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Drug Interactions between acetaminophen / magnesium salicylate and Dutrebis

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

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Interactions between your drugs

Moderate

magnesium salicylate raltegravir

Applies to: acetaminophen / magnesium salicylate and Dutrebis (lamivudine / raltegravir)

GENERALLY AVOID: Coadministration with aluminum- and magnesium-containing antacids has been shown to reduce the oral bioavailability of raltegravir. The proposed mechanism is chelation of raltegravir by polyvalent cations, but changes in solubility and lipophilicity of raltegravir related to pH increases may also contribute. In drug interaction studies, raltegravir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) decreased by 44%, 49% and 63%, respectively, when a single 20 mL dose of aluminum and magnesium hydroxide antacid was administered simultaneously with raltegravir (400 mg twice daily). The Cmax, AUC and Cmin of raltegravir decreased by 51%, 51% and 56%, respectively, when the antacid was given 2 hours before raltegravir, and by 22%, 30% and 57%, respectively, when the antacid was given 2 hours after raltegravir. When given 4 hours apart, raltegravir Cmax, AUC and Cmin decreased by 22%, 19% and 60% with antacid administered first, and by 30%, 32% and 62% with raltegravir administered first. Minimal changes in raltegravir Cmax and AUC were observed when administration was staggered by 6 hours; however Cmin was still diminished by approximately 50% regardless of whether antacid was administered before or after raltegravir. When given with a single dose of antacid containing calcium carbonate 3000 mg, raltegravir Cmax, AUC and Cmin decreased by 52%, 55% and 32%, respectively. These changes are not considered clinically significant by the manufacturer.

MANAGEMENT: It is not known to what extent non-antacid aluminum and magnesium salts may interact with raltegravir. Until more information is available, it may be advisable to avoid taking raltegravir with any aluminum- and/or magnesium-containing product. Antacids containing calcium carbonate should not be used with once-daily raltegravir (HD formulation), but may be used without dose adjustment for other raltegravir products.

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. "Product Information. Isentress (raltegravir)." Merck & Co., Inc (2007):
  4. Cerner Multum, Inc. "Australian Product Information." O 0
  5. Kiser JJ, Bumpass JB, Meditz AL, et al. "Effect of antacids on the pharmacokinetics of raltegravir in human immunodeficiency virus seronegative volunteers." Antimicrob Agents Chemother 54 (2010): 4999-5003
  6. Moss DM, Siccardi M, Murphy M, et al. "Divalent metals and pH alter raltegravir disposition in vitro." Antimicrob Agents Chemother 56 (2012): 3020-6
View all 6 references

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Drug and food interactions

Major

acetaminophen food

Applies to: acetaminophen / magnesium salicylate

GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

References

  1. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med 145 (1985): 2019-23
  2. O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7
  3. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404
  4. Thummel KE, Slattery JT, Nelson SD "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther 245 (1988): 129-36
  5. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA 244 (1980): 251-3
  6. Kartsonis A, Reddy KR, Schiff ER "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med 105 (1986): 138-9
  7. Prescott LF, Critchley JA "Drug interactions affecting analgesic toxicity." Am J Med 75 (1983): 113-6
  8. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical PROD (2002):
  9. Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50
  10. Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  11. Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  12. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73
View all 12 references

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Moderate

magnesium salicylate food

Applies to: acetaminophen / magnesium salicylate

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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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

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