Risks of Adverse Events Following Coprescription of Statins and Calcium Channel Blockers

Abstract

Some statins (simvastatin, lovastatin, and atorvastatin) are metabolized by cytochrome P450s 3A4 (CYP3A4). Inhibitors of CYP3A4 including some calcium channel blockers (CCBs) might increase statin blood concentration, owing to drug–drug interactions. Risk of adverse events such as acute kidney injury might occur following the coprescription of CYP3A4-metabolized statins and CCBs that inhibit CYP3A4.This was a population-based cohort study. The study analyzed data of patients treated between 1997 and 2011, retrieved from Taiwan's National Health Insurance database. We enrolled 32,801 patients who received coprescription of statins and CCBs that inhibit CYP3A4 (amlodipine, diltiazem, felodipine nicardipine, nifedipine, and verapamil). These patients were divided into 2 groups, according to whether they had received CYP3A4-metabolized statins (lovastatin, simvastatin, and atorvastatin) or non-CYP3A4-metabolized statins (fluvastatin, rosuvastatin, and pitavastatin). These 2 groups were 1:1 matched by age, gender, and Carlson comorbidity index. All outcomes were assessed within 90 days following drug coprescription.In this study, 5857 patients received coprescription of CYP3A4-metabolized statins and CCBs that inhibit CYP3A4. There were no differences in comorbidity or use of antihypertensive drugs between patients who received CYP3A4-metabolized statins and those who received non-CYP3A4-metabolized statins. Patients who received CYP3A4-metabolized statins had significantly higher risk of acute kidney injury (adjusted odds ratio [OR] = 2.12; 95% CI = 1.35–3.35), hyperkalemia (adjusted OR = 2.94; 95% CI = 1.36–6.35), acute myocardial infarction (adjusted OR = 1.55; 95% CI = 1.16–2.07), and acute ischemic stroke (adjusted OR = 1.35; 95% CI = 1.08–1.68) than those who received non-CYP3A4-metabolized statins.This nationwide cohort study demonstrated the increased risk of adverse events following the coprescription of CYP3A4-metabolized statins and CCBs that inhibit CYP3A4. Therefore, it is important to take into account the potential adverse events while coprescribing CYP3A4-metabolized statins and CCBs that inhibit CYP3A4.

Drug–Drug Interactions between Atorvastatin and Dronedarone Mediated by Monomeric CYP3A4

“…In order to extend this previously developed approach to pharmacologically important systems, we used a combination of experimental and theoretical methods for a detailed investigation of the metabolism of two drugs, Atorvastatin (a cholesterol lowering drug, Lipitor®) and Dronedarone (an antiarrythmic drug, Multaq®) which are involved in the drug-drug interactions mediated by CYP3A4 (36–39). Both drugs are metabolized by CYP3A4 (37, 40–44) as shown in Figure 1, and both are involved in drug-drug interactions (36–39, 41).…”

“…Both drugs are metabolized by CYP3A4 (37, 40–44) as shown in Figure 1, and both are involved in drug-drug interactions (36–39, 41). Importantly, the highly lever-aged effects of Multaq interactions with multiple cardiac ion channels(45) make interaction with other commonly prescribed medications, such as Lipitor, extremely relevant.…”

Association Between Stroke Risk and Metformin Use in Hemodialysis Patients With Diabetes Mellitus: A Nested Case–Control Study

“…All dialysis patients with catastrophic illness registration certificates are enrolled in the National Health Insurance program because such patients are not required to pay deductibles for the treatment of a catastrophic illness or its related conditions during the valid period of the certificate. The NHIRD is one of the highest quality databases of its type in the world and has been widely used for longitudinal cohort studies, [11][12][13]15,[17][18][19][20][21][22] including our previous reports. 15,[17][18][19][20][21]…”

“…We used standardized difference to evaluate the balance of baseline characteristics between the case and control patients' difference, which was assessed in some studies 28,29 and in our study. 19 The threshold of standardized difference can indicate an important imbalance such that a value >10% is interpreted as significant difference in the mean of a covariate between treatment groups. 30,31 Conditional logistic regression was used to estimate the crude odds ratios (ORs), adjusted ORs, and 95% confidence intervals (CIs) for the association between metformin use and the risk of stroke.…”

Antiarrhythmic Drugs Use in Elderly Patients. Vaughan Williams Class III and IV Drugs

“…В опытах in vitro верапамил и дилтиазем повышали AUC симвастатина и ловастатина в 3-8 раз [53,54]. При совместном применении со статинами, метабо-лизирующимися с участием CYP3A4 (симвастатин, ло-вастатин и аторвастатин), препараты IV класса способны повышать риск развития острой почечной недостаточ-ности, гиперкалиемии, инфаркта миокарда и ишеми-ческого инсульта [55]. Одновременное применение дилтиазема со статинами, в метаболизме которых участвует CYP3A4, повышает риск развития рабдомиолиза [56].…”