An Evaluation of the Early Pharmacodynamic Response After Simultaneous Initiation of Warfarin and Amiodarone

Abstract

Amiodarone inhibits the metabolism of warfarin. Previous studies characterizing this drug interaction have focused on the effect of adding amiodarone to stable doses of warfarin. The objective of this study was to assess whether simultaneous initiation of warfarin and amiodarone results in early alteration of the international normalized ratio (INR) response to warfarin. Patients initiated on warfarin and amiodarone during the same hospitalization were included in the amiodarone (AMIO) group. Patients initiated on warfarin alone (n = 42) were identified for the CONTROL group. The AMIO and CONTROL groups were matched based on age, gender, and ejection fraction <40% using propensity score matching (final n = 18 patients per group). Total and average daily warfarin dose was lower in the AMIO group, yet INR values were similar on each day between the 2 groups. More patients in the AMIO group had an INR greater than 2 during the 5-day observation period as compared to the CONTROL group. In addition, there were trends toward greater deviation from INR values expected with a 5-mg daily warfarin dose among AMIO group patients. Simultaneous initiation of warfarin and amiodarone leads to an enhanced pharmacodynamic response to warfarin early in therapy. Although these data should be viewed as hypothesis generating, cautious dosing and monitoring with simultaneous initiation of warfarin and amiodarone may be warranted.

Herb-drug Pharmacokinetic Interaction between Carica Papaya Extract and Amiodarone in Rats

“…In fact, amiodarone has a variable oral bioavailability and undergoes extensive enterohepatic recirculation (28); moreover, the parent drug and its main metabolite are highly lipophilic and tend to extensively accumulate in several tissues (29). On the other hand, amiodarone has been associated with a variety of life-threatening adverse events, including thyroid dysfunction, pulmonary toxicity and hepatic toxicity (29)(30)(31), and relevant clinical drug interactions have been reported (32)(33)(34)(35). Thus, taking into account all the reasons aforementioned, this work was planned in order to investigate if a standardized extract of the fruit of C. papaya influence the rate and extent of amiodarone exposure in rats, following their simultaneous oral co-administration and after a 14-day pre-treatment period with C. papaya extract.…”

Risks and Benefits of Combined Use of Bucolome and Warfarin in Anticoagulation Therapy

“…However, enhancement due to competitive inhibition of CYP2CP, eg, amiodarone, might be more exaggerated in bucolome combination therapy because the serum level of warfarin is increased. 18,19) In the present study, such an influence of a change in combined drug therapy could not be evaluated, but the possibility of a sudden increase of warfarin action should be monitored during bucolome combination therapy. TTR in cases of warfarin resistance: In this study, there was a significant negative correlation between the dosage of warfarin and TTR in cases of warfarin monotherapy, indicating that when a higher dosage of warfarin is required, lower TTR during the maintenance period of warfarin therapy tends to be exhibited.…”

Conservative management of an iliopsoas hematoma causing walking difficulty in an elderly patient on anticoagulation therapy: a case report

“…8 Other drugs risking the patient for bleeding during warfarin use are amiodarone, salicylate, fibric acid derivatives, phenytoin, rifampicin, alcohol use and herbal products like ginseng and green tea. 5,9,10 The absolute contraindications of warfarin use are pregnancy for fear of Fetal warfarin syndrome causing fetal malformations and an increased risk of spontaneous abortion and stillbirths. 11 The INR need to be repeated within 1 to 7 days in all patients on anticoagulants to ensure it within the therapeutic range of 2.0 to 3.0 and at least 2 to 4 weekly during the maintenance phase.…”