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Drug Interactions between astemizole and voriconazole

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

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Interactions between your drugs

Major

astemizole voriconazole

Applies to: astemizole and voriconazole

CONTRAINDICATED: Coadministration with azole antifungal agents may significantly increase the plasma concentrations of astemizole. The proposed mechanism is azole inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of astemizole. High plasma levels of astemizole have been associated with prolongation of the QT interval on the ECG; ventricular arrhythmias including ventricular tachycardia and torsade de pointes; cardiac arrest; and sudden death. Within the azole class, ketoconazole and itraconazole are considered the most potent inhibitors, while fluconazole is comparatively weak and generally causes clinically significant interactions with CYP450 3A4 substrates only at dosages of 200 mg/day or more.

MANAGEMENT: The use of astemizole with most azole antifungal agents is considered contraindicated. Some authorities consider concomitant administration of astemizole and itraconazole to be contraindicated during and for 2 weeks after treatment with itraconazole (AU). Loratadine, cetirizine, or fexofenadine may be safer alternatives during therapy with azole antifungal agents.

References

  1. "Product Information. Nizoral (ketoconazole)." Janssen Pharmaceuticals 1992 (2001):
  2. "Product Information. Sporonox (itraconazole)." Janssen Pharmaceutica, Titusville, NJ.
  3. "Product Information. Hismanal (astemizole)." Janssen Pharmaceuticals PROD (2002):
  4. "Product Information. Diflucan (fluconazole)." Roerig Division PROD (2002):
  5. Craft TM "Torsade de pointes after astemizole overdose." Br Med J 292 (1986): 660
  6. Simons FE, Kesselman MS, Giddins NG, Pelech AN, Simons KJ "Astemizole-induced torsade de pointes." Lancet 2 (1988): 624
  7. Snook J, Boothman-Burrell D, Watkins J, Colin-Jones D "Torsade de pointes ventricular tachycardia associated with astemizole overdose." Br J Clin Pract 42 (1988): 257-9
  8. Saviuc P, Danel V, Dixmerias F "Prolonged QT interval and torsade de pointes following astemizole overdose." J Toxicol Clin Toxicol 31 (1993): 121-5
  9. Goss JE, Ramo BW, Blake K "Torsades de pointes associated with astemizole (hismanal) therapy." Arch Intern Med 153 (1993): 2705
  10. Honig PK, Cantilena LR "Ketoconazole and fluconazole drug interactions." Arch Intern Med 154 (1994): 1038-41
  11. Rao KA, Adlakha A, Vermaansil B, Meloy TD, Stanton MS "Torsades de pointes ventricular tachycardia associated with overdose of astemizole." Mayo Clin Proc 69 (1994): 589-93
  12. Smith SJ "Cardiovascular toxicity of antihistamines." Otolaryngol Head Neck Surg 111 Suppl (1994): 348-54
  13. Salata JJ, Jurkiewicz NK, Wallace AA, Stupienski RF, Guinosso PJ, Lynch JJ "Cardiac electrophysiological actions of the histamine h-1-receptor antagonists astemizole and terfenadine compared with chlorpheniramine and pyrilamine." Circ Res 76 (1995): 110-9
  14. Berul CI, Morad M "Regulation of potassium channels by nonsedating antihistamines." Circulation 91 (1995): 2220-5
  15. "Product Information. Diflucan (fluconazole)." Roerig Division PROD (2001):
  16. Heidemann SM, Sarnaik AP "Arrhythmias after astemizole overdose." Pediatr Emerg Care 12 (1996): 102-4
  17. Woosley RL "Cardiac actions of antihistamines." Annu Rev Pharmacol Toxicol 36 (1996): 233-52
  18. Vorperian VR, Zhou ZF, Mohammad S, Hoon TJ, Studenik C, January CT "Torsade de pointes with an antihistamine metabolite: potassium channel blockade with desmethylastemizole." J Am Coll Cardiol 28 (1996): 1556-61
  19. Tsai WC, Tsai LM, Chen JH "Combined use of astemizole and ketoconazole resulting in torsade de pointes." J Formos Med Assoc 96 (1997): 144-6
  20. Ament PW, Paterson A "Drug interactions with the nonsedating antihistamines." Am Fam Physician 56 (1997): 223
  21. Pratt CM, Mason J, Russell T, Reynolds R, Ahlbrandt R "Cardiovascular safety of fexofenadine HCl." Am J Cardiol 83 (1999): 1451-4
  22. Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57
  23. Venkatakrishnan K, von Moltke LL, Greenblatt DJ "Effects of the antifungal agents on oxidative drug metabolism: clinical relevance." Clin Pharmacokinet 38 (2000): 111-80
  24. "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals (2002):
  25. "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation (2006):
  26. Cerner Multum, Inc. "Australian Product Information." O 0
View all 26 references

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Drug and food interactions

Major

astemizole food

Applies to: astemizole

GENERALLY AVOID: Some beverages such as tonic water contain varying amounts of quinine. Coadministration of a single 430 mg dose of quinine has been shown to increase plasma concentrations of astemizole and its metabolite, desmethylastemizole. Elevated levels of these agents may cause a prolongation of the electrocardiographic QT interval and potentially fatal ventricular arrhythmias. Although pharmacokinetic data have indicated that the amounts of quinine in beverages (up to 80 mg quinine in 32 oz of tonic water) are not sufficient to produce a significant effect, the potential for an interaction exists if large amounts of tonic water are ingested. Also, grapefruit juice has been shown to inhibit CYP450 enzymes, which may lead to increased serum astemizole concentrations. The risk of life-threatening ventricular arrhythmias may be increased.

MANAGEMENT: Patients should be counseled to limit consumption of quinine-containing beverages and avoid grapefruit juice while they are taking astemizole.

References

  1. "Product Information. Hismanal (astemizole)." Janssen Pharmaceuticals PROD (2002):

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Moderate

voriconazole food

Applies to: voriconazole

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.

References

  1. "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals (2002):
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 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

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

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