NDC 52584-360 Calcium Gluconate

Calcium Gluconate

NDC Product Code 52584-360

NDC 52584-360-01

Package Description: 1 VIAL, PLASTIC in 1 BAG > 10 mL in 1 VIAL, PLASTIC

NDC 52584-360-03

Package Description: 1 VIAL, PLASTIC in 1 BAG > 50 mL in 1 VIAL, PLASTIC

NDC Product Information

Calcium Gluconate with NDC 52584-360 is a a human prescription drug product labeled by General Injectables And Vaccines, Inc.. The generic name of Calcium Gluconate is calcium gluconate. The product's dosage form is injection, solution and is administered via intravenous form.

Labeler Name: General Injectables And Vaccines, Inc.

Dosage Form: Injection, Solution - A liquid preparation containing one or more drug substances dissolved in a suitable solvent or mixture of mutually miscible solvents that is suitable for injection.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Calcium Gluconate Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • CALCIUM GLUCONATE MONOHYDRATE 98 mg/mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • CALCIUM SACCHARATE (UNII: 6AP9J91K4V)
  • HYDROCHLORIC ACID (UNII: QTT17582CB)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intravenous - Administration within or into a vein or veins.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Blood Coagulation Factor - [EPC] (Established Pharmacologic Class)
  • Increased Coagulation Factor Activity - [PE] (Physiologic Effect)
  • Calcium - [CS]
  • Cations -
  • Divalent - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: General Injectables And Vaccines, Inc.
Labeler Code: 52584
FDA Application Number: NDA208418 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 02-12-2018 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

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Calcium Gluconate Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Indications And Usage

These highlights do not include all the information needed to use CALCIUM GLUCONATE INJECTION safely and effectively. See full prescribing information for CALCIUM GLUCONATE INJECTION.CALCIUM GLUCONATE injection, for intravenous useInitial U.S. Approval: 1941Calcium Gluconate Injection is indicationd for pediatric and adult patients for the treatment of acute symptomatic hypocalcemia.Limitations of UseThe safety of Calcium Gluconate Injection for long term use has not been established.

Dosage And Administration

  • 2.1 Important Administration InstructionsCalcium Gluconate Injection contains 100 mg of calcium gluconate per mL which contains 9.3 mg (i.e., 0.465 mEq) of elemental calcium.Dilute Calcium Gluconate Injection prior to use in 5% dextrose or normal saline and assess for potential drug or IV fluid incompatibilities [see Dosage and Administration (2.5)].Inspect Calcium Gluconate Injection visually prior to administration. The solution should appear clear and colorless to slightly yellow. Do not administer if there is particulate matter or discoloration.Use the diluted solution immediately after preparation.Administer Calcium Gluconate Injection intravenously via a secure intravenous line to avoid calcinosis cutis and tissue necrosis [see Warnings and Precautions(5.3)].Administer Calcium Gluconate Injection by bolus administration nor continuous infusion:For bolus intravenous administration:Dilute the dose [see Dosage and Administration (2.2)] of Calcium Gluconate Injection in 5% dextrose or normal saline to a concentration 10-50 mg/mL prior to administration. Administer the dose slowly and DO NOT exceed an infustion rate of 200 mg/minute in adults or 100 mg/minute in pediatric patients, including neonates. Monitor patients, vitals and electrocardiograph (ECG) during administration [see Warnings and Precautions (5.4)].For continuous intravenous infusion:Dilute Calcium Gluconate Injection in 5% dextrose or normal saline to a concentration of 5.8-10 mg/mL prior to administration. Administer at the rate recommended in Table 1 [see Dosage and Administration (2.2)] and monitor patients, vitals, calcium and ECG during the infusion [see Warnings and Precautions (5.4)].Calcium Gluconate Injection is supplied in single-dose vials and pharmacy bulk packages [see Dosage and Administration (2.6)].2.2 Recommended DosageIndividualize the dose of Calcium Gluconate Injection within the recommended range depending on the severity of symptoms of hypocalcemia, the serum clacium level, and the acuity of onset of hypocalcemia.Table 1 provides dosing recommendations for Calcium Gluconate Injection in mg of calcium gluconate for neonates, pediatric and adult patients.Table 1. Dosing Recommendations in mg of Calcium Gluconate for Neonate, Pediatric, and Adult Patients2.3 Serum Calcium MonitoringMeasure serum calcium every 4 to 6 hours during intermittent infusions with Calcium Gluconate Injection and measure serum calcium every 1 to 4 hours during continuous infusion.2.4 Dosage in Renal ImpairmentFor patients with renal impairment, initiate Calcium Gluconate Injection at the lowest dose of the recommended dose ranges for all age groups and monitor serum calcium levels every 4 hours.2.5 Drug IncompatibilitiesDo not mix Calcium Gluconate Injection with ceftriaxone. Concurrent use of intravenous ceftriaxone and Calcium Gluconate Injection can lead to the formation of ceftriaxone-calcium precipitates. Concomitant use of ceftriaxone and intravenous calcium-containing products is contraindicated in neonates (28 days of age or younger) see Contraindications (4)]. In patients older than 28 days of age, ceftriaxone and calcium-containing products may be administered sequentially, provided the infusion lines are thoroughly flushed between infusions with a compatible fluid. Ceftriaxone must not be administered simultaneously with intravenous calcium-containing solutions via a Y-site in any age group [see Warnings and Precautions (5.2), Drug Interactions (7.3)].Do not mix Calcium Gluconate Injection with fluids containing bicarbonate or phosphate. Calcium Gluconate Injection is not physically compatible with fluids containing phosphate or bicarbonate. Precipitation may result if mixed.Do not mix Calcium Gluconate Injection with minocycline injection. Calcium complexes minocycline rendering it inactive.2.6 Preparation of Pharmacy Bulk PackageThe pharmacy bulk package (PBP) of Calcium Gluconate Injection is intended for dispensing of single doses to multiple patients in a pharmacy admixture program. Penetrate the container closure only one time with a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents. Use the PBP only in a suitable ISO Class 5 work area such as a laminar flow hood (or an equivalent clean air compounding area). Complete dispensing from the pharmacy bulk vial within 4 hours after the container closure is penetrated. Each dose dispensed from the Pharmacy Bulk Package vial must be used immediately.

Dosage Forms And Strengths

  • Calcium Gluconate Injection, USP is a clear, colorless to slightly yellow, solution avaialbe in the following:Single-dose vial: 1,000 mg per 10 mL (100 mg per mL)Single-dose vial: 5,000 mg per 50 mL (100 mg per mL)Pharmacy bulk package: 10,000 mg per 10 mL (100 mg per mL)Each mL of Calcium Gluconate Injection, USP contains 9.3 mg (0.465 mEq) of elemental calcium.

Contraindications

  • Calcium Gluconate Injection is contraindicated in:HypercalcemiaNeonates (28 days of age or younger) receiving ceftriaxone [see Warnings and Precautions (5.2)]

Warnings And Precautions

5.1 Arrhythmias with Concomitant Cardiac Glycoside UseCardiac arrhythmias may occur if calcium and cardiac glycosides are administered together. Hyperclacemia increases the risk of digoxin toxicity. Adminsitration of Calcium Gluconate Injection should be avoided in patients receiving cardiac glycosides. If concomitant therapy is necessary, Calcium Gluconate Injection should be given slowly in small amounts and with close ECG monitoring [see Drug Interactions (7.1)].5.2 End-Organ Damage due to Intravascular Ceftriaxone-Calcium PrecipitatesConcomitant use of ceftriaxone and Calcium Gluconate Injection is contraindicated in neonates (28 days of ane or younger) due to cases of fatal outcomes in neonates in which a crystalline material was observed in the lungs and kidneys at autopsy after ceftriaxone and calcium were administrated simultaneously through the same intravenous line. Concomitant administration can lead to the formation of ceftriaxone-calcium precipitates that may act as emboli, resulting in vascular spasm or infarction [see Contraindications (4)].In patients older than 28 days of age, ceftriaxone and Calcium Gluconate Injection may be administered sequentially, provided the infusion lines are thoroughly flushed between infusions with a compatible fluid. Do not administer Ceftriaxone simultaneously with Calcium Gluconate Injection via a Y-site in any age group.5.3 Tissue Necrosis and CalcinosisIntravenous administration of Calcium Gluconate Injection and local trauma may result in calcinosis cutis due to transient increase in local calcium concentration. Calcinosis cutis can occur with or without extravasation of Calcium Gluconate Injection, is characterized by abnormal dermal deposits of calcium salts, and clinically manifests as papules, plaques, or nodules that may be associated with erythema, sweling, or induration. Tissue necrosis, ulceration, and secondary infection are the most serious complications.If extravasation occurs or clinical manifestations of calcinosis cutis are noted, immediately discontinue intravenous administration at that site and treat as needed.5.4 Hypotension, Bradycardia, and Cardiac Arrhythmias with Rapid AdministrationRapid injection of Calcium Gluconate Injection may cause vasodilation, decreased blood pressure, bradycardia, cardiac arrhythmias, syncope and cardiac arrest. To avoid adverse reactions that may follow rapid intravenous administration, Calcium Gluconate Injection should be diluted with 5% dextrose or normal saline and infused slowly. If rapid intravenous bolus of Calcium Gluconate Injection is required, the rate of intravenous administration should not exceed 200 mg/minute in adults and 100 mg/minute in pediatric patients and ECG monitoring during administration is recommended [see Dosage and Administration(2.1)].5.5 Aluminum ToxicityCalcium Gluconate Injection contains contains aluminum, up to 400 mcg per liter, that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 mcg/kg/day to 5 mcg/kg/day accumulate aluminum levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Adverse Reactions

  • The following serious adverse reactions are also described elsewhere in the labeling:Arrhythmias with Concomitant Cardiac Glycoside Use [see Warnings and Precautions (5.1)]End-Organ Damage due to Intravascular Ceftriaxone-Calcium Precipitates [see Warnings and Precautions (5.2)]Tissue Necrosis and Calcinosis [see Warnings and Precautions (5.5)]Hypotension, Bradycardia, and Cardiac Arrhythmias [see Warnings and Precautions (5.5)]Aluminum toxicity [see Warnings and precautions (5.5)]The following adverse reactions associated with the use of calcium gluconate were identified in the literature. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.Cardiovascular: Vasodilation, decreased blood pressure, bradycardia, cardiac arrhythmia, syncope, cardiac arrestAdministration site reactions:Local soft tissue inflammation, local necrosis, calcinosis cutis and calcification due to extravasation

Drug Interactions

7.1 Cardiac GlycosidesHypercalcemia increases the risk of digoxin toxicity, while digoxin may be therapeutically ineffective in the presence of hypocalcemia. Synergistic arrhythmias may occur if calcium and cardiac glycosides are administered together. Avoid administration of Calcium Gluconate Injection in patients receiving cardiac glycosides; if considered necessary, administer Calcium Gluconate injection slowly in small amounts and monitor ECG closely during administration.7.2 Calcium Channel BlockersAdministration of calcium may reduce the response to calcium channel blockers.7.3 Drugs that may cause HypercalcemiaVitamin D, vitamin A, thiazide diuretics, estrogen, calcipotriene and teriparatide administration may cause hypercalcemia. Monitor plasma calcium concentrations in patients taking these drugs concurrently.

Use In Specific Populations

8.1 PregnancyRisk summaryLimited available data with Calcium Gluconate Injection use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. There are risks to the mother and the fetus associated with hypocalcemia in pregnancy [see Clinical Considerations].The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.Clinical ConsiderationsDisease-associated maternal riskMaternal hypocalcemia can result in an increased rate of spontaneous abortion, premature and dysfunctional labor, and possibly preeclampsia.Fetal/Neonatal adverse reactionsInfants born to mothers with hypocalcemia can have associated fetal and neonatal hyperparathyroidism, which in turn can cause fetal and neonatal skeletal demineralization, subperiosteal bone resorption, osteitis fibrosa cystica and neonatal seizures. Infants born to mothers with hypocalcemia should be carefully monitored for signs of hypocalcemia or hypercalcemia, including neuromuscular irritability, apnea, cyanosis and cardiac rhythm disorders.8.2 LactationRisk summaryCalcium is present in human milk as a natural component of human milk. It is not known whether intravenous administration of Calcium Gluconate Injection can alter calcium concentration in human milk. There are no data on the effects of Calcium Gluconate Injection on the breastfed infant, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Calcium Gluconate Injection and any potential adverse effects on the breastfed child from Calcium Gluconate Injection or from the underlying maternal condition.8.4 Pediatric UseThe safety and effectiveness of Calcium Gluconate Injection have been established in pediatric patients for the treatment of acute, symptomatic hypocalcemia.Pediatric approval for Calcium Gluconate Injection, including doses, is not based on adequate and well-controlled clinical studies. Safety and dosing recommendations in pediatric patients are based on published literature and clinical experience [see Dosage and Administration (2.2).Concomitant use of ceftriaxone and Calcium Gluconate Injection is contraindicated in neonates (28 days of age or younger) due to reports of fatal outcomes associated with the presence of lung and kidney ceftriaxone-calcium precitpiates. In patients older than 28 days of age, ceftriaxone and Calcium Gluconate Injection may be administered sequentially, provided the infusion lines are thoroughly flushed between infusions with a compatible fluid [see Contraindications (4) and Warnings and Precautions (5.2)]. This product contains up to 400 mcg/mL aluminum which may be toxic, particularly for premature neonates due to immature renal function. parenteral administration of aluminum greater than 4 to 5 mcg/kg/day is associated with central nervous system and bone toxicity [see Warnings and Precautions (5.5)].8.5 Geriatric UseIn general dose selection for an elderly patient should start at the lowest dose of the recommended dose range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or oether drug therapy.8.6 Renal ImpairmentFor patients with renal impairment, initiate Calcium Gluconate Injection at the loest dose of the recommended dose ranges across all age groups. Monitor serum calcium levels every 4 hours [see Dosage and Administration (2.4)].8.7 Hepatic ImpairmentHepatic function does not impact the availability of ionized calcium after clacium gluconate intravenous administration. Dose adjustment in hepatically imapired patients may not be necessary.

Overdosage

Overdosage of Calcium Gluconate Injection may result in hypercalcemia. Symptoms of hypercalcemia typically develop when the total serum calcium concentration is ≥12 mg/dL. Neurologic symptoms include depression, weakness, fatigue, and confusion at lower levels, with patients experiencing hallucinations, disorientation, hypotonicity, seizures, and coma. Effects on the kidney include diminished ability to concentrate urine and diuresis.If overdose of Calcium Gluconate Injection occurs immediately discontinue administration and provide supportive treatments to restore intravascular volume as well as promote calcium excretion in the urine if necessary.

Description

Calcium Gluconate Injection, USP is a sterile, preservative-free, nonpyrogenic, supersaturated solution of calcium gluconate, a form of calcium, for intravenous use.Calcium Gluconate is calcium D-gluconate (1:2) monohydrate. The structural formula is:Molecular formula: C12H22CaO14• H2OMolecular weight: 448.39Solubility in water: 3.5 g/100 mL at 25°CCalcium Gluconate Injection, USP is available as 1,000 mg per 10 mL (100 mg per mL) or 5,000 mg per 50 mL (100 mg per mL) in a single-dose vial, or 10,000 mg per 100 mL (100 mg per mL) in a pharmacy bulk package.Each mL of Calcium Gluconate Injection, USP contains 100 mg of calcium gluconate (equivalent to 94 mg of calcium gluconate and 4.5 mg of calcium saccharate tetrahydrate), hydrochloric acid and/or sodium hydroxide for pH adjustment (6.0 to 8.2) and sterile water for injection, q.s. It contains no antimicrobial agent.Each mL of Calcium Gluconate Injection, USP contains 9.3 mg (0.465 mEq) of elemental calcium.

Clinical Pharmacology

12.1 Mechanism of ActionIntravenous administration of calcium gluconate increases serum ionized calcium level. Calcium gluconate dissociates into ionized calcium in plasma. Ionized calcium and gluconate are normal constituents of body fluids.12.3 PharmacokineticsAbsorptionCalcium Gluconate Injection is 100% bioavailable following intravenous injection.MetabolismCalcium iteself does not undergo direct metabolism. The release of ionized calcium from intravenous administration of calcium gluconate is direct and does not seem to be affected by the first pass through the liver.DistributionCalcium in the body is distributed mainly in skeleton (99%). Only 1% of the total body calcium is distributed within the extracellular fluids and soft tissues. About 50% of total serum calcium is in the ionized form and represents the biologically active part. 8% to 10% serum calcium is bound to organic and inorganic acid and approximately 40% is protein-bound (primarily to ablumin).EliminationStudies have shown a relationship between urinary calcium excretion and the intravenous administration of calcium gluconate, with a significant increase in urinary calcium excretion observed after the intravenous administration of calcium gluconate.

Nonclinical Toxicology

13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityLong-term studies in animals have not been conducted to evaluate the carcinogenic potential of Calcium Gluconate Injection. Calcium gluconate was not mutagenic with or without metabolic activation in the Ames test with Salmonella typhimurium (strains TA-1535, TA-1537, and TA-1538) or Saccharomyces cerevisiae (Strain D4). Fertility studies in animals have not been conducted with calcium gluconate administered by the intravenous route.

How Supplied/Storage And Handling

Calcium Gluconate Injection, USP is a clear, colorless to slightly yellow solution supplied as follows:Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Do not freeze.Preservative Free. Discard any unused portion in the single-dose vial immediately or the Pharmacy Bulk Package vial within 4 hours after initial closure puncture.Each dose dispensed from the Pharmacy Bulk Package vial must be used immediately.The diluted solution must be used immediately.NOTE: Supersaturated solutions are prone to precipitation. The precipitate, if present, may be dissolved by warming the vial to 60° to 80°C, with occasional agitation, until the solution becomes clear. Shake vigorously. Allow to cool to room temperature before dispensing. Use injection only if clear immediately prior to use.

Patient Counseling Information

  • Advise the patient that the risks associated with infusion including local tissue inflammation, local necrosis and calcinosis. [see Warnings and Precautions (5.3)].

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