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Drug Interactions between lomefloxacin and methadone

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

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Major

methadone lomefloxacin

Applies to: methadone and lomefloxacin

MONITOR CLOSELY: Methadone may cause dose-related prolongation of the QT interval. 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. High dosages of methadone alone have been associated with QT interval prolongation and torsade de pointes. In a retrospective study of 17 methadone-treated patients who developed torsade de pointes, the mean daily dose was approximately 400 mg (range 65 to 1000 mg) and the mean corrected QT (QTc) interval on presentation was 615 msec. The daily methadone dose correlated positively with the QTc interval. Fourteen patients had at least one predisposing risk factor for arrhythmia (hypokalemia, hypomagnesemia, concomitant use of a medication known to prolong the QT interval or inhibit the metabolism of methadone, and structural heart disease), but these were not predictive of QTc interval. It is not known if any of the patients had congenital long QT syndrome.

MANAGEMENT: Caution is recommended if methadone is used in combination with other drugs that can prolong the QT interval, particularly in the setting of chronic pain management or methadone maintenance for opioid dependency where high dosages may be employed. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. If taking drugs that also cause CNS-depressant or orthostatic effects (e.g., sedating antihistamines, psychotropic drugs like tricyclic antidepressants, phenothiazines, and neuroleptics), patients should be made aware of the possibility of additive effects with methadone and counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Krantz MJ, Lewkowiez L, Hays H, et al. "Torsade de pointes associated with very-high-dose methadone." Ann Intern Med 137 (2002): 501-4
  2. Walker PW, Klein D, Kasza L "High dose methadone and ventricular arrhythmias: a report of three cases." Pain 103 (2003): 321-4
  3. Krantz MJ, Kutinsky IB, Robertson AD, Mehler PS "Dose-related effects of methadone on QT prolongation in a series of patients with torsade de pointes." Pharmacotherapy 23 (2003): 802-5
  4. De Bels D, Staroukine M, Devriendt J "Torsades de pointes due to methadone." Ann Intern Med 139 (2003): E156
  5. Krantz MJ, Mehler PS "Synthetic opioids and QT prolongation." Arch Intern Med 163 (2003): 1615; author reply 1615
  6. Sala M, Anguera I, Cervantes M "Torsade de pointes due to methadone." Ann Intern Med 139 (2003): W64
  7. Mokwe EO, Ositadinma O "Torsade de pointes due to methadone." Ann Intern Med 139 (2003): W64
  8. Gil M, Sala M, Anguera I, et al. "QT prolongation and Torsades de Pointes in patients infected with human immunodeficiency virus and treated with methadone." Am J Cardiol 92 (2003): 995-7
  9. Martell BA, Arnsten JH, Krantz MJ, Gourevitch MN "Impact of methadone treatment on cardiac repolarization and conduction in opioid users." Am J Cardiol 95 (2005): 915-8
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  11. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  12. Ehret GB, Desmeules JA, Broers B "Methadone-associated long QT syndrome: improving pharmacotherapy for dependence on illegal opioids and lessons learned for pharmacology." Expert Opin Drug Saf 6 (2007): 289-303
  13. Cerner Multum, Inc. "Australian Product Information." O 0
  14. EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852" (2013):
View all 14 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

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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Moderate

lomefloxacin food

Applies to: lomefloxacin

ADJUST DOSING INTERVAL: Oral preparations that contain magnesium, aluminum, or calcium may significantly decrease the gastrointestinal absorption of quinolone antibiotics. Absorption may also be reduced by sucralfate, which contains aluminum, as well as other polyvalent cations such as iron and zinc. The mechanism is chelation of quinolones by polyvalent cations, forming a complex that is poorly absorbed from the gastrointestinal tract. The bioavailability of ciprofloxacin has been reported to decrease by as much as 90% when administered with antacids containing aluminum or magnesium hydroxide.

MANAGEMENT: When coadministration cannot be avoided, quinolone antibiotics should be dosed either 2 to 4 hours before or 4 to 6 hours after polyvalent cation-containing products to minimize the potential for interaction. When coadministered with Suprep Bowel Prep (magnesium/potassium/sodium sulfates), the manufacturer recommends administering fluoroquinolone antibiotics at least 2 hours before and not less than 6 hours after Suprep Bowel Prep to avoid chelation with magnesium. Please consult individual product labeling for specific recommendations.

References

  1. Polk RE, Helay DP, Sahai J, Drwal L, Racht E "Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers." Antimicrob Agents Chemother 33 (1989): 1841-4
  2. Nix DE, Watson WA, Lener ME, et al. "Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin." Clin Pharmacol Ther 46 (1989): 700-5
  3. Garrelts JC, Godley PJ, Peterie JD, Gerlach EH, Yakshe CC "Sucralfate significantly reduces ciprofloxacin concentrations in serum." Antimicrob Agents Chemother 34 (1990): 931-3
  4. Frost RW, Lasseter KC, Noe AJ, Shamblen EC, Lettieri JT "Effects of aluminum hydroxide and calcium carbonate antacids on the bioavailability of ciprofloxacin." Antimicrob Agents Chemother 36 (1992): 830-2
  5. Yuk JH "Ciprofloxacin levels when receiving sucralfate." J Am Geriatr Soc 262 (1989): 901
  6. Deppermann KM, Lode H, Hoffken G, Tschink G, Kalz C, Koeppe P "Influence of ranitidine, pirenzepine, and aluminum magnesium hydroxide on the bioavailability of various antibiotics, including amoxicillin, cephalexin, doxycycline, and amoxicillin-clavulanic acid." Antimicrob Agents Chemother 33 (1989): 1901-7
  7. Campbell NR, Kara M, Hasinoff BB, Haddara WM, McKay DW "Norfloxacin interaction with antacids and minerals." Br J Clin Pharmacol 33 (1992): 115-6
  8. Parpia SH, Nix DE, Hejmanowski LG, Goldstein HR, Wilton JH, Schentag JJ "Sucralfate reduces the gastrointestinal absorption of norfloxacin." Antimicrob Agents Chemother 33 (1989): 99-102
  9. Nix DE, Wilton JH, Ronald B, Distlerath L, Williams VC, Norman A "Inhibition of norfloxacin absorption by antacids." Antimicrob Agents Chemother 34 (1990): 432-5
  10. Akerele JO, Okhamafe AO "Influence of oral co-administered metallic drugs on ofloxacin pharmacokinetics." J Antimicrob Chemother 28 (1991): 87-94
  11. Wadworth AN, Goa KL "Lomefloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use." Drugs 42 (1991): 1018-60
  12. Shimada J, Shiba K, Oguma T, et al. "Effect of antacid on absorption of the quinolone lomefloxacin." Antimicrob Agents Chemother 36 (1992): 1219-24
  13. Sahai J, Healy DP, Stotka J, Polk RE "The influence of chronic administration of calcium carbonate on the bioavailability of oral ciprofloxacin." Br J Clin Pharmacol 35 (1993): 302-4
  14. Lehto P, Kivisto KT "Effect of sucralfate on absorption of norfloxacin and ofloxacin." Antimicrob Agents Chemother 38 (1994): 248-51
  15. Noyes M, Polk RE "Norfloxacin and absorption of magnesium-aluminum." Ann Intern Med 109 (1988): 168-9
  16. Grasela TH Jr, Schentag JJ, Sedman AJ, et al. "Inhibition of enoxacin absorption by antacids or ranitidine." Antimicrob Agents Chemother 33 (1989): 615-7
  17. Lehto P, Kivisto KT "Different effects of products containing metal ions on the absorption of lomefloxacin." Clin Pharmacol Ther 56 (1994): 477-82
  18. Spivey JM, Cummings DM, Pierson NR "Failure of prostatitis treatment secondary to probable ciprofloxacin-sucralfate drug interaction." Pharmacotherapy 16 (1996): 314-6
  19. "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical PROD (2001):
  20. "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome PROD (2001):
  21. "Product Information. Zagam (sparfloxacin)." Rhone Poulenc Rorer PROD (2001):
  22. "Product Information. Trovan (trovafloxacin)." Pfizer U.S. Pharmaceuticals PROD (2001):
  23. Teng R, Dogolo LC, Willavize SA, Friedman HL, Vincent J "Effect of Maalox and omeprazole on the bioavailability of trovafloxacin." J Antimicrob Chemother 39 Suppl B (1997): 93-7
  24. Zix JA, Geerdes-Fenge HF, Rau M, Vockler J, Borner K, Koeppe P, Lode H "Pharmacokinetics of sparfloxacin and interaction with cisapride and sucralfate." Antimicrob Agents Chemother 41 (1997): 1668-72
  25. Honig PK, Gillespie BK "Clinical significance of pharmacokinetic drug interactions with over-the-counter (OTC) drugs." Clin Pharmacokinet 35 (1998): 167-71
  26. Johnson RD, Dorr MB, Talbot GH, Caille G "Effect of Maalox on the oral absorption of sparfloxacin." Clin Ther 20 (1998): 1149-58
  27. Lober S, Ziege S, Rau M, Schreiber G, Mignot A, Koeppe P, Lode H "Pharmacokinetics of gatifloxacin and interaction with an antacid containing aluminum and magnesium." Antimicrob Agents Chemother 43 (1999): 1067-71
  28. Allen A, Vousden M, Porter A, Lewis A "Effect of Maalox((R)) on the bioavailability of oral gemifloxacin in healthy volunteers." Chemotherapy 45 (1999): 504-11
  29. Kamberi M, Nakashima H, Ogawa K, Oda N, Nakano S "The effect of staggered dosing of sucralfate on oral bioavailability of sparfloxacin." Br J Clin Pharmacol 49 (2000): 98-103
  30. "Product Information. Factive (gemifloxacin)." *GeneSoft Inc (2003):
  31. "Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates)." Braintree Laboratories (2010):
  32. "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc. (2017):
View all 32 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.

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

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