warfarin and Hepatitis-C--Chronic

Anticoagulation therapy is the main line of treatment for acute portal vein thrombosis (PVT) in the absence of cirrhosis. However, the use of this therapy in cirrhotic PVT is still with doubtful evidence. We aimed to evaluate the efficacy and safety of rivaroxaban compared to warfarin for the management of acute non-neoplastic PVT in Hepatitis C virus (HCV)-related compensated cirrhosis.. Out of 578 patients with chronic HCV infection, 80 patients with acute PVT who had undergone splenectomy due to hypersplenism and 4 patients with acute PVT due to portal pyemia were selected. The patients were randomly assigned (1:1) to the study group (n = 40), in which the patients received rivaroxaban 10 mg/12 h, or the control group (n = 40), in which the patients received warfarin.. In the rivaroxaban group, the resolution of PVT was achieved in 34 patients (85%) within 2.6 ± 0.4 months and delayed, partial recanalization after 6.7 ± 1.2 months (n = 6.15%). Complications such as major bleeding, abnormal liver functions, death, or recurrence did not occur during treatment, and patients in this group showed improved short-term survival rate (20.4 ± 2.2 months) compared to the survival rate in the control group (10.6 ± 1.8 months) in which warfarin achieved complete resolution in 45% of patients. Complications such as severe upper GI tract bleeding (43.3%), hepatic decompensation (22.5%), progression to mesenteric ischemia (12.5%), recurrence (10%), and death (20%) were observed in the control group. The duration until complete resolution of thrombus correlated with age, the extent of the thrombus, creatinine level, and MELD score. The recurrence after complete resolution of thrombus correlated with age, the extent of the thrombus, thrombogenic gene polymorphism, and the use of warfarin.. Rivaroxaban was effective and safe in acute HCV-related non-neoplastic PVT with improved short-term survival rate; ClinicalTrials.gov Identifier: NCT03201367.

Topics: Adult; Anticoagulants; Blood Coagulation; Computed Tomography Angiography; Egypt; Factor Xa Inhibitors; Female; Hemorrhage; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Male; Middle Aged; Phlebography; Portal Vein; Recurrence; Rivaroxaban; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Color; Venous Thrombosis; Warfarin

The aim of this study was to evaluate the effects of danoprevir in combination with low-dose ritonavir (danoprevir/r) and placebo plus low-dose ritonavir on the pharmacokinetics of probe drugs for cytochrome P450 (CYP) 3A and CYP2C9, in patients with chronic hepatitis C.. A total of 54 patients infected with hepatitis C virus genotype 1 received an oral drug cocktail (2 mg midazolam, 10 mg warfarin and 10 mg vitamin K) before and after 14 days of dosing with either danoprevir/r or placebo plus low-dose ritonavir (placebo/r). Serial pharmacokinetic samples were collected up to 24 (midazolam) and 72 (S-warfarin) h post-dose. Plasma concentrations of midazolam, α-hydroxymidazolam and S-warfarin were measured using validated assays. Pharmacokinetic parameters were estimated using non-compartmental analysis, and geometric mean ratios (GMRs) and 90 % confidence intervals (CIs) for the differences between baseline and post-dosing values were calculated.. Danoprevir/r and placebo/r significantly increased midazolam area under the time-concentration curve (AUC0-∞) and reduced the midazolam metabolic ratio while S-warfarin AUC0-∞ was modestly decreased. When danoprevir data were pooled across doses, the midazolam GMR (90 % CI) AUC0-∞ was 9.41 (8.11, 10.9) and 11.14 (9.42, 13.2) following danoprevir/r and placebo/r dosing, respectively, and the S-warfarin GMR (90 % CI) AUC0-∞ was 0.72 (0.68, 0.76) and 0.76 (0.69, 0.85), respectively. The effects of danoprevir/r and placebo/r appeared to be qualitatively similar.. Substantial inhibition of CYP3A- and modest induction of CYP2C9- activity were observed with danoprevir/r and low-dose ritonavir.

Topics: Adult; Antiviral Agents; Aryl Hydrocarbon Hydroxylases; Cyclopropanes; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP3A; Drug Interactions; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Isoindoles; Lactams; Lactams, Macrocyclic; Male; Midazolam; Middle Aged; Proline; Ritonavir; Sulfonamides; Vitamin K; Warfarin; Young Adult

Previous studies suggested that direct-acting antivirals (DAAs) against hepatitis C increased the blood coagulability of patients on warfarin. This study aims to descriptively investigate the effects of DAAs on the blood coagulability and liver function of patients on warfarin in Japan.. The Medical Information Database Network (MID-NET. For the 16 eligible patients, the mean values of both PT-INR and WSI (warfarin sensitivity index) defined as the value obtained by dividing the PT-INR by the warfarin daily dose slightly decreased at the date of completion of the DAA treatment in comparison with those at the date of initiation and subsequently increased at 12 weeks after treatment completion. In contrast, the warfarin daily dose increased at the date of completion of the DAA treatment, followed by a decrease at 12 weeks after its completion. Several laboratory tests related to the liver function also revealed a similar decrease at the end of the DAA treatment.. The analysis of MID-NET

Topics: Antiviral Agents; Hepatitis C; Hepatitis C, Chronic; Humans; Japan; Pharmaceutical Preparations; Warfarin

A case of increased warfarin requirements during treatment with sofosbuvir and ribavirin for chronic hepatitis C virus (HCV) infection is reported.. A 63-year-old white man receiving long-term anticoagulation with warfarin for atrial fibrillation and a history of cardioembolic stroke was initiated in September 2014 on a 12-week course of sofosbuvir 400 mg orally daily and weight-based ribavirin 600 mg orally twice daily for HCV genotype 2 infection. Before starting this treatment regimen, the patient had been stable on warfarin 52.5 mg weekly, with therapeutic International Normalized Ratio (INR) values. During the 12-week course of sofosbuvir and ribavirin, the patient's dose of warfarin progressively increased from 52.5 to 77.5 mg weekly due to subtherapeutic INRs, with the first adjustment in the warfarin dose occurring 9 days after initiation of HCV treatment. Three weeks after completion of the sofosbuvir and ribavirin regimen, the patient's INR was 3.06, and his warfarin dose was then decreased to 70 mg weekly. The patient continued with this warfarin dosage until 18 weeks after completion of his HCV regimen. The dosage was then decreased to 65 mg weekly after an INR of 3.86. Three weeks later, his INR was 2.19, and warfarin 65 mg weekly was continued. As of June 2016, the patient has continued to require warfarin 62.5-65 mg weekly to maintain a therapeutic INR.. A 63-year-old man on a stable dose of warfarin experienced a decrease in INR values after the initiation of a 12-week course of sofosbuvir and ribavirin for the treatment of chronic HCV infection.

Topics: Anticoagulants; Antiviral Agents; Drug Interactions; Drug Therapy, Combination; Hepatitis C, Chronic; Humans; International Normalized Ratio; Male; Middle Aged; Ribavirin; Sofosbuvir; Warfarin

Topics: Anticoagulants; Antiviral Agents; Carbamates; Drug Combinations; Drug Interactions; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Middle Aged; Sofosbuvir; Thrombosis; Treatment Outcome; Warfarin

Paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD) is a direct-acting antiviral (DAA) approved for the treatment of chronic hepatitis C virus. We report on a probable interaction between PrOD with ribavirin and warfarin.. Two weeks after the start of PrOD with ribavirin, the patient's international normalized ratio (INR) became subtherapeutic. Eleven weeks into therapy and following a 125% total increase in the weekly warfarin dose, therapeutic INR was achieved. Thirteen days after DAA therapy was completed and discontinued, the patient's INR became critically supratherapeutic.. Patients on PrOD plus ribavirin with warfarin should have INR followed closely upon initiation and discontinuation of therapy due to a probable drug interaction.

Topics: 2-Naphthylamine; Anilides; Anticoagulants; Antiviral Agents; Carbamates; Cyclopropanes; Drug Interactions; Drug Therapy, Combination; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Macrocyclic Compounds; Male; Middle Aged; Proline; Ribavirin; Ritonavir; Sulfonamides; Uracil; Valine; Warfarin

To describe international normalized ratio (INR) trends and warfarin dosage adjustments required for four veterans who were receiving warfarin therapy and started treatment for hepatitis C virus (HCV) with ledipasvir/sofosbuvir with or without ribavirin.. Case series.. Pharmacist-led anticoagulation clinic in a Veterans Affairs Health Care System.. Four patients aged 59-66 years who were receiving warfarin and had stable, therapeutic INRs and started ledipasvir/sofosbuvir therapy with or without ribavirin for HCV infection.. All four patients developed subtherapeutic INRs after the addition of ledipasvir/sofosbuvir with or without ribavirin. An increase in weekly warfarin dose ranging from 14-67% was required, with changes in warfarin doses starting 2-3 weeks after ledipasvir/sofosbuvir initiation. Two patients required dose reductions after HCV treatment completion, whereas the other two did not. Use of the Drug Interaction Probability Scale indicated that the interaction between warfarin and ledipasvir/sofosbuvir was doubtful (score of 1 [two patients]) or possible (score of 4 [two patients]). The mechanism of this interaction is unknown but may be related to improvements in hepatic function during HCV treatment.. To our knowledge, this is the first case series describing a possible drug interaction between warfarin and ledipasvir/sofosbuvir (with or without ribavirin). Close monitoring is warranted when ledipasvir/sofosbuvir is initiated in patients receiving anticoagulation therapy with warfarin, especially those with evidence of cirrhosis prior to treatment. This is particularly important in the first month after starting treatment and the first month after completion. Failure to monitor and achieve therapeutic INR after HCV therapy completion may have the potential to result in adverse outcomes.

Topics: Aged; Anticoagulants; Antiviral Agents; Benzimidazoles; Dose-Response Relationship, Drug; Drug Interactions; Fluorenes; Hepatitis C, Chronic; Humans; International Normalized Ratio; Male; Middle Aged; Pharmaceutical Services; Pharmacists; Ribavirin; Sofosbuvir; Treatment Outcome; Uridine Monophosphate; Veterans; Warfarin

An 84-year-old woman with hepatitis C virus-related cirrhosis, hepatocellular carcinoma and atrial fibrillation, who presented with hematemesis, was initially treated with endoscopic variceal ligation (EVL) for an esophageal varix hemorrhage. However, computed tomography (CT) upon admission had revealed portal vein thrombosis, despite having received warfarin for existing atrial fibrillation. We subsequently initiated a 2-week treatment with danaparoid;warfarin being discontinued in order to reduce the risk of re-hemorrhage. A follow-up CT after treatment revealed complete reduction of the portal vein thrombosis. This is the first successful report of danaparoid use in the treatment of portal vein thrombosis that developed in a patient who had received warfarin.

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chondroitin Sulfates; Dermatan Sulfate; Female; Heparitin Sulfate; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Portal Vein; Thrombosis; Warfarin

A probable interaction between warfarin and a recently approved protease inhibitor used in a triple-drug regimen for hepatitis C virus (HCV) infection is reported.. A 45-year-old Hispanic man seen at an anticoagulation clinic was found to have an International Normalized Ratio (INR) of 6.0; for the preceding eight months, INR values in the therapeutic range (2.5-3.5) had been maintained on a stable regimen of warfarin sodium 6 mg daily. Two days before the clinic visit, triple therapy with peginterferon alfa-2a, ribavirin, and telaprevir had been initiated for chronic HCV infection. The patient was instructed to skip two warfarin sodium doses and then resume its use at a reduced daily dose (5 mg), but he reported missing five doses, resulting in a below-target INR. An increase in the weekly warfarin dose of 50% above the baseline dose was required to reattain a target INR. The warfarin dosing requirement began to decline only after the man finished the prescribed 12-week course of telaprevir.. The INR of an HCV-infected man who was on a stable warfarin regimen was found to be above the target range two days after triple therapy including telaprevir was begun. The INR fell below the target range after warfarin therapy was ceased for five days and returned to that range after warfarin was restarted and its dosage gradually increased to 1.5 times the baseline dosage. The warfarin dosage needed to maintain a target INR fell to nearly its baseline level after telaprevir was discontinued.

Topics: Dose-Response Relationship, Drug; Drug Interactions; Hepatitis C, Chronic; Humans; International Normalized Ratio; Male; Middle Aged; Oligopeptides; Warfarin

Causes of gross hematuria in a patient with end-stage renal disease are limited compared with those in patients with normal renal function. Given the increased likelihood of patients with end-stage renal disease developing renal cell carcinoma, the workup focuses on a careful evaluation of the collecting system. The workup for gross hematuria in a renal transplant recipient is similar; however, the focus shifts toward a more thorough evaluation of the transplanted kidney and bladder because immunosuppression increases the overall risk for malignancy. An immunosuppressed patient also is at risk for infectious processes in the transplanted kidney manifesting as gross hematuria. Concerns for chronic rejection also should be investigated, although microscopic hematuria is more common in this scenario. If this is unrevealing, then close scrutiny of the native kidneys for possible sources of bleeding is warranted. We present an interesting and unusual cause of painless gross hematuria in a patient with end-stage renal disease and transplant nephrectomy 3 months before the onset of bleeding.

Topics: BK Virus; Diagnosis, Differential; Embolization, Therapeutic; Fistula; Graft Rejection; Hematuria; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Nephrectomy; Nephritis; Polyomavirus Infections; Postoperative Complications; Renal Artery; Renal Dialysis; Suture Techniques; Thrombosis; Tumor Virus Infections; Urinary Fistula; Urologic Neoplasms; Valsalva Maneuver; Vascular Diseases; Warfarin; Weight Lifting

Topics: Adenocarcinoma; Adult; Anticoagulants; Arterial Occlusive Diseases; Autoimmune Diseases; Drug Resistance; Female; Heparin; Heparin, Low-Molecular-Weight; Hepatitis C, Chronic; Hirudins; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Neoplasms, Unknown Primary; Platelet Aggregation Inhibitors; Portal Vein; Pulmonary Embolism; Recombinant Proteins; Recurrence; Thrombocytopenia; Vena Cava, Inferior; Venous Thrombosis; Warfarin