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Drug Interactions between Rythmol SR and Tequin Teqpaq

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

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Interactions between your drugs

Major

propafenone gatifloxacin

Applies to: Rythmol SR (propafenone) and Tequin Teqpaq (gatifloxacin)

GENERALLY AVOID: Certain quinolones, including gatifloxacin and moxifloxacin, 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 have been reported in patients taking gatifloxacin. These cases primarily involved patients with underlying medical conditions for which they were receiving concomitant medications known to prolong the QTc interval. Rare cases of tachycardia have been reported with moxifloxacin. 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: Coadministration of gatifloxacin or moxifloxacin with other drugs that can prolong the QT interval should generally be avoided. Caution and clinical monitoring are recommended if concomitant use is required. 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. Avelox (moxifloxacin)." Bayer
  2. (2001) "Product Information. Tequin (gatifloxacin)." Bristol-Myers Squibb
  3. Siepmann M, Kirch W (2001) "Drug points - Tachycardia associated with moxifloxacin." Br Med J, 322, p. 23
  4. Owens RC (2001) "Risk assessment for antimicrobial agent-induced QTc interval prolongation and torsades de pointes." Pharmacotherapy, 21, p. 301-19
  5. Iannini PB, Circiumaru I (2001) "Gatifloxacin-induced QTc prolongation and ventricular tachycardia." Pharmacotherapy, 21, p. 361-2
  6. Demolis JL, Kubitza D, Tenneze L, Funck-Bretano C (2000) "Effect of a single oral dose of moxifloxacin (400 mg and 800 mg) on ventricular repolarization in healthy subjects." Clin Pharmacol Ther, 68, p. 658-66
  7. 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
  8. Ball P (2000) "Quinolone-induced QT interval prolongation: a not-so-unexpected class effect." J Antimicrob Chemother, 45, p. 557-9
  9. 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
  10. White CM, Grant EM, Quintiliani R (2001) "Moxifloxacin does increase the corrected QT interval." Clin Infect Dis, 33, p. 1441-2
  11. Frothingham R (2001) "Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin." Pharmacotherapy, 21, p. 1468-72
  12. Bertino JS Jr, Owens RC Jr, Carnes TD, Iannini PB (2002) "Gatifloxacin-associated corrected QT interval prolongation, torsades de pointes, and ventricular fibrillation in patients with known risk factors." Clin Infect Dis, 34, p. 861-3
  13. Oliphant CM, Green GM (2002) "Quinolones: a comprehensive review." Am Fam Physician, 65, p. 455-64
  14. Owens RC Jr, Ambrose PG (2002) "Torsades de pointes associated with fluoroquinolones." Pharmacotherapy, 22, 663-8; discussion 668-72
  15. 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
  16. Ansari SR, Chopra N (2004) "Gatifloxacin and Prolonged QT Interval." Am J Med Sci, 327, p. 55-6
  17. Iannini PB (2002) "Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval." Expert Opin Drug Saf, 1, p. 121-8
  18. Owens RC (2004) "QT Prolongation with Antimicrobial Agents : Understanding the Significance." Drugs, 64, p. 1091-124
  19. Katritsis D, Camm AJ (2003) "Quinolones: cardioprotective or cardiotoxic." Pacing Clin Electrophysiol, 26, p. 2317-20
  20. Stahlmann R (2002) "Clinical toxicological aspects of fluoroquinolones." Toxicol Lett, 127, p. 269-77
  21. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  22. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  23. Dale KM, Lertsburapa K, Kluger J, White CM (2007) "Moxifloxacin and torsade de pointes." Ann Pharmacother, 41, p. 336-40
  24. Falagas ME, Rafailidis PI, Rosmarakis ES (2007) "Arrhythmias associated with fluoroquinolone therapy." Int J Antimicrob Agents, 29, p. 374-9
  25. Tsikouris JP, Peeters MJ, Cox CD, Meyerrose GE, Seifert CF (2006) "Effects of three fluoroquinolones on QT analysis after standard treatment courses." Ann Noninvasive Electrocardiol, 11, p. 52-6
  26. Cerner Multum, Inc. "Australian Product Information."
View all 26 references

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Drug and food interactions

Moderate

propafenone food

Applies to: Rythmol SR (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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Minor

gatifloxacin food

Applies to: Tequin Teqpaq (gatifloxacin)

Concurrent ingestion of calcium-fortified foods (i.e., cereal, orange juice) may alter the bioavailability of gatifloxacin. The mechanism is chelation of calcium and the quinolone, resulting in decreased bioavailability. In the case of orange juice, inhibition of intestinal transport mechanisms (P-glycoprotein or organic anion-transporting polypeptides) by flavones may also be involved. Data have been conflicting: One study has reported no effect with milk coadministration. Another study reported a modest decrease in gatifloxacin bioavailability (13.5% decrease in Cmax,12% decrease in AUC, 15% increase in total clearance) when taken with 12 ounces of calcium-fortified orange juice instead of water, which could be clinically significant if the infecting organisms have borderline susceptibilities. The manufacturer states that gatifloxacin may be taken without regard to food, milk, or calcium. Clinicians should be aware of the possibility of an interaction if subtherapeutic effects are observed.

References

  1. (2001) "Product Information. Tequin (gatifloxacin)." Bristol-Myers Squibb
  2. Wallace AW, Victory JM, Amsden GW (2003) "Lack of bioequivalence of gatifloxacin when coadministered with calcium-fortified orange juice in healthy volunteers." J Clin Pharmacol, 43, p. 92-6

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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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