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Drug Interactions between givinostat and Nolvadex

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

tamoxifen givinostat

Applies to: Nolvadex (tamoxifen) 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)
  1. (2024) "Product Information. Duvyzat (givinostat)." ITF Therapeutics, LLC
  2. Chifotides HT, bose p, Verstovsek S (2020) "Givinostat: an emerging treatment for polycythemia vera." Expert Opin Investig Drugs, 29, p. 525-36
  3. 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

Moderate

tamoxifen food

Applies to: Nolvadex (tamoxifen)

GENERALLY AVOID: Due to their estrogenic effect, isoflavones present in soy such as genistein and daidzein may stimulate breast tumor growth and antagonize the antiproliferative action of tamoxifen. Supportive data are derived primarily from in vitro and animal studies. In vitro, low concentrations of these phytoestrogens have been found to promote DNA synthesis and reverse the inhibitory effect of tamoxifen on estrogen-dependent breast cancer cell proliferation. In contrast, high concentrations of genistein greater than 10 microM/L have been found to enhance tamoxifen effects by inhibiting breast cancer cell growth. It is not known if these high concentrations are normally achieved in humans. Plasma concentrations below 4 microM/L have been observed in healthy volunteers given a soy diet for one month or large single doses of genistein. These concentrations are comparable to the low plasma concentrations associated with tumor stimulation reported in animals. In a study of 155 female breast cancer survivors with substantially bothersome hot flashes, a product containing 50 mg of soy isoflavones (40% to 45% genistein; 40% to 45% daidzein; 10% to 20% glycitein) taken three times a day was found to be no more effective than placebo in reducing hot flashes. No toxicity or recurrence of breast cancer was reported during the 9-week study period.

Green tea does not appear to have significant effects on the pharmacokinetics of tamoxifen or its primary active metabolite, endoxifen. In a study consisting of 14 patients who have been receiving tamoxifen treatment at a stable dose of 20 mg (n=13) or 40 mg (n=1) once daily for at least 3 months, coadministration with green tea supplements twice daily for 14 days resulted in no significant differences in the pharmacokinetics of either tamoxifen or endoxifen with respect to peak plasma concentration (Cmax), systemic exposure (AUC), and trough plasma concentration (Cmin) compared to administration of tamoxifen alone. The combination was well tolerated, with all reported adverse events categorized as mild (grade 1) and none categorized as serious or severe (grade 3 or higher) during the entire study. Although some adverse events such as headache, polyuria, gastrointestinal side effects (e.g., constipation, dyspepsia), and minor liver biochemical disturbances were reported more often during concomitant treatment with green tea, most can be attributed to the high dose of green tea used or to the caffeine in green tea. The green tea supplements used were 1000 mg in strength and contained 150 mg of epigallocatechin-3-gallate (EGCG), the most abundant and biologically active catechin in green tea. According to the investigators, the total daily dose of EGCG taken by study participants is equivalent to the amount contained in approximately 5 to 6 cups of regular green tea. However, it is not known to what extent the data from this study may be applicable to other preparations of green tea such as infusions, since the bioavailability of EGCG and other catechins may vary between preparations.

MANAGEMENT: Until more information is available, patients treated with tamoxifen may consider avoiding or limiting the consumption of soy-containing products. Consumption of green tea and green tea extracts during tamoxifen therapy appears to be safe.

References (2)
  1. Therapeutic Research Faculty (2008) Natural Medicines Comprehensive Database. http://www.naturaldatabase.com
  2. Braal CL, Hussaarts KGAM, Seuren L, et al. (2020) "Influence of green tea consumption on endoxifen steady-state concentration in breast cancer patients treated with tamoxifen." Breast Cancer Res Treat, 184, p. 107-13
Moderate

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)
  1. (2024) "Product Information. Duvyzat (givinostat)." ITF Therapeutics, LLC
  2. 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.


Report options

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.