Toxicity assessment of concurrent gabapentin/pregabalin administration with high-dose melphalan in autologous hematopoietic cell transplant recipients

• Published in: Supportive care in cancer 2021-12, Vol.29 (12), p.7925-7930
• Main Authors: Angus, Jonathan, Cumpston, Aaron, Veltri, Lauren, Ross, Kelly G., Wen, Sijin, Dillaman, Megan
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; Aprepitant; Blood platelets; Cancer; Dosage and administration; Drug dosages; Drug interactions; Gabapentin - administration & dosage; Gabapentin - toxicity; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Humans; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Melphalan - administration & dosage; Melphalan - toxicity; Mucositis; Multiple myeloma; Multiple Myeloma - drug therapy; Narcotics; Nausea; Neutrophils; Nursing; Nursing Research; Oncology; Organ transplant recipients; Original Article; Pain; Pain Medicine; Patient satisfaction; Peripheral neuropathy; Pharmacokinetics; Pregabalin - administration & dosage; Pregabalin - toxicity; Prospective Studies; Rehabilitation Medicine; Retrospective Studies; Stem cell transplantation; Transplant Recipients; Transplantation; Transplantation Conditioning; Transplantation, Autologous; Transplants & implants; Vomiting
• ISSN: 0941-4355; 1433-7339
• DOI: 10.1007/s00520-021-06385-5

A theoretical pharmacokinetic interaction mediated through l -amino acid transporter 1 and 2 exists between gabapentin (GP) and pregabalin (PG) with melphalan. Peripheral neuropathy is a common toxicity of various multiple myeloma regimens commonly utilized prior to autologous hematopoietic cell transplant (auto-HCT) with high-dose melphalan (HD-Mel). Therefore, it is likely concurrent administration of either GP or PG will occur in patients receiving HD-Mel conditioning for auto-HCT, which could potentially increase cellular uptake and worsen the mucosal injury. A retrospective chart review of adult patients from January 2012 to July 2016 who received HD-Mel (140–200 mg/m 2 ) at West Virginia University Medicine was performed to assess toxicity and outcomes in these patients. A total of 80 patients were included in the study, with 30 patients receiving GP or PG and 50 control patients. There were no significant differences in grade 2 or higher mucositis, admissions for nausea/vomiting/diarrhea, intravenous opioid requirements, oral topical therapies, antidiarrheal medication use, rescue anti-emetics, days of nausea or vomiting, pain scores, neutrophil or platelet engraftment, treatment-related mortality, progression-free survival, or overall survival. Our data suggest that it is safe to continue GP/PG therapy throughout HD-Mel therapy, with no negative transplant outcomes. Prospective studies or evaluations of larger databases are necessary to better characterize the clinical effect of concomitant therapy.