Levofloxacin and Warfarin Interaction

2002 ◽  
Vol 36 (10) ◽  
pp. 1554-1557 ◽  
Author(s):  
Cade B Jones ◽  
Susan E Fugate
Keyword(s):  
Binding Sites ◽  
Warfarin Therapy ◽  
Case Reports ◽  
Anticoagulation Therapy ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Minor Bleeding ◽  
Protein Binding Sites ◽  
Case Summary

OBJECTIVE: To report 4 cases of hypoprothrombotic response resulting from addition of levofloxacin therapy to chronic warfarin therapy and to review related literature to support or refute a warfarin—levofloxacin interaction. CASE SUMMARY: Four patients, 34–81 years old, were prescribed levofloxacin concomitantly with stable warfarin therapy. Three patients had a target international normalized ratio (INR) range of 2.0–3.0 and experienced an increase in INR to 3.5, 8.12, and 11.5 on days 11, 5, and 4 of a 10-day course of levofloxacin, respectively. The fourth patient experienced minor bleeding, with a slightly elevated INR on the second day of levofloxacin therapy that required up to a 19% warfarin dose reduction during levofloxacin treatment. DISCUSSION: An initial premarketing clinical trial concluded that levofloxacin had no effect on warfarin's pharmacokinetics and pharmacodynamic response. Two case reports have since documented an increase in INR in patients taking long-term warfarin on completion of levofloxacin therapy. Our case reports provide further evidence of a significant increase in INR observed during concomitant levofloxacin therapy. The proposed mechanism of this interaction is displacement of warfarin from protein binding sites, reduction in gut flora producing vitamin K, and decreased warfarin metabolism. CONCLUSIONS: Prolonged prothrombin response in patients undergoing chronic warfarin therapy has been well documented with many antibiotics, including fluoroquinolones. Recognition of newer antibiotics' effects on warfarin therapy is important to guide safe use and monitoring of anticoagulation therapy. Our case studies demonstrate significant elevations in INR values during and up to 1 day after levofloxacin therapy in patients undergoing stable warfarin therapy.

scholarly journals Genetic and Non-Genetic Factors Association with Warfarin Long Term Therapy Stability in Sudan

2016 ◽  
Vol 8 (4) ◽  
pp. 100
Author(s):  
Azza A. M. H. Swar Aldahab ◽  
Abdallah. O. Elkhawad
Keyword(s):  
Vitamin K ◽  
Genetic Factors ◽  
Warfarin Therapy ◽  
Anticoagulation Therapy ◽  
Warfarin Dose ◽  
Term Therapy ◽  
P Value ◽  
Retrospective Case ◽  
The Impact

Anticoagulation with warfarin is characterized by a wide inter-individual variations in dose requirements and INR (International Normalised Ratio) stability, as there are evidences that warfarin response variability is associated with CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) and VKORC1 (Vitamin K epoxide reductase complex1) genetic polymorphisms. Carriers of CYP2C9*2 and VKORC11639G>A variant alleles are at greater risk of unstable anticoagulation therapy. Objectives: This retrospective case control study was directed to analyze the impact of genetic and non-genetic factors on warfarin therapy in Sudanese out-patients who were on long term warfarin therapy. Method: 118 Sudanese outpatients receiving warfarin treatment for at least six months, were interviewed for their non-genetic factors that included age, sex, indication for warfarin therapy, compliance, Vitamin K rich foods intake and concomitant drug therapy, in addition to their blood samples which were taken for DNA extraction and genotyping of CYP2C9*2 and VKORC11639G>A gene polymorphisms to study the genetic factors. INR stability % index was calculated, accordingly patients were classified into 2 groups, stable and unstable groups. Results: The frequencies of VKORC11639G>A alleles in Sudanese out-patients who were on long term warfarin therapy were 70.3% and 29.7% for the VKORC1/G and VKORC1/A alleles respectively. The frequencies of CYP2C9*2 alleles in Sudanese out-patients were 92.4% and 7.6% for CYP2C9*1 and CYP2C9*2 alleles respectively. Variables associated with low INR stability were VKCOR1/AA genotype (p-value = 0.028) and sex (p = 0.017). Variables that showed no association with INR stability were age (p-value = 0.259), compliance (p-value = 0.058). Vitamin K rich foods intake (p- value = 0.743), and mean stable warfarin dose (p-value = 0.439). Conclusion: Polymorphism in warfarin drug target gene VKORC1-11639G>A and sex are important elements of INR stability in Sudanese out- patients on long term warfarin therapy.

Patient Factors That Influence Warfarin Dose Response

2010 ◽  
Vol 23 (3) ◽  
pp. 194-204 ◽  
Author(s):  
Pamela J. White
Keyword(s):  
Dose Response ◽  
Warfarin Therapy ◽  
Anticoagulation Therapy ◽  
Warfarin Dose ◽  
Therapeutic Index ◽  
International Normalized Ratio ◽  
Patient Factors ◽  
Disease States ◽  
Treatment And Prevention ◽  
Number Of Factors

Warfarin has long been the mainstay of oral anticoagulation therapy for the treatment and prevention of venous and arterial thrombosis. The narrow therapeutic index of warfarin, and the complex number of factors that influence international normalized ratio (INR) response, makes optimization of warfarin therapy challenging. Determination of the appropriate warfarin dose during initiation and maintenance therapy requires an understanding of patient factors that influence dose response: age, body weight, nutritional status, acute and chronic disease states, and changes in concomitant drug therapy and diet. This review will examine specific clinical factors that can affect the pharmacokinetics and pharmacodynamics of warfarin, as well as the role of pharmacogenetics in optimizing warfarin therapy.

Potentiation of Warfarin Anticoagulation Associated with Topical Methyl Salicylate

2000 ◽  
Vol 34 (6) ◽  
pp. 729-733 ◽  
Author(s):  
Jacqueline D Joss ◽  
Richard F LeBlond
Keyword(s):  
Binding Sites ◽  
Significant Interaction ◽  
Methyl Salicylate ◽  
Low Dose ◽  
Healthcare Providers ◽  
International Normalized Ratio ◽  
High Dose ◽  
Potential Hazard ◽  
Protein Binding Sites ◽  
Case Summary

OBJECTIVE: To report a case of international normalized ratio (INR) elevation resulting from the administration of topical methyl salicylate in a patient whose INR was previously stable while she received warfarin anticoagulation. CASE SUMMARY: A 22-year-old white woman presented with an INR of 12.2 after applying a topical pain-relieving gel to her knees daily for eight days. The potentiation of the warfarin anticoagulation was attributed to the low-dose methyl salicylate contained in the product. DISCUSSION: Methyl salicylate is systemically absorbed through the skin in measurable amounts, and may increase warfarin action by affecting vitamin K metabolism or by displacing warfarin from protein-binding sites. While several investigators have reported this interaction with use of high-dose methyl salicylate, this case indicates that a significant interaction can occur with the use of lower topical doses of methyl salicylate as well. CONCLUSIONS: Healthcare providers and patients taking warfarin must be aware of the potential hazard of using topical methyl salicylate in combination with warfarin.

Dietary Vitamin K Variability Affects International Normalized Ratio (INR) Coagulation Indices

2006 ◽  
Vol 76 (2) ◽  
pp. 65-74 ◽  
Author(s):  
Rebecca Couris ◽  
Gary Tataronis ◽  
William McCloskey ◽  
Lynn Oertel ◽  
Gerard Dallal ◽  
...  
Keyword(s):  
Anticoagulant Therapy ◽  
Vitamin K ◽  
Warfarin Therapy ◽  
Anticoagulation Therapy ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Adverse Outcomes ◽  
Dietary Vitamin ◽  
Prescription Medications ◽  
Oral Warfarin

Background: Changes in daily vitamin K intake may contribute to marked variations in the International Normalized Ratio (INR) coagulation index in patients receiving oral warfarin anticoagulant therapy, with potentially serious adverse outcomes. Thus, patients receiving warfarin therapy are routinely counseled regarding this drug-nutrient interaction and are instructed to maintain consistent vitamin K intakes, though little quantitative information about this relationship is available. Objective: To determine the quantitative impact of variability in dietary vitamin K1 (phylloquinone) intake, assessed by a validated patient self-monitoring instrument, on weekly INR in patients receiving warfarin anticoagulant therapy. Methods: A prospective dietary assessment study was conducted at the Massachusetts General Hospital in Boston. Sixty outpatients (37 males and 23 females) were selected with a mean age 60.3 ± 16.8 years, who began oral warfarin anticoagulant therapy within 14 days prior to their first clinic visit to an outpatient anticoagulation therapy unit. Exclusion criteria included more than 2 drinks of alcohol per day, inability to speak English, and concurrent disease states affecting warfarin therapy such as liver disease and terminal illness. Over the five-week study period, participants recorded daily intakes in specified amounts of all food items appearing on a validated dietary self-assessment tool. Concomitant use of prescription and/or non-prescription medications was also obtained. Concurrent daily warfarin dose and adherence to the drug regimen, concomitant use of prescription and/or non-prescription medications known to interact with warfarin, and weekly INR were obtained. Week-to-week changes in vitamin K intake, warfarin dose, and INR were determined and cross-correlated. Results: Forty-three patients (28 males and 15 females) completed the study and 17 dropped out. Pearson’s correlation coefficient revealed the variability in INR and changes in vitamin K intake were inversely correlated (r = –0.600, p < 0.01). Multiple regression analysis (r = 0.848) indicated that a weekly change of 714 mug dietary vitamin K significantly altered weekly INR by 1 unit (p < 0.01) and a weekly change of 14.5 mg warfarin significantly altered weekly INR by 1 unit (p < 0.01) after adjustment for age, sex, weight, height, and concomitant use of medications known to interact with warfarin. Conclusions: Patients taking warfarin and consuming markedly changing amounts of vitamin K may have a variable weekly INR with potentially unstable anticoagulant outcomes.

Where the Kidney is Concerned, How Much Mannitol is Too Much?

1993 ◽  
Vol 27 (1) ◽  
pp. 25-28 ◽  
Author(s):  
Gary M. Rabetoy ◽  
Michael R. Fredericks ◽  
Charles F. Hostettler
Keyword(s):  
Renal Failure ◽  
Cerebral Edema ◽  
Warfarin Therapy ◽  
Case Reports ◽  
Clonic Seizure ◽  
Midline Shift ◽  
Computed Tomography Scan ◽  
Case Summary ◽  
Tomography Scan

OBJECTIVE: To report a case of mannitol-induced acute renal failure (ARF). CASE SUMMARY: A 31-year-old woman who had been on long-term warfarin therapy for atrial fibrillation was admitted to the hospital with hemoptysis. Following reversal of her anticoagulation, she had a tonic-clonic seizure nine days after admission. An emergency computed tomography scan revealed cerebral edema, which was initially treated with hyperventilation and steroids. Two days later, a repeat scan showed progression of the cerebral edema with midline shift. Mannitol 550 g was infused over the next 28 hours, precipitating ARF. Despite prompt hemodialysis to reverse the renal failure, the patient died. This case of apparent mannitol-induced ARF illustrates several pathophysiologic effects of this agent. DISCUSSION: Case reports in the literature discussing mannitol-induced ARF are reviewed and compared. A relationship between dose and ARF and its reversal with hemodialysis is postulated. CONCLUSIONS: It is likely that sufficient doses of mannitol may lead to ARF. Limitation of dose may prevent and treatment with hemodialysis may reverse ARF in these instances.

Possible Warfarin Interaction with Menthol Cough Drops

2005 ◽  
Vol 39 (2) ◽  
pp. 365-367 ◽  
Author(s):  
Paul J Kassebaum ◽  
Don L Shaw ◽  
Dave J Tomich
Keyword(s):  
Warfarin Therapy ◽  
Causality Assessment ◽  
White Male ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Warfarin Interaction ◽  
Case Summary ◽  
First Case ◽  
Patient Reported

OBJECTIVE: To report a case of possible interaction of menthol cough drops (Halls) with warfarin in a patient awaiting cardioversion. CASE SUMMARY: A 57-year-old white male awaiting cardioversion for atrial fibrillation was prescribed warfarin. His dosage was adjusted to 7 mg daily to provide stable international normalized ratio (INR) values of 2.28–2.68. Approximately one week later, his INR fell to 1.45. During a follow-up interview, the patient reported that he experienced a flu-like illness during the previous week and had been using menthol cough drops. No other potential causes for the decreased INR were found. Illness will most often elevate the INR; we therefore concluded that the cough drops were the likely cause of this reaction, and the warfarin dose was increased to 53 mg/wk. After discontinuing use of menthol cough drops, the warfarin dose was returned to the previous amount and the INR remained stabilized. DISCUSSION: An objective causality assessment suggests that the decreased INR was possibly related to the use of menthol cough drops during warfarin therapy. The active ingredient in these cough drops is menthol. Menthol has been shown to affect the pharmacokinetics of other drugs by inducing or inhibiting cytochrome P450 isoenzymes and slowing drug absorption. It is not clear whether these mechanisms played a role in this case. As of January 5, 2005 this is the first case report documenting an interaction between warfarin and cough drops containing menthol. CONCLUSIONS: This case documents a significant decrease in the INR following the use of menthol cough drops. Patients who are ill have several factors that can potentially affect their INR and should be monitored closely.

scholarly journals Impact of CYP2C9 and VKORC1 Polymorphisms on Warfarin Sensitivity and Responsiveness in Jordanian Cardiovascular Patients during the Initiation Therapy

Genes ◽  
2018 ◽  
Vol 9 (12) ◽  
pp. 578 ◽  
Author(s):  
Laith AL-Eitan ◽  
Ayah Almasri ◽  
Rame Khasawneh
Keyword(s):  
Warfarin Therapy ◽  
Catalytic Properties ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Haplotype Blocks ◽  
Cardiovascular Patients ◽  
Cyp2c9 Gene ◽  
Vkorc1 Gene

Warfarin is an oral anticoagulant frequently used in the treatment of different cardiovascular diseases. Genetic polymorphisms in the CYP2C9 and VKORC1 genes have produced variants with altered catalytic properties. A total of 212 cardiovascular patients were genotyped for 17 Single Nucleotide Polymorphisms (SNPs) within the CYP2C9 and VKORC1 genes. This study confirmed a genetic association of the CYP2C9*3 and VKORC1 rs10871454, rs8050894, rs9934438, and rs17708472 SNPs with warfarin sensitivity. This study also found an association between CYP2C9 and VKORC1 genetic haplotype blocks and warfarin sensitivity. The initial warfarin dose was significantly related to the CYP2C9*3 polymorphism and the four VKORC1 SNPs (p < 0.001). There were significant associations between rs4086116 SNP and TAT haplotype within CYP2C9 gene and rs17708472 SNP and CCGG haplotype within VKORC1 gene and warfarin responsiveness. However, possessing a VKORC1 variant allele was found to affect the international normalized ratio (INR) outcomes during initiation of warfarin therapy. In contrast, there was a loose association between the CYP2C9 variant and INR measurements. These findings can enhance the current understanding of the great variability in response to warfarin treatment in Arabs.

Decreased Warfarin Effect after Initiation of High-Protein, Low-Carbohydrate Diets

2005 ◽  
Vol 39 (4) ◽  
pp. 744-747 ◽  
Author(s):  
Stuart J Beatty ◽  
Bella H Mehta ◽  
Jennifer L Rodis
Keyword(s):  
Serum Albumin ◽  
Warfarin Therapy ◽  
Anticoagulation Therapy ◽  
Warfarin Dose ◽  
High Protein ◽  
Carbohydrate Diet ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate ◽  
High Protein Diets ◽  
Protein Diets

OBJECTIVE: To report 2 cases of decreased international normalized ratio (INR) after initiation of a high-protein, low-carbohydrate diet. CASE SUMMARIES: Case 1. A 67-year-old white woman had been receiving warfarin for 3 years for venous thromboembolism. After initiation of a high-protein, low-carbohydrate diet, the patient required a 22.2% increase (from 45 to 57.5 mg/wk) in warfarin dose. Her INR remained in the therapeutic range on this dose for 8 weeks. When the patient stopped the high-protein, low-carbohydrate diet, a decrease back to the original warfarin dose was required to return to a therapeutic INR. Case 2. A 58-year-old white man had been receiving warfarin for 8 years for a cerebrovascular accident. Initiation of a high-protein, low-carbohydrate diet resulted in a 30% increase (from 26.25 to 37.5 mg/wk) in warfarin dose. His warfarin dose was reduced to the original dose after he stopped the high-protein, low-carbohydrate diet. DISCUSSION: The Naranjo probability scale indicated a possible adverse effect between warfarin and high-protein diets. High-protein diets have been shown to increase serum albumin levels. This may result in more warfarin binding to serum albumin, thereby decreasing the anticoagulant effect of warfarin. The increase of albumin occurs rapidly after initiation of a high-protein diet and appears to promptly affect anticoagulation therapy with warfarin. CONCLUSIONS: These cases indicate a significant interaction between high-protein, low-carbohydrate diets and warfarin therapy. Patients receiving warfarin therapy should be educated on and monitored for the potential interaction that occurs with warfarin therapy and high-protein, low-carbohydrate diets.

Fenofibrate Potentiates Warfarin Effects

2003 ◽  
Vol 37 (2) ◽  
pp. 212-215 ◽  
Author(s):  
Karissa Y Kim ◽  
Michael A Mancano
Keyword(s):  
White Woman ◽  
Chart Review ◽  
Warfarin Therapy ◽  
Dosage Reduction ◽  
International Normalized Ratio ◽  
Drug Regimen ◽  
Warfarin Dosage ◽  
Therapeutic Doses ◽  
Anticoagulant Response

OBJECTIVE: To describe 2 patients in whom the initiation of fenofibrate potentiated warfarin's anticoagulant effects. CASE SUMMARY: A 71-year-old white woman and an 80-year-old white woman with multiple medical conditions were both stabilized on long-term warfarin therapy. During the course of anticoagulation, both patients were prescribed fenofibrate and experienced threefold and twofold increases in international normalized ratio (INR), respectively, requiring total weekly warfarin dosage reductions of 30–40%. Before starting fenofibrate therapy, both patients' coagulation values were within the therapeutic range. When interviewed, patients and caregivers denied bleeding, bruising, changes in diet, alcohol ingestion, nonadherence with therapy, or changes in drug regimen except for the addition of fenofibrate. Upon chart review, evaluation of potentially contributory parameters, such as other changes in drug therapy, thyroid function, liver function, and drug–disease interactions, showed that these parameters remained stable and were ruled noncontributory. DISCUSSION: The addition of fenofibrate in 2 patients on stable and therapeutic doses of warfarin increased the anticoagulant response to warfarin. A clear temporal relationship with the addition of fenofibrate and the appearance of the interaction was seen. Fenofibrate is highly protein bound, with the potential to displace warfarin from its binding protein, leading to an enhanced hypoprothrombinemic effect. Fenofibrate is also a mild to moderate inhibitor of CYP2C9, the enzyme responsible for warfarin metabolism. The combination of these effects — displacement of warfarin by fenofibrate coupled with decreased metabolism of warfarin — may increase the anticoagulant response to warfarin. Using the Naranjo probability scale, these interactions were designated as probable. CONCLUSIONS: We suggest serial monitoring of INR and consider an empiric 20% reduction in warfarin dosage when fenofibrate is initiated, with the possibility for a greater warfarin dosage reduction based on INR results.

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