Jantoven
Warfarin Sodium · Tablet · Oral
Uses
1 INDICATIONS AND USAGE JANTOVEN ® is indicated for: Prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (PE). Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (AF) and/or cardiac valve replacement. Reduction in the risk of death, recurrent myocardial infarction (MI), and thromboembolic events such as stroke or systemic embolization after myocardial infarction. Limitations of Use Warfarin Sodium has no direct effect on an established thrombus, nor does it reverse ischemic tissue damage. Once a thrombus has occurred, however, the goals of anticoagulant treatment are to prevent further extension of the formed clot and to prevent secondary thromboembolic complications that may result in serious and possibly fatal sequelae. JANTOVEN is a vitamin K antagonist indicated for: Prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism ( 1 ) Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement ( 1 ) Reduction in the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction ( 1 ) Limitations of Use Warfarin Sodium has no direct effect on an established thrombus, nor does it reverse ischemic tissue damage. ( 1 )
Dosage and administration
Individualize dosing regimen for each patient, and adjust based on INR response. ( 2.1 , 2.2 ) Knowledge of genotype can inform initial dose selection. ( 2.3 ) Monitoring: Obtain daily INR determinations upon initiation until stable in the therapeutic range. Obtain subsequent INR determinations every 1 to 4 weeks. ( 2.4 ) Review conversion instructions from other anticoagulants. ( 2.8 ) 2.1 Individualized Dosing The dosage and administration of JANTOVEN must be individualized for each patient according to the patient's International Normalized Ratio (INR) response to the drug. Adjust the dose based on the patient's INR and the condition being treated. Consult the latest evidence-based clinical practice guidelines regarding the duration and intensity of anticoagulation for the indicated conditions. 2.2 Recommended Target INR Ranges and Durations for Individual Indications An INR of greater than 4.0 appears to provide no additional therapeutic benefit in most patients and is associated with a higher risk of bleeding. Venous Thromboembolism (including deep venous thrombosis [DVT] and PE) Adjust the warfarin dose to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations. The duration of treatment is based on the indication as follows: For patients with a DVT or PE secondary to a transient (reversible) risk factor, treatment with warfarin for 3 months is recommended. For patients with an unprovoked DVT or PE, treatment with warfarin is recommended for at least 3 months. After 3 months of therapy, evaluate the risk-benefit ratio of long-term treatment for the individual patient. For patients with two episodes of unprovoked DVT or PE, long-term treatment with warfarin is recommended. For a patient receiving long-term anticoagulant treatment, periodically reassess the risk-benefit ratio of continuing such treatment in the individual patient. Atrial Fibrillation In patients with non-valvular AF, anticoagulate with warfarin to target INR of 2.5 (range, 2.0 to 3.0). In patients with non-valvular AF that is persistent or paroxysmal and at high risk of stroke (i.e., having any of the following features: prior ischemic stroke, transient ischemic attack, or systemic embolism, or 2 of the following risk factors: age greater than 75 years, moderately or severely impaired left ventricular systolic function and/or heart failure, history of hypertension, or diabetes mellitus), long-term anticoagulation with warfarin is recommended. In patients with non-valvular AF that is persistent or paroxysmal and at an intermediate risk of ischemic stroke (i.e., having 1 of the following risk factors: age greater than 75 years, moderately or severely impaired left ventricular systolic function and/or heart failure, history of hypertension, or diabetes mellitus), long-term anticoagulation with warfarin is recommended. For patients with AF and mitral stenosis, long-term anticoagulation with warfarin is recommended. For patients with AF and prosthetic heart valves, long-term anticoagulation with warfarin is recommended; the target INR may be increased and aspirin added depending on valve type and position, and on patient factors. Mechanical and Bioprosthetic Heart Valves For patients with a bileaflet mechanical valve or a Medtronic Hall (Minneapolis, MN) tilting disk valve in the aortic position who are in sinus rhythm and without left atrial enlargement, therapy with warfarin to a target INR of 2.5 (range, 2.0 to 3.0) is recommended. For patients with tilting disk valves and bileaflet mechanical valves in the mitral position, therapy with warfarin to a target INR of 3.0 (range, 2.5 to 3.5) is recommended. For patients with caged ball or caged disk valves, therapy with warfarin to a target INR of 3.0 (range, 2.5 to 3.5) is recommended. For patients with a bioprosthetic valve in the mitral position, therapy with warfarin to a target INR of 2.5 (range, 2.0 to 3.0) for the first 3 months after valve insertion is recommended. If additional risk factors for thromboembolism are present (AF, previous thromboembolism, left ventricular dysfunction), a target INR of 2.5 (range, 2.0 to 3.0) is recommended. Post-Myocardial Infarction For high-risk patients with MI (e.g., those with a large anterior MI, those with significant heart failure, those with intracardiac thrombus visible on transthoracic echocardiography, those with AF, and those with a history of a thromboembolic event), therapy with combined moderate-intensity (INR, 2.0 to 3.0) warfarin plus low-dose aspirin (≤100 mg/day) for at least 3 months after the MI is recommended. Recurrent Systemic Embolism and Other Indications Oral anticoagulation therapy with warfarin has not been fully evaluated by clinical trials in patients with valvular disease associated with AF, patients with mitral stenosis, and patients with recurrent systemic embolism of unknown etiology. However, a moderate dose regimen (INR 2.0 to 3.0) may be used for these patients. 2.3 Initial and Maintenance Dosing The appropriate initial dosing of JANTOVEN varies widely for different patients. Not all factors responsible for warfarin dose variability are known, and the initial dose is influenced by: Clinical factors including age, race, body weight, sex, concomitant medications, and comorbidities Genetic factors (CYP2C9 and VKORC1 genotypes) [see Clinical Pharmacology (12.5) ] Select the initial dose based on the expected maintenance dose, taking into account the above factors. Modify this dose based on consideration of patient-specific clinical factors. Consider lower initial and maintenance doses for elderly and/or debilitated patients and in Asian patients [see Use in Specific Populations (8.5) and Clinical Pharmacology (12.3) ]. Routine use of loading doses is not recommended as this practice may increase hemorrhagic and other complications and does not offer more rapid protection against clot formation. Individualize the duration of therapy for each patient.
Dosage forms and strengths
3 DOSAGE FORMS AND STRENGTHS JANTOVEN tablets are single scored, compressed tablets with one side scored and debossed with WRF above the score and 1, 2, 2½, 3, 4, 5, 6, 7½, or 10 below the score and with 832 debossed on the opposite side. JANTOVEN tablets are supplied in the following strengths: JANTOVEN Tablets Strength Color 1 mg pink 2 mg lavender 2½ mg green 3 mg tan 4 mg blue 5 mg peach 6 mg teal 7½ mg yellow 10 mg white (dye free) Scored tablets: 1, 2, 2½, 3, 4, 5, 6, 7½, or 10 mg ( 3 )
Contraindications
4 CONTRAINDICATIONS JANTOVEN is contraindicated in: Pregnancy JANTOVEN is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism [see Warnings and Precautions (5.7) and Use in Specific Populations (8.1) ]. JANTOVEN can cause fetal harm when administered to a pregnant woman. JANTOVEN exposure during pregnancy causes a recognized pattern of major congenital malformations (warfarin embryopathy and fetotoxicity), fatal fetal hemorrhage, and an increased risk of spontaneous abortion and fetal mortality. If JANTOVEN is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations (8.1) ]. JANTOVEN is contraindicated in patients with: Hemorrhagic tendencies or blood dyscrasias Recent or contemplated surgery of the central nervous system or eye, or traumatic surgery resulting in large open surfaces [see Warnings and Precautions (5.8) ] Bleeding tendencies associated with: Active ulceration or overt bleeding of the gastrointestinal, genitourinary, or respiratory tract Central nervous system hemorrhage Cerebral aneurysms, dissecting aorta Pericarditis and pericardial effusions Bacterial endocarditis Threatened abortion, eclampsia, and preeclampsia Unsupervised patients with conditions associated with potential high level of non-compliance Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding Hypersensitivity to warfarin or to any other components of this product (e.g., anaphylaxis) [see Adverse Reactions (6) ] Major regional or lumbar block anesthesia Malignant hypertension Pregnancy, except in women with mechanical heart valves ( 4 , 5.7 , 8.1 ) Hemorrhagic tendencies or blood dyscrasias ( 4 ) Recent or contemplated surgery of the central nervous system (CNS) or eye, or traumatic surgery resulting in large open surfaces ( 4 , 5.8 ) Bleeding tendencies associated with certain conditions ( 4 ) Threatened abortion, eclampsia, and preeclampsia ( 4 ) Unsupervised patients with potential high levels of non-compliance ( 4 ) Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding ( 4 ) Hypersensitivity to warfarin or any component of the product ( 4 ) Major regional or lumbar block anesthesia ( 4 ) Malignant hypertension ( 4 )
Warnings and precautions
Tissue necrosis: Necrosis or gangrene of skin or other tissues can occur, with severe cases requiring debridement or amputation. Discontinue JANTOVEN and consider alternative anticoagulants if necessary. ( 5.2 ) Calciphylaxis: Fatal and serious cases have occurred. Discontinue JANTOVEN and consider alternative anticoagulation therapy. ( 5.3 ) Acute kidney injury may occur during episodes of excessive anticoagulation and hematuria. ( 5.4 ) Systemic atheroemboli and cholesterol microemboli: Some cases have progressed to necrosis or death. Discontinue JANTOVEN if such emboli occur. ( 5.5 ) Heparin-induced thrombocytopenia (HIT): Initial therapy with Warfarin Sodium in HIT has resulted in cases of amputation and death. Warfarin Sodium may be considered after platelet count has normalized. ( 5.6 ) Pregnant women with mechanical heart valves: Warfarin Sodium may cause fetal harm; however, the benefits may outweigh the risks. ( 5.7 ) 5.1 Hemorrhage JANTOVEN can cause major or fatal bleeding. Bleeding is more likely to occur within the first month. Risk factors for bleeding include high intensity of anticoagulation (INR >4.0), age greater than or equal to 65, history of highly variable INRs, history of gastrointestinal bleeding, hypertension, cerebrovascular disease, anemia, malignancy, trauma, renal impairment, certain genetic factors [see Clinical Pharmacology (12.5) ], certain concomitant drugs [see Drug Interactions (7) ], and long duration of warfarin therapy. Perform regular monitoring of INR in all treated patients. Those at high risk of bleeding may benefit from more frequent INR monitoring, careful dose adjustment to desired INR, and a shortest duration of therapy appropriate for the clinical condition. However, maintenance of INR in the therapeutic range does not eliminate the risk of bleeding. Drugs, dietary changes, and other factors affect INR levels achieved with JANTOVEN therapy. Perform more frequent INR monitoring when starting or stopping other drugs, including botanicals, or when changing dosages of other drugs [see Drug Interactions (7) ]. Instruct patients about prevention measures to minimize risk of bleeding and to report signs and symptoms of bleeding [see Patient Counseling Information (17) ]. 5.2 Tissue Necrosis JANTOVEN can cause necrosis and/or gangrene of skin and other tissues, which is an uncommon but serious risk (<0.1%). Necrosis may be associated with local thrombosis and usually appears within a few days of the start of JANTOVEN therapy. In severe cases of necrosis, treatment through debridement or amputation of the affected tissue, limb, breast, or penis has been reported. Careful clinical evaluation is required to determine whether necrosis is caused by an underlying disease. Although various treatments have been attempted, no treatment for necrosis has been considered uniformly effective. Discontinue JANTOVEN therapy if necrosis occurs. Consider alternative drugs if continued anticoagulation therapy is necessary. 5.3 Calciphylaxis JANTOVEN can cause fatal and serious calciphylaxis or calcium uremic arteriolopathy, which has been reported in patients with and without end-stage renal disease. When calciphylaxis is diagnosed in these patients, discontinue JANTOVEN and treat calciphylaxis as appropriate. Consider alternative anticoagulation therapy. 5.4 Acute Kidney Injury In patients with altered glomerular integrity or with a history of kidney disease, acute kidney injury may occur with JANTOVEN, possibly in relation to episodes of excessive anticoagulation and hematuria [ see Use in Specific Populations (8.6) ]. More frequent monitoring of anticoagulation is advised in patients with compromised renal function. 5.5 Systemic Atheroemboli and Cholesterol Microemboli Anticoagulation therapy with JANTOVEN may enhance the release of atheromatous plaque emboli. Systemic atheroemboli and cholesterol microemboli can present with a variety of signs and symptoms depending on the site of embolization. The most commonly involved visceral organs are the kidneys followed by the pancreas, spleen, and liver. Some cases have progressed to necrosis or death. A distinct syndrome resulting from microemboli to the feet is known as "purple toes syndrome." Discontinue JANTOVEN therapy if such phenomena are observed. Consider alternative drugs if continued anticoagulation therapy is necessary. 5.6 Limb Ischemia, Necrosis, and Gangrene in Patients with HIT and HITTS Do not use JANTOVEN as initial therapy in patients with heparin-induced thrombocytopenia (HIT) and with heparin-induced thrombocytopenia with thrombosis syndrome (HITTS). Cases of limb ischemia, necrosis, and gangrene have occurred in patients with HIT and HITTS when heparin treatment was discontinued and warfarin therapy was started or continued. In some patients, sequelae have included amputation of the involved area and/or death. Treatment with JANTOVEN may be considered after the platelet count has normalized. 5.7 Use in Pregnant Women with Mechanical Heart Valves JANTOVEN can cause fetal harm when administered to a pregnant woman. While JANTOVEN is contraindicated during pregnancy, the potential benefits of using JANTOVEN may outweigh the risks for pregnant women with mechanical heart valves at high risk of thromboembolism. In those individual situations, the decision to initiate or continue JANTOVEN should be reviewed with the patient, taking into consideration the specific risks and benefits pertaining to the individual patient's medical situation, as well as the most current medical guidelines. JANTOVEN exposure during pregnancy causes a recognized pattern of major congenital malformations (warfarin embryopathy and fetotoxicity), fatal fetal hemorrhage, and an increased risk of spontaneous abortion and fetal mortality.
Side effects
The following serious adverse reactions to JANTOVEN are discussed in greater detail in other sections of the labeling: Hemorrhage [see Boxed Warning , Warnings and Precautions (5.1) , and Overdosage (10) ] Tissue Necrosis [see Warnings and Precautions (5.2) ] Calciphylaxis [see Warnings and Precautions (5.3) ] Acute Kidney Injury [see Warnings and Precautions (5.4) ] Systemic Atheroemboli and Cholesterol Microemboli [see Warnings and Precautions (5.5) ] Limb Ischemia, Necrosis, and Gangrene in Patients with HIT and HITTS [see Warnings and Precautions (5.6) ] Other Clinical Settings with Increased Risks [see Warnings and Precautions (5.8) ] Other adverse reactions to JANTOVEN include: Immune system disorders: hypersensitivity/allergic reactions (including urticaria and anaphylactic reactions) Vascular disorders: vasculitis Hepatobiliary disorders: hepatitis, elevated liver enzymes. Cholestatic hepatitis has been associated with concomitant administration of warfarin sodium and ticlopidine. Gastrointestinal disorders: nausea, vomiting, diarrhea, taste perversion, abdominal pain, flatulence, bloating Skin disorders: rash, dermatitis (including bullous eruptions), pruritus, alopecia Respiratory disorders: tracheal or tracheobronchial calcification General disorders: chills Most common adverse reactions to Warfarin Sodium are fatal and nonfatal hemorrhage from any tissue or organ. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Upsher-Smith Laboratories, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
Drug interactions
Concomitant use of drugs that increase bleeding risk, antibiotics, antifungals, botanical (herbal) products, and inhibitors and inducers of CYP2C9, 1A2, or 3A4. ( 7 ) Consult labeling of all concurrently used drugs for complete information about interactions with JANTOVEN or increased risks for bleeding. ( 7 ) 7.1 General Information Drugs may interact with JANTOVEN through pharmacodynamic or pharmacokinetic mechanisms. Pharmacodynamic mechanisms for drug interactions with JANTOVEN are synergism (impaired hemostasis, reduced clotting factor synthesis), competitive antagonism (vitamin K), and alteration of the physiologic control loop for vitamin K metabolism (hereditary resistance). Pharmacokinetic mechanisms for drug interactions with JANTOVEN are mainly enzyme induction, enzyme inhibition, and reduced plasma protein binding. It is important to note that some drugs may interact by more than one mechanism. More frequent INR monitoring should be performed when starting or stopping other drugs, including botanicals, or when changing dosages of other drugs, including drugs intended for short-term use (e.g., antibiotics, antifungals, corticosteroids) [see Boxed Warning ]. Consult the labeling of all concurrently used drugs to obtain further information about interactions with JANTOVEN or adverse reactions pertaining to bleeding. 7.2 CYP450 Interactions CYP450 isozymes involved in the metabolism of warfarin include CYP2C9, 2C19, 2C8, 2C18, 1A2, and 3A4. The more potent warfarin S -enantiomer is metabolized by CYP2C9 while the R -enantiomer is metabolized by CYP1A2 and 3A4. Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the effect (increase INR) of warfarin by increasing the exposure of warfarin. Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the effect (decrease INR) of warfarin by decreasing the exposure of warfarin. Examples of inhibitors and inducers of CYP2C9, 1A2, and 3A4 are below in Table 2; however, this list should not be considered all-inclusive. Consult the labeling of all concurrently used drugs to obtain further information about CYP450 interaction potential. The CYP450 inhibition and induction potential should be considered when starting, stopping, or changing dose of concomitant medications. Closely monitor INR if a concomitant drug is a CYP2C9, 1A2, and/or 3A4 inhibitor or inducer. Table 2: Examples of CYP450 Interactions with Warfarin Enzyme Inhibitors Inducers CYP2C9 amiodarone, capecitabine, cotrimoxazole, etravirine, fluconazole, fluvastatin, fluvoxamine, metronidazole, miconazole, oxandrolone, sulfinpyrazone, tigecycline, voriconazole, zafirlukast aprepitant, bosentan, carbamazepine, phenobarbital, rifampin CYP1A2 acyclovir, allopurinol, caffeine, cimetidine, ciprofloxacin, disulfiram, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, norfloxacin, oral contraceptives, phenylpropanolamine, propafenone, propranolol, terbinafine, thiabendazole, ticlopidine, verapamil, zileuton montelukast, moricizine, omeprazole, phenobarbital, phenytoin, cigarette smoking CYP3A4 alprazolam, amiodarone, amlodipine, amprenavir, aprepitant, atorvastatin, atazanavir, bicalutamide, cilostazol, cimetidine, ciprofloxacin, clarithromycin, conivaptan, cyclosporine, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, imatinib, indinavir, isoniazid, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, nilotinib, oral contraceptives, posaconazole, ranitidine, ranolazine, ritonavir, saquinavir, telithromycin, tipranavir, voriconazole, zileuton armodafinil, amprenavir, aprepitant, bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenytoin, pioglitazone, prednisone, rifampin, rufinamide 7.3 Drugs that Increase Bleeding Risk Examples of drugs known to increase the risk of bleeding are presented in Table 3. Because bleeding risk is increased when these drugs are used concomitantly with warfarin, closely monitor patients receiving any such drug with warfarin. Table 3: Drugs that Can Increase the Risk of Bleeding Drug Class Specific Drugs Anticoagulants argatroban, dabigatran, bivalirudin, desirudin, heparin, lepirudin Antiplatelet Agents aspirin, cilostazol, clopidogrel, dipyridamole, prasugrel, ticlopidine Nonsteroidal Anti-Inflammatory Agents celecoxib, diclofenac, diflunisal, fenoprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, naproxen, oxaprozin, piroxicam, sulindac Serotonin Reuptake Inhibitors citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, venlafaxine, vilazodone 7.4 Antibiotics and Antifungals There have been reports of changes in INR in patients taking warfarin and antibiotics or antifungals, but clinical pharmacokinetic studies have not shown consistent effects of these agents on plasma concentrations of warfarin. Closely monitor INR when starting or stopping any antibiotic or antifungal in patients taking warfarin. 7.5 Botanical (Herbal) Products and Foods More frequent INR monitoring should be performed when starting or stopping botanicals. Few adequate, well-controlled studies evaluating the potential for metabolic and/or pharmacologic interactions between botanicals and JANTOVEN exist. Due to a lack of manufacturing standardization with botanical medicinal preparations, the amount of active ingredients may vary. This could further confound the ability to assess potential interactions and effects on anticoagulation. Some botanicals may cause bleeding events when taken alone (e.g., garlic and Ginkgo biloba) and may have anticoagulant, antiplatelet, and/or fibrinolytic properties. These effects would be expected to be additive to the anticoagulant effects of JANTOVEN. Conversely, some botanicals may decrease the effects of JANTOVEN (e.g., co-enzyme Q 10 , St. John's wort, ginseng).
Use in specific populations
Pregnant women with mechanical heart valves: JANTOVEN may cause fetal harm; however, the benefits may outweigh the risks. ( 8.1 ) Lactation: Monitor breastfeeding infants for bruising or bleeding. ( 8.2 ) Renal Impairment: Instruct patients with renal impairment to frequently monitor their INR. ( 8.6 ) 8.1 Pregnancy Risk Summary JANTOVEN is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism, and for whom the benefits of JANTOVEN may outweigh the risks [see Warnings and Precautions (5.7) ]. JANTOVEN can cause fetal harm. Exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. Because these data were not collected in adequate and well-controlled studies, this incidence of major birth defects is not an adequate basis for comparison to the estimated incidences in the control group or the U.S. general population and may not reflect the incidences observed in practice. Consider the benefits and risks of JANTOVEN and possible risks to the fetus when prescribing JANTOVEN to a pregnant woman. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions In humans, warfarin crosses the placenta, and concentrations in fetal plasma approach the maternal values. Exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. Warfarin embryopathy is characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) and growth retardation (including low birth weight). Central nervous system and eye abnormalities have also been reported, including dorsal midline dysplasia characterized by agenesis of the corpus callosum, Dandy-Walker malformation, midline cerebellar atrophy, and ventral midline dysplasia characterized by optic atrophy. Mental retardation, blindness, schizencephaly, microcephaly, hydrocephalus, and other adverse pregnancy outcomes have been reported following warfarin exposure during the second and third trimesters of pregnancy [see Contraindications (4) ]. 8.2 Lactation Risk Summary Warfarin was not present in human milk from mothers treated with warfarin from a limited published study. Because of the potential for serious adverse reactions, including bleeding in a breastfed infant, consider the developmental and health benefits of breastfeeding along with the mother's clinical need for JANTOVEN and any potential adverse effects on the breastfed infant from JANTOVEN or from the underlying maternal condition before prescribing JANTOVEN to a lactating woman. Clinical Considerations Monitor breastfeeding infants for bruising or bleeding. Data Human Data Based on published data in 15 nursing mothers, warfarin was not detected in human milk. Among the 15 full-term newborns, 6 nursing infants had documented prothrombin times within the expected range. Prothrombin times were not obtained for the other 9 nursing infants. Effects in premature infants have not been evaluated. 8.3 Females and Males of Reproductive Potential Pregnancy Testing JANTOVEN can cause fetal harm [see Use in Specific Populations (8.1) ]. Verify the pregnancy status of females of reproductive potential prior to initiating JANTOVEN therapy. Contraception Females Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the final dose of JANTOVEN. 8.4 Pediatric Use Adequate and well-controlled studies with warfarin sodium have not been conducted in any pediatric population, and the optimum dosing, safety, and efficacy in pediatric patients is unknown. Pediatric use of warfarin sodium is based on adult data and recommendations, and available limited pediatric data from observational studies and patient registries. Pediatric patients administered JANTOVEN should avoid any activity or sport that may result in traumatic injury. The developing hemostatic system in infants and children results in a changing physiology of thrombosis and response to anticoagulants. Dosing of warfarin in the pediatric population varies by patient age, with infants generally having the highest, and adolescents having the lowest milligram per kilogram dose requirements to maintain target INRs. Because of changing warfarin requirements due to age, concomitant medications, diet, and existing medical condition, target INR ranges may be difficult to achieve and maintain in pediatric patients, and more frequent INR determinations are recommended. Bleeding rates varied by patient population and clinical care center in pediatric observational studies and patient registries. Infants and children receiving vitamin K-supplemented nutrition, including infant formulas, may be resistant to warfarin therapy, while human milk-fed infants may be sensitive to warfarin therapy. 8.5 Geriatric Use Of the total number of patients receiving warfarin sodium in controlled clinical trials for which data were available for analysis, 1885 patients (24.4%) were 65 years and older, while 185 patients (2.4%) were 75 years and older. No overall differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Patients 60 years or older appear to exhibit greater than expected INR response to the anticoagulant effects of warfarin [see Clinical Pharmacology (12.3) ]. JANTOVEN is contraindicated in any unsupervised patient with senility.
Pregnancy
8.1 Pregnancy Risk Summary JANTOVEN is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism, and for whom the benefits of JANTOVEN may outweigh the risks [see Warnings and Precautions (5.7) ]. JANTOVEN can cause fetal harm. Exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. Because these data were not collected in adequate and well-controlled studies, this incidence of major birth defects is not an adequate basis for comparison to the estimated incidences in the control group or the U.S. general population and may not reflect the incidences observed in practice. Consider the benefits and risks of JANTOVEN and possible risks to the fetus when prescribing JANTOVEN to a pregnant woman. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions In humans, warfarin crosses the placenta, and concentrations in fetal plasma approach the maternal values. Exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. Warfarin embryopathy is characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) and growth retardation (including low birth weight). Central nervous system and eye abnormalities have also been reported, including dorsal midline dysplasia characterized by agenesis of the corpus callosum, Dandy-Walker malformation, midline cerebellar atrophy, and ventral midline dysplasia characterized by optic atrophy. Mental retardation, blindness, schizencephaly, microcephaly, hydrocephalus, and other adverse pregnancy outcomes have been reported following warfarin exposure during the second and third trimesters of pregnancy [see Contraindications (4) ].
Pediatric use
8.4 Pediatric Use Adequate and well-controlled studies with warfarin sodium have not been conducted in any pediatric population, and the optimum dosing, safety, and efficacy in pediatric patients is unknown. Pediatric use of warfarin sodium is based on adult data and recommendations, and available limited pediatric data from observational studies and patient registries. Pediatric patients administered JANTOVEN should avoid any activity or sport that may result in traumatic injury. The developing hemostatic system in infants and children results in a changing physiology of thrombosis and response to anticoagulants. Dosing of warfarin in the pediatric population varies by patient age, with infants generally having the highest, and adolescents having the lowest milligram per kilogram dose requirements to maintain target INRs. Because of changing warfarin requirements due to age, concomitant medications, diet, and existing medical condition, target INR ranges may be difficult to achieve and maintain in pediatric patients, and more frequent INR determinations are recommended. Bleeding rates varied by patient population and clinical care center in pediatric observational studies and patient registries. Infants and children receiving vitamin K-supplemented nutrition, including infant formulas, may be resistant to warfarin therapy, while human milk-fed infants may be sensitive to warfarin therapy.
Geriatric use
8.5 Geriatric Use Of the total number of patients receiving warfarin sodium in controlled clinical trials for which data were available for analysis, 1885 patients (24.4%) were 65 years and older, while 185 patients (2.4%) were 75 years and older. No overall differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Patients 60 years or older appear to exhibit greater than expected INR response to the anticoagulant effects of warfarin [see Clinical Pharmacology (12.3) ]. JANTOVEN is contraindicated in any unsupervised patient with senility. Conduct more frequent monitoring for bleeding with administration of JANTOVEN to elderly patients in any situation or with any physical condition where added risk of hemorrhage is present. Consider lower initiation and maintenance doses of JANTOVEN in elderly patients [see Dosage and Administration (2.2 , 2.3) ].
Overdosage
10.1 Signs and Symptoms Bleeding (e.g., appearance of blood in stools or urine, hematuria, excessive menstrual bleeding, melena, petechiae, excessive bruising or persistent oozing from superficial injuries, unexplained fall in hemoglobin) is a manifestation of excessive anticoagulation. 10.2 Treatment The treatment of excessive anticoagulation is based on the level of the INR, the presence or absence of bleeding, and clinical circumstances. Reversal of JANTOVEN anticoagulation may be obtained by discontinuing JANTOVEN therapy and, if necessary, by administration of oral or parenteral vitamin K 1 . The use of vitamin K 1 reduces response to subsequent JANTOVEN therapy and patients may return to a pretreatment thrombotic status following the rapid reversal of a prolonged INR. Resumption of JANTOVEN administration reverses the effect of vitamin K, and a therapeutic INR can again be obtained by careful dosage adjustment. If rapid re-anticoagulation is indicated, heparin may be preferable for initial therapy. Prothrombin complex concentrate (PCC), fresh frozen plasma, or activated Factor VII treatment may be considered if the requirement to reverse the effects of JANTOVEN is urgent. A risk of hepatitis and other viral diseases is associated with the use of blood products; PCC and activated Factor VII are also associated with an increased risk of thrombosis. Therefore, these preparations should be used only in exceptional or life-threatening bleeding episodes secondary to JANTOVEN overdosage.
Description
(Warfarin Sodium Tablets, USP) is an anticoagulant that acts by inhibiting vitamin K-dependent coagulation factors. The chemical name of warfarin sodium is 3-(α-acetonylbenzyl)-4-hydroxycoumarin sodium salt, which is a racemic mixture of the R - and S -enantiomers. Crystalline warfarin sodium is an isopropanol clathrate. Its empirical formula is C 19 H 15 NaO 4 , and its structural formula is represented by the following: Crystalline warfarin sodium occurs as a white, odorless, crystalline powder that is discolored by light. It is very soluble in water, freely soluble in alcohol, and very slightly soluble in chloroform and ether. JANTOVEN tablets for oral use contain: 1 mg, 2 mg, 2½ mg, 3 mg, 4 mg, 5 mg, 6 mg, 7½ mg or 10 mg of warfarin sodium, USP. They also contain: All strengths: Lactose monohydrate, magnesium stearate, povidone, and pregelatinized starch (corn). 1 mg: FD&C Red #40 Aluminum Lake 2 mg: FD&C Blue #2 Aluminum Lake and FD&C Red #40 Aluminum Lake 2½ mg: D&C Yellow #10 Aluminum Lake and FD&C Blue #1 Aluminum Lake 3 mg: Brown #75 Synthetic Brown Iron Oxide 4 mg: FD&C Blue #1 Aluminum Lake 5 mg: FD&C Yellow #6 Aluminum Lake 6 mg: Yellow #10 Synthetic Yellow Iron Oxide, Black #85 Synthetic Black Iron Oxide and FD&C Blue #1 Aluminum Lake 7½ mg: D&C Yellow #10 Aluminum Lake and FD&C Yellow #6 Aluminum Lake 10 mg: Dye Free Chemical Structure
Mechanism of action
12.1 Mechanism of Action Warfarin acts by inhibiting the synthesis of vitamin K-dependent clotting factors, which include Factors II, VII, IX, and X, and the anticoagulant proteins C and S. Vitamin K is an essential cofactor for the post ribosomal synthesis of the vitamin K-dependent clotting factors. Vitamin K promotes the biosynthesis of γ-carboxyglutamic acid residues in the proteins that are essential for biological activity. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K 1 epoxide [see Clinical Pharmacology (12.5) ].
How supplied
Tablets JANTOVEN tablets are single scored, compressed tablets with one side scored and debossed with WRF above the score and 1, 2, 2½, 3, 4, 5, 6, 7½, or 10 below the score and with 832 debossed on the opposite side. JANTOVEN is available in bottles and unit dose blister packages with potencies and colors as follows: 1 mg – Compressed tablet, pink, round; in bottles of 100 (NDC 0832-1211-00) and 1000 (NDC 0832-1211-10) and in unit dose cartons of 100 tablets (10 cards containing 10 tablets each) (NDC 0832-1211-01). 2 mg – Compressed tablet, lavender, round; in bottles of 100 (NDC 0832-1212-00) and 1000 (NDC 0832-1212-10) and in unit dose cartons of 100 tablets (10 cards containing 10 tablets each) (NDC 0832-1212-01). 2½ mg – Compressed tablet, green, round; in bottles of 100 (NDC 0832-1213-00) and 1000 (NDC 0832-1213-10) and in unit dose cartons of 100 tablets (10 cards containing 10 tablets each) (NDC 0832-1213-01). 3 mg – Compressed tablet, tan, round; in bottles of 100 (NDC 0832-1214-00) and 1000 (NDC 0832-1214-10) and in unit dose cartons of 100 tablets (10 cards containing 10 tablets each) (NDC 0832-1214-01). 4 mg – Compressed tablet, blue, round; in bottles of 100 (NDC 0832-1215-00) and 1000 (NDC 0832-1215-10) and in unit dose cartons of 100 tablets (10 cards containing 10 tablets each) (NDC 0832-1215-01). 5 mg – Compressed tablet, peach, round; in bottles of 100 (NDC 0832-1216-00) and 1000 (NDC 0832-1216-10) and in unit dose cartons of 100 tablets (10 cards containing 10 tablets each) (NDC 0832-1216-01). 6 mg – Compressed tablet, teal, round; in bottles of 100 (NDC 0832-1217-00) and 1000 (NDC 0832-1217-10) and in unit dose cartons of 100 tablets (10 cards containing 10 tablets each) (NDC 0832-1217-01). 7½ mg – Compressed tablet, yellow, round; in bottles of 100 (NDC 0832-1218-00) and 500 (NDC 0832-1218-50) and in unit dose cartons of 100 tablets (10 cards containing 10 tablets each) (NDC 0832-1218-01). 10 mg – Compressed tablet, white (dye-free), round; in bottles of 100 (NDC 0832-1219-00) and 500 (NDC 0832-1219-50) and in unit dose cartons of 100 tablets (10 cards containing 10 tablets each) (NDC 0832-1219-01). Store at 20° to 25°C (68° to 77°F). Excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.] Protect from light and moisture. Dispense in a tight, light-resistant container with a child-resistant closure. Special Handling Procedures for proper handling and disposal of potentially hazardous drugs should be considered. Guidelines on this subject have been published [see References (15) ]. Pharmacy and clinical personnel who are pregnant should avoid exposure to crushed or broken tablets [see Use in Specific Populations (8.1) ].
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Instructions for Patients Advise patients to: Strictly adhere to the prescribed dosage schedule [see Dosage and Administration (2.1) ]. If the prescribed dose of JANTOVEN is missed, take the dose as soon as possible on the same day but do not take a double dose of JANTOVEN the next day to make up for missed doses [see Dosage and Administration (2.6) ]. Obtain prothrombin time tests and make regular visits to their physician or clinic to monitor therapy [see Dosage and Administration (2.1) ]. Be aware that if therapy with JANTOVEN is discontinued, the anticoagulant effects of JANTOVEN may persist for about 2 to 5 days [see Clinical Pharmacology (12.2) ]. Avoid any activity or sport that may result in traumatic injury [see Use in Specific Populations (8.4) ]. And to tell their physician if they fall often as this may increase their risk for complications. Eat a normal, balanced diet to maintain a consistent intake of vitamin K. Avoid drastic changes in dietary habits, such as eating large amounts of leafy, green vegetables [see Drug Interactions (7.5) ]. Contact their physician to report any serious illness, such as severe diarrhea, infection, or fever [see Warnings and Precautions (5) and Adverse Reactions (6) ]. Immediately contact their physician when experiencing pain and discoloration of the skin (a purple bruise like rash) mostly on areas of the body with a high fat content, such as breasts, thighs, buttocks, hips and abdomen [see Warnings and Precautions (5.2) ]. Immediately contact their physician when experiencing any unusual symptom or pain since JANTOVEN may cause small cholesterol or athero emboli. On feet it may appear as a sudden cool, painful, purple discoloration of toe(s) or forefoot [see Warnings and Precautions (5.5) ]. Immediately contact their physician when taking JANTOVEN after any heparin formulation therapy and experiencing bloody or black stools or appearance of bruises, or bleeding [see Warnings and Precautions (5.6) ]. To tell all of their healthcare professionals and dentists that they are taking JANTOVEN. This should be done before they have any surgery or dental procedure [see Dosage and Administration (2.7) ]. Carry identification stating that they are taking JANTOVEN. Bleeding Risks Advise patients to: Notify their physician immediately if any unusual bleeding or symptoms occur. Signs and symptoms of bleeding include: pain, swelling or discomfort, prolonged bleeding from cuts, increased menstrual flow or vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or dark brown urine, red or tar black stools, headache, dizziness, or weakness [see Box Warning and Warnings and Precautions (5.1) ]. Concomitant Medications and Botanicals (Herbals) Advise patients to: Not take or discontinue any other drug, including salicylates (e.g., aspirin and topical analgesics), other over-the-counter drugs, and botanical (herbal) products except on advice of your physician [see Drug Interactions (7) ]. Pregnancy and Nursing Advise patients to: Notify their physician if they are pregnant or planning to become pregnant or considering breast feeding [ see Use in Specific Populations (8.1 , 8.2 , 8.3) ]. Avoid JANTOVEN during pregnancy except in pregnant women with mechanical heart valves, who are at risk of thromboembolism [ see Contraindications (4) ]. Use effective measures to avoid pregnancy while taking JANTOVEN. This is very important because their unborn baby could be seriously harmed if they take JANTOVEN while they are pregnant [ see Use in Specific Populations (8.1 , 8.3) ]. JANTOVEN is a registered trademark of Upsher-Smith Laboratories, LLC. Manufactured by UPSHER-SMITH LABORATORIES, LLC Maple Grove, MN 55369 Revised 0917
Label text from the FDA structured product label by Upsher-Smith Laboratories, LLC (revised Jul 8, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Warfarin Sodium in 9 products
Jantoven NDC products (9)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0832-1211 | Warfarin Sodium 1 mg/1 Tablet | Upsher-Smith Laboratories, LLC | ANDA |
| 0832-1212 | Warfarin Sodium 2 mg/1 Tablet | Upsher-Smith Laboratories, LLC | ANDA |
| 0832-1213 | Warfarin Sodium 2.5 mg/1 Tablet | Upsher-Smith Laboratories, LLC | ANDA |
| 0832-1214 | Warfarin Sodium 3 mg/1 Tablet | Upsher-Smith Laboratories, LLC | ANDA |
| 0832-1215 | Warfarin Sodium 4 mg/1 Tablet | Upsher-Smith Laboratories, LLC | ANDA |
| 0832-1216 | Warfarin Sodium 5 mg/1 Tablet | Upsher-Smith Laboratories, LLC | ANDA |
| 0832-1217 | Warfarin Sodium 6 mg/1 Tablet | Upsher-Smith Laboratories, LLC | ANDA |
| 0832-1218 | Warfarin Sodium 7.5 mg/1 Tablet | Upsher-Smith Laboratories, LLC | ANDA |
| 0832-1219 | Warfarin Sodium 10 mg/1 Tablet | Upsher-Smith Laboratories, LLC | ANDA |
Frequently asked questions
What is Jantoven used for?
1 INDICATIONS AND USAGE JANTOVEN ® is indicated for: Prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (PE). Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (AF) and/or cardiac valve replacement. Reduction in the risk of death, recurrent myocardial infarction (MI), and thromboembolic events such as stroke or systemic…
What are the side effects of Jantoven?
The following serious adverse reactions to JANTOVEN are discussed in greater detail in other sections of the labeling: Hemorrhage [see Boxed Warning , Warnings and Precautions (5.1) , and Overdosage (10) ] Tissue Necrosis [see Warnings and Precautions (5.2) ] Calciphylaxis [see Warnings and Precautions (5.3) ] Acute Kidney Injury [see Warnings and Precautions (5.4) ] Systemic Atheroemboli and… See the full label for the complete list.
Who makes Jantoven?
Jantoven is listed by 1 labeler in the FDA NDC directory, including Upsher-Smith Laboratories, LLC.