From the Guidelines
Momelotinib can potentially cause acute renal injury, and if a patient develops acute kidney injury while on momelotinib, the medication should be temporarily discontinued and renal function closely monitored. According to the most recent and highest quality study, 1, acute kidney injury (AKI) is a complex condition with various pathophysiologic processes, and no single intervention has been reported to prevent, mitigate, or treat AKI. The study highlights the importance of patient enrichment strategies, prevention and attenuation studies, treatment studies, and innovative trial designs to address AKI.
Key Considerations
- Patients taking momelotinib should have regular kidney function tests, including serum creatinine and estimated glomerular filtration rate (eGFR), especially during the first few months of treatment 1.
- Risk factors that may increase the likelihood of renal injury include dehydration, concomitant use of nephrotoxic medications, and pre-existing kidney disease 1.
- The mechanism behind momelotinib-associated renal injury is not fully understood but may involve JAK inhibition effects on renal blood flow and filtration.
- Adequate hydration and avoiding concurrent use of other potentially nephrotoxic drugs when possible can help minimize the risk of kidney injury.
Management of Acute Kidney Injury
- If a patient develops AKI while on momelotinib, the medication should be temporarily discontinued, and renal function closely monitored 1.
- Dosage adjustment may be necessary when treatment is resumed, particularly in patients with pre-existing renal impairment.
- Consultation with a nephrologist is recommended for comprehensive management if severe renal impairment occurs.
Biomarkers and Diagnosis
- Novel biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL) and serum cystatin C, may help detect AKI earlier and more accurately than traditional biomarkers like serum creatinine and urine output 1.
- The diagnosis of AKI should be based on a combination of clinical findings, laboratory results, and biomarkers.
From the Research
Momelotinib and Acute Renal Injury
- The study 2 evaluated the pharmacokinetics and safety of momelotinib in subjects with hepatic or renal impairment and found no clinically significant difference in plasma exposures of momelotinib between subjects with moderate or severe renal impairment and healthy control subjects.
- The same study 2 also found that the safety profile following a single dose of momelotinib was similar between subjects with hepatic or renal dysfunction and healthy control subjects, indicating that dose adjustment is not necessary for momelotinib in patients with renal impairment.
- Another study 3 analyzed the long-term safety and survival of momelotinib in myelofibrosis and found that the most common nonhematologic treatment-emergent adverse event was diarrhea, but did not specifically report on acute renal injury.
- Studies 4 and 5 discussed acute kidney injury in general, but did not provide information specific to momelotinib.
- A case report 6 described acute renal failure associated with imatinib mesylate, a different tyrosine kinase inhibitor, highlighting the importance of monitoring renal function during therapy with such agents.
Renal Impairment and Momelotinib
- The study 2 suggested that momelotinib can be used in patients with renal impairment without dose adjustment, based on the pharmacokinetic and safety results.
- However, the study 2 did recommend dose reduction in patients with severe hepatic impairment, but this is not directly related to renal impairment.
- The long-term analysis 3 of momelotinib in myelofibrosis did not report any specific concerns regarding renal impairment or acute renal injury.