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Drug Interactions between Entereg and Methadone Diskets

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

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Interactions between your drugs

Major

methadone alvimopan

Applies to: Methadone Diskets (methadone) and Entereg (alvimopan)

CONTRAINDICATED: Recent exposure to opioids can increase the sensitivity to mu opioid receptor antagonists.

MANAGEMENT: The use of alvimopan is contraindicated in patients who have received therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan administration. Caution is advised in patients who have received more than 3 doses of an opioid within the week prior to surgery, as these patients were not studied in the postoperative ileus clinical trials. Patients with recent exposure to opioids should be monitored for increased adverse effects such as abdominal pain, nausea and vomiting, and diarrhea.

References

  1. "Product Information. Entereg (alvimopan)." GlaxoSmithKline (2008):

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Drug and food interactions

Moderate

methadone food

Applies to: Methadone Diskets (methadone)

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of methadone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In 8 study subjects stabilized on methadone maintenance treatment, ingestion of regular strength grapefruit juice (200 mL one-half hour before and 200 mL simultaneously with the daily methadone dose) for five days resulted in an approximately 17% mean increase in methadone peak plasma concentration (Cmax) and systemic exposure (AUC) and a 14% mean decrease in apparent clearance for both the R(+) and S(-) enantiomers. Grapefruit juice did not affect the time to peak level (Tmax), terminal half-life, or apparent volume of distribution of methadone. No signs or symptoms of methadone toxicity or changes in intensity of withdrawal symptoms were reported in the study.

MANAGEMENT: Given the interindividual variability in the pharmacokinetics of methadone, a more significant interaction with grapefruit juice in certain patients cannot be ruled out. Patients treated with methadone should preferably avoid or limit the consumption of grapefruit juice, particularly during the induction of maintenance treatment.

References

  1. Iribarne C, Berthou F, Baird S, Dreano Y, Picart D, Bail JP, Beaune P, Menez JF "Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes." Chem Res Toxicol 9 (1996): 365-73
  2. Oda Y, Kharasch ED "Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation." J Pharmacol Exp Ther 298 (2001): 1021-32
  3. Benmebarek M, Devaud C, Gex-Fabry M, et al. "Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone." Clin Pharmacol Ther 76 (2004): 55-63
  4. Foster DJ, Somogyi AA, Bochner F "Methadone N-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4." Br J Clin Pharmacol 47 (1999): 403-12
View all 4 references

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Moderate

methadone food

Applies to: Methadone Diskets (methadone)

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

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Minor

alvimopan food

Applies to: Entereg (alvimopan)

Coadministration with a high-fat meal may decrease the rate and extent of alvimopan absorption. According to the product labeling, alvimopan peak plasma concentration (Cmax) and systemic exposure (AUC) were decreased by approximately 38% and 21%, respectively, and the time to reach peak plasma concentration (Tmax) was prolonged by approximately 1 hour when taken with a high-fat meal. The clinical significance is unknown. In postoperative ileus clinical trials, the preoperative dose of alvimopan was administered in a fasting state, and subsequent doses were given without regard to meals.

References

  1. "Product Information. Entereg (alvimopan)." GlaxoSmithKline (2008):

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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

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