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Disease-related concerns: • Achlorhydria: Calcium absorption is impaired in achlorhydria; common in elderly, use an alternate salt (eg, citrate) and administer with food. • Hypoparathyroid disease: Hypercalcemia and hypercalciuria are most likely to occur in hypoparathyroid patients receiving high doses of vitamin D. • Kidney stones (calcium-containing): Use caution when administering calcium supplements to patients with a history of kidney stones. • Renal impairment: Use with caution in patients with renal failure to avoid hypercalcemia; frequent monitoring of serum calcium and phosphorus is necessary.

Dosage form specific issues: • Phenylalanine: Some products may contain phenylalanine. • Shellfish: Some products may be derived from shellfish. • Soy: Some products may contain soy. • Tartrazine: Some products may contain tartrazine.

Other warnings/precautions: • Absorption: Taking calcium (≤500 mg) with food improves absorption. Metabolism/Transport Effects None known. Drug Interactions (For additional information: Launch Lexi-Interact™ Drug Interactions Program ) ACE Inhibitors: Antacids may decrease the serum concentration of ACE Inhibitors. Management: Separate fosinopril administration from antacids by at least 2 hours. US and Canadian recommendations for use of other ACE- inhibitors with antacids may vary. Consult appropriate labeling. Monitor for decreased therapeutic effects of ACE-inhibitors.

Exceptions: Enalaprilat; Ramipril. Risk D: Consider therapy modification Allopurinol: Antacids may decrease the absorption of Allopurinol. Risk D: Consider therapy modification Alpha-/Beta-Agonists: Antacids may decrease the excretion of Alpha-/Beta-Agonists.

Exceptions: Dipivefrin. Risk C: Monitor therapy Amphetamines: Antacids may decrease the excretion of Amphetamines. Risk C: Monitor therapy Anticonvulsants (Hydantoin): Antacids may decrease the serum concentration of Anticonvulsants (Hydantoin). Risk C: Monitor therapy Antipsychotic Agents (Phenothiazines): Antacids may decrease the absorption of Antipsychotic Agents (Phenothiazines). Risk C: Monitor therapy Atazanavir: Antacids may decrease the absorption of Atazanavir. Risk D: Consider therapy modification Bisacodyl: Antacids may diminish the therapeutic effect of Bisacodyl. Antacids may cause the delayed-release bisacodyl tablets to release drug prior to reaching the large intestine. Gastric irritation and/or cramps may occur. Risk D: Consider therapy modification Bisphosphonate Derivatives: Calcium Salts may decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral calcium supplements within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate.

Exceptions: Pamidronate; Zoledronic Acid. Risk D: Consider therapy modification Bisphosphonate Derivatives: Antacids may decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of antacids containing polyvalent cations within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate.

Exceptions: Pamidronate; Zoledronic Acid. Risk D: Consider therapy modification Bosutinib: Antacids may decrease the serum concentration of Bosutinib. Management: Administer antacids more than 2 hours before or after bosutinib. Risk D: Consider therapy modification Calcium Acetate: Calcium Salts may enhance the adverse/toxic effect of Calcium Acetate. Risk X: Avoid combination Calcium Channel Blockers: Calcium Salts may diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy Calcium Polystyrene Sulfonate: Antacids may enhance the adverse/toxic effect of Calcium Polystyrene Sulfonate. The combined use of these two agents may result in metabolic alkalosis and/or loss of efficacy of the cation exchange resin. Management: To minimize this interaction, consider: a)separating doses by 2 or more hours; b)rectal administration of the exchange resin; or c)alternatives to antacids. Monitor for metabolic alkalosis and attenuation of CPS effects. Avoid magnesium hydroxide. Risk D: Consider therapy modification Cefditoren: Antacids may decrease the serum concentration of Cefditoren. Management: Concomitant use of cefditoren with antacids is not recommended. Consider alternative methods to control acid reflux (eg, diet modification) or alternative antimicrobial therapy. If antacid therapy can not be avoided, separate dosing by several hours. Risk D: Consider therapy modification Cefpodoxime: Antacids may decrease the serum concentration of Cefpodoxime. Risk C: Monitor therapy Cefuroxime: Antacids may decrease the serum concentration of Cefuroxime. Management: Consider administering antacids and cefuroxime at least 2 hours apart. Risk D: Consider therapy modification Chloroquine: Antacids may decrease the serum concentration of Chloroquine. Management: Separate administration of antacids and chloroquine by at least 4 hours to minimize any potential negative impact of antacids on chloroquine bioavailability. Risk D: Consider therapy modification Corticosteroids (Oral): Antacids may decrease the bioavailability of Corticosteroids (Oral). Management: Consider separating doses by 2 or more hours. Budesonide enteric coated tablets could dissolve prematurely if given with drugs that lower gastric acid, with unknown impact on budesonide therapeutic effects. Risk D: Consider therapy modification

Corticosteroids (Oral): Antacids may decrease the bioavailability of Corticosteroids (Oral). Management: Consider separating doses by 2 or more hours. Budesonide enteric coated tablets could dissolve prematurely if given with drugs that lower gastric acid, with unknown impact on budesonide therapeutic effects. Risk D: Consider therapy modification Dabigatran Etexilate: Antacids may decrease the serum concentration of Dabigatran Etexilate. Management: Dabigatran etexilate Canadian product labeling recommends avoiding concomitant use with antacids for 24 hours after surgery. In other situations, administer dabigatran etexilate 2 hours prior to antacids. Monitor clinical response to dabigatran therapy. Risk D: Consider therapy modification Dasatinib: Antacids may decrease the absorption of Dasatinib. Risk D: Consider therapy modification Deferiprone: Antacids 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 Deferiprone: Calcium Salts 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 Delavirdine: Antacids may decrease the serum concentration of Delavirdine. Management: Separate doses of delavirdine and antacids by at least 1 hour. Monitor for decreased delavirdine therapeutic effects with this combination. Risk D: Consider therapy modification Dexmethylphenidate: Antacids may increase the absorption of Dexmethylphenidate. Specifically, antacids may interfere with the normal release of drug from the extended-release capsules (Focalin XR brand), which could result in both increased absorption (early) and decreased delayed absorption. Risk C: Monitor therapy DOBUTamine: Calcium Salts may diminish the therapeutic effect of DOBUTamine. Risk C: Monitor therapy Eltrombopag: Calcium Salts may decrease the serum concentration of Eltrombopag. Management: Separate administration of eltrombopag and any polyvalent cation (e.g., calcium-containing products) by at least 4 hours. Risk D: Consider therapy modification

DOBUTamine: Calcium Salts may diminish the therapeutic effect of DOBUTamine. Risk C: Monitor therapy Eltrombopag: Calcium Salts may decrease the serum concentration of Eltrombopag. Management: Separate administration of eltrombopag and any polyvalent cation (e.g., calcium-containing products) by at least 4 hours. Risk D: Consider therapy modification Elvitegravir: Antacids may decrease the serum concentration of Elvitegravir. Management: Separate administration of antacids and the elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate combination product by at least 2 hours in order to minimize the risk for an interaction. Risk D: Consider therapy modification Erlotinib: Antacids may decrease the serum concentration of Erlotinib. Management: Separate the administration of erlotinib and any antacid by several hours in order to minimize the risk of a significant interaction. Risk D: Consider therapy modification Estramustine: Calcium Salts may decrease the absorption of Estramustine. Risk D: Consider therapy modification Gabapentin: Antacids may decrease the serum concentration of Gabapentin. Management: Administer gabapentin at least 2 hours after antacid administration. Monitor patients closely for evidence of reduced response to gabapentin therapy when both of these drugs are being used. Risk D: Consider therapy modification HMG-CoA Reductase Inhibitors: Antacids may decrease the serum concentration of HMG-CoA Reductase Inhibitors. Risk C: Monitor therapy Iron Salts: Antacids may decrease the absorption of Iron Salts.

Exceptions: Ferric Gluconate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Risk D: Consider therapy modification Isoniazid: Antacids may decrease the absorption of Isoniazid. Risk D: Consider therapy modification Itraconazole: Antacids may decrease the serum concentration of Itraconazole. Management: Administer itraconazole at least 1 hour after and 2 hours before administration of any antacids. Itraconazole oral suspension may be less sensitive to the effects of decreased gastric acidity. Risk D: Consider therapy modification Ketoconazole (Systemic): Antacids may decrease the serum concentration of Ketoconazole (Systemic). Management: Administer oral ketoconazole at least 2 hours prior to use of any antacid product. Monitor patients closely for signs of inadequate clinical response to ketoconazole. Risk D: Consider therapy modification Mesalamine: Antacids may diminish the therapeutic effect of Mesalamine. Antacid-mediated increases in gastrointestinal pH may cause the premature release of mesalamine from specific sustained-release mesalamine products. Management: Avoid concurrent administration of antacids with sustained-release mesalamine products. Separating antacid and mesalamine administration, and/or using lower antacid doses may be adequate means of avoiding this interaction. Risk D: Consider therapy modification Methenamine: Antacids may diminish the therapeutic effect of Methenamine. Risk D: Consider therapy modification Methylphenidate: Antacids may increase the absorption of Methylphenidate. Specifically, antacids may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. Risk C: Monitor therapy Multivitamins/Minerals (with ADEK, Folate, Iron): Antacids may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, antacids may decrease the absorption of orally administered iron. Management: Separate dosing of oral iron-containing multivitamin preparations and antacids by as much time as possible in order to minimize impact on therapeutic efficacy of the iron preparation. Risk D: Consider therapy modification Multivitamins/Minerals (with ADEK, Folate, Iron): May increase the serum concentration of Calcium Salts. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): Antacids may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, antacids may decrease the absorption of orally administered iron. Management: Separate dosing of oral iron-containing multivitamin preparations and antacids by as much time as possible in order to minimize impact on therapeutic efficacy of the iron preparation. Risk D: Consider therapy modification Multivitamins/Minerals (with ADEK, Folate, Iron): May increase the serum concentration of Calcium Salts. Risk C: Monitor therapy Mycophenolate: Antacids may decrease the absorption of Mycophenolate. Management: Separate doses of mycophenolate and antacids by at least 2 hours. Monitor for reduced effects of mycophenolate if taken concomitant with antacids. Risk D: Consider therapy modification Nilotinib: Antacids may decrease the serum concentration of Nilotinib. Management: Separate the administration of nilotinib and any antacid by several hours whenever possible in order to minimize the risk of a significant interaction. Risk D: Consider therapy modification PenicillAMINE: Antacids may decrease the serum concentration of PenicillAMINE. Risk D: Consider therapy modification Phosphate Supplements: Antacids may decrease the absorption of Phosphate Supplements.

Exceptions: Darunavir. Risk C: Monitor therapy QuiNIDine: Antacids may decrease the excretion of QuiNIDine. Risk C: Monitor therapy Quinolone Antibiotics: Antacids may decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of quinolones. Risk D: Consider therapy modification Quinolone Antibiotics: Calcium Salts may decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents.

Exceptions: Moxifloxacin (Systemic). Risk D: Consider therapy modification Rilpivirine: Antacids may decrease the serum concentration of Rilpivirine. Management: Administer antacids at least 2 hours before or 4 hours after rilpivirine. Risk D: Consider therapy modification Sodium Polystyrene Sulfonate: Antacids may enhance the adverse/toxic effect of Sodium Polystyrene Sulfonate. The combined use of these two agents may result in metabolic alkalosis and/or loss of efficacy of the exchange resin. Management: To minimize this interaction, consider: a)separating doses by 2 or more hours; b)rectal administration of the exchange resin; or c)alternatives to antacids. Monitor for metabolic alkalosis and attenuation of SPS effects. Avoid magnesium hydroxide. 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 Tetracycline Derivatives: Antacids may decrease the absorption of Tetracycline Derivatives. Risk D: Consider therapy modification Tetracycline Derivatives: Calcium Salts may decrease the serum concentration of Tetracycline Derivatives. Management: If coadministration of oral calcium with oral tetracyclines can not be avoided, consider separating administration of each agent by several hours. Risk D: Consider therapy modification Thiazide 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. Risk D: Consider therapy modification Trientine: Antacids may decrease the absorption of Trientine. Management: Separate trientine dosing from other oral drugs (eg, antacids) by at least 1 hour. Monitor for decreased therapeutic effects of trientine if an antacid is initiated/dose increased, or increased effects if an antacid is discontinued/dose decreased. Risk D: Consider therapy modification

Trientine: Antacids may decrease the absorption of Trientine. Management: Separate trientine dosing from other oral drugs (eg, antacids) by at least 1 hour. Monitor for decreased therapeutic effects of trientine if an antacid is initiated/dose increased, or increased effects if an antacid is discontinued/dose decreased. Risk D: Consider therapy modification Trientine: Calcium Salts may decrease the serum concentration of Trientine. Trientine may decrease the serum concentration of Calcium Salts. Risk D: Consider therapy modification Vismodegib: Antacids may decrease the serum concentration of Vismodegib. Management: Carefully consider the need for any medication that increases the pH of the upper GI tract (PPIs, H2RAs, antacids), as these could significantly reduce vismodegib systemic exposure. Vismodegib dose increases are unlikely to compensate for this effect. Risk D: Consider therapy modification Vitamin D Analogs: Calcium Salts may enhance the adverse/toxic effect of Vitamin D Analogs. Risk C: Monitor therapy Ethanol/Nutrition/Herb Interactions Ethanol: Avoid ethanol (may increase risk of osteoporosis). Food: Food may increase calcium absorption. Calcium may decrease iron absorption. Bran, foods high in oxalates, or whole grain cereals may decrease calcium absorption. Pregnancy Implications Available evidence suggests safe use during pregnancy. Breast-Feeding Considerations Available evidence suggests safe use during lactation. Dietary Considerations Take (preferably with food) 2 hours before or after other medications to minimize GI upset. Some products may contain phenylalanine (avoid use in phenylketonurics). Pricing: U.S. (Medi-Span®)

Tablets (RA Hi-Cal Plus Vitamin D Oral) 500-200 mg-unit (60): $5.19 Monitoring Parameters Monitor serum calcium (particularly if used in patients with severe renal impairment) International Brand Names Calcio 600 + D (CO); Calperos D3 (HK); Calporosis D (ID); Calsical (ID); Caltrate + D 300 (HK); CDR Fortos (ID); Os-Cal + D (SG); Os-Cal 500 + D (HK) Use of UpToDate is subject to the Subscription and License Agreement . Topic 9162 Version 40.0 © 2013 UpToDate, Inc. All rights reserved. | Subscription and License Agreement | Release: 21.6- C21.56 Licensed to: AsanBook Dig. Med. Lib. | Support Tag: [1004-61.234.146.186-CAE323FBD7-S244013.14]