Duvyzat® Q & A
Adverse event reporting information can be found at the bottom of this page.
Click HERE for prescribing information.
Below are a list of frequently asked questions and answers. Click on the green arrows and plus symbols to expand the content and view the answers. If you have further questions, please email UK.Medical.Information@italfarmacogroup.com
About Italfarmaco / ITF Pharma UK
Who is ITALFARMACO?
Who is ITF Pharma UK?
ITF Pharma UK is a specialised pharmaceutical company with a focus on pioneering treatments for rare diseases. We are part of the Italian-based ITALFARMACO group. Please visit our website to find out more: https://itfpharma.co.uk/
Duvyzat® dosage and storage
How is Duvyzat® stored?
What if a dose of Duvyzat® is missed?
Duvyzat® approval status
Is Duvyzat® licensed in the UK?
Why is Duvyzat® a black triangle product?
A black triangle, given by the UK regulatory the MHRA, adjacent to a medicine in the UK signifies that it is subject to additional monitoring, which allows quick identification of adverse events or safety information. When a medicine comes onto the market, we may have limited information about their safety from clinical trials, as clinical trials are not always reflective of the real world setting. Therefore, new medicines are intensively monitored to ensure that any new safety signals are identified promptly. For more information, please see the MHRA website: https://www.gov.uk/drug-safety-update/the-black-triangle-scheme-or
Clinical benefits of Duvyzat®
Is Duvyzat® restricted to patients with certain genotypes/mutations?
Can Duvyzat® be used in combination with corticosteroids and if so, which corticosteroids? Can it be used with vamorolone?
Clinical studies with Duvyzat® were conducted in boys already on stable corticosteroid treatment (for at least 6 months). All available corticosteroids were allowed as well as different regimens (daily, intermittent). In the pivotal study, EPIDYS, boys were randomised 2:1 to receive either Duvyzat® oral suspension BID after a meal, in combination with established clinical management, including standard CS therapy; or matching placebo oral suspension in combination with established clinical management, including standard CS therapy. Deflazacort was the most common available corticosteroid at the time and most boys in both groups received corticosteroids daily.
It would be at the discretion and responsibility of the prescribing physician to give a patient corticosteroids during treatment with Duvyzat®.
Can Duvyzat® be used in a patient who has been taking other medications?
Avoid concomitant use of Duvyzat® with other product(s) with a known potential to prolong the QTc interval. If concomitant use cannot be avoided, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Withhold Duvyzat® if the QTc interval is > 500 ms or the change from baseline is > 60 ms.
Duvyzat® can cause QTc interval prolongation. Caution is advised when prescribing Duvyzat® with medicinal products known to prolong the QTc interval with known or possible risk for torsades de pointes, e.g. anaesthetics (e.g. sevoflurane, propofol), class III antiarrhythmics (e.g. amiodarone, sotalol), antiemetics (ondansetron), antibiotics (fluconazole, azithromycin, clarithromycin, ciprofloxacin), antipsychotics (aripiprazole, risperidone), and antihistamines (e.g. famotidine).
This list is indicative and not exhaustive.
In Vitro
Duvyzat® is not a substrate of cytochrome P450 (CYP450) enzymes and uridine diphosphate glucuronosyltransferase (UGT). Therefore, coadministration of drugs that are inducers or inhibitors of major metabolizing enzymes will not significantly affect the systemic exposure of Duvyzat®.
Duvyzat® and its metabolites ITF2374, ITF2375, ITF2440, and ITF2563 were investigated as inhibitors of the main CYP450 subfamilies, and the results indicated no inhibition is expected of CYP1A2, 2C9, 2C19, 2D6, 2B6, 2C8, and 3A4. Duvyzat® showed induction of CYP1A2, 2B6, and CYP3A4.
In vitro studies indicate that Duvyzat® is a substrate of the intestinal transporters: P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Duvyzat® showed the potential to inhibit the intestinal transporter P-gp (MDR1) and BCRP based on in vitro results. However, these interactions are not expected to be clinically meaningful.
In Vivo
A weak inhibition of the renal uptake transporter OCT2 by Duvyzat® was seen in clinical trials by creatinine (OCT2 substate) measurements.
A clinical drug interaction study was conducted in healthy volunteers to assess the effects of coadministration of Duvyzat® with other drugs and results indicated that:
- Duvyzat® has a weak inhibition of the intestinal CYP3A4 enzyme based on the exposure of a CYP3A4 substrate, midazolam.
- Duvyzat® does not likely inhibit P-gp transporters based on the exposure of dabigatran.
- Strong P-gp inhibitors have a weak effect on givinostat based on exposure of clarithromycin, which had an increase in Cmax by about 40% without a significant change of AUC.
The effect of BCRP inhibitors on Duvyzat® PK was not studied in a clinical study. However, the effect of BCRP inhibitors on Duvyzat® PK is expected to be smaller than P-gp inhibitors based on the comparison of the two transporters mediated efflux ratios determined in the in vitro cell models.
Will my patient still be able to receive Duvyzat® when they turn 18 years old?
Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store.
Adverse events should also be reported to ITF Pharma Ltd Medical Information on: 0800 098 4040 or UK.Medical.Information@italfarmacogroup.com
Product Quality Complaints should also be reported to ITF Pharma Ltd Medical Information on: 0800 098 4040 or UK.Medical.Information@italfarmacogroup.com
References
- Duvyzat Summary of Product Characteristics, MHRA, https://www.medicines.org.uk/emc/product/100605/smpc
