Skip to main content

Drug Interactions between astemizole and itraconazole

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

itraconazole astemizole

Applies to: itraconazole and astemizole

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

Switch to consumer interaction data

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. (2002) "Product Information. Hismanal (astemizole)." Janssen Pharmaceuticals

Switch to consumer interaction data

Moderate

itraconazole food

Applies to: itraconazole

ADJUST DOSING INTERVAL: Food increases the absorption of itraconazole capsules but decreases the absorption of itraconazole oral solution. Cola beverages may increase the bioavailability of itraconazole capsules. Itraconazole capsules require an acidic gastric pH for adequate dissolution and subsequent absorption. Cola beverages help lower gastric pH and improve absorption.

GENERALLY AVOID: Grapefruit juice may impair the absorption of itraconazole capsules, resulting in decreased antifungal effects. In a small, randomized, crossover study, the administration of itraconazole capsules with double-strength grapefruit juice (compared to water) was associated with significantly decreased (43%) plasma concentrations of itraconazole and its pharmacologically active hydroxy metabolite, as well as delayed times to reach peak concentrations of both. The exact mechanism of interaction is unknown but may involve reduced absorption of itraconazole secondary to enhanced activity of intestinal P-glycoprotein drug efflux pumps and delayed gastric emptying induced by certain compounds present in grapefruits. Another study reported no pharmacokinetic changes with single-strength grapefruit juice. Whether or not these observations apply to itraconazole oral solution is unknown.

MANAGEMENT: The manufacturer recommends that the capsules be taken immediately after a full meal and the solution be taken on an empty stomach to ensure maximal absorption. Cola beverages may help increase the bioavailability of itraconazole capsules, particularly in patients with hypochlorhydria or those treated concomitantly with gastric acid suppressants. Until more information is available, it may be advisable to avoid the consumption of grapefruits and grapefruit juice during itraconazole therapy.

References

  1. Van Peer A, Woestenborghs R, Heykants J, et al. (1989) "The effects of food and dose on the oral systemic availability of itraconazole in healthy subjects." Eur J Clin Pharmacol, 36, p. 423-6
  2. Wishart JM (1987) "The influence of food on the pharmacokinetics of itraconazole in patients with superficial fungal infection." J Am Acad Dermatol, 17, p. 220-3
  3. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  4. Barone JA, Koh JG, Bierman RH, Colaizzi JL, Swanson KA, Gaffar MC, Moskovitz BL, Mechlinski W, Van de Velde V (1993) "Food interaction and steady-state pharmacokinetics of itraconazole capsules in healthy male volunteers." Antimicrob Agents Chemother, 37, p. 778-84
  5. Zimmermann T, Yeates RA, Albrecht M, Laufen H, Wildfeuer A (1994) "Influence of concomitant food intake on the gastrointestinal absorption of fluconazole and itraconazole in japanese subjects." Int J Clin Pharmacol Res, 14, p. 87-93
  6. (2022) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  7. Kawakami M, Suzuki K, Ishizuka T, Hidaka T, Matsuki Y, Nakamura H (1998) "Effect of grapefruit juice on pharmacokinetics of itraconazole in healthy subjects." Int J Clin Pharmacol Ther, 36, p. 306-8
  8. Barone JA, Moskotitz BL, Guarnieri J, Hassell AE, Colaizzi JL, Bierman RH, Jessen L (1998) "Food interaction and steady-state pharmacokinetics of itraconazole oral solution in healthy volunteers." Pharmacotherapy, 18, p. 295-301
  9. Penzak SR, Gubbins PO, Gurley BJ, Wang PL, Saccente M (1999) "Grapefruit juice decreases the systemic availability of itraconazole capsules in healthy volunteers." Ther Drug Monit, 21, p. 304-9
  10. Katz HI (1999) "Drug interactions of the newer oral antifungal agents." Br J Dermatol, 141, p. 26-32
View all 10 references

Switch to consumer interaction data

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.

See also

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer