Aprepitant: drug–drug interactions in perspective

A number of prognostic factors have been identified as risk factors for chemotherapy-induced emesis. This post-hoc analysis addressed whether: (1) these prognostic factors can identify a low-risk group for whom ondansetron plus dexamethasone alone provide a high level of protection (≥80% no emesis); (2) the NK1 receptor antagonist aprepitant improves antiemetic outcome regardless of emetic risk. Breast cancer patients in a phase III double-blind, placebo-controlled trial were randomized to antiemetic regimens including ondansetron and dexamethasone, or aprepitant, ondansetron, and dexamethasone. Multivariate logistic regression models were used to assess the impact on emesis (but not nausea) of the regimen with aprepitant, and previously reported risk factors, including age (<55 and ≥55 years), ethanol use (0–4 or ≥5 drinks/week), history of pregnancy-related morning sickness, and history of motion sickness, using a modified intent-to-treat approach. Treatment with aprepitant (P < 0.0001), older age (P = 0.006), ethanol use (P = 0.0048), and no history of morning sickness (P = 0.0007) were all significantly associated with reduced likelihood of emesis. The proportion of patients with one, two, or three risk factors who remained emesis free was significantly higher with the aprepitant-containing regimen than with the active control (70.2–82.8% vs. 38.6–66.4%, respectively). Aprepitant markedly improved control of emesis in patients with one or more risk factors. This analysis did not support using risk factors for modifying the antiemetic approach. A low-risk group with zero risk factors for whom aprepitant provided little benefit was of questionable clinical utility, since they comprised less than 3% of patients.

Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of phase 3 trial of aprepitant in patients receiving adriamycin-cyclophosphamide-based chemotherapy.

Objective. To review the scientific evidence related to serotonin and substance P and the clinical impact targeting these two neurotransmitters have had managing chemotherapy-induced nausea and vom...

Chemotherapy-induced nausea and vomiting: antiemetic trials that impacted clinical practice.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Nausea and vomiting are the most distressing side-effects of a high dose melphalan regimen.

• Aprepitant in addition to an antiemetic standard regimen has been reported to improve significantly both acute and delayed chemotherapy-induced nausea and vomiting.

WHAT THIS STUDY ADDS

• Anti-emetic regimens including aprepitant have no clinically relevant effect on the pharmacokinetics of the anticancer agent melphalan when administered 1 h before high dose melphalan infusion.

AIMS
The objective of this investigation was to assess the effect of aprepitant on the pharmacokinetics of high-dose melphalan used as conditioning therapy before blood stem cell transplantation in multiple myeloma.

METHODS
Aprepitant (125 mg) or placebo was administered 1 h before melphalan therapy (1 h infusion of 100 mg m−2). Eleven plasma samples were obtained over 8 h and melphalan was quantified using an LC/MS/MS method. Standard pharmacokinetic parameters were calculated and nonparametric testing was applied to assess the differences between aprepitant and placebo treatment.

RESULTS
Twenty patients received placebo and 10 patients aprepitant treatment. There were no differences observed for Cmax at the end of melphalan infusion (placebo 3431 ± 608 ng ml−1vs. aprepitant 3269 ± 660 ng ml−1). In addition, AUC and terminal elimination half-life were not changed by aprepitant. Total clearance of melphalan was 304 ± 58 ml min−1 m−2 (placebo) which was not influenced by aprepitant (288 ± 78 ml min−1 m−2).

CONCLUSIONS
The administration of the NK1 receptor antagonist aprepitant 1 h before a high-dose chemotherapy does not influence the exposure and the elimination of melphalan. Therefore, oral administration of 125 mg aprepitant 1 h before melphalan infusion does not alter the disposition of intravenously administered melphalan.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2125.2010.03792.x

The NK1 receptor antagonist aprepitant does not alter the pharmacokinetics of high‐dose melphalan chemotherapy in patients with multiple myeloma

Two postmenopausal women with breast cancer developed acute confusion and seizures, less than 24 hours after the first cycle of neoadjuvant chemotherapy with fluorouracil, epirubicin and low-dose cyclophosphamide. They were found to have severe, life-threatening hyponatraemia with sodium levels of 113 and 115 mEq/L, respectively. Both women made a full recovery within 24 hours of admission with slow correction of sodium levels. Following investigational workup, the most likely diagnosis was cyclophosphamide-associated syndrome of inappropriate antidiuretic hormone secretion (SIADH). Aprepitant - a commonly used antiemetic and moderate cytochromeP450 3A4 inhibitor was identified as the precipitating factor. Aprepitant was discontinued and both women were successfully re-challenged with full dose cyclophosphamide in an outpatient setting with no subsequent adverse events. This is a typical case of a rare cause of a common medical problem. A systematic approach to diagnosis and treatment of hyponatraemia in an oncology patient requires awareness of toxicities of systemic anticancer agents.

Severe hyponatraemia in two patients with breast cancer caused by low-dose cyclophosphamide and precipitated by aprepitant

588 Background: AP, a moderate inhibitor of CYP3A4, is a selective neurokinin 1 receptor antagonist recommended by the ASCO guidelines for prevention of high and some moderately emetogenic chemothe...

Effect of aprepitant (AP) on cyclophosphamide (CPA) pharmacokinetics (PK) in early breast cancer patients

Immune thrombocytopenic purpura (ITP) has been reported following vaccinations such as MMR as well as after viral infections such as hepatitis C and HIV. Few case reports have been reported of ITP after COVID-19 infections and COVID-19 vaccines. Herein, we present a patient who presented with severe ITP with a platelet count of 0 after receiving the second dose of the BNT162b2 mRNA COVID-19 vaccine (also known as the Pfizer BioNTech). She subsequently recovered with a prolonged treatment course.

/pdf/bnt162b2-covid-19-vaccine-induced-immune-thrombocytopenic-d9nsr0hv.pdf

BNT162b2 COVID-19 Vaccine Induced Immune Thrombocytopenic Purpura

Pos-094 infections in kidney transplant recipients :single center experience from tertiary care center in south india

Pos-056 postpartum aki and sepsis : a tertiary care centre experience

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Effect of aprepitant (AP) on cyclophosphamide (CPA) pharmacokinetics (PK) in early breast cancer patients

BNT162b2 COVID-19 Vaccine Induced Immune Thrombocytopenic Purpura

Pos-094 infections in kidney transplant recipients :single center experience from tertiary care center in south india

Pos-056 postpartum aki and sepsis : a tertiary care centre experience