Halothane Phenytoin

Allopurinol, amoxicillin/clavulanic acid, dicloxacillin, erythromycin derivatives, halothane, phenytoin, and trimethoprim/sul-famethoxazole... 

A4 34.1 Acetaminophen, caffeine carbamazepine, codeine, cortisol, erythromycin, cyclophosphamide, (S)-and (R)-warfarin, phenytoin, testosterone, halothane, zidovudine... 

Acute hepatocellular necrosis. This reaction varies from a transient disturbance of liver function tests to acute hepatitis. It can be induced by several drugs including general anaesthetics (halothane), antiepileptics (carbamazepine, phenytoin, sodium valproate, phenobarbital), antidepressants (MAO inhibitors), antiinflammatory drugs (indomethacin, ibuprofen), antimicrobials (isoniazid, sulphonamides, nitrofurantoin) and cardiovascular drugs (methyldopa, hydralazine). 

Clinically important, potentially hazardous interactions with acetazolamide, aminoglycosides, anticholinesterases, bambuterol, calcium channel blockers, chloroquine, chlorpromazine, clindamycin, d-pencillamine, ecothiophate iodine, enflurane, furosemide, halothane, hexomethonium, isoflurane, ketamine, lidocaine, lincomycin, lithium salts, magnesium salts, mannitol, MAO inhibitors, organophosphates, pancuronium, phenytoin, polymyxins, procainamide, quinidine, sevoflurane, spectinomycin, tetracyclines... 

Halothane, enflurane, and isoflurane potentiate the activity of doxacurium, and phenytoin and carbamazepine shorten the duration of doxacurium block. 

Phenytoin toxicity occurred in a child following halothane anaesthesia. A near fatai hepatic reaction occurred in a woman given rifampicin (rifampin) after haiothane anaesthesia, and hepatitis occurred in a patient taking phenobarbitai who was given halothane anaesthesia. See aiso Anaesthetics, generai H- Isoniazid , p.lOO and Anaesthetics, general Methoxyflurane H- Antibacterials or Barbiturates , p.l07. 

A 10-year-old girl receiving long-term treatment with phenytoin 300 mg daily was found to have phenytoin plasma levels of 25 micrograms/mL before surgery. Three days after anaesthesia with halothane her plasma phenytoin levels had risen to 41 micrograms/mL and she had marked signs of phenytoin toxicity. ... 

It seems possible that the general adverse hepatotoxic effects of halothane can slow the normal rate of phenytoin metabolism. One suggested explanation for the increased adverse effects on the liver is that, just as in animals, pre-treatment with phenobarbital and phenytoin increases the rate of drug metabolism and therefore the hepatotoxicity of halogenated hydrocarbons, including carbon tetrachloride and halothane. As well as increased metabolism, the halothane-rifampicin interaction might also involve additive hepatotoxicity. 

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