Dilantin Infatabs and Tepadina

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Ask your doctor before using thiotepa together with phenytoin. This combination may reduce the effects of thiotepa. Ask your doctor to consider an alternative to phenytoin. If phenytoin is required, consideration should be given to dosage reduction of the chemotherapeutic agents. If your doctor prescribes these medications together, you may need a dose adjustment or special tests to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

GENERALLY AVOID: Coadministration with phenytoin may result in significantly decreased plasma concentrations of cyclophosphamide and thiotepa, while concentrations of their main active metabolites increase. The proposed mechanism is induction of CYP450 2B6 metabolism by phenytoin. In one study, pharmacokinetics of cyclophosphamide and thiotepa, as well as that of their main active metabolites, were determined in a 42-year-old male patient with relapsing germ-cell cancer receiving two 4-day courses (4 weeks apart) of high-dose chemotherapy with cyclophosphamide (1500 mg/m2/day), thiotepa (60 mg/m2 twice a day), and carboplatin. Blood samples were collected on day 1 of each treatment cycle. Five days prior to the second cycle, the patient began treatment with phenytoin for a generalized epileptic seizure that developed 3 weeks after the first chemotherapy course. Compared to the first cycle, plasma exposure (AUC) to cyclophosphamide and thiotepa was reduced 67% and 29%, respectively, while exposure to 4-hydroxycyclophosphamide and tepa was increased by 51% and 115%, respectively. Because high exposure to these metabolites is associated with increased toxicity, the patient's cyclophosphamide dose was reduced nearly 50% and the thiotepa dose reduced nearly 40% on the third and fourth day of the second cycle. Plasma levels of carboplatin were similar in both courses, so no dose adjustment was made.

MANAGEMENT: Given the magnitude of the interaction, use of cyclophosphamide or thiotepa in combination with phenytoin should be avoided if possible. Anticonvulsants with no significant effects on CYP450 hepatic enzymes such as valproic acid, lamotrigine, or gabapentin may be appropriate alternatives. If phenytoin is required, consideration should be given to dosage reduction of the chemotherapeutic agents. In addition, plasma levels of the active metabolites should be monitored to guide further dosing.

Dilantin Infatabs

Generic Name: phenytoin

Brand name: Dilantin, Phenytek, Dilantin Infatabs, Phenytoin Sodium, Prompt

Synonyms: Dilantin

What is Dilantin Infatabs?

Tepadina

Generic Name: thiotepa

Brand name: Tepadina, Thioplex

Synonyms: Tepadina Injection

What is Tepadina?