Note: Dose expressed in mg of calcium acetate. Phosphate binding capacity: Calcium acetate 1 g binds 45 mg of phosphorus (KDOQI 2005)
Control of hyperphosphatemia in end-stage renal failure: Limited data available; dose should be individualized: Children and Adolescents: Oral: Reported initial dose: 667 to 1,000 mg with each meal; titrate (every 2 to 4 weeks) to response and as serum calcium levels allow (Gulati 2010; Wallot 1996). Note: KDOQI guidelines recommend limiting the calcium provided from phosphate binders to 1,500 mg elemental calcium per day and total intake to 2,000 mg elemental calcium from all sources (KDOQI 2010)
No dosage adjustment necessary.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Calcium acetate: Drug information")
Control of serum phosphorus (end-stage renal disease, on dialysis) (Rx): Oral: Initial: 1334 mg with each meal, can be increased gradually (ie, every 2 to 3 weeks) to bring the serum phosphate to target range as long as hypercalcemia does not develop (usual dose: 2,001 to 2,668 mg calcium acetate with each meal); do not give additional calcium supplements.
Dietary supplement (OTC): 1 to 3 tablets with meals (3 times daily).
No dosage adjustment necessary.
No dosage adjustment provided in manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 667 mg
Solution, Oral:
Phoslyra: 667 mg/5 mL (473 mL) [contains methylparaben, propylene glycol]
Tablet, Oral:
Calphron: 667 mg
Generic: 667 mg, 668 mg
May be product dependent
Calcium acetate is approximately 25% elemental calcium
Calcium acetate 667 mg = elemental calcium 169 mg = calcium 8.45 mEq = calcium 4.23 mmol
Oral: Administer with plenty of fluids with meals to optimize effectiveness
Oral: Administer with meals.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Treatment of hyperphosphatemia in end-stage renal failure (FDA approved in adults)
PhosLo may be confused with Phos-Flur, ProSom
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Hypercalcemia
Gastrointestinal: Diarrhea (oral solution)
1% to 10%: Gastrointestinal: Nausea, vomiting
Postmarketing and/or case reports: Dizziness, edema, pruritus, weakness
Hypercalcemia.
Concerns related to adverse effects:
• Gastrointestinal effects: Constipation, bloating, and gas are common with calcium supplements (especially carbonate salt).
• Hypercalcemia: Mild to severe hypercalcemia may occur; decrease calcium acetate dose or temporarily discontinue, depending on severity of hypercalcemia; in addition, decrease or discontinue any concomitant vitamin D therapy. Chronic hypercalcemia may result in generalized vascular and soft tissue calcification, exacerbate nephrolithiasis, and has been associated with increased mortality in adults with chronic kidney disease (CKD) (KDIGO 2017).
Disease-related concerns:
• Arrhythmias: Use with caution in patients who may be at risk of cardiac arrhythmias.
• Chronic kidney disease: In CKD patients receiving phosphate-lowering treatment, consider using non-calcium-based phosphate-lowering agents (eg, sevelamer, lanthanum) as an alternative to calcium-based phosphate-lowering agents (eg, calcium acetate, calcium carbonate) or restricting the dose of the calcium-based phosphate-lowering agents (Allison 2013; KDIGO 2017). A meta-analysis observed a trend toward a decrease in all-cause mortality in CKD patients receiving non-calcium-based phosphate-lowering agents compared with those receiving calcium-based phosphate-lowering agents (Jamal 2013); however, further research is needed to identify causes of mortality and fully assess safety of long-term use based on phosphate-lowering agent type.
• Hypoparathyroid disease: Hypercalcemia and hypercalciuria are most likely to occur in hypoparathyroid patients receiving high doses of vitamin D.
Concurrent drug therapy issues:
• Digitalis: Use with caution in digitalized patients; hypercalcemia may precipitate cardiac arrhythmias.
• Minerals/other oral drugs: Calcium administration interferes with absorption of some minerals and drugs; use with caution.
Dosage form specific issues:
• Maltitol: Oral solution may contain maltitol (a sugar substitute) which may cause a laxative effect.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.
Other warnings/precautions:
• Appropriate product selection: Multiple salt forms of calcium exist; close attention must be paid to the salt form when ordering and administering calcium; incorrect selection or substitution of one salt for another without proper dosage adjustment may result in serious over or under dosing.
Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP, 1997; Shehab, 2009).
None known.
Alpha-Lipoic Acid: Calcium Salts may decrease the absorption of Alpha-Lipoic Acid. Alpha-Lipoic Acid may decrease the absorption of Calcium Salts. Management: Separate administration of alpha-lipoic acid from that of any calcium-containing compounds by several hours. If alpha-lipoic acid is given 30 minutes before breakfast, then administer oral calcium-containing products at lunch or dinner. Risk D: Consider therapy modification
Baloxavir Marboxil: Polyvalent Cation Containing Products may decrease the serum concentration of Baloxavir Marboxil. Risk X: Avoid combination
Bictegravir: Calcium Salts may decrease the serum concentration of Bictegravir. Management: Bictegravir, emtricitabine, and tenofovir alafenamide can be administered with calcium salts under fed conditions, but coadministration with or 2 hours after a calcium salt is not recommended under fasting conditions. Risk D: Consider therapy modification
Bisphosphonate Derivatives: Polyvalent Cation Containing Products may decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral medications containing polyvalent cations within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Risk D: Consider therapy modification
Cabotegravir: Polyvalent Cation Containing Products may decrease the serum concentration of Cabotegravir. Management: Administer polyvalent cation containing products at least 2 hours before or 4 hours after oral cabotegravir. Risk D: Consider therapy modification
Calcium Channel Blockers: Calcium Salts may diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
Calcium Salts: May enhance the adverse/toxic effect of Calcium Acetate. Risk X: Avoid combination
Cardiac Glycosides: Calcium Salts may enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy
CefTRIAXone: Calcium Salts (Intravenous) may enhance the adverse/toxic effect of CefTRIAXone. Ceftriaxone binds to calcium forming an insoluble precipitate. Management: Use of ceftriaxone is contraindicated in neonates (28 days of age or younger) who require (or are expected to require) treatment with IV calcium-containing solutions. In older patients, flush lines with compatible fluid between administration. Risk D: Consider therapy modification
Deferiprone: Polyvalent Cation Containing Products may decrease the serum concentration of Deferiprone. Management: Separate administration of deferiprone and oral medications or supplements that contain polyvalent cations by at least 4 hours. Risk D: Consider therapy modification
DOBUTamine: Calcium Salts may diminish the therapeutic effect of DOBUTamine. Risk C: Monitor therapy
Dolutegravir: Calcium Salts may decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral calcium. Administer dolutegravir/rilpivirine at least 4 hours before or 6 hours after oral calcium salts. Alternatively, dolutegravir and oral calcium can be taken together with food. Risk D: Consider therapy modification
Eltrombopag: Polyvalent Cation Containing Products may decrease the serum concentration of Eltrombopag. Management: Administer eltrombopag at least 2 hours before or 4 hours after oral administration of any polyvalent cation containing product. Risk D: Consider therapy modification
Elvitegravir: Polyvalent Cation Containing Products may decrease the serum concentration of Elvitegravir. Management: Administer elvitegravir 2 hours before or 6 hours after the administration of polyvalent cation containing products. Risk D: Consider therapy modification
Estramustine: Calcium Salts may decrease the absorption of Estramustine. Management: Administer estramustine on an empty stomach, at least 1 hour before or 2 hours after the dose of an oral calcium supplement. If coadministered with calcium salts, monitor for decreased estramustine therapeutic effects. Risk D: Consider therapy modification
Multivitamins/Fluoride (with ADE): May increase the serum concentration of Calcium Salts. Calcium Salts may decrease the serum concentration of Multivitamins/Fluoride (with ADE). More specifically, calcium salts may impair the absorption of fluoride. Management: Avoid eating or drinking dairy products or consuming vitamins or supplements with calcium salts one hour before or after of the administration of fluoride. Risk D: Consider therapy modification
Multivitamins/Minerals (with ADEK, Folate, Iron): May increase the serum concentration of Calcium Salts. Risk C: Monitor therapy
PenicillAMINE: Polyvalent Cation Containing Products may decrease the serum concentration of PenicillAMINE. Management: Separate the administration of penicillamine and oral polyvalent cation containing products by at least 1 hour. Risk D: Consider therapy modification
Phosphate Supplements: Calcium Salts may decrease the absorption of Phosphate Supplements. Management: This applies only to oral phosphate and calcium administration. Administering oral phosphate supplements as far apart from the administration of an oral calcium salt as possible may be able to minimize the significance of the interaction. Risk D: Consider therapy modification
Quinolones: Calcium Salts may decrease the absorption of Quinolones. Of concern only with oral administration of both agents. Management: Consider administering an oral quinolone at least 2 hours before or 6 hours after the dose of an oral calcium supplement to minimize this interaction. Monitor for decrease therapeutic effects of quinolones during coadministration. Risk D: Consider therapy modification
Raltegravir: Polyvalent Cation Containing Products may decrease the serum concentration of Raltegravir. Management: Administer raltegravir 2 hours before or 6 hours after administration of the polyvalent cations. Dose separation may not adequately minimize the significance of this interaction. Risk D: Consider therapy modification
Strontium Ranelate: Calcium Salts may decrease the serum concentration of Strontium Ranelate. Management: Separate administration of strontium ranelate and oral calcium salts by at least 2 hours in order to minimize this interaction. Risk D: Consider therapy modification
Tetracyclines: Calcium Salts may decrease the serum concentration of Tetracyclines. Management: If coadministration of oral calcium with oral tetracyclines cannot be avoided, consider separating administration of each agent by several hours. Risk D: Consider therapy modification
Thiazide and Thiazide-Like Diuretics: May decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy
Thyroid Products: Calcium Salts may diminish the therapeutic effect of Thyroid Products. Management: Separate the doses of the thyroid product and the oral calcium supplement by at least 4 hours. Monitor for decreased therapeutic effects of thyroid products if an oral calcium supplement is initiated/dose increased. Risk D: Consider therapy modification
Trientine: Polyvalent Cation Containing Products may decrease the serum concentration of Trientine. Management: Avoid concomitant administration of trientine and oral products that contain polyvalent cations. If oral iron supplements are required, separate the administration by 2 hours. If other oral polyvalent cations are needed, separate administration by 1 hour. Risk D: Consider therapy modification
Vitamin D Analogs: Calcium Salts may enhance the adverse/toxic effect of Vitamin D Analogs. Risk C: Monitor therapy
Foods that contain maltitol may have an additive laxative effect with the oral solution formulation (contains maltitol).
Oral dosage forms must be administered with meals to be effective.
Calcium crosses the placenta (IOM 2011).
The amount of calcium reaching the fetus is determined by maternal physiological changes. Intestinal absorption of calcium increases during pregnancy (IOM 2011). Administration of calcium acetate to pregnant patients with kidney failure on dialysis is not expected to cause adverse maternal or fetal outcomes; however, untreated maternal kidney failure and hypercalcemia may lead to pregnancy complications. Maternal calcium concentrations should be monitored and maintained within normal limits.
Serum calcium (twice weekly during initial dose adjustments), serum phosphorus; serum calcium-phosphorus product; intact parathyroid hormone (iPTH)
Corrected total serum calcium: Children, Adolescents, and Adults: CKD stages 2 to 5D: Maintain normal ranges; preferably on the lower end for stage 5 (KDIGO 2009; KDOQI 2005)
Phosphorus (KDIGO 2009):
CKD stages 3 to 5: Maintain normal ranges
CKD stage 5D: Lower elevated phosphorus levels toward the normal range
Combines with dietary phosphate to form insoluble calcium phosphate which is excreted in feces
Absorption: 30% to 40%; requires vitamin D; minimal unless chronic, high doses are given; calcium is absorbed in soluble, ionized form; solubility of calcium is increased in an acid environment
Excretion: Primarily feces (as unabsorbed calcium); urine (20%)
Due to a poor correlation between the serum ionized calcium (free) and total serum calcium, particularly in states of low albumin or acid/base imbalances, direct measurement of ionized calcium is recommended. If ionized calcium is unavailable, in low albumin states, the corrected total serum calcium may be estimated by this equation (assuming a normal albumin of 4 g/dL); [(4 – patient's albumin) x 0.8] + patient's measured total calcium
Calcium Salt |
Elemental Calcium (mg/1 g of salt form) |
Calcium (mEq/g) |
---|---|---|
Calcium acetate |
253 |
12.7 |
Calcium carbonate |
400 |
20 |
Calcium chloride |
273 |
13.6 |
Calcium citrate |
211 |
10.5 |
Calcium glubionate |
63.8 |
3.2 |
Calcium gluconate |
93 |
4.65 |
Calcium lactate |
130 |
6.5 |
Calcium phosphate (tribasic) |
390 |
19.3 |
Chronic kidney disease (CKD) (KDIGO 2013; KDOQI 2002): Children ≥2 years, Adolescents, and Adults: GFR <60 mL/minute/1.73 m2 or kidney damage for >3 months; stages of CKD are described below:
CKD Stage 1: Kidney damage with normal or increased GFR; GFR >90 mL/minute/1.73 m2
CKD Stage 2: Kidney damage with mild decrease in GFR; GFR 60 to 89 mL/minute/1.73 m2
CKD Stage 3: Moderate decrease in GFR; GFR 30 to 59 mL/minute/1.73 m2
CKD Stage 4: Severe decrease in GFR; GFR 15 to 29 mL/minute/1.73 m2
CKD Stage 5: Kidney failure; GFR <15 mL/minute/1.73 m2 or dialysis
Capsules (Calcium Acetate (Phos Binder) Oral)
667 mg (per each): $0.44 - $1.03
Solution (Phoslyra Oral)
667 mg/5 mL (per mL): $0.43
Tablets (Calcium Acetate (Phos Binder) Oral)
667 mg (per each): $0.15 - $0.53
Tablets (Calcium Acetate Oral)
667 mg (per each): $1.80
668 (169 Ca) mg (per each): $0.10
Tablets (Calphron Oral)
667 mg (per each): $0.17
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