Doxycycline Phenytoin

DOXYCYCLINE ANTIEPILEPTICS -BARBITURATES, CARBAMAZEPINE, PHENYTOIN i doxycydine levels, with risk of therapeutic failure Induction of hepatic metabolism Monitor for i clinical efficacy and t dose as required... 

Doxycycline at recommended doses does not accumulate significantly in patients with renal failure and thus is one of the safest of the tetracyclines for use in patients with renal impairment. The drug is excreted in the feces. Its half-life may be significantly shortened by concurrent therapy with barbiturates, phenytoin, rifampin, or other inducers of hepatic microsomal enzymes. 

The serum levels of doxycycline are reduced and may fall below the accepted minimum inhibitory concentration in patients receiving long-term treatment with barbiturates, phenytoin or car-bamazepine. Other tetracyclines do not appear to be affected. 

A study in 14 patients taking phenytoin 200 to 500 mg daily, car-bamazepine 300 mg to 1 g daily, or both, found that the half-life of doxycycline was approximately halved from 15.1 hours in patients not taking antiepilepties, to 7.2 hours in patients taking phenytoin, 8.4 hours in patients taking carbamazepine, and 7.4 hours in patients taking both drugs. ... 

Similar results were found in 16 other patients taking various combinations of phenytoin, carbamazepine, primidone or phenobarbital. The serum doxycycline levels of almost all of them fell below 0.5 micrograms/mL during the 12 to 24 hour period following their last dose of doxycycline 100 mg. Tetracycline, methacycline, oxytetracycline, demeclocycline and chlortetracycline levels were not significantly affected by these antiepilepties. Other studies confirm this interaction between some barbiturates (amobarbital, pentobarbital, phenobarbital) and doxycycline. ... 

Carbamazepine levels are increased by CYP3A4 inhibitors (cimetidine, macrolides, diltiazem, fluoxetine, ketoconazole, verapamil, valproate) levels are decreased by CYP3A4 inducers (cisplatin, doxorubicin, felbamate, phenobarbital, phenytoin, primidone, rifampin, theophylline). Carbamazepine may increase levels of clomipramine, phenytoin, and primidone and lithium toxicity may decrease levels of phenytoin, warfarin, oral contraceptives, doxycycline, theophylline, haloperidol, alprazolam, clozapine, ethosuximide, and valproate may interfere with other anticonvulsants. 

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