Hospital Pharmacy - October 2019 - 330

802586
research-article2018

HPXXXX10.1177/0018578718802586Hospital PharmacySabins et al

Original Article

Stability and Compatibility of
Diphenhydramine Hydrochloride in
Intravenous Admixtures: A New
Look at an Old Drug

Hospital Pharmacy
2019, Vol. 54(5) 330-334
© The Author(s) 2018
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https://doi.org/10.1177/0018578718802586
DOI: 10.1177/0018578718802586
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Daniel Sabins1, Tuong Diep2, Pamela McCartan2,
Shashi Patel2, and Fang Zhao1

Abstract
Purpose: Intravenous (IV) admixtures of diphenhydramine are widely used in hospitalized patients to prevent or treat
hypersensitivity reactions. However, there is limited data to support the admixture preparation in this manner. This study
was designed to investigate the stability and compatibility of diphenhydramine in IV admixtures with a goal to establish a 14day beyond-use dating with storage under refrigeration. Methods: The commercially available 50 mg/mL diphenhydramine
hydrochloride injection vials were used to prepare the 0.2 and 1.0 mg/mL IV admixtures in 0.9% sodium chloride injection
and 5% dextrose injection in 50 mL polyvinyl chloride (PVC) bags. The IV bags were sealed and stored under refrigeration
(2°C-8°C) for the stability study. At each predetermined time point, samples were taken for visual inspection, pH measurement,
and analysis by a stability-indicating high-performance liquid chromatography (HPLC) method. Results: The freshly prepared
IV admixtures appeared clear, colorless, and particulate-free with pH readings of 4.44 to 4.60. The initial drug concentrations
of all samples were confirmed by HPLC to be within 101.8% to 103.6% of the label claims. Over the 14 days of the study
period, there was no significant change in the appearance or pH values for all stability samples. The HPLC results also
confirmed that there was no more than ±2% change of the initial drug concentration in any stability samples. Conclusion:
Diphenhydramine hydrochloride IV admixtures of 0.2 and 1.0 mg/mL are compatible with 0.9% sodium chloride injection and
5% dextrose injection in PVC bags. These IV admixtures are stable chemically and physically for up to 14 days when stored
under refrigeration (2°C-8°C).
Keywords
Benadryl, diphenhydramine, anaphylaxis, compounding, stability, compatibility, IV, admixture

Introduction
Diphenhydramine, a first-generation H1 antihistamine introduced back in 1946,1,2 has been used to treat a variety of
conditions, such as allergies, insomnia, motion sickness, and
parkinsonism.3 Currently, systemic diphenhydramine is
widely used in therapies as an adjunctive agent to prevent or
treat hypersensitivity reactions caused by many agents.4 In
particular, many published studies have used either oral or
intravenous (IV) diphenhydramine as part of a premedication series before administering chemotherapy or immunotherapy treatments.5
The IV administration of diphenhydramine provides rapid
achievement of therapeutic effects and bypasses potential
absorption issues. It is an attractive choice for some therapies
and can be administered via IV push or IV infusion. While
IV push of diphenhydramine would yield a fast onset, it may
lead to potential side effects and thus requires additional

nursing time to monitor patients. IV infusion of diphenhydramine, as diluted IV admixtures, allows the medication to be
safely administered to patients.3,6
Even though the IV infusion therapy of diphenhydramine
is widely used, there is limited information from the manufacturers or published literature to support the stability and
compatibility of diphenhydramine IV admixtures at commonly used dosages.7-9 A typical dose of 25 to 50 mg of
diphenhydramine hydrochloride (HCl) prepared in a commercially available 50 or 100 mL IV bag would result in a
theoretical concentration range of 0.25 to 1.0 mg/mL. The
1

St. John Fisher College, Rochester, NY, USA
Rochester Regional Health, NY, USA

2

Corresponding Author:
Fang Zhao, Wegmans School of Pharmacy, St. John Fisher College, 3690
East Ave, Rochester, NY 14618-3537, USA.
Email: fzhao@sjfc.edu
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