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Drug Interactions between cimetidine and Empirin with Codeine

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

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Interactions between your drugs

Moderate

codeine cimetidine

Applies to: Empirin with Codeine (aspirin / codeine) and cimetidine

MONITOR: Drugs that are inhibitors of CYP450 2D6 may interfere with the analgesic effect of codeine. The mechanism is decreased in vivo conversion of codeine to morphine, a metabolic reaction mediated by CYP450 2D6. If an inhibitor is started after a stable dose of codeine is achieved, reduced analgesia and possible opioid withdrawal may result. Conversely, ceasing CYP450 2D6 inhibitor therapy may lead to increased morphine levels, increasing the risk of opioid-related adverse effects.

MANAGEMENT: The possibility of reduced or inadequate pain relief should be considered in patients receiving codeine with drugs that inhibit CYP450 2D6. An increase in the codeine dosage or a different analgesic agent may be necessary in patients requiring therapy with CYP450 2D6 inhibitors. If concurrent therapy is used and the CYP450 2D6 inhibitor is stopped, the dose of codeine may need to be reduced and the patient should be monitored for signs and symptoms of respiratory depression or sedation. In addition, it should be noted that rolapitant, a moderate CYP450 2D6 inhibitor, may interfere with the analgesic effects of codeine for at least 28 days after administration of rolapitant. The manufacturer's prescribing information should be consulted for further information.

References

  1. Desmeules J, Dayer P, Gascon MP, Magistris M (1989) "Impact of genetic and environmental factors on codeine analgesia." Clin Pharmacol Ther, 45, p. 122
  2. Sindrup SH, Arendt-Nielsen L, Brosen K, et al. (1992) "The effect of quinidine on the analgesic effect of codeine." Eur J Clin Pharmacol, 42, p. 587-92
  3. Sindrup SH, Hofmann U, Asmussen J, Mikus G, Brosen K, Nielsen F, Ingwersen SH, Broen Christensen C (1996) "Impact of quinidine on plasma and cerebrospinal fluid concentrations of codeine and morphine after codeine intake." Eur J Clin Pharmacol, 49, p. 503-9
  4. Sindrup SH, Brosen K, Bjerring P, et al. (1991) "Codeine increases pain threshold to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine." Clin Pharmacol Ther, 49, p. 686-93
  5. Poulsen L, Brosen K, Srendt-Nielsen L, Gram LF, Elbaek K, Sindrup SH (1996) "Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects." Eur J Clin Pharmacol, 51, p. 289-95
  6. Desmeules J, Gascon MP, Dayer P, Magistris M (1991) "Impact of environmental and genetic factors on codeine analgesia." Eur J Clin Pharmacol, 41, p. 23-6
  7. Caraco Y, Sheller J, Wood JJ (1996) "Pharmacogenetic determination of the effects of codeine and prediction of drug interactions." J Pharmacol Exp Ther, 278, p. 1165-74
  8. Caraco Y, Sheller J, Wood AJJ (1999) "Impact of ethnic origin and quinidine coadministration on codeine's disposition and pharmacodynamic effects." J Pharmacol Exp Ther, 290, p. 413-22
  9. Hersh EV, Moore PA (2004) "Drug interactions in dentistry: the importance of knowing your CYPs." J Am Dent Assoc, 135, p. 298-311
  10. Vevelstad M, Pettersen S, Tallaksen C, Brors O (2009) "O-demethylation of codeine to morphine inhibited by low-dose levomepromazine." Eur J Clin Pharmacol, 65, p. 795-801
  11. Thorn CF, Klein TE, Altman RB (2009) "Codeine and morphine pathway." Pharmacogenet Genomics, 19, p. 556-8
  12. Zhou SF (2009) "Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II." Clin Pharmacokinet, 48, p. 761-804
  13. (2015) "Product Information. Varubi (rolapitant)." Tesaro Inc.
  14. (2023) "Product Information. Codeine Sulfate (codeine)." Hikma USA (formerly West-Ward Pharmaceutical Corporation)
View all 14 references

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Drug and food interactions

Moderate

codeine food

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

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Moderate

aspirin food

Applies to: Empirin with Codeine (aspirin / codeine)

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

cimetidine food

Applies to: cimetidine

Concurrent use of cimetidine and ethanol may result in increased ethanol concentrations. The mechanism appears to be due to inhibition of gastric alcohol dehydrogenase by cimetidine, leading to increased bioavailability of the alcohol and inhibition of hepatic metabolism of alcohol. The clinical significance of this interaction is limited. More importantly, patients requiring cimetidine for gastrointestinal disease should be counseled to avoid alcohol to prevent worsening of their disease. The other H-2 receptor antagonists appear to have minimal effects on the concentrations of alcohol.

References

  1. Feely J, Wood AJ (1982) "Effects of cimetidine on the elimination and actions of ethanol." JAMA, 247, p. 2819-21
  2. Hansten PD (1992) "Effects of H2-receptor antagonists on blood alcohol levels." JAMA, 267, p. 2469

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Minor

cimetidine food

Applies to: cimetidine

Caffeine effects may be increased in patients also taking cimetidine. The mechanism may be due to decreased caffeine metabolism induced by cimetidine. Although adequate clinical data are lacking, a reduction in dose or elimination of caffeine may be needed if excess CNS stimulation is observed.

References

  1. (2001) "Product Information. Tagamet (cimetidine)." SmithKline Beecham
  2. Broughton LJ, Rodgers HJ (1981) "Decreased systenuc clearance of caffeine due to cimetidine." Br J Clin Pharmacol, 12, p. 155-9

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Minor

aspirin food

Applies to: Empirin with Codeine (aspirin / codeine)

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

cimetidine food

Applies to: cimetidine

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.

References

  1. Bendayan R, Sullivan JT, Shaw C, Frecker RC, Sellers EM (1990) "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol, 38, p. 165-9

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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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