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Drug Interactions between Dalalone and Methadose

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

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Interactions between your drugs

Major

methadone dexAMETHasone

Applies to: Methadose (methadone) and Dalalone (dexamethasone)

MONITOR CLOSELY: Coadministration with inducers of various CYP450 isoenzymes may decrease the plasma concentrations of methadone, which is metabolized by CYP450 3A4, 2B6, 2C19, 2C9, and 2D6. Reduced analgesic efficacy or withdrawal symptoms may occur in patients maintained on methadone following the addition of an inducer. Conversely, discontinuation of the inducer may increase methadone plasma concentrations and potentiate the risk of overdose and fatal respiratory depression. The interaction has been reported with several moderate and potent inducers including rifampin, phenytoin, phenobarbital, nevirapine, and efavirenz. In one report, evidence of withdrawal was observed in 21 of 30 patients maintained on methadone who received rifampin for tuberculosis, compared to zero out of 26 who received other antituberculous agents. In a study of 11 patients on stable methadone maintenance treatment, mean methadone peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 48% and 57%, respectively, following initiation of antiretroviral therapy containing efavirenz 600 mg once a day. Nine patients developed symptoms consistent with methadone withdrawal an average of 8 to 10 days after start of efavirenz, which required a 22% mean increase in methadone dosage. In a similar study with nevirapine given at 200 mg once daily for 2 weeks followed by 200 mg twice daily, the reduction in mean methadone Cmax and AUC was 36% and 52%, respectively, in 8 patients stabilized on methadone treatment. Withdrawal symptoms occurred in six patients 8 to 10 days after start of nevirapine, and methadone dosage was subsequently increased an average of 16%. Dosage increases of up to 100% and eventual discontinuation of the non-nucleoside reverse-transcriptase inhibitor have also been described in some reports.

MANAGEMENT: Caution is advised if methadone is prescribed with CYP450 2B6, 2C19, 2C9 and/or 3A4 inducers. Pharmacologic response to methadone should be monitored more closely whenever an inducer is added to or withdrawn from therapy, and the dosage adjusted as necessary.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. Raistrick D, Hay A, Wolff K "Methadone maintenance and tuberculosis treatment." BMJ 313 (1996): 925-6
  9. Altice FL, Friedland GH, Cooney EL "Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone." AIDS 13 (1999): 957-62
  10. 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
  11. Pinzani V, Faucherre V, Peyriere H, Blayac JP "Methadone withdrawal symptoms with nevirapine and efavirenz." Ann Pharmacother 34 (2000): 405-7
  12. "Product Information. Diskets (methadone)." Cebert Pharmaceuticals Inc (2007):
View all 12 references

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Drug and food interactions

Moderate

methadone food

Applies to: Methadose (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: Methadose (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.

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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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