Drug Interactions between givinostat and Zoloft
This report displays the potential drug interactions for the following 2 drugs:
- givinostat
- Zoloft (sertraline)
Interactions between your drugs
sertraline givinostat
Applies to: Zoloft (sertraline) and givinostat
GENERALLY AVOID: Givinostat can cause prolongation of the QTc interval. Theoretically, coadministration with other agents that can also prolong the QTc interval may result in additive effects and adverse reactions associated with QT prolongation (e.g., other serious arrhythmias, torsade de pointes, sudden death). The largest mean increase observed in the QTc interval of healthy subjects receiving givinostat at approximately 5 times the dose recommended for Duchenne muscular dystrophy (DMD) in patients weighing 60 kg or more was 13.6 ms (upper confidence interval of 17.1 ms) and occurred 5 hours after dose administration. Clinical trials evaluating the use of givinostat in patients with myeloproliferative neoplasms like polycythemia vera have also documented cases of QTc 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 including, but not limited to, cardiac disease, uncontrolled hypothyroidism, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation may vary depending on the dosage(s) and specific drug(s) involved.
MANAGEMENT: Coadministration of givinostat with other agents that can prolong the QT interval should generally be avoided. The manufacturer of givinostat recommends avoiding its use in patients at an increased risk for ventricular arrhythmias, including those with congenital long QT syndrome, coronary artery disease, and/or electrolyte disturbances. If concurrent administration cannot be avoided, electrocardiograms (ECGs) should be obtained at baseline and during concomitant use as clinically indicated. Givinostat should be withheld if the QTc interval is greater than 500 ms or if there is a change from baseline of greater than 60 ms. The labeling of any other QTc prolonging medication(s) should also be consulted for additional guidance on therapeutic management in the event of QTc prolongation.
References (3)
- (2024) "Product Information. Duvyzat (givinostat)." ITF Therapeutics, LLC
- Chifotides HT, bose p, Verstovsek S (2020) "Givinostat: an emerging treatment for polycythemia vera." Expert Opin Investig Drugs, 29, p. 525-36
- Italfarmaco Spa (2024) Center for drug evaluation and research. Application number: 217865Orig1s000. Integrated review. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/217865Orig1s000IntegratedR.pdf
Drug and food interactions
sertraline food
Applies to: Zoloft (sertraline)
GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of sertraline. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, limited clinical data suggest that consumption of grapefruit juice during treatment with sertraline may result in increased plasma concentrations of sertraline. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit. An in-vitro study demonstrated that grapefruit juice dose-dependently inhibits the conversion of sertraline to its metabolite, desmethylsertraline. In a study with eight Japanese subjects, mean plasma levels of sertraline increased by approximately 100% and maximum plasma concentrations increased by 66% after the ingestion of three 250 mL glasses of grapefruit juice per day for 5 days and administration of a single dose of sertraline 75 mg on the sixth day. In another small study with 5 patients, mean sertraline trough levels increased by 47% after taking sertraline for at least 6 weeks, then taking sertraline with 240 mL grapefruit juice daily for 1 week. The clinical significance is unknown; however, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability. The possibility of significant interaction in some patients should be considered.
MANAGEMENT: Patients receiving sertraline should be 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 sertraline affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Some authorities recommend that consumption of grapefruit juice should be avoided during sertraline therapy.
References (4)
- (2001) "Product Information. Zoloft (sertraline)." Roerig Division
- Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Ueda N, Yoshimura R, Umene-Nakano W, et al. (2009) "Grapefruit juice alters plasma sertraline levels after single ingestion of sertraline in healthy volunteers." World J Biol Psychiatry, 10(4 Pt 3), p. 832-5
givinostat food
Applies to: givinostat
ADJUST DOSING INTERVAL: Food increases the systemic exposure of givinostat. An open-label, randomized, crossover, single dose food effect study conducted in 12 healthy males used givinostat liquid filled capsules. Subjects received a single oral dose of givinostat (100 mg) in the fasting state or after a high-fat standard meal, with a washout period of at least 1 week in between. The high-fat standard meal resulted in an increase in systemic exposure (AUC) and maximum plasma concentration (Cmax) of about 40% and 23%, respectively, when compared to the fasted state. Additionally, the time to maximum concentration (Tmax) was delayed slightly from 2 to 3 hours.
MANAGEMENT: Givinostat should be administered with food to increase its absorption. In the case of the oral suspension, this can also help mask its bitter taste.
References (2)
- (2024) "Product Information. Duvyzat (givinostat)." ITF Therapeutics, LLC
- Italfarmaco Spa (2024) Center for drug evaluation and research. Application number: 217865Orig1s000. Integrated review. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/217865Orig1s000IntegratedR.pdf
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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