Effect of pitavastatin vs. rosuvastatin on international normalized ratio in healthy volunteers on steady-state warfarin

Yu, Christine; Campbell, Stuart; Zhu, Baojin; Knadler, Mary Pat; Small, David S.; Sponseller, Craig A.; Hunt, Thomas L.; Morgan, Roger

doi:10.1185/03007995.2011.648264

Cited by 25 publications

(23 citation statements)

References 12 publications

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“…Two studies have shown a significant increase in INR, whereas 1 study did not. [141][142][143] The mechanism of the rosuvastatin interaction is not completely established, although CYP2C9 seems a likely contributor. Several studies have demonstrated no interaction with warfarin for pitavastatin 130,142 and atorvastatin.…”

Section: Anticoagulants Warfarinmentioning

confidence: 99%

“…[141][142][143] The mechanism of the rosuvastatin interaction is not completely established, although CYP2C9 seems a likely contributor. Several studies have demonstrated no interaction with warfarin for pitavastatin 130,142 and atorvastatin. 144 No clinically significant drug interactions have been reported or are anticipated with statins and the novel anticoagulants dabigatran, apixaban, rivaroxaban, and edoxaban.…”

Section: Anticoagulants Warfarinmentioning

confidence: 99%

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Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association

Wiggins¹,

Saseen²,

Page³

et al. 2016

Circulation

247

194

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A drug-drug interaction (DDI) is a pharmacokinetic or pharmacological influence of 1 medication on another that differs from the known or anticipated effects of each agent alone.1 A DDI may result in a change in either drug efficacy or drug toxicity for 1 or both of the interacting medications.2 Pharmacokinetic DDIs result in altered absorption, distribution, metabolism, or excretion of a medication. A pharmacodynamic DDI occurs when 1 medication modifies the pharmacological effect of another in an additive, a synergistic, or an antagonistic fashion.It is estimated that ≈2.8% of hospital admissions occur as a direct result of DDIs. 3 However, the actual incidence of hospitalization secondary to clinically significant DDIs is likely to be highly underestimated because medication-related issues are more commonly reported as adverse drug reactions. Complex underlying disease states also may make recognizing a DDI more challenging, further contributing to a lower reported incidence. The overall clinical impact of a DDI can range from mild to life-threatening. Therefore, not all DDIs require a modification in therapy. The variability in the clinical significance of a DDI depends on both medication-specific and patient-specific factors. Medication-specific factors include the individual pharmacokinetic characteristics of each medication implicated in the DDI (eg, binding affinity, half-life [t 1/2 ]), dose of the medications, serum concentrations, timing and sequence of administration, and duration of therapy. Patient-specific factors include age, sex, lifestyle, genetic polymorphisms causing differences in enzyme expression or activity, and disease impairment affecting drug metabolism (eg, hepatic or renal impairment, cardiac failure) or predisposition to differences in efficacy or safety (eg, statin intolerance in patients with a history of myopathy). Clinically significant DDIs are usually preventable. To optimize patient safety, healthcare providers must have an understanding of the mechanisms, magnitude, and potential consequences of any given DDI. Interpreting this information will assist clinicians in the safe prescribing of medications and permits careful consideration of the benefits and risks of concomitant medications.Statins reduce morbidity and mortality in patients with known atherosclerotic cardiovascular disease (ASCVD) and in many primary prevention patients.4-9 Current guidelines recommend high-intensity statin therapy in all patients with ASCVD age ≤75 years and moderate-to high-intensity statin therapy in patients with ASCVD and age >75 years, diabetes mellitus, and familial hypercholesterolemia and in primary prevention patients with 10-year ASCVD risk ≥7.5%.10 Given the important role of statins in patients with ASCVD and those at high ASCVD risk, combination therapy with statins and other cardiovascular medications is highly likely, and potentially significant DDIs must be considered in patients treated with statins.Another important aspect of prescribing medications in combination is evalu...

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Section: Anticoagulants Warfarinmentioning

confidence: 99%

Section: Anticoagulants Warfarinmentioning

confidence: 99%

Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association

Wiggins¹,

Saseen²,

Page³

et al. 2016

Circulation

247

194

View full text Add to dashboard Cite

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“…Patients on vitamin K antagonists (VKAs) often have or develop arterial cardiovascular morbidity [1], for which they require cardiovascular drugs like statins [2]. Statins are competitive inhibitors of HMG-CoA reductase that reduce cholesterol biosynthesis [3], but may also reduce the risk of venous thrombosis [4, 5].…”

Section: Introductionmentioning

confidence: 99%

“…However, the anticoagulant properties of statins are not well defined and it is unclear how statins could lower the risk of venous thrombosis [5]. Currently, three randomised studies and one observational study have been conducted as to observe if statins have anticoagulant properties in VKA users [2, 6–8]. These studies showed conflicting results possibly due to the low number of participants enrolled or because (for the observational study) of residual confounding [2, 6–8].…”

Section: Introductionmentioning

confidence: 99%

“…Currently, three randomised studies and one observational study have been conducted as to observe if statins have anticoagulant properties in VKA users [2, 6–8]. These studies showed conflicting results possibly due to the low number of participants enrolled or because (for the observational study) of residual confounding [2, 6–8]. In addition, it is unclear whether potential anticoagulant properties of statins in VKA users are due to drug-drug interactions with VKA or due to pharmacodynamic effects of the statins.…”

Section: Introductionmentioning

confidence: 99%

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Statin use decreases coagulation in users of vitamin K antagonists

Rein

Biedermann

Bonafacio

et al. 2016

Eur J Clin Pharmacol

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PurposeThe purpose of the study is to determine the immediate and long-term effect of statins on coagulation in patients treated with vitamin K antagonists (VKAs).MethodsWe selected patients on VKAs of two Dutch anticoagulation clinics who initiated treatment with a statin between 2009 and 2013. Patients who initiated or stopped concomitant drugs that interact with VKAs or were hospitalised during follow-up were excluded. The VKA dosage (mg/day) after statin initiation was compared with the last VKA dosage before the statin was started. Immediate and long-term differences in VKA dosage (at 6 and 12 weeks) were calculated with a paired student t test.ResultsFour hundred thirty-five phenprocoumon users (mean age 70 years, 60 % men) and 303 acenocoumarol users (mean age 69 years, 58 % men) were included. After start of statin use, the immediate phenprocoumon dosage was 0.02 mg/day (95 % CI, 0.00 to 0.03) lower. At 6 and 12 weeks, these phenprocoumon dosages were 0.03 (95 % CI, 0.01 to 0.05) and 0.07 mg/day (95 % CI, 0.04 to 0.09) lower as compared with the dosage before first statin use. In acenocoumarol users, VKA dosage was 0.04 mg/day (95%CI, 0.01 to 0.07) (immediate effect), 0.10 (95 % CI, 0.03 to 0.16) (at 6 weeks), and 0.11 mg/day (95 % CI, 0.04 to 0.18) (after 12 weeks) lower.ConclusionsInitiation of statin treatment was associated with an immediate and long-term minor although statistically significant decrease in VKA dosage in both phenprocoumon and acenocoumarol users, which suggests that statins may have anticoagulant properties.

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Pitavastatin Concentrations Are Not Increased by CYP3A4 Inhibitor Itraconazole in Healthy Subjects

Nakagawa

Gosho

Inazu

et al. 2013

Clinical Pharm in Drug Dev

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Itraconazole is a synthetic triazole antifungal agent which is known to be a potent inhibitor of cytochrome P450 (CYP) 3A4, and may cause drug-drug interactions with the many drugs metabolized by this route, including some statins. In this study, the influence of concomitant administration of a single oral dose of pitavastatin with itraconazole at steady state was investigated to determine the potential for pharmacokinetic interaction and any effects on safety. Eighteen subjects were enrolled into the study. The AUC and Cmax of pitavastatin alone were 138 ng h/mL and 63.8 ng/mL, and pitavastatin with itraconazole were 106 ng h/mL and 49.5 ng/mL, respectively. Comparison of the 90% confidence interval of the geometric mean ratio of AUC0-t and Cmax against a standard reference of 0.80-1.25 demonstrated that the lower limit was breached for both pitavastatin and its lactone metabolite (0.71-0.84 and 0.69-0.88 for AUC0-t and Cmax , respectively, for pitavastatin, 0.86-0.97 and 0.76-0.86 for AUC0-t and Cmax , respectively, for pitavastatin lactone). The safety and tolerability of pitavastatin was not affected by co-administration with itraconazole. This study suggests that pitavastatin is not a CYP3A4 substrate in humans.

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Effect of pitavastatin vs. rosuvastatin on international normalized ratio in healthy volunteers on steady-state warfarin

Cited by 25 publications

References 12 publications

Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association

Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association

Statin use decreases coagulation in users of vitamin K antagonists

Pitavastatin Concentrations Are Not Increased by CYP3A4 Inhibitor Itraconazole in Healthy Subjects

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