Drug Interactions between fexinidazole and hydroxyzine
This report displays the potential drug interactions for the following 2 drugs:
- fexinidazole
- hydroxyzine
Interactions between your drugs
hydrOXYzine fexinidazole
Applies to: hydroxyzine and fexinidazole
GENERALLY AVOID: Fexinidazole can cause concentration-dependent prolongation of the QT interval. Coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. Based on the exposure-response relationship, treatment with fexinidazole is predicted to cause an average increase of 19 msec in the Fridericia-corrected QT interval (QTcF) at the recommended dosing regimen. In addition, drugs that are inducers of hepatic CYP450 enzymes, such as apalutamide and enzalutamide, may significantly increase the plasma concentration of fexinidazole's active metabolites, fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2). The observed increase in QTcF appears to be associated with the sulfone (M2) metabolite of fexinidazole; therefore, an increase in the plasma concentration of the sulfone (M2) metabolite may increase the risk of QT prolongation. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).
MANAGEMENT: The concurrent use of fexinidazole with other medications that can prolong the QT interval, block cardiac potassium channels, and/or induce bradycardia should generally be avoided. If coadministration is unavoidable, treatment with fexinidazole should not be initiated until the opposing drug is eliminated from the body (allow a washout period of 5 half-lives) or do not initiate treatment with the opposing drug until fexinidazole is eliminated from the body (allow a washout period of 7 days). All QT-prolonging drugs including fexinidazole should be interrupted in patients who develop clinically significant ventricular arrhythmia or a QTcF interval greater than 500 msec confirmed by repeat ECG. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitations, irregular heartbeat, shortness of breath, or syncope.
References
- (2021) "Product Information. Fexinidazole (fexinidazole)." sanofi-aventis
Drug and food interactions
hydrOXYzine food
Applies to: hydroxyzine
GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
References
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
fexinidazole food
Applies to: fexinidazole
GENERALLY AVOID: Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients. There have been a few case reports involving metronidazole, although data overall are not convincing. The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by metronidazole in a manner similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. However, some investigators have questioned the disulfiram-like properties of metronidazole. One study found neither elevations in blood acetaldehyde nor objective or subjective signs of a disulfiram-like reaction to ethanol in six subjects treated with metronidazole (200 mg three times a day for 5 days) compared to six subjects who received placebo.
GENERALLY AVOID: The potential exists for pharmacodynamic interactions and/or toxicities between fexinidazole and herbal medicines and supplements. In addition, grapefruit and grapefruit juice may, theoretically, increase the plasma concentrations of fexinidazole and the risk of adverse effects. The mechanism is decreased clearance of fexinidazole due to inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
ADJUST DOSING INTERVAL: Food significantly increases the oral absorption and bioavailability of fexinidazole. Compared with the fasted state, the systemic exposure (AUC) of fexinidazole and its metabolites (fexinidazole sulfoxide [M1], fexinidazole sulfone [M2]) were 4- to 5-fold higher following administration with food.
MANAGEMENT: To ensure maximal oral absorption, fexinidazole should be administered with food each day at about the same time of day (e.g., during or immediately after the main meal of the day). Coadministration of fexinidazole with grapefruit, grapefruit juice, or herbal medicines or supplements should be avoided. Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction and instructed to avoid alcoholic beverages and products containing alcohol or propylene glycol while using oral, intravenous, or vaginal preparations of a nitroimidazole. Alcoholic beverages should not be consumed for at least 48 hours after completion of fexinidazole therapy.
References
- Giannini AJ, DeFrance DT (1983) "Metronidazole and alcohol: potential for combinative abuse." J Toxicol Clin Toxicol, 20, p. 509-15
- Alexander I (1985) "Alcohol-antabuse syndrome in patients receiving metronidazole during gynaecological treatment." Br J Clin Pract, 39, p. 292-3
- Harries DP, Teale KF, Sunderland G (1990) "Metronidazole and alcohol: potential problems." Scott Med J, 35, p. 179-80
- Edwards DL, Fink PC, Van Dyke PO (1986) "Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole." Clin Pharm, 5, p. 999-1000
- (2002) "Product Information. Flagyl (metronidazole)." Searle
- Williams CS, Woodcock KR (2000) "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother, 34, p. 255-7
- Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP (2002) "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother, 36, p. 971-4
- Krulewitch CJ (2003) "An unexpected adverse drug effect." J Midwifery Womens Health, 48, p. 67-8
- (2004) "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc
- (2021) "Product Information. Fexinidazole (fexinidazole)." sanofi-aventis
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
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