Relevant pharmacological interactions between alkylating agents and antiepileptic drugs: Preclinical and clinical data.
Pharmacol Res
; 175: 105976, 2022 01.
Article
in En
| MEDLINE
| ID: mdl-34785318
ABSTRACT
Seizures are relatively common in cancer patients, and co-administration of chemotherapeutic and antiepileptic drugs (AEDs) is highly probable and necessary in many cases. Nonetheless, clinically relevant interactions between chemotherapeutic drugs and AEDs are rarely summarized and pharmacologically described. These interactions can cause insufficient tumor and seizure control or lead to unforeseen toxicity. This review focused on pharmacokinetic and pharmacodynamic interactions between alkylating agents and AEDs, helping readers to make a rational choice of treatment optimization, and thus improving patients' quality of life. As an example, phenobarbital, phenytoin, and carbamazepine, by increasing the hepatic metabolism of cyclophosphamide, ifosfamide and busulfan, yield smaller peak concentrations and a reduced area under the plasma concentration-time curve (AUC) of the prodrugs; alongside, the maximum concentration and AUC of their active products were increased with the possible onset of severe adverse drug reactions. On the other side, valproic acid, acting as histone deacetylase inhibitor, showed synergistic effects with temozolomide when tested in glioblastoma. The present review is aimed at providing evidence that may offer useful suggestions for rational pharmacological strategies in patients with seizures symptoms undertaking alkylating agents. Firstly, clinicians should avoid the use of enzyme-inducing AEDs in combination with alkylating agents and prefer the use of AEDs, such as levetiracetam, that have a low or no impact on hepatic metabolism. Secondly, a careful therapeutic drug monitoring of both alkylating agents and AEDs (and their active metabolites) is necessary to maintain therapeutic ranges and to avoid serious adverse reactions.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alkylating Agents
/
Anticonvulsants
Aspects:
Patient_preference
Limits:
Animals
/
Humans
Language:
En
Journal:
Pharmacol Res
Journal subject:
FARMACOLOGIA
Year:
2022
Document type:
Article
Affiliation country:
Italy