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Wang ZY, Chen M, Zhu LL, et al. Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy. Ther Clin Risk Manag. 2015;11:449-67doi: 10.2147/TCRM.S80437.
Wang, Z. Y., Chen, M., Zhu, L. L., Yu, L. S., Zeng, S., Xiang, M. X., & Zhou, Q. (2015). Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy. Therapeutics and clinical risk management, 11449-67. https://doi.org/10.2147/TCRM.S80437
Wang, Zhi-Yu, et al. "Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy." Therapeutics and clinical risk management vol. 11 (2015): 449-67. doi: https://doi.org/10.2147/TCRM.S80437
Wang ZY, Chen M, Zhu LL, Yu LS, Zeng S, Xiang MX, Zhou Q. Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy. Ther Clin Risk Manag. 2015 Mar 19;11:449-67. doi: 10.2147/TCRM.S80437. eCollection 2015. PMID: 25848291; PMCID: PMC4373598.
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Ther Clin Risk Manag. 2015 Mar 19;11:449-67. doi: 10.2147/TCRM.S80437. eCollection 2015.

Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy.

Therapeutics and clinical risk management

Zhi-Yu Wang, Meng Chen, Ling-Ling Zhu, Lu-Shan Yu, Su Zeng, Mei-Xiang Xiang, Quan Zhou

Affiliations

  1. Department of Pharmacy, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
  2. VIP Care Ward, Division of Nursing, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
  3. Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
  4. Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.

PMID: 25848291 PMCID: PMC4373598 DOI: 10.2147/TCRM.S80437

Abstract

BACKGROUND: Coprescribing of clopidogrel and other drugs is common. Available reviews have addressed the drug-drug interactions (DDIs) when clopidogrel is as an object drug, or focused on combination use of clopidogrel and a special class of drugs. Clinicians may still be ignorant of those DDIs when clopidogrel is a precipitant drug, the factors determining the degree of DDIs, and corresponding risk management.

METHODS: A literature search was performed using PubMed, MEDLINE, Web of Science, and the Cochrane Library to analyze the pharmacokinetic DDIs of clopidogrel and new P2Y12 receptor inhibitors.

RESULTS: Clopidogrel affects the pharmacokinetics of cerivastatin, repaglinide, ferulic acid, sibutramine, efavirenz, and omeprazole. Low efficacy of clopidogrel is anticipated in the presence of omeprazole, esomeprazole, morphine, grapefruit juice, scutellarin, fluoxetine, azole antifungals, calcium channel blockers, sulfonylureas, and ritonavir. Augmented antiplatelet effects are anticipated when clopidogrel is coprescribed with aspirin, curcumin, cyclosporin, St John's wort, rifampicin, and angiotensin-converting enzyme inhibitors. The factors determining the degree of DDIs with clopidogrel include genetic status (eg, cytochrome P540 [CYP]2B6*6, CYP2C19 polymorphism, CYP3A5*3, CYP3A4*1G, and CYP1A2-163C.A), species differences, and dose strength. The DDI risk does not exhibit a class effect, eg, the effects of clopidogrel on cerivastatin versus other statins, the effects of proton pump inhibitors on clopidogrel (omeprazole, esomeprazole versus pantoprazole, rabeprazole), the effects of rifampicin on clopidogrel versus ticagrelor and prasugrel, and the effects of calcium channel blockers on clopidogrel (amlodipine versus P-glycoprotein-inhibiting calcium channel blockers). The mechanism of the DDIs with clopidogrel involves modulating CYP enzymes (eg, CYP2B6, CYP2C8, CYP2C19, and CYP3A4), paraoxonase-1, hepatic carboxylesterase 1, P-glycoprotein, and organic anion transporter family member 1B1.

CONCLUSION: Effective and safe clopidogrel combination therapy can be achieved by increasing the awareness of potential changes in efficacy and toxicity, rationally selecting alternatives, tailoring drug therapy based on genotype, checking the appropriateness of physician orders, and performing therapeutic monitoring.

Keywords: P2Y12 receptor inhibitors; clopidogrel; drug metabolism; drug transporter; drug–drug interactions; genotype; pharmacogenetics; pharmacokinetics; polypharmacy; risk management

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