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Drug Interactions between Aspirin Buffered and Diucardin

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

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Moderate

aspirin calcium carbonate

Applies to: Aspirin Buffered (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide) and Aspirin Buffered (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide)

MONITOR: Chronic administration of antacids may reduce serum salicylate concentrations in patients receiving large doses of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to urinary alkalinization by antacids, resulting in increased renal salicylate clearance. In three children treated with large doses of aspirin for rheumatic fever, serum salicylate levels declined 30% to 70% during coadministration with a magnesium and aluminum hydroxide antacid. Other studies have found similar, albeit less dramatic results. Antacids reportedly have no effect on the oral bioavailability of aspirin in healthy adults. However, administration of antacids containing either aluminum and magnesium hydroxide or calcium carbonate two hours before aspirin dosing led to reduced absorption of aspirin in uremic patients.

MANAGEMENT: Patients treated chronically with antacids (or oral medications that contain antacids such as didanosine buffered tablets or pediatric oral solution) and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

References

  1. D'Arcy PF, McElnay JC "Drug-antacid interactions: assessment of clinical importance." Drug Intell Clin Pharm 21 (1987): 607-17
  2. Gaspari F, Vigano G, Locatelli M, Remuzzi G "Influence of antacid administrations on aspirin absorption in patients with chronic renal failure on maintenance hemodialysis." Am J Kidney Dis 11 (1988): 338-42
  3. Furst DE "Clinically important interactions of nonsteroidal antiinflammatory drugs with other medications." J Rheumatol Suppl 17 (1988): 58-62
  4. Miners JO "Drug interactions involving aspirin (acetylsalicylic acid) and salicylic acid." Clin Pharmacokinet 17 (1989): 327-44
  5. Levy G, Lampman T, Kamath BL, Garrettson LK "Decreased serum salicylate concentrations in children with rheumatic fever treated with antacid." N Engl J Med 293 (1975): 323-5
  6. Shastri RA "Effect of antacids on salicylate kinetics." Int J Clin Pharmacol Ther Toxicol 23 (1985): 480-4
  7. Covington TR, eds., Lawson LC, Young LL "Handbook of Nonprescription Drugs." Washington, DC: American Pharmaceutical Association (1993):
  8. Brouwers JRBJ, Desmet PAGM "Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs." Clin Pharmacokinet 27 (1994): 462-85
  9. "Product Information. Diflunisal (diflunisal)." Chartwell RX, LLC. (2023):
View all 9 references

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Moderate

calcium carbonate hydroflumethiazide

Applies to: Aspirin Buffered (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide) and Diucardin (hydroflumethiazide)

MONITOR: Coadministration of thiazide diuretics with high dosages of calcium and/or vitamin D has been associated with reports of hypercalcemia in some patients. Thiazide diuretics inhibit the renal excretion of calcium and may also enhance responsiveness of bone and renal tubule to parathyroid hormone, thus concurrent use of large amounts of calcium or vitamin D can lead to excessively high plasma levels of calcium. Patients who are particularly susceptible include those with hyperparathyroidism, those being treated for osteoporosis, and those receiving high dosages of vitamin D for hypoparathyroidism. Metabolic alkalosis and the milk-alkali syndrome have been reported during prolonged therapy with thiazide diuretics and calcium.

MANAGEMENT: Patients receiving thiazide diuretic therapy should be cautioned against self-treatment with calcium and vitamin D supplements without first talking to their healthcare provider. Serum calcium should be monitored if thiazide diuretics are coadministered with high dosages of calcium and/or vitamin D. Patients should be advised to seek medical attention if they experience signs and symptoms of hypercalcemia such as dizziness, weakness, lethargy, headache, myalgia, anorexia, nausea, vomiting, and seizures.

References

  1. Alon U, Costanzo LS, Chan JC "Additive hypocalciuric effects of amiloride and hydrochlorothiazide in patients treated with calcitriol." Miner Electrolyte Metab 10 (1984): 379-86
  2. Parfitt AM "Thiazide-induced hypercalcemia in vitamin D-treated hypoparathyroidism." Ann Intern Med 77 (1972): 557-63
  3. Popovtzer MM, Subryan VL, Alfrey AC, Reeve EB, Schrier RW "The acute effect of chlorothiazide on serum-ionized calcium. Evidence for a parathyroid hormone-dependent mechanism." J Clin Invest 55 (1975): 1295-302
  4. Parfitt AM "The interactions of thiazide diuretics with parathyroid hormone and vitamin D. Studies in patients with hypoparathyroidism." J Clin Invest 51 (1972): 1879-88
  5. Middler S, Pak CY, Murad F, Bartter FC "Thiazide diuretics and calcium metabolism." Metabolism 22 (1973): 139-46
  6. Parfitt AM "Chlorothiazide-induced hypercalcemia in juvenile osteoporosis and hyperparathyroidism." N Engl J Med 281 (1969): 55-9
  7. Gora ML, Seth SK, Bay WH, Visconti JA "Milk-alkali syndrome associated with use of chlorothiazide and calcium carbonate." Clin Pharm 8 (1989): 227-9
  8. Hakim R, Tolis G, Goltzman D, Meltzer S, Friedman R "Severe hypercalcemia associated with hydrochlorothiazide and calcium carbonate therapy." Can Med Assoc J 121 (1979): 591-4
  9. Duarte CG, Winnacker JL, Becker KL, Pace A "Thiazide-induced hypercalcemia." N Engl J Med 284 (1971): 828-30
  10. Franciosa JA, Pierpont G "Cardiovascular clinical pharmacology of impedance reducing agents." J Chronic Dis 34 (1981): 341-52
  11. Santos F, Smith MJ, Chan JC "Hypercalciuria associated with long-term administration of calcitriol (1,25-dihydroxyvitamin D3). Action of hydrochlorothiazide." Am J Dis Child 140 (1986): 139-42
  12. Riis B, Christiansen C "Actions of thiazide on vitamin D metabolism: a controlled therapeutic trial in normal women early in the postmenopause." Metabolism 34 (1985): 421-4
  13. Ljunghall S, Backman U, Danielson BG, Fellstrom B, Johansson G, Wikstrom B "Calcium and magnesium metabolism during long-term treatment with thiazides." Scand J Urol Nephrol 15 (1981): 257-62
  14. Drinka PJ, Nolten WE "Hazards of treating osteoporosis and hypertension concurrently with calcium, vitamin D, and distal diuretics." J Am Geriatr Soc 32 (1984): 405-7
  15. Braunwald E, Hauser SL, Kasper DL, Fauci AS, Isselbacher KJ, Longo DL, Martin JB, eds., Wilson JD "Harrison's Principles of Internal Medicine." New York, NY: McGraw-Hill Health Professionals Division (1998):
View all 15 references

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Moderate

aspirin aluminum hydroxide

Applies to: Aspirin Buffered (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide) and Aspirin Buffered (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide)

MONITOR: Chronic administration of antacids may reduce serum salicylate concentrations in patients receiving large doses of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to urinary alkalinization by antacids, resulting in increased renal salicylate clearance. In three children treated with large doses of aspirin for rheumatic fever, serum salicylate levels declined 30% to 70% during coadministration with a magnesium and aluminum hydroxide antacid. Other studies have found similar, albeit less dramatic results. Antacids reportedly have no effect on the oral bioavailability of aspirin in healthy adults. However, administration of antacids containing either aluminum and magnesium hydroxide or calcium carbonate two hours before aspirin dosing led to reduced absorption of aspirin in uremic patients.

MANAGEMENT: Patients treated chronically with antacids (or oral medications that contain antacids such as didanosine buffered tablets or pediatric oral solution) and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

References

  1. D'Arcy PF, McElnay JC "Drug-antacid interactions: assessment of clinical importance." Drug Intell Clin Pharm 21 (1987): 607-17
  2. Gaspari F, Vigano G, Locatelli M, Remuzzi G "Influence of antacid administrations on aspirin absorption in patients with chronic renal failure on maintenance hemodialysis." Am J Kidney Dis 11 (1988): 338-42
  3. Furst DE "Clinically important interactions of nonsteroidal antiinflammatory drugs with other medications." J Rheumatol Suppl 17 (1988): 58-62
  4. Miners JO "Drug interactions involving aspirin (acetylsalicylic acid) and salicylic acid." Clin Pharmacokinet 17 (1989): 327-44
  5. Levy G, Lampman T, Kamath BL, Garrettson LK "Decreased serum salicylate concentrations in children with rheumatic fever treated with antacid." N Engl J Med 293 (1975): 323-5
  6. Shastri RA "Effect of antacids on salicylate kinetics." Int J Clin Pharmacol Ther Toxicol 23 (1985): 480-4
  7. Covington TR, eds., Lawson LC, Young LL "Handbook of Nonprescription Drugs." Washington, DC: American Pharmaceutical Association (1993):
  8. Brouwers JRBJ, Desmet PAGM "Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs." Clin Pharmacokinet 27 (1994): 462-85
  9. "Product Information. Diflunisal (diflunisal)." Chartwell RX, LLC. (2023):
View all 9 references

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Moderate

aspirin magnesium hydroxide

Applies to: Aspirin Buffered (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide) and Aspirin Buffered (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide)

MONITOR: Chronic administration of antacids may reduce serum salicylate concentrations in patients receiving large doses of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to urinary alkalinization by antacids, resulting in increased renal salicylate clearance. In three children treated with large doses of aspirin for rheumatic fever, serum salicylate levels declined 30% to 70% during coadministration with a magnesium and aluminum hydroxide antacid. Other studies have found similar, albeit less dramatic results. Antacids reportedly have no effect on the oral bioavailability of aspirin in healthy adults. However, administration of antacids containing either aluminum and magnesium hydroxide or calcium carbonate two hours before aspirin dosing led to reduced absorption of aspirin in uremic patients.

MANAGEMENT: Patients treated chronically with antacids (or oral medications that contain antacids such as didanosine buffered tablets or pediatric oral solution) and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

References

  1. D'Arcy PF, McElnay JC "Drug-antacid interactions: assessment of clinical importance." Drug Intell Clin Pharm 21 (1987): 607-17
  2. Gaspari F, Vigano G, Locatelli M, Remuzzi G "Influence of antacid administrations on aspirin absorption in patients with chronic renal failure on maintenance hemodialysis." Am J Kidney Dis 11 (1988): 338-42
  3. Furst DE "Clinically important interactions of nonsteroidal antiinflammatory drugs with other medications." J Rheumatol Suppl 17 (1988): 58-62
  4. Miners JO "Drug interactions involving aspirin (acetylsalicylic acid) and salicylic acid." Clin Pharmacokinet 17 (1989): 327-44
  5. Levy G, Lampman T, Kamath BL, Garrettson LK "Decreased serum salicylate concentrations in children with rheumatic fever treated with antacid." N Engl J Med 293 (1975): 323-5
  6. Shastri RA "Effect of antacids on salicylate kinetics." Int J Clin Pharmacol Ther Toxicol 23 (1985): 480-4
  7. Covington TR, eds., Lawson LC, Young LL "Handbook of Nonprescription Drugs." Washington, DC: American Pharmaceutical Association (1993):
  8. Brouwers JRBJ, Desmet PAGM "Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs." Clin Pharmacokinet 27 (1994): 462-85
  9. "Product Information. Diflunisal (diflunisal)." Chartwell RX, LLC. (2023):
View all 9 references

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Moderate

hydroflumethiazide magnesium hydroxide

Applies to: Diucardin (hydroflumethiazide) and Aspirin Buffered (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide)

MONITOR: The chronic use or abuse of laxatives may potentiate the pharmacologic effects of diuretics. Laxatives can cause significant losses of fluid and electrolytes, including sodium, potassium, magnesium and zinc, and these effects may be additive to those of diuretics.

MANAGEMENT: In general, laxatives should only be used on a short-term, intermittent basis in recommended dosages. During concomitant use with diuretics, patients should be advised to contact their physician if they experience signs and symptoms of fluid and electrolyte depletion such as dizziness, lightheadedness, dry mouth, thirst, fatigue, weakness, lethargy, muscle cramps, decreased urination, postural hypotension, and tachycardia. If maintenance of bowel regularity is required, patients should be advised to exercise and increase fiber in the diet and/or consider the use of bulk-forming laxatives.

References

  1. Brinckmann J, Blumenthal M, eds., Goldberg A "Herbal Medicine: Expanded Commission E Monographs." Newton, MA: Integrative Medicine Communications (2000):
  2. Chin RL "Laxative-induced hypokalemia." Ann Emerg Med 32 (1998): 517-8
  3. Leary WP, Reyes AJ "Drug interactions with diuretics." S Afr Med J 65 (1984): 455-61
  4. Muller-Lissner SA "Adverse effects of laxatives: fact and fiction." Pharmacology 47 (1993): 138-45
  5. Atsmon J, Dolev E "Drug-induced hypomagnesaemia : scope and management." Drug Saf 28 (2005): 763-88
View all 5 references

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Drug and food interactions

Major

aluminum hydroxide food

Applies to: Aspirin Buffered (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide)

GENERALLY AVOID: The concomitant administration of aluminum-containing products (e.g., antacids and phosphate binders) and citrates may significantly increase serum aluminum concentrations, resulting in toxicity. Citrates or citric acid are contained in numerous soft drinks, citrus fruits, juices, and effervescent and dispersible drug formulations. Citrates enhance the gastrointestinal absorption of aluminum by an unknown mechanism, which may involve the formation of a soluble aluminum-citrate complex. Various studies have reported that citrate increases aluminum absorption by 4.6- to 50-fold in healthy subjects. Patients with renal insufficiency are particularly at risk of developing hyperaluminemia and encephalopathy. Fatalities have been reported. Patients with renal failure or on hemodialysis may also be at risk from soft drinks and effervescent and dispersible drug formulations that contain citrates or citric acid. It is unknown what effect citrus fruits or juices would have on aluminum absorption in healthy patients.

MANAGEMENT: The concomitant use of aluminum- and citrate-containing products and foods should be avoided by renally impaired patients. Hemodialysis patients should especially be cautioned about effervescent and dispersible over-the-counter remedies and soft drinks. Some experts also recommend that healthy patients should separate doses of aluminum-containing antacids and citrates by 2 to 3 hours.

ADJUST DOSING INTERVAL: The administration of aluminum-containing antacids with enteral nutrition may result in precipitation, formation of bezoars, and obstruction of feeding tubes. The proposed mechanism is the formation of an insoluble complex between the aluminum and the protein in the enteral feeding. Several cases of esophageal plugs and nasogastric tube obstructions have been reported in patients receiving high-protein liquids and an aluminum hydroxide-magnesium hydroxide antacid or an aluminum hydroxide antacid.

MANAGEMENT: Some experts recommend that antacids should not be mixed with or given after high protein formulations, that the antacid dose should be separated from the feeding by as much as possible, and that the tube should be thoroughly flushed before administration.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67

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Moderate

calcium carbonate food

Applies to: Aspirin Buffered (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide)

ADJUST DOSING INTERVAL: Administration with food may increase the absorption of calcium. However, foods high in oxalic acid (spinach or rhubarb), or phytic acid (bran and whole grains) may decrease calcium absorption.

MANAGEMENT: Calcium may be administered with food to increase absorption. Consider withholding calcium administration for at least 2 hours before or after consuming foods high in oxalic acid or phytic acid.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. Agencia EspaƱola de Medicamentos y Productos Sanitarios Healthcare "Centro de informaciĆ³n online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008):
  5. Mangels AR "Bone nutrients for vegetarians." Am J Clin Nutr 100 (2014): epub
  6. Davies NT "Anti-nutrient factors affecting mineral utilization." Proc Nutr Soc 38 (1979): 121-8
View all 6 references

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Moderate

aspirin food

Applies to: Aspirin Buffered (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide)

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

hydroflumethiazide food

Applies to: Diucardin (hydroflumethiazide)

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595
View all 8 references

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Minor

aspirin food

Applies to: Aspirin Buffered (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide)

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.


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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.