Janssen Dear Doctor letter: Prezista (darunavir), Rezolsta ▼(darunavir/cobicistat)and Symtuza ▼(darunavir/cobicistat/emtricitabine/tenofovir alafenamide)
Direct Healthcare Professional Communication:
Darunavir/cobicistat: Increased risk of treatment failure and increased risk of mother-to-child transmission of HIV infection when darunavir and cobicistat co-administered, due to low exposure values during the second and third trimesters of pregnancy.
Dear Healthcare Professional
Janssen in agreement with the European Medicines Agency (EMA) and the Medicines and Healthcare products Regulatory Agency (MHRA) would like to inform you of the following:
- Therapy with darunavir/cobicistat should not be initiated during pregnancy.
- Women who become pregnant during therapy with darunavir/cobicistat should be switched to an alternative regimen: darunavir/ritonavir may be considered as an alternative.
- This is because pharmacokinetic data showed low exposure values of darunavir and cobicistat during the second and third trimesters of pregnancy.
- Low darunavir exposure may be associated with an increased risk of treatment failure and an increased risk of mother-to-child transmission of HIV infection.
The pharmacokinetic data from the Phase 3b study TMC114HIV3015 in 6 pregnant women demonstrated that the mean exposure (AUC) of darunavir boosted with cobicistat was 56% and 50% lower during the second and third trimesters of pregnancy, respectively, compared with 6 to 12 weeks postpartum. Mean darunavir Cmin concentrations were around 90% lower during the second and third trimesters of pregnancy as compared to postpartum.
Exposure of cobicistat was 63% and 49% lower during the second and third trimesters of pregnancy, respectively, as compared to postpartum.
- Low darunavir exposure may be associated with an increased risk of treatment failure and an increased risk of HIV-1 transmission to the child. Therefore, therapy with darunavir/cobicistat should not be initiated during pregnancy and women who become pregnant during therapy with darunavir/cobicistat should be switched to an alternative regimen.
Based upon this information, the product information for PREZISTA (darunavir), REZOLSTA (darunavir and cobicistat) and SYMTUZA (darunavir, cobicistat, emtricitabine, tenofovir alafenamide), will be updated, as recommended by the European Medicines Agency (EMA).
Call for reporting
▼This medicinal product is subject to additional monitoring to support risk management and it is therefore important to report any suspected adverse events.
Please continue to report suspected adverse reactions with any medicine or vaccine to the MHRA through the Yellow Card Scheme.
It is easiest and quickest to report adverse drug reactions online via the Yellow Card website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Alternatively, prepaid Yellow Cards for reporting are available by:
- Write to: FREEPOST YELLOW CARD (no other address details necessary)
- Emai: firstname.lastname@example.org
- See the form at the back of the British National Formulary (BNF).
- Telephone the Commission on Human Medicines (CHM) free phone line: 0800 731 6789,
- Download and print a form from the Yellow Card section of the MHRA website.
When reporting please provide as much information as possible, including information about medical history, any concomitant medication, onset, treatment dates, product brand name and batch numbers.
Suspected adverse reactions should also be reported to Janssen-Cilag Limited on telephone: 01494 567447, fax: 01494 567799 or by email at email@example.com.
Company contact points
If you have further questions or require additional information, please contact: Janssen- Cilag Ltd. Medical Information Department: email: firstname.lastname@example.org, telephone: 0800 731 8450 or 01494 567 444.
Janssen, UK & Ireland, 50–100 Holmers Farm Way,
High Wycombe, Buckinghamshire, HP12 4EG. Telephone: (01494) 567567.