Names and pronunciation
(war′far-in) Jantoven
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Drug reference
(war′far-in) Jantoven
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Func. class.: Anticoagulant, vitamin K antagonist
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Chem. class.: Coumarin derivative
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Do not confuse: Coumadin/Cardura/Avandia Jantoven/Janumet/Januvia
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ACTION: Interferes with blood clotting by indirect means; depresses hepatic synthesis of vit K–dependent coagulation factors (II, VII, IX, X)
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USES: Antiphospholipid antibody syndrome, arterial thromboembolism prophylaxis, DVT, MI prophylaxis, after MI, stroke prophylaxis, thrombosis prophylaxis, pulmonary embolism
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CONTRAINDICATIONS: Preg- nancy, breastfeeding, hypersensitivity, hemophilia, leukemia with bleeding, peptic ulcer disease, thrombocytopenic purpura, hepatic disease (severe), malignant hyper- tension, subacute bacterial endocarditis, acute nephritis, blood dyscrasias, eclamp- sia, preeclampsia, hemorrhagic tendencies; surgery of CNS, eye; traumatic surgery with large open surface, bleeding tendencies of GI/GU/respiratory tract, stroke, aneurysms, pericardial effusion, spinal puncture, major regional/lumbar block anesthesia
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Black Box Warning: Bleeding Precautions: Geriatric patients, alco- holism, HF, debilitated patients, trauma, indwelling catheters, severe hyperten- sion, active infections, protein C defi- ciency, polycythemia vera, vasculitis, severe diabetes, Asian patients (CYP2C9), protein C, S deficiency or VKORC1 AA genotype DOSAGE AND ROUTES–NTI • Adult: PO 2-5 mg/day × 2-4 days, then titrated to INR/PT • Adolescent/child/infant: PO 0.2 mg/ kg/day × 2 days titrated to INR, max 10 mg Black Box Warning: Blood studies (Hct, PT, platelets, occult blood in stools) q3mo; INR: in hospital daily after 2nd or 3rd dose; when in therapeutic range (2-3) for 2 consecutive days, monitor 2-3× wk for 1-2 wk, then less frequently, depend- ing on stability of INR results; Outpatient: monitor every few days until stable dose, then periodically thereafter, depending on stability of INR results, usually at least monthly Black Box Warning: Bleeding: bleeding gums, petechiae, ecchymosis, black tarry stools, hematuria, occult bleeding (cere bral, intraabdominal; fatal hemorrhage can occur; do not use in uncontrolled bleeding • Fever, skin rash, urticaria • Pregnancy/breastfeeding: do not use in pregnancy; use effective contraception during and for 1 mo after final dose; cau- tious use in breastfeeding Black Box Warning: Bleeding: to report any signs of bleeding: gums, nosebleed, under skin, urine, stools; to use soft-bris- tle toothbrush to avoid bleeding gums; to use electric razor • To avoid hazardous activities (e.g., football, hockey, skiing), dangerous work that can induce bleeding epi- sodes • To inform all health care providers of anticoagulant intake • To take exactly as prescribed; dosage changes are common for desired effect; not to skip, double doses; take missed dose when remembered W • To eat a diet that is not varied; several foods contain vitamin K and can alter warfarin effect • To report to prescriber fever, rash, trouble breathing • That continuing follow-up exams and lab work will be needed
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SIDE EFFECTS GI: Nausea, cramps, calciphylaxis GU: Hematuria HEMA: Hemorrhage, agranulocytosis, leukopenia, eosinophilia, anemia, ecchy- mosis, petechiae INTEG: Rash, dermal necrosis MISC: Fever MS: Bone fractures SYST: Anaphylaxis, coma, cholesterol, microembolism, exfoliative dermatitis, purple toe syndrome
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INTERACTIONS Increase: warfarin action—allopurinol, amiodarone, azithromycin, chloral hy- drate, chloramphenicol, cimetidine, clofi- brate, cotrimoxazole, COX-2 selective in- hibitors, dextrothyroxine, diflunisal, disulfiram, erythromycin, ethacrynic acids, furosemide, glucagon, heparin, HMG-CoA reductase inhibitors, indomethacin, isoni- azid, levoFLOXacin, mefenamic acid, met- roNIDAZOLE, miFEPRIStone, NSAIDs, oxyphenbutazone, penicillins, phenylbuta- zone, quiNIDine, quinolone antiinfectives, RU-486, salicylates, sulfinpyrazone, sul- fonamides, sulindac, SSRIs, steroids, thrombolytics, thyroid, tricyclics Increase/decrease: effectiveness— assess for use of products that may increase or decrease effect Increase: toxicity—oral sulfonylureas, phenytoin Decrease: warfarin action—aprepitant, azaTHIOprine, barbiturates, bile acid sequestrants, bosentan, carBAMazepine, dicloxacillin, estrogens, ethchlorvynol, factor IX/VIIa, griseofulvin, nafcillin, oral contraceptives, phenytoin, rifAMPin, sucralfate, sulfaSALAzine, vit K, vit K foods Drug/Herb Increase: risk for bleeding—anise, chamomile, dong quai, evening prim- rose, feverfew, fish oil, garlic, ginger, ginkgo, ginseng, horse chestnut, lico- rice, melatonin, red yeast rice, saw palmetto Decrease: anticoagulant effect—coen- zyme Q10, St. John’s wort Drug/Lab Test Increase: T3 uptake, LFTs, INR, PT, PTT
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TREATMENT OF OVERDOSE: Administer vit K
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Available forms: Tabs 1, 2, 2.5, 3, 4, 5, 6, 7.5, 10 mg
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Administer: PO route • Obtain coagulation studies—INR, PT— before use; INR level should be 2.0-3.0 • At same time each day to maintain steady blood levels without regard to food; food decreases rate but not extent of absorption; do not change brands • Tabs whole or crushed • Avoiding all IM inj that may cause bleeding • Store in tight container
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Assess:
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Evaluate: • Therapeutic response: decrease in deep venous thrombosis, absence of pul- monary embolism
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To avoid OTC preparations that may cause serious product interactions un- less directed by prescriber; to avoid alco- hol, herbs, supplements • To carry emergency ID identifying product taken • About the importance of compliance with exams and doses
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PHARMACOKINETICS PO: Onset 12-24 hr, peak 11⁄2-4 days, duration 3-5 days, effective half-life 20-60 hr; metabolized in liver; excreted in urine, feces (active/inactive metabo- lites); crosses placenta, 99% bound to plasma proteins
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