warfarin and Influenza--Human

Oseltamivir is a very commonly prescribed anti-viral medication by the Emergency Medicine (EM) physicians for the prophylactic and therapeutic treatment of Influenza infection. While the drug interaction of Warfarin with various antibiotics is known, the drug interaction between Oseltamivir and Warfarin is not common. We present a case where an 83-year female patient, on Warfarin for Pulmonary Embolism, had worsening of coagulopathy after she was started on Oseltamivir. The INR was monitored daily in our patient and Warfarin was stopped when the INR became supra-therapeutic. Our patient did not have any minor or major bleeding complication. This is the first reported case of Oseltamivir related worsening coagulopathy in patient on Warfarin to the best of our knowledge. Keeping in mind the possible interaction between the two as it was evident in our case and few other published reports, we recommend monitoring the INR closely in patients using Warfarin after they are started on Oseltamivir therapy.

Topics: Aged, 80 and over; Anticoagulants; Antiviral Agents; Dose-Response Relationship, Drug; Drug Interactions; Emergency Medicine; Female; Humans; Influenza, Human; International Normalized Ratio; Oseltamivir; Physicians; Pulmonary Embolism; Treatment Outcome; Warfarin

An 8-year-old boy with hypoplastic left heart syndrome with a previous history of thrombosis within the inferior vena cava receiving stable warfarin dosing for anticoagulation was diagnosed with influenza B. He was subsequently placed on oseltamivir therapy according to the Centers for Disease Control and Prevention clinical practice guidelines. During the hospitalization, his international normalized ratio steadily increased to supratherapeutic levels and returned to baseline after discontinuation of oseltamivir therapy. This case represents a drug-drug interaction that has not been previously reported in children or adolescents. An extensive review of the pharmacokinetic and pharmacodynamic literature did not uncover a definitive etiology for this interaction. However, several undefined aspects in each drug's disposition pathway need further elucidation. Until this interaction is understood, caution is warranted, and close monitoring of the international normalized ratio should be performed in all patients prescribed oseltamivir concomitantly with warfarin.

Topics: Anticoagulants; Antiviral Agents; Child; Drug Interactions; Humans; Hypoplastic Left Heart Syndrome; Influenza, Human; International Normalized Ratio; Male; Oseltamivir; Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Antiviral Agents; Child; Evidence-Based Medicine; Humans; Influenza, Human; Integrative Medicine; International Normalized Ratio; Obesity; Oseltamivir; Pain Management; Warfarin

The effects on anticoagulation of a purified trivalent sub-unit influenza vaccine and a 14-valent pneumococcal vaccine were investigated in a single-blind controlled study involving 69 well-stabilised warfarin recipients. There were no clinically or statistically significant alterations of anticoagulant control in vaccine recipients as compared with controls at 2, 7 and 21 days after vaccination. On the basis of these data, concern about warfarin-vaccine interaction should not deter practitioners from immunising warfarin recipients against influenza or infection with Streptococcus pneumoniae.

Topics: Aged; Bacterial Vaccines; Blood Coagulation; Female; Heart Valve Diseases; Humans; Influenza Vaccines; Influenza, Human; Male; Middle Aged; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccination; Warfarin

During the 2009 H1N1 influenza pandemic, the UK Medicines and Healthcare Products Regulatory Agency received case reports suggesting a potentiation of warfarin anticoagulation by the antiviral drug oseltamivir. We evaluated this putative interaction using Medicare data.. To determine the frequency of bleeding following addition of oseltamivir or comparator drugs among Medicare beneficiaries taking warfarin.. This was a retrospective cohort evaluation using Medicare nationwide data. Cohort members were Medicare Parts A, B, and D beneficiaries from June 30, 2006 to October 31, 2010 receiving warfarin for at least 1 month prior to a concomitant drug of interest (oseltamivir, ampicillin, trimethoprim-sulfamethoxazole (TMP-SMX), and angiotensin-converting enzyme (ACE) inhibitors). Bleeding within 14 days of new prescriptions for oseltamivir or comparators was identified using inpatient or emergency department ICD-9 (International Classification of Diseases, ninth revision) discharge diagnosis codes for gastrointestinal hemorrhage, epistaxis, hematuria, and intracranial bleeding. Patients with bleeding within 30 days preceding the prescription concomitant to warfarin were excluded.. With concomitant ACE inhibitors as reference, adjusted odds ratios (ORs) for any bleeding events within 14 days were 1.47 (95% confidence interval [CI] = 1.08-1.88), 1.24 (95% CI = 0.97-1.57), and 2.74 (95% CI = 2.53-3.03), for warfarin plus ampicillin, oseltamivir, and TMP-SMX, respectively. In a sensitivity analysis, adjusted ORs over a 7-day period were 1.89 (95% CI = 1.29-2.59), 1.47 (95% CI = 1.06-2.02), and 3.07 (95% CI = 2.76-3.49) for warfarin plus ampicillin, oseltamivir, and TMP-SMX, respectively.. Bleeding with oseltamivir plus warfarin was not significantly increased over a 14-day observation period; a sensitivity analysis showed a statistically significant increase over a 7-day period; in contrast, the data consistently showed the known tendency of TMP-SMX to potentiate the effects of warfarin. The results should be interpreted with the limitations of this approach in mind, including the inability to control for unmeasured confounders.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antiviral Agents; Cohort Studies; Drug Interactions; Female; Hemorrhage; Humans; Influenza, Human; International Classification of Diseases; Logistic Models; Male; Medicare; Middle Aged; Multivariate Analysis; Oseltamivir; Pandemics; Retrospective Studies; United States; Warfarin

Warfarin is a commonly used oral anticoagulant and its interaction with other drugs can result in serious thrombotic or bleeding events. Currently, there is no definitive evidence on the possibility of an interaction between warfarin and oseltamivir.. The objective of this study was to investigate whether a possible drug interaction between oseltamivir and warfarin exists.. A retrospective review of patients on anticoagulation therapy who took oseltamivir from 1 September 2009 to 28 February 2010 at Seoul National University Hospital, Seoul, Korea, was carried out.. Among 15 patients who were tested for prothrombin time/international normalized ratio (PT/INR) [hereafter referred to as INR] within 10 days of starting oseltamivir therapy and had previously stable INR values, seven patients had an increase in INR levels after oseltamivir administration, and the other eight patients maintained stable INR levels. The mean ± SD INR value was 2.08 ± 0.46 prior to the administration of oseltamivir and 5.15 ± 2.00 after treatment with oseltamivir (measured a mean ± SD 5.7 ± 2.5 days after the first dose of oseltamivir) in the INR-increased group and, respectively, 2.03 ± 0.40 and 1.97 ± 0.54 (measured 6.4 ± 2.5 days after the first dose of oseltamivir) in the INR-unaffected group. The dosage and duration of oseltamivir treatment were similar whether the INR values increased or not. There were bleeding events such as blood-tinged sputum and bloody ascites in three patients in the INR-increased group. The INR level recovered within 5 days after discontinuation of warfarin in these three patients. The positivity rates for influenza A H1N1 were not different between the INR-increased group and the INR-unaffected group.. This case series suggests the possibility of a potential interaction between warfarin and oseltamivir. Further well designed prospective studies and genetic evaluations are needed to determine the exact nature of the interaction between warfarin and oseltamivir.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors; Female; Hemorrhage; Hospitals, University; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; International Normalized Ratio; Male; Middle Aged; Oseltamivir; Prothrombin Time; Retrospective Studies; Time Factors; Warfarin

Topics: Adipose Tissue; Anticoagulants; Blood Glucose; C-Reactive Protein; Conflict of Interest; Disease Outbreaks; Female; Health Care Reform; Humans; Hyperglycemia; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Mass Screening; MicroRNAs; Overweight; Social Support; Warfarin