The effects of genetic polymorphism on toxicity and pharmacokinetics of methotrexate in Egyptian adult patients with leukaemia or lymphoma.

Polymorphisms in genes coding folate-metabolising enzymes might alter the pharmacokinetics and sensitivity for methotrexate "MTX".The aim of the study aimed to investigate the influence of MTHFR C677T, DHFR19 Ins/del, GGH -401 C > T, and MTR A2756G polymorphisms on MTX toxicity and pharmacokinetics in Egyptian patients with Acute lymphoblastic leukaemia (ALL) or Non-Hodgkin lymphoma (NHL).Fifty adult Egyptian patients with ALL and NHL, treated with high dose MTX, were prospectively enrolled in the study. Clinical and biochemical data was collected objectively from medical records after each cycle of MTX. Plasma concentrations of MTX were measured after 72 h of initiation of infusion. Genotyping was done with a PCR-ARMS and PCR-RFLP assays.The MTHFR C677T T variants significantly increased the risk of leukopoenia, whereas the genotype MTHFR 677 C > T TT significantly associated with lymphocytopenia, thrombocytopenia, and anaemia. The genotype GGH-401 TT was significantly correlated with anaemia. Plasma MTX level was significantly higher in patients with MTR A2756G G variants.MTHFR polymorphism played the main role in MTX toxicities. The pharmacokinetics of MTX was affected by MTR polymorphism. GGH mutation was mainly concerned with anaemia. Pharmacogenetic testing are recommended to optimise MTX therapy.

Prevalence of Drug-Drug Interactions in Primary Care Prescriptions in Egypt: A Cross-Sectional Retrospective Study.

In clinical practice, drug-drug interactions (DDIs) pose significant risks to a large number of patients. Consequently, healthcare providers are required to diligently identify, monitor, and effectively handle these interactions in order to enhance patient outcomes. In Egypt, DDIs are poorly addressed, with no reports for DDIs in primary care. In our cross-sectional, retrospective, observational study, we collected a total of five thousand, eight hundred and twenty prescriptions across eight major governorates in Egypt. Prescriptions were collected over a span of 15 months between 1 June 2021 and 30 September 2022. These prescriptions were analyzed for potential DDIs using the Lexicomp® drug interactions tool. The prevalence of DDIs was found to be 18%, with 22% of the prescriptions having two or more potential DDIs. Moreover, we found 1447 DDIs of categories C (monitoring therapy recommended), D (therapy modification suggested), and X (avoid combination). The most commonly interacting drugs in our study were diclofenac, aspirin, and clopidogrel, while non-steroidal anti-inflammatory drugs (NSAIDs) were the most reported therapeutic class implicated in pharmacologic DDIs. Pharmacodynamic agonistic activity was the most common mechanism of interaction. Therefore, it is crucial to conduct screenings, detect early signs, and closely monitor drug-drug interactions (DDIs) to enhance patients' overall health outcomes, medication responses, and safety. In this regard, the clinical pharmacist assumes a vital role in implementing these preventive measures.