Nicoumalone (Acenocoumarol)

Indications

Nicoumalone (Acenocoumarol) is used for: Thromboembolic disorders

Adult Dose

Oral Thromboembolic disorders 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. Hepatic impairment: Severe: Contraindicated.

Child Dose

Renal Dose

Renal impairment: Severe: Contraindicated.

Administration

Contra Indications

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.

Precautions

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. Monitoring Parameters 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.

Pregnancy-Lactation

Interactions

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.

Adverse Effects

Side effects of Nicoumalone (Acenocoumarol) : Rarely, urticaria, rash, dermatitis, purpura, skin necrosis; fever, decreased appetite, nausea, vomiting, diarrhoea; alopecia; hepatic dysfunction, jaundice, pancreatitis; purple toe syndrome. Potentially Fatal: Haemorrhage.

Mechanism of Action

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.