Skip to main content

Drug Interactions between acetaminophen / codeine and Plavix

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

codeine clopidogrel

Applies to: acetaminophen / codeine and Plavix (clopidogrel)

MONITOR: Coadministration with opioid agonists may delay and reduce the absorption of orally administered P2Y12 inhibitors (e.g., clopidogrel, prasugrel, ticagrelor). The proposed mechanism may involve opioid-mediated slowed gastric emptying. In one study, IV morphine (5 mg) given immediately prior to a loading dose of clopidogrel (600 mg) decreased the systemic exposure (AUC) and maximum concentration (Cmax) of the active metabolite of clopidogrel by 34% and increased the time to peak concentration (Tmax) of clopidogrel when compared with placebo (105 minutes vs 83 minutes, respectively). In addition, morphine reduced the pharmacodynamic (antiplatelet) effects of clopidogrel. In another study, IV morphine (5 mg) given immediately prior to a loading dose of ticagrelor (180 mg) decreased the AUC of ticagrelor and its active metabolite by approximately 36%, doubled the Tmax of ticagrelor, and reduced the antiplatelet effects of ticagrelor. The clinical relevance of this interaction is unknown. The risks associated with other opioid agonists are also unknown.

MANAGEMENT: Although data are limited, caution is recommended when orally administered P2Y12 inhibitors are given concomitantly with opioid agonists. In acute coronary syndrome patients who require an opioid agonist, the use of a parenteral antiplatelet agent, such as cangrelor, should be considered.

References

  1. "Product Information. Plavix (clopidogrel)." Bristol-Myers Squibb PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. Agencia Española de Medicamentos y Productos Sanitarios Healthcare "Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008):
  5. "Product Information. Effient (prasugrel)." Lilly, Eli and Company (2009):
  6. "Product Information. Brilinta (ticagrelor)." Astra-Zeneca Pharmaceuticals (2011):
  7. Hobl EL, Stimpfl T, Ebner J, et al. "Morphine Decreases Clopidogrel Concentrations and Effects: A Randomized, Double Blind, Placebo-Controlled Trial." J Am Coll Cardiol (2013):
  8. Cerner Multum, Inc. "Canadian Product Information." O 0 (2015):
  9. Hobl EL, Reiter B, Schoergenhofer C, et al. "Morphine Decreases Ticagrelor Concentrations but not its Antiplatelet Effects: A Randomized Trial in Healthy Volunteers." Eur J Clin Invest 46 (2015): 7-14
  10. Hobl EL, Reiter B, Schoergenhofer C, et al. "Morphine interaction with prasugrel: a double-blind, cross-over trial in healthy volunteers." Clin Res Cardiol 105 (2015): 349-55
  11. Kubica J, Adamski P, Ostrowska M, et al. "Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial." Eur Heart J (2015):
  12. Kubica J, Kubica A, Jilma B, et al. "Impact of morphine on antiplatelet effects of oral P2Y12 receptor inhibitors." Int J Cardiol 215 (2016): 201-208
View all 12 references

Switch to consumer interaction data

Drug and food interactions

Major

acetaminophen food

Applies to: acetaminophen / codeine

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

Switch to consumer interaction data

Moderate

codeine food

Applies to: acetaminophen / codeine

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

References

  1. Linnoila M, Hakkinen S "Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving." Clin Pharmacol Ther 15 (1974): 368-73
  2. Sturner WQ, Garriott JC "Deaths involving propoxyphene: a study of 41 cases over a two-year period." JAMA 223 (1973): 1125-30
  3. Girre C, Hirschhorn M, Bertaux L, et al. "Enhancement of propoxyphene bioavailability by ethanol: relation to psychomotor and cognitive function in healthy volunteers." Eur J Clin Pharmacol 41 (1991): 147-52
  4. Levine B, Saady J, Fierro M, Valentour J "A hydromorphone and ethanol fatality." J Forensic Sci 29 (1984): 655-9
  5. Sellers EM, Hamilton CA, Kaplan HL, Degani NC, Foltz RL "Pharmacokinetic interaction of propoxyphene with ethanol." Br J Clin Pharmacol 19 (1985): 398-401
  6. Carson DJ "Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases." Lancet 1 (1977): 894-7
  7. Rosser WW "The interaction of propoxyphene with other drugs." Can Med Assoc J 122 (1980): 149-50
  8. Edwards C, Gard PR, Handley SL, Hunter M, Whittington RM "Distalgesic and ethanol-impaired function." Lancet 2 (1982): 384
  9. Kiplinger GF, Sokol G, Rodda BE "Effect of combined alcohol and propoxyphene on human performance." Arch Int Pharmacodyn Ther 212 (1974): 175-80
View all 9 references

Switch to consumer interaction data

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

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer