Version May 2024
Note: Calcium acetate 667 mg contains 169 mg elemental calcium.
Hyperphosphatemia in chronic kidney disease, treatment: Note: Use in combination with dietary phosphate restriction (KDIGO 2017).
Oral: Initial: 1,334 mg calcium acetate with each meal.
Dosage adjustment: Increase or decrease dose (eg, by 667 mg per meal) at 2- or 3-week intervals as needed to obtain targeted serum phosphorus concentrations; usual dosage range: 1,334 to 2,001 mg calcium acetate with each meal (Quarles 2022; Kovesdy 2018; manufacturer’s labeling).
Note: Do not exceed 6,003 mg/day calcium acetate (1,500 mg/day elemental calcium) and limit total elemental calcium intake from all sources (ie, dietary and phosphate binders) to ≤2,000 mg/day (K/DOQI 2003; Kovesdy 2018). Monitor serum calcium concentrations and consider non–calcium-containing phosphate binders if hypercalcemia develops; do not administer additional calcium supplements.
Dietary supplement (OTC): Oral: 1 to 3 tablets with meals (3 times daily) or as directed by health care provider.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary (expert opinion).
eGFR <60 mL/minute/1.73 m2: There are no specific dosage adjustments recommended; however, a positive calcium balance (calculated by subtracting total body calcium losses from total calcium inputs) has been associated with increased mortality in patients with chronic kidney disease (CKD) (KDIGO 2017). Daily elemental calcium intake (including dietary sources and calcium-based phosphate binders) recommendations in patients with CKD G3A through G5D (patients on hemodialysis, peritoneal dialysis) vary; one guideline recommends not exceeding 2,000 mg/day (K/DOQI 2003), but more recent short-term studies in nondialysis patients suggest limiting intake to 800 to 1,000 mg/day (Hill 2013; Hill Gallant 2017; Spiegel 2012). Decisions regarding calcium acetate use and dose must be individualized to the patient, and hypercalcemia should be avoided (KDIGO 2017).
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
(For additional information see "Calcium acetate: Pediatric drug information")
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.
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 patients with hypoparathyroidism who are 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).
Calcium acetate is approximately 25% elemental calcium
Calcium acetate 667 mg = elemental calcium 169 mg = calcium 8.45 mEq = calcium 4.23 mmol
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Generic: 667 mg
Solution, Oral:
Phoslyra: 667 mg/5 mL (473 mL [DSC]) [contains methylparaben, propylene glycol]
Tablet, Oral:
Calphron: 667 mg
Generic: 667 mg, 668 mg
May be product dependent
Capsules (Calcium Acetate (Phos Binder) Oral)
667 mg (per each): $0.17 - $1.03
Tablets (Calcium Acetate (Phos Binder) Oral)
667 mg (per each): $0.15 - $1.16
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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Oral: Administer with meals. Do not chew tablets.
Oral: Administer with plenty of fluids with meals to optimize effectiveness
Hyperphosphatemia in chronic kidney disease (treatment): Control of serum phosphorous in patients with chronic kidney disease (CKD) on hemodialysis.
Note: Based on the Kidney Disease: Improving Global Outcome guideline update for the diagnosis, evaluation, prevention, and treatment of CKD–mineral and bone disorder (CKD-MBD), calcium acetate may also be used to control serum phosphorous in patients with grades 3 to 5 CKD not on hemodialysis who exhibit progressively or persistently elevated serum phosphate levels (KDIGO 2017).
Dietary supplement (OTC): Dietary calcium supplementation.
PhosLo may be confused with Phos-Flur, ProSom
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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
Levonadifloxacin: Calcium Salts may decrease the serum concentration of Levonadifloxacin. Risk X: Avoid combination
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 oral calcium to minimize this interaction. Monitor for decreased 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
Roxadustat: Polyvalent Cation Containing Products may decrease the serum concentration of Roxadustat. Management: Administer roxadustat at least 1 hour after the administration of oral polyvalent cation containing products. 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 increase the serum concentration of Calcium Salts. 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 use of trientine and polyvalent cations. If oral iron supplements are required, separate the administration by 2 hours. For other oral polyvalent cations, give trientine 1 hour before, or 1 to 2 hours after the polyvalent cation. Risk D: Consider therapy modification
Unithiol: May diminish the therapeutic effect of Polyvalent Cation Containing Products. Risk X: Avoid combination
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).
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.
Calcium and acetate are present in breast milk.
The amount of calcium in breast milk is homeostatically regulated and not altered by maternal calcium intake (IOM 2011).
Oral dosage forms must be administered with meals to be effective.
Serum calcium (twice weekly during initial dose adjustments), serum phosphorus; serum calcium-phosphorus product; intact parathyroid hormone (iPTH)
KDIGO guidelines:
Serum calcium, phosphorus, and parathyroid hormone (PTH): Frequency of measurement may be dependent upon the presence and magnitude of abnormalities, the rate of progression of chronic kidney disease (CKD), and the use of treatments for chronic kidney disease-mineral and bone disorder (CKD-MBD) (KDIGO 2017):
CKD stage G3a to G3b: Serum calcium and phosphate: Every 6 to 12 months; PTH: Frequency based on baseline level and progression of CKD
CKD stage G4: Serum calcium and phosphate: Every 3 to 6 months; PTH: Every 6 to 12 months
CKD stage G5 and G5D: Serum calcium and phosphate: Every 1 to 3 months; PTH: Every 3 to 6 months
Note: Due to the complexity and interdependency of the laboratory parameters used for therapeutic decisions in chronic kidney disease-mineral and bone disorder (CKD-MBD) patients, serial assessments of phosphate, calcium, and parathyroid hormone (PTH) levels should be considered together (KDIGO 2017)
Calcium (total): Normal range: Adults: 8.6 to 10.2 mg/dL (SI: 2.2 to 2.6 mmol/L). Avoid hypercalcemia for chronic kidney disease (CKD) stages G3a to G5D (KDIGO 2017)
Phosphorus: 3 to 4.5 mg/dL (SI: 1 to 1.5 mmol/L). Lower elevated phosphorus levels toward the normal range for CKD stages G3a to G5D (KDIGO 2017)
PTH:
CKD stage G3a to G5: Optimal PTH level is unknown; evaluate patients with progressively elevated intact PTH levels or if levels are consistently above the normal range (assay-dependent) (KDIGO 2017)
Dialysis patients: Maintain intact parathyroid hormone (iPTH) within 2 to 9 times the upper limit of normal for the assay used (KDIGO 2017)
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%)
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