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Drug Interactions between methadone and sparfloxacin

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

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Interactions between your drugs

Major

methadone sparfloxacin

Applies to: methadone and sparfloxacin

CONTRAINDICATED: Sparfloxacin may cause dose-related prolongation of the QT interval in some patients. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. Torsade de pointes has been reported in a few patients receiving sparfloxacin alone and with antiarrhythmic agents like amiodarone and disopyramide.

MANAGEMENT: Coadministration of sparfloxacin with other drugs that can prolong the QT interval is considered contraindicated.

References

  1. Thomas M, Maconochie JG, Fletcher E (1996) "The dilemma of the prolonged QT interval in early drug studies." Br J Clin Pharmacol, 41, p. 77-81
  2. Jaillon P, Morganroth J, Brumpt I, Talbot G (1996) "Overview of electrocardiographic and cardiovascular safety data for sparfloxacin. Sparfloxacin Safety Group." J Antimicrob Chemother, 37(suppl a), p. 161-7
  3. Zix JA, GeerdesFenge HF, Rau M, Vockler J, Borner K, Koeppe P, Lode H (1997) "Pharmacokinetics of sparfloxacin and interaction with cisapride and sucralfate." Antimicrob Agents Chemother, 41, p. 1668-72
  4. (2001) "Product Information. Zagam (sparfloxacin)." Rhone Poulenc Rorer
  5. Demolis JL, Charransol A, Funck-Brentano C, Jaillon P (1996) "Effects of a single oral dose of sparfloxacin on ventricular repolarization in healthy volunteers." Br J Clin Pharmacol, 41, p. 499-503
  6. Dupont H, Timsit JF, Souweine B, Gachot B, Wolff M, Regnier B (1996) "Torsades de pointe probably related to sparfloxacin." Eur J Clin Microbiol Infect Dis, 15, p. 350-1
  7. Lipsky BA, Dorr MB, Magner DJ, Talbot GH (1999) "Safety profile of sparfloxacin, a new fluoroquinolone antibiotic." Clin Ther, 21, p. 148-59
  8. Owens RC (2001) "Risk assessment for antimicrobial agent-induced QTc interval prolongation and torsades de pointes." Pharmacotherapy, 21, p. 301-19
  9. Iannini PB, Doddamani S, Byazrova E, Curciumaru I, Kramer H (2001) "Risk of torsades de pointes with non-cardiac drugs." BMJ, 322, p. 46-7
  10. Ball P (2000) "Quinolone-induced QT interval prolongation: a not-so-unexpected class effect." J Antimicrob Chemother, 45, p. 557-9
  11. Kang J, Wang L, Chen XL, Triggle DJ, Rampe D (2001) "Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG." Mol Pharmacol, 59, p. 122-6
  12. Oliphant CM, Green GM (2002) "Quinolones: a comprehensive review." Am Fam Physician, 65, p. 455-64
  13. Owens RC Jr, Ambrose PG (2002) "Torsades de pointes associated with fluoroquinolones." Pharmacotherapy, 22, 663-8; discussion 668-72
  14. Iannini PB (2002) "Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval." Expert Opin Drug Saf, 1, p. 121-8
  15. Owens RC (2004) "QT Prolongation with Antimicrobial Agents : Understanding the Significance." Drugs, 64, p. 1091-124
  16. Katritsis D, Camm AJ (2003) "Quinolones: cardioprotective or cardiotoxic." Pacing Clin Electrophysiol, 26, p. 2317-20
  17. Stahlmann R (2002) "Clinical toxicological aspects of fluoroquinolones." Toxicol Lett, 127, p. 269-77
  18. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  19. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  20. Falagas ME, Rafailidis PI, Rosmarakis ES (2007) "Arrhythmias associated with fluoroquinolone therapy." Int J Antimicrob Agents, 29, p. 374-9
  21. Cerner Multum, Inc. "Australian Product Information."
View all 21 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 (1996) "Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes." Chem Res Toxicol, 9, p. 365-73
  2. Oda Y, Kharasch ED (2001) "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, p. 1021-32
  3. Benmebarek M, Devaud C, Gex-Fabry M, et al. (2004) "Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone." Clin Pharmacol Ther, 76, p. 55-63
  4. Foster DJ, Somogyi AA, Bochner F (1999) "Methadone N-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4." Br J Clin Pharmacol, 47, p. 403-12
View all 4 references

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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 (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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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

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