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Drug Interactions between methadone and rufinamide

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

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Interactions between your drugs

Moderate

methadone rufinamide

Applies to: methadone and rufinamide

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of opioids that are metabolized by the isoenzyme such as butorphanol, fentanyl, hydrocodone, methadone, and oxycodone. Reduced efficacy or withdrawal symptoms may occur in patients maintained on their narcotic pain regimen following the addition of a CYP450 3A4 inducer. Conversely, discontinuation of the inducer may increase opioid plasma concentrations and potentiate the risk of overdose and fatal respiratory depression.

MANAGEMENT: Pharmacologic response to the opioid should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the opioid dosage adjusted as necessary.

References

  1. Holmes VF "Rifampin-induced methadone withdrawal in AIDS." J Clin Psychopharmacol 10 (1991): 443-4
  2. Liu S-J, Wang RI "Case report of barbiturate-induced enhancement of methadone metabolism and withdrawal syndrome." Am J Psychiatry 141 (1984): 1287-8
  3. Bell J, Seres V, Bowron P, Lewis J, Batey R "The use of serum methadone levels in patients receiving methadone maintenance." Clin Pharmacol Ther 43 (1988): 623-9
  4. Finelli PF "Phenytoin and methadone tolerance." N Engl J Med 294 (1976): 227
  5. Tong TG, Pond SM, Kreek MJ, et al. "Phenytoin-induced methadone withdrawal." Ann Intern Med 94 (1981): 349-51
  6. Kreek MJ, Garfield JW, Gutjahr CL, Giusti LM "Rifampin-induced methadone withdrawal." N Engl J Med 294 (1976): 1104-6
  7. Bending MR, Skacel PO "Rifampicin and methadone withdrawal." Lancet 1 (1977): 1211
  8. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  9. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company PROD (2001):
  10. Raistrick D, Hay A, Wolff K "Methadone maintenance and tuberculosis treatment." BMJ 313 (1996): 925-6
  11. Altice FL, Friedland GH, Cooney EL "Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone." AIDS 13 (1999): 957-62
  12. Otero MJ, Fuertes A, Sanchez R, Luna G "Nevirapine-induced withdrawal symptoms in HIV patients on methadone maintenance programme: an alert." AIDS 13 (1999): 1004-5
  13. Pinzani V, Faucherre V, Peyriere H, Blayac JP "Methadone withdrawal symptoms with nevirapine and efavirenz." Ann Pharmacother 34 (2000): 405-7
  14. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  15. "Product Information. Ionsys (fentanyl)." Ortho McNeil Pharmaceutical (2006):
  16. "Product Information. Diskets (methadone)." Cebert Pharmaceuticals Inc (2007):
  17. Cerner Multum, Inc. "Australian Product Information." O 0
  18. "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc (2013):
  19. "Product Information. Butorphanol Tartrate (butorphanol)." Apotex Corporation (2017):
View all 19 references

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Drug and food interactions

Moderate

methadone food

Applies to: 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

rufinamide food

Applies to: rufinamide

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of rufinamide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of rufinamide. In healthy volunteers, administration of a single 400 mg dose of rufinamide with food resulted in an approximately 56% increase in mean peak plasma concentration (Cmax) and a 34% increase in systemic exposure (AUC) compared to administration during a fasting state.

MANAGEMENT: To ensure maximal oral absorption, it is preferable to administer rufinamide with food. Patients receiving rufinamide should be advised to avoid consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how rufinamide affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. "Product Information. Banzel (rufinamide)." Eisai Inc (2008):

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Moderate

methadone food

Applies to: 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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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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