Phenytoin Antineoplastics

There is an increased risk for bone marrow suppression when levamisole or hydroxyurea are administered witii other antineoplastic dni. Use of levamisole witii phenytoin increases die risk of phenytoin toxicity. Pegaspargase may alter drug response of the anticoagulants. When procarbazine is administered with other central nervous system (CNS) depressants, such as alcohol, antidepressants, antihistamines, opiates, or the sedatives, an additive CNS effect may be seen. Procarbazine may potentiate hypoglycemia when administered witii insulin or oral antidiabetic dru . ... 

Phase II metabolism accounts for between 5 to 22% of the dose. Clinically significant interactions between epipodophyllotoxins and CYP3A4 inducers, such as phenytoin, phenobarbital, and St. John s wort, have been documented, and coadministration can enhance antineoplastic drug clearance by as much as... 

The product information for levamisole states that levamisole, taken with fluorouracil, may increase in the plasma levels of phenytoin. Note that fluorouracil alone inereases phenytoin levels, see Antiepileptics + Antineoplastics Cytotoxic , p.518. 

Fincham RW, Schottelius DD. Case report. Decreased phenytoin levels in antineoplastic therapy. Ther Drug Monit (1979) 1, 277-83. 

Bollini P, Riva R, Albani F, Ida N, Cacciari L, Bollini C, Baruzzi A. Decreased phenytoin level during antineoplastic therapy a case report Epilepsia (1983) 24, 75-8. 

Gattis WA, May DB. Possible interaction involving phenytoin, dexamethasone, and antineoplastic agents a case report and review. Ann Pbarmacother 99G) 30, 520-6. 

Not fully understood, but a suggested reason for the fall in serum antiepileptic levels is that these anti neoplasties damage the intestinal wall, whieh reduces the absorption of the antiepileptic. Other mechanisms may also have some part to play. The raised serum phenytoin levels possibly occur because the liver metabolism of the phenytoin is reduced by these antineoplastics. Changes in plasma protein binding may also have been involved. 

Wakisaka S, Shimauchi M, Kaji Y, Nonaka A, Kinoshita K. Acute phenytoin intoxication associated wiA die antineoplastic agent UFT. Fukuoka IgakuZasshi (1990) 81,192-6. 

Low ketoconazole levels in a patient with leukaemia receiving various antineoplastics was attributed to the concurrent use of phenytoin and phenobarbital therapy. It may be prudent to monitor the effects of ketoconazole if phenobarbital is also given. 

These enzyme-inducing antiepileptics increase the metabolism of vincristine by the cytochrome P450 isoenzyme CYTBA4. However, in vitro studies have shown that phenytoin may potentiate the antineoplastic (antimitotic) effects of the vinca alkaloids. Thus, further study is required to determine the overall effect of phenytoin on the efficacy and toxicity of vincristine and other vinca alkaloids. Carbamazepine would be expected to reduce the efficacy of vincristine. 

While the majority of the hazardous active substances in the NIOSH fist are antineoplastics, active substances from other classes are included, such as phenytoin and tacrolimus [8]. As part of the categorisation some reference is given about which hazard is the main reason for being included in the list. This NIOSH list is updated regularly which is a great advantage, however as said only the most hazardous substances are included. 

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