warfarin and Vomiting

The association between cancer and venous thromboembolism (VTE) is well established. Importantly, VTE is a significant cause of mortality in cancer patients. Although long-term warfarin (Coumadin(trade mark); Bristol-Myers Squibb; New York, NY) therapy is the mainstay of treatment for cancer patients with VTE, there are many practical problems with its use in this population. In particular, achieving therapeutic drug levels is difficult in cancer patients due to the increased risk of drug interactions, malnutrition, vomiting, and liver dysfunction in these patients. Moreover, cancer patients are at an increased risk of adverse effects of warfarin therapy. In contrast, low-molecular-weight heparins (LMWHs) are associated with a lower risk of adverse events compared with warfarin in patients with cancer. These agents also offer practical advantages compared with warfarin, including more predictable anticoagulant effects and ease of administration in addition to possible antineoplastic effects. Several LMWHs have demonstrated superior efficacy to warfarin in the secondary prevention of VTE. In particular, the LMWH, dalteparin (Fragmin; Pfizer; New York, NY), has recently been shown to have superior efficacy to warfarin in a large trial of patients with cancer and VTE without increasing the risk of bleeding. A randomized trial of dalteparin has also shown improved response rates and survival in patients with small cell lung cancer. In view of the availability of more effective and reliable alternatives to warfarin therapy in cancer patients, it is appropriate to reassess the role of warfarin therapy in patients with cancer and VTE. Further evaluation of the LMWHs for effects on cancer outcome is indicated.

Topics: Administration, Oral; Anticoagulants; Drug Interactions; Heparin, Low-Molecular-Weight; Humans; Malnutrition; Neoplasms; Risk Factors; Thromboembolism; Vomiting; Warfarin

Belinostat is a potent small molecule inhibitor that exerts its antitumor effect through inhibition of histone deacetylase. The purpose of this study was to evaluate the pharmacokinetics and pharmacodynamics of warfarin (as a reference drug metabolized by CYP2C9) in the presence and absence of belinostat.. We conducted a phase I, single-center, open-label, drug-drug interaction study between belinostat and warfarin. In part I, patients were given warfarin 5 mg orally (day-14 and 3) and belinostat 1000 mg/m(2) (days 1 through 5). Patients receiving benefit continued belinostat on days 1 through 5 every 21 days until disease progression, unacceptable toxicity, or per patient preference.. A total of 18 patients were treated. With belinostat, the least-squared means for maximum concentration (C max), area under the curve0-∞, and area under the curve0-t of R-warfarin were slightly increased. However, for the more potent S-warfarin isomer, the same parameters were primarily contained within the pre-specified equivalence limits of 0.80 and 1.25, indicating there was no statistically significant interaction between S-warfarin and belinostat. The most common adverse events were nausea, vomiting, and fatigue. Three grade 3 adverse events (diarrhea 5.6 %, nausea 5.6 %, and vomiting 5.6 %) were thought to be treatment related. Progression-free survival ranged from 0.2 to 13.8 months in all patients.. Belinostat did not significantly affect the pharmacokinetics and pharmacodynamics of warfarin, indicating no clinically relevant effect on the enzymatic activity of CYP2C9.

Topics: Adult; Aged; Anticoagulants; Area Under Curve; Cytochrome P-450 CYP2C9; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Interactions; Fatigue; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Middle Aged; Neoplasms; Sulfonamides; Treatment Outcome; Vomiting; Warfarin

Topics: Adult; Anti-Inflammatory Agents; Aspirin; Biphenyl Compounds; Blood Coagulation; Blood Urea Nitrogen; Chlorides; Clinical Trials as Topic; Constipation; Diarrhea; Digestive System; Drug Tolerance; Exanthema; Flatulence; Flufenamic Acid; Fluorine; Headache; Heartburn; Humans; Kidney Function Tests; Male; Mefenamic Acid; Methods; Muscle Cramp; Occult Blood; ortho-Aminobenzoates; Placebos; Potassium; Prothrombin; Sleep Initiation and Maintenance Disorders; Sodium; Uric Acid; Vertigo; Vision Disorders; Vomiting; Warfarin

Wild pigs (Sus scrofa) cause widespread environmental and economic damage, and as a result are subjected to extensive control. Current management strategies have proven insufficient, and there is growing interest in use of toxicants to control invasive populations of this species. In 2017 a low-dose warfarin bait was federally approved for use in controlling wild pigs in the United States. However, no states have allowed use of this bait due to unanswered questions regarding welfare concerns, field efficacy, and non-target impacts.. All captive wild pigs fed 0.005% warfarin baits in no choice feeding trials succumbed in an average of 8 days from exposure. Behavioral symptoms of warfarin exposure included vomiting, external bleeding, abnormal breathing, incoordination, and limping. Postmortem examinations revealed hemorrhaging in organs and muscles, particularly the legs, gastrointestinal tract, and abdomen. Warfarin residues in tissues averaged 1.0 mg kg. Our results suggest wild pigs are susceptible to low-dose warfarin, and warfarin residues in pig tissues postmortem are generally low. However, although warfarin-based baits are currently approved for use by the US Environmental Protection Agency, further improvements to pig-specific bait delivery systems and bait palatability are needed, as well as additional research to quantify efficacy, cost, and non-target impacts prior to widespread implementation. © 2021 Society of Chemical Industry. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Topics: Animals; Liver; Sus scrofa; Swine; Vomiting; Warfarin

Management of anticoagulated patients after head injury is unclear due to lack of robust evidence. This study aimed to determine the adverse outcome rate in these patients and identify risk factors associated with poor outcome.. Multicentre, observational study using routine patient records.. 33 emergency departments in England and Scotland.. 3566 adults (aged ≥16 years) who had suffered blunt head injury and were currently taking warfarin.. Primary outcome measure was rate of adverse outcome defined as death or neurosurgery following initial injury, clinically significant CT scan finding or reattendance with related complication within 10 weeks of initial hospital attendance. Secondary objectives included identifying risk factors for adverse outcome using univariable and multivariable analyses.. Clinical data available for 3534/3566 patients (99.1%), median age 79 years; mean initial international normalised ratio (INR) 2.67 (SD 1.34); 81.2% Glasgow Coma Scale (GCS) 15: 59.8% received a CT scan with significant head injury-related finding in 5.4% (n=208); 0.5% underwent neurosurgery; 1.2% patients suffered a head injury-related death. Overall adverse outcome rate was 5.9% (95% CI 5.2% to 6.7%). Patients with GCS=15 and no associated symptoms had lowest risk of adverse outcome (risk 2.7%; 95% CI 2.1 to 3.6). Patients with GCS=15 multivariable analysis (using imputation) found risk of adverse outcome to increase when reporting at least one associated symptom: vomiting (relative risk (RR) 1.8; 95% CI 1.0 to 3.4), amnesia (RR 3.5; 95% CI 2.1 to 5.7), headache (RR 1.3; 95% CI 0.8 to 2.2), loss of consciousness (RR 1.75; 95% CI 1.0 to 3.0). INR measurement did not predict adverse outcome in patients with GCS=15 (RR 1.1; 95% CI 1.0 to 1.2).. In alert warfarinised patients following head injury, the presence of symptoms is associated with greater risk of adverse outcome. Those with GCS=15 and no symptoms are a substantial group and have a low risk of adverse outcome.. NCT02461498.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amnesia; Anticoagulants; Brain Injuries, Traumatic; Emergency Service, Hospital; Female; Glasgow Coma Scale; Head Injuries, Closed; Headache; Humans; Male; Middle Aged; Risk Factors; Tomography, X-Ray Computed; Unconsciousness; Vomiting; Warfarin; Young Adult

Sepsis is a syndrome of life-threatening organ dysfunction caused by a dysregulated host response to infection. It can have devastating consequences, including bilateral adrenal hemorrhage, particularly in patients at high thrombotic risk, such as those with antiphospholipid syndrome and those on long-term anticoagulation.. A 49-year-old white woman re-presented to hospital with a history suggestive of sepsis. She had a medical background of primary antiphospholipid syndrome on lifelong warfarin. Ten days prior to this presentation, she had been hospitalized following Escherichia coli bacteremia, commenced on intravenous antibiotics, and discharged 2 days later with a prescribed 5-day course of oral amoxicillin. On readmission, she had ongoing fever, myalgia, malaise, and hypotension. Investigations revealed anemia with thrombocytopenia, hyponatremia, and acute-on-chronic kidney injury. Despite treatment for urosepsis, she became tachypneic, clammy, light-headed, drowsy, and hypothermic. Computed tomography revealed bilateral adrenal hemorrhage, and biochemical examination confirmed hypoadrenalism. Following discharge, she had persistent renal and hepatic injury lasting 3 months.. Early identification, intensive monitoring, and aggressive support may reduce the acquired thrombotic risk and avoid potentially life-threatening outcomes of sepsis.

Topics: Abdominal Pain; Adrenal Gland Diseases; Adrenal Glands; Adrenal Insufficiency; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antiphospholipid Syndrome; Diarrhea; Escherichia coli; Female; Hemorrhage; Humans; Hydrocortisone; Middle Aged; Sepsis; Tomography, X-Ray Computed; Treatment Outcome; Vomiting; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Facial Dermatoses; Female; Humans; International Normalized Ratio; Purpura; Vomiting; Warfarin

Better identification and triage of acute posterior circulation (PC) stroke patients is needed as the PC ischemic stroke (IS) patients may be allowed longer thrombolysis window than anterior circulation (AC) IS patients and PC patients with hemorrhagic stroke (ICH) may require care in a neurosurgical unit possibly remote from stroke unit.. Consecutive stroke patients treated at a tertiary center with thrombolysis (100% for IS) and/or comprehensive stroke unit care.. Altogether, 1641 patients had AC (75%) and 553 PC strokes. The PC-IS patients were younger (65 vs 70), had less often prior hypertension (51 vs 61%), and were twice more often on warfarin. They presented 3.5 times more often with seizure, vomited five times more often, had headache twice as often, and required intubation 2 to 3 times more often despite equal NIHSS (9 vs 8) or GCS (15 both) scores with AC-IS patients. Among PC patients, IS (n = 190) associated with younger age, prior atrial fibrillation (AF) in 25% and dyslipidemia in ~40%. One-third of PC-ICH patients (n = 363) had headache and vomited at the onset. PC-ICH patients had BP median of 177/92 mmHg and blood glucose 7.4 mmol/l on ER arrival. Warfarin use was twice as common in PC-ICH.. Despite being of typical age for multiple cardiovascular conditions the PC-ICH patients less often have a previous history of AF or dyslipidemia than IS patients do. The vomiting PC-ICH patient with hypertensive BP values often has headache and a red flag for hemorrhage is warfarin treatment.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Infarction; Female; Headache; Humans; Male; Middle Aged; Vomiting; Warfarin

To report a case of prolonged vomiting during warfarin therapy, leading to an elevated international normalized ratio (INR).. A 32-year-old female with a history of cyclic vomiting syndrome since early childhood and bilateral pulmonary emboli diagnosed 4 months prior to this acute event presented to the clinic for routine monitoring of warfarin therapy. The warfarin dose had been maintained at 35 mg/wk for 3½ months (INR 2-3.5), but it was increased to 37.5 mg/wk because the INR had trended down to the low goal range over the preceding month. At presentation, the patient reported a 15-day history of vomiting with minimal oral intake that required intravenous fluids to prevent dehydration. The INR was 4.7; warfarin was withheld, and oral vitamin K 5 mg as well as subcutaneous vitamin K 10 mg was administered the following day. The INR then decreased to 1.3. Therapy was transitioned to subcutaneous enoxaparin 1 mg/kg every 12 hours for the duration of the patient's anticoagulation therapy.. Multiple reports have demonstrated malabsorption of warfarin and decreased INR response in the presence of underlying gastrointestinal disease. Despite a prolonged episode of cyclic vomiting syndrome, our patient had an elevated INR. In normal circumstances, warfarin is rapidly absorbed from the gastrointestinal tract and reaches maximum serum concentrations in approximately 90 minutes. Studies have shown that although the presence of food does not affect overall absorption of the medication, it can decrease the rate of absorption. Our patient was vomiting 20-30 minutes after oral dose administration. Because the patient was not consuming food, absorption of warfarin was potentially prompt, thus contributing to the elevated INR. The variability of vitamin K in the diet also can have significant impact on the response to warfarin. Our patient's INR had been stable while she consumed 3 servings each week of foods rich in vitamin K. This consumption was abruptly discontinued with the onset of the cyclic vomiting syndrome. We believe that decreased intake and retention of oral vitamin K-containing foods from the diet due to the prolonged vomiting coupled with the rapid onset of absorption resulted in a notably increased INR and subsequent bruising in our patient.. In the presence of prolonged vomiting, warfarin therapy requires more frequent monitoring than usual to detect fluctuations in INR that may increase the risk of adverse events.

Topics: Adult; Female; Humans; International Normalized Ratio; Risk Factors; Time Factors; Vitamin K; Vomiting; Warfarin

We sought to identify contributors to unstable anticoagulation in African Americans.. Sixty African Americans on warfarin were enrolled. Cytochrome P450 2C9 and vitamin K epoxide reductase genotypes and vitamin K intake were assessed, and clinical and dietary data during the 12 months prior to enrollment were collected. Data were compared between stable and unstable patients, classified based on the proportion of international normalized ratio (INR) values outside the therapeutic range.. The median proportion of out-of-range INRs among study participants was 44%; 28 patients had a higher proportion of INRs out-of-range and were included in the unstable group, with the remaining constituting the stable group. The median (IQR) number of clinic visits/year was higher among unstable versus stable patients [18 (15-22) vs. 16 (13-19); P = 0.03]. Higher warfarin doses, lower adherence, vomiting or diarrhea, and use of antiinfective agents were more common among unstable patients. Genotype was not associated with anticoagulation stability. After regression analysis, only poor adherence and gastrointestinal illness remained predictive of unstable anticoagulation. In a control group of Caucasians of similar age and sex distribution, poor adherence, but not gastrointestinal illness, was associated with unstable anticoagulation.. We conclude that poor warfarin adherence and gastrointestinal illness are major contributors to unstable anticoagulation in African Americans. Our data suggest that, similar to Caucasians, improving warfarin adherence rates may be an important mean to improve anticoagulation control in African Americans. In addition, close monitoring during acute illness may be particularly important in this population.

Topics: Aged; Anticoagulants; Black or African American; Female; Follow-Up Studies; Humans; International Normalized Ratio; Male; Middle Aged; Mixed Function Oxygenases; Patient Compliance; Predictive Value of Tests; Retrospective Studies; Vitamin K Epoxide Reductases; Vomiting; Warfarin

Topics: Adenosine Diphosphate; Adult; Anticoagulants; Blood Platelet Disorders; Diagnosis, Differential; Dizziness; Epinephrine; Female; Humans; Platelet Aggregation; Syndrome; Thromboembolism; Vertigo; Vomiting; Warfarin

A 35-year-old healthy male with no history of any past medical illness developed severe headache, vomiting and drowsiness while at high altitude (4,572 m) in the eastern Himalayan ranges. He was evacuated to a tertiary-care hospital where he was diagnosed to have cerebral sinus venous thrombosis (CSVT) on magnetic resonance imaging, with deep vein thrombosis (DVT) of his right popliteo-femoral vein on color Doppler study. Investigation for thrombophilia revealed protein S (PS) deficiency in this patient. Family screening revealed low levels of PS in two elder brothers. One brother had a history of 'stroke in young' at the age of 20 years with the other being asymptomatic. This established the hereditary nature of PS deficiency. We are not aware of any previously published report on hereditary PS deficiency combined with CSVT and DVT occurring at high altitude. However, 1 case of protein C deficiency with CSVT has been reported previously.

Topics: Acclimatization; Adult; Altitude Sickness; Anticoagulants; Anticonvulsants; Cerebral Infarction; Family Health; Hemiplegia; Humans; Male; Military Personnel; Papilledema; Protein S Deficiency; Radiography; Recurrence; Sinus Thrombosis, Intracranial; Thrombophilia; Thrombophlebitis; Ultrasonography; Vomiting; Warfarin