phenprocoumon and fluindione

The purpose of this review article is to summarize the literature on diseases that are documented to have an effect on response to warfarin and other VKAs.. We searched the English literature from 1946 to September 2015 via PubMed, EMBASE, and Scopus for the effect of diseases on response vitamin K antagonists including warfarin, acenocoumarol, phenprocoumon, and fluindione.. Among many factors modifying response to VKAs, several disease states are clinically relevant. Liver disease, hyperthyroidism, and CKD are well documented to increase response to VKAs. Decompensated heart failure, fever, and diarrhea may also elevate response to VKAs, but more study is needed. Hypothyroidism is associated with decreased effect of VKAs, and obese patients will likely require higher initial doses of VKAs.. In order to minimize risks with VKAs while ensuring efficacy, clinicians must be aware of the effect of disease states when prescribing these oral anticoagulants.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Cardiovascular Diseases; Diarrhea; Fibrinolytic Agents; Heart Failure; Humans; Hyperthyroidism; Kidney Failure, Chronic; Liver Diseases; Obesity; Phenindione; Phenprocoumon; Vitamin K; Warfarin

Numerous factors are well documented to affect the response to vitamin K antagonists (VKA), including dietary vitamin K, other drugs, age, pharmacogenetics, and disease states. Body weight is perhaps not as well known as a variable affecting VKA dose. Our aim was to review the literature regarding body weight and VKA dose requirements.. We reviewed the English-language literature via PubMed and Scopus using the search terms VKA, warfarin, acenocoumarol, phenprocoumon, fluindione, AND body weight.. Among 32 studies conducted since the widespread use of the international normalized ratio, 29 found a correlation with body weight or body surface area and VKA dose requirement. Warfarin was evaluated in 27 studies and acenocoumarol, phenprocoumon, or fluindione were assessed in 5 investigations.. Because of varying study methodologies, further study is warranted. Based on current evidence, clinicians should include body weight, along with other established variables when dosing VKA. Most important, obese and morbidly obese patients may require a 30% to 50% increase with the initial dosing of VKA.

Topics: Acenocoumarol; Anticoagulants; Body Weight; Comorbidity; Drug Dosage Calculations; Humans; Obesity; Obesity, Morbid; Phenindione; Phenprocoumon; Vitamin K; Warfarin

Due to improved implementation of guidelines, new scoring approaches to improve risk categorisation, and introduction of novel oral anticoagulants, medical management of patients with atrial fibrillation (AF) is continuously improving. The PREFER in AF registry enrolled 7,243 consecutive patients with ECG-confirmed AF in seven European countries in 2012-2013 (mean age: 71.5 ± 10.7 years; 60.1% males; mean CHA2DS2-VASc score: 3.4). While patient characteristics were generally homogeneous across countries, anticoagulation management showed important differences: the proportion of patients taking vitamin K antagonists (VKAs) varied between 86.0% (in France) and 71.4% (in Italy). Warfarin was used predominantly in the UK and Italy (74.9% and 62.0%, respectively), phenprocoumon in Germany (74.1%), acenocoumarol in Spain (67.3%), and fluindione in France (61.8 %). The major sites for international normalised ratio (INR) measurements were biology laboratories in France, anticoagulation clinics in Italy, Spain, and the UK, and physicians' offices or self-measurement in Germany. Temporary VKA discontinuation and bridging with other anticoagulants was frequent (at least once in the previous 12 months for 22.9% of the patients, on average; ranging from 29.7% in Germany to 14.9% in the UK). Time in therapeutic range (TTR), defined as at least two of the last three available INR values between 2.0-3.0 prior to enrolment, ranged from 70.3% in Spain to 81.4% in Germany. TTR was constantly overestimated by physicians. While the type and half-lives of VKA as well as the mode of INR surveillance differed, overall quality of anticoagulation management by TTR was relatively homogenous in AF patients across countries.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Europe; Female; Humans; Male; Middle Aged; Phenindione; Phenprocoumon; Practice Guidelines as Topic; Registries; Vitamin K; Warfarin; Withholding Treatment

Vitamin K antagonists (VKA) are known to act as teratogens; however, there is still uncertainty about the relative risk for birth defects and the most sensitive period. In a multi-centre (n = 12), observational, prospective study we compared 666 pregnant women exposed to phenprocoumon (n = 280), acenocoumarol (n = 226), fluindione (n = 99), warfarin (n = 63) and phenindione (n = 2) to a non-exposed control group (n = 1,094). Data were collected by institutes collaborating in the European Network of Teratology Information Services (ENTIS) during individual risk counselling between 1988 and 2004. Main outcome measures were coumarin embryopathy and other birth defects, miscarriage rate, birth-weight, and prematurity. The rate of major birth defects after 1st trimester exposure was significantly increased (OR 3.86, 95% CI 1.86-8.00). However, there were only two coumarin embryopathies (0.6%; both phenprocoumon). Prematurity was more frequent (16.0% vs. 7.6%, OR 2.61, 95% CI 1.76-3.86), mean gestational age at delivery (37.9 vs.39.4, p<0.001), and mean birth weight of term infants (3,166 g vs. 3,411 g; p < 0.001) were lower compared to the controls. Using the methodology of survival analysis, miscarriage rate reached 42% vs. 14% (hazard ratio 3.36; 95% CI 2.28-4.93). In conclusion, use of VKA during pregnancy increases the risk of structural defects and other adverse pregnancy outcomes. The risk for coumarin embryopathy is, however, very small, in particular when therapy during the 1(st) trimester did not take place later than week 8 after the 1(st) day of the last menstrual period. Therefore, elective termination of a wanted pregnancy is not recommended if (inadvertent) exposure took place in early pregnancy. Close follow-up by the obstetrician including level II ultrasound should be recommended in any case of VKA exposure during pregnancy.

Topics: Abnormalities, Drug-Induced; Abortion, Induced; Abortion, Spontaneous; Acenocoumarol; Adverse Drug Reaction Reporting Systems; Anticoagulants; Birth Weight; Female; Fetal Diseases; Gestational Age; Humans; Phenindione; Phenprocoumon; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Premature Birth; Prospective Studies; Vitamin K; Warfarin