Adult: Initially: 2-4 mg daily for 2 days. Alternatively, 6 mg on the 1st day as loading dose, followed by 4 mg on the 2nd day. Subsequent dose adjusted according to response. Maintenance: 1-8 mg daily. Administer at the same time each day. Elderly: Reduce dose if necessary.
Haemorrhagic diathesis and blood dyscrasia (e.g. haemophilia, thrombocytopenic purpura, leukaemia), peptic ulcer or haemorrhage of the GI tract, urogenital tract or resp system; cerebrovascular haemorrhage, acute pericarditis, pericardial effusion, infective endocarditis, severe HTN. Recent or potential surgery of the eyes/CNS. Recent surgery resulting in increased fibrinolytic activity (e.g. surgery of the lung, prostate, uterus). Uncooperative patient (e.g. unsupervised senile, alcoholic, psychotic, w/ dementia). Severe hepatic and renal impairment. Pregnancy.
Patient w/ severe heart failure, known or suspected protein C or S and vit K deficiency. Mild to moderate hepatic and renal impairment. Elderly. Lactation.
Determine prothrombin time (PT)/INR (daily or on alternate days in early days of treatment, then at longer intervals depending on response). Monitor CBC, hepatic and renal function.
Symptoms: Haemorrhage, haematemesis, haemoptysis, haematuria (w/ renal colic), haematoma, menorrhagia, GI and cutaneous haemorrhage, vaginal, gingival, joint, and nose bleeding; tachycardia, hypotension, peripheral circulatory disorder, nausea, vomiting, diarrhoea, abdominal pain, high PT/INR value, prolonged thromboplastin time. Management: Oral vit K1 (phytomenadione) may be given for moderate to severe haemorrhage. Administer fresh blood/frozen plasma, complex concentrate/recombinant factor VIIa supplemented w/ vit K1 for severe and life-threatening haemorrhage.
Increased effect w/ antiarrhythmics (e.g. amiodarone, quinidine), antibiotics (e.g. broad spectrum antibiotics, tetracyclines, chloramphenicol), antifungal (e.g. metronidazole), SSRIs (e.g. citalopram, fluoxetine, sertraline, paroxetine), antigout (e.g. allopurinol), lipid-regulating drugs (e.g. atorvastatin, fluvastatin, simvastatin), and inhibitors of CYP2C9 isoenzyme. Reduced anticoagulant effect w/ antineoplastics (e.g. azathioprine, 6-mercaptopurine), antivirals (e.g. ritonavir, nelfinavir), thiazide diuretics, oral contraceptives, and inducers of CYP2C9, CYP2C19, and CYP3A4 isoenzymes. May increase the serum hydantoin concentration of phenytoin. May potentiate the hypoglycaemic effect of sulphonylurea derivatives (e.g. glibenclamide, glimepiride). Potentially Fatal: Increased risk of haemorrhage w/ other anticoagulants (e.g. warfarin, heparin, LMWH), antiplatelets (e.g. dipyridamole, clopidogrel, ticlopidine), antibiotics (e.g. clindamycin), analgesics (e.g. salicylates, pyrazolone derivatives, COX-2 inhibitors), high dose IV methylprednisolone.
Reversed anticoagulant effect w/ foods high in vit K (e.g. beef and pork liver, green tea, green leafy vegetables). Increased metabolism and reduced PT/INR w/ chronic alcohol consumption; conversely, acute ingestion reduces metabolism and increases PT/INR. Increased INR and may cause severe bleeding w/ cranberry juice. Reduced effect w/ St. John’s wort.
Description: Acenocoumarol, a coumarin derivative, is a vitamin K-epoxide-reductase complex 1 (VKORC1) antagonist, depleting functional vit K reserves, thus, reducing the synthesis of coagulation factors II (prothrombin), VII, IX, and X, as well as proteins C and S. It also reduces γ-carboxylation of certain glutamic acid molecules, important for blood clotting initiation. Pharmacokinetics: Absorption: Rapidly absorbed from the GI tract. Bioavailability: 60%. Time to peak plasma concentration: 1-3 hr. Distribution: Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 0.16-0.34 L/kg. Plasma protein binding: 99%, mainly to albumin. Metabolism: Both S- and R- isomers are metabolised in the liver by CYP2C9 isoenzyme via oxidation; R-isomer is also metabolised by CYP1A2 and CYP2C19. Undergoes nitro-reduction by gut flora. Excretion: Via urine (approx 60%, as inactive metabolites) and faeces (29%, as metabolites). Elimination half-life: 8-11 hr.