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CALCIUM SALTS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Calcium salts are classified as soluble (glubionate, gluceptate, chloride, lactate); sparingly soluble (gluconate, glycerophosphate), or insoluble (carbonate, phosphate).
    B) Soluble salts are generally used as calcium supplements and insoluble salts as antacids or excipients in pharmaceuticals or cosmetics.

Specific Substances

    A) CALCIUM ACETATE
    1) Acetic acid, calcium salt
    2) Brown acetate
    3) Calcium diacetate
    4) Gray acetate
    5) Lime acetate
    6) Lime pyrolignite
    7) CAS 62-54-4
    CALCIUM CARBONATE
    1) Aragonite
    2) Calcii carbonas
    3) Calcite
    4) Calcium(II) carbonate (1:1)
    5) Carbonic acid, calcium salt (1:1)
    6) Carbonic acid, calcium salt
    7) Chalk
    8) Creta preparada
    9) Dolomite
    10) Limestone
    11) Marble
    12) Portland stone
    13) Precipitated calcium carbonate
    14) Precipitated chalk
    15) Sohnhofen stone
    16) Vaterite
    17) CAS 1317-65-3
    CALCIUM CHLORIDE
    1) Calcii chloridum
    2) Calcium chloride dihydrate
    3) Cloreto de calcio
    4) Cloruro de calcio
    5) CAS 10035-04-8
    CALCIUM GLUBIONATE
    1) Calcium gluconate lactobionate
    2) Calcium gluconogalactogluconate
    3) CAS 31959-85-0 (anhydrous)
    4) CAS 12569-38-9 (monohydrate)
    CALCIUM GLUCEPTATE
    1) Calcium glucoheptonate
    2) CAS 17140-60-2 (anhydrous)
    3) CAS 29039-00-7 (anhydrous)
    CALCIUM GLUCONATE
    1) Calcii gluconas
    2) Calcium gluconicum
    3) Calcium glyconate
    4) CAS 299-28-5 (anhydrous)
    CALCIUM HYDROGEN PHOSPHATE
    1) Dibasic calcium phosphate
    2) Dicalcium orthophosphate
    3) Dicalcium phosphate
    4) CAS 7757-93-9 (anhydrous)
    5) CAS 7789-77-7 (dihydrate)
    CALCIUM LACTATE
    1) Calcii lactas
    2) Calcium 2-hydroxypropionate
    3) CAS 814-80-2 (anhydrous)
    4) CAS 41372-22-9 (hydrate)
    5) CAS 5743-47-5 (pentahydrate)
    6) CAS 63690-56-2 (pentahydrate)
    CALCIUM PHOSPHATE
    1) Calcium orthophosphate
    2) E341
    3) Fosfato tricalcico
    4) Neutral calcium phosphate
    5) Phosphate tertiaire de calcium
    6) Precipitated calcium phosphate
    7) Tribasic calcium phosphate
    8) Tricalcium phosphate
    9) CAS 7758-87-4

    1.2.1) MOLECULAR FORMULA
    1) CALCIUM ACETATE: C4H6CaO4

Available Forms Sources

    A) FORMS
    1) Calcium salts are classified as soluble (glubionate, gluceptate, chloride, lactate); sparingly soluble (gluconate, glycerophosphate), or insoluble (carbonate, phosphate).
    a) Soluble salts are generally used as calcium supplements and insoluble salts as antacids or excipients in pharmaceuticals or cosmetics.
    2) The elemental calcium content of various calcium salts are listed below: One mEq of elemental calcium is equivalent to 20 mg. One mmol of elemental calcium is equivalent to 40 mg.
    Calcium SaltCa(2+)%mg/gmEq/gmmol/g
    Acetate Anhydrous25.325312.66.3
    Carbonate Anhydrous40.044002010
    Chloride Dihydrate27.227213.66.8
    Glubionate Monohydrate6.5663.31.6
    Gluceptate Anhydrous8.2824.12
    Gluconate Monohydrate9904.52.2
    Glycerophosphate Anhydrous19.11919.64.8
    Hydrogen Phosphate Anhydrous2929014.57.3
    Hydrogen Phosphate Dihydrate2323011.55.8
    Lactate Pentahydrate131306.53.2
    Phosphate Tribasic Anhydrous393902010

    3) Pepto-Bismol(R) tablets contain 350 mg of calcium carbonate.
    4) Hemostatic compresses may contain 4.6% to 6.8% weight/weight of calcium acetate (Texier, 1982).
    B) USES
    1) CALCIUM is used as a dietary supplement and/or nutrient (Sax & Lewis, 1989).
    2) CALCIUM ACETATE is used in dying, tanning, and curing of skins; in lubricants; as corrosion inhibitor; as food stabilizer and thickener; as an antifoam additive in antifreeze; as a mordant in printing of textiles; as a stabilizer in resins; as an ingredient in antiseptics, blood coagulant tablets, and skin preparations; and in the manufacturing of acetate, acetic acid, and acetone (HSDB , 2002).
    3) CALCIUM CARBONATE is an air contaminant (Sax & Lewis, 1989), antacid (Gosselin et al, 1984), antidiarrheal (Budavari, 1996), and antidote for oxalic acid poisoning (Gosselin et al, 1984).
    4) CALCIUM CHLORIDE is used as refrigeration brines; as dust-proofing agent and antifreeze for roads; and in the manufacture of decolored active carbon (ITI, 1988). Hydrates of calcium chloride are fire-retardant for textile, fire extinguishing agent, wood preservative, and concrete hardening accelerator (ITI, 1988).
    5) CALCIUM GLUCONATE is used as a sequestering agent; as a food additive; as a gelling agent; in coffee powders to prevent caking; in sewage purification; and as a buffer (HSDB , 2002).
    6) CALCIUM PHOSPHATE Dibasic is used chiefly in animal feeds, mineral supplement in cereals and other foods; manufacturing of glass, in dental products and fertilizers. Therapeutic category: calcium replenisher (O'Neil et al, 2006).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Calcium carbonate is used medically as an antacid. Calcium citrate and calcium carbonate are used as dietary supplements. Calcium chloride and gluconate are used medically for treatment of hypocalcemia, hyperkalemia, and hypermagnesemia. Calcium salts are used in manufacturing, mining and other industries.
    B) PHARMACOLOGY: Calcium is a cation that is necessary for many physiological activities, some of which are poorly understood. It is essential for the normal functioning of organ systems including the muscles, nervous system, and cardiac function.
    C) TOXICOLOGY: Hypercalcemia may cause abdominal pain, delirium and renal stones. Prolonged ingestion of alkaline calcium salts may cause metabolic alkalosis and hypercalcemia (the "milk-alkali syndrome").
    D) EPIDEMIOLOGY: Exposure to calcium containing antacids is common, but significant toxicity is very rare.
    E) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Calcium supplements may cause GI upset or constipation. Patients with renal insufficiency may develop hypercalcemia. Extravasation of calcium chloride salts may cause local irritation or necrosis. Rapid intravenous administration of calcium salts may cause hypotension, bradycardia, syncope, and cardiac dysrhythmias.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Acute calcium poisoning is rare, and almost exclusively from intravenous administration. Symptoms of hypercalcemia include lethargy, muscle weakness, vomiting, nausea and constipation. Some calcium salts cause gastrointestinal irritation. Minor skin exposure to caustic calcium salts may cause dermal irritation.
    2) SEVERE TOXICITY: Life threatening manifestations are very rare and include complications from altered mental status such as aspiration pneumonia, and cardiac dysrhythmias.
    0.2.20) REPRODUCTIVE
    A) Calcium is classified as FDA pregnancy category C. There are no adequate and well-controlled studies of calcium use in pregnant women. The teratogenic risk associated with a normal calcium concentration in the blood appears to be minimal. A case report described milk-alkali syndrome in a pregnant woman who ingested large quantities of calcium carbonate, milk, and cheese for hyperemesis. A stillborn fetus with short limbs, low-set ears, normal chromosomes, and lack of evidence of tissue calcification was delivered at week 37 gestation. Calcium is secreted in breast milk in significant amounts; infant harm is not expected if the maternal calcium levels are maintained within the normal range.

Laboratory Monitoring

    A) Following an inadvertent exposure, an asymptomatic patient does not require routine testing, unless the ingestion was very large.
    B) A patients with a massive ingestion and being treated with IV hydration should have baseline renal function testing and hourly serum calcium determinations.
    C) If milk-alkali syndrome is suspected, serum electrolytes (including calcium and phosphorus), serum pH and renal function should be measured.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) There is no specific antidote for calcium salts poisoning. Most cases of hypercalcemia can be treated with saline hydration. Gastrointestinal or skin irritation is usually self-limited and does not require specific treatment beyond decontamination. There is no role for bisphosphonates or calcitonin in the treatment of hypercalcemia due to calcium salt exposure.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Most cases of hypercalcemia will resolve with hydration in patients with normal renal function. Hemodialysis can be used if emergent clearance is required of if the patient's renal function is impaired. There is no role for bisphosphonates or calcitonin in the treatment of hypercalcemia due to calcium salt exposure.
    C) DECONTAMINATION
    1) PREHOSPITAL: DERMAL EXPOSURE: Remove clothes and wash the body with copious amounts of water following dermal exposure to caustic salts.
    2) HOSPITAL: Gastric decontamination is not indicated for ingestion of salts. Patients who ingest caustic salts should rinse their mouth and may ingest a small amount (30 to 60 mL) of water.
    D) ANTIDOTE
    1) There is no antidote for calcium salts.
    E) EXTRAVASATION INJURY
    1) If extravasation occurs, stop the infusion. Disconnect the IV tubing, but leave the cannula or needle in place. Attempt to aspirate the extravasated drug from the needle or cannula. If possible, withdraw 3 to 5 mL of blood and/or fluids through the needle/cannula. Administer hyaluronidase (see below). Elevate the affected area. Apply warm packs for 15 to 20 minutes at least 4 times daily. Administer analgesia for severe pain. If pain persists, there is concern for compartment syndrome, or injury is apparent, an early surgical consult should be considered. Close observation of the extravasated area is suggested. If tissue sloughing, necrosis or blistering occurs, treat as a chemical burn (ie, antiseptic dressings, silver sulfadiazine, antibiotics when applicable). Surgical or enzymatic debridement may be required. Risk of infection is increased in chemotherapy patients with reduced neutrophil count following extravasation. Consider culturing any open wounds. Monitor the site for the development of cellulitis, which may require antibiotic therapy.
    F) ENHANCED ELIMINATION PROCEDURE
    1) Calcium is rapidly cleared by hemodialysis. However, dialysis is rarely indicated unless the patient has renal failure.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient who is asymptomatic or has mild GI irritation after an inadvertent exposure can be observed at home.
    2) OBSERVATION CRITERIA: A symptomatic patient and/or those with a deliberate overdose should be evaluated in a healthcare facility.
    3) ADMISSION CRITERIA: Patients who have high serum calcium concentrations that do not improve with hydration, or have concomitant renal insufficiency, should be admitted for hydration and monitoring.

Range Of Toxicity

    A) TOXIC DOSE: Persons who consume more than 10 g of CaCO3 (= 4 g Ca) are at risk of developing milk-alkali syndrome, but the condition has been reported in at least one person consuming only 2.5 g/day of CaCO3 ( =1 g Ca), an amount usually considered moderate and safe. Patients with predisposing conditions such as renal insufficiency may develop the syndrome after chronic ingestion of 5 to 10 g/day CaCO3, and those with dialysis dependent renal failure can develop hypercalcemia after 3.2 to 6.4 g/day. Normal total serum calcium concentrations are 9 to 10.4 mg/dL (4.5 to 5.2 mEq/L). Symptoms may appear when plasma calcium concentrations reach 6.6 mEq/L.
    B) THERAPEUTIC DOSE: In cases of hyperkalemia, hypermagnesemia, or calcium channel blocker overdose, administer calcium gluconate or chloride: 1 to 2 g IV titrated to clinical response. In patents with severe calcium channel blocker overdose, higher doses of calcium may be needed. Calcium repletion: 1 to 2 g/day of elemental calcium.

Clinical Effects

Summary Of Exposure

    A) USES: Calcium carbonate is used medically as an antacid. Calcium citrate and calcium carbonate are used as dietary supplements. Calcium chloride and gluconate are used medically for treatment of hypocalcemia, hyperkalemia, and hypermagnesemia. Calcium salts are used in manufacturing, mining and other industries.
    B) PHARMACOLOGY: Calcium is a cation that is necessary for many physiological activities, some of which are poorly understood. It is essential for the normal functioning of organ systems including the muscles, nervous system, and cardiac function.
    C) TOXICOLOGY: Hypercalcemia may cause abdominal pain, delirium and renal stones. Prolonged ingestion of alkaline calcium salts may cause metabolic alkalosis and hypercalcemia (the "milk-alkali syndrome").
    D) EPIDEMIOLOGY: Exposure to calcium containing antacids is common, but significant toxicity is very rare.
    E) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Calcium supplements may cause GI upset or constipation. Patients with renal insufficiency may develop hypercalcemia. Extravasation of calcium chloride salts may cause local irritation or necrosis. Rapid intravenous administration of calcium salts may cause hypotension, bradycardia, syncope, and cardiac dysrhythmias.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Acute calcium poisoning is rare, and almost exclusively from intravenous administration. Symptoms of hypercalcemia include lethargy, muscle weakness, vomiting, nausea and constipation. Some calcium salts cause gastrointestinal irritation. Minor skin exposure to caustic calcium salts may cause dermal irritation.
    2) SEVERE TOXICITY: Life threatening manifestations are very rare and include complications from altered mental status such as aspiration pneumonia, and cardiac dysrhythmias.

Heent

    3.4.3) EYES
    A) IRRITATION: Solid particles of calcium chloride have caused transient eye irritation and superficial injury. Aqueous solutions are not irritating. Calcium carbonate has not produced eye irritation (Grant & Schuman, 1993).
    B) CONJUNCTIVITIS: Calcium deposition may result in conjunctivitis in patients with chronic "milk alkali" syndrome. Band keratopathy is a more severe variation (Grant & Schuman, 1993).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CARDIOVASCULAR FINDING
    1) Effects of hypercalcemia on the heart might include bradyarrhythmias, bundle-branch blocks, prolonged PR interval, prolonged QRS interval, shortened QT interval, or cardiac arrest (Schaiff et al, 1989).
    B) HYPERTENSIVE EPISODE
    1) CASE REPORT: Hypertension was associated with 4 incidences of hypercalcemia in a 40-year-old woman with hyperparathyroidism. Episodes were triggered by untreated hyperparathyroidism, vitamin D administration, and IV calcium infusion (Blum et al, 1977).
    C) ATRIAL FIBRILLATION
    1) CASE REPORT: Within 15 seconds of combined infusion of calcium gluconate 2 mg/kg and pentagastrin, atrial fibrillation occurred in a 51-year-old man (Drucker, 1981).
    D) VASODILATATION
    1) Vasodilatation may occur due to rapid IV injection of calcium salts, resulting in hypotension, bradycardia, arrhythmias, and cardiac arrest (Carlon et al, 1978).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) Neurologic effects might include confusion, coma, decreased deep tendon reflexes, depression, fatigue, hallucinations, lethargy, or weakness (Schaiff et al, 1989).
    B) CALCINOSIS
    1) MILK-ALKALI SYNDROME: Chronic ingestion of calcium carbonate may result in neurologic symptoms secondary to hypercalcemia and acid-base disturbances (Orwoll, 1982). Symptoms range from irritability and lethargy to stupor and coma, depending on the amount and duration of ingestion.

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) Initial neurologic effects may be accompanied by anorexia, constipation, nausea, or vomiting (Schaiff et al, 1989).
    B) CONSTIPATION
    1) There is no substantiating clinical evidence to support allegations that calcium carbonate causes constipation (Clemens & Feinstein, 1977).
    2) Mean transit time was not altered in 8 subjects ingesting 6 g calcium carbonate daily for 3 weeks (Saunders et al, 1988).
    3) Fecal output increased by 25 g (20%) in 8 subjects ingesting 6 g calcium carbonate daily for 3 weeks (Saunders et al, 1988).
    C) GASTROINTESTINAL IRRITATION
    1) Calcium chloride is more irritating than other calcium salts.
    D) FLATULENCE/WIND
    1) Flatulence may occur secondary to the release of carbon dioxide from calcium carbonate (JEF Reynolds , 1991).
    E) MALABSORPTION SYNDROME
    1) FATTY ACID/BILE ACID EXCRETION: Calcium carbonate 6 g daily was associated with an increased fecal excretion of fatty acids (113%) and bile acids (87%) (Saunders et al, 1988).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ABNORMAL RENAL FUNCTION
    1) Renal effects include acute renal failure, increased excretion of magnesium, potassium, and sodium, nephrocalcinosis, nephrolithiasis, and polyuria (Schaiff et al, 1989).
    2) Renal dysfunction is a primary feature of the "milk-alkali" syndrome (D'Souza et al, 2013; Canning & Slater, 1987). BUN, creatinine, and phosphate are elevated, and proteinuria, pyuria, and casts may be noted. The urine may be either acidic or alkaline. Hypercalciuria may or may not be present.
    3) CASE REPORTS: Acute renal insufficiency, metabolic acidosis, and low parathyroid hormone (PTH), PTH-related peptide, and 1,25-dihydroxyvitamin D concentrations were reported in 2 patients after taking calcium carbonate supplements 1 and 2 g/day and 1 patient who took Mylanta(R) gelcaps containing 550 mg of calcium carbonate for epigastric pain (quantity unknown) (Picolos & Orlander, 2005).
    B) KIDNEY STONE
    1) NEPHROCALCINOSIS has been described in patients chronically consuming large amounts of calcium carbonate (Carroll & Clark, 1983; Orwoll, 1982).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) Calcium chloride may produce acidosis when given orally. Calcium chloride reacts in the intestine with phosphate and carbonate to form insoluble basic salts which are excreted in the feces. The chloride ion is absorbed, resulting in acidification of the serum and urine.
    2) IV administration is less likely to produce acidosis, since only that portion secreted into the intestine will react (Haldane et al, 1923).
    3) CASE REPORTS: Acute renal insufficiency, metabolic acidosis, and low parathyroid hormone (PTH), PTH-related peptide, and 1,25-dihydroxyvitamin D concentrations were reported in 2 patients after taking calcium carbonate supplements 1 and 2 g/day and 1 patient who took Mylanta(R) gelcaps containing 550 mg of calcium carbonate for epigastric pain (quantity unknown) (Picolos & Orlander, 2005).
    B) ALKALOSIS
    1) Alkalosis is a predominant feature of the "milk-alkali" syndrome, resulting from chronic ingestion of calcium carbonate (D'Souza et al, 2013).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) CHEMICAL BURN
    1) CASE REPORT: Calcium chloride is more irritating than other calcium salts. Application of a calcium chloride electrolyte paste to a 10-year-old girl's forehead, which had been cleansed with isopropyl alcohol, resulted in burns requiring debridement and scar revision (Anon, 1985).
    B) SKIN NODULE
    1) Severe local reactions, consisting of subcutaneous nodules, inflammatory reactions, or cellulitis-appearing lesions, have been described in infants and adults following extravasation of IV infusions of calcium gluconate and calcium chloride (Goldminz et al, 1988; Ramamurthy et al, 1975; Berger et al, 1974).
    a) Lesions appear after 3 to 20 days of infusion and resolve spontaneously.
    b) Radiologic studies show calcification of tissue.
    C) SKIN NECROSIS
    1) INTRA-ARTERIAL ADMINISTRATION: Infusion of calcium gluconate via umbilical artery catheters in neonates resulted in full-thickness skin necrosis, with extensive scarring and evidence of subcutaneous calcium deposits; gastrointestinal bleeding was also noted (Book et al, 1978).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HORMONE ABNORMALITY
    1) CASE REPORTS: Acute renal insufficiency, metabolic acidosis, and low parathyroid hormone (PTH), PTH-related peptide, and 1,25-dihydroxyvitamin D concentrations were reported in 2 patients after taking calcium carbonate supplements 1 and 2 g/day and 1 patient who took Mylanta(R) gelcaps containing 550 mg of calcium carbonate for epigastric pain (quantity unknown) (Picolos & Orlander, 2005).

Reproductive

    3.20.1) SUMMARY
    A) Calcium is classified as FDA pregnancy category C. There are no adequate and well-controlled studies of calcium use in pregnant women. The teratogenic risk associated with a normal calcium concentration in the blood appears to be minimal. A case report described milk-alkali syndrome in a pregnant woman who ingested large quantities of calcium carbonate, milk, and cheese for hyperemesis. A stillborn fetus with short limbs, low-set ears, normal chromosomes, and lack of evidence of tissue calcification was delivered at week 37 gestation. Calcium is secreted in breast milk in significant amounts; infant harm is not expected if the maternal calcium levels are maintained within the normal range.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) There are no adequate and well-controlled studies of calcium use in pregnant women (Prod Info calcium acetate oral capsules, 2012; Prod Info calcium gluconate intravenous injection, 2011; Prod Info CALCIUM CHLORIDE intravenous injection solution, 2009).
    B) LACK OF EFFECT
    1) The teratogenic risk associated with a normal calcium concentration in the blood appears to be minimal (TERIS , 1991). Hypercalcemia during pregnancy may increase the risk for maternal and neonatal complications, such as stillbirth, preterm delivery, and neonatal hypocalcemia and hypoparathyroidism (Prod Info calcium acetate oral capsules, 2012).
    C) ANIMAL STUDIES
    1) MICE: Administration of calcium acetate in aqueous solutions ("hard water") was associated with a higher frequency (18%) of exencephalic mouse fetuses than those administered "soft water" (Johnson, 1977). Additional studies are needed to validate this observation.
    2) MICE: Decreased fetal weight and retarded skeletal and dental calcification were noted in offspring of CD1 female mice that were maintained for 2 weeks on high calcium diets and then mated (Liebgott & Srebrolow, 1989).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) The manufacturer has classified calcium as FDA pregnancy category C (Prod Info calcium acetate oral capsules, 2012; Prod Info calcium gluconate intravenous injection, 2011; Prod Info CALCIUM CHLORIDE intravenous injection solution, 2009).
    B) MILK-ALKALI SYNDROME
    1) Hypercalcemia, dehydration, renal insufficiency, and pancreatitis developed in a 31-year-old woman who ingested large quantities of calcium carbonate, milk, and cheese for hyperemesis during her second pregnancy. The hypercalcemia and related electrolyte abnormalities were treated during week 23 of her pregnancy. A stillborn fetus with short limbs, low-set ears, normal chromosomes, and lack of evidence of tissue calcification was delivered at 37 weeks gestation (Ullian & Linas, 1988).
    2) CASE REPORT: A 29-year-old pregnant woman, with a history of GERD, presented to the hospital at 31-weeks gestation for a possible emergency cesarean section due to worsening hypertension and unexplained reduced fetal heart rate variability. Laboratory data revealed severe hypercalcemia, hypophosphatemia, acute renal dysfunction, metabolic alkalosis, and suppressed parathyroid hormone. Prior to her pregnancy, the patient had been taking a proton-pump inhibitor to treat her symptoms of GERD; however, during her pregnancy, the patient switched to an antacid containing calcium carbonate and ingested approximately 3 to 3.6 g of elemental calcium daily (recommended daily allowance is 1 g). Based on her laboratory findings and her history of chronic excessive calcium carbonate ingestion, a diagnosis of milk-alkali syndrome was made. With supportive care, the patient recovered with normalization of her calcium level, and she delivered, via cesarean section at 39 weeks gestation, a healthy infant (D'Souza et al, 2013).
    C) NEONATAL HYPOCALCEMIA
    1) Maternal ingestion of 10 to 14 calcium carbonate tablets (Tums(R)) daily, at a dose of 750 mg each, from midway through the first trimester to the onset of labor resulted in neonatal hypocalcemia. This manifested as generalized clonic activity noted first at 8 days of age. Admission calcium was 6.3 mg/dL; other laboratory aberrations included elevated phosphorus to 8.2 mg/dL and reduced 1,25-dihydroxyvitamin D (12 nanograms/dL); parathormone was low normal (20 picograms/mL). Phenobarbital and intravenous calcium were used for treatment; 5 episodes of all-limb jerking led to admission, and 3 additional episodes were noted during the first 10 hours. Serology gradually improved over 6 days, with discharge on day 8, and the child had a normal 3-month evaluation. Maternal serology was not available for comparison (Robertson, 2002).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Calcium is secreted in breast milk in significant amounts (Hardman et al, 1996). However, infant harm is not expected if the maternal calcium levels are maintained within the normal range (Prod Info calcium acetate oral capsules, 2012).
    2) In a study involving 60 women from the rural villages of Gambia (16 to 41 years of age), measured calcium levels in breast milk did not differ significantly between those receiving calcium supplementation and those receiving placebo. Lactating women were randomly assigned to receive placebo (n=30) or calcium carbonate 1000 mg (n=30) 5 days a week for 12 months. Samples of breast milk, fasting blood, and a 24-hour urine collection were taken at baseline and at 13, 52, and 78 weeks postpartum. Additional samples of breast milk were also collected on weeks 6, 19, 26, 39, and 65. There were no significant differences among the placebo and supplement group during any time of the study from weeks 6 to 78 regarding breast milk calcium concentration adjusted for stage of lactation, age, parity, season, or calcium intake (Prentice et al, 1995).
    3.20.5) FERTILITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects on fertility from exposure to calcium (Prod Info calcium acetate oral capsules, 2012; Prod Info CALCIUM CHLORIDE intravenous injection solution, 2009).

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) NEOPLASM
    1) Calcium chloride is classified as equivocal tumorigenic agent by RTECS criteria (RTECS , 2002).
    2) Thyroid tumors were observed in rats treated with calcium chloride 112 g/kg for 20 weeks continuously (RTECS , 2002).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Following an inadvertent exposure, an asymptomatic patient does not require routine testing, unless the ingestion was very large.
    B) A patients with a massive ingestion and being treated with IV hydration should have baseline renal function testing and hourly serum calcium determinations.
    C) If milk-alkali syndrome is suspected, serum electrolytes (including calcium and phosphorus), serum pH and renal function should be measured.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Serum calcium concentrations should be obtained in symptomatic patients.
    2) Serum electrolytes and renal function tests should be monitored in symptomatic patients.
    B) ENDOCRINE
    1) N-terminal parathyroid hormone and calcitriol concentrations may be useful in differentiating milk-alkali syndrome from hyperparathyroidism (Broadus et al, 1980; Dorsch, 1986).
    a) Low concentrations of N-terminal parathyroid hormone and calcitriol are thought to be consistent with milk-alkali syndrome.
    b) Vitamin D and calcitriol concentrations were within normal limits in a 52-year-old woman who was consuming 2 g elemental calcium per day.
    4.1.4) OTHER
    A) OTHER
    1) ECG
    a) ECG should be monitored in symptomatic patients.

Radiographic Studies

    A) ABDOMINAL RADIOGRAPH
    1) If present, renal calculi and nephrocalcinosis can often be demonstrated on a plain film of the abdomen.

Methods

    A) SPECTROSCOPY/SPECTROMETRY
    1) Blood and urine samples can be analyzed by atomic absorption methods (Trudeau & Freier, 1967; Bentley & Lee, 1967; Hanig & Aprison, 1967; Fuwa, 1967).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients who have high serum calcium concentrations that do not improve with hydration, or have concomitant renal insufficiency, should be admitted for hydration and monitoring.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patients who is asymptomatic or has mild GI irritation after an inadvertent exposure can be observed at home.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) A symptomatic patient and/or those with a deliberate overdose should be evaluated in a healthcare facility.

Monitoring

    A) Following an inadvertent exposure, an asymptomatic patient does not require routine testing, unless the ingestion was very large.
    B) A patients with a massive ingestion and being treated with IV hydration should have baseline renal function testing and hourly serum calcium determinations.
    C) If milk-alkali syndrome is suspected, serum electrolytes (including calcium and phosphorus), serum pH and renal function should be measured.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) DERMAL EXPOSURE: Following a dermal exposure to caustic salts, remove clothes and wash the body with copious amount of water.
    6.5.2) PREVENTION OF ABSORPTION
    A) Gastric decontamination is not indicated for the ingestion of salts. Patients who ingest caustic salts should rinse their mouth and may ingest a small amount (30 to 60 mL) of water.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Acute ingestion will seldom require treatment.
    2) Mild hypercalcemia and renal dysfunction without severe neurologic signs (stupor, coma) are readily reversible within a few days of discontinuation of calcium supplementation in chronic ingestion.
    3) Symptomatic hypercalcemia in chronic ingestion may require fluids and diuretic therapy.
    B) MONITORING OF PATIENT
    1) Following an inadvertent exposure, an asymptomatic patient does not require routine testing unless the ingestion is very large.
    2) Patients who have a massive ingestion and who are being treated with IV hydration should have baseline renal function testing and hourly serum calcium determinations.
    3) If milk-alkali syndrome is suspected, serum electrolytes (including calcium and phosphorus), serum pH and renal function should be measured.
    C) FLUID/ELECTROLYTE BALANCE REGULATION
    1) REHYDRATION: Vigorous IV fluid administration is critical in the treatment of acute symptomatic hypercalcemia. The treatment of dehydration will lower the serum calcium concentration by 1 to 2 mg/dL (Blythe et al, 1968).
    2) SALINE DIURESIS: Increased urinary excretion of calcium may also be accomplished by inducing a saline diuresis that utilizes the coupling of sodium and calcium transport in the proximal tubules.
    a) The intravascular space must be primed with an initial 1 to 2 L of normal saline within the first 2 hours of treatment. Otherwise, diuretics will induce a volume contraction, which will limit sodium and, thus calcium excretion, by the kidneys.
    b) Potassium and magnesium replacement should be given intravenously, as well.
    c) Forced saline diuresis may decrease serum calcium concentration by an average of 3.1 mg/dL over 24 hours (Suki et al, 1970).
    3) PRECAUTIONS: Patients with congestive heart failure or oliguric renal failure may not tolerate the massive fluid load required for calciuresis. In an emergency, hemodialysis or peritoneal dialysis are safer modes of treatment under these circumstances.
    4) DOSE RECOMMENDATION
    a) 1 to 2 L of 5% dextrose in normal saline with potassium chloride, 20 to 40 mEq/L plus 10 to 20 mg magnesium/L infused rapidly, with measurement of central venous or pulmonary wedge pressure, if indicated, to monitor volume status.
    b) Administer same solution to maintain urine volume at 500 mL/hr. Replace urinary volume losses equally every hour. IV rate may be 1000 to 1500 mL/hr for 24 to 48 hours.
    c) Measure spot urinary sodium and potassium levels every 4 to 6 hours to determine the electrolyte replacement needs of the patient. Magnesium deficits will also require replacement in the setting of saline diuresis; a rate of 15 mg/hr is recommended (Agus et al, 1982).
    5) ONSET: Effect on serum calcium concentration is generally rapid (Schaiff et al, 1989).
    D) DIURETIC
    1) Although the use of the loop diuretics furosemide or ethacrynic acid have been recommended, the dose required to produce calcium diuresis was 1 g/day in one study, which required extensive fluid-electrolyte monitoring (Suki et al, 1970).
    2) ONSET: Effect on serum calcium concentration is within 4 hours for furosemide in IV doses of 80 to 120 mg every 2 to 6 hours (Schaiff et al, 1989).
    E) CALCITONIN
    1) MECHANISM: Calcitonin lowers serum calcium concentration by decreasing renal calcium reabsorption and inhibiting bone resorption (Hosking & Heller, 1986; Hosking & Gilson, 1984; Stevenson & Evans, 1981; Friedman & Raisz, 1965; Martin et al, 1966).
    2) EFFICACY: In patients with hyperparathyroidism or malignancy-associated hypercalcemia, calcitonin produced a hypocalcemic effect in 74% to 90% in uncontrolled trials using various types of calcitonin (Silva & Becker, 1973; Koelmeyer & Stephens, 1978; Vaughn & Vaitkevicius, 1974; Nilsson et al, 1978; Wisneski et al, 1978).
    3) PRECAUTIONS: The manufacturer recommends skin testing with 1 international unit/0.2 mL intracutaneously due to the peptide structure and the potential systemic or local anaphylactoid reactions (Prod Info Calcimar(R), Calcitonin, 1985).
    4) DOSE: Doses of 8 international units/kg given subQ or IM every 6 hr; higher doses have not been associated with increased calcium lowering effects (Silva & Becker, 1973).
    5) ADVERSE EFFECTS: Transient nausea and vomiting may occur in 10% of patients (Koelmeyer & Stephens, 1978; Stevenson & Evans, 1981).
    6) ONSET: Effect on serum calcium concentration is usually within 2 to 4 hours for calcitonin given IM or subQ in doses of 4 to 8 international units every 6 to 12 hours (Schaiff et al, 1989).
    F) ETIDRONATE DISODIUM
    1) MECHANISM: Decreased urinary excretion of calcium, phosphate, and hydroxyproline, which is indicative of decreased bone resorption, is the suggested mechanism for lowering serum calcium (Jacobs et al, 1987).
    2) EFFICACY: In patients with malignancy-associated hypercalcemia, IV etidronate administration produced normocalcemia in 75% to 100% in uncontrolled trials (Ryzen et al, 1985; Kanis et al, 1987; Jacobs et al, 1987).
    3) PRECAUTIONS: Etidronate should be used cautiously in patients with renal insufficiency. Renal structural abnormalities were associated with bolus injections of large doses of etidronate in dogs (Hintze & D'Amate, 1982). Two patients developed acute renal failure associated with IV etidronate administration (Bounameaux et al, 1983).
    4) DOSE: Administer 7.5 mg/kg IV daily (Schaiff et al, 1989).
    5) ONSET: Effect on serum calcium concentration occurs between 24 and 28 hours for etidronate disodium given IV in doses of 7.5 mg/kg daily (Schaiff et al, 1989).
    G) PLICAMYCIN
    1) MECHANISM: Plicamycin inhibits bone resorption (Cortes et al, 1972; Minkin, 1973; Kiang et al, 1979; Cram et al, 1972).
    2) INDICATION: Plicamycin (formerly mithramycin) is indicated in severe acute hypercalcemia which is unresponsive to 12 to 24 hours of saline diuresis.
    3) EFFICACY: Single injections of plicamycin 25 mcg/kg body weight induced a substantial decrease in serum calcium concentration in 93% to 100% of patients within 48 hours and produced normocalcemia in 61% to 78% of patients (Perlia et al, 1970; Slayton et al, 1971).
    4) DOSE: Administer 25 mcg/kg as a single IV injection; may repeat in 24 to 48 hours if lowering of serum calcium level is not achieved from the first dose. An effect is generally seen within 12 to 24 hours following injection, and lasts 4 to 6 days.
    5) HEPATIC/RENAL DISEASE: Administer 12.5 mcg/kg IV every 48 to 72 hours (Schaiff et al, 1989).
    6) ONSET: Effect on serum calcium concentration usually occurs within 24 hours for recommended dosages of plicamycin (Schaiff et al, 1989).
    H) EXPERIMENTAL THERAPY
    1) CALCIUM ANTAGONISTS
    a) In rats, verapamil 2.5 mg/kg IV reversed the experimental calcium-induced cardiac arrest and improved survival (83% treated vs 0% control) (Zaloga et al, 1987). Magnesium chloride infused slowly to a total dose of 100 mg/kg had no therapeutic effect on experimental calcium-induced cardiac arrest.
    b) Additional studies are needed to demonstrate efficacy of verapamil or other calcium antagonists in the treatment of calcium-induced cardiac arrest in humans.
    2) INORGANIC PHOSPHATES
    a) MECHANISM: Administration of phosphate IV results in a dose-dependent decrease in serum calcium concentration that peaks between 12 and 24 hours, with a duration of several days (Schaiff et al, 1989).
    b) The risk of complications from this method of treating hypercalcemia is great and, therefore, rarely recommended (Schaiff et al, 1989).
    3) CORTICOSTEROIDS
    a) EFFICACY: Controlled studies are lacking. Corticosteroids have been ineffective in the treatment of hyperparathyroidism (Stewart, 1983). Several patients with lymphoproliferative malignancies were treated successfully in uncontrolled trials (Breslau et al, 1984; Lazor & Rosenbert, 1964; Ashkar et al, 1971).
    4) NSAIDs
    a) MECHANISM: In vitro data indicate that prostaglandins of the E series cause bone resorption (Klein & Raisz, 1970; Harris et al, 1973).
    b) EFFICACY: Lowering of serum calcium concentration has been noted in small numbers of patients treated with NSAIDs for malignancy-associated hypercalcemia. These patients have elevated plasma concentration of prostaglandin E or increased urinary excretion of prostaglandin E metabolites (Smith et al, 1983; Robertson, 1981; Robertson & Baylink, 1975; Robertson et al, 1976; Seyberth et al, 1975; Brenner et al, 1982; Mundy et al, 1983).
    c) Additional studies are needed to demonstrate the efficacy of NSAID treatment for hypercalcemia.
    5) GALLIUM NITRATE
    a) MECHANISM: A concentration-dependent reduction in the osteolytic response to parathyroid hormone and certain lymphokines in vitro (Warrell et al, 1984).
    b) EFFICACY: Two-thirds of patients who received IV infusions of gallium nitrate for 7 days for treatment of lymphoma developed transient hypocalcemia (Warrell et al, 1983).
    c) Serum calcium concentration was normalized in 86% of patients receiving the 200 mg/m(2) and 60% of patients receiving the 100 mg/m(2). The difference in response compared with dosage was not statistically significant in this study (Warrell et al, 1986).
    d) Response was statistically different when gallium nitrate 200 mg/m(2) (daily for 5 days) was compared with calcitonin in patients with cancer-related hypercalcemia (Warrell et al, 1988).
    e) DOSE: The dose utilized for treatment of malignancy-associated hypercalcemia are one-half the dose used as an antitumor agent. The usual dose ranges from 100 to 200 mg/m(2) daily by IV infusion for 5 days (Warrell et al, 1988).
    f) ADVERSE EFFECTS: Gallium nitrate induced nephrotoxicity can be minimized by maintaining a urine output of at least 2 L/day (Warrell et al, 1983).
    g) Additional studies of safety and efficacy are needed before this treatment can be routinely recommended (Schaiff et al, 1989).
    6) ETHIOFOS
    a) MECHANISM: Evidence indicates that the hypocalcemic effect of this agent is mediated by decreased release of parathyroid hormone and possible inhibition of renal tubular calcium reabsorption (Hirschel-Scholz et al, 1986).
    b) Hypocalcemia was observed in patients who received this drug as a radioprotectant (Yuhas et al, 1980). This is an investigational agent requiring additional studies of safety and efficacy before its role in the treatment of hypercalcemia can be determined.
    7) AMINOHYDROXYPROLINE DIPHOSPHONATE
    a) MECHANISM: Aminohydroxyproline diphosphonate (APD) is an investigational diphosphonate. It inhibits bone resorption at dosages that have little effect on bone mineralization (Gasser et al, 1972; Shinoda et al, 1983).
    b) DOSE: Hypocalcemic effect is reported from oral doses of 1200 mg daily; normocalcemia usually ensues within 6 days (Thiebaud et al, 1986).
    c) Additional studies are indicated to determine the safety and efficacy of this investigational agent.

Enhanced Elimination

    A) HEMODIALYSIS
    1) Serum calcium concentration can be safely and effectively lowered by hemodialysis in the management of hypercalcemic crisis (Kaiser et al, 1989).
    2) Mean serum calcium concentration decreased from 3.96 mmol/L (15.87 mg/dL) to 2.71 mmol/L (10.86 mg/dL) following 3 hours of calcium free acetate hemodialysis in 4 patients with hypercalcemic crisis due to malignancy (Kaiser et al, 1989).
    3) There are 8 additional reports of successful management of severe hypercalcemia using hemodialysis (Leroy et al, 1973; Raphael et al, 1971; Cardella et al, 1979; Eisenberg & Gotch, 1968; Strauch & Ball, 1976; Leow & Wagner, 1973; Chaves, 1970). Five patients were successfully treated by hemodialysis with low dialysate calcium and 3 patients by hemodialysis with calcium free dialysate.

Abstracts

Case Reports

    A) ADULT
    1) CASE REPORT: A 40-year-old woman with a documented serum calcium concentration of 5.35 mmol/L (21.4 mg/dL) presented with constipation, dizziness, fatigue, myalgia, nausea, urinary frequency, vomiting, and weakness. She had a history of surgical hypoparathyroidism and hypothyroidism and hypertension. Treatment management consisted of saline diuresis, furosemide, calcitonin, and hydrocortisone. Symptoms resolved in 24 hours when her serum calcium concentration was 3.59 mmol/L (14.4 mg/dL) (McAlister et al, 1990).

Range Of Toxicity

Summary

    A) TOXIC DOSE: Persons who consume more than 10 g of CaCO3 (= 4 g Ca) are at risk of developing milk-alkali syndrome, but the condition has been reported in at least one person consuming only 2.5 g/day of CaCO3 ( =1 g Ca), an amount usually considered moderate and safe. Patients with predisposing conditions such as renal insufficiency may develop the syndrome after chronic ingestion of 5 to 10 g/day CaCO3, and those with dialysis dependent renal failure can develop hypercalcemia after 3.2 to 6.4 g/day. Normal total serum calcium concentrations are 9 to 10.4 mg/dL (4.5 to 5.2 mEq/L). Symptoms may appear when plasma calcium concentrations reach 6.6 mEq/L.
    B) THERAPEUTIC DOSE: In cases of hyperkalemia, hypermagnesemia, or calcium channel blocker overdose, administer calcium gluconate or chloride: 1 to 2 g IV titrated to clinical response. In patents with severe calcium channel blocker overdose, higher doses of calcium may be needed. Calcium repletion: 1 to 2 g/day of elemental calcium.

Therapeutic Dose

    7.2.1) ADULT
    A) DISEASE STATE
    1) DIETARY SUPPLEMENT: The recommended daily allowance (RDA) of elemental calcium is 800 mg for adults and 1.2 g for pregnant or lactating women.
    2) OSTEOPOROSIS: For prevention of osteoporosis in postmenopausal women, the usual oral dose is 1 to 2 g elemental calcium/day.
    3) CARDIAC RESUSCITATION
    a) INDICATIONS: Hyperkalemia, hypocalcemia, or calcium channel blocker toxicity (CPR-ECC, 1986; Vincent, 1987)
    b) DOSE
    1) The dose of elemental calcium associated with safe use in adults is 5 to 7 mg/kg (CPR-ECC, 1986).
    2) CALCIUM CHLORIDE: 2 to 4 mg/kg or 2 mL of a 10% solution (contains 1.36 mEq of calcium/100 mg of calcium salt/mL) is administered intravenously (CPR-ECC, 1986)
    3) CALCIUM GLUCEPTATE: 90 to 126 mg of calcium (5 to 7 mL of calcium gluceptate) is administered intravenously (CPR-ECC, 1986)
    4) CALCIUM GLUCONATE: 500 to 800 mg of calcium (5 to 8 mL of calcium gluconate) is administered intravenously (CPR-ECC, 1986) .
    7.2.2) PEDIATRIC
    A) DISEASE STATE
    1) DIETARY SUPPLEMENT: The recommended daily allowance (RDA) of elemental calcium is:
    a) Less than 6 mo: 360 mg/day
    b) 6 to 12 mo: 540 mg/day
    c) 1 to 10 yr: 800 mg/day
    d) 10 to 18 yr: 1.2 g/day
    2) CARDIAC RESUSCITATION
    a) INDICATIONS: Hypocalcemia, hyperkalemia, hypermagnesemia, and calcium channel blocker overdose (CPR-ECC, 1986; Vincent, 1987)
    b) DOSE
    1) CALCIUM CHLORIDE: Administer 5.4 mg/kg of elemental calcium or 20 mg/kg of the calcium chloride or 0.2 mL/kg of calcium chloride containing 100 mg/mL by slow intravenous infusion; the dose may be repeated in 10 minutes if needed (CPR-ECC, 1986).

Maximum Tolerated Exposure

    A) CHRONIC
    1) CHRONIC ADMINISTRATION of 4 to 60 g/day for 2 to 60 days of calcium carbonate or calcium salts combined with sodium bicarbonate have produced the "milk-alkali" syndrome (Ginsburg et al, 1973).
    2) Cases where doses have been lower (5 to 10 g/day) have generally involved predisposing factors (Madias & Zelman, 1982; Gora et al, 1989).
    3) Chronic renal failure patients on hemodialysis have developed hypercalcemia after 3.2 to 6.4 g/day (Ginsburg et al, 1973).
    4) CASE REPORT (ADULT): A 29-year-old pregnant woman, with a history of GERD, presented to the hospital at 31-weeks gestation for a possible emergency cesarean section due to worsening hypertension and unexplained reduced fetal heart rate variability. Laboratory data revealed severe hypercalcemia, hypophosphatemia, acute renal dysfunction, metabolic alkalosis, and suppressed parathyroid hormone. Prior to her pregnancy, the patient had been taking a proton-pump inhibitor to treat her symptoms of GERD; however, during her pregnancy, the patient switched to an antacid containing calcium carbonate and ingested approximately 3 to 3.6 g of elemental calcium daily (recommended daily allowance is 1 g). Based on her laboratory findings and her history of chronic excessive calcium carbonate ingestion, a diagnosis of milk-alkali syndrome was made. With supportive care, the patient recovered with normalization of her calcium level, and she delivered, via cesarean section at 39 weeks gestation, a healthy infant (D'Souza et al, 2013).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CONCENTRATION LEVEL
    a) Normal total serum calcium is 9 to 10.4 mg/dL or 4.5 to 5.2 mEq/L or 2.2 to 2.6 mmol/L.
    b) At concentrations greater than 12 mg/dL, toxicity may occur. Symptoms usually begin when plasma calcium reaches 3.3 mmol/L (6.6 mEq/L) and are always present at 4 mmol/L (8 mEq/L).
    2) CASE REPORTS
    a) ADULT: A 40-year-old woman with a documented serum calcium concentration of 5.35 mmol/L (21.4 mg/dL) presented with constipation, dizziness, fatigue, myalgia, nausea, urinary frequency, vomiting, and weakness (McAlister et al, 1990).
    b) PEDIATRIC: Hypercalcemia was reported in 2 children following ingestion of a product called Damp-Rid(TM) that contained calcium chloride and was used as a moisture absorber for prevention of household mold and mildew. The serum calcium levels, obtained within one hour postingestion, were 20 mg/dL and 16.7 mg/dL in the 17-month-old boy and 16-month-old girl, respectively (Slattery et al, 1995).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) CALCIUM CARBONATE
    1) LD50- (ORAL)RAT:
    a) 6450 mg/kg (Sax & Lewis, 1989a)
    B) CALCIUM CHLORIDE
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 210 mg/kg (RTECS , 2002a)
    2) LD50- (ORAL)RAT:
    a) 1000 mg/kg (RTECS , 2002a)
    C) CALCIUM GLUCONATE
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 2200 mg/kg (RTECS , 2002a)
    2) LD50- (SUBCUTANEOUS)MOUSE:
    a) 2890 mg/kg (RTECS , 2002a)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Calcium helps maintain the nervous, muscular and skeletal system functions, and is essential to nerve transmission, muscle contraction, renal function, respiration, and blood coagulation.
    B) Calcium chloride should be the calcium salt of choice for parenteral indications because the body's retention of calcium chloride is greater and more predictable than the gluconate salt and the positive inotropic effect of calcium chloride is greater than for calcium gluconate (Worthley & Phillips, 1980).
    C) The increase in extracellular ionized calcium concentration is unpredictable for calcium gluconate (Worthley & Phillips, 1980).
    D) Calcium supplementation (2000 mg daily) was not as effective as estrogen therapy for the prevention of early postmenopausal bone loss in a double-blind, controlled trial in 43 women (Riis et al, 1987).

Toxicologic Mechanism

    A) There is wide individual variability in the amount of calcium absorbed. In individuals ingesting large doses of calcium carbonate where sufficient absorption occurs and renal calcium excretion is impaired due to alkalosis, hypercalcemia can result.
    B) Calcium carbonate produces alkalosis through several mechanisms. Due to increased renal tubule calcium, sodium excretion is increased. Volume depletion results, stimulating increased tubule bicarbonate reabsorption. Suppression of parathyroid hormone release may also impair bicarbonate excretion. Hypercalcemia may also directly increase bicarbonate reabsorption (Orwoll, 1982).
    C) Renal insufficiency results from hypercalcemia-induced decreases in glomerular filtration rate and creatinine clearance. Calcification then occurs in renal tissue. Renal insufficiency further impairs the excretion of calcium, perpetuating the syndrome.
    D) Extreme hypercalcemia increases the threshold for excitation of nerve and muscle tissue, resulting in weakness, stupor, and coma.

Physicochemical

Physical Characteristics

    A) CALCIUM ACETATE: Colorless crystals with slight odor of acetic acid (Budavari, 1989)
    B) CALCIUM CARBONATE: Odorless, tasteless crystals or powder (Sax & Lewis, 1989)
    C) CALCIUM CHLORIDE (ITI, 1988):
    1) ANHYDROUS: Colorless, deliquescent, hexagonal crystals
    2) DIHYDRATE: Deliquescent flakes, granules, or powder
    3) HEXAHYDRATE: Trigonal crystals
    D) CALCIUM GLUCEPTATE: White to light yellow amorphous powder (Sweetman, 2002)
    E) CALCIUM GLUCONATE: Odorless, tasteless, white granules or fluffy powder (Sax & Lewis, 1989)
    F) CALCIUM HYDROGEN PHOSPHATE: Odorless, tasteless, white, crystalline powder (Sweetman, 2002)
    G) CALCIUM LACTATE: Nearly odorless, slightly efflorescent, white granules or powder (Budavari, 1996)

Ph

    A) CALCIUM ACETATE: 7.6 (Budavari, 1996)
    B) CALCIUM CHLORIDE: 4.5 to 9.2 (5% solution in water) (Sweetman, 2002)
    C) CALCIUM GLUCEPTATE: 6 to 8 (10% solution in water) (Sweetman, 2002)
    D) CALCIUM GLUCONATE: 6 to 7 (Budavari, 1996)

Molecular Weight

    A) CALCIUM ACETATE: 158.17 (Prod Info PHOSLO(R) oral gelcaps, 2011)
    B) CALCIUM CARBONATE: 100.09
    C) CALCIUM CHLORIDE: 147
    D) CALCIUM GLUBIONATE: 610.5
    E) CALCIUM GLUCEPTATE: 490.4
    F) CALCIUM GLYCEROPHOSPHATE: 210.15
    G) CALCIUM GLUCONATE: 448.4
    H) CALCIUM HYDROGEN PHOSPHATE ANHYDROUS: 172.1
    I) CALCIUM LACTATE: 218.2

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