Calcium Chloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: 10% (10 mL)

Solution, Intravenous [preservative free]:

Generic: 10% (10 mL)

Pharmacology

Mechanism of Action

Moderates nerve and muscle performance via action potential excitation threshold regulation

Pharmacokinetics/Pharmacodynamics

Excretion

Primarily feces (80% as insoluble calcium salts); urine (20%)

Protein Binding

~40%, primarily to albumin (Wills, 1971)

Use: Labeled Indications

Treatment of hypocalcemia and conditions secondary to hypocalcemia (eg, tetany, seizures, arrhythmias); emergent treatment of severe hypermagnesemia

Use: Off Label

Beta-blocker overdosecyes

Data from one human case report and an animal study suggest that calcium chloride may be helpful in beta blocker overdose Love 1996, Pertoldi 1998. Clinical experience also suggests the utility of calcium chloride in the treatment of beta blocker overdose Kerns 2007.

Based on the American Heart Association (AHA) Guideline for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, calcium chloride is a recommended treatment option in the setting of beta-blocker overdose (refractory to glucagon and high-dose inotropes/vasopressors).

Calcium channel blocker overdosecyes

Data from a limited number of patients suggest the use of calcium chloride may be beneficial for the treatment of hemodynamically unstable calcium channel blocker overdose refractory to other treatments Perkins 1978, Ramoska 1993. Clinical experience also suggests the utility of calcium chloride in the treatment of calcium channel blocker overdose Kerns 2007.

Based on the American Heart Association (AHA) Guideline for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, the Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults, and the American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) Guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay, calcium chloride is an effective and recommended treatment option in the setting of calcium channel blocker overdose.

Hyperkalemia, severeyes

Based on the American Heart Association (AHA) Guideline for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, calcium chloride is an effective and recommended treatment to stabilize the myocardial cell membrane in patients with severe hyperkalemia (K+ >6.5 mEq/L with toxic ECG changes).

Malignant arrhythmias (including cardiac arrest) associated with hypermagnesemiayes

Based on the American Heart Association (AHA) Guideline for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, calcium chloride is effective and recommended for the treatment of malignant arrhythmias (including cardiac arrest) in patients with hypermagnesemia.

Contraindications

Known or suspected digoxin toxicity; not recommended as routine treatment in cardiac arrest (includes asystole, ventricular fibrillation, pulseless ventricular tachycardia, or pulseless electrical activity)

Dosage and Administration

Dosing: Adult

Note: One gram of calcium chloride salt is equal to 270 mg of elemental calcium.

Dosages are expressed in terms of the calcium chloride salt based on a solution concentration of 100 mg/mL (10%) containing 1.4 mEq (27 mg)/mL elemental calcium.

Beta-blocker overdose (off-label use): Based on limited data: IV: Initial: Using a 10% solution: 20 mg/kg over 5 to 10 minutes (maximum: 1 to 2 g/dose); may repeat every 10 to 20 minutes for 3 to 4 additional doses or initiate a continuous infusion of 20 to 40 mg/kg/hour titrated to improve hemodynamic response (AHA [Vanden Hoek 2010]; DeWitt 2004; Kerns 2007).

Calcium channel blocker overdose (off-label use): Based on limited data: IV: Initial: Using a 10% solution: 20 mg/kg over 5 to 10 minutes (maximum: 1 to 2 g/dose); may repeat every 10 to 20 minutes for 3 to 4 additional doses or initiate a continuous infusion of 20 to 40 mg/kg/hour titrated to improve hemodynamic response (ACC/AHA/HRS [Kusumoto 2018]; AHA [Vanden Hoek 2010]; DeWitt 2004; Kerns 2007; St-Onge 2017). Note: Some recommend maintaining serum ionized calcium at a goal of twice normal (Kerns 2007).

Cardiac arrest or cardiotoxicity in the presence of hyperkalemia, hypocalcemia, or hypermagnesemia: IV: 500 to 1,000 mg over 2 to 5 minutes; may repeat as necessary (AHA [Vanden Hoek 2010])

Note: Routine use in cardiac arrest is not recommended due to the lack of improved survival (AHA [Neumar 2010]).

Hypocalcemia: IV:

Acute, symptomatic: Manufacturer's labeling: 200 to 1,000 mg every 1 to 3 days

Severe, symptomatic (eg, seizure, tetany): 1,000 mg over 10 minutes; repeat every 60 minutes until symptoms resolve (French 2012)

Note: In general, IV calcium gluconate is preferred over IV calcium chloride in nonemergency settings due to the potential for more severe extravasation with calcium chloride.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: 1 g of calcium chloride salt is equal to 273 mg of elemental calcium.

Daily maintenance calcium: Dosage expressed in terms of elemental calcium.

Infants and Children <25 kg: IV: 1 to 2 mEq/kg/day.

Children 25 to 45 kg: IV: 0.5 to 1.5 mEq/kg/day.

Children >45 kg and Adolescents: IV: 0.2 to 0.3 mEq/kg/day or 10 to 20 mEq/day.

Parenteral nutrition, maintenance calcium requirement (ASPEN [Mirtallo 2004]): Note: Dosage expressed in terms of elemental calcium.

Infants and Children ≤50 kg: IV: 0.5 to 4 mEq/kg/day as an additive to parenteral nutrition solution.

Children >50 kg and Adolescents: IV: 10 to 20 mEq/day as an additive to parenteral nutrition solution.

Hypocalcemia: Note: In general, IV calcium gluconate is preferred over IV calcium chloride in nonemergency settings due to the potential for extravasation with calcium chloride. Dosage expressed in mg of calcium chloride.

Infants, Children, and Adolescents:

Manufacturer's recommendations: IV: 2.7 to 5 mg/kg/dose every 4 to 6 hours; maximum dose: 1,000 mg.

Alternative dosing: IV: 10 to 20 mg/kg/dose; maximum dose: 1,000 mg; repeat every 4 to 6 hours if needed.

Cardiac arrest in the presence of hyperkalemia or hypocalcemia, hypermagnesemia, or calcium channel antagonist toxicity (PALS recommendations): Infants, Children, and Adolescents: Dosage expressed in mg of calcium chloride: IV, Intraosseous: 20 mg/kg/dose (maximum dose: 2,000 mg); may repeat in 10 minutes if necessary; if effective, consider IV infusion of 20 to 50 mg/kg/hour; Note: Routine use in cardiac arrest is not recommended due to the lack of improved survival (Hegenbarth 2008; Kleinman 2010).

Calcium channel blocker toxicity: Infants, Children, and Adolescents: Dosage expressed in mg of calcium chloride: IV: 20 mg/kg/dose infused over 5 to 10 minutes; if effective, consider IV infusion of 20 to 50 mg/kg/hour (Kleinman 2010).

Hypocalcemia secondary to citrated blood infusion: Infants, Children, and Adolescents: IV: 0.45 mEq elemental calcium for each 100 mL citrated blood infused.

Tetany: Infants, Children, and Adolescents: Dosage expressed in mg of calcium chloride: IV: 10 mg/kg over 5 to 10 minutes; may repeat after 6 hours or follow with an infusion with a maximum dose of 200 mg/kg/day.

Reconstitution

IV: For intermittent IV infusion, dilute to a maximum concentration of 20 mg/mL.

Administration

IV: For IV administration only. Not for IM or SubQ administration (severe necrosis and sloughing may occur). Avoid rapid administration (do not exceed 100 mg/minute except in emergency situations). For intermittent IV infusion, infuse diluted solution over 1 hour or no greater than 45 to 90 mg/kg/hour (0.6 to 1.2 mEq/kg/hour); administration via a central or deep vein is preferred; do not use small hand or foot veins for IV administration (severe necrosis and sloughing may occur). Typical rates of administration may vary with indication; refer to institutional protocol. Monitor ECG if calcium is infused faster than 2.5 mEq/minute; stop the infusion if the patient complains of pain or discomfort. Warm solution to body temperature prior to administration. Do not infuse calcium chloride in the same IV line as phosphate-containing solutions.

Vesicant; ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave needle/cannula in place); gently aspirate extravasated solution (do NOT flush the line).

Early/acute calcium extravasation: Initiate hyaluronidase antidote; remove needle/cannula; apply dry cold compresses; elevate extremity (Hurst 2004; Reynolds 2014).

Hyaluronidase: Intradermal or SubQ: Inject a total of 1 to 1.7 mL (15 units/mL) as five separate 0.2 to 0.3 mL injections (using a 25-gauge needle) into area of extravasation at the leading edge in a clockwise manner (MacCara 1983; Reynolds 2014; Zenk 1981). May also inject hyaluronidase through the catheter that caused the infiltration (Reynolds 2014).

Delayed calcium extravasation: Closely monitor site; most calcifications spontaneously resolve. However, if a severe manifestation of calcinosis cutis occurs, may initiate sodium thiosulfate antidote.

Sodium thiosulfate: IV: 12.5 g over 30 minutes; may increase gradually to 25 g 3 times per week; monitor for non-anion gap acidosis, hypocalcemia, severe nausea (Reynolds 2014).

Storage

Store intact vials at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not refrigerate solutions; IV infusion solutions in D5W, LR, NS, or other appropriate solutions are stable for 24 hours at room temperature.

Although calcium chloride is not routinely used in the preparation of parenteral nutrition, it is important to note that phosphate salts may precipitate when mixed with calcium salts. Solubility is improved in amino acid parenteral nutrition solutions. Check with a pharmacist to determine compatibility.

Drug Interactions

Baloxavir Marboxil: Polyvalent Cation Containing Products may decrease the serum concentration of Baloxavir Marboxil. Avoid combination

Bictegravir: Calcium Salts may decrease the serum concentration of Bictegravir. Management: Bictegravir, emtricitabine, and tenofovir alafenamide can be administered with calcium salts under fed conditions, but coadministration with or 2 hours after a calcium salt is not recommended under fasting conditions. Consider therapy modification

Bisphosphonate Derivatives: Polyvalent Cation Containing Products may decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral medications containing polyvalent cations within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Exceptions: Pamidronate; Zoledronic Acid. Consider therapy modification

Calcium Acetate: Calcium Salts may enhance the adverse/toxic effect of Calcium Acetate. Avoid combination

Calcium Channel Blockers: Calcium Salts may diminish the therapeutic effect of Calcium Channel Blockers. Monitor therapy

Cardiac Glycosides: Calcium Salts may enhance the arrhythmogenic effect of Cardiac Glycosides. Monitor therapy

CefTRIAXone: Calcium Salts (Intravenous) may enhance the adverse/toxic effect of CefTRIAXone. Ceftriaxone binds to calcium forming an insoluble precipitate. Management: Use of ceftriaxone is contraindicated in neonates (28 days of age or younger) who require (or are expected to require) treatment with IV calcium-containing solutions. In older patients, flush lines with compatible fluid between administration. Consider therapy modification

Deferiprone: Polyvalent Cation Containing Products may decrease the serum concentration of Deferiprone. Management: Separate administration of deferiprone and oral medications or supplements that contain polyvalent cations by at least 4 hours. Consider therapy modification

DOBUTamine: Calcium Salts may diminish the therapeutic effect of DOBUTamine. Monitor therapy

Dolutegravir: Calcium Salts may decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral calcium. Administer dolutegravir/rilpivirine at least 4 hours before or 6 hours after oral calcium salts. Alternatively, dolutegravir and oral calcium can be taken together with food. Consider therapy modification

Eltrombopag: Polyvalent Cation Containing Products may decrease the serum concentration of Eltrombopag. Management: Administer eltrombopag at least 2 hours before or 4 hours after oral administration of any polyvalent cation containing product. Consider therapy modification

Multivitamins/Fluoride (with ADE): May increase the serum concentration of Calcium Salts. Calcium Salts may decrease the serum concentration of Multivitamins/Fluoride (with ADE). More specifically, calcium salts may impair the absorption of fluoride. Management: Avoid eating or drinking dairy products or consuming vitamins or supplements with calcium salts one hour before or after of the administration of fluoride. Consider therapy modification

Multivitamins/Minerals (with ADEK, Folate, Iron): May increase the serum concentration of Calcium Salts. Monitor therapy

PenicillAMINE: Polyvalent Cation Containing Products may decrease the serum concentration of PenicillAMINE. Management: Separate the administration of penicillamine and oral polyvalent cation containing products by at least 1 hour. Consider therapy modification

Phosphate Supplements: Calcium Salts may decrease the absorption of Phosphate Supplements. Management: This applies only to oral phosphate and calcium administration. Administering oral phosphate supplements as far apart from the administration of an oral calcium salt as possible may be able to minimize the significance of the interaction. Exceptions: Sodium Glycerophosphate Pentahydrate. Consider therapy modification

Raltegravir: Polyvalent Cation Containing Products may decrease the serum concentration of Raltegravir. Management: Administer raltegravir 2 hours before or 6 hours after administration of the polyvalent cations. Dose separation may not adequately minimize the significance of this interaction. Consider therapy modification

Tetracyclines: Calcium Salts may decrease the serum concentration of Tetracyclines. Management: If coadministration of oral calcium with oral tetracyclines can not be avoided, consider separating administration of each agent by several hours. Exceptions: Eravacycline. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Monitor therapy

Thyroid Products: Calcium Salts may diminish the therapeutic effect of Thyroid Products. Management: Separate the doses of the thyroid product and the oral calcium supplement by at least 4 hours. Consider therapy modification

Trientine: Polyvalent Cation Containing Products may decrease the serum concentration of Trientine. Management: Avoid concomitant administration of trientine and oral products that contain polyvalent cations. If oral iron supplements are required, separate the administration by 2 hours. If other oral polyvalent cations are needed, separate administration by 1 hour. Consider therapy modification

Vitamin D Analogs: Calcium Salts may enhance the adverse/toxic effect of Vitamin D Analogs. Monitor therapy

Adverse Reactions

Frequency not defined. IV:

Cardiovascular (following rapid IV injection): Bradycardia, cardiac arrest, cardiac arrhythmia, hypotension, syncope, vasodilation

Central nervous system: Feeling abnormal (sense of oppression; with rapid IV injection), tingling sensation (with rapid IV injection)

Endocrine & metabolic: Hot flash (with rapid IV injection), hypercalcemia

Gastrointestinal: Dysgeusia (chalky taste), gastrointestinal irritation, increased serum amylase

Local: Local tissue necrosis (following extravasation)

Renal: Nephrolithiasis

Postmarketing and/or case reports: Cutaneous calcification

Warnings/Precautions

Concerns related to adverse effects:

• Extravasation: Vesicant; ensure proper catheter or needle position prior to and during infusion. Avoid extravasation. Extravasation may result in severe necrosis and sloughing. Monitor the IV site closely.

Disease-related concerns:

• Acidosis: Use with caution in patients with respiratory acidosis, renal impairment, or respiratory failure; acidifying effect of calcium chloride may potentiate acidosis.
• Hyperphosphatemia: Use with caution in patients with severe hyperphosphatemia as elevated levels of phosphorus and calcium may result in soft tissue and pulmonary arterial calcium-phosphate precipitation.
• Hypokalemia: Use with caution in patients with severe hypokalemia as acute rises in serum calcium levels may result in life-threatening cardiac arrhythmias.
• Hypomagnesemia: Hypomagnesemia is a common cause of hypocalcemia; therefore, correction of hypocalcemia may be difficult in patients with concomitant hypomagnesemia. Evaluate serum magnesium and correct hypomagnesemia (if necessary), particularly if initial treatment of hypocalcemia is refractory.
• Renal impairment: Use with caution in patients with chronic renal failure to avoid hypercalcemia; frequent monitoring of serum calcium and phosphorus is necessary.

Concurrent drug therapy issues:

• Ceftriaxone: Ceftriaxone may complex with calcium causing precipitation. Fatal lung and kidney damage associated with calcium-ceftriaxone precipitates has been observed in premature and term neonates. Due to reports of precipitation reaction in neonates, do not coadminister ceftriaxone with calcium-containing solutions, even via separate infusion lines/sites or at different times in any neonate. Ceftriaxone should not be administered simultaneously with any calcium-containing solution via a Y-site in any patient. However, ceftriaxone and calcium-containing solutions may be administered sequentially of one another for use in patients other than neonates if infusion lines are thoroughly flushed (with a compatible fluid) between infusions.
• Digoxin: Use with caution in digitalized patients; hypercalcemia may precipitate cardiac arrhythmias; use is contraindicated with known or suspected digoxin toxicity.

Dosage form specific issues:

• Aluminum: The parenteral product may contain aluminum; toxic aluminum concentrations may be seen with high doses, prolonged use, or renal dysfunction. Premature neonates are at higher risk due to immature renal function and aluminum intake from other parenteral sources. Parenteral aluminum exposure of >4 to 5 mcg/kg/day is associated with CNS and bone toxicity; tissue loading may occur at lower doses (Federal Register, 2002). See manufacturer’s labeling.

Other warnings/precautions:

• Appropriate product selection: Multiple salt forms of calcium exist; close attention must be paid to the salt form when ordering and administering calcium; incorrect selection or substitution of one salt for another without proper dosage adjustment may result in serious over or under dosing.
• Duration of use: Avoid metabolic acidosis (ie, administer only up to 2 to 3 days then change to another calcium salt).
• IV administration: For IV use only; do not inject SubQ or IM Avoid too rapid IV administration (do not exceed 100 mg/minute except in emergency situations).

Monitoring Parameters

Serum calcium and ionized calcium; albumin; serum phosphate; magnesium (to facilitate calcium repletion); ECG when appropriate. Monitor infusion site.

Calcium channel blocker overdose, beta-blocker overdose (off-label uses): Monitor hemodynamic response; monitor serum ionized calcium levels every 30 minutes initially then every 2 hours and maintain ionized calcium ~2 times the ULN; avoid severe hypercalcemia (ionized calcium levels >2 times ULN) (Kerns 2007).

Pregnancy

Pregnancy Considerations

Calcium crosses the placenta. The amount of calcium reaching the fetus is determined by maternal physiological changes. Calcium requirements are the same in pregnant and nonpregnant females (IOM 2011). Information related to use as an antidote in pregnancy is limited. In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey 2003). Medications used for the treatment of cardiac arrest in pregnancy are the same as in the non-pregnant woman. Doses and indications should follow current Advanced Cardiovascular Life Support guidelines. Appropriate medications should not be withheld due to concerns of fetal teratogenicity (Jeejeebhoy [AHA] 2015).

Patient Education

What is this drug used for?

• It is used to treat or prevent low calcium levels.
• It is used to protect the heart from high potassium levels.
• It is used to protect the heart and lungs from high magnesium levels.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Bad taste
• Hot flashes
• Lack of appetite
• Nausea
• Vomiting
• Constipation
• Loss of strength and energy
• Increased thirst
• Bone pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Dizziness
• Passing out
• Mood changes
• Change in amount of urine passed
• Abnormal heartbeat
• Kidney stone like back pain, abdominal pain, or blood in the urine.
• Severe injection site pain, redness, burning, edema, or irritation
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.