phenprocoumon and Obesity

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

Initiation of phenprocoumon therapy is associated with a variable individual response. The CYP2C9 genotype has been shown to influence the response to warfarin therapy, but such an effect on phenprocoumon therapy remains uncertain.. Two hundred sixty hospital patients started on phenprocoumon were recruited for this study. Body mass index (BMI), waist and hip circumference, dietary habits, comorbidity, and comedication were initially assessed. A 5' exonuclease assay (TaqManR) was used to analyze the presence of five polymorphisms of the CYP2C9 gene in each of the study patients. Study endpoints included the time necessary to achieve the international normalized ratio (INR) target (INR >2) and the total drug amount required to attain target INR. For 250 of 260 patients, the subsequent required daily maintenance dose of phenprocoumon was also recorded.. Both the necessary time and total dose required to attain target INR correlated significantly with BMI. The leaner the patient, the shorter the required time interval [BMI <22 (n=31), 5.48+/-2.49 days; BMI 22-25 (n=70), 6.09+/-2.40; BMI 25-30 (n=113), 6.76+/-3.61; BMI >30 (n=46), 8.50+/-5.75; p=0.001] and the lower the required dosage until the therapeutic range was achieved [BMI <22 (n=31), 23.8+/-12.1 mg; BMI 22-25 (n=70), 25.9+/-11.4 mg; BMI 25-30 (n=113), 29.6+/-25.2; BMI >30 (n=46), 35.8+/-19.7; p=0.027]. Overweight and waist circumference as a surrogate marker for abdominal fat were also associated significantly with these two parameters. Moreover, obesity was associated with a lower body-weight-adjusted maintenance dosage. All CYP2C9 genotypes that were tested failed to reveal an association with individual response variability.. Patient obesity appears to directly correspond to the amount of phenprocoumon required during initiation of therapy. The CYP2C9 genotype was not shown to influence the necessary therapeutic dosage.

Topics: Aged; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Body Mass Index; Cytochrome P-450 CYP2C9; Female; Genotype; Humans; International Normalized Ratio; Male; Middle Aged; Obesity; Phenprocoumon; Prospective Studies; Sex Characteristics; Vitamin K

In three patients painful reddening of a well-circumscribed area of the skin occurred within five days of starting anticoagulant treatment with phenprocoumon (Marcumar), and within a short time it developed into a full-blown picture of coumarin necrosis. The indication for phenprocoumon was, in the first patient (a 29-year-old mother lying-in after her second child had been born) an increased platelet count and the presence of high risk factors for thromboembolism. In the second patient (25-year-old man) and the third one (45-year-old woman) it was secondary prophylaxis after pulmonary embolus and deep-vein thrombosis, respectively. All three patients were very obese and had a drug allergy, as well as other allergies (bronchial asthma in Cases 1 and 2; allergic rhinitis in Case 3). Phenprocoumon was at once discontinued in all three patients and low-dose heparin administration (Cases 1 and 3) or dextran infusion (Case 2: heparin intolerance) started. All three needed excision of the necrotic tissue with grafting to the skin defect. The coexistence of obesity and allergic diathesis may thus present an especially high risk for coumarin necrosis.

Topics: Adult; Coumarins; Drug Hypersensitivity; Drug Therapy, Combination; Female; Heparin; Humans; Middle Aged; Necrosis; Obesity; Phenprocoumon; Pulmonary Embolism; Risk Factors; Skin Diseases; Thrombophlebitis; Time Factors

A case of primary vascular pulmonary hypertension (PVPH) in a 53-year old woman (160 cm, 90 kg) is reported. She first complained of symptoms of breathlessness on exertion 2-3 months after completion of three courses of fenfluramine (Ponderax). The courses began in October 1977 and ended in May 1978. Despite persisting symptoms no relevant clinical findings were obtained. The patient was admitted to this hospital after complaining of short syncopal attacks on exertion, in November 1981. Typical signs of PVPH were now demonstrable, with a resting pulmonary pressure of 98/45 mm Hg. Clinical findings showed a similarity to those obtained in patients suffering from aminorex-induced PVPH, although fenfluramine shows some biological differences to aminorex. A causality between the development of PVPH and fenfluramine intake is probable on the basis of the patient's history, but it cannot be proven.

Topics: Chronic Disease; Female; Fenfluramine; Humans; Hypertension, Pulmonary; Middle Aged; Nifedipine; Obesity; Phenprocoumon; Syncope