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Drug Interactions between conivaptan and Seldane-D

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

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Interactions between your drugs

Major

terfenadine conivaptan

Applies to: Seldane-D (pseudoephedrine / terfenadine) and conivaptan

GENERALLY AVOID: Coadministration with conivaptan may significantly increase the plasma concentrations of astemizole and terfenadine. The mechanism is conivaptan inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of these antihistamines. Although the interaction has not been specifically studied, 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. In pharmacokinetic studies with other drugs that are primarily metabolized by CYP450 3A4 such as midazolam, simvastatin, and amlodipine, conivaptan has increased systemic exposure (AUC) by 2- to 3-fold.

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 conivaptan should be avoided. Loratadine, cetirizine, or fexofenadine may be safer alternatives during therapy with conivaptan.

References

  1. 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
  2. Zimmermann M, Duruz H, Guinand O, et al. "Torsades de Pointes after treatment with terfenadine and ketoconazole." Eur Heart J 13 (1992): 1002-3
  3. Mathews DR, McNutt B, Okerholm R, et al. "Torsades de pointes occurring in association with terfenadine use." JAMA 266 (1991): 2375-6
  4. Honig PK, Wortham DC, Zamani K, et al. "Terfenadine-ketoconazole interaction: pharmacokinetic and electrocardiographic consequences." JAMA 269 (1993): 1513-8
  5. Pohjola-Sintonen S, Viitasalo M, Toivonene L, Neuvonen P "Torsades de pointes after terfenadine-itraconazole interaction." BMJ 306 (1993): 186
  6. Craft TM "Torsade de pointes after astemizole overdose." Br Med J 292 (1986): 660
  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. Hasan RA, Zureikat GY, Nolan BM "Torsade de pointes associated with astemizole overdose treated with magnesium sulfate." Pediatr Emerg Care 9 (1993): 23-5
  10. Crane JK, Shih HT "Syncope and cardiac arrhythmia due to an interaction between itraconazole and terfenadine." Am J Med 95 (1993): 445-6
  11. 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
  12. 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
  13. 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
  14. Kivisto KT, Neuvonen PJ, Klotz U "Inhibition of terfenadine metabolism - pharmacokinetic and pharmacodynamic consequences." Clin Pharmacokinet 27 (1994): 1-5
  15. Smith SJ "Cardiovascular toxicity of antihistamines." Otolaryngol Head Neck Surg 111 Suppl (1994): 348-54
  16. 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
  17. 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
  18. Heidemann SM, Sarnaik AP "Arrhythmias after astemizole overdose." Pediatr Emerg Care 12 (1996): 102-4
  19. Woosley RL "Cardiac actions of antihistamines." Annu Rev Pharmacol Toxicol 36 (1996): 233-52
  20. 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
  21. 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
  22. 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
  23. Ament PW, Paterson A "Drug interactions with the nonsedating antihistamines." Am Fam Physician 56 (1997): 223
  24. Rankin AC "Non-sedating antihistamines and cardiac arrhythmia." Lancet 350 (1997): 1115-6
  25. Gonzalez MA, Estes KS "Pharmacokinetic overview of oral second-generation H-1 antihistamines." Int J Clin Pharmacol Ther 36 (1998): 292-300
  26. Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57
  27. DuBuske LM "Second-generation antihistamines: the risk of ventricular arrhythmias." Clin Ther 21 (1999): 281-95
  28. "Product Information. Vaprisol (conivaptan)." Cumberland Pharmaceuticals Inc (2006):
View all 28 references

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Drug and food interactions

Major

terfenadine food

Applies to: Seldane-D (pseudoephedrine / terfenadine)

CONTRAINDICATED: The consumption of grapefruit juice has been associated with significantly increased plasma concentrations of terfenadine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. Terfenadine in high serum levels has been associated with prolongation of the QT interval and development of torsade de pointes, a potentially fatal ventricular arrhythmia.

MANAGEMENT: Due to the risk of cardiotoxicity, patients receiving the drug should be advised to avoid consumption of grapefruit products. Loratadine, cetirizine, and fexofenadine may be safer alternatives in patients who may have trouble adhering to the dietary restriction.

References

  1. 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
  2. Zimmermann M, Duruz H, Guinand O, et al. "Torsades de Pointes after treatment with terfenadine and ketoconazole." Eur Heart J 13 (1992): 1002-3
  3. Mathews DR, McNutt B, Okerholm R, et al. "Torsades de pointes occurring in association with terfenadine use." JAMA 266 (1991): 2375-6
  4. Monahan BP, Ferguson CL, Killeavy ES, et al. "Torsades de pointes occurring in association with terfenadine use." JAMA 264 (1990): 2788-90
  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. Cortese LM, Bjornson DC "Potential interaction between terfenadine and macrolide antibiotics." Clin Pharm 11 (1992): 675
  8. 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
  9. Zechnich AD, Haxby DG "Drug interactions associated with terfenadine and related nonsedating antihistamines." West J Med 164 (1996): 68-9
  10. Honig PK, Wortham DC, Lazarev A, Cantilena LR "Grapefruit juice alters the systemic bioavailability and cardiac repolarization of terfenadine in poor metabolizers of terfenadine." J Clin Pharmacol 36 (1996): 345-51
  11. Woosley RL "Cardiac actions of antihistamines." Annu Rev Pharmacol Toxicol 36 (1996): 233-52
  12. Benton RE, Honig PK, Zamani K, Cantilena LR, Woosley RL "Grapefruit juice alters terfenadine pharmacokinetics resulting in prolongation of repolarization on the electrocardiogram." Clin Pharmacol Ther 59 (1996): 383-8
  13. Hsieh MH, Chen SA, Chiang CE, et al. "Drug-induced torsades de pointes in one patient with congenital long QT syndrome." Int J Cardiol 54 (1996): 85-8
  14. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol 42 (1996): p662
  15. Rau SE, Bend JR, Arnold JMO, Tran LT, Spence JD, Bailey DG "Grapefruit juice terfenadine single-dose interaction: Magnitude, mechanism, and relevance." Clin Pharmacol Ther 61 (1997): 401-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  17. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
View all 17 references

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Moderate

pseudoephedrine food

Applies to: Seldane-D (pseudoephedrine / terfenadine)

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res 1 (1979): 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther 11 (1970): 656
  3. "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  4. "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
  5. "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
  6. "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
  7. "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
View all 7 references

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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.

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