Product Monograph - Calcium Chloride Injection BP
RECENT MAJOR LABEL CHANGES
| 2 CONTRAINDICATIONS | 09/2024 |
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TABLE OF CONTENTS
Sections or subsections that are not applicable at the time of authorization are not listed.
PART I: HEALTH PROFESSIONAL INFORMATION ........................................................................3
1 INDICATIONS .............................................................................................................4
2 CONTRAINDICATIONS ................................................................................................4
4 DOSAGE AND ADMINISTRATION. ...............................................................................4
4.1 Dosing Considerations ....................................................................................... 4
4.2 Recommended Dose and Dosage Adjustment .................................................... 4
4.4 Administration .................................................................................................. 5
4.5 Missed Dose...................................................................................................... 5
5 OVERDOSAGE ............................................................................................................5
6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................5
7 WARNINGS AND PRECAUTIONS .................................................................................6
7.1 Special Populations ........................................................................................... 7
7.1.1 Pregnant Women .............................................................................................. 7
7.1.2 Breastfeeding.................................................................................................... 7
7.1.3 Pediatrics .......................................................................................................... 7
7.1.4 Geriatrics .......................................................................................................... 7
8 ADVERSE REACTIONS .................................................................................................7
8.2 Clinical Trial Adverse Reactions.......................................................................... 8
8.2.1 Clinical Trial Adverse Reactions – Pediatrics ....................................................... 8
8.3 Less Common Clinical Trial Adverse Reactions.................................................... 8
8.3.1 Less Common Clinical Trial Adverse Reactions – Pediatrics ................................. 8
8.4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data .............................................................................................. 8
8.5 Post-Market Adverse Reactions ......................................................................... 8
9 DRUG INTERACTIONS .................................................................................................8
9.4 Drug-Drug Interactions ...................................................................................... 8
9.5 Drug-Food Interactions......................................................................................... 9
9.6 Drug-Herb Interactions ........................................................................................ 9
9.7 Drug-Laboratory Test Interactions........................................................................ 9
10 CLINICAL PHARMACOLOGY ...................................................................................... 10
10.1 Mechanism of Action........................................................................................10
10.2 Pharmacodynamics ..........................................................................................10
10.3 Pharmacokinetics .............................................................................................10
11 STORAGE, STABILITY AND DISPOSAL ........................................................................ 10
12 SPECIAL HANDLING INSTRUCTIONS .......................................................................... 10
PART II: SCIENTIFIC INFORMATION ........................................................................................ 11
- 13. PHARMACEUTICAL INFORMATION........................................................................... 11
14 CLINICAL TRIALS ....................................................................................................... 11
14.1 Trial Design and Study Demographics ...............................................................11
14.2 Study Results ...................................................................................................11
14.3 Comparative Bioavailability Studies ..................................................................11
14.4 Immunogenicity ...............................................................................................12
15 MICROBIOLOGY ....................................................................................................... 12
16 NON-CLINICAL TOXICOLOGY .................................................................................... 12
17 SUPPORTING PRODUCT MONOGRAPHS ................................................................... 12
PATIENT MEDICATION INFORMATION .................................................................................... 13
PART I: HEALTH PROFESSIONAL INFORMATION
1 INDICATIONS
Calcium Chloride Injection BP is indicated:
- For the treatment of hypocalcemia in those conditions requiring a prompt increase in blood plasma calcium levels,
- In the treatment of magnesium intoxication due to overdosage of magnesium sulfate
- To combat the deleterious effects of hyperkalemia as measured by electrocardiography (ECG), pending correction of the increased potassium level in the extracellular fluid.
- In cardiac resuscitation when weak or inadequate contractions return following defibrillation or when epinephrine injection has failed to strengthen myocardial contractions.
2 CONTRAINDICATIONS
Calcium Chloride Injection BP is contraindicated:
- For cardiac resuscitation in the presence of ventricular fibrillation.
- In patients with the risk of existing digitalis toxicity.
- In the treatment of asystole and electromechanical dissociation.
- When mixed or administered simultaneously with ceftriaxone intravenous solutions, even via different infusion lines or at different infusion sites, as it can lead to precipitation of ceftriaxone-calcium (see 7 WARNINGS AND PRECAUTIONS).
- For injection into tissues, since it is irritating to veins and severe necrosis and sloughing may occur. In patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
4 DOSAGE AND ADMINISTRATION
4.1 Dosing Considerations
Caution: This solution must not be injected intramuscularly or subcutaneously.
4.2 Recommended Dose and Dosage Adjustment
- The usual adult dosage in hypocalcemic disorders ranges from 200 mg to 1000 mg at intervals of 1 to 3 days, depending on the response of the patient and/or results of serum calcium determinations. Repeated injections may be required because of rapid excretion of calcium.
- In magnesium intoxication, an initial adult dose of 500 mg (5 mL) should be administered promptly and the patient observed for signs of recovery before further doses are given.
- In hyperkalemic ECG disturbances of cardiac function, the dosage of calcium chloride injection should be titrated by constant monitoring of ECG changes during administration.
- In cardiac resuscitation, the usual adult dosage ranges from 500 mg to 1 g (5 to 10 mL) intravenously, or from 200 to 800 mg (2 to 8 mL) when injected into the ventricular cavity.
4.4 Administration
Calcium Chloride Injection BP is administered only by slow intravenous injection (not to exceed 1 mL/min) and/or in cardiac resuscitation, by injection into the ventricular cavity. It must not be injected into the myocardium.
The usual precautions for intravenous therapy should be observed. If time permits, the solution should be warmed to body temperature. The injection should be halted if the patient complains of any discomfort; it may be resumed when symptoms disappear. Following injection, the patient should remain recumbent for a short time.
To prevent needle-stick injuries, needles should not be recapped, purposely bent or broken by hand. Place all needles in a sharps disposal container immediately after they have been used.
4.5 Missed Dose
This information is not applicable for this drug product.
5 OVERDOSAGE
Too rapid injection may produce lowering of blood pressure and cardiac syncope. Persistent hypercalcemia from calcium overdosage is unlikely because of rapid excretion. In the event of untoward effects from excessive calcium administration, the drug should be discontinued promptly, the patient re-evaluated and appropriate countermeasures instituted, if necessary. Symptoms of overdosage include: anorexia, nausea, vomiting, constipation, abdominal pain, muscle weakness, mental disturbances, polydipsia, polyuria, bone pain, nephrocalcinosis, renal calculi and, in severe cases, cardiac arrhythmias and coma (see 7 WARNING AND PRECAUTIONS and 8 ADVERSE REACTIONS).
| For management of a suspected drug overdose, contact your regional poison control centre. |
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6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING
Table 1 – Dosage Forms, Strengths, Composition and Packaging
| Route of Administration | Dosage Form / Strength / Composition | Non-medicinal Ingredients |
|---|---|---|
| Intravenous or intraventricular cavity injection | 10 mL Calcium Chloride solution in a pre-filled, single use syringe (see Table 2 Dosage Forms) / 100 mg / mL / Calcium Chloride Dihydrate | Hydrochloric Acid and / or Sodium Hydroxide for pH adjustment, Water for Injection |
Calcium Chloride Injection BP is supplied in single-use containers as follows:
Table 2 – Dosage Forms & Packaging
| Container | Volume | Needle |
|---|---|---|
| HYPAK SCFTM Syringe | 10 mL | Luer lock |
The HYPAK SCFTM Syringe includes a glass syringe barrel with luer tip and PRTC (plastic rigid tip cap) with twist-off mechanism for closure security, as well as a plastic HYPAKTM plunger rod and HYPAK SCFTM plunger stopper. Medication and fluid path are sterile and nonpyrogenic if tip cap is undisturbed and package intact.
7 WARNINGS AND PRECAUTIONS
General
Risk of Ceftriaxone-Calcium Precipitation
Ceftriaxone must not be mixed or administered simultaneously with any calcium-containing IV solutions, even via different infusion lines or at different infusion sites as it can lead to precipitation of ceftriaxone-calcium (see 2 CONTRAINDICATIONS).
Calcium chloride and ceftriaxone intravenous solutions may be administered sequentially one after another if infusion lines at different sites are used, or if the infusion lines are replaced or thoroughly flushed between infusions with physiological salt solution to avoid precipitation.
Aluminum Toxicity
This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired.
Research indicates that patients with impaired kidney function, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicities. Tissue loading may occur at even lower rates of administration.
Risk of Cardiac Toxicity
Because of its additive effect, calcium should be administered very cautiously to a patient who is digitalized or who is taking effective doses of digitalis or digitalis-like preparations (see 9 DRUG INTERACTIONS).
It is particularly important to prevent a high concentration of calcium from reaching the heart because of the danger of cardiac syncope. Too rapid an injection exceeding 1 mL/min may lead to hypotension and cardiac syncope (see 4 DOSAGE AND ADMINISTRATION). If injected into the ventricular cavity in cardiac resuscitation, it must not be injected into the myocardial tissue.
Injection Site Reactions
Calcium Chloride Injection BP is irritating to veins and must not be injected into tissues, since severe necrosis and sloughing may occur (see 2 CONTRAINDICATIONS).
Injections should be made slowly through a small needle into a large vein to minimize venous irritation and avoid undesirable reactions. Great care should be taken to avoid extravasation or accidental injection into perivascular tissues. Should perivascular infiltration occur, intravenous administration at that site should be discontinued at once. Local infiltration of the affected area with 1% procaine hydrochloride, to which hyaluronidase may be added, will often reduce venospasm and dilute the calcium remaining in the tissues locally. Local application of heat may also be helpful.
7.1 Special Populations
7.1.1 Pregnant Women
Calcium crosses the placenta. There are no adequate and well-controlled studies in pregnant women. Therefore, it is not known whether developmental toxicity may occur with the use of calcium chloride. There are no available animal data that evaluate the drug-associated risk. Calcium chloride should be given to a pregnant woman only if clearly needed.
7.1.2 Breastfeeding
It is not known whether calcium chloride injection would have an impact on the calcium content of the human milk in lactating women. Calcium chloride should be administered to lactating women only if clearly indicated. Studies assessing the effects of calcium chloride in breastfed children have not been performed. Studies to assess the effect of calcium chloride on milk production or excretion have not been performed. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for calcium chloride, and any potential adverse effects on the breastfed child from calcium chloride or from the underlying maternal condition.
7.1.3 Pediatrics
Pediatrics (< 18 years of age): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.
7.1.4 Geriatrics
Patients over 65 years of age: An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
8 ADVERSE REACTIONS
8.2 Clinical Trial Adverse Reactions
This information is not available for this drug product.
8.2.1 Clinical Trial Adverse Reactions – Pediatrics
This information is not available for this drug product.
8.3 Less Common Clinical Trial Adverse Reactions
This information is not available for this drug product.
8.3.1 Less Common Clinical Trial Adverse Reactions – Pediatrics
This information is not available for this drug product.
8.4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data
This information is not available for this drug product.
8.5 Post-Market Adverse Reactions
Nervous system disorders: Paraesthesia (upon rapid injection), calcium taste
General disorders and administration site conditions: Sense of oppression, sense of “heat wave”, local burning sensation, injection site extravasation, injection site reactions
Vascular disorders: Peripheral vasodilatation
Investigations: Blood pressure decreased
9 DRUG INTERACTIONS
9.4 Drug-Drug Interactions
The drugs listed in this table are based on either drug interaction case reports or studies, or potential interactions due to the expected magnitude and seriousness of the interaction (i.e., those identified as contraindicated).
Table 3 - Established or Potential Drug-Drug Interactions
Proper/Common name | Source of Evidence | Effect | Clinical comment |
|---|---|---|---|
| Calcium Channel Blockers | C | Administration of calcium may reduce the response to calcium channel blockers. | Calcium-containing products, like Calcium Chloride Injection, may decrease the effectiveness of calcium channel blocker. |
| Ceftriaxone | C | Ceftriaxone must not be mixed or administered simultaneously with any calcium-containing IV solutions, even via different infusion lines or at different infusion sites as it can lead to precipitation of ceftriaxone-calcium (see 2 CONTRAINDICATIONS). | Calcium chloride and ceftriaxone intravenous solutions may be administered sequentially one after another if infusion lines at different sites are used, or if the infusion lines are replaced or thoroughly flushed between infusions with physiological salt solution to avoid precipitation. |
| Digitalis or digitalis- like preparations | C | Because of its additive effect, calcium should be administered very cautiously to a patient who is digitalized or who is taking effective doses of digitalis or digitalis-like preparations see 7 WARNINGS AND PRECAUTIONS). |
Legend: C = Case Study
9.5 Drug-Food Interactions
Interactions with food have not been established.
9.6 Drug-Herb Interactions
Interactions with herbal products have not been established.
9.7 Drug-Laboratory Test Interactions
Interactions with laboratory tests have not been established.
10 CLINICAL PHARMACOLOGY
10.1 Mechanism of Action
Calcium chloride in water dissociates to provide calcium (Ca++) and chloride (CI-) ions. They are normal constituents of the body fluids and are dependent on various physiologic mechanisms for maintenance of balance between intake and output.
10.2 Pharmacodynamics
The normal serum calcium concentrations range from 8.8 to 10.4 mg/dL (2.2 to 2.6 mM).
10.3 Pharmacokinetics
Distribution
Body calcium exists in two major compartments in which the skeleton accounts for 99% of the total body calcium, and only 1% of the total body calcium is in the body fluids. The calcium in the body fluids can exist in three forms: ionized (~50%), protein-bound (~40%) and complexed with other anions (~10%). The main calcium-binding proteins include albumin and globulin in serum.
Metabolism
Calcium does not undergo any direct metabolism.
Elimination
Approximately 80% of body calcium is excreted in the feces as insoluble salts; urinary excretion accounts for the remaining 20%.
Specific Populations and Conditions
The effect of age, gender, race, renal or hepatic impairments on the pharmacokinetics of calcium have not been evaluated in clinical studies.
11 STORAGE, STABILITY AND DISPOSAL
Store between 15°C and 30°C. Protect from freezing. Avoid excessive heat.
Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit. Do not use unless the solution is clear and the container or seal is intact. Discard if the solution contains a precipitate.
Single-use; discard unused portion.
12 SPECIAL HANDLING INSTRUCTIONS
Liquid in glass vial. Handle with care. Inspect vial for damage prior to assembly.
PART II: SCIENTIFIC INFORMATION
13. PHARMACEUTICAL INFORMATION
Drug Substance
Proper name: Calcium chloride
Chemical name: Calcium; dichloride; dihydrate
Molecular formula and molecular mass: CaCl2 2H2O (dihydrate) 147.01 g/mol
Structural formula:
2H2O
Physicochemical properties:
Calcium Chloride Injection BP is a sterile, nonpyrogenic, hypertonic solution containing 100 mg / mL (0.7 mmol / mL or 1.4 mEq / mL) of calcium chloride, dihydrate (0.7 mmol / mL or 1.4 mEq / mL of Ca++ and 1.4 mmol / mL or 1.4 mEq / mL of Cl-) in Water for Injection Ph. Eur. It is provided in a 10 mL prefilled syringe to facilitate intravenous injection. The solution is administered only by intravenous or intraventricular cavity injection as a calcium replenisher.
The solution contains no bacteriostat, antimicrobial agent nor added buffer (except for pH adjustment) and is intended only for use as a single-use injection. When smaller doses are required, the unused portion should be discarded. The pH of calcium chloride injection is 5.5 to 7.5. The solution may contain hydrochloric acid and / or calcium hydroxide for pH adjustment. The osmolar concentration is 2.04 mOsm / mL (calc.).
Calcium Chloride dihydrate Ph. Eur. is chemically designated CaCl2 · 2H2O (dihydrate) white, odourless fragments or granules freely soluble in water.
14 CLINICAL TRIALS
14.1 Trial Design and Study Demographics
This information is not available for this drug product.
14.2 Study Results
This information is not available for this drug product.
14.3 Comparative Bioavailability Studies
This information is not available for this drug product.
14.4 Immunogenicity
This information is not available for this drug product.
15 MICROBIOLOGY
No microbiological information is required for this drug product.
16 NON-CLINICAL TOXICOLOGY
This information is not available for this drug product.
17 SUPPORTING PRODUCT MONOGRAPHS
- 1 - Calcium Chloride Injection USP, solution, 100 mg / mL, submission control 262054, Product Monograph, Pfizer Canada ULC. (AUG 25, 2022)