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Darunavir Tablets and Quiphile

Determining the interaction of Darunavir Tablets and Quiphile and the possibility of their joint administration.

Check result:

Darunavir Tablets <> Quiphile

Relevance: 17.05.2023 Reviewer: Shkutko P.M., M.D., in

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:

Darunavir may increase the blood levels and effects of quiNINE. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Let your doctor know if you experience increased side effects of quiNINE such as headache, flushing, sweating, nausea, vomiting, diarrhea, abdominal pain, dizziness, ringing in the ears, hearing impairment, blurred vision, vision impairment, and irregular heart rhythm. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of quinine, which is primarily metabolized by the isoenzyme. In ten healthy volunteers, administration of a single 600 mg oral dose of quinine sulfate in combination with the potent CYP450 3A4 inhibitor troleandomycin (500 mg orally every 8 hours for 48 hours) significantly increased the mean quinine peak plasma concentration (Cmax), systemic exposure (AUC) and terminal elimination half-life by 26%, 90% and 63%, respectively, and decreased the mean oral clearance (Cl/F) by 45% compared to administration of quinine alone. Troleandomycin also reduced the average Cmax, AUC and apparent formation clearance of the main metabolite, 3-hydroxyquinine, by 75%, 58% and 81%, respectively. Likewise, in a study of nine healthy volunteers, administration of a single 500 mg oral dose of quinine hydrochloride in combination with another potent CYP450 3A4 inhibitor ketoconazole (100 mg twice daily for 3 days) resulted in a 45% increase in mean quinine AUC and a 31% decrease in mean oral clearance compared to administration of quinine alone. Clinically, high plasma levels of quinine may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death. Fatal torsade de pointes arrhythmia was reported in an elderly patient who received quinine in combination with erythromycin, a moderately potent CYP450 3A4 inhibitor, and dopamine. However, a causal relationship was not established in this case. The risk of other quinine toxicities such as cinchonism may also be increased.

MANAGEMENT: Caution is advised if quinine is used in combination with potent and moderate CYP450 3A4 inhibitors. Patients should be monitored closely for adverse reactions associated with quinine such as hematologic toxicities and cardiac arrhythmias including torsade de pointes and atrial fibrillation. Patients should be advised to contact their physician if they experience increased side effects such as headache, flushing, sweating, nausea, vomiting, diarrhea, abdominal pain, tinnitus, dizziness, vertigo, hearing impairment, blurred vision, vision impairment, and irregular heart rhythm.

References

Mirghani RA, Yasar U, Zheng T, et al "Enzyme kinetics for the formation of 3-hydroxyquinine and three new metabolites of quinine in vitro; 3-hydroxylation by CYP3A4 is indeed the major metabolic pathway." Drug Metab Dispos 30 (2002): 1368-71
Cerner Multum, Inc. "Australian Product Information." O 0
Mirghani RA, Hellgren U, Westerberg PA, Ericsson O, Bertilsson L, Gustafsson LL "The roles of cytochrome P450 3A4 and 1A2 in the 3-hydroxylation of quinine in vivo." Clin Pharmacol Ther 66 (1999): 454-60
Wanwimolruk S, Paine MF, Pusek SN, Watkins PB "Is quinine a suitable probe to assess the hepatic drug-metabolizing enzyme CYP3A4?" Br J Clin Pharmacol 54 (2002): 643-51
Zhang H, Coville PF, Walker RJ, Miners JO, Birkett DJ, Wanwimolruk S "Evidence for involvement of human CYP3A in the 3-hydroxylation of quinine." Br J Clin Pharmacol 43 (1997): 245-52
Mirghani RA, Ericsson O, Tybring G, Gustafsson LL, Bertilsson L "Quinine 3-hydroxylation as a biomarker reaction for the activity of CYP3A4 in man." Eur J Clin Pharmacol 59 (2003): 23-8
Zhao XJ, Ishizaki T "A further interaction study of quinine with clinically important drugs by human liver microsomes: determinations of inhibition constant (K-i) and type of inhibition." Eur J Drug Metab Pharm 24 (1999): 272-8
Mirghani RA, Hellgren U, Bertilsson L, Gustafsson LL, Ericsson O "Metabolism and elimination of quinine in healthy volunteers." Eur J Clin Pharmacol (2003):
Zhao XJ, Ishizaki T "Metabolic interactions of selected antimalarial and non-antimalarial drugs with the major pathway (3-hydroxylation) of quinine in human liver microsomes." Br J Clin Pharmacol 44 (1997): 505-11
Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
"Product Information. Qualaquin (quinine)." AR Scientific Inc, Philadelphia, PA.

Darunavir Tablets

Generic Name: darunavir

Brand name: Prezista

Synonyms: Darunavir

What is Darunavir Tablets?

Quiphile

Generic Name: quinine

Brand name: Qualaquin, QM-260, Quinamm

Synonyms: Quinine, QuiNINE

What is Quiphile?

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In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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