CALCIUM SALTS: ORAL
Pharmacology: Calcium is the most abundant mineral in the human body and is essential for maintaining the functional integrity of nervous and musculoskeletal systems as well as cell membrane and capillary permeability. The majority (99%) of body calcium is contained in bone with the remainder equally distributed between intra- and extracellular fluids. Calcium is an activator in many enzymatic reactions and is necessary for nerve impulse transmission, renal function, respiration and blood coagulation.
Pharmacokinetics: Calcium is actively absorbed, mainly in the duodenum and proximal jejunum. Calcium must be in a soluble, ionized form to be absorbed. Factors such as an acidic intestinal pH, the presence of Vitamin D, and pregnancy and lactation tend to favor calcium absorption. However, absorption may be impeded in the elderly, or by a deficiency of parathyroid hormone, calcitonin or Vitamin D, the presence of anions or fatty acids which may precipitate or complex with calcium, or in certain disease states such as achlorhydria, renal osteodystrophy, steatorrhea or uremia.
Once absorbed into the bloodstream, most calcium is rapdily incorporated into skeletal muscle; the remainder is equally distributed between intra- and extracellular fluids. Normal total serum calcium concentrations range from 2.2 to 2.6 mmol/L, although only the ionized fraction is physiologically active. Of the total serum calcium, 50% is ionized, 5% is complexed with anions such as phosphates or citrates and 45% is protein bound. Hyperproteinemia is associated with an increase in total serum calcium; hypoproteinemia has the opposite effect. Acidosis favors an increase in ionic calcium concentration, while alkalosis leads to a decrease in the ionized fraction.
CSF calcium concentrations tend to be similar to the serum concentration of ionized calcium, i.e., approximately 50% of total serum calcium.
Calcium crosses the placenta, reaching higher levels in fetal blood than in the mother. Calcium is excreted in breast milk.
Calcium is excreted mainly in the feces, either as a result of passing through the gut unabsorbed or through biliary or pancreatic secretion into the gut lumen. Very small amounts of calcium are excreted in the urine as most renally filtered calcium is reabsorbed. Urinary excretion of calcium is promoted by growth hormone, calcitonin and nonthiazide diuretics, whereas parathyroid hormone, Vitamin D, thiazide diuretics or a decrease in ionized calcium concentration tend to decrease the amount of calcium excreted in the urine. Calcium is also excreted in sweat.
Indications: As a dietary supplement where calcium intake may be inadequate: childhood and adolescence, pregnancy and lactation, postmenopausal females and in the aged.
In the treatment of calcium deficiency states which may occur in diseases such as: tetany of the newborn (as a supplement to parenterally administered calcium), hypoparathyroidism (acute and chronic), pseudohypoparathyroidism, postmenopausal and senile osteoporosis (as an adjunct to estrogen, exercise, etc.), rickets and osteomalacia.
Calcium carbonate is used in the management of dyspepsia, gastroesophageal reflux and peptic ulcer disease.
Contraindications: Hypercalcemia and hypercalciuria (e.g., in hyperparathyroidism, vitamin D overdosage, decalcifying tumors such as plasmocytoma, bone metastases); severe renal or cardiac disease; calcium loss due to immobilization.
Precautions: In mild hypercalciuria (exceeding 300 mg/24 hours) as well as in chronic renal failure, or where there is evidence of stone formation in the urinary tract, adequate checks must be kept on urinary calcium excretion. If necessary, the dosage should be reduced or calcium therapy discontinued.
Studies done in recent years have shown that many calcium supplements contain varying amounts of lead. Supplements derived from bone meal, fossil or oyster shells, or dolomite contain the highest amounts. Certain patients may be at higher risk such as children or patients who rely on supplementation to meet their daily calcium requirements. Patients on chronic calcium therapy, especially children, infants, pregnant or lactacting women and chronic renal failure or dialysis patients, may be advised to avoid products derived from dolomite, fossil or oyster shells or bone meal, in favor of sources with lower lead content such as refined calcium carbonate or chelated calcium (gluconate and lactate salts).
Drug Interactions : Tetracyclines, Bisphosphonates (alendronate, clodronate, etidronate, pamidronate), Iron Supplements: Calcium decreases the absorption of these drugs and should be taken 3 hours after a dose of any of these agents.
Phenytoin: May form a nonabsorbable complex with calcium; calcium should be taken 3 hours after a phenytoin dose.
In addition to the specific medications mentioned in this monograph, the rate and/or extent of absorption of other oral medications may vary when taken concurrently with calcium supplements, especially the carbonate salt. Patients should generally be advised to take calcium supplements at least 3 hours after taking other oral medications.
Food Interactions : The absorption of calcium may be reduced in the presence of phosphorus (e.g., dairy products), oxalic acid (e.g., spinach, rhubarb) and phytic acid (e.g., bran and whole cereals).
Adverse Effects: Gastrointestinal: gastric irritation, constipation.
CNS: Irritability, lethargy, stupor and coma may occur with chronic ingestion.
Renal: Systemic alkalosis and hypercalcemia or the milk-alkali syndrome; generalized calcinosis leading to renal impairment may occur with chronic ingestion.
tag_OverdoseOverdose: Symptoms: Acute ingestion of calcium salts may cause mild gastric symptoms but has not caused hypercalcemia or other toxicity. Chronic ingestion of calcium salts may produce more significant toxicity (see Adverse Effects).
Treatment: Acute ingestion of calcium salts seldom requires treatment. Symptomatic hypercalcemia following chronic ingestion may require fluid resuscitation and general supportive care including cardiac monitoring, central venous pressure and wedge pressure measurement, pulmonary artery catheterization and monitoring of urinary output.
Dosage: Increased dietary intake of calcium is preferred over supplementation whenever possible. For information on food sources of calcium see Mineral Food Sources in the Clin-Info section. Table I lists the recommended daily calcium intake for various patient groups.
Calcium replacement requirements can be estimated by clinical condition and/or serum calcium determinations. Prophylactic administration of calcium supplements may be necessary in some patients in order to maintain serum calcium above 2.25 mmol/L (9 mg/dL). The average adult oral dosage of elemental calcium for prevention of hypocalcemia is 1 g daily, and the usual oral dosage for treatment of calcium depletion is 1 to 2 g or more daily. For the prevention of osteoporosis in women, elemental calcium intake of 1 to 1.5 g daily has been recommended.
Children: The usual supplemental dosage of elemental calcium is 45 to 65 mg/kg daily. In neonatal hypocalcemia, the daily dosage of elemental calcium is 50 to 150 mg/kg and should not exceed 1 g.
Oral calcium supplements are usually administered in 3 or 4 doses daily. Solid dosage forms should be taken with food (see Precautions, Food Interactions). Doses of syrup may be diluted in water, fruit juice or formula for children or infants.
With advancing age or in the presence of achlorhydria, calcium absorption from the gastrointestinal tract is reduced; calcium dosage may need to be adjusted accordingly.
Calcium supplements contain varying amounts of lead, depending on the source (see Precautions). Lead content should be among the many factors considered when recommending a calcium supplement to a patient.
CALCIUM SALTS: ORALGeneral MonographCalcium Therapy