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Indications and Dosage
Oral
Thromboembolic disorders Adult: Initially, 200 mg on day 1 followed by 100 mg on day 2. From day 3, adjust dose according to coagulation tests. Maintenance: 50-150 mg daily (resistant patients may require ≥200 mg daily while sensitive patients may require <50 mg daily).
Elderly: Dosage reduction may be needed. |
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Renal Impairment
Severe: Contraindicated.
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Hepatic Impairment
Severe: Contraindicated.
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Contraindications
Hypersensitivity. Significant bleeding, haemorrhagic conditions (e.g. haemorrhagic stroke), bacterial endocarditis, uncontrolled HTN; w/in 48 hr postpartum. Severe renal and hepatic impairment. Pregnancy and lactation. Concomitant use of fibrinolytic agents.
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Special Precautions
Patient w/ risk factors for bleeding (e.g. risk of falling, cerebrovascular disease, serious heart disease, anaemia, malignancy, trauma); genetic variability in relation to VKORC1, recent ischaemic stroke, previous GI bleeding, active peptic ulcers, hyper- or hypothyroidism, acute illnesses; wt loss/gain, protein C or S deficiency, hyperphosphataemia, hypercalcaemia, hypoalbuminaemia. Patient undergoing surgery. Mild to moderate renal impairment. Elderly.
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Adverse Reactions
Significant: Hypersensitivity reactions (including fever, lymphadenopathy, agranulocytosis, eosinophilia, leukocytosis, pancytopenia, leukaemoid syndrome, diarrhoea, vomiting, jaundice, rash, alopecia, skin necrosis, exfoliative dermatitis, renal damage w/ tubular necrosis, albuminuria), haemorrhage. Rarely, calciphylaxis.
Nervous: Cerebral haemorrhage, cerebral subdural haematoma. CV: Haemorrhage. GI: GI haemorrhage, rectal haemorrhage, haematemesis, pancreatitis, dysgeusia, nausea, melaena. Resp: Haemothorax, epistaxis. Hepatic: Hepatitis. Genitourinary: Pink- or orange- coloured urine, haematuria. Haematologic: Decreased hematocrit, decreased Hb; leucopenia. Dermatologic: Purpura, blue toe syndrome, ecchymosis, exanthema. |
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Monitoring Parameters
Regularly monitor prothrombin time and assess the need for therapy.
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Overdosage
Symptoms: Spontaneous bruising, haematomas, haematuria, rectal bleeding, haemorrhage into any internal organ. Management: Give activated charcoal if ingestion is recent (w/in 1 hr) and ingested amount is >0.25 mg/kg or more than the patient’s therapeutic dose. If prothrombin time is prolonged w/ no active bleeding, give vit K 0.5-1 mg by slow IV infusion. If w/ active bleeding, give fresh frozen plasma and vit K 1 mg by slow IV infusion. If w/ life threatening haemorrhage, give fresh frozen plasma or factor concentrate.
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Drug Interactions
Risk of haemorrhage w/ antineoplastics. antiplatelets, unfractionated heparins and heparin derivatives, LMWH, NSAIDs, SSRIs, SNRIs, bivalirudin, clofibrate, dipyridamole, eptifibatide, fondaparinux, miconazole, prostacyclin, sulfinpyrazone. May cause potentiated effect w/ ACTH, allopurinol, amiodarone, amitriptyline/nortriptyline, cimetidine, dextropropoxyphene, disulfiram, glucagon, phenformin, propafenone, thyroid compd, tolbutamide, zafirlukast, broad spectrum antibacterials, steroids, OCs. Antagonised effect w/ barbiturates, carbamazepine, griseofulvin, phenytoin. Decreased absorption w/ cholestyramine, sucralfate.
Potentially Fatal: Significantly increased risk of haemorrhage w/ fibrinolytic agents (e.g. streptokinase, alteplase). |
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Food Interaction
Reduced effects w/ ingestion of food rich in vit K.
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Action
Description:
Mechanism of Action: Phenindione is an indanedione anticoagulant. It antagonises the effects of vitamin K and interferes w/ the formation of clotting factors II, VII, IX and X. Onset: 36-48 hr. Duration: 48-72 hr. Pharmacokinetics: Absorption: Rapidly and completely absorbed from the GI tract. Time to peak plasma concentration: 1-3 hr. Distribution: Crosses placenta and enters breast milk. Excretion: Via urine (as metabolites). |
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Chemical Structure
 Source: National Center for Biotechnology Information. PubChem Database. Phenindione, CID=4760, https://pubchem.ncbi.nlm.nih.gov/compound/Phenindione (accessed on Jan. 22, 2020) |
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ATC Classification
B01AA02 - phenindione ; Belongs to the class of vitamin K antagonists. Used in the treatment of thrombosis.
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References
Buckingham R (ed). Phenindione. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. ttps://www.medicinescomplete.com. Accessed 17/10/2017. Dindevan 25 mg Tablets (Mercury Pharma Group Ltd). MHRA. https://products.mhra.gov.uk/. Accessed 23/11/2017. Joint Formulary Committee. Phenindione. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 17/10/2017.
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