Jantoven

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.

0) is recommended. 5) is recommended. 5) is recommended. 0) for the first 3 months after valve insertion is recommended. 0) is recommended. 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.

0) may be used for these patients. 3 Initial and Maintenance Dosing The appropriate initial dosing of JANTOVEN varies widely for different patients. 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. 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. 2) ]. Dosing Recommendations without Consideration of Genotype If the patient's CYP2C9 and VKORC1 genotypes are not known, the initial dose of JANTOVEN is usually 2 to 5 mg once daily.

Determine each patient's dosing needs by close monitoring of the INR response and consideration of the indication being treated. Typical maintenance doses are 2 to 10 mg once daily. 5) ]. If the patient's CYP2C9 and/or VKORC1 genotype are known, consider these ranges in choosing the initial dose.

Patients with CYP2C9 *1/*3, *2/*2, *2/*3, and *3/*3 may require more prolonged time (>2 to 4 weeks) to achieve maximum INR effect for a given dosage regimen than patients without these CYP variants.

Table 1:

Three Ranges of Expected Maintenance JANTOVEN Daily Doses Based on CYP2C9 and VKORC1 Genotypes Ranges are derived from multiple published clinical studies. VKORC1–1639G>A (rs9923231) variant is used in this table. Other co-inherited VKORC1 variants may also be important determinants of warfarin dose.

4 Monitoring to Achieve Optimal Anticoagulation JANTOVEN has a narrow therapeutic range (index), and its action may be affected by factors such as other drugs and dietary vitamin K. Therefore, anticoagulation must be carefully monitored during JANTOVEN therapy.

Determine the INR daily after the administration of the initial dose until INR results stabilize in the therapeutic range. After stabilization, maintain dosing within the therapeutic range by performing periodic INRs. The frequency of performing INR should be based on the clinical situation but generally acceptable intervals for INR determinations are 1 to 4 weeks.

Perform additional INR tests when other warfarin products are interchanged with JANTOVEN, as well as whenever other medications are initiated, discontinued, or taken irregularly. 8) and Drug Interactions (7) ]. Determinations of whole blood clotting and bleeding times are not effective measures for monitoring of JANTOVEN therapy.

5 Renal Impairment No dosage adjustment is necessary for patients with renal failure. 6) ]. 6 Missed Dose The anticoagulant effect of JANTOVEN persists beyond 24 hours. If a patient misses a dose of JANTOVEN at the intended time of day, the patient should take the dose as soon as possible on the same day.

The patient should not double the dose the next day to make up for a missed dose. 7 Treatment during Dentistry and Surgery Some dental or surgical procedures may necessitate the interruption or change in the dose of JANTOVEN therapy.

Consider the benefits and risks when discontinuing JANTOVEN even for a short period of time. Determine the INR immediately prior to any dental or surgical procedure. In patients undergoing minimally invasive procedures who must be anticoagulated prior to, during, or immediately following these procedures, adjusting the dosage of JANTOVEN to maintain the INR at the low end of the therapeutic range may safely allow for continued anticoagulation.

8 Conversion from Other Anticoagulants Heparin Since the full anticoagulant effect of JANTOVEN is not achieved for several days, heparin is preferred for initial rapid anticoagulation. During initial therapy with JANTOVEN, the interference with heparin anticoagulation is of minimal clinical significance.

Conversion to JANTOVEN may begin concomitantly with heparin therapy or may be delayed 3 to 6 days. To ensure therapeutic anticoagulation, continue full dose heparin therapy and overlap JANTOVEN therapy with heparin for 4 to 5 days and until JANTOVEN has produced the desired therapeutic response as determined by INR, at which point heparin may be discontinued.

As heparin may affect the INR, patients receiving both heparin and JANTOVEN should have INR monitoring at least: 5 hours after the last intravenous bolus dose of heparin, or 4 hours after cessation of a continuous intravenous infusion of heparin, or 24 hours after the last subcutaneous heparin injection.

JANTOVEN may increase the activated partial thromboplastin time (aPTT) test, even in the absence of heparin. A severe elevation (>50 seconds) in aPTT with an INR in the desired range has been identified as an indication of increased risk of postoperative hemorrhage.

Other Anticoagulants Consult the labeling of other anticoagulants for instructions on conversion to JANTOVEN.

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.

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. 6) ]. More frequent monitoring of anticoagulation is advised in patients with compromised renal function. 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. " Discontinue JANTOVEN therapy if such phenomena are observed. Consider alternative drugs if continued anticoagulation therapy is necessary. 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. 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. 1) ].

, sprue, antibiotic therapy) Use of an indwelling catheter Severe to moderate hypertension Deficiency in protein C-mediated anticoagulant response: JANTOVEN reduces the synthesis of the naturally occurring anticoagulants, protein C and protein S.

Hereditary or acquired deficiencies of protein C or its cofactor, protein S, have been associated with tissue necrosis following warfarin administration. Concomitant anticoagulation therapy with heparin for 5 to 7 days during initiation of therapy with JANTOVEN may minimize the incidence of tissue necrosis in these patients.

Eye surgery:

In cataract surgery, JANTOVEN use was associated with a significant increase in minor complications of sharp needle and local anesthesia block but not associated with potentially sight-threatening operative hemorrhagic complications.

As JANTOVEN cessation or reduction may lead to serious thromboembolic complications, the decision to discontinue JANTOVEN before a relatively less invasive and complex eye surgery, such as lens surgery, should be based upon the risks of anticoagulant therapy weighed against the benefits.

9 Endogenous Factors Affecting INR The following factors may be responsible for increased INR response: diarrhea, hepatic disorders, poor nutritional state, steatorrhea, or vitamin K deficiency. The following factors may be responsible for decreased INR response: increased vitamin K intake or hereditary warfarin resistance.