SODIUM BICARBONATE

INDICATIONS AND USAGE: Sodium Bicarbonate Injection, USP is indicated in the treatment of metabolic acidosis which may occur in severe renal disease, uncontrolled diabetes, circulatory insufficiency due to shock or severe dehydration, extracorporeal circulation of blood, cardiac arrest and severe primary lactic acidosis. Sodium bicarbonate is further indicated in the treatment of certain drug intoxications, including barbiturates (where dissociation of the barbiturate-protein complex is desired), in poisoning by salicylates or methyl alcohol and in hemolytic reactions requiring alkalinization of the urine to diminish nephrotoxicity of hemoglobin and its breakdown products. Sodium bicarbonate also is indicated in severe diarrhea which is often accompanied by a significant loss of bicarbonate. Treatment of metabolic acidosis should, if possible, be superimposed on measures designed to control the basic cause of the acidosis — e.g., insulin in uncomplicated diabetes, blood volume restoration in shock. But since an appreciable time interval may elapse before all of the ancillary effects are brought about, bicarbonate therapy is indicated to minimize risks inherent to the acidosis itself. Vigorous bicarbonate therapy is required in any form of metabolic acidosis where a rapid increase in plasma total CO 2 content is crucial — e.g., cardiac arrest, circulatory insufficiency due to shock or severe dehydration, and in severe primary lactic acidosis or severe diabetic acidosis.

DOSAGE & ADMIINISTRATION Sodium Bicarbonate Injection, USP is administered by the intravenous route. In cardiac arrest, a rapid intravenous dose of one to two 50 mL vials (44.6 to 100 mEq) may be given initially and continued at a rate of 50 mL (44.6 to 50 mEq) every 5 to 10 minutes if necessary (as indicated by arterial pH and blood gas monitoring) to reverse the acidosis. Caution should be observed in emergencies where very rapid infusion of large quantities of bicarbonate is indicated. Bicarbonate solutions are hypertonic and may produce an undesirable rise in plasma sodium concentration in the process of correcting the metabolic acidosis. In cardiac arrest, however, the risks from acidosis exceed those of hypernatremia. In infants (up to two years of age), the 4.2% solution is recommended for intravenous administration at a dose not to exceed 8 mEq/kg/day. Slow administration rates and the 4.2% solution are recommended in neonates, to guard against the possibility of producing hypernatremia, decreasing cerebrospinal fluid pressure and inducing intracranial hemorrhage. In less urgent forms of metabolic acidosis, Sodium Bicarbonate Injection, USP may be added to other intravenous fluids. The amount of bicarbonate to be given to older children and adults over a four-to-eight-hour period is approximately 2 to 5 mEq/kg of body weight — depending upon the severity of the acidosis as judged by the lowering of total CO2 content, blood pH and clinical condition of the patient. In metabolic acidosis associated with shock, therapy should be monitored by measuring blood gases, plasma osmolarity, arterial blood lactate, hemodynamics and cardiac rhythm. Bicarbonate therapy should always be planned in a stepwise fashion since the degree of response from a given dose is not precisely predictable. Initially an infusion of 2 to 5 mEq/kg body weight over a period of 4 to 8 hours will produce a measurable improvement in the abnormal acid-base status of the blood. The next step of therapy is dependent upon the clinical response of the patient. If severe symptoms have abated, then the frequency of administration and the size of the dose may be reduced. In general, it is unwise to attempt full correction of a low total CO2 content during the first 24 hours of therapy, since this may be accompanied by an unrecognized alkalosis because of a delay in the readjustment of ventilation to normal. Owing to this lag, the achievement of total CO2 content of about 20 mEq/liter at the end of the first day of therapy will usually be associated with a normal blood pH. Further modification of the acidosis to completely normal values usually occurs in the presence of normal kidney function when and if the cause of the acidosis can be controlled. Values for total CO2 which are brought to normal or above normal within the first day of therapy are very likely to be associated with grossly alkaline values for blood pH, with ensuing undesired side effects. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS. Do not use unless solution is clear and the container or seal is intact. Discard unused portion.

3 DOSAGE FORMS AND STRENGTHS Sodium Bicarbonate Injection is a clear, colorless, sterile, nonpyrogenic, isotonic solution intended for intravenous use and available as: Injection: 12.6 mg/mL (0.150 mEq/mL), 12,600 mg of sodium bicarbonate injection in 1,000 mL single-dose Viaflo container Injection: 12.6 mg/mL (0.150 mEq/mL), 12,600 mg of Sodium Bicarbonate Injection in 1,000 mL single-dose Viaflo container. ( 3 )

WARNINGS Solutions containing sodium ions should be used with great care, if at all, in patients with congestive heart failure, severe renal insufficiency and in clinical states in which there exists edema with sodium retention. In patients with diminished renal function, administration of solutions containing sodium ions may result in sodium retention. The intravenous administration of these solutions can cause fluid and/or solute overloading resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. Extravascular infiltration should be avoided, see ADVERSE REACTIONS .

ADVERSE REACTIONS: Overly aggressive therapy with Sodium Bicarbonate Injection, USP can result in metabolic alkalosis (associated with muscular twitchings, irritability and tetany) and hypernatremia. Inadvertent extravasation of intravenously administered hypertonic solutions of sodium bicarbonate have been reported to cause chemical cellulitis because of their alkalinity, with tissue necrosis, ulceration or sloughing at the site of infiltration. Prompt elevation of the part, warmth and local injection of lidocaine or hyaluronidase are recommended to reduce the likelihood of tissue sloughing of extravasated I.V. solutions. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions Additives may be incompatible; norepinephrine and dobutamine are incompatible with sodium bicarbonate solution. The addition of sodium bicarbonate to parenteral solutions containing calcium should be avoided, except where compatibility has been previously established. Precipitation or haze may result from sodium bicarbonate-calcium admixtures. NOTE: Do not use the injection if it contains precipitate. Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, consult with pharmacist, if available. When introducing additives, use aseptic technique, mix thoroughly and do not store.

8 USE IN SPECIFIC POPULATIONS • Pediatric Use: Rapid injection in neonates and children under two years of age may produce hypernatremia, a decrease in cerebrospinal fluid pressure and possible intracranial hemorrhage. ( 8.4 ) 8.1 Pregnancy Risk Summary Available data from published literature over decades of use have not identified a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Physiological replacement of sodium bicarbonate is not expected to lead to increased risk of adverse fetal or maternal outcomes. Animal reproduction studies have not been conducted with sodium bicarbonate. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. 8.2 Lactation Risk Summary There are no data on the presence of sodium bicarbonate in either human or animal milk, the effects on the breast-fed infant or the effects on milk production following administration of sodium bicarbonate injection. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for sodium bicarbonate injection and any potential adverse effects on the breast-fed child from sodium bicarbonate or from the underlying maternal condition. 8.4 Pediatric Use Sodium bicarbonate injection is indicated in pediatric patients: • To raise plasma pH in pediatric patients with clinically significant metabolic acidosis • To alkalinize the urine in drug poisoning in cases in which urinary drug elimination is enhanced by urinary alkalinization Rapid injection of sodium bicarbonate injection solutions into neonates and children under two years of age may produce hypernatremia, a decrease in cerebrospinal fluid pressure and possible intracranial hemorrhage. The rate of administration in such patients should therefore be limited to no more than 8 mEq/kg/day. 8.5 Geriatric Use Clinical studies of sodium bicarbonate injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

12.1 Mechanism of Action Intravenous sodium bicarbonate therapy increases plasma bicarbonate, buffers excess hydrogen ion concentration, raises blood pH.

11 DESCRIPTION Sodium bicarbonate is an alkalinizing agent. Chemically, it is sodium hydrogen carbonate. Sodium bicarbonate is a white, crystalline powder. It is soluble in water and insoluble in alcohol. Sodium bicarbonate has the empirical formula NaHCO 3 , a calculated molecular weight of 84.01 and the following structural formula: Sodium Bicarbonate Injection is a sterile, non-pyrogenic, isotonic solution for intravenous infusion. Each mL contains 12.6 mg sodium bicarbonate which is equal to 0.150 milliequivalent each of Na + and HCO 3 - injection. The pH is adjusted between 7.00 and 9.25 with carbon dioxide. The solution contains no bacteriostat, antimicrobial agent or added buffer and is intended only for use as a single-dose injection. Viaflo container is a flexible plastic container fabricated from a multilayer sheeting composed of Polypropylene (PP), Polyamide (PA) and Polyethylene (PE). The amount of water that can permeate from the container into the overwrap is insufficient to affect the solution significantly. Solutions in contact with the flexible container can leach out certain of the container’s chemical components in very small amounts within the expiration period. The suitability of the container material has been confirmed by tests in animals according to USP biological tests for plastic containers. structural-formula-sodium-bicarbonate-1

HOW SUPPLIED Sodium bicarbonate injection, USP is supplied in the following dosage form: NDC Code: Conc % mg/mL (NaHC3) mEq/mL (Na+) mEq/mL (HCO3) mEq/ Container size (mL) mOsmol 68462-951-50 (vial) 68462-951-65 (25 vials per carton) 8.4 84 1 1 50/50 2/mL The 50 mL sodium bicarbonate injection vials are supplied as 25 vials per carton, with a single package insert. Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. Store at 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature.] Distributed by: Glenmark Pharmaceuticals Inc., USA Elmwood Park, NJ 07407 Questions? 1 (888) 721-7115 www.glenmarkpharma-us.com Manufactured by: Anthea Pharma Private Limited Hyderabad, 502307, INDIA August 2025 logo

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Sodium bicarbonate injection USP, 150 mEq/1,000 mL (0.15 mEq/mL) is supplied as a sterile, nonpyrogenic, clear, colorless solution available in a ready-to-use infusion bag in the following dosage form: Unit of Sale Unit of Use Conc % mg/mL (NaHCO 3 ) mEq/mL (Na + ) mEq/mL (HCO 3 - ) mEq/Container size (mL) mOsmol NDC 80830-2613-2 Carton containing 6 Pouch NDC 80830-2613-1 1,000 mL Single-dose Infusion Bag in a Pouch 1.26 12.6 0.15 0.15 150/1,000 0.3/mL 16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Avoid excessive heat. Protect from freezing. Keep covered in the pouch until time of use. Each ready-to-use infusion bag contains no preservatives. Once the ready-to-use infusion bag has been removed from the pouch, the ready-to-use infusion bag should be used within 24 hours, with any unused portion discarded.