Drug Interactions between clofazimine and Qualaquin
This report displays the potential drug interactions for the following 2 drugs:
- clofazimine
- Qualaquin (quinine)
Interactions between your drugs
quiNINE clofazimine
Applies to: Qualaquin (quinine) and clofazimine
Consumer information for this interaction is not currently available.
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
- Zhao XJ, Ishizaki T (1997) "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, p. 505-11
- Mirghani RA, Hellgren U, Westerberg PA, Ericsson O, Bertilsson L, Gustafsson LL (1999) "The roles of cytochrome P450 3A4 and 1A2 in the 3-hydroxylation of quinine in vivo." Clin Pharmacol Ther, 66, p. 454-60
- Zhao XJ, Ishizaki T (1999) "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, p. 272-8
- Wanwimolruk S, Paine MF, Pusek SN, Watkins PB (2002) "Is quinine a suitable probe to assess the hepatic drug-metabolizing enzyme CYP3A4?" Br J Clin Pharmacol, 54, p. 643-51
- Mirghani RA, Ericsson O, Tybring G, Gustafsson LL, Bertilsson L (2003) "Quinine 3-hydroxylation as a biomarker reaction for the activity of CYP3A4 in man." Eur J Clin Pharmacol, 59, p. 23-8
- Mirghani RA, Hellgren U, Bertilsson L, Gustafsson LL, Ericsson O (2003) "Metabolism and elimination of quinine in healthy volunteers." Eur J Clin Pharmacol
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2006) "Product Information. Qualaquin (quinine)." AR Scientific Inc
- Cerner Multum, Inc. "Australian Product Information."
- Zhang H, Coville PF, Walker RJ, Miners JO, Birkett DJ, Wanwimolruk S (1997) "Evidence for involvement of human CYP3A in the 3-hydroxylation of quinine." Br J Clin Pharmacol, 43, p. 245-52
- Mirghani RA, Yasar U, Zheng T, et al. (2002) "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, p. 1368-71
Drug and food interactions
quiNINE food
Applies to: Qualaquin (quinine)
Information for this minor interaction is available on the professional version.
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
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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