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Drug Interactions between diroximel fumarate and Magnaprin

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

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Moderate

aspirin calcium carbonate

Applies to: Magnaprin (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide) and Magnaprin (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 (1987) "Drug-antacid interactions: assessment of clinical importance." Drug Intell Clin Pharm, 21, p. 607-17
  2. Gaspari F, Vigano G, Locatelli M, Remuzzi G (1988) "Influence of antacid administrations on aspirin absorption in patients with chronic renal failure on maintenance hemodialysis." Am J Kidney Dis, 11, p. 338-42
  3. Furst DE (1988) "Clinically important interactions of nonsteroidal antiinflammatory drugs with other medications." J Rheumatol Suppl, 17, p. 58-62
  4. Miners JO (1989) "Drug interactions involving aspirin (acetylsalicylic acid) and salicylic acid." Clin Pharmacokinet, 17, p. 327-44
  5. Levy G, Lampman T, Kamath BL, Garrettson LK (1975) "Decreased serum salicylate concentrations in children with rheumatic fever treated with antacid." N Engl J Med, 293, p. 323-5
  6. Shastri RA (1985) "Effect of antacids on salicylate kinetics." Int J Clin Pharmacol Ther Toxicol, 23, p. 480-4
  7. Covington TR, eds., Lawson LC, Young LL (1993) "Handbook of Nonprescription Drugs." Washington, DC: American Pharmaceutical Association
  8. Brouwers JRBJ, Desmet PAGM (1994) "Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs." Clin Pharmacokinet, 27, p. 462-85
  9. (2023) "Product Information. Diflunisal (diflunisal)." Chartwell RX, LLC.
View all 9 references

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Moderate

aspirin aluminum hydroxide

Applies to: Magnaprin (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide) and Magnaprin (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 (1987) "Drug-antacid interactions: assessment of clinical importance." Drug Intell Clin Pharm, 21, p. 607-17
  2. Gaspari F, Vigano G, Locatelli M, Remuzzi G (1988) "Influence of antacid administrations on aspirin absorption in patients with chronic renal failure on maintenance hemodialysis." Am J Kidney Dis, 11, p. 338-42
  3. Furst DE (1988) "Clinically important interactions of nonsteroidal antiinflammatory drugs with other medications." J Rheumatol Suppl, 17, p. 58-62
  4. Miners JO (1989) "Drug interactions involving aspirin (acetylsalicylic acid) and salicylic acid." Clin Pharmacokinet, 17, p. 327-44
  5. Levy G, Lampman T, Kamath BL, Garrettson LK (1975) "Decreased serum salicylate concentrations in children with rheumatic fever treated with antacid." N Engl J Med, 293, p. 323-5
  6. Shastri RA (1985) "Effect of antacids on salicylate kinetics." Int J Clin Pharmacol Ther Toxicol, 23, p. 480-4
  7. Covington TR, eds., Lawson LC, Young LL (1993) "Handbook of Nonprescription Drugs." Washington, DC: American Pharmaceutical Association
  8. Brouwers JRBJ, Desmet PAGM (1994) "Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs." Clin Pharmacokinet, 27, p. 462-85
  9. (2023) "Product Information. Diflunisal (diflunisal)." Chartwell RX, LLC.
View all 9 references

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Moderate

aspirin magnesium hydroxide

Applies to: Magnaprin (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide) and Magnaprin (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 (1987) "Drug-antacid interactions: assessment of clinical importance." Drug Intell Clin Pharm, 21, p. 607-17
  2. Gaspari F, Vigano G, Locatelli M, Remuzzi G (1988) "Influence of antacid administrations on aspirin absorption in patients with chronic renal failure on maintenance hemodialysis." Am J Kidney Dis, 11, p. 338-42
  3. Furst DE (1988) "Clinically important interactions of nonsteroidal antiinflammatory drugs with other medications." J Rheumatol Suppl, 17, p. 58-62
  4. Miners JO (1989) "Drug interactions involving aspirin (acetylsalicylic acid) and salicylic acid." Clin Pharmacokinet, 17, p. 327-44
  5. Levy G, Lampman T, Kamath BL, Garrettson LK (1975) "Decreased serum salicylate concentrations in children with rheumatic fever treated with antacid." N Engl J Med, 293, p. 323-5
  6. Shastri RA (1985) "Effect of antacids on salicylate kinetics." Int J Clin Pharmacol Ther Toxicol, 23, p. 480-4
  7. Covington TR, eds., Lawson LC, Young LL (1993) "Handbook of Nonprescription Drugs." Washington, DC: American Pharmaceutical Association
  8. Brouwers JRBJ, Desmet PAGM (1994) "Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs." Clin Pharmacokinet, 27, p. 462-85
  9. (2023) "Product Information. Diflunisal (diflunisal)." Chartwell RX, LLC.
View all 9 references

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Moderate

aspirin diroximel fumarate

Applies to: Magnaprin (aluminum hydroxide / aspirin / calcium carbonate / magnesium hydroxide) and diroximel fumarate

MONITOR: The use of fumaric acid esters in combination with medications that can cause nephrotoxicity, including aspirin at anti-inflammatory dosages, may increase the potential for adverse renal reactions. In clinical trials in patients with multiple sclerosis treated with dimethyl fumarate, a fumaric acid ester that is converted to the active metabolite monomethyl fumarate (MMF), adverse events of proteinuria were reported at slightly higher frequencies than in patients receiving placebo. The clinical significance of these observations is unknown. Cases of Fanconi syndrome have been reported for a medicinal product containing dimethyl fumarate in combination with other fumaric acid esters. Renal toxicity, including tubular changes and/or interstitial fibrosis, has been observed in animal studies with dimethyl fumarate and diroximel fumarate. In healthy volunteers, administration of 325 mg non-enteric coated aspirin approximately 30 minutes prior to dimethyl fumarate for up to 4 weeks did not alter the pharmacokinetics of dimethyl fumarate or MMF.

MANAGEMENT: Administration of non-enteric coated aspirin (up to 325 mg) prior to fumaric acid esters such as monomethyl fumarate or its prodrugs, dimethyl fumarate or diroximel fumarate, may help reduce the incidence and/or severity of flushing. However, as there are no long-term studies evaluating the continuous use of aspirin in this situation for longer than 4 weeks, caution is advised. Assessment of renal function (e.g., serum creatinine, blood urea nitrogen, urinalysis) is recommended prior to initiating treatment with fumaric acid esters and as clinically indicated during treatment.

References

  1. (2022) "Product Information. Vumerity (diroximel fumarate)." Biogen Australia Pty Ltd
  2. (2023) "Product Information. Tecfidera (dimethyl fumarate)." Biogen Idec Inc, SUPPL-29
  3. (2022) "Product Information. Tecfidera (dimethyl fumarate)." Biogen Idec Ltd
  4. (2022) "Product Information. Skilarence (dimethyl fumarate)." Almirall Ltd
  5. (2022) "Product Information. Vumerity (diroximel fumarate)." Biogen Idec Ltd
  6. (2023) "Product Information. Vumerity (diroximel fumarate)." Biogen Idec Inc, SUPPL-9
  7. (2022) "Product Information. Furatec (dimethyl fumarate)." Pharmacor Pty Ltd, 03
  8. (2023) "Product Information. Bafiertam (monomethyl fumarate)." Banner Life Sciences
View all 8 references

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Drug and food interactions

Major

aluminum hydroxide food

Applies to: Magnaprin (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."
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67

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Moderate

calcium carbonate food

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

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Moderate

diroximel fumarate food

Applies to: diroximel fumarate

GENERALLY AVOID: Food does not significantly affect the oral bioavailability of diroximel fumarate. Administration of diroximel fumarate with a high-fat, high-calorie (900 to 1000 calories; 50% from fat) meal did not affect the systemic exposure (AUC) of its active metabolite, monomethyl fumarate (MMF), but decreased its peak plasma concentration (Cmax) by 44% and prolonged the time to reach peak concentration (Tmax) from 2.5 to 7.0 hours relative to administration in the fasted state. In comparison, administration of diroximel fumarate with low-fat, low-calorie (350 to 400 calories; 10 to 15 g fat) and medium-fat, medium-calorie (650 to 700 calories; 25 to 30 g fat) meals decreased the MMF Cmax by approximately 12% and 25%, respectively, while also leaving the AUC unaffected.

GENERALLY AVOID: Coadministration of diroximel fumarate with ethanol may reduce the plasma concentrations of monomethyl fumarate (MMF). The mechanism has not been reported. Following coadministration with 240 mL of 5% v/v and 40% v/v ethanol, the mean Cmax of MMF was reduced by 9% and 21%, respectively, relative to coadministration with water. The AUC of MMF was not significantly altered, indicating that ethanol did not induce dose dumping.

MANAGEMENT: Diroximel fumarate may be taken with or without food; however, high-fat, high-calorie meals or snacks should be avoided. The manufacturer recommends meals or snacks containing no more than 700 calories and no more than 30 grams of fat. Taking diroximel fumarate with food may improve tolerability for patients experiencing flushing or gastrointestinal adverse reactions. The manufacturer also recommends avoiding concomitant use of diroximel fumarate with ethanol.

References

  1. (2022) "Product Information. Vumerity (diroximel fumarate)." Biogen Australia Pty Ltd
  2. (2022) "Product Information. Vumerity (diroximel fumarate)." Biogen Idec Ltd
  3. (2023) "Product Information. Vumerity (diroximel fumarate)." Biogen Idec Inc, SUPPL-9

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Moderate

aspirin food

Applies to: Magnaprin (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. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn

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Minor

aspirin food

Applies to: Magnaprin (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 (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.