Chemistry - Several different salts of calcium are available in various formulations. Calcium gluceptate and calcium chloride are freely soluble in water; calcium lactate is soluble in water; calcium gluconate and calcium glycerophosphate are sparingly soluble in water, and calcium phosphate and carbonate are insoluble in water. Calcium gluconate for injection has a pH of 6-8.2; calcium chloride for injection has a pH of 5.5-7.5; and calcium gluceptate for injection has a pH of 5.6-7.
Storage/Stability/Compatibility - Calcium gluconate tablets should be stored in well-closed containers at room temperature. Calcium lactate tablets should be stored in tight containers at room temperature. Calcium gluconate injection, calcium gluceptate injection, and calcium chloride injection should be stored at room temperature and protected from freezing.
Calcium chloride for injection is reportedly compatible with the following intravenous solutions and drugs: amikacin sulfate, ascorbic acid, bretylium tosylate, cephapirin sodium, chloramphenicol sodium succinate, dopamine HCl, hydrocortisone sodium succinate, isoproterenol HCl, lidocaine HCl, methicillin sodium, norepinephrine bitartrate, penicillin G potassium/sodium, pentobarbital sodium, phenobarbital sodium, sodium bicarbonate, verapamil HCl, and vitamin B-complex with C.
Calcium chloride for injection compatibility information conflicts or is dependent on diluent or concentration factors with the following drugs or solutions: fat emulsion 10%, dobutamine HCl, oxytetracycline HCl, and tetracycline HCl. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references (e.g., Handbook on Injectable Drugs by Trissel; see bibliography) for more specific information.
Calcium chloride for injection is reportedly incompatible with the following solutions or drugs: amphotericin B, cephalothin sodium, and chlorpheniramine maleate.
Calcium gluceptate for injection is reportedly compatible with the following intravenous solutions and drugs: sodium chloride for injection 0.45% and 0.9%, Ringer’s injection, lactated Ringer’s injection, dextrose 2.5%-10%, dextrose-Ringer’s injection, dextrose-lactated Ringer’s injection, dextrose-saline combinations, ascorbic acid injection, isoproterenol HCl, lidocaine HCl, norepinephrine bitartrate, phytonadione, and sodium bicarbonate.
Calcium gluceptate for injection is reportedly incompatible with the following solutions or drugs: cefamandole naftate, cephalothin sodium, magnesium sulfate, prednisolone sodium succinate, and prochlorperazine edisylate. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references (e.g., Handbook on Injectable Drugs by Trissel; see bibliography) for more specific information.
Calcium gluconate for injection is reportedly compatible with the following intravenous solutions and drugs: sodium chloride for injection 0.9%, lactated Ringer’s injection, dextrose 5%-20%, dextrose-lactated Ringer’s injection, dextrose-saline combinations, amikacin sulfate, aminophylline, ascorbic acid injection, bretylium tosylate, cephapirin sodium, chloramphenicol sodium succinate, corticotropin, dimenhydrinate, erythromycin gluceptate, heparin sodium, hydrocortisone sodium succinate, lidocaine HCl, methicillin sodium, norepinephrine bitartrate, penicillin G potassium/sodium, phenobarbital sodium, potassium chloride, tobramycin sulfate, vancomycin HCl, verapamil and vitamin B-complex with C.
Calcium gluconate compatibility information conflicts or is dependent on diluent or concentration factors with the following drugs or solutions: phosphate salts, oxytetracycline HCl, prochlorperazine edisylate, and tetracycline HCl. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references (e.g., Handbook on Injectable Drugs by Trissel; see bibliography) for more specific information.
Calcium gluconate is reportedly incompatible with the following solutions or drugs: intravenous fat emulsion, amphotericin B, cefamandole naftate, cephalothin sodium, dobutamine HCl, methylprednisolone sodium succinate, and metoclopramide HCl.
Pharmacology – Calcium is an essential element that is required for many functions within the body, including proper nervous and musculoskeletal system function, cell-membrane and capillary permeability, and activation of enzymatic reactions.
Uses/Indications - Calcium salts are used for the prevention or treatment of hypocalcemic conditions.
Pharmacokinetics - Calcium is absorbed in the small intestine in the ionized form only. Presence of vitamin D (in active form) and an acidic pH is necessary for oral absorption. Parathormone (parathyroid hormone) increases with resultant increased calcium absorption in calcium deficiency states and decreases as serum calcium levels rise. Dietary factors (high fiber, phytates, fatty acids), age, drugs (corticosteroids, tetracyclines), disease states (steatorrhea, uremia, renal osteodystrophy, achlorhydria), or decreased serum calcitonin levels may all cause reduced amounts of calcium to be absorbed.
After absorption, ionized calcium enters the extracellular fluid and then is rapidly incorporated into skeletal tissue. Calcium administration does not necessarily stimulate bone formation. Approximately 99% of total body calcium is found in bone. Of circulating calcium, approximately 50% is bound to serum proteins or complexed with anions and 50% is in the ionized form. Total serum calcium is dependent on serum protein concentrations. Total serum calcium changes by approximately 0.8 mg/dl for every 1.09 g/dl change in serum albumin. Calcium crosses the placenta and is distributed into milk.
Calcium is eliminated primarily in the feces, contributed by both unabsorbed calcium and calcium excreted into the bile and pancreatic juice. Only small amounts of the drug are excreted in the urine, as most of the cation filtered by the glomeruli is reabsorbed by the tubules and ascending loop of Henle. Vitamin D, parathormone, and thiazide diuretics decrease the amount of calcium excreted by the kidneys. Loop diuretics (e.g., furosemide), calcitonin, and somatotropin increase calcium renal excretion.
Contraindications/Precautions/Reproductive Safety - Calcium is contraindicated in patients with ventricular fibrillation or with hypercalcemia. Parenteral calcium should not be administered to patients with above normal serum calcium levels. Calcium should be used very cautiously in patients receiving digitalis glycosides, or with cardiac or renal disease. Calcium chloride, because it can be acidifying, should be used with caution in patients with respiratory failure, respiratory acidosis, or renal disease.
Although parenteral calcium products have not been proven to be safe to use during pregnancy, they are often used before, during, and after parturition in cows, ewes, bitches, and queens to treat parturient paresis secondary to hypocalcemia.
Adverse Effects/Warnings - Hypercalcemia can be associated with calcium therapy, particularly in patients with cardiac or renal disease; animals should be adequately monitored. Other effects that may be seen include GI irritation and/or constipation after oral administration, mild to severe tissue reactions after IM or SQ administration of calcium salts and venous irritation after IV administration. Calcium chloride may be more irritating than other parenteral salts and is more likely to cause hypotension. Too rapid intravenous injection of calcium can cause hypotension, cardiac arrhythmias and cardiac arrest.
Should calcium salts be infused perivascularly, first stop the infusion. Ttreatment may then include: infiltrate the affected area with normal saline, corticosteroids administered locally, apply heat and elevate the area, and infiltrate affected area with 1% procaine and hyaluronidase.
Overdosage/Acute Toxicity - Unless other drugs are given concurrently that enhance the absorption of calcium, oral overdoses of calcium containing products are unlikely to cause hypercalcemia. Hypercalcemia can occur with parenteral therapy or oral therapy in combination with vitamin D or increased parathormone levels. Hypercalcemia should be treated by withholding calcium therapy and other calcium elevating drugs (e.g., vitamin D analogs). Mild hypercalcemias generally will resolve without further intervention when renal function is adequate.
More serious hypercalcemias (>12 mg/dl) should generally be treated by hydrating with IV normal saline and administering a loop diuretic (e.g., furosemide) to increase both sodium and calcium excretion. Potassium and magnesium must be monitored and replaced as necessary. ECG should also be monitored during treatment. Corticosteroids, and in humans, calcitonin and hemodialysis have also been employed in treating hypercalcemia.
Drug Interactions - Patients on digitalis therapy are more apt to develop arrhythmias if receiving IV calcium—use with caution. Calcium may antagonize the effects of verapamil (and other calcium-channel blocking agents). Thiazide diuretics used in conjunction with large doses of calcium may cause hypercalcemia. Oral magnesium products with oral calcium may lead to increased serum magnesium and/or calcium, particularly in patients with renal failure.
Parenteral calcium can neutralize the effects of hypermagnesemia or magnesium toxicity secondary to parenteral magnesium sulfate. Parenteral calcium may reverse the effects of nondepolarizing neuromuscular blocking agents (e.g., metubine, gallamine, pancuronium, atracurium, & vecuronium). Calcium has been reported to prolong or enhance the effects of tubocurarine. Oral calcium can reduce the amount of phenytoin or tetracyclines absorbed from the GI tract. Patients receiving both parenteral calcium and potassium supplementation may have an increased chance of developing cardiac arrhythmias—use cautiously.
Excessive intake of vitamin A may stimulate calcium loss from bone and cause hypercalcemia.
Concurrent use of large doses of vitamin D or its analogs may cause enhanced calcium absorption and induce hypercalcemia.
Drug/Laboratory Interactions - Parenteral calcium may cause false-negative results for serum and urinary magnesium when using the Titan yellow method of determination.
a) Calcium gluconate injection: 150 - 250 mg/kg IV slowly to effect (intraperitoneal route may also be used). Monitor respirations and cardiac rate and rhythm during administration. (USPC 1990)
b) Calcium gluconate 23% injection: 250 - 500 ml IV slowly, or IM or SQ (divided and given in several locations, with massage at sites of injection). (Label directions; Calcium Gluconate Injection 23%—TechAmerica)
c) For lactation tetany: 250 ml per 450 kg body weight of a standard commercially available solution that also contains magnesium and phosphorous IV slowly while ascultating heart. If no improvement after 10 minutes, repeat. Intensity in heart sounds should be noted, with only an infrequent extrasystole. Stop infusion immediately if a pronounced change in rate or rhythm is detected. (Brewer 1987)
a) An Asian cow (~ 3750 kg) in dystocia was given an IV infusion of 750 ml Ca-Mg-borogluconate containing 12 g calcium borogluconate (Schaftenaar, 1996).
b) Calcium borogluconate: 50-900 ml / animal IV; as a peristaltic, calcium pantothenate, 35-50 g / animal IV (Cheeran, et.al. 1995).
1996. Vaginal vestibulotomy in an Asian elephant (Elephas maximus).
Proceedings American Association of Zoo Veterinarians. Pages: 434-439
b) Cheeran,J.V., Chandrasekharan,K., and Radhakrishnan,K., 1995. Principles and Practice of Fixing Dose of Drugs for Elephants. In: Daniel,J.C. (Editor), A Week with Elephants; Proceedings of the International Seminar on Asian Elephants. Bombay Natural History Society; Oxford University Press, Bombay, India pp. 430-438
Monitoring Parameters -
1) Serum calcium
2) Serum magnesium, phosphate, and potassium when indicated
3) Serum PTH (parathormone) if indicated
4) Renal function tests initially and as required
5) ECG during intravenous calcium therapy if possible
6) Urine calcium if hypercalcuria develops
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Veterinary-Approved Products (not necessarily a complete list)
Calcium Gluconate (as calcium borogluconate) 23% [230 mg/ml; 20.7 mg (1.06 mEq) calcium per ml]; in 500 ml bottles; Generic; (Rx) Depending on the product, approved for use in cattle, horses, swine, sheep, cats, and dogs. No withdrawal times are required.
Products are also available that include calcium, phosphorus, potassium and/or dextrose; refer to the individual product’s labeling for specific dosage information. Trade names for these products include: Norcalciphos®—SKB, and Cal-Dextro® Special, #2, C, & K—Fort Dodge. They are legend (Rx) drugs.
Oral Products: No products containing only calcium (as a salt) are available commercially with veterinary labeling. There are several products (e.g., Pet-Cal® and Osteoform® Improved) that contain calcium with phosphorous and vitamin D (plus other ingredients in some preparations).
Human-Approved Products (not a complete list):
Calcium Gluconate Injection 10% [100 mg/ml; 9 mg (0.47 mEq) calcium per ml] in 10 ml amps, 10 & 50 ml, 100 ml, & 200 ml vials; Generic; (Rx)
Calcium Chloride Injection 10% [100 mg/ml; 27.2 mg (1.36 mEq) calcium per ml] in 10 ml amps, vials, and syringes; Generic; (Rx)
Calcium Gluceptate Injection 1.1 g/5 ml in 5 ml amps and 5 ml fill in 10 ml vial; Calcium Gluceptate® (Abbott) (Rx)
Calcium Gluconate (9% calcium) Tablets: 500 mg (45 mg of calcium), 650 mg (58.5 mg of calcium), 975 mg (87.75 mg calcium), 1 gram (90 mg of calcium); Generic; (OTC)
Calcium Lactate (13% calcium) Tablets : 325 mg (42.25 mg calcium), 650 mg (84.5 mg calcium); Generic; (OTC)
Also available are calcium glubionate syrup, calcium carbonate tablets, suspension & capsules, calcium citrate tablets, dibasic calcium phosphate dihydrate tablets, and tricalcium phosphate tablets.
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