Characterization of the occurrence of ifosfamide-induced neurotoxicity with concomitant aprepitant

Howell, Josh; Szabatura, Audrea; Seung, Amy Hatfield; Nesbit, Suzanne

doi:10.1177/1078155208093930

Cited by 50 publications

(50 citation statements)

References 13 publications

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“…This, and the renal failure, could explain the delay of the neurotoxic effects encountered in our second case [3]. Previous publications have reported an increased risk of central nervous system toxicity when IFO was associated with aprepitant [8, 10, 11]. An increase of 66.7% in 2d-Ifo and 37.3% in 3d-Ifo was reported when aprepitant was given concomitantly with IFO in one patient [6].…”

Section: Discussionmentioning

confidence: 59%

Two Cases of Fatal Encephalopathy Related to Ifosfamide: An Adverse Role of Aprepitant

Séjourné¹,

Noal²,

Boone³

et al. 2014

Case Rep Oncol

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Ifosfamide is used in the treatment of sarcomas and other tumors. It sometimes provokes encephalopathy, which is a serious complication even if it is usually reversible within 48-72 h after drug cessation. Ifosfamide is required to be activated by hepatic cytochrome P450 (CYP), especially the 3A4 subtype, leading to 4-hydroxy-ifosfamide. Ifosfamide is also converted by CYP3A4 to inactive but neurotoxic metabolites. Aprepitant is a neurokinin-1 receptor antagonist that is a potent antiemetic used in combination with 5-HT₃ antagonists and corticosteroids. Aprepitant has an inhibitory effect, as well as a possible inductive effect, on CYP3A4. Since ifosfamide and aprepitant are both substrates of CYP3A4, a pharmacokinetic interaction could result in secondary effects such as the potentialization of neurological side effects. In this report, we describe 2 cases of fatal encephalopathy in patients who have received both ifosfamide and aprepitant, and we discuss the mechanisms that could be involved. Our observations draw attention to the fact that aprepitant must be avoided, or at least used with caution, in patients who are receiving ifosfamide due to the risk of severe neurological side effects.

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Section: Discussionmentioning

confidence: 59%

Two Cases of Fatal Encephalopathy Related to Ifosfamide: An Adverse Role of Aprepitant

Séjourné¹,

Noal²,

Boone³

et al. 2014

Case Rep Oncol

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“…This, of course, cannot exclude an interrelationship between the two agents. 25 Risk factors: In our study, patients taking opiates had a significantly higher risk (P ¼ 0.02) of not completely responding to the administered prophylaxis. This observation highlights the role of confounding factors in patients receiving HDC and should be considered when planning a randomized trial.…”

Section: Discussionmentioning

confidence: 86%

The NK-1 receptor-antagonist aprepitant in high-dose chemotherapy (highdose melphalan and high-dose T-ICE: paclitaxel, ifosfamide, carboplatin, etoposide): efficacy and safety of a triple antiemetic combination

Jordan

Jahn

et al. 2010

Bone Marrow Transplant

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Complete protection from nausea/vomiting is currently achieved in a minority of patients receiving high-dose chemotherapy (HDC). Currently the use of 5-HT 3 -antagonists and dexamethasone (DEX) represents the standard of care. The role of the NK-1-antagonist aprepitant in HDC remains to be better defined. A total of 64 patients undergoing multiple days of HDC received granisetron, DEX plus aprepitant during chemotherapy. After the end of chemotherapy aprepitant plus DEX was given for a further 2 days. Primary end point was CR defined as no vomiting and no use of rescue medication in the overall phase (day 1 until 5 days after end of chemotherapy). Acute/delayed and overall CR were achieved in 83%/70% and 63%, respectively. Acute and delayed nausea were observed in 20 and 38% of the patients. The tolerability of the aprepitant regimen over 4-5 days was comparable with the 3-day antiemetic regimen. In our study, aprepitant demonstrated good tolerability. Taking into account the methodological constraints of comparing our results with those from the available literature, the addition of aprepitant to the antiemetic treatment regimen may provide improved prevention of chemotherapy-induced nausea and vomiting during HDC.

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“…The incidence of neurotoxicity or encephalopathy is 10-30% and is increased with concomitant aprepitant use as seen in a few recent case reports [12][13][14]. Here we present one such case along with a review of the latest literature.…”

Section: Introductionmentioning

confidence: 81%

“…Ifosfamide induced neurotoxicity is one of the rarer side effects seen with this drug [15], with a few cases showing increased incidence with aprepitant use [12][13][14]. Aprepitant is a neurokinin-1 inhibitor which is used as an antiemetic.…”

Section: Discussionmentioning

confidence: 99%

Ifosfamide Induced Neurotoxicity Secondary to Concomitant Aprepitant Use

Malhotra¹,

Poiesz²

2012

Adv Pharmacoepidem Drug Safety

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Characterization of the occurrence of ifosfamide-induced neurotoxicity with concomitant aprepitant

Abstract: An increased risk was identified for ifosfamide-induced neurotoxicity associated with aprepitant use; however, the observed difference was not statistically significant. The necessity of aprepitant given in association with ifosfamide may need to be reconsidered due to this risk.

Cited by 50 publications

References 13 publications

Two Cases of Fatal Encephalopathy Related to Ifosfamide: An Adverse Role of Aprepitant

Two Cases of Fatal Encephalopathy Related to Ifosfamide: An Adverse Role of Aprepitant

The NK-1 receptor-antagonist aprepitant in high-dose chemotherapy (highdose melphalan and high-dose T-ICE: paclitaxel, ifosfamide, carboplatin, etoposide): efficacy and safety of a triple antiemetic combination

Ifosfamide Induced Neurotoxicity Secondary to Concomitant Aprepitant Use

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