Antineoplastics Antiepileptics

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. 

Glyceryl trinitrate overdose should be treated with the patient s head lowered. Other measures include respiration maintenance, use of plasma expanders, and electrolyte balance. Withdrawal of heparin treatment or dose reduction should be performed with the overdose of heparin. Protamine sulfate may be used to reduce severe bleeding. Heparin should be used with caution with glyceryl trinitrate, aprotinine, alcohol, tobacco, and ACE inhibitors. Nifedipine should be used with care when coadministering with immunosuppressants, magnesium salts, tobacco, digoxin, antineoplastics, calcium channel blockers, antihistamines, antifungals, antiepileptics, antiarrhythmics, and alcohol. 

Treatment for verapamil overdose includes gastric lavage, administration of activated charcoal, symptomatic and supportive cardiovascular treatment, and calcium gluconate injection. Verapamil should be used carefully with calcium salts, beta-blockers, antineoplastics, antiepileptics, antibacterials, anxiolytics, and anti-arrhythmics. 

Antiviral agents acyclovir, amantadine, azidofhymidine Diuretics furosemide, hydrochlorothiazide, efhacrynic acid ACE inhibitors captopril, enalapril, ramipril, delapril, quinapril Antineoplastics methotrexate, azathioprine, doxorubicin, 5-fluouracil Antiepileptics valproic acid (from Ref. [95])... 

Antiepileptic, psychiatric drug Lipid regulator (active metabolite) Metabolite of nicotine Antineoplastic Analgesic/antiinflammatory Analgesic/antiinflammatory Psychiatric drug (Prozac)... 

Be on the alert with any drugs that have a narrow therapeutic window or where it is necessary to keep serum levels at or above a suitable level (e.g. anticoagulants, antidiabetic drugs, antiepileptics, antihypertensives, anti-infectives, antineoplastic cytotoxics, digitalis glycosides, immunosuppressants, etc.). 

Table 14.1 Reduced antiepileptic levels during antineoplastic therapy...

A number of antiepileptic drugs affect the levels of various antineoplastics. These are discussed elsewhere. See ... 

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. 

Information is scattered and incomplete. However, it appears that both altered antiepileptic levels and altered antineoplastic levels can occur, possibly leading to loss of efficacy or toxicity. Where possible, it may be prudent to avoid concurrent use of enzyme-inducing antiepileptics and antineoplastics. If this is not possible, serum antiepileptic levels should be closely monitored during treatment with any of these antineoplastics, making dosage adjustments as necessary, and the efficacy of the antineoplastics should also be closely monitored. 

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. 

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