Water

Uses and Indications

Sterile Water for Injection, USP is indicated for use in the aseptic preparation of parenteral solutions and as a diluent or solvent for the preparation of parenteral solutions. It is specifically indicated for:

• Use with automated compounding devices for preparing intravenous admixtures in the pharmacy.

• Diluting or dissolving drugs for intravenous, intramuscular, or subcutaneous injection, according to the instructions of the manufacturer of the drug to be administered.

• Use as a solvent or diluent vehicle for parenterally administered drugs or solutions.

• Serving as a source of water for parenteral fluid replenishment after suitable additives are introduced.

Sterile Water for Irrigation, USP is indicated for:

• Use as an irrigating fluid or pharmaceutic aid.

• General irrigation, washing, rinsing, and dilution purposes that permit the use of sterile, nonpyrogenic, solute-free water.

• Use as an adjunct in the preparation of non-intravenously administered nutrient mixtures.

Limitations of Use:

• Sterile Water for Injection is not indicated for use in neonates.

• AQUALITE™ is indicated for intraperitoneal, irrigation, and topical use only and is not for injection.

Dosage and Administration

Dosage and administration of Sterile Water for Injection, USP, are determined by the prescribing physician based on the patient's age, weight, clinical condition, and laboratory determinations. The volume of Sterile Water used for diluting or dissolving any drug for injection is dependent on the vehicle concentration, dose, and route of administration as recommended by the manufacturer.

Sterile Water for Injection is intended for intravenous use only after appropriate admixture or dilution to achieve isotonicity with the addition of suitable solutes. Following the introduction of additives, it is essential to use aseptic technique, mix thoroughly, and not store any unused portions. Parenteral drug products must be visually inspected for particulate matter and discoloration prior to administration whenever the solution and container permit.

When compounding intravenous admixtures, Sterile Water for Injection should be prepared under the direction of a pharmacist using strict aseptic techniques in a laminar flow hood. The Pharmacy Bulk Package is specifically designed for use with automated compounding devices and should not be used for direct infusion. Once the outlet port has been accessed, the contents should be withdrawn promptly in one continuous operation, and any remaining solution should be discarded no later than 4 hours after initial closure puncture.

For administration, the following steps should be adhered to:

1. Prepare the additive port using aseptic technique and an appropriate delivery needle.

2. Puncture the resealable additive port and inject the medication, ensuring to withdraw the needle after injecting.

3. Mix the container contents thoroughly.

4. Close the flow control clamp of the administration set and remove the cover from the outlet port.

5. Insert the piercing pin of the administration set into the port with a twisting motion until securely seated.

6. Suspend the container and establish the proper fluid level in the drip chamber by squeezing and releasing it.

7. Open the flow control clamp to clear air from the set, then close the clamp.

8. Attach the set to the venipuncture device, prime if necessary, and regulate the rate of administration.

Compounded admixtures may be stored under refrigeration for up to 24 hours, and administration should be completed within this timeframe after removal from refrigeration. It is crucial to consult with a pharmacist regarding the compatibility of any additives prior to their introduction into the solution.

Contraindications

Sterile Water for Injection, USP is contraindicated for intravenous administration without the addition of a solute due to its hemolytic properties and hypotonicity. It must be made approximately isotonic prior to use to prevent adverse effects. Direct infusion of Sterile Water is not recommended, and it should not be used for non-automated admixture preparations. Additionally, Sterile Water is not suitable for injection by usual parenteral routes and should not be administered in series connections.

Bacteriostatic Water for Injection, which contains benzyl alcohol, is contraindicated in neonates due to the potential toxicity of benzyl alcohol. It should also not be used for fluid replacement or in epidural or spinal anesthesia procedures.

Warnings and Precautions

FOR DILUTION ONLY Sterile Water for Injection is intended for compounding and dilution purposes only. It must not be used for direct infusion. Intravenous administration without a solute may result in hemolysis, which can lead to hemoglobin-induced renal failure.

Hypotonicity and Hemolysis This solution is hypotonic and can cause hemolysis if injected without appropriate solutes. It is crucial to ensure that the solution is made approximately isotonic before administration to prevent serious adverse reactions.

Fluid and Solute Overload The administration of Sterile Water for Injection, especially with additives, can lead to fluid and/or solute overload. This may result in dilution of serum electrolyte concentrations, overhydration, congested states, or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentrations of administered solutions, while the risk of solute overload causing congested states is directly proportional to these concentrations.

Aluminum Toxicity Warning WARNING: This product contains aluminum, which may be toxic. Prolonged parenteral administration can lead to toxic levels, particularly in patients with impaired kidney function. Premature neonates are at heightened risk due to their immature kidneys and the need for calcium and phosphate solutions that contain aluminum. Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral aluminum levels greater than 4 to 5 mcg/kg/day may accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Monitoring Requirements Patients receiving this solution should be monitored for absorption of clinically relevant amounts of fluid during and after administration, particularly those at increased risk of complications from fluid overload or hyponatremia.

General Precautions

• Do not heat the solution above 66°C (150°F).

• Inspect the final infusate for cloudiness or precipitation immediately after mixing and periodically during administration.

• Avoid using plastic containers in series connections.

• If using a pumping device for administration, discontinue pumping before the container runs dry to prevent air embolism.

• Ensure that the solution is clear and that the container and seals are intact before use.

• The drug product contains no more than 25 mcg/L of aluminum.

Irrigation Use Sterile Water for Irrigation is hypotonic and will cause hemolysis; it is not recommended for use during surgical procedures. After opening, the contents should be used promptly to minimize bacterial growth or pyrogen formation, and any unused portion should be discarded as it contains no preservative.

Side Effects

Reactions associated with the administration of Sterile Water for Injection may vary based on the solution, added drugs, or the technique of reconstitution or administration. The following adverse reactions have been reported:

Serious Adverse Reactions

• Hemolysis: Intravenous administration of Sterile Water for Injection without a solute may result in hemolysis, which can lead to hemoglobin-induced renal failure.

• Aluminum Toxicity: This product contains aluminum that may be toxic, particularly with prolonged parenteral administration in patients with impaired kidney function. Premature neonates are at increased risk due to immature kidney function and the need for calcium and phosphate solutions that contain aluminum. Accumulation of aluminum at levels greater than 4 to 5 mcg/kg/day has been associated with central nervous system and bone toxicity.

Common Adverse Reactions

• Febrile Response

• Local Tenderness

• Abscess

• Tissue Necrosis or Infection: This may occur at the site of injection.

• Venous Thrombosis or Phlebitis: Extending from the site of injection.

• Extravasation

• Hypervolemia: Particularly relevant when large volumes are administered, especially in neonates or very small infants.

Warnings

• The administration of intravenous solutions can cause fluid and/or solute overload, resulting in dilution of serum electrolyte concentrations, overhydration, congested states, or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentrations of administered solutions.

• Accidental Contamination: Careless technique may transmit infection.

Precautions

• Sterile Water for Injection should only be used as a diluent or solvent and must not be administered without the addition of a solute to avoid hemolysis.

• The solution must be clear, and the seal intact before use. Containers should be discarded if damaged or if the solution is not clear.

Overdosage

• In the event of overhydration or solute overload, re-evaluate the patient and institute appropriate corrective measures. Manifestations of water intoxication may include behavioral changes, central nervous system disturbances, and weight gain.

Pediatric Use

• Safety and effectiveness have been established in pediatric patients; however, caution is advised in neonates or very small infants due to the potential for fluid and electrolyte imbalance.

Drug Interactions

Some drugs for injection may exhibit incompatibilities when combined in a given vehicle, particularly when the vehicle contains benzyl alcohol. It is advisable to consult with a pharmacist when considering the use of Sterile Water for injection in conjunction with other medications.

Additives introduced into Sterile Water may also be incompatible. When adding such substances, it is essential to employ aseptic techniques, ensure thorough mixing, and avoid storage of the mixture. Additionally, parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration, whenever the solution and container permit.

No specific drug interactions or laboratory test interactions have been provided for Sterile Water.

Pediatric Use

Safety and effectiveness of Sterile Water have been established in pediatric patients. The data supporting its use in this population are based on the similarity of clinical conditions between pediatric and adult populations.

In neonates or very small infants, caution is advised as the volume of fluid administered may affect fluid and electrolyte balance. Pediatric patients are at a higher risk compared to adults for developing complications such as encephalopathy due to hyponatremia if there is excessive absorption of Sterile Water for Irrigation.

This product contains no more than 25 mcg/L of aluminum. No specific pediatric use information, recommended ages, dosing differences, safety concerns, or special precautions for children are provided in the insert for certain formulations.

Geriatric Use

Elderly patients may require cautious use of Sterile Water for Irrigation due to the potential for decreased cardiac, renal, or hepatic function, as well as the presence of other diseases or concomitant drug therapy. While no specific information regarding dosage adjustments or safety concerns for geriatric patients is provided in the product insert, healthcare professionals should consider these factors when administering the product. It is advisable to refer to the package insert of the solute used for additional warnings, particularly regarding aluminum content. Monitoring of elderly patients is recommended to ensure safety and efficacy during treatment.

Pregnancy

Animal reproduction studies have not been conducted with Sterile Water for Injection or Sterile Water for Irrigation. The effects of sterile water containing additives on fetal harm or reproduction capacity when administered to pregnant patients are not known. Therefore, Sterile Water for Injection with additives should be given to pregnant patients only if clearly needed.

Sterile Water for Injection and Sterile Water for Irrigation are classified as Pregnancy Category C. This indicates that risk cannot be ruled out, and there are no adequate and well-controlled studies in pregnant women. It is important to note that all pregnancies carry a background risk of birth defects, loss, or other adverse outcomes, with the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies being 2 to 4% and 15 to 20%, respectively.

For any specific concerns regarding the use of Sterile Water in pregnant patients, healthcare providers should refer to the package insert of the solute used.

Lactation

Nursing mothers should be aware of the potential for excretion of Sterile Water in breast milk. There is an associated risk to breastfed infants when this medication is used during lactation. Caution is advised when administering this medication to nursing mothers, as it is not known whether the components of Sterile Water can affect breastfed infants or the production of breast milk.

While there are no specific warnings or recommendations regarding the use of Sterile Water in nursing mothers, the lack of clinical data during lactation necessitates careful consideration of the mother's clinical need for the medication against any potential adverse effects on the breastfed infant. The developmental and health benefits of breastfeeding should also be taken into account.

Renal Impairment

Patients with renal impairment may require careful consideration when using Sterile Water for Injection or Solution due to the potential toxicity of aluminum, which is present in these products. Prolonged parenteral administration of aluminum can lead to toxic levels, particularly in individuals with compromised kidney function. Research indicates that patients, including premature neonates, receiving parenteral aluminum at doses exceeding 4 to 5 mcg/kg/day are at risk of accumulating aluminum to levels associated with central nervous system and bone toxicity. Tissue loading may occur even at lower administration rates.

For patients with reduced kidney function, dosage adjustments may be necessary, and renal function tests should be monitored closely. It is advisable to consider a reduced dose for those with decreased creatinine clearance. Additionally, caution is warranted when using solutions for urologic irrigation in patients with severe cardiopulmonary or renal dysfunction, as these patients are at increased risk of complications related to fluid overload syndrome. Avoiding procedures that require prolonged irrigation times or high irrigation fluid pressure is also recommended to prevent absorption issues in patients with renal impairment.

Hepatic Impairment

Patients with hepatic impairment do not have specific dosage adjustments, special monitoring requirements, or precautions outlined for the use of Sterile Water or Bacteriostatic Water. The available information does not indicate any need for alterations in administration or monitoring parameters related to liver function. Therefore, no specific recommendations can be made for this patient population regarding the use of these products.

Overdosage

The administration of large amounts of Sterile Water for Injection, USP, particularly when used with additives, can lead to fluid and/or solute overload. This condition may result in dilution of serum electrolyte concentrations, overhydration, congested states, or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentrations of the administered solutions, while the risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the electrolyte concentrations of such solutions.

In cases of overdosage, particularly hypotonic expansion, an increase in fluid intake over fluid output may occur, leading to water intoxication. This can manifest as behavioral changes such as confusion, apathy, and disorientation, as well as central nervous system disturbances including weakness, muscle twitching, headaches, nausea, vomiting, convulsions, and weight gain. Overdosage may be particularly concerning in patients with impaired kidney function, including premature neonates, who are at risk of accumulating aluminum from prolonged parenteral administration, potentially leading to central nervous system and bone toxicity.

In the event of overhydration or solute overload, it is essential to re-evaluate the patient and institute appropriate corrective measures. Treatment may involve withholding fluids until excessive water is excreted. In cases of severe hyponatremia, cautious administration of hypertonic saline may be necessary to increase extracellular osmotic pressure and facilitate the excretion of excess water by the kidneys.

Monitoring is crucial, especially in neonates or very small infants, as they are at a higher risk of fluid overload. Clinicians should be vigilant for signs of excessive fluid absorption during procedures involving irrigation with hypotonic fluids, as this can lead to serious complications such as hyponatremia, hypoosmolality, and fluid overload. Immediate intervention may be required if clinically relevant absorption occurs.

Nonclinical Toxicology

Teratogenic Effects

Animal reproduction studies have not been conducted with Sterile Water for Injection. It is unknown whether sterile water containing additives can cause fetal harm when administered to a pregnant woman or affect reproductive capacity. Therefore, Sterile Water for Injection with additives should be given to a pregnant woman only if clearly needed.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with Sterile Water for Irrigation, USP have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility. No relevant information regarding these aspects is available from the other sources.

Non-Teratogenic Effects

No specific non-teratogenic effects are mentioned in the provided data.

Animal Pharmacology and Toxicology

No specific animal pharmacology and toxicology details are mentioned in the provided data.

Storage and Handling

Sterile Water is supplied in various forms, including Injection and Solution, and is available in single-dose flexible plastic containers, plastic vials, and larger irrigation containers. The packaging is designed to be sterile and nonpyrogenic, with some containers being non-PVC and non-DEHP. Each vial is intended for single-dose use, with no preservatives added, and any unused portion should be discarded.

The recommended storage conditions for Sterile Water are at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is crucial to protect the product from freezing and to minimize exposure to excessive heat. While brief exposure up to 40°C (104°F) does not adversely affect the product, it is advisable to avoid prolonged exposure to high temperatures.

For optimal handling, it is important to ensure that the solution is clear and that the container seal is intact before use. Stock should be rotated frequently to maintain product integrity.