Impact of Rifampin on Serum Amiodarone Concentrations in a Patient with Congenital Heart Disease

Zarembski, Dawn G.; Fischer, Staci A.; Santucci, Peter; Porter, Mary; Costanzo, María Rosa; Trohman, Richard G.

doi:10.1592/phco.19.3.249.30929

Cited by 22 publications

(7 citation statements)

References 14 publications

(9 reference statements)

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“…However, the ndings in the present paper are in accordance with the increase of MDEA (and AMI) clearance, when AMI and RIF were co-administered to a patient (Zarembski et al 1999). This drug interaction may be explained at least in part by the increase of the MDEA hydroxylase activity of RIF-induced enzyme(s).…”

supporting

confidence: 83%

Metabolism of amiodarone (Part III): identification of rabbit cytochrome P450 isoforms involved in the hydroxylation of mono-N-desethylamiodarone

Kozlik¹,

Ha²,

Stieger³

et al. 2001

Xenobiotica

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1. Amiodarone (AMI) is a potent anti-arrhythmic drug and mono-N-desethylamiodarone (MDEA) is its only known metabolite. It was found recently that in rabbit liver microsomes MDEA was biotransformed to n-3-hydroxybutyl-MDEA (3OH-MDEA). 2. In liver microsomes isolated from the untreated rabbit, the formation of 3OH-MDEA obeyed Michaelis-Menten enzyme kinetics with Km = 6.39 +/- 1.07 microM and Vmax = 0.56 +/- 0.21 nmolmin(-1) mg(-1) protein. 3. Furthermore, (1) among chemicals usually used as inhibitors of cytochrome P450, only midazolam (MDZ), cyclosporin A and ketoconazole inhibited the MDEA hydroxylase activity significantly (>60% inhibition), (2) MDZ, a substrate of CYP3A, inhibited the 30OH-MDEA formation competitively (Ki = 10 +/- 5 microM), (3) the formation rates of 3OH-MDEA correlated positively with those of 1'OH-MDZ (r = 0.81; n = 6), and (4) MDEA hydroxylase activity of microsomes isolated from rabbit rifampicin-induced cultured hepatocytes was 4-fold more active than the control. 4. Since CYP3A6 is mainly induced by rifampicin in rabbit-cultured hepatocytes, the data suggest that this isoform is involved in the biotransformation of MDEA to 3OH-MDEA. 5. Since alpha-naphthoflavone, cimetidine and quinidine also partially inhibited the MDEA hydroxylase activity, it is possible that other CYPs, such as 1A, 2C and 2D, may also be active in the metabolism of amiodarone.

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supporting

confidence: 83%

Metabolism of amiodarone (Part III): identification of rabbit cytochrome P450 isoforms involved in the hydroxylation of mono-N-desethylamiodarone

Kozlik¹,

Ha²,

Stieger³

et al. 2001

Xenobiotica

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“…Interestingly, the authors found an increase in MDEA serum concentrations at the end of the study period [45]; however, whether this increase in metabolite serum concentrations with ongoing CYP3A4 induction would be sustained over longer observation periods remains to be seen given the possible role of 3A4 in the elimination of MDEA [15]. Another potent inducer of the P450 enzyme system, rifampin, has also been reported to lead to subtherapeutic amiodarone and MDEA serum concentrations and subsequent palpitations [46,47]. In both patient cases, amiodarone and MDEA levels returned to the therapeutic range and resolution of cardiac symptoms occurred after a dosage increase and/or the discontinuation of rifampin [46,47].…”

Section: Amiodarone and Antiretroviral Drug Interactionsmentioning

confidence: 99%

Amiodarone and Concurrent Antiretroviral Therapy: A Case Report and Review of the Literature

et al. 2013

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Therapy for HIV often can make pharmacologic management of comorbidities challenging since many antiretroviral agents significantly modulate drug metabolism pathways. Amiodarone is commonly used to control cardiac arrhythmias; however, it is recognized as having a narrow therapeutic window with potential for significant drug toxicity. Amiodarone is metabolized by CYP3A4, CYP2C8 and CYP1A1 to an active metabolite and therefore may be affected by comedications that modulate these isoenzymes. Since amiodarone is frequently associated with toxicity, the Heart Rhythm Society (formerly the North American Society of Pacing and Electrophysiology) developed guidelines to minimize the potential for adverse events. However, recommendations for the management of situations where amiodarone must be given with a drug that significantly affects its metabolism are lacking. This paper will discuss our experience with a case of concurrent amiodarone and antiretroviral therapy, as well as provide a review of interactions that may lead to toxicity or potential treatment failure with amiodarone. Primary literature was identified through Medline (1946 to May 2013) and Embase (1980 to May 2013), using the following terms: amiodarone, antiretroviral, HIV, cytochrome P450 and drug interaction. Case reports, studies of xenobiotic interactions with amiodarone in healthy volunteers, and in vitro studies that investigated metabolic pathways of amiodarone were reviewed. Although clinical data was limited, several cases support the finding that potent inhibitors or inducers of cytochrome P450 may lead to amiodarone toxicity or lack of therapeutic effect, respectively. As well, several case reports, in vitro data and clinical investigations have associated some of the antiretrovirals with QT prolongation, which may result in additive cardiotoxicity in patients also receiving amiodarone. Therefore, to manage situations where amiodarone must be used with concurrent interacting antiretrovirals, we recommend a monitoring plan that follows the Heart Rhythm Society guidelines, however with the addition of serial therapeutic drug level monitoring and frequent electrocardiography to minimize potential toxicity and successfully manage both conditions.

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“…As far as the interaction of rifampicin with amiodarone is concerned, only single reports have demonstrated the effect of a 40% reduction in serum concentration of amiodarone and the resultant need to double the dose of an antiarrhythmic drug, which in turn was associated with a sudden increase in the concentration of amiodarone and its metabolites after the withdrawal of rifampicin [107].…”

Section: Rifampicinmentioning

confidence: 99%

Farmakokinetyczne interakcje międzylekowe w oddziale intensywnej terapii – obserwacje jednoośrodkowe i przegląd piśmiennictwa

Łój¹,

Olender²,

Ślęzak³

et al. 2014

Anaesthesiol Intensive Ther

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Background: Drug-drug interactions constitute a serious health hazard in everyday clinical practice in critically ill patients. Drug-drug interactions may be pharmacokinetic or pharmacodynamic in their nature. We aimed to investigate the quantity and quality of possible drug-drug interactions, and their possible side effects in intensive care unit patients in a 12-month period. Methods: This retrospective study covered data on pharmacological treatment of 43 consecutive patients (11 females, 32 males) aged 62 ± 15 years, hospitalized between January 2015 and February 2016. Pharmacokinetic DDIs were identified and graded. Only severe and clinically important drug-drug interactions were subjected for further analysis. Results: Median baseline SAPS III was 53 (IQR 38-67) points. Median intensive care unit stay was 12 (6-25) days. Subjects were treated with a median number of 22 (12-27) drugs. We identified 27 (16-41) possible drug-drug interactions per patient, including 3 (1-7) drug-drug interactions of a severe grade. The total number of severe and clinically important drug-drug interactions was 253 of which 227 were analyzed in detail. No possible side-effects of drug-drug interactions were identified. Conclusions: DDIs as well as their side-effects are challenging regarding their precise evaluation, especially due to the need for multidrug treatment in critically ill patients. Concentration-controlled therapy should be recommended, especially for treatment with vancomycin, digoxin and valproate. Pantoprazole should be a proton pump-inhibitor of choice. Drug dose modification is necessary in combined treatment with fluconazole and amiodarone or rifampicin. From a clinical point of view, the most important impact of drug-drug interactions is on antibiotic treatment effectiveness, especially with meropenem when valproate is also prescribed.

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Impact of Rifampin on Serum Amiodarone Concentrations in a Patient with Congenital Heart Disease

Cited by 22 publications

References 14 publications

Metabolism of amiodarone (Part III): identification of rabbit cytochrome P450 isoforms involved in the hydroxylation of mono-N-desethylamiodarone

Metabolism of amiodarone (Part III): identification of rabbit cytochrome P450 isoforms involved in the hydroxylation of mono-N-desethylamiodarone

Amiodarone and Concurrent Antiretroviral Therapy: A Case Report and Review of the Literature

Farmakokinetyczne interakcje międzylekowe w oddziale intensywnej terapii – obserwacje jednoośrodkowe i przegląd piśmiennictwa

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