Merck Sharp and Dohme LLC. has received initial U.S. Approval: 2017 PREVYMIS™ (letermovir) injection, for intravenous use.
In the first Full Prescribing Information issued in November 2017, safety data about hydroxypropyl betadex (HPBCD) was less emphasized and were scattered throughout the document. Here is the cumulated content:
PREVYMIS injection, which contains hydroxypropyl betadex, should be used only in patients unable to take
oral therapy. In patients with CLcr less than 50 mL/min receiving PREVYMIS injection, accumulation of the
intravenous vehicle, hydroxypropyl betadex, may occur. Closely monitor serum creatinine levels in
these patients. Hydroxypropyl betadex present in the intravenous letermovir formulation is mainly eliminated by glomerular filtration. Decreased elimination of hydroxypropyl betadex has been reported in the literature in patients with severe renal impairment.
In the newest issue of the leaflet (August 2024), these instructions were cumulated under section 5.2 (Warnings and Precautions) and were supplemented with the following additional information:
- If possible, intravenous administration should not exceed 4 weeks
- Close monitoring of serum creatinine is also advised for pediatric patients with a similar degree of renal impairment (based on age appropriate assessment of renal function)
- Animal studies have shown the potential for hydroxypropyl betadex to cause ototoxicity
Merck Sharp and Dohme LLC. had a postmarketing commitment to conduct a study to determine the pharmacokinetics and safety of letermovir in kidney transplant recipients less than 18 years of age and
weighing less than 40 kg. Draft protocol submission is due in 02/2025, while final report submission is expected in 01/2029.
Hopefully, further post-marketing studies will be designed so that the results might shed light on how justifiable the new 5.2 section statements are. An analogue procedure on the example of Veklury containing SBECD has been discussed on our blog earlier:
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209939orig1s000,209940orig1s000lbl.pdf
https://www.merck.com/product/usa/pi_circulars/p/prevymis/prevymis_pi.pdf