AHFS Class:

28:24.08 Benzodiazepines

Generic Name

• Midazolam Hydrochloride

Midazolam hydrochloride is available at concentrations equivalent to midazolam 1 and 5 mg/mL in packages containing 1, 2, 5, or 10 mL of solution.³²⁰⁶; ³⁵⁹⁰; ³⁵⁹¹; ³⁵⁹² The drug also is available in a 100-mL pharmacy bulk package at a concentration equivalent to midazolam 5 mg/mL.³²⁵⁰ Formulations generally also contain sodium chloride 0.8%.³²⁰⁶; ³²⁵⁰; ³⁵⁹⁰; ³⁵⁹¹; ³⁵⁹² Some formulations contain disodium edetate 0.01%, with or without benzyl alcohol 1%.³²⁰⁶; ³²⁵⁰; ³⁵⁹⁰ Preservative-free formulations of midazolam hydrochloride also are available.³⁵⁹¹; ³⁵⁹² The pH of both the preservative-containing and preservative-free formulations of the injection is adjusted with hydrochloric acid and, if necessary, sodium hydroxide.³²⁰⁶; ³²⁵⁰; ³⁵⁹⁰; ³⁵⁹¹; ³⁵⁹²

Midazolam hydrochloride (Seizalam) also is available at a concentration equivalent to midazolam 5 mg/mL in multidose vials containing 10 mL labeled only for intramuscular administration.³⁵⁹³ Each mL also contains sodium chloride 0.8%, disodium edetate 0.01%, and benzyl alcohol 1%.³⁵⁹³ The pH of the injection is adjusted with hydrochloric acid and, if necessary, sodium hydroxide.³⁵⁹³

pH

The pH of the injection (Hospira) is approximately 3;³⁵⁹⁰; ³⁵⁹¹; ³⁵⁹² pH ranges including 3 also have been reported for other products.³²⁰⁶; ³²⁵⁰

The pH of the injection (Seizalam) labeled only for intramuscular administration is approximately 3.³⁵⁹³

Midazolam (Roche) 0.625, 1.25, and 1.67 mg/mL in sodium chloride 0.9% had pH values of 3.6, 3.4, and 3.4, respectively.²¹⁶¹

Osmolality

Midazolam (Roche) 0.625, 1.25, and 1.67 mg/mL in sodium chloride 0.9% had osmolalities of 274, 262, and 259 mOsm/kg, respectively.²¹⁶¹

Trade Name(s)

Versed, Seizalam

Midazolam hydrochloride is administered intramuscularly by injection deep into a large muscle mass or intravenously by slow intermittent injection in incremental doses or by continuous infusion.³⁵⁹⁰; ³⁵⁹¹; ³⁵⁹² Use of the 1-mg/mL concentration or dilution of the 1- or 5-mg/mL concentration is recommended to facilitate slower injection.³⁵⁹⁰; ³⁵⁹¹; ³⁵⁹² While the 5-mg/mL concentration is recommended for dilution for continuous intravenous infusion, both the 1- and 5-mg/mL concentrations may be diluted with sodium chloride 0.9% or dextrose 5%.³⁵⁹⁰; ³⁵⁹¹; ³⁵⁹²

Administration of midazolam hydrochloride by rapid intravenous injection should be avoided, especially in neonatal and non-neonatal pediatric populations.³⁵⁹⁰; ³⁵⁹¹; ³⁵⁹²

Intra-arterial injection and extravasation should be avoided.³⁵⁹⁰; ³⁵⁹¹; ³⁵⁹²

Midazolam hydrochloride (Seizalam) is labeled only for intramuscular administration, specifically into the mid-outer thigh (i.e., vastus lateralis muscle).³⁵⁹³

Intact vials and cartridges should be stored at controlled room temperature.³⁵⁹⁰; ³⁵⁹¹; ³⁵⁹²; ³⁵⁹³

pH Effects

Midazolam hydrochloride is highly water soluble at pH 4 or less; at higher pH values, increased lipid solubility occurs.¹¹⁴⁵ The rate of photodecomposition increases with increasing pH from 1.3 to 6.4.¹⁹⁴⁴

Light Effects

Exposure of the commercially available injection (Roche) to sunlight for 4 months resulted in the yellowing of the solution in 1 month and a midazolam loss of about 8% in 4 months.¹⁹⁴⁴

Syringes

In 2015, reports of decreased potency of certain drugs (e.g., midazolam hydrochloride) stored in Becton Dickinson syringes for extended periods (i.e., exceeding 24 hours) were confirmed by the manufacturer of these syringes; the cause of this change was later identified to be the inclusion of an alternate rubber stopper in the plunger of certain product lots of syringes.³⁰²⁹; ³⁰³⁶; ³⁰³⁷; ³⁰³⁹; ³⁰⁴¹; ³⁰⁴² Decreased potency was not observed when the syringes were filled and used promptly.³⁰³⁷ Use of the alternate stopper was later discontinued and use of the primary stopper in such syringes was resumed; however, Becton Dickinson states that its general-use syringes are cleared by FDA for immediate use in fluid aspiration and injection and that such syringes, regardless of the stopper material, have not been cleared by FDA for use as a closed-container system.³³⁹¹

Midazolam hydrochloride (Hospira) undiluted at a midazolam concentration of 5 mg/mL and diluted to a midazolam concentration of 0.4 mg/mL in dextrose 5% was packaged as 5 mL in 10-mL polypropylene syringes (Becton Dickinson) and stored at ambient room temperature protected from light.³⁸⁸⁷ The solutions remained clear and colorless with little loss of drug in 100 days.³⁸⁸⁷

Midazolam hydrochloride (Roche) prepared at a midazolam concentration of 2 mg/mL in sodium chloride 0.9% was packaged as 3 mL in 10-mL polypropylene infusion pump syringes (Pharmacia Deltec). Little or no loss occurred during 10 days of storage at 5 and 30°C.¹⁹⁶⁷

Midazolam hydrochloride (Roche) prepared at a midazolam concentration of 3 mg/mL in sodium chloride 0.9% exhibited no visual changes and had losses of 6.5% at 20°C and 8.7% at 32°C in polypropylene syringes (Terumo) and of 8.9% at 32°C in glass vials after 13 days.¹⁵⁹⁵

The stability of midazolam (salt form unspecified) 1 mg/mL repackaged in polypropylene syringes was evaluated. Little change in concentration was found after 4 weeks of storage at room temperature not exposed to direct light.²¹⁶⁴

Midazolam hydrochloride (Roche) at a midazolam concentration of 5 mg/mL was packaged as 10 mL in 12-mL polypropylene syringes (Sherwood). No loss occurred in 36 days stored at 25°C protected from light.²⁰⁸⁸

Standardize 4 Safety

One or more standardized concentrations for this drug have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. (See Standardize 4 Safety in Users Guide.) Recommendations developed to date through this initiative are available at www.ashp.org/pharmacy-practice/standardize-4-safety-initiative.

Table 1. Standardize 4 Safety Continuous IV Infusion Standard Concentrations for Midazolam³⁶³⁵; ³⁶³⁶

Table 2. Standardize 4 Safety PCA Standard Concentrations for Midazolam³⁹⁹⁰

Solution Compatibility

Additive Compatibility

Drugs in Syringe Compatibility

Y-Site Injection Compatibility (1:1 Mixture)

Additional Compatibility Information

Other Drugs

One manufacturer (Hospira) states that midazolam hydrochloride may be administered in the same syringe as atropine sulfate, meperidine hydrochloride, morphine sulfate, and scopolamine hydrobromide.³⁵⁹⁰; ³⁵⁹¹; ³⁵⁹²

For a list of references cited in the text of this monograph, search the monograph titled References.

ASHP^® Injectable Drug Information^TM. Selected Revisions December 5, 2024. © Copyright, 2024. American Society of Health-System Pharmacists^®, 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.