Potential Interaction between Warfarin and Fluvastatin

Trilli, Lauren E.; Kelley, Catherine L.; Aspinall, Sherrie L.; Kroner, Beverly A.

doi:10.1177/106002809603001207

Cited by 48 publications

(27 citation statements)

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“…134 This may explain the varying magnitude of effect in clinical studies. 135 Case reports of INR changes after statin initiation have been published with fluvastatin, [136][137][138] lovastatin, 139 and rosuvastatin. 140 One study indicated that lovastatin and simvastatin affected warfarin metabolite concentrations.…”

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

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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%

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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“…Three reports described interactions between warfarin and lovastatin in which prothrombin times were increased (98-100). In addition, two reports (case series) of possible interactions with fluvastatin and warfarin cited three cases each (101,102).…”

Section: Major Statin-drug Interactionsmentioning

confidence: 99%

Drug interactions with statins

Causevic-Ramosevac¹,

Semiz²

2013

Acta Pharmaceutica

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All important drug interactions, with the possible exception of idiosyncratic or allergic reactions, have a pharmacokinetic or pharmacodynamic basis, or both (1). A study of the mechanisms of drug interactions is of much value in selecting proper drug combinations in order to provide rational therapy, especially for drugs that have a narrow margin of safety and where drugs are used for a prolonged period of time. Most recently, pharmacogenetics has linked drug interaction outcomes to variations in genes encoding cytochrome P450 (CYP) enzymes (2) and transporter genes.Statins (or HMG-CoA reductase inhibitors) represent a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. As of 2010, a number of statins have been on the market: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin (3).Statins are associated with two uncommon, but important, adverse effects, asymptomatic elevation in liver enzyme activity and myopathy. In 2001, cerivastatin was withdrawn from the market worldwide because of an unacceptably high incidence of serious The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are generally well tolerated as monotherapy. Statins are associated with two important adverse effects, asymptomatic elevation in liver enzymes and myopathy. Myopathy is most likely to occur when statins are administered with other drugs. Statins are substrates of multiple drug transporters (including OAT--P1B1, BCRP and MDR1) and several cytochrome P450 (CYP) enzymes (including CYP3A4, CYP2C8, CYP2C19, and CYP2C9). Possible adverse effects of statins can occur due to interactions in concomitant use of drugs that substantially inhibit or induce their methabolic pathway. This review summarizes the most important interactions of statins.

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“…23 Three patients receiving stable doses of the anticoagulant warfarin exhibited increased international normalized ratios when fluvastatin was added to the regimen. 24 International normalized ratios are of clinical significance in establishing a therapeutic range for oral anticoagulation in patients at risk for thromboembolic events. There is also the potential for elevated plasma levels of phenytoin, tolbutamide, and diclofenac when these agents are given concomitantly with fluvastatin.…”

Section: -32mentioning

confidence: 99%

“…21,22 Fluvastatin is chiefly metabolized by CYP2C9 isoform, although modest metabolism by 3A4 and 2D6 also occurs. 23,24 In contrast, pravastatin does not undergo substantial metabolism by CYP450 isoenzymes. It modestly inhibits CYP3A4, 2C9, and 2D6, but is without specificity for any of these isoforms.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Long-term Safety of Hepatic Hydroxymethyl Glutaryl Coenzyme A Reductase Inhibitors

Bottorff¹,

Hansten²

2000

Arch Intern Med

122

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Potential Interaction between Warfarin and Fluvastatin

Abstract: The exact mechanism for the potential interaction between warfarin and fluvastatin is unknown. Until more is known, it is advisable to monitor patients more frequently when fluvastatin is initiated, discontinued, or adjusted in patients taking warfarin.

Cited by 48 publications

References 0 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

Drug interactions with statins

Long-term Safety of Hepatic Hydroxymethyl Glutaryl Coenzyme A Reductase Inhibitors

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