Skip to main content

Drug Interactions between Niravam and tucatinib

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

ALPRAZolam tucatinib

Applies to: Niravam (alprazolam) and tucatinib

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations and pharmacologic effects of orally administered alprazolam, midazolam and triazolam, which undergo intestinal (first-pass) and hepatic metabolism by the isoenzyme. Itraconazole and ketoconazole have been reported to increase the systemic exposure (AUC) of alprazolam by 2.7- and 4-fold, respectively, compared to placebo. Up to 3-fold increases in peak plasma concentration (Cmax) and 5- to 10-fold increases in AUC have been reported for oral midazolam during coadministration with potent CYP450 3A4 inhibitors like ritonavir, boceprevir, telaprevir, itraconazole, and ketoconazole. Similarly, up to 3-fold increases in Cmax and 14- to 22-fold increases in AUC have been observed for triazolam during coadministration with these agents. The interaction also occurs with intravenous midazolam, but to a lesser extent, with increases of 2.5- to 5-fold in AUC reported.

MANAGEMENT: Given the potential for prolonged and/or increased sedation and respiratory depression associated with excessive benzodiazepine blood levels, concomitant use of alprazolam, oral midazolam or triazolam with potent CYP450 3A4 inhibitors is considered contraindicated. Caution and close clinical monitoring are recommended when administering parenteral midazolam in combination with these agents. Appropriate medical management should be readily available in case of respiratory depression and/or prolonged sedation. Dosage adjustment for midazolam may be appropriate, especially if more than a single dose of midazolam is administered.

References

  1. Brown MW, Maldonado AL, Meredith CG, Speeg KV (1985) "Effect of ketoconazole on hepatic oxidative drug metabolism." Clin Pharmacol Ther, 37, p. 290-7
  2. (2002) "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn
  3. (2001) "Product Information. Halcion (triazolam)." Pharmacia and Upjohn
  4. Olkkola KT, Backman JT, Neuvonen PJ (1994) "Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole." Clin Pharmacol Ther, 55, p. 481-5
  5. (2001) "Product Information. Versed (midazolam)." Roche Laboratories
  6. Wrighton SA, Ring BJ (1994) "Inhibition of human CYP3A catalyzed 1'-hydroxy midazolam formation by ketoconazole, nifedipine, erythromycin, cimetidine, and nizatidine." Pharm Res, 11, p. 921-4
  7. Varhe A, Olkkola KT, Neuvonen PJ (1994) "Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole." Clin Pharmacol Ther, 56, p. 601-7
  8. Greenblatt DJ, Vonmoltke LL, Harmatz JS, Harrel LM, Tobias S, Shader RI, Wright CE (1995) "Interaction of triazolam and ketoconazole." Lancet, 345, p. 191
  9. Ahonen J, Olkkola KT, Neuvonen PJ (1995) "Effect of itraconazole and terbinafine on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers." Br J Clin Pharmacol, 40, p. 270-2
  10. Varhe A, Olkkola KT, Neuvonen PJ (1996) "Fluconazole, but not terbinafine, enhances the effects of triazolam by inhibiting its metabolism." Br J Clin Pharmacol, 41, p. 319-23
  11. Neuvonen PJ, Varhe A, Olkkola KT (1996) "The effect of ingestion time interval on the interaction between itraconazole and triazolam." Clin Pharmacol Ther, 60, p. 326-31
  12. Vonmoltke LL, Greenblatt DJ, Schmider J, Duan SX, Wright CE, Harmatz JS, Shader RI (1996) "Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents." J Clin Pharmacol, 36, p. 783-91
  13. Merry C, Mulcahy F, Barry M, Gibbons S, Back D (1997) "Saquinavir interaction with midazolam: pharmacokinetic considerations when prescribing protease inhibitors for patients with HIV disease." AIDS, 11, p. 268-9
  14. Eagling VA, Back DJ, Barry MG (1997) "Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir." Br J Clin Pharmacol, 44, p. 190-4
  15. Michalets EL (1998) "Update: clinically significant cytochrome P-450 drug interactions." Pharmacotherapy, 18, p. 84-112
  16. Backman JT, Kivisto KT, Olkkola KT, Neuvonen PJ (1998) "The area under the plasma concentration-time curve for oral midazolam is 400-fold larger during treatment with itraconazole than with rifampicin." Eur J Clin Pharmacol, 54, p. 53-8
  17. Greenblatt DJ, Wright CE, vonMoltke LL, Harmatz JS, Ehrenberg BL, Harrel LM, Corbett K, Counihan M, Tobias S, Shader RI (1998) "Ketoconazole inhibition of triazolam and alprazolam clearance: Differential kinetic and dynamic consequences." Clin Pharmacol Ther, 64, p. 237-47
  18. Malaty LI, Kuper JJ (1999) "Drug interactions of HIV protease inhibitors." Drug Safety, 20, p. 147-69
  19. Decker CJ, Laitinen LM, Bridson GW, Raybuck SA, Tung RD, Chaturvedi PR (1998) "Metabolism of amprenavir in liver microsomes: role of CYP3A4 inhibition for drug interactions." J Pharm Sci, 87, p. 803-7
  20. Barry M, Mulcahy F, Merry C, Gibbons S, Back D (1999) "Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection." Clin Pharmacokinet, 36, p. 289-304
  21. Palkama VJ, Ahonen J, Neuvonen PJ, Olkkola KT (1999) "Effect of saquinavir on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam." Clin Pharmacol Ther, 66, p. 33-9
  22. Tsunoda SM, Velez RL, vonMoltke LL, Greenblatt DJ (1999) "Differentiation of intestinal and hepatic cytochrome P450 3A activity with use of midazolam as an in vivo probe: Effect of ketoconazole." Clin Pharmacol Ther, 66, p. 461-71
  23. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  24. Greenblatt DJ, von Moltke LL, Harmatz JS, et al. (2000) "Differential impairment of triazolam and zolpidem clearance by ritonavir." J Acquir Immune Defic Syndr, 24, p. 129-36
View all 24 references

Switch to consumer interaction data

Drug and food interactions

Moderate

ALPRAZolam food

Applies to: Niravam (alprazolam)

GENERALLY AVOID: The pharmacologic activity of oral midazolam, triazolam, and alprazolam may be increased if taken after drinking grapefruit juice. The proposed mechanism is CYP450 3A4 enzyme inhibition. In addition, acute alcohol ingestion may potentiate CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: The manufacturer recommends that grapefruit juice should not be taken with oral midazolam. Patients taking triazolam or alprazolam should be monitored for excessive sedation. Alternatively, the patient could consume orange juice which does not interact with these drugs. Patients should be advised to avoid alcohol during benzodiazepine therapy.

References

  1. (2002) "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn
  2. (2002) "Product Information. Valium (diazepam)." Roche Laboratories
  3. (2001) "Product Information. Halcion (triazolam)." Pharmacia and Upjohn
  4. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  5. Kupferschmidt HHT, Ha HR, Ziegler WH, Meier PJ, Krahenbuhl S (1995) "Interaction between grapefruit juice and midazolam in humans." Clin Pharmacol Ther, 58, p. 20-8
  6. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  7. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
View all 7 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