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Calcium Chloride

Pronunciation

(KAL see um KLOR ide)

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)

Pharmacologic Category

  • Calcium Salt
  • Electrolyte Supplement, Parenteral

Pharmacology

Moderates nerve and muscle performance via action potential excitation threshold regulation

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: Unlabeled

Calcium channel blocker overdose; beta-blocker overdose (refractory to glucagon and high-dose vasopressors); severe hyperkalemia (K+ >6.5 mEq/L with toxic ECG changes) [ACLS guidelines]; malignant arrhythmias (including cardiac arrest) associated with hypermagnesemia [ACLS guidelines]

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)

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.

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 extravasation with calcium chloride.

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]).

Beta-blocker overdose, refractory to glucagon and high-dose vasopressors (off-label use): Note: Optimal dose has not been established (DeWitt, 2004): IV: 20 mg/kg over 5 to 10 minutes followed by an infusion of 20 mg/kg/hour titrated to adequate hemodynamic response (AHA [Vanden Hoek, 2010])

Calcium channel blocker overdose (off-label use): Note: Optimal dose has not been established (DeWitt, 2004).

IV: Initial: 1,000 to 2,000 mg over 5 minutes; may repeat every 10 to 20 minutes with 3 to 4 additional doses or 1,000 mg every 2 to 3 minutes until clinical effect is achieved (DeWitt, 2004); if favorable response obtained, consider IV infusion

IV infusion: 20 to 40 mg/kg/hour (DeWitt, 2004; Salhanick, 2003)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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.

Hypocalcemia: Acute, symptomatic: Manufacturer’s recommendations: Children: IV: 2.7 to 5 mg/kg/dose every 4 to 6 hours

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

Cardiac arrest or cardiotoxicity in the presence of hyperkalemia, hypocalcemia, or hypermagnesemia: Infants and Children: IV, I.O.: 20 mg/kg (maximum: 2,000 mg/dose); may repeat as necessary (AHA [Kleinman, 2010]; Hegenbarth, 2008)

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

Calcium channel blocker overdose (off-label use): Note: Optimal dose has not been established (DeWitt, 2004): Infants and Children:

IV, I.O.: Initial: 10 to 20 mg/kg (maximum: 2,000 mg/dose) over 10 to 15 minutes; may repeat every 10 to 15 minutes (AHA [Kleinman, 2010]; Arroyo, 2009); if favorable response obtained, consider IV infusion

IV infusion: 20 to 50 mg/kg/hour (Arroyo, 2009)

Dosing: Renal Impairment

No initial dosage adjustment necessary; however, accumulation may occur with renal impairment and subsequent doses may require adjustment based on serum calcium concentrations.

Dosing: Hepatic Impairment

No initial dosage adjustment necessary; subsequent doses should be guided by serum calcium concentrations.

Reconstitution

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

Administration

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 45-90 mg/kg/hour (0.6-1.2 mEq/kg/hour); administration via a central or deep vein is preferred; do not use scalp, small hand or foot veins for IV administration (severe necrosis and sloughing may occur). 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); initiate hyaluronidase antidote; remove needle/cannula; apply dry cold compresses (Hurst, 2004); elevate extremity.

Hyaluronidase: Intradermal or SubQ: Inject a total of 1 mL (15 units/mL) as five separate 0.2 mL injections (using a 25-gauge needle) into area of extravasation at the leading edge in a clockwise manner (MacCara, 1983; Zenk, 1981).

Compatibility

Stable in D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10W, LR, NS; variable (consult detailed reference) in fat emulsion 10%.

Y-site administration: Incompatible with amphotericin B cholesteryl sulfate complex, propofol, sodium bicarbonate.

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 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

Bisphosphonate Derivatives: Calcium Salts may decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral calcium supplements 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 with calcium-containing solutions within 48 hours of one another is contraindicated in neonates (28 days of age or younger). In older patients, flush lines with compatible fluid between administration. Consider therapy modification

Deferiprone: Calcium Salts 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. Alternatively, dolutegravir and oral calcium can be taken together with food. Consider therapy modification

Eltrombopag: Calcium Salts may decrease the serum concentration of Eltrombopag. Management: Administer eltrombopag at least 2 hours before or 4 hours after oral administration of any calcium-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

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

Tetracycline Derivatives: Calcium Salts may decrease the serum concentration of Tetracycline Derivatives. Management: If coadministration of oral calcium with oral tetracyclines can not be avoided, consider separating administration of each agent by several hours. 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: Calcium Salts may decrease the serum concentration of Trientine. Trientine may decrease the serum concentration of Calcium Salts. 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, vasodilatation

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 (Limited to important or life-threatening): Cutaneous calcification

Warnings/Precautions

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.

• 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.

• 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

Monitor infusion site, ECG when appropriate; serum calcium and ionized calcium (normal: 8.5-10.2 mg/dL [total]; 4.5-5.0 mg/dL [ionized]), albumin, serum phosphate; magnesium (to facilitate calcium repletion)

Calcium channel blocker overdose, beta-blocker overdose: Hemodynamic response, serum ionized calcium concentration

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. 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).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber dizziness, passing out, or severe injection site pain, redness, burning, edema, or irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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