Coumarins systemic

Author:Prof. Dr. med. Peter Altmeyer

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Last updated on: 12.11.2021

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Synonym(s)

Coumarin derivatives; Phenprocoumon; Vitamin K antagonists

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DefinitionThis section has been translated automatically.

Coumarins are vitamin K antagonists (see also Cumnarin general). The basic structure is the 4-hydroxycoumarin, variants derived from it are the dicumarins like:

  • Dicumarol
  • Tromexan

and the monocoumaroles such as:

  • Coumar
  • Coumarin (warfarin)
  • Sintron

Coumarins are almost completely resorbed enterally. The plasma protein binding is >90%. The half-life for Marcumar is 6-7 days, for Warfarin 33-45 hours. Vitamin K antagonists (VKA) were the cornerstone of anticoagulation therapy for over 50 years before newer agents, the non-vitamin K-dependent oral anticoagulants (NOAK), became available for clinical use.

IndicationThis section has been translated automatically.

Recurrence prophylaxis after thromboses and embolisms.

Limited indicationThis section has been translated automatically.

Abortus imminens, alcoholism, age > 65 years, epilepsy, angiography, blood formation disorders, severe diabetes, decompensated heart failure, pericardial effusion, vasculitis.

Dosage and method of useThis section has been translated automatically.

See Table 1.

Undesirable effectsThis section has been translated automatically.

Remember!

Bleeding complications (antidote: vitamin K 20 mg/day p.o., in case of life-threatening bleeding: 2.000 IU prothrombin complex as short infusion i.v., repeated every 6-8 hours over 48 hours as well as vitamin K 20 mg/day p.o. until the quick value is stabilized). Also: Allergic reactions, pruritus, hair loss, coumarin necrosis, toxic liver damage, intestinal necrosis.

InteractionsThis section has been translated automatically.

See Table 1.

ContraindicationThis section has been translated automatically.

Pregnancy (chondrodysplasia), lactation, aneurysms, bleeding tendency, chronic inflammatory intestinal diseases, florid endocarditis lenta, brain injuries, hypertension (> 180 mm Hg systolic or 105 mm Hg diastolic), visceral carcinomas, leukaemia with bleeding tendency, cavernous pulmonary tuberculosis, ulcers ventriculi or duodeni, manifest renal insufficiency, kidney stones, surgery on CNS, eye, prostate, retinopathy with risk of bleeding, apoplexy, thrombocytopenic purpura, severe thrombocytopenia, open wounds.

PreparationsThis section has been translated automatically.

Marcumar, Phenpro-ratiopharm, Coumadin

Note(s)This section has been translated automatically.

Remember! For therapy control determination of the Quick- or INR-value every 3-4 weeks!

PatientinformationThis section has been translated automatically.

Remember! All patients who receive coumarins should carry an identification card with the daily dose and the quick values (INR values). Patients should be informed in detail about foods that contain a particularly high proportion of vitamin K (antagonizes coumarin effect) and avoid these foods!

TablesThis section has been translated automatically.

Major interactions of coumarins

Allopurinol

Bleeding tendency ↑

Anion exchange resins

Coumarin effects ↓

Antirheumatic agents, nonsteroidal

Bleeding tendency ↑, risk of hemorrhagic peptic ulcers

Barbiturates

Coumarin effect ↓

Benzodiarone

Bleeding tendency ↑

Carbamazepine

Coumarin effect ↓

Cephalosporins

Bleeding tendency ↑

Ciclosporin A

Coumarin effect ↓

Cimetidine

Bleeding tendency ↑ with warfarin

Ergotamine

Bleeding tendency ↑

Fibrates

Bleeding tendency ↑

Fibrinolytics

Bleeding tendency ↑

Heparin

Bleeding tendency ↑

Contraceptives, oral

Coumarin effect ↓

Food

Coumarin effect ↓ due to broccoli, beetroot, avocado

Penicillins i.v.

Bleeding tendency ↑

Thyroid hormones

Bleeding tendency ↑

Sulfonylureas

Hypoglycemia

Valproic acid

Bleeding tendency ↑

Major coumarins, dosage, pharmacology.

Substance

HWZ

Dosage

Preparation

Phenprocoumon

160 hrs.

Initial: Day 1: 6-18 mg; Day 2: 6-12 mg. From day 3 dosage based on INR/Quick value: Quick > 30%: Up to 4.5 mg; Quick 20-30%: Max. 1.5 mg.

Marcumar

Maintenance dose: 1.5-6 mg/day

Warfarin

42 hr.

2.5-10 mg/day for 2-4 days

Coumadin

Maintenance dose: 2-10 mg/day (based on Quick/INR)

The dosage must be monitored and individually adjusted by determining the thromboplastin time (INR/Quick value); the initial determination must always be made before the start of treatment! The aim is to achieve an effective range of INR 2.0-3.5 or a Quick value of 15-30% of the norm, depending on the type of disease. Daily monitoring of therapy using the INR method. INR values to aim for: Treatment of deep vein thrombosis, pulmonary embolism, thromboembolism with atrial fibrillation: 2.0-3.0. In the case of recurrent deep vein thrombosis, pulmonary embolism, arterial diseases including myocardial infarction: In patients with a high risk of thromboembolism, it may be necessary to aim for a higher INR value. However, an INR value > 4.0 does not provide any additional therapeutic benefit.

Vitamin K content of important foods

100 g contain

Vitamin K (mg)

Prohibited foods

Broccoli

0,2

Kale, fresh

0,7

Cabbage, fresh (savoy, rose, flower, kale)

0,2

Liver (cod, codfish)

0,1

Liver (beef, ox, sheep, veal)

0,3

Muscle (beef, sheep, pork)

0,2

Salad, fresh

0,1

Asparagus, fresh

0,4

Spinach, fresh

0,4

Allowed food

Bananas

0,002

Peas, beans

0,02

Strawberries, rose hips

0,01

Chicken egg, whole

0,05

Potatoes

0,05

Cow's milk

0,004

Liver (pork)

0,03

Tomatoes

0,008

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Last updated on: 12.11.2021