Version May 2024
Note: 90-day treatment regimen involves sequential administration of two products within the packaging; not to be taken concurrently. The first blister card contains white tablets containing etidronate disodium, while the remaining four blister cards contains blue, capsule-shaped tablets containing calcium carbonate. If bone mass is not stabilized within 4 cycles (1 year) of therapy, consider discontinuation of treatment.
Corticosteroid-induced osteoporosis, postmenopausal osteoporosis: Oral: Etidronate disodium 400 mg once daily for 14 days, followed by calcium carbonate 1,250 mg (500 mg elemental calcium) once daily for 76 days.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution and monitor closely. The IV form of etidronate has been noted to be nephrotoxic.
There are no dosage adjustments provided in the manufacturer’s labeling.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. Also see individual agents.
>10%:
Gastrointestinal: Diarrhea (37%), dyspepsia (12%), flatulence (17%), nausea (18%)
Nervous system: Dizziness (16%), headache (13%)
Frequency not defined:
Gastrointestinal: Gastritis
Neuromuscular & skeletal: Lower limb cramp
Postmarketing:
Dermatologic: Alopecia, erythema multiforme, Stevens-Johnson syndrome
Gastrointestinal: Esophagitis, exacerbation of peptic ulcer, glossitis
Hematologic & oncologic: Agranulocytosis, leukemia, leukopenia, pancytopenia
Hypersensitivity: Hypersensitivity reaction (including angioedema)
Nervous system: Glossopyrosis, paresthesia, psychiatric disturbance (including amnesia, confusion, depression, and hallucination)
Neuromuscular & skeletal: Arthropathy (including arthralgia and arthritis), bone fracture, osteomalacia
Respiratory: Exacerbation of asthma
Hypersensitivity to etidronate disodium or any component of the formulation; clinically-overt osteomalacia (appropriate treatment to resolve osteomalacia should be initiated before prescribing etidronate/calcium carbonate therapy).
Concerns related to adverse effects:
• Bone fractures: Atypical femur fractures have been reported in patients receiving bisphosphonates for treatment/prevention of osteoporosis. The fractures include subtrochanteric femur (bone just below the hip joint) and diaphyseal femur (long segment of the thigh bone). Some patients experience prodromal pain weeks or months before the fracture occurs. It is unclear if bisphosphonate therapy is the cause for these fractures, although the majority have been reported in patients taking bisphosphonates. Patients receiving long-term (>3 to 5 years) therapy may be at an increased risk (Adler 2016; NOF [Cosman 2014]); however, benefits of therapy (when used for osteoporosis) generally outweigh absolute risk of AFF within the first 5 years of treatment (Adler 2016). Patients presenting with thigh or groin pain with a history of receiving bisphosphonates should be evaluated for femur fracture. Consider interrupting bisphosphonate therapy in patients who develop a femoral shaft fracture; assess for fracture in the contralateral limb.
• Bone/joint/muscle pain: Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Consider discontinuing therapy in patients who experience severe symptoms; symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy.
• Diarrhea: Diarrhea is common with therapy and may occur more frequently at higher dosages; use with caution in patients with GI disease prone to diarrhea (eg, ulcerative colitis, Crohn disease, irritable bowel syndrome).
• Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Esophagitis, dysphagia, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Discontinue use if new or worsening symptoms develop.
• Hypocalcemia: Hypocalcemia has been reported with the use of bisphosphonates. Prior to therapy initiation, hypocalcemia must be corrected; ensure adequate vitamin D and calcium intake from all sources.
• Ocular effects: Conjunctivitis, iritis, uveitis, scleritis and episcleritis have been observed with bisphosphonates; patients with complicated or severe inflammation may require therapy discontinuation and should be referred for ophthalmic evaluation.
• Osteonecrosis of the jaw: Bisphosphonate therapy has been associated with osteonecrosis of the jaw (ONJ), also referred to as medication-related osteonecrosis of the jaw (MRONJ); this has been observed primarily following dental procedures such as tooth extractions and in cancer patients receiving intravenous bisphosphonates, but has also occurred in patients with postmenopausal osteoporosis and other diagnoses receiving oral bisphosphonates. Risk factors include a diagnosis of cancer, concomitant chemotherapy, radiotherapy, or corticosteroids; anemia, infection, or preexisting dental disease. According to a position paper by the American Association of Maxillofacial Surgeons (AAOMS), MRONJ has been associated with bisphosphonate and other antiresorptive agents (denosumab), and antiangiogenic agents (eg, bevacizumab, sunitinib) used for the treatment of osteoporosis or malignancy; risk of MRONJ is significantly higher in cancer patients receiving antiresorptive therapy compared to patients receiving osteoporosis treatment (regardless of medication used or dosing schedule). MRONJ risk is also increased with intravenous antiresorptive use compared to the minimal risk associated with oral bisphosphonate use, although risk appears to increase with oral bisphosphonates when duration of therapy exceeds 4 years (AAOMS [Ruggiero 2014]). The manufacturer’s labeling recommends dental exams and preventive dentistry be performed prior to placing patients with risk factors (eg, cancer, immune suppression, head/neck radiotherapy, poor hygiene) on chronic bisphosphonate therapy. During treatment, invasive dental procedures should be avoided if possible. For patients requiring dental procedures, there are no available data suggesting whether discontinuation of bisphosphonates decreases the risk of ONJ and clinical judgment should guide the decision. The AAOMS also suggests there is currently no evidence that interrupting oral bisphosphonate therapy alters the risk of ONJ following tooth extraction, and that in patients receiving oral bisphosphonates for <4 years who have no clinical risk factors, no alternations or delay in any procedure common to oral/maxillofacial surgeons, periodontists, and other dental providers is necessary (special considerations apply to patients receiving dental implants). Conversely, in patients receiving oral bisphosphonates for >4 years or in patients receiving oral bisphosphonates for <4 years who have also taken corticosteroids or antiangiogenic medications concomitantly, the AAOMS recommends considering a 2-month drug-free period prior to invasive dental procedures (recommendation based on a theoretical benefit). Patients developing ONJ during therapy should receive care by an oral surgeon (AAOMS [Ruggiero 2014]).
Disease-related concerns:
• Bariatric surgery: Altered absorption and ulceration risk: Avoid oral bisphosphates after bariatric surgery; inadequate oral absorption and potential anastomotic ulceration may occur. If therapy is indicated, IV administered bisphosphonates are recommended.
• Renal impairment: Use with caution in patients with renal impairment; monitor serum and urine calcium and other relevant parameters, if therapy is initiated.
Special populations:
• Calcium/vitamin D restricted patients: Use with caution in patients with restricted calcium and vitamin D intake.
Other warnings/precautions:
• Absorption: Calcium carbonate absorption is impaired in achlorhydria (common in elderly); administer calcium component with food.
Not available in the US
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Kit, Oral:
Generic: Etidronate disodium 400 mg tablets and calcium carbonate 1,250 mg (500 mg elemental calcium) tablets [DSC]
Oral: Administer etidronate tablets with a full glass of water on an empty stomach 2 hours before or after meals (preferably at bedtime). The calcium carbonate tablets may be administered with food (recommended in patients with achlorhydria).
Note: Not approved in the US
Corticosteroid-induced osteoporosis: Prevention of corticosteroid-induced osteoporosis
Postmenopausal osteoporosis: Treatment and prevention of established postmenopausal osteoporosis
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.
Acalabrutinib: Antacids may decrease the serum concentration of Acalabrutinib. Management: Separate administration of acalabrutinib capsules from the administration of any antacid by at least 2 hours in order to minimize the potential for a significant interaction. Acalabrutinib tablets are not expected to interact with antacids. Risk D: Consider therapy modification
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
Aminoglycosides: May enhance the hypocalcemic effect of Bisphosphonate Derivatives. Aminoglycosides may enhance the nephrotoxic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Angiogenesis Inhibitors (Systemic): May enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. 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. Management: Administer antacids 1 to 2 hours before or 2 hours after atazanavir to minimize the risk of a clinically significant interaction. Risk D: Consider therapy modification
Baloxavir Marboxil: Polyvalent Cation Containing Products may decrease the serum concentration of Baloxavir Marboxil. Risk X: Avoid combination
Belumosudil: Antacids may decrease the serum concentration of Belumosudil. Management: Consider separating administration of belumosudil and antacids by 2 hours and monitor for reduced belumosudil efficacy. Risk D: Consider therapy modification
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
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. Management: Antacids should not be used within 1 hour before bisacodyl administration. Risk D: Consider therapy modification
Bismuth Subcitrate: Antacids may diminish the therapeutic effect of Bismuth Subcitrate. Management: Avoid administration of antacids within 30 minutes of bismuth subcitrate (tripotassium bismuth dicitrate) administration. 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
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
Bromperidol: Antacids may decrease the absorption of Bromperidol. Risk C: Monitor therapy
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 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. Risk C: Monitor therapy
Captopril: Antacids may decrease the serum concentration of Captopril. Risk C: Monitor therapy
Cardiac Glycosides: Calcium Salts may enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy
Cefditoren: Antacids may decrease the serum concentration of Cefditoren. Risk X: Avoid combination
Cefpodoxime: Antacids may decrease the serum concentration of Cefpodoxime. Risk C: Monitor therapy
Cefuroxime: Antacids may decrease the serum concentration of Cefuroxime. Management: Administer cefuroxime axetil at least 1 hour before or 2 hours after the administration of short-acting antacids. Risk D: Consider therapy modification
Chloroquine: Antacids may decrease the serum concentration of Chloroquine. Management: Separate the 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
Cysteamine (Systemic): Antacids may diminish the therapeutic effect of Cysteamine (Systemic). Risk C: Monitor therapy
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 serum concentration of Dasatinib. Management: Simultaneous administration of dasatinib and antacids should be avoided. Administer antacids 2 hours before or 2 hours after dasatinib. Risk D: Consider therapy modification
Deferasirox: Bisphosphonate Derivatives may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy
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
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
Diacerein: Antacids may decrease the absorption of Diacerein. Risk C: Monitor therapy
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: Antacids may decrease the serum concentration of Elvitegravir. Management: Separate administration of aluminum and magnesium containing antacids and elvitegravir-containing products by at least 2 hours in order to minimize the risk for an interaction. Risk D: Consider therapy modification
Erdafitinib: Serum Phosphate Level-Altering Agents may diminish the therapeutic effect of Erdafitinib. Management: Avoid coadministration of serum phosphate level-altering agents with erdafitinib before initial dose increase period based on serum phosphate levels (Days 14 to 21). 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. 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
Fosinopril: Antacids may decrease the serum concentration of Fosinopril. Management: The US and Canadian fosinopril manufacturer labels recommend separating the doses of antacids and fosinopril by 2 hours. Risk D: Consider therapy modification
Gefitinib: Antacids may decrease the serum concentration of Gefitinib. Management: Administer gefitinib at least 6 hours before or 6 hours after administration of an antacid, and closely monitor clinical response to gefitinib. Risk D: Consider therapy modification
Hyoscyamine: Antacids may decrease the serum concentration of Hyoscyamine. Management: Administer immediate release and sublingual oral hyoscyamine before meals, and antacids after meals, when these agents are given in combination. Risk D: Consider therapy modification
Infigratinib: Antacids may decrease serum concentrations of the active metabolite(s) of Infigratinib. Antacids may decrease the serum concentration of Infigratinib. Management: Avoid coadministration of infigratinib with antacids or other gastric acid-lowering agents. If antacids cannot be avoided, administer infigratinib 2 hours before or after administration of antacids. Risk D: Consider therapy modification
Inhibitors of the Proton Pump (PPIs and PCABs): May diminish the therapeutic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Iron Preparations: Antacids may decrease the absorption of Iron Preparations. Management: No action is likely necessary for the majority of patients who only use antacids intermittently or occasionally. Consider separating doses of oral iron and antacids in patients who require chronic use of both agents and monitor for reduced iron efficacy. Risk D: Consider therapy modification
Isoniazid: Antacids may decrease the absorption of Isoniazid. Risk C: Monitor therapy
Itraconazole: Antacids may decrease the serum concentration of Itraconazole. Antacids may increase the serum concentration of Itraconazole. Management: Administer Sporanox brand itraconazole at least 2 hours before or 2 hours after administration of any antacids. Exposure to Tolsura brand itraconazole may be increased by antacids; consider itraconazole dose reduction. Risk D: Consider therapy modification
Ketoconazole (Systemic): Antacids may decrease the serum concentration of Ketoconazole (Systemic). Management: Administer antacids at least 1 hour prior to, or 2 hours after, ketoconazole. Additionally, administer ketoconazole with an acidic beverage (eg, non-diet cola) and monitor patients closely for signs of inadequate clinical response to ketoconazole. Risk D: Consider therapy modification
Lanthanum: Antacids may diminish the therapeutic effect of Lanthanum. Management: Administer antacid products at least 2 hours before or after lanthanum. Risk D: Consider therapy modification
Ledipasvir: Antacids may decrease the serum concentration of Ledipasvir. Management: Separate the administration of ledipasvir and antacids by 4 hours. Risk D: Consider therapy modification
Levoketoconazole: Antacids may decrease the absorption of Levoketoconazole. Management: Advise patients to take antacids at least 2 hours after taking levoketoconazole. Risk D: Consider therapy modification
Levonadifloxacin: Calcium Salts may decrease the serum concentration of Levonadifloxacin. Risk X: Avoid combination
Levonadifloxacin: Antacids may decrease the serum concentration of Levonadifloxacin. Risk X: Avoid combination
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 the Apriso brand of mesalamine extended-release capsules. The optimal duration of dose separation is unknown. Other mesalamine products do not contain this interaction warning. Risk D: Consider therapy modification
Methenamine: Antacids may diminish the therapeutic effect of Methenamine. Management: Consider avoiding the concomitant use of medications that alkalinize the urine, such as antacids, and methenamine. Monitor for decreased therapeutic effects of methenamine if used concomitant with antacids. 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): 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 multivitamins and antacids by as much time as possible to minimize impact of this interaction. Monitor for decreased therapeutic efficacy of oral iron preparations during coadministration. Risk D: Consider therapy modification
Neratinib: Antacids may decrease the serum concentration of Neratinib. Specifically, antacids may reduce neratinib absorption. Management: Separate the administration of neratinib and antacids by giving neratinib at least 3 hours after the antacid. Risk D: Consider therapy modification
Nilotinib: Antacids may decrease the serum concentration of Nilotinib. Management: Separate the administration of nilotinib and any antacid by at least 2 hours whenever possible in order to minimize the risk of a significant interaction. Risk D: Consider therapy modification
Nirogacestat: Antacids may decrease the serum concentration of Nirogacestat. Management: If acid-reducing therapy is required, separate nirogacestat administration from antacids by 2 hours. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor therapy
Octreotide: Antacids may decrease the serum concentration of Octreotide. Risk C: Monitor therapy
PAZOPanib: Antacids may decrease the serum concentration of PAZOPanib. Management: Avoid the use of antacids in combination with pazopanib whenever possible. Separate doses by several hours if antacid treatment is considered necessary. The impact of dose separation has not been investigated. Risk D: Consider therapy modification
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
Pexidartinib: Antacids may decrease the serum concentration of Pexidartinib. Management: Administer pexidartinib at least 2 hours before or 2 hours after antacids. Risk D: Consider therapy modification
Phosphate Supplements: Antacids may decrease the absorption of Phosphate Supplements. Management: This applies only to oral phosphate administration. Separating administration of oral phosphate supplements from antacid administration by as long as possible may minimize the interaction. 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
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
Potassium Phosphate: Antacids may decrease the serum concentration of Potassium Phosphate. Management: Consider separating administration of antacids and oral potassium phosphate by at least 2 hours to decrease risk of a significant interaction. Risk D: Consider therapy modification
Quinolones: Antacids may decrease the absorption of Quinolones. Of concern only with oral administration of quinolones. Management: Avoid concurrent administration of quinolones and antacids to minimize the impact of this interaction. Recommendations for optimal dose separation vary by specific quinolone; see full monograph for details. 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: Calcium Carbonate may decrease the serum concentration of Raltegravir. Management: Use of once-daily raltegravir with calcium carbonate is not recommended; dose separation does not appear to be adequate to minimize the significance of this interaction. Use of other raltegravir products do not require any dose change. 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 oral rilpivirine when used with most rilpivirine products. However, administer antacids at least 6 hours before or 4 hours after the rilpivirine/dolutegravir combination product. Risk D: Consider therapy modification
Riociguat: Antacids may decrease the serum concentration of Riociguat. Management: Separate the administration of antacids and riociguat by at least 1 hour in order to minimize any potential interaction. Monitor clinical response to riociguat more closely in patients using this combination. Risk D: Consider therapy modification
Rosuvastatin: Antacids may decrease the serum concentration of Rosuvastatin. Risk C: Monitor therapy
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
Selpercatinib: Antacids may decrease the serum concentration of Selpercatinib. Management: Coadministration of selpercatinib and antacids should be avoided. If coadministration cannot be avoided, selpercatinib should be administered 2 hours before or 2 hours after antacids. Risk D: Consider therapy modification
Sodium Polystyrene Sulfonate: Antacids may enhance the adverse/toxic effect of Sodium Polystyrene Sulfonate. Specifically, the risk of metabolic alkalosis may be increased. Antacids may diminish the therapeutic effect of Sodium Polystyrene Sulfonate. Risk C: Monitor therapy
Sotalol: Antacids may decrease the serum concentration of Sotalol. Management: Avoid simultaneous administration of sotalol and antacids. Administer antacids 2 hours after sotalol. Risk D: Consider therapy modification
Sotorasib: Antacids may decrease the serum concentration of Sotorasib. Management: Avoid coadministration of sotorasib and antacids. If use of a gastric acid suppressing medication cannot be avoided, administer sotorasib 4 hours before or 10 hours after oral antacid administration. Risk D: Consider therapy modification
Sparsentan: Antacids may decrease the serum concentration of Sparsentan. Management: Administer sparsentan 2 hours before or 2 hours after antacids. 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
Sucralfate: Antacids may diminish the therapeutic effect of Sucralfate. Management: Consider separating the administration of antacids and sucralfate by at least 30 minutes. Risk D: Consider therapy modification
Sulpiride: Antacids may decrease the serum concentration of Sulpiride. Management: Separate administration of antacids and sulpiride by at least 2 hours in order to minimize the impact of antacids on sulpiride absorption. Risk D: Consider therapy modification
Technetium Tc 99m Medronate: Etidronate may diminish the diagnostic effect of Technetium Tc 99m Medronate. Management: Consider performing bone scintigraphy with technetium Tc 99m medronate before, or at least 2 to 4 weeks after, etidronate administration. Risk D: Consider therapy modification
Tetracyclines: Antacids may decrease the absorption of Tetracyclines. Management: Separate administration of antacids and oral tetracycline derivatives by several hours when possible to minimize the extent of this potential interaction. Monitor for decreased therapeutic effects of tetracyclines. 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
Velpatasvir: Antacids may decrease the serum concentration of Velpatasvir. Management: Separate administration of velpatasvir and antacids by at least 4 hours. Risk D: Consider therapy modification
Vitamin D Analogs: Calcium Salts may enhance the adverse/toxic effect of Vitamin D Analogs. Risk C: Monitor therapy
Food decreases the absorption and bioavailability of etidronate. Management: Administer on an empty stomach with a full glass of water 2 hours before or after food/supplements with calcium, iron, or magnesium.
Bisphosphonates are incorporated into the bone matrix and gradually released over time. Because exposure prior to pregnancy may theoretically increase the risk of fetal harm, most sources recommend discontinuing bisphosphonate therapy in females of reproductive potential as early as possible prior to a planned pregnancy. Use in premenopausal females should be reserved for special circumstances when rapid bone loss is occurring; a bisphosphonate with the shortest half-life should then be used (Bhalla 2010; Pereira 2012; Stathopoulos 2011).
Oral bisphosphonates can be considered for the prevention of glucocorticoid-induced osteoporosis in premenopausal females with moderate to high risk of fracture who do not plan to become pregnant during the treatment period and who are using effective birth control (or are not sexually active); intravenous therapy should be reserved for high risk patients only (Buckley [ACR 2017]).
It is not known if bisphosphonates cross the placenta, but based on their lower molecular weight, fetal exposure is expected (Djokanovic 2008; Stathopoulos 2011).
Information related to the use of etidronate in pregnancy is available from case reports and small retrospective studies (Levy 2009; Sokol 2019; Vjuasinovic-Stupar 2012).
Bisphosphonates are incorporated into the bone matrix and gradually released over time. The amount available in the systemic circulation varies by drug, dose, and duration of therapy. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy (hypocalcemia, low birth weight, and decreased gestation have been observed in some case reports); however, available data have not shown that exposure to bisphosphonates during pregnancy significantly increases the risk of adverse fetal events (Djokanovic 2008; Green 2014; Levy 2009; Sokal 2019; Stathopoulos 2011). Exposed infants should be monitored for hypocalcemia after birth (Djokanovic 2008; Stathopoulos 2011).
This product is not intended for use in pregnant women.
Calcium is present in breast milk (refer to calcium carbonate monograph for additional information); excretion of etidronate is not known.
This product is not intended for use in breastfeeding women. Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.
Etidronate: Administer tablet with water on an empty stomach; avoid administering foods/supplements with calcium, iron, or magnesium within 2 hours of drug; maintain adequate intake of calcium and vitamin D.
Calcium: As a dietary supplement, should be given with meals to increase absorption. May decrease iron absorption, so should be administered 1 to 2 hours before or after iron supplementation; limit intake of with bran, foods high in oxalates, or whole grain cereals which may decrease calcium absorption. Dietary calcium should be adjusted to supply at least 1500 mg/day (ACT Etidrocal supplies 500 mg/day), and dietary vitamin D intake should provide 400 units/day.
Bone mineral density (BMD) should be evaluated 1 to 2 years after initiating therapy and every 1 to 2 years (or less frequently if stable) thereafter (AACE/ACE [Camacho 2016]; NOF [Cosman 2014]); serum and urine calcium (particularly in renal impairment or a history of nephrolithiasis); serum 25(OH)D and phosphorous; dental exam and preventive dentistry prior to initiation of therapy for patients at risk for osteonecrosis (eg, cancer patients, immunosuppressed, head/neck radiotherapy)
Calcium (total): Adults: 9 to 11 mg/dL (2.25 to 2.74 mmol/L), may slightly decrease with aging.
Phosphorus: 2.5 to 4.5 mg/dL (0.81 to 1.45 mmol/L).
Vitamin D: There is no clear consensus on a reference range for total serum 25(OH)D concentrations or the validity of this level as it relates clinically to bone health. In addition, there is significant variability in the reporting of serum 25(OH)D levels as a result of different assay types in use; however, the following ranges have been suggested:
Adults (IOM 2011): Sufficient levels in practically all persons: ≥20 ng/mL (50 nmol/L); concern for risk of toxicity: >50 ng/mL (125 nmol/L).
Osteoporosis patients (NOF 2013): Recommended level to reach and maintain: ~30 ng/mL (75 nmol/L).
See individual agents.
See individual agents.
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