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Cyclophosphamide Tablets and Equetro

Determining the interaction of Cyclophosphamide Tablets and Equetro and the possibility of their joint administration.

Check result:
Cyclophosphamide Tablets <> Equetro
Relevance: 14.09.2022 Reviewer: Shkutko P.M., M.D., in

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.

Consumer:

Talk to your doctor before using carBAMazepine together with cyclophosphamide. Combining these medications may increase the blood levels and effects of cyclophosphamide. You may have increased side effects such as nausea, vomiting, mouth ulcers, and low blood cell counts, which can make you more likely to develop anemia, bleeding problems, and infections. Contact your doctor if you experience potential signs and symptoms of these conditions such as paleness of skin, fatigue, dizziness, fainting, unusual bleeding or bruising, fever, chills, sore throat, body aches, or other flu-like symptoms. You may need a dose adjustment or more frequent monitoring by your doctor 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.

Professional:

GENERALLY AVOID: Coadministration with carbamazepine may result in decreased plasma concentrations of cyclophosphamide and thiotepa, while concentrations of their main active metabolites increase. The proposed mechanism is carbamazepine induction of CYP450 2B6 and 3A4, the isoenzymes responsible for the bioactivation of cyclophosphamide and thiotepa to 4-hydroxycyclophosphamide and tepa, respectively. In one study, pharmacokinetics of the prodrugs and their active metabolites were determined in a 52-year-old female patient with metastatic breast cancer receiving three 4-day courses (4 weeks apart) of high-dose chemotherapy with cyclophosphamide (1000 mg/m2/day), thiotepa (40 mg/m2 twice a day), and carboplatin. The patient used carbamazepine and vigabatrin for epilepsy during cycles 1 and 2, but anticonvulsant treatment was discontinued after the second cycle due to severe nausea and vomiting that made it difficult for the patient to ingest the medications. Compared to day 1 of cycle 3, plasma exposure (AUC) to cyclophosphamide and thiotepa on day 1 of the first two cycles was reduced 40% and 43%, respectively, while exposure to 4-hydroxycyclophosphamide and tepa was increased by 58% and 75%, respectively. The effect of carbamazepine appeared to diminish after the first day, presumably because cyclophosphamide itself is also an inducer of CYP450 2B6 and 3A4 and may have had the same effect as carbamazepine during subsequent days of cycle 3. Thus, the overall AUCs were only moderately affected by carbamazepine in this case, and it is possible that the interaction may be more clinically relevant in single-dose administrations of the antineoplastic agents.

MANAGEMENT: Given the potential for interaction and the high degree of interpatient variability with respect to hepatic enzyme activities, the use of cyclophosphamide or thiotepa in combination with carbamazepine 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 carbamazepine 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.

References
  • Chang TK, Yu L, Maurel P, Waxman DJ "Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: response to cytochrome P-450 inducers and autoinduction by oxazaphosphorines." Cancer Res 57 (1997): 1946-54
  • Joerger M, Huitema AD, Richel DJ, et al. "Population Pharmacokinetics and Pharmacodynamics of Doxorubicin and Cyclophosphamide in Breast Cancer Patients : A Study by the EORTC-PAMM-NDDG." Clin Pharmacokinet 46 (2007): 1051-1068
  • Ekhart C, Rodenhuis S, Beijnen JH, Huitema AD "Carbamazepine induces bioactivation of cyclophosphamide and thiotepa." Cancer Chemother Pharmacol 63 (2008): 543-7
Cyclophosphamide Tablets

Generic Name: cyclophosphamide

Brand name: Cytoxan, Neosar, Cytoxan Lyophilized

Synonyms: Cyclophosphamide (oral and injection), Cyclophosphamide

Equetro

Generic Name: carbamazepine

Brand name: Carbatrol, Epitol, Equetro, Tegretol, Tegretol XR, Tegretol, Tegretol XR

Synonyms: n.a.

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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Disease interaction