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Drug Interactions between etidronate and naproxen

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

naproxen etidronate

Applies to: naproxen and etidronate

MONITOR: Theoretical concerns exist regarding the potential for increased risk and severity of gastrointestinal toxicity during coadministration of oral bisphosphonates and nonsteroidal anti-inflammatory drugs (NSAIDs) due to additive or synergistic irritant effects on the gastrointestinal mucosa. Because NSAIDs reduce the rate of ulcer healing in the stomach and duodenum, it is also possible that NSAIDs may delay healing and exaggerate the mucosal injury caused by oral bisphosphonates. In a blinded, randomized, crossover study consisting of 26 healthy volunteers, investigators using endoscopic techniques reported a significantly higher incidence of gastric ulcers following combined treatment with alendronate 10 mg once a day and naproxen 500 mg twice a day for 14 days than after treatment with either alendronate or naproxen alone (38% vs. 8% and 12%, respectively). In contrast, a 3-year controlled clinical study found no significant difference in the incidence of upper gastrointestinal adverse events between alendronate 5 or 10 mg/day and placebo given to more than 2000 subjects, most of whom received concomitant NSAIDs. Likewise, the incidence of upper gastrointestinal adverse events was similar for risedronate (24.5%) and placebo (24.8%) among patients who were regular users (>= 3 days/week) of aspirin or NSAIDs in phase 3 osteoporosis studies, which enrolled a total of over 5700 patients. Aspirin use was reported by 31% of patients and NSAID use by 48% of patients, 24% and 21% of whom were regular users, respectively.

MONITOR: Theoretical concerns exist regarding the potential for increased risk and severity of renal impairment during coadministration of bisphosphonates with high dosages or chronic use of NSAIDs due to additive or synergistic nephrotoxic effects on the kidney. The use of bisphosphonates has been associated with nephrotoxicity manifested as deterioration of renal function and renal failure. Cases have primarily involved intravenous formulations of the drugs such as pamidronic acid and zoledronic acid, especially when they are administered too rapidly. The risk of hypocalcemia may also be increased, as drug-induced renal tubular damage can lead to renal loss of calcium and other electrolytes such as magnesium. Bisphosphonates alone often cause mild, asymptomatic hypocalcemia via inhibitive effects on bone resorption and possibly chelation of blood calcium. Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with renal toxicities including elevations in serum creatinine and BUN, tubular necrosis, glomerulitis, renal papillary necrosis, acute interstitial nephritis, nephrotic syndrome, and renal failure.

MANAGEMENT: Caution is advised if bisphosphonates are prescribed in combination with NSAIDs. Patients receiving oral bisphosphonates should be closely monitored for the development of gastrointestinal toxicity and advised to immediately report potential signs and symptoms such as severe abdominal pain, nausea, vomiting, diarrhea, loss of appetite, dizziness, lightheadedness, and/or black, tarry stools. Patients receiving intravenous formulations of bisphosphonates should have renal function and serum electrolytes closely monitored. Serum creatinine should be assessed prior to each treatment, and treatment should be withheld in the presence of renal deterioration. In patients treated for bone metastases, treatment should not be resumed until renal function returns to baseline.

References

  1. (2022) "Product Information. Didronel I.V. (etidronate)." MGI Pharma Inc
  2. (2022) "Product Information. Didronel (etidronate)." Procter and Gamble Pharmaceuticals
  3. (2001) "Product Information. Aredia (pamidronate)." Novartis Pharmaceuticals
  4. (2001) "Product Information. Fosamax (alendronate)." Merck & Co., Inc
  5. (2001) "Product Information. Actonel (risedronate)." Procter and Gamble Pharmaceuticals
  6. (2001) "Product Information. Zometa (zoledronic acid)." Novartis Pharmaceuticals
  7. Graham DY, Malaty HM (2001) "Alendronate and naproxen are synergistic for development of gastric ulcers." Arch Intern Med, 161, p. 107-10
  8. Graham, Malaty (2001) "Alendronate and naproxen are synergistic for development of gastric ulcers (Vol 161, pg 107, 1921)." Arch Intern Med, 161, p. 1862
  9. (2001) "Product Information. Bonefos (clodronate)." Rhone-Poulenc Rorer Canada Inc
  10. (2005) "Product Information. Boniva (ibandronate)." Roche Laboratories
  11. Cerner Multum, Inc. "UK Summary of Product Characteristics."
View all 11 references

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Drug and food interactions

Moderate

etidronate food

Applies to: etidronate

ADJUST DOSING INTERVAL: Food, especially calcium-containing food such as dairy products, significantly decreases the bioavailability of oral etidronate.

MANAGEMENT: Oral etidronate should be administered on an empty stomach and no other food or drink should be taken within least 2 hours of administration.

References

  1. (2022) "Product Information. Didronel (etidronate)." Procter and Gamble Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."

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Moderate

naproxen food

Applies to: naproxen

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn

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Moderate

etidronate food

Applies to: etidronate

ADJUST DOSING INTERVAL: Products containing aluminum, calcium, magnesium and other polyvalent cations such as antacids or vitamin with mineral supplements are likely to interfere with the gastrointestinal absorption of oral bisphosphonates. For example, the bioavailability of tiludronate has been shown to decrease 80% during simultaneous administration with calcium, and 60% when aluminum- or magnesium-containing antacids were administered one hour before tiludronate.

MANAGEMENT: Antacids or other oral medications containing aluminum, calcium, magnesium and other polyvalent cations should be administered at least 2 hours before or 2 hours after the bisphosphonate dose.

References

  1. (2001) "Product Information. Fosamax (alendronate)." Merck & Co., Inc
  2. Darcy PF (1995) "Nutrient-drug interactions." Adverse Drug React Toxicol Rev, 14, p. 233-54
  3. "Product Information. Skelid (tiludronate)." Sanofi Winthrop Pharmaceuticals
  4. (2001) "Product Information. Actonel (risedronate)." Procter and Gamble Pharmaceuticals
  5. (2001) "Product Information. Bonefos (clodronate)." Rhone-Poulenc Rorer Canada Inc
  6. (2005) "Product Information. Boniva (ibandronate)." Roche Laboratories
View all 6 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.