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FRESENIUS CALCIUM GLUCONATE IN SODIUM CHLORIDE INJECTION

Calcium Gluconate in Sodium Chloride Injection is a sterile, preservative-free, nonpyrogenic, solution of calcium gluconate, a form of calcium, for intravenous use.

Calcium Gluconate is calcium D-gluconate (1:2) monohydrate.

Molecular formula: C₁₂H₂₂CaO₁₄• H₂O Molecular weight: 448.39 Solubility in water: 3.5 g/100 mL at 25°C

Calcium Gluconate in Sodium Chloride Injection is available as 1,000 mg per 50 mL (18.8 mg per mL) or 2,000 mg per 100 mL (18.8 mg per mL) in single-dose bags.

Each mL of Calcium Gluconate in Sodium Chloride Injection contains 20 mg of calcium gluconate (equivalent to 18.8 mg of calcium gluconate and 0.9 mg of calcium saccharate tetrahydrate), hydrochloric acid and/or sodium hydroxide for pH adjustment (6.0 to 8.2) and sodium chloride 6.75 mg/mL as tonicity adjustor.

Each mL of Calcium Gluconate in Sodium Chloride Injection contains 1.86 mg (0.093 mEq) of elemental calcium.

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.

INDICATIONS AND USAGE

Calcium Gluconate in Sodium Chloride 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.

DOSAGE AND ADMINISTRATION

Calcium Gluconate in Sodium Chloride Injection contains 20 mg of calcium gluconate per mL which contains 1.86 mg (i.e. 0.093 mEq) of elemental calcium. See Table 1 for amounts of elemental calcium in Calcium Gluconate in Sodium Chloride Injection.

Do not dilute Calcium Gluconate in Sodium Chloride Injection prior to use. Any unused portion should be discarded.
Inspect Calcium Gluconate in Sodium Chloride Injection visually prior to administration. The solution should appear clear and colorless. Do not administer if there is particulate matter or discoloration.
Administer Calcium Gluconate in Sodium Chloride Injection intravenously via a secure intravenous line to avoid calcinosis cutis and tissue necrosis
Administer Calcium Gluconate in Sodium Chloride Injection by continuous infusion at the rate recommended in Table 2 and monitor patients, vitals, calcium and ECG during the infusion.
Check solution container composition, lot number, and expiry date.
Do not admix with other drugs.
Do not use solution containers in series connections.
Do not remove solution container from its overwrap until immediately before use.
The intact port cap provides visual tamper evidence. Do not use if port cap is prematurely removed. Maintain strict aseptic technique during handling.

INSTRUCTIONS FOR USE:

Always inspect the solution container before and after removal from the overwrap.
Place the solution container on a clean, flat surface. Remove the solution container from the overwrap.

Check the solution container for leaks by squeezing firmly. If leaks are found, discard.
Do not use if the solution is cloudy or a precipitate is present. To Prepare for Administration:
Immediately before inserting the infusion set, break off BLUE Infusion Port Cap with the arrow pointing away from the solution container.
Use a non-vented infusion set or close the air-inlet on a vented set.
Close the roller clamp of the infusion set
Hold the base of the BLUE infusion port, twist and push spike until fully inserted.
The BLUE infusion port contains a self-sealing septum that helps prevent leakage after removing the spike. The infusion port is not intended to be spiked more than once.
Suspend solution container from hanger hole.
For Single Use Only. Discard unused portion.

Recommended Dosage

Individualize the dose of Calcium Gluconate in Sodium Chloride 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 2 provides dosing recommendations for Calcium Gluconate in Sodium Chloride Injection in mg of calcium gluconate for neonates, pediatric and adult patients.

Table 2. Dosing Recommendations in mg of Calcium Gluconate for Neonate, Pediatric, and Adult Patients

Serum Calcium Monitoring

Measure serum calcium every 4 to 6 hours during intermittent infusions with Calcium Gluconate in Sodium Chloride Injection and measure serum calcium every 1 to 4 hours during continuous infusion.

Dosage in Renal Impairment

For patients with renal impairment, initiate Calcium Gluconate in Sodium Chloride Injection at the lowest dose of the recommended dose ranges for all age groups and monitor serum calcium levels every 4 hours.

Drug Incompatibilities

Do not mix Calcium Gluconate in Sodium Chloride Injection with ceftriaxone. Concurrent use of intravenous ceftriaxone and Calcium Gluconate in Sodium Chloride 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). 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.
Do not mix Calcium Gluconate in Sodium Chloride 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 in Sodium Chloride Injection with minocycline injection. Calcium complexes minocycline rendering it inactive.

CONTRAINDICATIONS

Calcium Gluconate in Sodium Chloride Injection is contraindicated in:

Hypercalcemia
Neonates (28 days of age or younger) receiving ceftriaxone.

WARNINGS AND PRECAUTIONS

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 in Sodium Chloride Injection should be avoided in patients receiving cardiac glycosides. If concomitant therapy is necessary, Calcium Gluconate in Sodium Chloride Injection should be given slowly in small amounts and with close ECG monitoring.

End-Organ Damage due to Intravascular Ceftriaxone-Calcium Precipitates: Concomitant use of ceftriaxone and Calcium Gluconate in Sodium Chloride 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.

Tissue Necrosis and Calcinosis: Intravenous administration of Calcium Gluconate in Sodium Chloride 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 in Sodium Chloride 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.

Hypotension, Bradycardia, and Cardiac Arrhythmias with Rapid Administration: Rapid injection of Calcium Gluconate in Sodium Chloride 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 in Sodium Chloride Injection should be 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.

Aluminum Toxicity: Calcium Gluconate in Sodium Chloride Injection contains aluminum, up to 100 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.

DRUG INTERACTIONS

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 in Sodium Chloride Injection in patients receiving cardiac glycosides; if considered necessary, administer Calcium Gluconate in Sodium Chloride Injection slowly in small amounts and monitor ECG closely during administration.

Calcium Channel Blockers: Administration of calcium may reduce the response to calcium channel blockers.

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.

USE IN SPECIFIC POPULATIONS

Pregnancy: 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.

Maternal hypocalcemia can result in an increased rate of spontaneous abortion, premature and dysfunctional labor, and possibly preeclampsia.

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.

Lactation: Calcium is present in human milk as a natural component of human milk. It is not known whether intravenous administration of Calcium Gluconate in Sodium Chloride 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 in Sodium Chloride Injection and any potential adverse effects on the breastfed child from Calcium Gluconate in Sodium Chloride Injection or from the underlying maternal condition.

Pediatric Use: The safety and effectiveness of Calcium Gluconate in Sodium Chloride Injection have been established in pediatric patients for the treatment of acute, symptomatic hypocalcemia.

Pediatric approval for Calcium Gluconate in Sodium Chloride 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.

Concomitant use of ceftriaxone and Calcium Gluconate in Sodium Chloride 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. This product contains up to 100 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.

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.

Renal Impairment: For patients with renal impairment, initiate Calcium Gluconate in Sodium Chloride Injection at the lowest dose of the recommended dose ranges across all age groups. Monitor serum calcium levels every 4 hours

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

Overdosage of Calcium Gluconate in Sodium Chloride 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 in Sodium Chloride Injection occurs immediately discontinue administration and provide supportive treatments to restore intravascular volume as well as promote calcium excretion in the urine if necessary.

FRESENIUS CALCIUM GLUCONATE IN SODIUM CHLORIDE INJECTION

FRESENIUS CALCIUM GLUCONATE IN SODIUM CHLORIDE INJECTION