Enhancement of Warfarin Response in a Patient Receiving Etoposide and Carboplatin Chemotherapy

1997 ◽  
Vol 31 (9) ◽  
pp. 1006-1008 ◽  
Author(s):  
Alyssa T Le ◽  
Noelle K Hasson ◽  
Bert L Lum
Keyword(s):  
Drug Interaction ◽  
Time Course ◽  
International Normalized Ratio ◽  
Average Dose ◽  
Concomitant Disease ◽  
Close Monitoring ◽  
Mixed Germ Cell Tumor ◽  
Monitoring Strategies ◽  
Altered Response ◽  
Clinically Significant

Objective To report a case of a possible drug interaction between warfarin, carboplatin, and etoposide resulting in a marked increase in a patient's response to warfarin, and to outline monitoring strategies for this interaction. Case Summary A 74-year-old white man receiving warfarin (average dose 42.5 mg/wk) for atrial fibrillation was diagnosed with a right testicular non-seminoma mixed germ cell tumor. Mediastinal metastases were subsequently discovered, and the patient was treated with a chemotherapy regimen including carboplatin and etoposide. Sixteen days after the first course of chemotherapy, the international normalized ratio (INR) was increased to 12.6 from a baseline range of 1.15–2.11 that was observed over the previous 8 months of therapy, indicating a clinically significant alteration in the pharmacodynamic response to warfarin. Discussion This patient had no concomitant disease or dietary changes to explain the altered response to warfarin. Carboplatin and etoposide have not been reported to inhibit warfarin metabolism. However, previous reports have suggested that etoposide may displace warfarin from its protein binding sites, resulting in an early elevation in prothrombin time following chemotherapy. The late elevation of INR observed in our patient suggests that his response to warfarin may have been due to the displacement of warfarin by elemental platinum, which has a long plasma half-life. Conclusions This case report suggests a possible drug interaction between carboplatin, etoposide, and warfarin. Because of the risk associated with an increased response to warfarin, we recommend close monitoring of the INR, perhaps twice weekly, early and later in the time course following chemotherapy with these agents. Appropriate dosage adjustments of warfarin should be performed if an altered response to warfarin is observed.

scholarly journals Concurrent Spontaneous Sublingual and Intramural Small Bowel Hematoma due to Warfarin Use

2015 ◽  
Vol 2015 ◽  
pp. 1-3 ◽  
Author(s):  
Gül Pamukçu Günaydın ◽  
Hatice Duygu Çiftçi Sivri ◽  
Serkan Sivri ◽  
Yavuz Otal ◽  
Ayhan Özhasenekler ◽  
...  
Keyword(s):  
Emergency Department ◽  
Small Bowel ◽  
Warfarin Therapy ◽  
International Normalized Ratio ◽  
Fresh Frozen Plasma ◽  
Close Monitoring ◽  
Observation Unit ◽  
Fresh Frozen ◽  
Tomography Scan ◽  
Frozen Plasma

Introduction. We present a case of concurrent spontaneous sublingual and intramural small bowel hematoma due to warfarin anticoagulation.Case. A 71-year-old man presented to the emergency department complaining of a swollen, painful tongue. He was on warfarin therapy. Physical examination revealed sublingual hematoma. His international normalized ratio was 11.9. The computed tomography scan of the neck demonstrated sublingual hematoma. He was admitted to emergency department observation unit, monitored closely; anticoagulation was reversed with fresh frozen plasma and vitamin K. 26 hours after his arrival to the emergency department, his abdominal pain and melena started. His abdomen tomography demonstrated intestinal submucosal hemorrhage in the ileum. He was admitted to surgical floor, monitored closely, and discharged on day 4.Conclusion. Since the patient did not have airway compromise holding anticoagulant, reversing anticoagulation, close monitoring and observation were enough for management of both sublingual and spontaneous intramural small bowel hematoma.

Inhibition of Hepatic Microsomal Drug Metabolism by the Hydrazines Ro 4-4602, MK 486, and Procarbazine Hydrochloride

1972 ◽  
Vol 50 (7) ◽  
pp. 721-724 ◽  
Author(s):  
Norman R. Bade ◽  
Stuart M. MacLeod ◽  
Kenneth W. Renton
Keyword(s):  
Drug Interaction ◽  
Drug Metabolism ◽  
Sleeping Time ◽  
Hydrazine Derivatives ◽  
Significant Drug Interaction ◽  
Microsomal Drug Metabolism ◽  
Clinically Significant ◽  
Hepatic Biotransformation

Preliminary experiments were undertaken to examine the effect of three hydrazine derivatives, viz. Ro 4-4602, MK 486, and procarbazine hydrochloride, on hepatic microsomal drug metabolism in rats. All three compounds when given as pretreatment significantly prolonged pentobarbital sleeping time. In vitro, the hepatic microsomal N-demethylation of aminopyrine was inhibited. It is concluded that all three drugs are possible sources of clinically significant drug interaction when administered in combination with other agents which undergo hepatic biotransformation.

scholarly journals International Normalized Ratio (INR) Increases amongst Two Patients Living with HIV on Warfarin after Being Switched from a Nevirapine to a Dolutegravir-Based Antiretroviral Regimen

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Natalie Sang ◽  
Sonak Pastakia ◽  
Samuel Nyanje
Keyword(s):  
Drug Interactions ◽  
International Normalized Ratio ◽  
Hiv Treatment ◽  
Treatment Programs ◽  
Cytochrome P450 Enzyme ◽  
Close Monitoring ◽  
Medication Regimen ◽  
Emergency Plan ◽  
First Case ◽  
Living With Hiv

The increased use of dolutegravir-based regimens in the treatment of HIV is unmasking drug interactions, particularly in patients who were previously on nevirapine. Nevirapine is an enzyme inducer and increases the dosing requirements for cytochrome P450 enzyme substrates including warfarin. Upon discontinuing nevirapine, close monitoring of drugs with narrow therapeutic indices is paramount since dosing requirements may significantly reduce, increasing the probability of toxicity development. We present two cases describing interactions experienced by patients living with HIV, while transitioning from nevirapine to dolutegravir-based HIV regimens. The first case describes a 70-year-old man living with HIV and diabetes, while the second case describes a 60-year-old woman living with HIV. They were diagnosed with unprovoked deep vein thrombi, and while receiving treatment with warfarin, their HIV medication regimen was changed from lamivudine, zidovudine, nevirapine, and septrin to lamivudine, tenofovir, dolutegravir, and septrin. During the weeks following this switch, warfarin requirements decreased resulting in supratherapeutic INRs. With the continued promotion of dolutegravir-based HIV regimens as the preferred option for the treatment of HIV in President’s Emergency Plan for AIDS Relief (PEPFAR) supported HIV treatment programs in Africa, clinicians must be aware of the potentially life-threatening consequences of switching antiretroviral regimens. It is hoped that a greater awareness of this potential side effect could lead to increased monitoring and prevention of the consequences of drug interactions.

Inductive Effect of a Ritonavir-Containing Hepatitis C Treatment Regimen on Warfarin in a Patient—A Case Report

2018 ◽  
Vol 32 (4) ◽  
pp. 470-473 ◽  
Author(s):  
Audrey C. Rosene ◽  
Jaymee L. Gaspar
Keyword(s):  
Hepatitis C ◽  
Treatment Regimen ◽  
Case Reports ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Close Monitoring ◽  
Anticoagulation Management ◽  
Hepatitis C Treatment ◽  
History Of ◽  
Repeated Use

The warfarin management strategy for a mechanical mitral valve patient initiated on a ritonavir-based hepatitis C treatment regimen is described. A 62-year-old male with a past medical history of hepatitis C genotype 1a and stable warfarin dose history was initiated on a concomitant Viekira Pak® (VP) regimen containing ritonavir. Prior to initiation of the VP for hepatitis C treatment, the patient was stable on a warfarin dose of 40 mg/wk for 5 months. During treatment with VP, the patient experienced a markedly decreased international normalized ratio (INR) and warfarin requirements ultimately increased 125% from baseline (90 mg/wk). Effective anticoagulation management throughout and surrounding the treatment period for hepatitis C involved frequent warfarin dose adjustments, including preemptive changes, close monitoring, and repeated use of enoxaparin to ensure adequate thrombotic prophylaxis. This is believed to be the first reported case describing the management of warfarin in a patient with hepatitis C who received VP and required a drastically increased weekly warfarin dose. The possible mechanisms suggestive of this interaction and similar case reports in the literature are discussed.

Possible Drug Interaction between Warfarin and Combination of Levamisole and Fluorouracil

1994 ◽  
Vol 28 (4) ◽  
pp. 464-467 ◽  
Author(s):  
Mary A. Scarfe ◽  
Marc K. Israel
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patient ◽  
Colon Cancer ◽  
Drug Interaction ◽  
Chemotherapy Regimen ◽  
Hepatic Metabolism ◽  
Chronic Atrial Fibrillation ◽  
Close Monitoring ◽  
Chemotherapeutic Regimen ◽  
Concurrent Use

OBJECTIVE: To report a possible drug interaction between the combination of fluorouracil (5-FU), levamisole, and warfarin. CASE SUMMARY: An elderly patient with chronic atrial fibrillation and prosthetic valve replacements had been taking warfarin 22.5 mg/wk. Following the diagnosis of colon cancer (Duke's classification D), a chemotherapy regimen of 5-FU and levamisole was started. Within four weeks after initiation of chemotherapy, the International Normalization Ratio (INR) increased from 3.04 to 39.56. Warfarin was discontinued and restarted at 7.5 mg/wk. Discontinuation of levamisole and 5-FU for a five-week period resulted in the INR falling to a subtherapeutic level. Reinstitution of the chemotherapeutic regimen once again led to an increase in INR. DISCUSSION: A literature search showed no reports of an interaction between warfarin and levamisole. However, prolongation of 5-FU half-life and an increase in INR have been reported with the concurrent use of 5-FU and warfarin. Inhibition of the hepatic metabolism of warfarin by 5-FU and levamisole is the postulated mechanism of this drug interaction. CONCLUSIONS: This case describes the clinically significant increase of INR in an elderly patient after adding a chemotherapy regimen of levamisole and 5-FU to a previous regimen of warfarin alone. The increasing incidence of both atrial fibrillation and colon cancer with age could potentially require the concomitant use of 5-FU, levamisole, and warfarin. Because of the potential severity of this interaction, close monitoring of INR and warfarin dosage adjustment is recommended in patients receiving warfarin along with levamisole and 5-FU.

Lack of a Clinically Significant Pharmacokinetic Drug Interaction Between Tiagabine and Valproate

1998 ◽  
Vol 5 (2) ◽  
pp. 73-80 ◽  
Author(s):  
Linda E. Gustavson ◽  
Kenneth W. Sommerville ◽  
Galen F. Witt ◽  
Helen J. Guenther ◽  
G. Richard Granneman ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Pharmacokinetic Drug Interaction ◽  
Clinically Significant ◽  
Pharmacokinetic Drug

Warfarin dose adjustment required after cannabidiol initiation and titration

2020 ◽  
Vol 77 (22) ◽  
pp. 1846-1851
Author(s):  
Josh Cortopassi
Keyword(s):  
Case Report ◽  
Interaction Potential ◽  
Significant Interaction ◽  
Dose Adjustment ◽  
Intractable Epilepsy ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Dose Titration ◽  
Published Report ◽  
Clinically Significant

Abstract Purpose A case of a possible interaction between cannabidiol and warfarin is presented along with a brief overview of cytochrome enzymes involved in these drugs’ metabolism. Summary A 46-year-old male taking warfarin for treatment of a deep venous thrombosis was initiated on a Food and Drug Administration (FDA)–approved cannabidiol product (Epidiolex, Greenwich Biosciences) for intractable epilepsy. The patient’s International Normalized Ratio (INR) was monitored closely during cannabidiol initiation and dose titration. The patient required a nearly 20% warfarin dose reduction to maintain an INR within the goal range after starting therapy with cannabidiol. There is 1 other case report describing a clinically significant interaction between cannabidiol (specifically Epidiolex) and warfarin in a patient receiving warfarin who was enrolled in a study involving the initiation and titration of cannabidiol; that patient developed a supratherapeutic INR of 6.86 and required a 30% reduction in the weekly warfarin dose to reachieve the goal INR. Conclusion A previously published report suggesting an interaction between cannabidiol and warfarin is supported by this case report. INR should be monitored frequently in patients taking warfarin who begin to take FDA-approved cannabidiol. Additional studies should be performed to clarify the interaction potential of cannabidiol and warfarin.

scholarly journals Lack of a clinically significant drug-drug interaction in healthy volunteers between the HCV protease inhibitor boceprevir and the proton pump inhibitor omeprazole

2013 ◽  
Vol 68 (6) ◽  
pp. 1415-1422 ◽  
Author(s):  
C. T. M. M. de Kanter ◽  
A. P. H. Colbers ◽  
M. I. Blonk ◽  
C. P. W. G. M. Verweij-van Wissen ◽  
B. J. J. W. Schouwenberg ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Proton Pump Inhibitor ◽  
Protease Inhibitor ◽  
Healthy Volunteers ◽  
Proton Pump ◽  
Hcv Protease ◽  
Drug Drug Interaction ◽  
Clinically Significant
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