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Drug Interactions between Aclasta and aspirin / diphenhydramine / phenylpropanolamine

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

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Interactions between your drugs

Moderate

aspirin zoledronic acid

Applies to: aspirin / diphenhydramine / phenylpropanolamine and Aclasta (zoledronic acid)

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. "Product Information. Didronel I.V. (etidronate)." MGI Pharma Inc (2022):
  2. "Product Information. Didronel (etidronate)." Procter and Gamble Pharmaceuticals (2022):
  3. "Product Information. Aredia (pamidronate)." Novartis Pharmaceuticals PROD (2001):
  4. "Product Information. Fosamax (alendronate)." Merck & Co., Inc PROD (2001):
  5. "Product Information. Actonel (risedronate)." Procter and Gamble Pharmaceuticals PROD (2001):
  6. "Product Information. Zometa (zoledronic acid)." Novartis Pharmaceuticals PROD (2001):
  7. Graham DY, Malaty HM "Alendronate and naproxen are synergistic for development of gastric ulcers." Arch Intern Med 161 (2001): 107-10
  8. Graham, Malaty "Alendronate and naproxen are synergistic for development of gastric ulcers (Vol 161, pg 107, 1921)." Arch Intern Med 161 (2001): 1862
  9. "Product Information. Bonefos (clodronate)." Rhone-Poulenc Rorer Canada Inc (2001):
  10. "Product Information. Boniva (ibandronate)." Roche Laboratories (2005):
  11. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
View all 11 references

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Drug and food interactions

Moderate

phenylpropanolamine food

Applies to: aspirin / diphenhydramine / phenylpropanolamine

GENERALLY AVOID: Alcohol may potentiate the central nervous system and cardiovascular effects of centrally-acting appetite suppressants. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state.

MANAGEMENT: Concomitant use of centrally-acting appetite suppressants and alcohol should be avoided if possible, especially in patients with a history of cardiovascular disease. Patients should be counselled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Mendelson J, Jones RT, Upton R, Jacob P 3rd "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther 57 (1995): 559-68
  2. "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn PROD (2001):
  3. "Product Information. Suprenza (phentermine)." Akrimax Pharmaceuticals (2012):

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Moderate

aspirin food

Applies to: aspirin / diphenhydramine / phenylpropanolamine

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

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Moderate

diphenhydrAMINE food

Applies to: aspirin / diphenhydramine / phenylpropanolamine

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol 6 (1973): 107-12

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Moderate

phenylpropanolamine food

Applies to: aspirin / diphenhydramine / phenylpropanolamine

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res 1 (1979): 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther 11 (1970): 656
  3. "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  4. "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
  5. "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
  6. "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
  7. "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
View all 7 references

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Minor

aspirin food

Applies to: aspirin / diphenhydramine / phenylpropanolamine

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 "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet 11 (1986): 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.

See also

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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.

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