Skip to main content

Drug Interactions between Hismanal and Telzir

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

astemizole fosamprenavir

Applies to: Hismanal (astemizole) and Telzir (fosamprenavir)

CONTRAINDICATED: Coadministration with protease inhibitors (PIs), particularly ritonavir, may significantly increase the plasma concentrations of astemizole and terfenadine. The mechanism is PI inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of both astemizole and terfenadine. Although the interaction has not been specifically studied with any of the available PIs, high plasma levels of astemizole and terfenadine (e.g., due to overdose or interaction with other potent 3A4 inhibitors such as macrolide antibiotics and azole antifungal agents) have been associated with prolongation of the QT interval on the ECG; ventricular arrhythmias including ventricular tachycardia, ventricular fibrillation, and torsade de pointes; cardiac arrest; and sudden death.

MANAGEMENT: Given the potential for serious and life-threatening adverse cardiac events associated with increased plasma levels of astemizole and terfenadine, use of these agents in patients treated with protease inhibitors is considered contraindicated. Loratadine, cetirizine, or fexofenadine may be safer alternatives during therapy with PIs.

References

  1. Eller MG, Okerholm RA "Pharmacokinetic interaction between terfenadine and ketoconazole." Clin Pharmacol Ther 49 (1991): 130
  2. Honig PK, Woosley RL, Zamani K, Conner DP, Cantilena LR Jr "Changes in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine with concomitant administration of erythromycin." Clin Pharmacol Ther 52 (1992): 231-8
  3. Zimmermann M, Duruz H, Guinand O, et al. "Torsades de Pointes after treatment with terfenadine and ketoconazole." Eur Heart J 13 (1992): 1002-3
  4. Mathews DR, McNutt B, Okerholm R, et al. "Torsades de pointes occurring in association with terfenadine use." JAMA 266 (1991): 2375-6
  5. Honig PK, Wortham DC, Zamani K, et al. "Terfenadine-ketoconazole interaction: pharmacokinetic and electrocardiographic consequences." JAMA 269 (1993): 1513-8
  6. Pohjola-Sintonen S, Viitasalo M, Toivonene L, Neuvonen P "Torsades de pointes after terfenadine-itraconazole interaction." BMJ 306 (1993): 186
  7. Craft TM "Torsade de pointes after astemizole overdose." Br Med J 292 (1986): 660
  8. 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
  9. Saviuc P, Danel V, Dixmerias F "Prolonged QT interval and torsade de pointes following astemizole overdose." J Toxicol Clin Toxicol 31 (1993): 121-5
  10. Hasan RA, Zureikat GY, Nolan BM "Torsade de pointes associated with astemizole overdose treated with magnesium sulfate." Pediatr Emerg Care 9 (1993): 23-5
  11. Crane JK, Shih HT "Syncope and cardiac arrhythmia due to an interaction between itraconazole and terfenadine." Am J Med 95 (1993): 445-6
  12. Biglin KE, Faraon MS, Constance TD, Lieh-Lai M "Drug-induced torsades de pointes: a possible interaction of terfenadine and erythromycin." Ann Pharmacother 28 (1994): 282
  13. Honig PK, Wortham DC, Hull R, Zamani K, Smith JE, Cantilena LR "Itraconazole affects single-dose terfenadine pharmacokinetics and cardiac repolarization pharmacodynamics." J Clin Pharmacol 33 (1993): 1201-6
  14. 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
  15. Kivisto KT, Neuvonen PJ, Klotz U "Inhibition of terfenadine metabolism - pharmacokinetic and pharmacodynamic consequences." Clin Pharmacokinet 27 (1994): 1-5
  16. Smith SJ "Cardiovascular toxicity of antihistamines." Otolaryngol Head Neck Surg 111 Suppl (1994): 348-54
  17. Paris DG, Parente TF, Bruschetta HR, Guzman E, Niarchos AP "Torsades-de-pointes induced by erythromycin and terfenadine." Am J Emerg Med 12 (1994): 636-8
  18. "Product Information. Invirase (saquinavir)." Roche Laboratories PROD (2001):
  19. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  20. "Product Information. Crixivan (indinavir)." Merck & Co., Inc PROD (2001):
  21. Ng PW, Chan WK, Chan TYK "Torsade de pointes during the concomitant use of terfenadine and cimetidine." Aust N Z J Med 26 (1996): 120-1
  22. Heidemann SM, Sarnaik AP "Arrhythmias after astemizole overdose." Pediatr Emerg Care 12 (1996): 102-4
  23. Woosley RL "Cardiac actions of antihistamines." Annu Rev Pharmacol Toxicol 36 (1996): 233-52
  24. Hey JA, Delprado M, Egan RW, Kreutner W "Terfenadine, astemizole, and ebastine produce QTc interval prolongation in an experimental model predictive of adverse clinical ECG effects." Ann Allergy Asthma Immunol 76 (1996): 476
  25. 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
  26. 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
  27. "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc PROD (2001):
  28. Ament PW, Paterson A "Drug interactions with the nonsedating antihistamines." Am Fam Physician 56 (1997): 223
  29. Jurima-Romet M, Crawford K, Cyr T, Inaba T "Terfenadine metabolism in human liver. In vitro inhibition by macrolide antibiotics and azole antifungals." Drug Metab Dispos 22 (1994): 849-57
  30. Rankin AC "Non-sedating antihistamines and cardiac arrhythmia." Lancet 350 (1997): 1115-6
  31. Gonzalez MA, Estes KS "Pharmacokinetic overview of oral second-generation H-1 antihistamines." Int J Clin Pharmacol Ther 36 (1998): 292-300
  32. "Product Information. Agenerase (amprenavir)." Glaxo Wellcome PROD (2001):
  33. Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57
  34. "Product Information. Fortovase (saquinavir)." Roche Laboratories PROD (2001):
  35. Mangum EM, Graham KK "Lopinavir-Ritonavir: a new protease inhibitor." Pharmacotherapy 21 (2001): 1352-63
  36. DuBuske LM "Second-generation antihistamines: the risk of ventricular arrhythmias." Clin Ther 21 (1999): 281-95
  37. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb (2003):
  38. "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline (2003):
  39. "Product Information. Prezista (darunavir)." Ortho Biotech Inc (2006):
View all 39 references

Switch to consumer interaction data

Drug and food interactions

Major

astemizole food

Applies to: Hismanal (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):

Switch to consumer interaction data

Moderate

fosamprenavir food

Applies to: Telzir (fosamprenavir)

ADJUST DOSING INTERVAL: Food may reduce the systemic bioavailability of amprenavir from fosamprenavir oral suspension. The mechanism of interaction has not been described. According to the product labeling, administration of fosamprenavir oral suspension (1400 mg single dose) with a high-fat meal (967 kcal, 67 g fat, 33 g protein, 58 g carbohydrate) reduced amprenavir peak plasma concentration (Cmax) by 46% and systemic exposure (AUC) by 28% compared to administration in a fasted state. The time to reach peak plasma level (Tmax) was delayed by 0.72 hours. In contrast, the same high-fat meal did not affect the pharmacokinetics of amprenavir from fosamprenavir tablets.

MANAGEMENT: Fosamprenavir suspension should be administered on an empty stomach in adults, but with food in pediatric patients to aid palatability and compliance. If emesis occurs within 30 minutes after dosing the suspension, the dose should be repeated. Fosamprenavir tablets may be taken with or without food.

References

  1. "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline (2003):

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