Phenytoin with chloramphenicol

The effects of oral hypoglycemic drugs, oral anticoagulants, and phenytoin may be increased when administered with chloramphenicol. Fhenobarbital or rifampin may decrease chloramphenicol blood levels. 

Phenytoin interacts widi many different drugp. For example isoniazid, chloramphenicol, sulfonamides, benzodiazepines, succinimides, and cimetidine all increase phenytoin blood levels. The barbiturates, rifampin, theophylline, and warfarin decrease phenytoin blood levels. When administering the hydantoins with meperidine, die analgesic effect of meperidine is decreased. 

Incompatibilities Do not mix IV minocycline before or during administration with any solutions containing the following Adrenocorticotropic hormone (ACTH), aminophylline, amobarbital sodium, amphotericin B, bicarbonate infusion mixtures, calcium gluconate or chloride, carbenicillin, cephalothin sodium, cefazolin sodium, chloramphenicol succinate, colistin sulfate, heparin sodium, hydrocortisone sodium succinate, iodine sodium, methicillin sodium, novobiocin, penicillin, pentobarbital, phenytoin sodium, polymyxin, prochlorperazine, sodium ascorbate, sulfadiazine, sulfisoxazole, thiopental sodium, vitamin K (sodium bisulfate or sodium salt), whole blood. 

Drugs that may interact with zalcitabine include antacids, chloramphenicol, cisplatin, dapsone, didanosine, disulfiram, ethionamide, glutethimide, gold, hydralazine, iodoquinol, isoniazid, metronidazole, nitrofurantoin, phenytoin, ribavirin, vincristine, cimetidine, metoclopramide, amphotericin, aminoglycosides, foscarnet, antiretroviral nucleoside analogs, pentamidine, and probenecid. 

Only a few well-documented drug combinations with phenytoin may necessitate dosage adjustment. Coadministration of the following drugs can result in elevations of plasma phenytoin levels in most patients cimetidine, chloramphenicol, disulfiram, sulthiame, and isoniazid (in slow acetylators). Phenytoin often causes a decline in plasma carbamazepine levels if these two drugs are given concomitantly. 

Certain concomitantly administered drugs may interfere with the effectiveness of the oral contraceptives or lead to an increased incidence of breakthrough bleeding. These include rifampin, isoniazid, ampiciUin, neomycin, penicillin V, chloramphenicol, sulfonamides, nitrofurantoin, phenytoin, barbiturates, primidone, analgesics, and phenothiazines. 

Incompatibilities of metoclopramide depend on drug concentration, pH, and temperature. It is incompatible with cephalosporins, chloramphenicol, sodium bicarbonate, doxorubicin, cisplatin, and cyclophosphamide. Caution should be exercised with simultaneous administration of metoclopramide with lithium, sym-pathomimetics, antidepressants, bromocriptine, and carbamazepine. Omperazole interacts with tolbutamide, clarithromycin, and phenytoin. Coadministration of rantidine and cisapride increases the plasma concentration of rantidine. Abuse of senna laxative has been reported and may cause hepatitis.176-178... 

Another study eonfirmed that this interaction occurred in 20 neonates, but no statistically significant effect was found in 40 infants. Decreased chloramphenicol levels have been described in a single case report of a child who was also being treated with phenytoin and phenobarbital. The serum chloramphenicol levels were 35.1 micrograms/mL prior to the antiepileptics, 19.1 micrograms/mL after 2 days of phenytoin and 13.2 micrograms/mL a month after the addition of phenobarbital. For more information on the interaetion of ehloramphenieol with phenytoin see Phenytoin + Chloramphenieol , p.555. 

This interaction has been described in a number of other reports. " One study found that intravenous chloramphenicol more than doubled the half-life of phenytoin. The AUC of phenytoin after a single intravenous dose of fosphenytoin was 23% higher (not significant) in children also given intravenous chloramphenicol when compared with those given intravenous cefotaxime. In addition, the phenytoin half-life was significantly prolonged by chloramphenicol (23.7 hours versus 15.5 hours). - ... 

It seems probable that chloramphenicol, a known enzyme inhibitor, affects the liver enzymes (possibly cytochrome P450 isoenzyme CYP2C19 ) concerned -with the metabolism of phenytoin thereby reducing its rate of clearance from the body. The changes in the pharmacokinetics of chloramphenicol in children are not understood. 

The rise in serum phenytoin levels with intravenous chloramphenicol in adults is well documented and clinically important. A two to fourfold rise can occur within a few days. Concurrent use should be avoided unless the effects can be closely monitored and appropriate phenytoin dosage reductions made as necessary. The use of a single prophylactic dose of phenytoin or fosphenytoin may be an exception to this. It seems very doubtful if enough chloramphenicol is absorbed from eye drops or ointments for an interaction to occur. 

Koup JR, Gibaldi M, McNamara P, Hilligoss DM, Colburn WA, Bruck E. Interaction of chloramphenicol with phenytoin and phenobarbital. Clin Pharmacol Ther( 91 ) 24, 571-5. 

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