Warfarin Amiodarone

Sanoski CA, Bauman JL. Clinical observations with the amiodarone/warfarin interaction dosing relationships with long-term therapy. Chest 2002 121(l) 19-23. 

Kerin NZ, Blevins RD, Goldman L, Faitel K, Rubenfire M. The incidence, magnitude, and time course of die amiodarone-warfarin interaction. Arch Intern Med (19SS ) 148, 1779-81. 

Kumik D, Loebstein R, Farfel Z, Ezra D, HaUdn H, Olchovsky D. Complex drug-drug-dis-ease interactions between amiodarone, warfarin, and tiie lh3n-oid gland. Medicine (2004) 83, 107-13. 

Maintenance doses widely vary among patients (e.g., from 1 to 20 mg/day for warfarin), and are influenced by diet (variable vitamin K intake) and medications that affect coumarin metabolism (decreased drug clearance e.g., cotrimoxazole, amiodarone, erythromycin increased clearance e.g., barbiturates, carbamaze-pine, rifampin). Thus, regular monitoring is needed... 

Amiodarone 5-7 mg/kg IV over 30-60 minutes 700-1200 mg over 24 hours Inhibits elimination of digoxin and warfarin... 

Acenocoumarol, amiodarone, celecoxib, coumadin, dexamethasone, diclofenac, etoposide, fluconazole, fluoxetine, fluvas-tatin, fluvoxamine, ghmepiride, ghpizide, glyburide, ibuprofen, irbesartan, isoniazid, losartan, midazolam, phenylbutazone, phenytoin, rifampin, teniposide, tenoxicam, thiotepa, tolbutamide, torsemide, vitamin D, warfarin... 

Drugs that may be affected by fosamprenavir include the following Amiodarone, amitriptyline, benzodiazepines, calcium channel blockers, cisapride, contraceptives (oral), cyclosporine, ergot derivatives, HMG-CoA reductase inhibitors, imipramine, itraconazole, ketoconazole, lidocaine (systemic), methadone, pimozide, quinidine, rifabutin, sildenafil, tacrolimus, vardenafil, warfarin. 

Imipramine (Tofranil) [Antidepressant/TCA] WARNING Close observation for suicidal thinking or unusual changes in behavior Uses Depres-sion, enuresis, panic attack, chronic pain Action TCA t CNS synaptic serotonin or norepinephrine Dose Adults. Hospitalized Initial 100 mg/24 h PO in doses T over several wk 300 mg/d max Output Maint 50-150 mg PO hs, 300 mg/24 h max Peds. Antidepressant 1.5-5 mg/kg/24 h daUy-qid Enuresis >6 y 10-25 mg PO qhs T by 10-25 mg at 1-2-wk int vals (max 50 mg for 6-12 y, 75 mg for >12 y) Rx for 2-3 mo, then tap Caution [D, /-] Contra Use w/ MAOIs, NAG, acute recovery from MI, PRG, CHF, angina, CVD, arrhythmias Disp Tabs, caps SE CV Sxs, dizziness, xerostomia, discolored urine Interactions t Effects W/ amiodarone, anticholinergics, BBs, cimetidine, diltiazem, Li, OCPs, quinidine, phenothiazines, ritonavir, verapamil, EtOH, evening primrose oil t effects OF CNS depressants, hypoglycemics, warfarin T risk of serotonin synd W/MAOIs 4-... 

Answer The half-life of amiodarone is 35 days. Approximately five half-Uves are required for functionally complete drug elimination. Thus, it will take approximately 6 months (5 half-lives) before the amiodarone is eliminated from the body. Since amiodarone strongly inhibits metabolism of S-warfarin (active enantiomer), it will continue to affect warfarin metabolism for 6 months following discontinuation of amiodarone. Thus, the dose of warfarin will have to be monitored approximately every month and adjusted if necessary. This monthly monitoring should be continued for at least 6 months, until the metabolism of warfarin stabilizes and a constant dose of warfarin can again be maintained. 

Amiodarone increases the hypoprothrombinemic response to warfarin (an oral anticoagulant) by reducing its metabolism. Patients receiving digoxin may undergo an increase in serum digoxin concentrations when amiodarone is added to the treatment regimen. Amiodarone interferes with hepatic and renal elimination of flecainide, phenytoin, and quinidine. 

Lopinavir/Ritonavir (Kaletra) [Anrirelroviral/Protease Inhibitor] Uses HIV Infxn Action Protease inhibitor Dose Adults. Tx naive 2 tab PO daily or 1 tab PO bid Tx experiencedpt 1 tab PO bid (T dose if w/ amprenavir, efavirenz, fosamprenavir, nelfinavir, nevirapine) Peds. 7-15 kg 12/3 mg/kg PO bid 15-40 kg 10/2.5 mg/kg PO bid >40 kg Adult dose w/ food Caution [C, /-] Numerous interactions Contra w/drugs dependent on CYP3A/CYP2D6 (Table VI-8) Disp Tab, soln SE Avoid disulfiram (soln has EtOH), metronidazole GI upset, asthenia, T cholesterol/triglycerides, pancreatitis protease metabolic synd Interactions T Effects Wl clarithromycin, erythromycin T effects OF amiodarone, amprenavir, azole andfungals, bepridil, cisapride, cyclosporine, CCBs, ergot alkaloids, flecainide, flurazepam, HMG-CoA reductase inhibitors, indinavir, lidocaine, meperidine, midazolam, pimozide, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, tacrolimus, terfenadine, triazolam, zolpidem 1 effects Wl barbiturates, carbamazepine, dexamethasone, didanosine, efavirenz, nevirapine, phenytoin, rifabutin, rifampin, St. John s wort 1 effects OF OCPs, warfarin EMS Use andarrhythmics and benzodiazepines... 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Simvastatin (Zocor) [Anrilipemic/HMG-CoA Reductase Inhibitor] Uses X Cholesterol Action HMG-CoA reductase inhibitor Dose Adults. 5-80 mg PO w/ meals X in renal insuff Peds. 10-17 y 10 mg, 40 mg/daily max Caution [X, —] Avoid concurrent use of gemfibrozil Contra PRG, liver Dz Disp Tabs 5,10, 20, 40, 80 mg SE HA, GI upset, myalgia, myopathy (muscle pain, tenderness or weakness w/ creatine kinase 10 x ULN), Hep Interactions T Effects OF digoxin, warfarin T risk of myopathy/iiiabdomyolysis W/ amiodarone, cyclosporine, CYP3A4 inhibitors, fibrates, HIV protease inhibitors, macrolides, niacin, verapamil, grapefruit juice X effects W/ cholestyramine, colestipol, fluvas-tatin, isradipine, propranolol EMS T Effects of warfarin use amiodarone and... 

C9 Warfarin, tolbutamide Fluconazole, amiodarone (use of PM vs. EM subjects) Rifampin... 

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