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Drug Warning: Once-daily Triple NRTI Regimen containing Didanosine, Lamivudine, and Tenofovir
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Accession Number
A00685
Author
US Department of Health and Human Services (HHS), Food and Drug Administration (FDA)
Source
FDA Press Release
Release Date
October 14, 2003
Major Descriptors
Clinical trial results
Didanosine (ddI)
Drug interactions
FDA
Lamivudine (3TC)
Safety
Topic
Drugs and Treatment
Text
IMPORTANT DRUG WARNING
RE: High Rate of Virologic Failure in Patients with HIV Infection Treated With a Once-
Daily Triple NRTI Regimen containing Didanosine, Lamivudine, and Tenofovir
Dear Health Care Professional,
Gilead Sciences, Inc (Gilead) is writing to inform you of a high rate of early virologic failure and
emergence of nucleoside reverse transcriptase inhibitor (NRTI) resistance associated mutations
observed in a clinical study of HIV-infected treatment-naïve patients receiving a once-daily triple
NRTI regimen containing didanosine enteric coated beadlets (Videx EC, Bristol-Myers
Squibb), lamivudine (Epivir, GlaxoSmithKline), and tenofovir disoproxil fumarate (Viread,
Gilead).
These new data are consistent with the high rates of virologic failure observed in several recent
clinical studies that have evaluated the use of triple NRTI regimens. Based on these results:
· Tenofovir DF in combination with didanosine and lamivudine is not recommended when
considering a new treatment regimen for therapy-naïve or experienced patients with HIVinfection.
Patients currently on this regimen should be considered for treatment
modification.
In a 24-week, single-site, pilot study (N=24) designed to evaluate the safety and efficacy of a
triple NRTI once-daily regimen of didanosine EC (250 mg), lamivudine (300 mg) and tenofovir
DF (300 mg) in HIV-infected treatment-naïve patients, Jemsek et al. (Oral Communication,
September 2003) have identified a high frequency of virologic failure (91%), which was defined
as < 2 log10 reduction in plasma HIV RNA level by Week 12. Resistance testing was performed
on 21 patients; 20 patients (95%) had M184I/V and 10 of these patients (50%) had K65R in
addition to M184V. As a result of this high early failure rate, study enrollment was stopped.
Sub-optimal virologic response has also been reported with the use of the triple NRTI regimen
abacavir/lamivudine/zidovudine (Trizivir) (Gulick 2003) and abacavir/didanosine/stavudine
(Gerstoft 2003), and similarly early virologic failure and high rates of resistance mutations have
been reported with abacavir/lamivudine/tenofovir DF (Farthing 2003, Gallant 2003). Overall,
these studies demonstrate a lower response rate in patients on a triple NRTI regimen.
Furthermore, they indicate that patients who achieve viral suppression on a triple NRTI regimen
have a higher rate of virologic failure.
Reporting of Adverse Events
Please report all adverse events, following or coincident with the use of Viread, to Gilead Global
Drug Safety at 1-800-GILEAD-5, option 3, or to the FDA MedWatch Program by phone (1-800-
FDA-1088), by fax (1-800-FDA-0178), by mail (using postage-paid form to MedWatch, FDA,
5600 Fishers Lane, Rockville, MD 20852-9787) or via the internet (www.accessdata.fda.gov/scripts/medwatch/).
We hope this information will be helpful to you in caring for your patients. Please consult the
enclosed Prescribing Information for complete product information. If you have any additional
questions, please contact Gilead Medical Information toll free at 1-800-GILEAD-5, option 2.
Sincerely,
Jay Toole, MD, Ph.D.
Senior Vice President
Clinical Research
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