The following Structured Product Label (SPL) was submitted to the FDA by Henry Schein, Inc. for the product Calcium Gluconate (NDC 0404-9764). This document serves as the official prescribing information, containing essential scientific data and clinical materials required for healthcare providers and patients.
This specific version of the label includes detailed information regarding 1 indications and usage, 2 dosage and administration, 3 dosage forms and strengths, 4 contraindications, 5 warnings and precautions, 6 adverse reactions, 7 drug interactions, 8 use in specific populations, and other regulatory disclosures. Use the navigation below to review specific sections of the FDA submission.
Calcium Gluconate Injection is indicated for pediatric and adult patients for the treatment of acute symptomatic hypocalcemia.
Limitations of Use
The safety of Calcium Gluconate Injection for long term use has not been established.
2.1 Important Administration Instructions
For bolus intravenous administration:
For continuous intravenous infusion:
2.2 Recommended Dosage
Individualize the dose of Calcium Gluconate Injection within the recommended range depending on the severity of symptoms of hypocalcemia, the serum calcium 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 Patients
Image1.jpg (Image1)
2.3 Serum Calcium Monitoring
Measure 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 Impairment
For 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 Incompatibilities
Calcium Gluconate Injection, USP is a clear, colorless to slightly yellow, solution free from visible particles available in the following:
Each mL of Calcium Gluconate Injection, USP contains 9.3 mg (0.465 mEq) of elemental calcium.
Calcium Gluconate Injection is contraindicated in:
5.1 Arrhythmias with Concomitant Cardiac Glycoside Use
Cardiac arrhythmias may occur if calcium and cardiac glycosides are administered together. Hypercalcemia increases the risk of digoxin toxicity. Administration 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 (7.3)].
5.2 End-Organ Damage due to Intravascular Ceftriaxone-Calcium Precipitates
Concomitant use of ceftriaxone and Calcium Gluconate Injection is contraindicated in neonates (28 days of age 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 Calcinosis
Intravenous 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, swelling, 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 Administration
Rapid 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 Toxicity
Calcium Gluconate Injection 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.
The following serious adverse reactions are also described elsewhere in the labeling:
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 arrest
Administration site reactions: Local soft tissue inflammation, local necrosis, calcinosis cutis and calcification due to extravasation
7.1 Cardiac Glycosides
Hypercalcemia 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 Blockers
Administration of calcium may reduce the response to calcium channel blockers.
7.3 Drugs that may cause Hypercalcemia
Vitamin D, vitamin A, thiazide diuretics, estrogen, calcipotriene and teriparatide administration may cause hypercalcemia. Monitor plasma calcium concentrations in patients taking these drugs concurrently.
8.1 Pregnancy
Risk summary
Limited 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 Considerations
Disease-associated maternal risk
Maternal hypocalcemia can result in an increased rate of spontaneous abortion, premature and dysfunctional labor, and possibly preeclampsia.
Fetal/Neonatal adverse reactions
Infants 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 Lactation
Risk summary
Calcium 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 Use
The 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 precipitates. 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/L 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 Use
In 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 other drug therapy.
8.6 Renal Impairment
For patients with renal impairment, initiate Calcium Gluconate Injection at the lowest 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 Impairment
Hepatic function does not impact the availability of ionized calcium after calcium gluconate intravenous administration. Dose adjustment in hepatically impaired patients may not be necessary.
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.
Calcium Gluconate Injection, USP is a clear, colorless to slightly yellow, 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:
Formula1.jpg (Formula1)
Molecular formula: C12H22CaO14• H2O
Molecular weight: 448.39
Solubility in water: 3.5 g/100 mL at 25°C
Calcium Gluconate Injection, USP is available as 1,000 mg per 10 mL (100 mg per mL) in a single-dose vial.
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 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.
12.1 Mechanism of Action
Intravenous 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 Pharmacokinetics
Absorption
Calcium Gluconate Injection is 100% bioavailable following intravenous injection.
Metabolism
Calcium itself 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.
Distribution
Calcium 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 albumin).
Elimination
Studies 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.
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-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.
Calcium Gluconate Injection, USP is a clear, colorless to slightly yellow solution free from visible particles supplied as follows:
Image2.jpg (Image2)
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.
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.
| From Original Manufacturer/Distributor's NDC and Unit of Sale | To Henry Schein Repackaged Product NDC and Unit of Sale | Total Strength/Total Volume (Concentration) per unit |
| NDC 0143-9180-25 Packaged in a carton of 25 | NDC 0404-9764-10 1 10 mL plastic single-dose vial in a bag (Vial bears NDC 0143-9180-01) | 1,000 mg calcium gluconate per 10 mL (100 mg per mL) |
•Advise the patient that the risks associated with infusion including local tissue inflammation, local necrosis and calcinosis. [see Warnings and Precautions (5.3)].
Manufactured for:
Nivagen Pharmaceuticals Inc.
Sacramento, CA 95827 USA
Distributed by:
Hikma Pharmaceuticals USA Inc.
Berkley Heights, NJ 07922
Rev. 05/2023
Label1.jpg (Label1)
* Please review the disclaimer below.
