Muscle spasms: an unexpected adverse drug reaction of pemetrexed?

Abstract

Abstract:In this report we describe a 53-year-old woman with advanced non-small cell lung cancer, treated with pemetrexed and cisplatin combination therapy, followed by pemetrexed monotherapy. The patient developed severe muscle spasms at least twice, shortly after administration of pemetrexed monotherapy. A possible explanation for this observation is that in combination with cisplatin therapy, the patient was hyperhydrated before administration to promote renal excretion and reduce toxicity. Pemetrexed is also renally excreted, which supports the finding that toxicity did not occur when the patient was hyperhydrated. After discontinuation of pemetrexed the symptoms did not reoccur. All aspects of this case point to a possible relationship between pemetrexed and an adverse drug reaction (ADR). We conclude that muscle spasms are a rare, but possibly dose-related ADR of pemetrexed-based therapy.

Hyperhydration with cisplatin does not influence pemetrexed exposure

“…Both pemetrexed and platinum clearance, and thus exposure, is highly dependent on renal function 3,4 . Earlier, we described a case of a patient who tolerated combination therapy of pemetrexed with cisplatin and hyperhydration very well, but experienced severe side effects during all cycles of pemetrexed monotherapy 5 . Hyperhydration is routinely used to ensure adequate diuresis and clearance during treatment with cisplatin to avoid nephrotoxicity 3 .…”

“… 3 , 4 Earlier, we described a case of a patient who tolerated combination therapy of pemetrexed with cisplatin and hyperhydration very well, but experienced severe side effects during all cycles of pemetrexed monotherapy. 5 Hyperhydration is routinely used to ensure adequate diuresis and clearance during treatment with cisplatin to avoid nephrotoxicity. 3 One of the proposed mechanisms is that forced diuresis enhances cisplatin excretion by enhancing renal blood flow and filtration, and decreasing the contact time of cisplatin and renal tubules.…”