Versed injection and Zykadia

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer information for this interaction is not currently available.CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations and pharmacologic effects of orally administered midazolam and triazolam, which undergo intestinal (first-pass) and hepatic metabolism by the isoenzyme. Up to 3-fold increases in peak plasma concentration (Cmax) and 5- to 10-fold increases in systemic exposure (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 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 Backman JT, Kivisto KT, Olkkola KT, Neuvonen PJ "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 (1998): 53-8 Michalets EL "Update: clinically significant cytochrome P-450 drug interactions." Pharmacotherapy 18 (1998): 84-112 Wrighton SA, Ring BJ "Inhibition of human CYP3A catalyzed 1'-hydroxy midazolam formation by ketoconazole, nifedipine, erythromycin, cimetidine, and nizatidine." Pharm Res 11 (1994): 921-4 Tsunoda SM, Velez RL, vonMoltke LL, Greenblatt DJ "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 (1999): 461-71 Ahonen J, Olkkola KT, Neuvonen PJ "Effect of itraconazole and terbinafine on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers." Br J Clin Pharmacol 40 (1995): 270-2 Greenblatt DJ, von Moltke LL, Harmatz JS, et al. "Differential impairment of triazolam and zolpidem clearance by ritonavir." J Acquir Immune Defic Syndr 24 (2000): 129-36 "Product Information. Halcion (triazolam)." Pharmacia and Upjohn, Kalamazoo, MI. Vonmoltke LL, Greenblatt DJ, Schmider J, Duan SX, Wright CE, Harmatz JS, Shader RI "Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents." J Clin Pharmacol 36 (1996): 783-91 Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57 Brown MW, Maldonado AL, Meredith CG, Speeg KV "Effect of ketoconazole on hepatic oxidative drug metabolism." Clin Pharmacol Ther 37 (1985): 290-7 Decker CJ, Laitinen LM, Bridson GW, Raybuck SA, Tung RD, Chaturvedi PR "Metabolism of amprenavir in liver microsomes: role of CYP3A4 inhibition for drug interactions." J Pharm Sci 87 (1998): 803-7 Palkama VJ, Ahonen J, Neuvonen PJ, Olkkola KT "Effect of saquinavir on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam." Clin Pharmacol Ther 66 (1999): 33-9 Merry C, Mulcahy F, Barry M, Gibbons S, Back D "Saquinavir interaction with midazolam: pharmacokinetic considerations when prescribing protease inhibitors for patients with HIV disease." AIDS 11 (1997): 268-9 Varhe A, Olkkola KT, Neuvonen PJ "Fluconazole, but not terbinafine, enhances the effects of triazolam by inhibiting its metabolism." Br J Clin Pharmacol 41 (1996): 319-23 Malaty LI, Kuper JJ "Drug interactions of HIV protease inhibitors." Drug Safety 20 (1999): 147-69 Greenblatt DJ, Wright CE, vonMoltke LL, Harmatz JS, Ehrenberg BL, Harrel LM, Corbett K, Counihan M, Tobias S, Shader RI "Ketoconazole inhibition of triazolam and alprazolam clearance: Differential kinetic and dynamic consequences." Clin Pharmacol Ther 64 (1998): 237-47 Neuvonen PJ, Varhe A, Olkkola KT "The effect of ingestion time interval on the interaction between itraconazole and triazolam." Clin Pharmacol Ther 60 (1996): 326-31 "Product Information. Versed (midazolam)." Roche Laboratories, Nutley, NJ. Olkkola KT, Backman JT, Neuvonen PJ "Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole." Clin Pharmacol Ther 55 (1994): 481-5 Eagling VA, Back DJ, Barry MG "Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir." Br J Clin Pharmacol 44 (1997): 190-4 Varhe A, Olkkola KT, Neuvonen PJ "Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole." Clin Pharmacol Ther 56 (1994): 601-7 Greenblatt DJ, Vonmoltke LL, Harmatz JS, Harrel LM, Tobias S, Shader RI, Wright CE "Interaction of triazolam and ketoconazole." Lancet 345 (1995): 191 Barry M, Mulcahy F, Merry C, Gibbons S, Back D "Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection." Clin Pharmacokinet 36 (1999): 289-304 View all 23 references

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations and pharmacologic effects of orally administered midazolam and triazolam, which undergo intestinal (first-pass) and hepatic metabolism by the isoenzyme. Up to 3-fold increases in peak plasma concentration (Cmax) and 5- to 10-fold increases in systemic exposure (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 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.

Versed injection

Generic Name: midazolam

Brand name: Versed, Nayzilam

Synonyms: Versed

What is Versed injection?

Zykadia

Generic Name: ceritinib

Brand name: Zykadia

Synonyms: n.a.

What is Zykadia?