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Drug Interactions between Levaquin and propafenone

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

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Interactions between your drugs

Moderate

propafenone levoFLOXacin

Applies to: propafenone and Levaquin (levofloxacin)

MONITOR: Certain quinolones, including levofloxacin, norfloxacin, and ofloxacin, 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. During postmarketing surveillance, rare cases of torsade de pointes and ventricular tachycardia have been reported in patients taking levofloxacin, norfloxacin, and ofloxacin. The levofloxacin cases primarily involved patients with underlying medical conditions or taking concomitant medications that may have been contributory. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Although the risk of a serious interaction is probably low, caution is recommended if levofloxacin, norfloxacin, or ofloxacin is used in combination with other drugs that can prolong the QT interval. Since the magnitude of QTc prolongation increases with increasing plasma concentrations of the quinolone, recommended dosages and intravenous infusion rates should not be exceeded. 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.

References

  1. (2001) "Product Information. Floxin (ofloxacin)." Ortho McNeil Pharmaceutical
  2. 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
  3. (2001) "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical
  4. Samaha FF (1999) "QTC interval prolongation and polymorphic ventricular tachycardia in association with levofloxacin." Am J Med, 107, p. 528-9
  5. Iannini PB, Doddamani S, Byazrova E, Curciumaru I, Kramer H (2001) "Risk of torsades de pointes with non-cardiac drugs. Prolongation of QT interval is probably a class effect of fluoroquinolones." Br Med J, 322, p. 46-7
  6. Owens RC (2001) "Risk assessment for antimicrobial agent-induced QTc interval prolongation and torsades de pointes." Pharmacotherapy, 21, p. 301-19
  7. Ball P (2000) "Quinolone-induced QT interval prolongation: a not-so-unexpected class effect." J Antimicrob Chemother, 45, p. 557-9
  8. 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
  9. Kahn JB (2001) "Latest industry information on the safety profile of levofloxacin in the US." Chemotherapy, 47 Suppl 3, p. 32-7
  10. Frothingham R (2001) "Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin." Pharmacotherapy, 21, p. 1468-72
  11. Oliphant CM, Green GM (2002) "Quinolones: a comprehensive review." Am Fam Physician, 65, p. 455-64
  12. Owens RC Jr, Ambrose PG (2002) "Torsades de pointes associated with fluoroquinolones." Pharmacotherapy, 22, 663-8; discussion 668-72
  13. Noel GJ, Natarajan J, Chien S, Hunt TL, Goodman DB, Abels R (2003) "Effects of three fluoroquinolones on QT interval in healthy adults after single doses." Clin Pharmacol Ther, 73, p. 292-303
  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. Nykamp DL, Blackmon CL, Schmidt PE, Roberson AG (2005) "QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine." Ann Pharmacother, 39, p. 543-6
  17. Katritsis D, Camm AJ (2003) "Quinolones: cardioprotective or cardiotoxic." Pacing Clin Electrophysiol, 26, p. 2317-20
  18. Stahlmann R (2002) "Clinical toxicological aspects of fluoroquinolones." Toxicol Lett, 127, p. 269-77
  19. Makaryus AN, Byrns K, Makaryus MN, Natarajan U, Singer C, Goldner B (2006) "Effect of ciprofloxacin and levofloxacin on the QT interval: is this a significant "clinical" event?" South Med J, 99, p. 52-6
  20. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  21. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  22. Falagas ME, Rafailidis PI, Rosmarakis ES (2007) "Arrhythmias associated with fluoroquinolone therapy." Int J Antimicrob Agents, 29, p. 374-9
  23. Cerner Multum, Inc. "Australian Product Information."
View all 23 references

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Drug and food interactions

Moderate

propafenone food

Applies to: propafenone

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of propafenone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. In over 90% of patients, propafenone is rapidly and extensively converted to 2 active metabolites: 5-hydroxypropafenone via CYP450 2D6 and N-depropylpropafenone (norpropafenone) via CYP450 3A4 and 1A2. In less than 10% of patients (approximately 6% of Caucasians in the U.S. population), however, metabolism of propafenone is slower because the 5-hydroxy metabolite is not formed, or minimally formed, due to a genetic deficiency in CYP450 2D6. In these poor metabolizers of CYP450 2D6, clearance of propafenone via the CYP450 3A4 and 1A2 metabolic pathways becomes more important, and inhibition of these pathways may substantially increase systemic exposure to propafenone. Likewise, patients taking concomitant inhibitors of CYP450 2D6 and 3A4 may experience similar pharmacokinetic effects. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased systemic exposure to propafenone may result in proarrhythmic events and exaggerated beta-adrenergic blocking activity.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with propafenone.

References

  1. Botsch S, Gautier JC, Beaune P, Eichelbaum M, Kroemer HK (1993) "Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites." Mol Pharmacol, 43, p. 120-6
  2. (2011) "Product Information. Rythmol SR (propafenone)." GlaxoSmithKline
  3. (2023) "Product Information. Apo-Propafenone (propafenone)." Apotex Incorporated
  4. (2022) "Product Information. Propafenone (propafenone)." Accord-UK Ltd
View all 4 references

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Moderate

levoFLOXacin food

Applies to: Levaquin (levofloxacin)

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of levofloxacin. According to the drug product labeling, administration of levofloxacin 500 mg with food prolonged the time to peak concentration by 1 hour and decreased the Cmax decreased by 25% following administration of the oral solution and by 14% following administration of the oral tablet.

MANAGEMENT: To ensure maximal and consistent oral absorption, levofloxacin oral solution should be taken at least one hour before or two hours after meals. For administration of the oral solution with continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for one hour before and two hours after the dose of levofloxacin. The oral tablets may be taken without regard to food.

References

  1. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67

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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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