What it is
Bacteriostatic water is sterile water for injection with a small amount of benzyl alcohol added, usually 0.9%. The benzyl alcohol is a preservative: it stops bacteria from multiplying in the container, which is what “bacteriostatic” means. That is why it is sold in multiple-dose containers, from which more than one withdrawal can be made.
It is not a medicine in its own right. Its FDA-approved label gives one purpose only: diluting or dissolving other injectable drugs, following the instructions of whoever makes that other drug. The label also says what it is not for. It must not be used in newborns, it is not for replacing body fluids, and it is not for spinal or epidural procedures.
It is a different product from plain sterile water for injection, which has no preservative and is meant for a single use.
Bacteriostatic Water for Injection, USP is Water for Injection containing 0.9% (9 mg/mL) or 1.1% (11 mg/mL) benzyl alcohol, pH 5.7 (4.5 to 7.0), supplied in multiple-dose containers. It contains no other solute, so it is hypotonic, and the label states that intravenous administration without a solute may cause haemolysis and that the preparation must be made approximately isotonic before use.
Benzyl alcohol (phenylmethanol, C7H8O, 108.14 g/mol) is an aromatic alcohol used as an antimicrobial preservative in parenteral products; FDA defines a multiple-dose container as one that has met antimicrobial effectiveness testing requirements. Its disposition explains the neonatal warning. Benzyl alcohol is normally oxidised rapidly to benzoic acid, conjugated with glycine in the liver and excreted in urine as hippuric acid. In premature infants that conjugation pathway may be immature, so benzoic acid can accumulate and cause metabolic acidosis. The label’s clinical pharmacology section is otherwise about water itself, noting that the small volumes involved are unlikely to affect fluid balance except possibly in very small infants.
Who made it and when
Bacteriostatic water is a pharmacopoeial product rather than an invention with a single discoverer. Its composition is defined by the United States Pharmacopeia, and several companies sell it.
The FDA’s records list Hospira’s Bacteriostatic Water for Injection, now part of Pfizer, as approved under a new drug application on 27 October 1982. Repackagers sell the same product under Hospira’s application.
The timing matters. In 1982, the year of that approval, US doctors reported a cluster of deaths in premature babies that were traced to benzyl alcohol in flush solutions. That episode is the reason the current labels carry a warning against use in newborns.
Drugs@FDA lists NDA 018802 (Hospira) for Bacteriostatic Water for Injection in a plastic container, with an original approval date of 27 October 1982; the current Hospira label on DailyMed (revised August 2019) covers 0.9% benzyl alcohol in plastic vials and 1.1% in glass vials. DailyMed also carries repackager labels that cite the same NDA.
The neonatal history is documented in two 1982 reports. MMWR of 11 June 1982 described 16 deaths of pre-term infants under 2,500 g whose central catheters had been flushed daily with bacteriostatic normal saline containing 9 mg/mL benzyl alcohol, at two centres (New Orleans and Portland). Estimated benzyl alcohol intake ranged from 99 to 405 mg/kg/day; urine showed benzoate and hippurate, and serum benzoic acid was elevated. The illness featured metabolic acidosis progressing to respiratory distress and gasping respirations. Gershanik and colleagues described the “gasping syndrome” in the New England Journal of Medicine that November. Both centres reported no further similar deaths after switching to preservative-free flush solutions.
What the data say
There are no efficacy trials of bacteriostatic water, and none would make sense. It is a diluent, not a treatment, so the questions researchers ask about drugs, such as whether it works for a condition, do not apply.
What exists instead is safety information on the FDA label and in the medical literature. The label lists reactions that can come from the solution, from the drug added to it, or from the injection itself: fever, tenderness, abscess, tissue damage or infection at the injection site, and vein inflammation or clotting. The most serious recorded harm is to newborns, where benzyl alcohol has been linked to deaths. The label also notes that giving about 9 mL to a 6 kg infant could affect blood pressure, and that plain intravenous use without an added solute can damage red blood cells.
There are no efficacy trials of Bacteriostatic Water for Injection, because it is a vehicle rather than an active treatment and has no therapeutic claim to test. The safety record comes from the label and from post-marketing and case literature.
Label adverse reactions are attributed to the solution, added drugs, or the technique of reconstitution or administration: febrile response, local tenderness, abscess, tissue necrosis or infection at the injection site, venous thrombosis or phlebitis extending from the site, and extravasation. For benzyl alcohol, the label cites experimental data estimating that up to 30 mL may be given intravenously to adults, while an estimated 9 mL to a 6 kg infant or neonate is potentially capable of producing blood pressure changes. The 1982 MMWR note gives the underlying animal data: an intravenous LD50 of roughly 300 mg/kg in rats under rapid infusion and a serum half-life of about 1.5 hours in adult dogs. Haemolysis with intravenous use of a hypotonic vehicle is a physical property of the solution, shared with plain sterile water.
Regulatory picture
Bacteriostatic water is an FDA-approved prescription product. Its approval covers exactly one use: as a diluent for other injectable drugs, in line with those drugs’ own instructions. It does not make any drug mixed into it approved, and it says nothing about unapproved substances.
The label does not give a discard date after the container is first opened. The 28-day figure often quoted comes from FDA guidance, which treats 28 days as the default limit for an opened multiple-dose container unless the manufacturer’s label says otherwise.
Pharmacy compounding rules for bulk drug substances do not apply to a finished, approved supply product like this one.
Bacteriostatic Water for Injection is marketed under NDA 018802 and related applications as a prescription (Rx only) pharmaceutical aid. Its sole labelled indication is diluting or dissolving drugs for intravenous, intramuscular or subcutaneous injection according to the instructions of the manufacturer of the drug to be administered. The compounding field is recorded as not applicable: it is a finished approved product, not a bulk drug substance nominated for the 503A list.
FDA’s October 2018 guidance on package-type terms defines a multiple-dose container as a container of sterile medication for parenteral administration that has met antimicrobial effectiveness testing requirements, generally holding 30 mL or less. It states that the beyond-use date for an opened or entered multiple-dose container is 28 days unless otherwise specified by the manufacturer on the label, and that multiple-dose containers therefore do not normally carry a discard statement. The neonatal contraindication traces to FDA’s 1982 recommendation that benzyl-alcohol-preserved flush solutions and diluents not be used for newborns.
