion: Urine (60% as metabolites; minimal amount as unchanged drug); feces (29% as metabolites)

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Acitrom;
(AR) Argentina: Acenocoumarol Rospaw | Acenocumarol Gen Med | Acenotromb | Antitrom | Azecar | Cumarol | Fortonol | Saxiom | Saxion | Sintrom;
(AT) Austria: Sintrom;
(BE) Belgium: Sintrom;
(BG) Bulgaria: Acenocumarol | Sintrom | Sintrom merus labs;
(CH) Switzerland: Sintrom;
(CL) Chile: Acebron | Acenox | Coarol | Isquelium | Neo-sintrom;
(DE) Germany: Sintrom;
(EE) Estonia: Syncumar;
(ES) Spain: Sintrom;
(FR) France: Minisintrom | Sintrom;
(GB) United Kingdom: Sinthrome;
(GR) Greece: Sintrom;
(HR) Croatia: Sintrom;
(HU) Hungary: Syncumar;
(IE) Ireland: Sinthrome;
(IL) Israel: Sintrom;
(IN) India: Aceno | Acenomac | Acitrom | Artiflo | Cenorol | Cgtrom | Nicotrom | Nicoz | Nistrom;
(IT) Italy: Sintrom;
(JO) Jordan: Sintrom;
(LB) Lebanon: Sintrom;
(LT) Lithuania: Acenocumarol | Niffcumar | Sintrom | Syncumar;
(LU) Luxembourg: Sintrom;
(LV) Latvia: Acenocumarol | Niffcumar | Sintrom | Syncumar;
(MA) Morocco: Sintrom;
(MX) Mexico: Acenocumarol | Fitromtec | Moll | Sintrom;
(NL) Netherlands: Acenocoumarol CF | Acenocoumarol Merck | Acenocoumarol pch | Acenocoumarol ratiopharm | Sintrom;
(NO) Norway: Sintrom;
(NZ) New Zealand: Sinthrome;
(PL) Poland: Acenocumarol | Acenocumarol wzf | Sintrom | Syncumar;
(PT) Portugal: Sintrom;
(PY) Paraguay: Azecar | Sintrom | Venohem;
(RO) Romania: Acenocumarol;
(RU) Russian Federation: Acenocumarol | Syncumar;
(SI) Slovenia: Sintrom;
(TN) Tunisia: Acenocumarol wzf | Mini sintrom | Sintrom;
(UA) Ukraine: Syncumar;
(UY) Uruguay: Sintrom;
(VN) Viet Nam: Azenmarol | Darius | Tegrucil | Vincerol

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Topic 9159 Version 256.0

خرید پکیج

Acenocoumarol (United States: Not available): Drug information