Drug Interactions Involving Warfarin: Practice Tool and Practical Management Tips

Bungard, Tammy J.; Yakiwchuk, Erin; Foisy, Michelle; Brocklebank, Cynthia

doi:10.3821/1913-701x-144.1.21

Cited by 32 publications

(49 citation statements)

References 52 publications

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“…Commonly used drug information resources suggest use of empiric VKA dose reductions, with dose decreases in the range of 25%-40% [65,67]. Preemptive VKA dosage reduction attempts to avoid potentially dangerous increases in INR that may occur rapidly before INR follow-up.…”

Section: Preemptive Warfarin Dose Reduction and Enhanced Monitoringmentioning

confidence: 99%

Interaction of vitamin K antagonists and trimethoprim-sulfamethoxazole: ignore at your patient’s risk

Hale

Lesar

2013

Drug Metabolism and Drug Interactions

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The aim of the study was to summarize available literature regarding the interaction between vitamin K antagonists (VKAs) and trimethoprim-sulfamethoxazole (co-trimoxazole, TMP-SMX), and to provide recommendations for managing patient risk from this interaction. Data sources were English-language publications in the medical literature and Internet databases. Relevant publications that directly or indirectly addressed the VKA-TMP-SMX interaction were selected and reviewed. The mechanism of the VKA-TMP-SMX interaction, frequency of concurrent use, effect on international normalized ratio (INR), increased risk of bleeding, and strategies for risk reduction are summarized. The concurrent use of VKA and TMP/SMX rapidly and consistently raises INR and is associated with a two- to five-fold increase in bleeding. Concurrent use of VKA and TMP-SMX should be avoided when possible. When VKA and TMP-SMX are co-prescribed, VKA dose reduction is usually required. Patient education as well as early and frequent INR monitoring is recommended to reduce risk from this interaction.

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Section: Preemptive Warfarin Dose Reduction and Enhanced Monitoringmentioning

confidence: 99%

Interaction of vitamin K antagonists and trimethoprim-sulfamethoxazole: ignore at your patient’s risk

Hale

Lesar

2013

Drug Metabolism and Drug Interactions

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“…It is an indirect anticoagulant, exerting its effect by preventing the internal recycling of oxidized vitamin K to reduced vitamin K. Reduced vitamin K is necessary to enable carboxylation of the terminal g-glutamic acid residue of the vitamin Kdependent clotting factors (factors II, VII, IX, and X). The metabolism of warfarin allows for both pharmacokinetic and pharmacodynamic mechanisms for drug interactions 77 . Unlike most small-molecule drugs that comprise a single chemical compound, many chlorophyll products are complex mixtures of chemical constituents.…”

Section: Potential For Warfarin/chlorophyll Interactionsmentioning

confidence: 99%

“…S warfarin is five times more potent an anticoagulant than R warfarin 78 , and it is metabolized primarily by the cytochrome P450 2C9 isozyme (CYP2C9), while R warfarin is metabolized by cytochrome P450 1A2 and 3A4 isozymes 77 . Drugs that induce or inhibit these enzyme systems have the ability to alter warfarin metabolism and to decrease or increase the INR, respectively.…”

Section: Induction or Inhibition Of Cytochrome P450 Isozymesmentioning

confidence: 99%

“…Inhibition of CYP3A4 liver enzymes by chlorophyllin may result in increased INR, although the interaction is thought to be of smaller impact than those affecting the CYP P450 2C9 component 77 . However, evidence to support this is lacking.…”

Section: Induction or Inhibition Of Cytochrome P450 Isozymesmentioning

confidence: 99%

“…As mentioned above, warfarin is highly bound to plasma protein, mainly albumin, and has the potential to interact with other high protein binding substances 77 . In vitro interactions between bovine serum albumin and chlorophyll, in aqueous solution under physiological conditions, indicated "low affinity binding" of bovine serum albumin and chlorophyll 64 .…”

Section: Displacement Of Binding With Plasma Proteinsmentioning

confidence: 99%

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Warfarin-chlorophyll herb-drug interactions

Siriwatanametanon¹

2017

Pharm Sci Asia

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Warfarin is one of the most commonly prescribed anticoagulants for preventing the formation of blood clots to reduce the risk of heart attack, stroke, deep vein thrombosis, and other serious conditions. Warfarin belongs to a group of vitamin K antagonists that has a narrow therapeutic index, slow onset of action and significant drug-drug, herb-drug interactions. Its unpredictable doseresponse relationship can increase risks of bleeding complications or inadequate anticoagulation. Consumption of foods and nutritional supplements rich in vitamin K can interfere with warfarin treatment because vitamin K can reduce the warfarin's effectiveness and potentially increase the risk of blood clots. There are chlorophyll products that are claimed to be beneficial to health when taken as a supplement in solid or liquid forms. Chlorophyll products are now increasingly distributed all over the world. These products make patients and healthcare providers confused about how they affect the effectiveness of warfarin treatment because they are derived from green vegetables, which have been known to cause significant herb-drug interactions. This review provides some information about chlorophylls and chlorophyll products that can potentially interact with warfarin, and some forms, such as chlorophyll drops or chlorophyll water, that can be taken safely because they contain the lowest amount of vitamin K.

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Pharmacoepidemiologic Screening of Potential Oral Anticoagulant Drug Interactions Leading to Thromboembolic Events

Zhou

Leonard

Brensinger

et al. 2020

Clin Pharma and Therapeutics

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Drug-drug interactions (DDIs) with oral anticoagulants may lead to under-anticoagulation and increased risk of thromboembolism. While warfarin is susceptible to numerous DDIs, few studies have examined DDIs resulting in thromboembolism or those involving direct-acting oral anticoagulants (DOACs). We aimed to identify medications that increase the rate of hospitalization for thromboembolic events when taken concomitantly with oral anticoagulants. We conducted a high-throughput pharmacoepidemiologic screening study using Optum Clinformatics Data Mart, 2000-2016. We performed self-controlled case series studies among adult users of oral anticoagulants (warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban) with at least one hospitalization for a thromboembolic event. Among eligible patients, we identified all oral medications frequently co-prescribed with oral anticoagulants as potential interacting precipitants. Conditional Poisson regression was used to estimate rate ratios comparing precipitant exposed vs. unexposed time for each anticoagulant-precipitant pair. To minimize within-person confounding by indication for the precipitant, we used pravastatin as a negative control object drug. Multiple estimation was adjusted using semi-Bayes shrinkage. We screened 1,622 oral anticoagulantprecipitant drug pairs and identified 226 (14%) drug pairs associated with statistically significantly elevated risk of thromboembolism. Using pravastatin as the negative control object drug, this list

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Drug Interactions Involving Warfarin: Practice Tool and Practical Management Tips

Cited by 32 publications

References 52 publications

Interaction of vitamin K antagonists and trimethoprim-sulfamethoxazole: ignore at your patient’s risk

Interaction of vitamin K antagonists and trimethoprim-sulfamethoxazole: ignore at your patient’s risk

Warfarin-chlorophyll herb-drug interactions

Pharmacoepidemiologic Screening of Potential Oral Anticoagulant Drug Interactions Leading to Thromboembolic Events

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