Warfarin with amiodarone

In a study of this interaction in 43 patients who took both amiodarone and warfarin for at least 1 year, the interaction peaked at 7 weeks and the mean dosage of warfarin fell by 44% from 5.2 to 2.9 mg/day (265). The dosage of warfarin correlated inversely with the maintenance dose of... 

With warfarin, one is always concerned about pharmacodynamic and pharmacokinetic drug interactions. None of the antiarrhythmic drugs mentioned above are likely to cause a pharmacodynamic interaction with warfarin. However, amiodarone is a cytochrome P450 enzyme inhibitor and increases warfarin s antithrombotic effects. Patients taking both drugs usually need to decrease their dose of warfarin. 

O Reilly RA, Trager WF, Rettie AE, Goulart DA. Interaction of amiodarone with racemic warfarin and its separate enantiomorphs in humans. CUn Pharmacol Ther( 9ST) 42,290-4. 

A 75-year-old female patient with no history of ocular disease was treated with warfarin and amiodarone due to arrhythmias that occurred after aortic valve replacement. As there were no rhythm problems, amiodarone was discontinued on day 45. Five days afterward, the patient noticed scotoma in the visual field of her left eye. After a couple of days, the patient was experiencing bilateral visual symptoms and the left eye felt foggy. A relative afferent pupillary defect was detected in the left eye and the optic nerve heads were swollen. Moreover, bilateral macular oedema was noted. Within 4 weeks of the first visual symptoms the patient had become blind. No improvement occurred during 8 months of follow-up. Other possible diagnoses were ruled out. Amiodarone-related optic neuropathy was the most likely reason for the profound visual loss [14]. 

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. 

Aminophylline Aminophylline should not be mixed with acidic drugs, as it becomes precipitated if the pH of the final solution falls below pH 8. Mixture with glucose may increase the pH above 10 where proteins, such as insulin and erythromycin, are unstable. Some drugs that are incompatible with aminophylline include amiodarone, benzylpenicillin potassium, cisatracurium, ceftazidime, ceftriaxone, dobutamine, tetracycline hydrochloride, verapamil hydrochloride, warfarin sodium, and vitamin B and C injection. Alcohol-free theophylline should be stored in amber-colored containers maximum care must be taken to protect it against exposure to light.92-94... 

That amiodarone can potentiate the action of warfarin by inhibiting its metabolism is well known (SEDA-11, 156). However, potentiation of the action of warfarin has been attributed to amiodarone-induced thyrotoxicosis (264). A metabolic interaction in this case was unlikely, because the patient had taken both drugs together for 2 years before the increase in response to warfarin, coincident with the emergence of thyrotoxicosis. 

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

A patient with a mechanical prosthetic mitral valve is seen in the clinic. He has been stable on 5 mg of warfarin taken every evening. His INRs have been ranging from 2.5 to 2.7 for the past 6 months. He was started on amiodarone 2 weeks ago for an arrhythmia. Today his INR is 5.1 and thyroid-stimulating hormone (TSH) level is 2.1 mlU/L. How does amiodarone play a part in this patient s anticoagulation therapy ... 

Increased levels with amiodarone. sulfonamides, isoniazid, fluconazole. Unpredictable effetts with VPA and PB, Decreased effectiveness of warfarin, CBZ, doxycycline, estrogens. 

Clinically important, potentially hazardous interactions with amiodarone, atorvastatin, bepridil, carbamazepine, delavirdine, dihydroergotamine, etravirine, flecainide, itraconazole, ketoconazole, lidocaine, lopinavir, lovastatin, midazolam, phenobarbital, phenytoin, pimozide, propafenone, quinidine, rifabutin, rifampin, sildenafil, simvastatin, St John s wort, triazolam, vardenafil, warfarin... 

Clinically important, potentially hazardous interactions with amiodarone, amprenavir, anisindione, antacids, anticoagulants, aprepitant, atazanavir, atovaquone, beclomethasone, buprenorphine, corticosteroids, cortisone, cyclosporine, cyproterone, dabigatran, dapsone, darunavir, delavirdine, dexamethasone, dicumarol, digoxin, eszopiclone, flunisolide, fosamprenavir, gadoxetate, gestrinone, halothane, imatinib, isoniazid, itraconazole, ketoconazole, lapatinib, lorcainide, methylprednisolone, midazolam, nelfinavir, nifedipine, oral contraceptives, phenylbutazone, prednisone, protease inhibitors, pyrazinamide, ramelteon, ritonavir, saquinavir, solifenacin, sunitinib, tacrolimus, telithromycin, temsirolimus, tipranavir, tolvaptan, trabectedin, triamcinolone, triazolam, voriconazole, warfarin, zaleplon... 

Clinically important, potentially hazardous interactions with amiodarone, anisindione, anticoagulants, corticosteroids, cyclosporine, dicumarol, indinavir, ritonavir, solifenacin, tacrolimus, warfarin... 

Clinically important, potentially hazardous interactions with amiodarone, atazanavir, azithromycin, bosentan, ciprofibrate, clarithromycin, clopidogrel, cyclosporine, darunavir, delavirdine, diltiazem, erythromycin, fosamprenavir, fusidic acid, gemfibrozil, grapefruit juice, imatinib, itraconazole, lopinavir, rabeprazole, ranolazine, red rice yeast, ritonavir, roxithromycin, selenium, St John s wort, tacrolimus, telithromycin, tipranavir, verapamil, warfarin... 

A significant number of patients with HCM develop atrial fibrillation. Amiodarone is one of the most effective agents available to maintain normal sinus rhythm in these patients. For patients in chronic atrial fibrillation requiring rate control, a -blocker or verapamil may be used." Anticoagulation should be considered because these patients are at a risk for systemic embolization and stroke. If amiodarone is added to a patient already receiving warfarin, the prothrombin time or international normalized ratio (INR) wfll be increased and should be monitored closely. 

Drug interactions also can result from inhibition of other CYPs. Amiodarone and its active metabolite desethylamiodarone promiscuously inhibit several CYPs, including CYP2C9, the principal enzyme that eliminates the active -enantiomer of warfarin. Because many patients treated with amiodarone e.g., subjects with atrial fibrillation) are also receiving warfarin, the potential exists for major bleeding complications. 

Herman D, LocateUi I, Grabnar I, Petemel P, Stegnar M, Lainscak M, Mrhar A, Breskvar K, Dolzan V. The influence of co-treatment with carbamazepine, amiodarone and statins on warfarin metabolism and maintenance dose. EurJ Clin Pharmacol (2006) 62,291-6. 

An amiodarone interaction was also indicated in a retrospective cohort study of patients over 65 years of age on at least six continuous months of warfarin therapy. The two cohorts, patients receiving amiodarone or not, were matched based on age, gender, year of cohort entry and a high-dimensional propensity score. The initiation of amiodarone among older patients taking warfarin was associated with a more than twofold increase in the risk of hospitalization for haemorrhage with a relatively high fatality rate [12 ]. 

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