Bot Detector
IJPC Seal
Download FREE Sample Issue or Article
LEARN MORE
Subscribe Today
A subscription to IJPC provides on-line access to full-text, full-color, printable PDF copies of your subscribed issues, individual articles, and purchased archives.

Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride

Author(s):  Wu George, Powers Dan, Yeung Stanley, Chen Frank, Neelon Kelly

Issue:  Jan/Feb 2018 - Volume 22, Number 1
View All Articles in Issue

Page(s):  86-94

Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride Page 1
Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride Page 2
Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride Page 3
Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride Page 4
Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride Page 5
Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride Page 6
Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride Page 7
Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride Page 8
Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride Page 9

Download in electronic PDF format for $75

Abstract:  Prophylaxis or therapy with a combination of a neurokinin 1 (NK-1) receptor antagonist (RA), a 5-hydroxytryptamine- 3 (5-HT3) RA, and dexamethasone is recommended by international antiemesis guidelines for the prevention of chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy and for select patients receiving moderately emetogenic chemotherapy. VARUBI (rolapitant) is a substance P/NK-1 RA that was recently approved by the U.S. Food and Drug Administration as an injectable emulsion in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. Granisetron Hydrochloride Injection USP is one of the 5-HT3 RAs indicated for the prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin. Herein, we describe the physical and chemical compatibility and stability of VARUBI (rolapitant) injectable emulsion (166.5 mg/92.5 mL [1.8 mg/mL], equivalent to 185 mg of rolapitant hydrochloride) admixed with Granisetron Hydrochloride Injection USP (1.0 mg/mL, equivalent to 1.12 mg/mL hydrochloride). Binary admixtures of VARUBI injectable emulsion and Granisetron Hydrochloride Injection USP were prepared and stored in VARUBI ready-to-use glass vials and in four types of commonly used intravenous administration (tubing) sets. Evaluation of the physical and chemical compatibility and stability of the admixtures in the VARUBI ready-to-use vials stored at room temperature (20°C to 25°C) under fluorescent light and under refrigeration (2°C to 8°C protected from light) was conducted at 0, 1, 6, 24, and 48 hours, and that of the admixtures in the intravenous tubing sets was evaluated at 0, 2, and 6 hours of storage at 20°C to 25°C. Physical stability was evaluated by visual examination of the container contents under normal room light, and measurement of turbidity, globule size, and particulate matter. Chemical stability was assessed by measuring the pH of the admixture and determining drug concentrations (potency) and impurity levels by high-performance liquid chromatographic analysis. The pH, turbidity, globule size, and particulate matter of all samples remained within narrow and acceptable ranges at all study time points, indicating that combining the two formulations into a binary admixture is physically and chemically compatible and stable. VARUBI injectable emulsion admixed with Granisetron Hydrochloride Injection USP demonstrated compatibility and stability in a ready-to-use glass vial for at least 24 hours at room temperature and 48 hours under refrigeration, as well as in the four intravenous tubing sets for at least 6 hours at 20°C to 25°C. No decrease of drug concentration (or potency) of any admixed components occurred in the samples stored at the two conditions and time periods studied based on high-performance liquid chromatographic analysis. The levels of impurities stayed below the safety limits set by International Conference on Harmonisation during the study period.

Related Keywords: George Wu, PhD, Dan Powers, DO, Stanley Yeung, PharmD, Frank Chen, PhD, Kelly Neelon, PhD, VARUBI, injectable emulsion, chemotherapy-induced nausea and vomiting, neurokinin 1 receptor antagonist, substance P receptor antagonist, emesis, antiemetic agent, triple combination therapy, 5-HT3 receptor antagonist, dexamethasone, rolapitant, drug admixtures, stability studies, granisetron hydrochloride, storage conditions, intravenous tubing set compatibility

Related Categories: CANCER AND AIDS, GASTROENTEROLOGY, PEER-REVIEWED, STABILITIES, COMPATIBILITIES, ALLERGY/IMMUNOLOGY/INFLAMMATION, NEUROLOGY

Printer-Friendly Version



Related Articles from IJPC
Title/Author
(Click for Abstract / Details / Purchase)
Issue/​Page
View/Buy
Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride
Wu George
, Powers Dan, Yeung Stanley, Chen Frank, Neelon Kelly
Jan/Feb 2018
Pg. 86-94

Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Palonosetron Hydrochloride Injection and Dexamethasone Sodium Phosphate Injection
Wu George
, Powers Dan, Yeung Stanley, Chen Frank
Jan/Feb 2018
Pg. 76-85

Compatibility and Stability of Rolapitant Injectable Emulsion Admixed with Intravenous Palonosetron Hydrochloride
Wu George
, Yeung Stanley, Chen Frank
Jan/Feb 2017
Pg. 76-82

Compatibility and Stability of Rolapitant Injectable Emulsion Admixed with Dexamethasone Sodium Phosphate
Wu George
, Yeung Stanley, Chen Frank
Jan/Feb 2017
Pg. 66-75

Rolapitant Injectable Emulsion with Palonosetron Hydrochloride Admixture
Allen Loyd V Jr
Mar/Apr 2018
Pg. 151

Rolapitant Injectable Emulsion with Dexamethasone Sodium Phosphate Admixture
Allen Loyd V Jr
May/Jun 2018
Pg. 237

The Basics of Compounding Emulsions, Part 2
Allen Loyd V Jr
May/Jun 2001
Pg. 198-201

Basics of Compounding for the Treatment of Warts
Allen Loyd V Jr
Mar/Apr 2004
Pg. 126-129

Physical Assessments of Lipid Injectable Emulsions via Microscopy: A Comparison to Methods Proposed in the United States Pharmacopeia Chapter <729>
Driscoll David F
, Nehne Jorg, Horst Peterss, Klutsch Karsten, Bistrian Bruce R, Wilhelm Niemann
Jul/Aug 2006
Pg. 309-315

Compatibility of Baclofen, Carvedilol, Hydrochlorothiazide, Mercaptopurine, Methadone Hydrochloride, Oseltamivir Phosphate, Phenobarbital, Propranolol Hydrochloride, Pyrazinamide, Sotalol Hydrochloride, Spironolactone, Tacrolimus Monohydrate, Ursodeoxycholic Acid, and Vancomycin Hydrochloride Oral Suspensions Compounded with SyrSpend SF pH4
Polonini Hudson
, da Silva Sharlene Loures, Brandão Marcos Antônio Fernandes, Bauters Tiene, De Moerloose Barbara, Ferreira Anderson de Oliveira
Nov/Dec 2018
Pg. 516-526

Microwave Freeze-thaw Technique for Injectable Drugs: A Review Updated from 1980 to 2021
Hecq Jean-Daniel
, Soumoy Laura, Closset Mélanie, Colsoul Marie-Lise, Jamart Jacques, Galanti Laurence
Nov/Dec 2021
Pg. 446-462

Rapid-Dissolve Technology: An Interview With Loyd V. Allen, Jr., PhD, RPh
Allen Loyd V Jr
Nov/Dec 2003
Pg. 449-450

Room Temperature Stability of Injectable Succinylcholine Dichloride
Roy Julie J
, Boismenu Daniel, Mamer Orval A, Nguyen Bao T, Forest Jean-Marc, Hildgen Patrice
Jan/Feb 2008
Pg. 83-85

Physico-chemical Stability of MabThera Drug-product Solution for Subcutaneous Injection under In-use Conditions with Different Administration Materials
Mueller Claudia
, Dietel Elde, Heynen Severin R, Nalenz Heiko, Goldbach Pierre, Mahler Hanns-Christian, Schmidt Johannes, Grauschopf Ulla, Schoenhammer Karin
May/Jun 2015
Pg. 261-267

Chemical and Physical Compatibility of an Intravenous Solution of Epinephrine with Calcium Chloride
Weeks Phillip A
, Teng Yang, Wu Lei, Sun Mary, Yang Zhen, Chow Diana S-L
Mar/Apr 2014
Pg. 152-158

Effect of Emulsifier Pairs on Physical Stability of Emulsions Containing Three Different Natural Oils
Boonme Prapaporn
, Maneenuan Duangkhae
Nov/Dec 2014
Pg. 516-519

Stability Studies of Fludrocortisone Acetate Capsules and Fludrocortisone Acetate Titrated Powders (Powder Triturates)
Brandin Thibaut
, Wasilewski Maya, Panuccio Camille, Bouguergour Cyrielle, Primas Nicolas, Lamy Edouard, Jean Christophe, Bertault-Peres Pierre, Rathelot Pascal, Curti Christophe, Vanelle Patrice
Mar/Apr 2022
Pg. 150-154

Basics of Sterile Compounding: Biopharmaceutics of Injectable Dosage Forms
Akers Michael J
Jan/Feb 2017
Pg. 47-56

Stability of Azathioprine, Clonidine Hydrochloride, Clopidogrel Bisulfate, Ethambutol Hydrochloride, Griseofulvin, Hydralazine Hydrochloride, Nitrofurantoin, and Thioguanine Oral Suspensions Compounded with SyrSpend SF pH4
Polonini Hudson
, Loures da Silva Sharlene, Neves Cunha Carolina, de Oliveira Ferreira Anderson, Anagnostou Korina, Dijkers Eli
May/Jun 2020
Pg. 252-262

Compatibility and Stability of Linezolid Injection Admixed with Gentamicin Sulfate and Tobramycin Sulfate
Xu Quanyun A
, Trissel Lawrence A, Zhang Yanping, Williams Kimberly Y
Nov/Dec 2000
Pg. 476-479

Return to Top