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Drug Interactions between acetaminophen / aspirin / caffeine / salicylamide and liraglutide

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

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Interactions between your drugs

Moderate

aspirin salicylamide

Applies to: acetaminophen / aspirin / caffeine / salicylamide and acetaminophen / aspirin / caffeine / salicylamide

MONITOR: The combined use of low-dose or high-dose aspirin with other nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the potential for serious gastrointestinal (GI) toxicity, including inflammation, bleeding, ulceration, and perforation. Aspirin at anti-inflammatory dosages or higher may also decrease the plasma concentrations of many NSAIDs. The decreases have ranged from none or small (piroxicam, meloxicam, naproxen, tolmetin) to substantial (flurbiprofen, ibuprofen). However, the therapeutic response does not appear to be affected. Investigators theorize that aspirin may displace NSAIDs from plasma protein binding sites, resulting in increased concentration of unbound, or free, drug available for clearance. The increase in NSAID free fraction, and possibly some contributory anti-inflammatory effect from aspirin, may account for the lack of overall effect on therapeutic response.

MANAGEMENT: Caution is advised if aspirin, particularly at anti-inflammatory dosages, is used with other NSAIDs. Concomitant administration of NSAIDs is considered contraindicated or not recommended with aspirin at analgesic/anti-inflammatory dosages by many NSAID manufacturers. During concomitant therapy, patients should be advised to take the medications with food and to immediately report signs and symptoms of GI ulceration and bleeding such as abdominal pain, bloating, sudden dizziness or lightheadedness, nausea, vomiting, hematemesis, anorexia, and melena.

References

  1. Furst DE, Sarkissian E, Blocka K, et al. (1987) "Serum concentrations of salicylate and naproxen during concurrent therapy in patients with rheumatoid arthritis." Arthritis Rheum, 30, p. 1157-61
  2. Abdel-Rahman MS, Reddi AS, Curro FA, Turkall RM, Kadry AM, Hansrote JA (1991) "Bioavailability of aspirin and salicylamide following oral co-administration in human volunteers." Can J Physiol Pharmacol, 69, p. 1436-42
  3. Gruber CM (1976) "Clinical pharmacology of fenoprofen: a review." J Rheumatol, 2, p. 8-17
  4. Cressman WA, Wortham GF, Plostnieks J (1976) "Absorption and excretion of tolemetin in man." Clin Pharmacol Ther, 19, p. 224-33
  5. Kwan KC, Breault GO, Davis RL, et al. (1978) "Effects of concomitant aspirin administration on the pharmacokinetics of indomethacin in man." J Pharmacokinet Biopharm, 6, p. 451-76
  6. Rubin A, Rodda BE, Warrick P, Gruber CM Jr, Ridolfo RS (1973) "Interactions of aspirin with nonsteroidal antiinflammatory drugs in man." Arthritis Rheum, 16, p. 635-45
  7. Brooks PM, Walker JJ, Bell MA, Buchanan WW, Rhymer AR (1975) "Indomethacin--aspirin interaction: a clinical appraisal." Br Med J, 3, p. 69-11
  8. Tempero KF, Cirillo VJ, Steelman SL (1977) "Diflunisal: a review of pharmacokinetic and pharmacodynamic properties, drug interactions, and special tolerability studies in humans." Br J Clin Pharmacol, 4, s31-6
  9. Willis JV, Kendall MJ, Jack DB (1980) "A study of the effect of aspirin on the pharmacokinetics of oral and intravenous diclofenac sodium." Eur J Clin Pharmacol, 18, p. 415-8
  10. Muller FO, Hundt HK, Muller DG (1977) "Pharmacokinetic and pharmacodynamic implications of long-term administration of non-steroidal anti-inflammatory agents." Int J Clin Pharmacol Biopharm, 15, p. 397-402
  11. Hobbs DC, Twomey TM (1979) "Piroxicam pharmacokinetics in man: aspirin and antacid interaction studies." J Clin Pharmacol, 19, p. 270-81
  12. Pawlotsky Y, Chales G, Grosbois B, Miane B, Bourel M (1978) "Comparative interaction of aspirin with indomethacin and sulindac in chronic rheumatic diseases." Eur J Rheumatol Inflamm, 1, p. 18-20
  13. Segre EJ, Chaplin M, Forchielli E, Runkel R, Sevelius H (1973) "Naproxen-aspirin interactions in man." Clin Pharmacol Ther, 15, p. 374-9
  14. Bird HA, Hill J, Leatham P, Wright V (1986) "A study to determine the clinical relevance of the pharmacokinetic interaction between aspirin and diclofenac." Agents Actions, 18, p. 447-9
  15. Brooks PM, Khong T (1977) "Flurbiprofen-aspirin interaction: a double-blind crossover study." Curr Med Res Opin, 5, p. 53-7
  16. Grennan DM, Ferry DG, Ashworth ME, Kenny RE, Mackinnnon M (1979) "The aspirin-ibuprofen interaction in rheumatoid arthritis." Br J Clin Pharmacol, 8, p. 497-503
  17. Williams RL, Upton RA, Buskin JN, Jones RM (1981) "Ketoprofen-aspirin interactions." Clin Pharmacol Ther, 30, p. 226-31
  18. Kaiser DG, Brooks CD, Lomen PL (1986) "Pharmacokinetics of flurbiprofen." Am J Med, 80, p. 10-5
  19. Kahn SB, Hubsher JA (1983) "Effects of oxaprozin alone or in combination with aspirin on hemostasis and plasma protein binding." J Clin Pharmacol, 23, p. 139-46
  20. (2001) "Product Information. Mobic (meloxicam)." Boehringer-Ingelheim
  21. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  22. Cerner Multum, Inc. "Australian Product Information."
View all 22 references

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Minor

aspirin caffeine

Applies to: acetaminophen / aspirin / caffeine / salicylamide and acetaminophen / aspirin / caffeine / salicylamide

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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Minor

acetaminophen liraglutide

Applies to: acetaminophen / aspirin / caffeine / salicylamide and liraglutide

Liraglutide delays gastric emptying, which may impact the absorption of concomitantly administered oral medications. In pharmacokinetic studies, liraglutide did not affect the absorption of several orally administered medications to any clinically significant extent (see below). For each interaction studied, administration of the interacting drug was timed so that its absorption peak would coincide with the peak plasma concentration of liraglutide (8 to 12 hours).

Acetaminophen: Administration of a single 1000 mg dose of acetaminophen eight hours after liraglutide dosing (1.8 mg/day) at steady state did not change acetaminophen systemic exposure (AUC). However, acetaminophen peak plasma concentration (Cmax) was decreased by 31% and median time to maximal concentration (Tmax) was delayed up to 15 minutes.

Atorvastatin: Administration of a single 40 mg dose of atorvastatin five hours after liraglutide dosing (1.8 mg/day) at steady state did not change atorvastatin systemic exposure (AUC). However, atorvastatin peak plasma concentration (Cmax) was decreased by 38% and median time to maximal concentration (Tmax) was delayed from 1 hour to 3 hours.

Digoxin: Administration of a single 1 mg dose of digoxin seven hours after liraglutide dosing (1.8 mg/day) at steady state resulted in a 31% and 16% reduction in digoxin peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, and a delay in digoxin median time to maximal concentration (Tmax) from 1 hour to 1.5 hours.

Griseofulvin: Coadministration of a single 500 mg dose of griseofulvin with liraglutide (1.8 mg/day) at steady state did not change griseofulvin systemic exposure (AUC) or median time to maximal concentration (Tmax). However, griseofulvin peak plasma concentration (Cmax) increased by 37%.

Lisinopril: Administration of a single 20 mg dose of lisinopril five minutes after liraglutide dosing (1.8 mg/day) at steady state resulted in a 27% and 15% reduction in lisinopril peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, and a delay in lisinopril median time to maximal concentration (Tmax) from 6 hours to 8 hours.

Oral Contraceptives: Administration of a single 0.03 mg-0.15 mg dose of ethinyl estradiol-levonorgestrel oral contraceptive under fed conditions seven hours after liraglutide dosing (1.8 mg/day) at steady state resulted in a 12% and 13% reduction in the peak plasma concentration (Cmax) of ethinyl estradiol and levonorgestrel, respectively, and a delay in median time to maximal concentration (Tmax) by 1.5 hours for both. Ethinyl estradiol systemic exposure (AUC) was not changed, while levonorgestrel AUC increased by 18%.

References

  1. (2010) "Product Information. Victoza (liraglutide)." Novo Nordisk Pharmaceuticals Inc

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Drug and food interactions

Major

acetaminophen food

Applies to: acetaminophen / aspirin / caffeine / salicylamide

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

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Moderate

liraglutide food

Applies to: liraglutide

MONITOR: Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists can delay gastric emptying, which may impact the absorption of concomitantly administered oral medications. Mild to moderate decreases in plasma concentrations of coadministered drugs have been demonstrated in pharmacokinetic studies for some GLP-1 receptor agonists (e.g., exenatide, lixisenatide), but not others. According to the prescribing information, liraglutide did not affect the absorption of several orally administered drugs to any clinically significant extent, including acetaminophen, atorvastatin, digoxin, griseofulvin, lisinopril, and an oral contraceptive containing ethinyl estradiol-levonorgestrel. Likewise, no clinically relevant effect on absorption was observed for concomitantly administered oral drugs studied with albiglutide (digoxin, ethinyl estradiol-norethindrone, simvastatin, warfarin), dulaglutide (acetaminophen, atorvastatin, digoxin, ethinyl estradiol-norelgestromin, lisinopril, metformin, metoprolol, sitagliptin, warfarin), or semaglutide (atorvastatin, digoxin, ethinyl estradiol-levonorgestrel, metformin, warfarin). The impact of dual GLP-1 and GIP receptor agonist tirzepatide on gastric emptying was reported to be dose- and time-dependent, with the greatest effect observed after a single 5 mg dose but diminished after subsequent doses. When acetaminophen was administered following a single 5 mg dose of tirzepatide, acetaminophen peak plasma concentration (Cmax) was decreased by 50% and its median time to peak plasma concentration (Tmax) delayed by 1 hour. However, no significant impact on acetaminophen Cmax and Tmax was observed after 4 consecutive weekly doses of tirzepatide (5 mg/5 mg/8 mg/10 mg), and the overall exposure (AUC) of acetaminophen was unaffected. Tirzepatide at lower doses of 0.5 mg and 1.5 mg also had minimal effects on acetaminophen exposure.

MANAGEMENT: Although no specific dosage adjustment of concomitant medications is generally recommended based on available data, potential clinical impact on some oral medications cannot be ruled out, particularly those with a narrow therapeutic index or low bioavailability, those that depend on threshold concentrations for efficacy (e.g., antibiotics), and those that require rapid gastrointestinal absorption (e.g., hypnotics, analgesics). Pharmacologic response to concomitantly administered oral medications should be monitored more closely following initiation, dose adjustment, or discontinuation of a GLP-1 receptor agonist or a dual GLP-1 and GIP receptor agonist.

References

  1. (2005) "Product Information. Byetta (exenatide)." Amylin Pharmaceuticals Inc
  2. (2010) "Product Information. Victoza (liraglutide)." Novo Nordisk Pharmaceuticals Inc
  3. (2014) "Product Information. Tanzeum (albiglutide)." GlaxoSmithKline
  4. (2014) "Product Information. Trulicity (dulaglutide)." Eli Lilly and Company
  5. (2016) "Product Information. Adlyxin (lixisenatide)." sanofi-aventis
  6. (2022) "Product Information. Ozempic (1 mg dose) (semaglutide)." Novo Nordisk Pharmaceuticals Inc
  7. (2023) "Product Information. Mounjaro (tirzepatide)." Eli Lilly and Company Ltd
  8. (2023) "Product Information. Mounjaro (tirzepatide)." Lilly, Eli and Company
  9. Eli Lilly Canada Inc. (2023) Product monograph including patient medication information MOUNJARO tirzepatide injection. https://pdf.hres.ca/dpd_pm/00068421.PDF
View all 9 references

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Moderate

aspirin food

Applies to: acetaminophen / aspirin / caffeine / salicylamide

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

salicylamide food

Applies to: acetaminophen / aspirin / caffeine / salicylamide

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

caffeine food

Applies to: acetaminophen / aspirin / caffeine / salicylamide

The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

References

  1. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  2. Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR (1996) "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy, 16, p. 1046-52

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Minor

aspirin food

Applies to: acetaminophen / aspirin / caffeine / salicylamide

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.

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.

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