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Drug Interactions between aspirin / dipyridamole and Binosto

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

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Interactions between your drugs

Moderate

aspirin alendronate

Applies to: aspirin / dipyridamole and Binosto (alendronate)

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

dipyridamole food

Applies to: aspirin / dipyridamole

ADJUST DOSING INTERVAL: Caffeine and other xanthine derivatives (e.g., theophylline) are nonspecific, competitive antagonists of adenosine receptors. As such, they may interfere with the vasodilating effect of dipyridamole, an adenosine receptor agonist. In studies of healthy volunteers, caffeine has been shown to reduce the hemodynamic response (i.e., heart rate increases, vasodilation, blood pressure changes) to dipyridamole infusions, and both caffeine and theophylline have been reported to cause false-negative results in myocardial scintigraphy tests using dipyridamole.

MANAGEMENT: Patients should avoid consumption of caffeine-containing products for at least 24 hours prior to administration of dipyridamole for myocardial perfusion imaging.

References

  1. Smits P, Aengevaeren WR, Corstens FH, Thien T (1989) "Caffeine reduces dipyridamole-induced myocardial ischemia." J Nucl Med, 30, p. 1723-6
  2. (2002) "Product Information. Persantine (dipyridamole)." Boehringer-Ingelheim
  3. Ranhosky A, Kempthorne-Rawson J, the Intravenous Dipyridamole Thallium Imaging Study Group (1990) "The safety of intravenous dipyridamole thallium myocardial perfusion imaging." Circulation, 81, p. 1205-9

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Moderate

alendronate food

Applies to: Binosto (alendronate)

ADJUST DOSING INTERVAL: Food significantly decreases the bioavailability of alendronate, possibly to negligible levels.

MANAGEMENT: Alendronate should be administered with 6 to 8 ounces of plain water, at least 30 minutes before the first food, beverage, or medication of the day. Patients should remain upright for at least 30 minutes following administration of alendronate.

References

  1. (2001) "Product Information. Fosamax (alendronate)." Merck & Co., Inc

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Moderate

aspirin food

Applies to: aspirin / dipyridamole

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

dipyridamole food

Applies to: aspirin / dipyridamole

ADJUST DOSING INTERVAL: Methylxanthines (e.g., caffeine, theophylline) are nonspecific, competitive antagonists of adenosine receptors. As such, they may interfere with the pharmacologic effects of adenosine and other adenosine receptor agonists such as dipyridamole and regadenoson. There have been case reports of patients receiving theophylline who required higher than normal dosages of adenosine for the treatment of paroxysmal supraventricular tachycardia. In studies of healthy volunteers, caffeine and theophylline have been shown to reduce the cardiovascular response to adenosine infusions (i.e., heart rate increases, vasodilation, blood pressure changes), and theophylline has also been shown to attenuate adenosine-induced respiratory effects and chest pain/discomfort. Similarly, caffeine has been found to reduce the hemodynamic response to dipyridamole, and both caffeine and theophylline have been reported to cause false-negative results in myocardial scintigraphy tests using dipyridamole. In a placebo-controlled study that assessed the effects of oral caffeine on regadenoson-induced increase in coronary flow reserve (CFR), healthy subjects who took caffeine 200 mg orally two hours prior to regadenoson administration exhibited a median CFR that was 92% that of subjects who took placebo. The study was done using positron emission tomography with radiolabeled water.

MANAGEMENT: Clinicians should be aware that adenosine and other adenosine receptor agonists may be less effective in the presence of methylxanthines. Methylxanthines including caffeine should be withheld for 12 to 24 hours (or five half-lives) prior to administration of adenosine receptor agonists for myocardial perfusion imaging. However, parenteral aminophylline should be readily available for treating severe or persistent adverse reactions to adenosine receptor agonists such as bronchospasm or chest pain.

References

  1. Conti CR (1991) "Adenosine: clinical pharmacology and applications." Clin Cardiol, 14, p. 91-3
  2. Smits P, Aengevaeren WR, Corstens FH, Thien T (1989) "Caffeine reduces dipyridamole-induced myocardial ischemia." J Nucl Med, 30, p. 1723-6
  3. Smits P, Schouten J, Thien T (1987) "Respiratory stimulant effects of adenosine in man after caffeine and enprofylline." Br J Clin Pharmacol, 24, p. 816-9
  4. Minton NA, Henry JA (1991) "Pharmacodynamic interactions between infused adenosine and oral theophylline." Hum Exp Toxicol, 10, p. 411-8
  5. (2002) "Product Information. Persantine (dipyridamole)." Boehringer-Ingelheim
  6. (2001) "Product Information. Adenocard (adenosine)." Fujisawa
  7. Ranhosky A, Kempthorne-Rawson J, the Intravenous Dipyridamole Thallium Imaging Study Group (1990) "The safety of intravenous dipyridamole thallium myocardial perfusion imaging." Circulation, 81, p. 1205-9
  8. (2001) "Product Information. Adenoscan (adenosine)." Fujisawa
  9. (2008) "Product Information. Lexiscan (regadenoson)." Astellas Pharma US, Inc
View all 9 references

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Minor

aspirin food

Applies to: aspirin / dipyridamole

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 71-6

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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.