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Drug Interaction Report

2 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Major

sparfloxacin lapatinib

Applies to: Zagam Respipac (sparfloxacin), Tykerb (lapatinib)

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

lapatinib food

Applies to: Tykerb (lapatinib)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of lapatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

ADJUST DOSING INTERVAL: Food can significantly increase the oral bioavailability of lapatinib. According to the manufacturer, lapatinib peak plasma concentration (Cmax) was approximately 2.5- and 3-fold higher and systemic exposure (AUC) 3- and 4-fold higher when administered with a low fat meal (5% fat; 500 calories) or with a high-fat meal (50% fat; 1000 calories), respectively, compared to fasting. Dividing the daily dose also resulted in an approximately 2-fold higher systemic exposure at steady state compared to the same total dose administered once daily.

MANAGEMENT: Patients treated with lapatinib should preferably avoid the consumption of grapefruit or grapefruit juice. The manufacturer recommends that lapatinib be administered at least one hour before or one hour after a meal. The lapatinib dose is administered once daily and should not be divided.

References

  1. (2007) "Product Information. Tykerb (lapatinib)." Novartis Pharmaceuticals

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Therapeutic duplication warnings

No duplication 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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Further information

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