Mécanismes des interactions médicamenteuses d’origine pharmacocinétique

Levêque, Dominique; Lemachatti, Jihane; Nivoix, Yasmine; Coliat, Pierre; Santucci, Raoul; Ubeaud-Séquier, Geneviève; Beretz, L.; Vinzio, S.

doi:10.1016/j.revmed.2009.07.009

Cited by 24 publications

(12 citation statements)

References 71 publications

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“…The proposed mechanism for the rifampicin-warfarin interaction involves the induction of the isoenzymes CYP2C9, CYP3A4, CYP1A2 and CYP2C19 [25,26], accelerating the clearance of both the R and the S enantiomers of warfarin. Enzyme induction typically exhibits a slow onset and long-term recovery time.…”

Section: Discussionmentioning

confidence: 99%

“…The onset of CYP stimulation is also dependent on the half-life of the inducer. As rifampicin exhibits a relatively short half-life, steady-state serum concentrations are obtained faster when rifampicin is compared with other inducing drugs with longer half-lives [26,27]. The dissipation of CYP induction after the discontinuation of rifampicin occurs gradually, depending on the drug´s elimination and the gradual decay of the enhanced enzymatic activity in the liver [8,26].…”

Section: Discussionmentioning

confidence: 99%

“…As rifampicin exhibits a relatively short half-life, steady-state serum concentrations are obtained faster when rifampicin is compared with other inducing drugs with longer half-lives [26,27]. The dissipation of CYP induction after the discontinuation of rifampicin occurs gradually, depending on the drug´s elimination and the gradual decay of the enhanced enzymatic activity in the liver [8,26]. The concurrent use of isoniazid may cause an opposite effect on the liver by inhibiting CYP3A4 [28-30], leading to the accumulation of the less potent R enantiomer.…”

Section: Discussionmentioning

confidence: 99%

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Rifampicin-warfarin interaction leading to macroscopic hematuria: a case report and review of the literature

Martins

Reis

Sales

et al. 2013

BMC Pharmacol Toxicol

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BackgroundRifampicin remains one of the first-line drugs used in tuberculosis therapy. This drug´s potential to induce the hepatic cytochrome P450 oxidative enzyme system increases the risk of drug-drug interactions. Thus, although the presence of comorbidities typically necessitates the use of multiple drugs, the co-administration of rifampicin and warfarin may lead to adverse drug events. We report a bleeding episode after termination of the co-administration of rifampicin and warfarin and detail the challenges related to international normalized ratio (INR) monitoring.Case presentationA 59-year-old Brazilian woman chronically treated with warfarin for atrial fibrillation (therapeutic INR range: 2.0-3.0) was referred to a multidisciplinary anticoagulation clinic at a university hospital. She showed anticoagulation resistance at the beginning of rifampicin therapy, as demonstrated by repeated subtherapeutic INR values. Three months of sequential increases in the warfarin dosage were necessary to reach a therapeutic INR, and frequent visits to the anticoagulation clinic were needed to educate the patient about her pharmacotherapy and to perform the warfarin dosage adjustments. The warfarin dosage also had to be doubled at the beginning of rifampicin therapy. However, four weeks after rifampicin discontinuation, an excessively high INR was observed (7.22), with three-day macroscopic hematuria and the need for an immediate reduction in the warfarin dosage. A therapeutic and stable INR was eventually attained at 50% of the warfarin dosage used by the patient during tuberculosis therapy.ConclusionsThe present case exemplifies the influence of rifampicin therapy on warfarin dosage requirements and the increased risk of bleeding after rifampicin discontinuation. Additionally, this case highlights the need for warfarin weekly monitoring after stopping rifampicin until the maintenance dose of warfarin has decreased to the amount administered before rifampicin use. In particular, patients with cardiovascular diseases and active tuberculosis represent a group with a substantial risk of drug-drug interactions. Learning how to predict and monitor drug-drug interactions may help reduce the incidence of clinically significant adverse drug events.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Rifampicin-warfarin interaction leading to macroscopic hematuria: a case report and review of the literature

Martins

Reis

Sales

et al. 2013

BMC Pharmacol Toxicol

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“…Drug-drug interactions (DDIs) are defined as two or more drugs interacting in such a manner that the effectiveness or toxicity of one or more drugs is altered [ 1 ]. In every DDI, we should distinguish between the molecule which is at the origin of an interaction (that is to say modifying the other drugs' concentration and action) and the molecule whose altered concentration, resulting from the same interaction, ultimately leads to the desired or undesired effects (in the case of a narrow therapeutic index drug) [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Detection and analysis of drug�drug interactions among hospitalized cardiac patients in the Mohammed V Military Teaching Hospital in Morocco

Fettah¹,

Moutaouakkil²,

Sefrioui³

et al. 2018

Pan Afr Med J

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IntroductionDrug-drug interactions (DDIs) are defined as two or more drugs interacting in such a manner that the effectiveness or toxicity of one or more drugs is altered. Patients with cardiovascular disorders are at higher risk for DDIs because of the types and number of drugs they receive. The aim of the present study was to assess the prevalence of DDIs in patients admitted to the cardiology department of a hospital in Morocco.MethodsA prospective observational study from June 2016 to September 2016 was carried out in the cardiology department of a hospital in Morocco. Those patients who were taking at least two drugs and had a hospital stay of at least 48 hours were included in the study. The medications of the patients were analysed for possible interactions. All the prescriptions of the study population were screened for drug-drug interactions using a computerized DDI database system (Theriaque®).ResultsDuring the study period, 138 patients were included; 360 interactions were detected among 94 patients, with an average number of drugs taken of 5.2. The prevalence of DDIs was estimated at 68.11%, the most common of which concerned Kardegic/Plavix (12.22%), Kardegic/Heparin (8.33%), and Lasilix/Spironolactone (5.83%). Among the 726 prescribed drugs, (372 [51.24%]) were drugs of the cardiovascular system, followed by blood and hematopoietic organ drugs (288 [39.67%]) according to the Anatomical Therapeutic Chemical Classification codes. These interactions were categorized on the basis of level of severity: interactions with major severity accounted for 11.11% (40) of the total DDIs while those with moderate and minor severity accounted for 37.22% (134) and 51.66% (186), respectively.ConclusionThis study reports the prevalence of DDIs in patients admitted to the cardiology department of a hospital in Morocco. This study shows that DDIs are frequent among hospitalized cardiac patients and highlights the need to screen prescriptions of cardiovascular patients for possible DDIs, as this helps in their detection and prevention.Pan African Medical Journal – ISSN: 1937- 8688 (www.panafrican-med-journal.com)Published in partnership with the African Field Epidemiology Network (AFENET). (www.afenet.net)Pan African Medical Journal – ISSN: 1937- 8688 (www.panafrican-med-journal.com)Published in partnership with the African Field Epidemiology Network (AFENET). (www.afenet.net)

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“…Besides, PPIs showed also in vitro inhibition of MTX transport via BCRP (Breast Cancer Resistance Protein) [10]. In fact, MTX elimination involves Organic Anion Transporter 3 (OAT3), Multidrug Resistance-associated Protein (MRP) and BCRP [1,11]. Therefore, the interaction between MTX and PPIs cannot be explained solely by the inhibitory effects of PPIs on renal BCRP.…”

Section: Discussionmentioning

confidence: 99%

Delayed Elimination of High Dose Methotrexate due to Co-Administration of Omeprazole: A Case Report

Aouinti¹

2013

J Hematol

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Methotrexate High Doses (HD-MTX) is indicated for the treatment of cancer diseases and its use requires strict precautions to prevent toxic side effects. It has also numerous drug interactions, the most known are interaction with trimethoprim -sulfamethoxazole (TMP-SMX) and Non Steroidal Anti-Inflammatory drugs (NSAIDs), which can exacerbate toxicity of MTX. We report herein a case of delayed elimination of HD-MTX due to co-administraion of omeprazole. B.A, a 17-year-old female having acute lymphoblastic leukemia (ALL). She is treated since September 2011 by HD-MTX every month for 6 months. The elimination of MTX was usually averaged at H 72 . Because of epigastralgia, the sixth cycle of HD-MTX was associated this time to omeprazole 20 mg/d during the entire cycle. MTX monitoring showed a high concentration at H 36 (23 µmol/L) and a delayed elimination. In fact, MTX remained above 0.2 µmol/L until H 164 . The patient's serum creatinin was normal but the liver function was altered marked by transaminases increase observed at H 48 (AST = 2N, ALT = 5N). Delayed elimination of MTX was not observed in every patient receiving PPIs and the reason remains unclear. Mechanisms may include the H+/K+ ATPase pump. It seems also that inhibition of renal transporters of MTX is involved in this interaction. Genetic factors may be associated with an accentuated risk of toxicity. Because of the severity of this type of drug interaction and the frequent ambulatory use of PPIs, it is important to mention such drug-drug interaction and to find an alternative for omeprazole during HD-MTX cycles.

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Mécanismes des interactions médicamenteuses d’origine pharmacocinétique

Cited by 24 publications

References 71 publications

Rifampicin-warfarin interaction leading to macroscopic hematuria: a case report and review of the literature

Rifampicin-warfarin interaction leading to macroscopic hematuria: a case report and review of the literature

Detection and analysis of drug�drug interactions among hospitalized cardiac patients in the Mohammed V Military Teaching Hospital in Morocco

Delayed Elimination of High Dose Methotrexate due to Co-Administration of Omeprazole: A Case Report

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