Calcium Chloride: Uses, Dosage, Precautions, Side Effects, and Pharmacological Aspects

Overview

Hypocalcemia, characterized by low blood calcium levels, has diverse causes and significant clinical implications. Calcium is vital in numerous physiological processes, including muscle contraction, nerve transmission, and bone health. Therefore, maintaining adequate calcium levels is crucial for normal bodily function. Calcium chloride, a widely used treatment for hypocalcemia, is a rapid and effective means of restoring serum calcium concentrations.

The 10 percent Calcium chloride injection, USP, or United States Pharmacopeia (NDA or New Drug Application 02117; Hospira, approved in 2000), is the sole authorized calcium formulation for addressing hypocalcemia in situations necessitating a rapid elevation of plasma calcium levels. The US FDA (United States Food and Drug Administration) approved 10 percent Calcium chloride injections on January 28, 2000. This article provides an overview of Calcium chloride as a therapeutic agent for hypocalcemia, emphasizing its mechanism of action, pharmacokinetics, dosing regimens, routes of administration, and clinical efficacy.

Drug Group

Calcium chloride belongs to the drug class known as electrolyte solutions or mineral supplements. It is classified as a mineral supplement because it provides the essential mineral calcium to the body. Additionally, Calcium chloride may be considered a calcium salt.

Indications

Calcium chloride injections are used to treat acute symptomatic hypocalcemia in both adult and pediatric patients.

Dosage Forms and Available Strengths

Calcium chloride is available in the injection form, USP (single-dose), and comes in two forms:

• 10 percent (1,000 mg or milligrams per 10 mL or milliliters) in a plastic syringe.

• 10 percent (1,000 mg per 10 mL) in a glass syringe.

Each mL of solution contains 100 mg of calcium, equivalent to 27 mg or 1.4 mEq (milliequivalent) of elemental calcium.

For Patients

What Is Hypocalcemia?

Hypocalcemia is a medical condition characterized by reduced blood calcium levels, resulting in symptoms like muscle cramps, twitching, numbness, and, in severe cases, seizures or abnormal heart rhythms.

How Does the Calcium Chloride Work?

Calcium chloride injections rapidly increase calcium ions (Ca2+) levels in the bloodstream when administered intravenously (IV). This increase in ionized calcium concentration helps to restore normal calcium levels in cases of hypocalcemia (low blood calcium levels) or to counteract the effects of certain poisonings like magnesium. Calcium chloride injections help support these functions and restore normal physiological processes that may be impaired due to low calcium levels by increasing the level of calcium ions in the bloodstream.

What Are the Clinical Uses of Calcium Chloride?

The clinical uses of Calcium chloride include:

• Treatment of Hypocalcemia: Calcium chloride raises blood calcium levels in individuals with hypocalcemia, particularly in cases requiring rapid correction.

• Antidote for Magnesium Intoxication: In cases of Magnesium sulfate overdose or toxicity, Calcium chloride may be administered as an antidote to counteract the effects of excess magnesium.

• Management of Hyperkalemia: Calcium chloride can temporarily stabilize the heart and cardiac rhythm in cases of hyperkalemia (high blood potassium levels) while other interventions are initiated to lower potassium levels.

• Cardiopulmonary Resuscitation (CPR): In emergencies such as cardiac arrest, Calcium chloride may be administered as part of advanced cardiac life support (ACLS) protocols to support myocardial function and vascular tone.

• Buffering Agent: Calcium chloride can act as a pH (potential of hydrogen) buffer in various medical procedures, helping to maintain appropriate pH levels in solutions and prevent acid-base imbalances.

What Is the Dosage of the Calcium Chloride?

• A typical adult dosage for acute hypocalcemia or calcium deficiency is 500 mg to one gram (5 to 10 mL of a 10 percent solution) administered slowly over five to 10 minutes.

• For pediatric patients, the dosage is adjusted based on the weight and severity of the condition, and it is typically administered at a rate of 20 to 40 mg/kg (milligrams per kilogram).

How Are Calcium Chloride Administered?

Calcium chloride injections are primarily administered in clinical settings such as hospitals, emergency rooms, and other healthcare facilities.

• Administer Calcium chloride injection slowly into a vein in adults and children, avoiding bolus administration. The recommended infusion rate is one mL or milliliter/minute.

• Do not inject into muscles or under the skin. Check for a clear solution and an intact seal before use. Stop administration if discomfort occurs.

• Discard the unused portion. Warm solution if possible.

• For adults, the suggested dosage is 200 milligrams (mg) to 1,000 mg, and for children, 2.7 to 5 mg/kg.

• Adjust the dose based on calcium levels, symptoms, and the onset of hypocalcemia. Repeated injections may be needed due to rapid calcium excretion.

• The starting dose for patients with kidney problems is

  • For Adults: 200 mg.

  • For Children: 2.7 mg/kg.

• Avoid mixing Calcium chloride injections with other drugs, especially Ceftriaxone, to prevent complications.

• In neonates, Calcium chloride injections should not be used with Ceftriaxone. Ceftriaxone and Calcium products should be given separately in older patients, flushing the infusion lines between doses.

What Are the Side Effects of Calcium Chloride?

Common side effects of Calcium chloride may include:

• Injection Site Reactions: Pain, redness, or swelling at the injection site.

• Local Burning Sensation: A feeling of heat or burning at the injection site.

• Sense of Oppression: A feeling of heaviness or discomfort.

• Peripheral Vasodilatation: Widening of blood vessels in the arms, legs, hands, or feet.

• Decreased Blood Pressure: Lowering blood pressure may lead to symptoms such as dizziness or fainting.

• Paraesthesia: Abnormal sensations like tingling or numbness, especially with rapid injection.

• Calcium Taste: An unusual taste sensation in the mouth after injection.

What Are the Things to Inform the Doctor Before Taking Calcium Chloride?

Before taking Calcium chloride injections, inform the doctor about:

• Medical history, especially kidney or heart conditions.

• Inform about allergies to calcium or medications.

• Current medications, including over-the-counter drugs and supplements.

• Inform about pregnancy, breastfeeding status, or if one is planning to conceive.

• Any previous adverse reactions to calcium supplements.

• Any other health concerns or ongoing medical treatments.

Patient Information:

• Arrhythmias with Concurrent Digoxin Use: When Calcium chloride injection and Digoxin are given together, arrhythmias (irregular heart rhythm) may develop.

• Tissue Necrosis and Calcinosis: Administering Calcium chloride injection can lead to calcinosis cutis (accumulation of calcium deposits in the skin and subcutaneous tissue), tissue necrosis, ulceration, and secondary infection.

• Aluminum Toxicity: Calcium chloride injection contains aluminum, which may pose a toxicity risk.

Dietary Considerations:

None, unless the doctor specifies anything.

Missed Dose:

If one misses a dose of Calcium chloride injections, contact the healthcare provider for guidance. Avoid doubling up on doses without professional advice, and stick to the regular dosing schedule.

Overdose:

An overdose of Calcium chloride injection can cause hypercalcemia, with symptoms typically appearing when the total serum calcium concentration is more than or equal to 12 mg/dL (milligram per deciliter). These symptoms include a shortened QT interval, bradycardia (slow heart rate), hypertension (high blood pressure), reduced appetite, feelings of nausea, vomiting, constipation, muscle weakness, bone pain, decreased focus, depression (prolonged sadness), fatigue, confusion, hallucinations (perceptions of something that is not present), disorientation, muscle weakness, seizures (sudden, uncontrolled electrical disturbances in the brain), and coma (a state of prolonged unconsciousness).

Hypercalcemia can also affect kidney function, reducing the ability to concentrate urine and causing increased urination. In case of overdose, discontinue Calcium chloride injection immediately, reassess the patient, and administer appropriate interventions as necessary.

Storage and Handling:

Store between 20°C (degrees Celsius) and 25°C (68 to 77 degrees Fahrenheit). Temperature excursions within the range of 15 to 30 degrees Celsius (59 to 86 degrees Fahrenheit) are permissible.

Disposal:

Calcium chloride injections are available in hospital settings, so hospital authorities do disposal. The disposal of Calcium chloride injections should follow FDA guidelines. Utilize local take-back programs if available. Flush if instructed on the label.

For Doctors

Description:

• Sterile, non-pyrogenic, hypertonic solution for single administration.

• Every milliliter contains 100 milligrams (equivalent to 1.4 milliequivalents per milliliter) of Calcium chloride dihydrate dissolved in water for injection.

• Supplied in a single-dose syringe of 10 mL for intravenous (IV) injection.

• Does not contain any bacteriostat, antimicrobial agent, or added buffer.

• pH ranges from 5.5 to 7.5 when diluted with water for injection to achieve a five percent solution.

• Hydrochloric acid or sodium hydroxide may be added for pH adjustment.

• Osmolar concentration is 2.04 mOsmol/mL (milliosmoles per milliliter).

• Sensitive to oxygen.

Chemical Composition:

• Active Ingredient: Calcium chloride, USP dihydrate (CaCl2 • 2H2O).

• Appearance: White, odorless fragments or granules freely soluble in water.

Aluminum Content:

• Contains no more than 1,000 mcg/L (micrograms per liter) of aluminum.

What Are the Pharmacological Actions of Calcium Chloride?

1. Pharmacodynamics: The relationship between exposure and response and the time course of pharmacodynamic effects concerning the safety and efficacy of Calcium chloride injection have yet to be thoroughly understood or characterized.

2. Mechanism of Action: Administering Calcium chloride intravenously elevates the level of ionized calcium in the blood. Calcium chloride dissociates into ionized calcium when introduced into the plasma.

3. Pharmacokinetics:

• Absorption: Calcium chloride injection is fully absorbed after intravenous injection.

• Distribution: Calcium is primarily found in the skeleton (99 percent), with one percent in extracellular fluids and soft tissues. About half of total serum calcium is in its active ionized form.

• Metabolism: Calcium does not undergo direct metabolism.

• Excretion: Calcium is primarily excreted by the kidneys, with intravenous Calcium chloride leading to increased urinary excretion.

Warnings and Precautions:

The associated warnings and precautions are:

• Intravenous Ceftriaxone-Calcium Precipitates and Organ Damage:

  • Avoid Calcium chloride injection in newborns needing or likely to need Ceftriaxone intravenous treatment up to 28 days old.

  • For patients older than 28 days, do not mix or give Calcium chloride injections with Ceftriaxone intravenous solutions simultaneously, as it may cause Ceftriaxone-calcium precipitation.

• Risks With Rapid Administration: Rapid injection exceeding one mL per minute may cause hypotension (low blood pressure), bradycardia, arrhythmias (irregular heartbeat), and syncope (fainting).

• Concerns With Digoxin Use:Avoid using Calcium chloride injection with Digoxin. Monitor ECG (echocardiogram) and calcium levels if co-administration is necessary.

• Tissue Necrosis and Calcinosis Prevention: Slowly inject Calcium chloride injection through a fine needle into a sizable vein to reduce the risk of tissue necrosis (tissue death), ulceration (open wounds), and calcinosis (abnormal calcium deposition). Avoid extravasation (leakage of fluids or drugs from a blood vessel into surrounding tissue, potentially causing tissue damage); halt administration if perivascular infiltration occurs.

• Risk of Aluminum Toxicity: Long-term administration may cause aluminum toxicity, especially in patients with impaired kidney function. Premature neonates are at higher risk. Limit daily exposure to aluminum to no more than 5 mcg/kg/day (micrograms per kilogram per day) when using parenteral nutrition solutions containing Calcium chloride injection.

Non-Clinical Toxicity

The potential for carcinogenicity, mutagenicity, and effects on fertility have not been evaluated for Calcium chloride injection.

What Are the Contraindications of Calcium Chloride?

Calcium chloride injection is contraindicated in the following cases:

• Patients with ventricular fibrillation (chaotic heart rhythm).

• Patients with asystole (absence of heart rhythm) and electromechanical dissociation.

• Newborns (up to 28 days old) needing or anticipated to need Ceftriaxone intravenous treatment due to the risk of Ceftriaxone-calcium precipitation, irrespective of administration timing or separate intravenous lines.

What Are the Drug Interactions of Calcium Chloride?

The drug interactions are as follows:

• Digoxin: It is advisable to refrain from using Calcium chloride injections concurrently with Digoxin. If simultaneous administration is necessary, closely monitor the electrocardiogram (ECG) during Calcium chloride injection administration. Concomitant use may lead to synergistic arrhythmias. The administration of Calcium chloride injection may induce hypercalcemia, heightening the risk of Digoxin toxicity.

• Calcium Channel Blockers: The simultaneous use of Calcium chloride injection and Calcium channel blockers may diminish the effectiveness of Calcium channel blockers. It is recommended to avoid concurrent usage. If simultaneous use cannot be avoided, blood pressure should be closely monitored during the administration of Calcium chloride injection.

• Medications Associated With Elevated Calcium Levels: Enhance the frequency of calcium concentration monitoring in patients concurrently using Calcium chloride injection and other medications known to elevate the risk of hypercalcemia (such as Calcipotriene, estrogen, lithium, parathyroid hormone, Teriparatide, Thiazide diuretics, vitamin A, and vitamin D).

Clinical Studies:

A hypothetical study aims to compare the effectiveness of Calcium gluconate and Calcium chloride in raising serum-ionized calcium levels in hypoalbuminemic animals (dogs). Animals are randomly assigned to receive either Calcium gluconate or Calcium chloride intravenously. Serum calcium levels are measured before and after treatment. The study concludes Calcium gluconate or Calcium chloride is more effective in increasing serum-ionized calcium concentration in hypoalbuminemic animals.

Use in Specific Populations

Pregnancy: Using Calcium chloride injection during pregnancy for acute symptomatic hypocalcemia is not expected to harm the mother or fetus, but hypocalcemia itself poses risks. Animal studies on its use during pregnancy are lacking, and background risks for birth defects and miscarriage are unknown. Maternal hypocalcemia can lead to complications like abortion and premature labor, affecting fetal health.

Lactation: Calcium chloride injection in breastfeeding mothers is likely safe for infants, though effects on the baby or milk production are poorly understood. Decisions should consider the benefits of breastfeeding and the mother's need for treatment.

Pediatric Use: Calcium chloride injection is effective for pediatric acute hypocalcemia, but it should be avoided in newborns needing Ceftriaxone due to the risks of Ceftriaxone-calcium precipitation. Sequential administration may be possible in older pediatric patients. Preterm infants on prolonged parenteral nutrition should be monitored for aluminum toxicity.

Geriatric Use: Limited data exist on how older adults respond to Calcium chloride injections compared to younger adults.

Renal Impairment: Using Calcium chloride injections in patients with kidney problems may increase calcium-phosphorus product risk. It is necessary to start at the lowest dose and monitor calcium levels frequently.