Acenocoumarol and phenytoin toxicity in the presence of CYP2C9 mutation.
This case report describes a rare interaction between therapeutic doses of phenytoin and acenocoumarol resulting in both acute phenytoin toxicity and increased international normalized ratio (INR). Interactions between these drugs are due to the pharmacokinetics and the common metabolising pathway by hepatic cytochrome P450 isoenzyme-CYP2C9. Our patient was detected to be homozygous for CYP2C9*3 by PCR-RFLP analysis resulting in markedly decreased metabolism of both the drugs. Given that these two drugs are often given concomitantly in the medical out patient department, and that CYP2C9 polymorphisms are not uncommon, clinicians should be aware of this interaction and suspect this in patients with toxicity to these drugs.
Jose
Linda
L
Department of Pharmacology, Christian Medical College, Vellore, Tamil Nadu.
Binila
Chacko
C
Chandy
S J
SJ
Mathews
J E
JE
Mathews
K P
KP
D000074:Acenocoumarol / Q000009:adverse effects*; D000328:Adult; D000925:Anticoagulants / Q000009:adverse effects*; D000927:Anticonvulsants / Q000506:poisoning*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004347:Drug Interactions; D005260:Female; D006801:Humans; D009154:Mutation; D010597:Pharmacogenetics; D010672:Phenytoin / Q000506:poisoning*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011250:Pregnancy Complications, Hematologic / Q000517:prevention & control; D012640:Seizures / Q000188:drug therapy
D000925:Anticoagulants; D000927:Anticonvulsants; D010672:Phenytoin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000074:Acenocoumarol