Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

DESCOVY (NDA-208215)

(EMTRICITABINE; TENOFOVIR ALAFENAMIDE FUMARATE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

06/20/2025 (SUPPL-23)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

. . .

Renal Laboratory Tests

In two 48-week trials in antiretroviral treatment-naïve adults with HIV-1 treated with FTC+TAF with EVG+COBI (N=866) with a median baseline eGFR of 115 mL per minute, mean serum creatinine increased by 0.1 mg per dL from baseline to Week 48. Median urine protein-to-creatinine ratio (UPCR) was 44 mg per gram at baseline and at Week 48. In a 48-week trial in virologically-suppressed TDF- treated adults with HIV-1 who switched to FTC+TAF with EVG+COBI (N=959) with a mean baseline eGFR of 112 mL per minute, mean serum creatinine was similar to baseline at Week 48; median UPCR was 61 mg per gram at baseline and 46 mg per gram at Week 48. Across these trials, renal serious adverse events or discontinuations due to renal adverse reactions were encountered in less than 1% of participants treated with FTC+TAF with EVG+COBI.

In a 24-week trial in adults with HIV-1 and renal impairment (baseline eGFR 30 to 69 mL per minute) who received FTC+TAF with EVG+COBI (N=248), mean serum creatinine was 1.5 mg per dL at both baseline and Week 24. Median UPCR was 161 mg per gram at baseline and 93 mg per gram at Week 24.

FTC+TAF with EVG+COBI was permanently discontinued due to worsening renal function in two of 80 (3%) participants.

Bone Mineral Density Effects

. . .

In 799 virologically-suppressed TDF-treated adult participants with HIV-1 that switched to FTC+TAF with EVG+COBI, at Week 48 mean BMD increased (1.86% lumbar spine, 1.95% total hip). BMD declines of 5% or greater at the lumbar spine were experienced by 1% of FTC+TAF with EVG+COBI participants. BMD declines of 7% or greater at the femoral neck were experienced by 1% of FTC+TAF with EVG+COBI participants.

Revised subheading:

Adverse Reactions in a Clinical Trial of FTC+TAF with EVG+COBI in Virologically-Suppressed Adults with HIV-1 and End Stage Renal Disease (ESRD) Receiving Chronic Hemodialysis

. . .

Adverse Reactions in Clinical Trials in Pediatric Participants with HIV-1

Study 106: Adverse Reactions in a Clinical Trial of FTC+TAF with EVG+COBI in Pediatric Participants Weighing at Least 25 kg

The safety profile of FTC+TAF in pediatric participants weighing at least 25 kg is informed by an open-label trial of antiretroviral treatment-naïve pediatric participants with HIV-1 between the ages of 12 to less than 18 years weighing at least 35 kg through 48 weeks (N=50; cohort 1) and virologically-suppressed participants with HIV-1 between the ages of 6 to less than 12 years weighing at least 25 kg (N=52; cohort 2). Participants received FTC+TAF with EVG+COBI through 48 weeks. With the exception of a decrease in the mean CD4+ cell count observed in cohort 2, the safety of this combination was similar to that in adults.

. . .

Study 1474: Adverse Reactions in a Clinical Trial of FTC+TAF with Bictegravir in Pediatric Participants Weighing at Least 14 to Less Than 25 kg

In a separate open-label trial of virologically-suppressed participants at least 2 years of age and weighing at least 14 to less than 25 kg (N=22; cohort 3) who received FTC+TAF with bictegravir through 24 weeks, no new adverse reactions or laboratory abnormalities were identified compared to those observed in adults. In this trial, the mean (SD) change from baseline to Week 24 in CD4+ cell count was -126 (264) cells per mm3 and the mean (SD) change in CD4% from baseline to Week 24 was 0.2% (4.4%).

Study 128: Adverse Reactions in a Clinical Trial of DESCOVY in combination with Darunavir+Cobicistat (DRV+COBI) in Pediatric Participants Weighing at Least 14 kg

The safety profile of DESCOVY is also informed by a separate open-label trial of virologically-suppressed pediatric participants between the ages of 6 to less than 12 years and weighing at least 25 to less than 40 kg (N=9; cohort 2), and virologically-suppressed pediatric participants at least 2 years of age and weighing at least 14 to less than 25 kg (N=11; cohort 3) who received DESCOVY in combination with DRV+COBI through Week 48. In this study, the safety profile of DESCOVY was similar to that in adults.

Bone Mineral Density Effects

Cohort 2: Pediatric Participants Weighing at Least 25 to Less Than 40 kg

Among the participants in cohort 2 who had both baseline and Week 48 measurements (n=8 and 9 for lumbar spine and TBLH, respectively), mean BMD increased from baseline to Week 48, +6.1% at lumbar spine and +4.4% for TBLH.

Cohort 3: Pediatric Participants Weighing at Least 15 to less Than 25 kg

Among the participants in cohort 3 who had both baseline and Week 48 measurements (n=7 and 10 for lumbar spine and TBLH, respectively), mean BMD increased from baseline to Week 48, +8.7% at lumbar spine and +6.9% for TBLH.

. . .

7 Drug Interactions

7.4 Drugs without Clinically Significant Interactions with DESCOVY

Additions and/or revisions underlined:

Based on drug interaction studies conducted with the components of DESCOVY, no clinically significant drug interactions have been either observed or are expected when DESCOVY is combined with the following antiretroviral agents: atazanavir with ritonavir, atazanavir with cobicistat (in those weighing greater than or equal to 35 kg), darunavir with ritonavir or cobicistat, dolutegravir, efavirenz, ledipasvir, lopinavir/ritonavir, maraviroc, nevirapine, raltegravir, rilpivirine, and sofosbuvir.

. . .

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to DESCOVY during pregnancy. Healthcare providers are encouraged to register individuals by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.

. . .

Data

Human Data

Prospective reports from the APR of overall major birth defects in pregnancies exposed to the components of DESCOVY are compared with a U.S. background major birth defect rate. Methodological limitations of the APR include the use of MACDP as the external comparator group. The MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at less than 20 weeks gestation.

Emtricitabine (FTC):

Based on prospective reports to the APR of over 7300 exposures to FTC- containing regimens during pregnancy resulting in live births (including over 5400 exposed in the first trimester and over 1800 exposed in the second/third trimester), the prevalence of birth defects in live births was 3.0% (95% CI: 2.5% to 3.5%) and 2.7% (95% CI: 2.0% to 3.6%) following first and second/third trimester exposure, respectively, to FTC-containing regimens.

Tenofovir Alafenamide (TAF):

Based on prospective reports to the APR of over 1600 exposures to TAF- containing regimens during pregnancy resulting in live births (including over 1300 exposed in the first trimester and over 300 exposed in the second/third trimester), the prevalence of birth defects in live births was 3.9% (95% CI: 2.9% to 5.2%) and 4.7% (95% CI: 2.6% to 7.7%) following first and second/third trimester exposure, respectively, to TAF-containing regimens.

. . .

8.2 Lactation

Additions and/or revisions underlined:

Data from the published literature report the presence of FTC, TAF, and tenofovir in human milk. Data from the published literature have not reported adverse effects of FTC or TAF on a breastfed child. There are no data on the effects of FTC or TAF on milk production.

Potential risks of breastfeeding include: 1) HIV transmission to infants without HIV-1; 2) developing viral resistance in infants with HIV-1; and 3) adverse reactions in a breastfed infant similar to those seen in adults.

8.4 Pediatric Use

Additions and/or revisions underlined:

. . .

Treatment of HIV-1 Infection

Adolescent Patients Weighing at Least 35 kg:

The safety and effectiveness of DESCOVY in combination with other antiretroviral agents for the treatment of HIV-1 infection was established in adolescent patients weighing at least 35 kg.

Use of DESCOVY in adolescent patients is supported by adequate and well controlled trials of FTC+TAF with EVG+COBI in adults and by an open-label trial in antiretroviral treatment-naïve pediatric participants with HIV-1 aged 12 to less than 18 years and weighing at least 35 kg through Week 48 (N=50; Study 106 [cohort 1]) administered FTC+TAF with EVG+COBI. The safety and effectiveness of FTC+TAF with EVG+COBI in adolescent participants was similar to that in adults on this regimen [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.2)].

Pediatric Patients Weighing at least 14 kg and Less than 35 kg:

The safety and effectiveness of DESCOVY in combination with other antiretroviral agents, including darunavir and cobicistat (DRV+COBI) but not including other protease inhibitors that require a CYP3A inhibitor, for the treatment of HIV-1 infection was established in pediatric patients weighing at least 14 kg to less than 35 kg [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.2)].

Use of DESCOVY in pediatric patients weighing at least 14 kg to less than 35 kg is supported by:

adequate and well controlled trials of FTC+TAF with EVG+COBI in adults;
an open-label trial in virologically-suppressed pediatric participants aged 6 to less than 12 years and weighing at least 25 kg (N=52; Study 106 [cohort 2]) administered FTC+TAF with EVG+COBI through Week 48;
an open-label trial of DESCOVY administered in combination with DRV+COBI in virologically-suppressed pediatric participants at least 2 years of age and weighing at least 14 kg to less than 40 kg (n=20; Study 128 [cohort 2 and 3]) through Week 48;
an open-label trial of FTC+TAF with bictegravir in virologically-suppressed pediatric participants at least 2 years of age and weighing at least 14 to less than 25 kg through Week 24 (N=22; Study 1474 [cohort 3]).

Overall, the safety and effectiveness of FTC+TAF in pediatric participants in these trials were similar to that observed in adults. Specifically, the safety and efficacy of FTC+TAF with EVG+COBI in participants 6 to 12 years of age and weighing at least 25 kg were similar to that in antiretroviral treatment-naïve adults and adolescents receiving this regimen, with the exception of a decrease from baseline in CD4+ cell count. The safety and effectiveness of DESCOVY when administered with DRV+COBI in pediatric participants weighing at least 14 kg to less than 40 kg were similar to that in adults.

Pediatric Patients Weighing less than 14 kg:

Safety and effectiveness of DESCOVY for treatment of HIV-1 infection in pediatric patients weighing less than 14 kg have not been established.

. . .

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

. . .

While you are taking DESCOVY for HIV-1 PrEP:

DESCOVY does not prevent other sexually transmitted infections (STIs). Practice safer sex by using a latex or polyurethane condom to reduce the risk of getting STIs.
You must stay HIV-1 negative to keep taking DESCOVY for HIV-1 PrEP.

. . .

Get tested for other STIs such as syphilis, chlamydia, and gonorrhea. These infections make it easier for HIV-1 to infect you.

. . .

What should I tell my healthcare provider before taking DESCOVY?

Before taking DESCOVY, tell your healthcare provider about all of your medical conditions, including if you:

. . .

are breastfeeding or plan to breastfeed. DESCOVY passes to your baby in your breast milk. Talk to your healthcare provider about the following risks to your baby from breastfeeding during treatment with DESCOVY:

the HIV-1 virus may pass to your baby if your baby does not have HIV-1.
the HIV-1 virus may become harder to treat if your baby has HIV-1.
your baby may get side effects from DESCOVY.

. . .

What are the possible side effects of DESCOVY? DESCOVY may cause serious side effects, including:

. . .

Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking medicines to treat HIV-1. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you have any new symptoms of infection after starting your HIV-1 medicine.

. . .

How should I store DESCOVY?

Store DESCOVY at room temperature between 68°F to 77°F (20°C to 25°C).

. . .

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

. . .

Lactation

Inform individuals with HIV-1 infection that the potential risks of breastfeeding include: (1) HIV-1 transmission to infants without HIV-1, (2) developing viral resistance in infants with HIV-1, and (3) adverse reactions in a breastfed infant similar to those seen in adults [see Use in Specific Populations (8.2)].

06/20/2025 (SUPPL-25)

Approved Drug Label (PDF)

7 Drug Interactions

7.3 Established and Other Potentially Significant Interactions

. . .

Table 6 Established and Other Potentially Significant Drug Intractions

Addition of atazanavir/cobicistat to the Concomitant Drug Class: Drug Name section of table; please refer to label for complete information.

7.4 Drugs without Clinically Significant Interactions with DESCOVY

Additions and/or revisions underlined:

. . .

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Pregnancy Exposure Registry

. . .

Data

Human Data

Emtricitabine (FTC):

Tenofovir Alafenamide (TAF):

. . .

8.2 Lactation

Additions and/or revisions underlined:

8.4 Pediatric Use

Additions and/or revisions underlined:

. . .

Use of DESCOVY with Other Protease Inhibitors that Require CYP3A Inhibition in Pediatric Patients Weighing at least 14 kg to Less than 35 kg:

The use of DESCOVY with atazanavir and cobicistat (ATV+COBI) is not recommended in pediatric patients weighing at least 14 kg to less than 35 kg.

The use of DESCOVY with ATV+COBI was studied in pediatric patients weighing at least 14 kg to less than 35 kg. In Study 128, participants who received ATV+COBI in cohort 2 (25 kg to <40 kg, n=14) and cohort 3 (14 kg to <25 kg, n=15) showed TAF exposures (Cmax and AUC) that exceeded adult exposures by 4–5-fold in cohort 2, and 2–3-fold in cohort 3. Limited safety data were available to support the increased TAF exposures. Therefore, the use of DESCOVY with ATV+COBI is not recommended in pediatric patients weighing at least 14 kg to less than 35 kg.

Safety and effectiveness of DESCOVY in combination with protease inhibitors that require ritonavir in pediatric patients weighing at least 14 kg to less than 35 kg have not been established.

Pediatric Patients Weighing less than 14 kg:

Safety and effectiveness of DESCOVY for treatment of HIV-1 infection in pediatric patients weighing less than 14 kg have not been established.

. . .

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

. . .

While you are taking DESCOVY for HIV-1 PrEP:

DESCOVY does not prevent other sexually transmitted infections (STIs). Practice safer sex by using a latex or polyurethane condom to reduce the risk of getting STIs.
You must stay HIV-1 negative to keep taking DESCOVY for HIV-1 PrEP.

. . .

Get tested for other STIs such as syphilis, chlamydia, and gonorrhea. These infections make it easier for HIV-1 to infect you.

. . .

What should I tell my healthcare provider before taking DESCOVY?

Before taking DESCOVY, tell your healthcare provider about all of your medical conditions, including if you:

. . .

are breastfeeding or plan to breastfeed. DESCOVY passes to your baby in your breast milk. Talk to your healthcare provider about the following risks to your baby from breastfeeding during treatment with DESCOVY:

the HIV-1 virus may pass to your baby if your baby does not have HIV-1.
the HIV-1 virus may become harder to treat if your baby has HIV-1.
your baby may get side effects from DESCOVY.

. . .

What are the possible side effects of DESCOVY? DESCOVY may cause serious side effects, including:

. . .

Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking medicines to treat HIV-1. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you have any new symptoms of infection after starting your HIV-1 medicine.

. . .

How should I store DESCOVY?

Store DESCOVY at room temperature between 68°F to 77°F (20°C to 25°C).

. . .

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

. . .

Lactation

01/07/2022 (SUPPL-20)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Extensive changes; please refer to label

7 Drug Interactions

7.3 Established and Other Potentially Significant Interactions

Additions and/or revisions underlined:

Table 6 provides a listing of established or potentially clinically significant drug interactions with recommended steps to prevent or manage the drug interaction (the table is not all inclusive). The drug interactions described are based on studies conducted with either DESCOVY, the components of DESCOVY (emtricitabine and tenofovir alafenamide) as individual agents, or are predicted drug interactions that may occur with DESCOVY. For magnitude of interaction, see Clinical Pharmacology (12.3).

Table 6 Established and Other Potentially Significant Drug Interactions

…

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

Treatment of HIV-1 Infection

The safety and effectiveness of DESCOVY, in combination with other antiretroviral agents, for the treatment of HIV-1 infection was established in pediatric patients with body weight greater than or equal to 14 kg [see Indication and Usage (1.1) and Dosage and Administration (2.3, 2.4)].

Use of DESCOVY in pediatric patients between 6 to less than 18 years of age and weighing at least 25 kg is supported by adequate and well controlled studies of FTC+TAF with EVG+COBI in adults and by an open-label trial in antiretroviral treatment-naïve HIV-1 infected pediatric subjects aged 12 to less than 18 years and weighing at least 35 kg through Week 48 (N=50; cohort 1) and in virologically-suppressed pediatric subjects aged 6 to less than 12 years and weighing at least 25 kg through Week 48 (N=52; cohort 2). The safety and efficacy of FTC+TAF with EVG+COBI in adolescent subjects was similar to that in adults on this regimen. The safety and efficacy of FTC+TAF with EVG+COBI in subjects 6 to 12 years of age weighing at least 25 kg was similar to that in antiretroviral treatment-naïve adults and adolescents on this regimen, with the exception of a decrease from baseline in CD4+ cell count [see Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14.2)].

Use of DESCOVY in pediatric patients between 2 to less than 6 years of age and weighing at least 14 to less than 25 kg is supported by adequate and well controlled studies of FTC+TAF with EVG+COBI in adults and by a separate open-label trial of FTC+TAF with bictegravir in virologically-suppressed pediatric patients at least 2 years of age and weighing at least 14 to less than 25 kg through Week 24 (N=22; cohort 3). The safety and efficacy of FTC+TAF in these pediatric subjects were similar to that observed in adults who received FTC+TAF with bictegravir [see Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14.2)].

Safety and effectiveness of DESCOVY coadministered with an HIV-1 protease inhibitor that is administered with either ritonavir or cobicistat have not been established in pediatric patients weighing less than 35 kg [see Dosage and Administration (2.4)].

Safety and effectiveness of DESCOVY for treatment of HIV-1 infection in pediatric patients weighing less than 14 kg have not been established.

HIV-1 PrEP

Safety and effectiveness of DESCOVY for HIV-1 PrEP in at-risk adolescents weighing at least 35 kg, excluding individuals at risk from receptive vaginal sex, is supported by data from an adequate and well-controlled trial of DESCOVY for HIV-1 PrEP in adults with additional data from safety and pharmacokinetic studies in previously conducted trials with the individual drug products, FTC and TAF, with EVG+COBI, in HIV-1 infected adults and pediatric subjects [see Dosage and Administration (2.5), Adverse Reactions (6.1), Clinical Pharmacology (12.3 and 12.4), and Clinical Studies (14)].

While using DESCOVY for HIV-1 PrEP, HIV-1 testing should be repeated at least every 3 months, and upon diagnosis of any other STIs. Previous studies in at-risk adolescents indicated waning adherence to a daily oral PrEP regimen once visits were switched from monthly to quarterly visits. Adolescents may therefore benefit from more frequent visits and counseling [see Warnings and Precautions (5.2)].

Safety and effectiveness of DESCOVY for HIV-1 PrEP in pediatric patients weighing less than 35 kg have not been established.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

…

What is DESCOVY?

DESCOVY is a prescription medicine that may be used in two different ways. DESCOVY is used:

to treat HIV-1 infection
- in adults and children who weigh at least 77 pounds (35 kg) together with other HIV-1 medicines
- in children who weigh at least 31 pounds (14 kg) and less than 77 pounds (35 kg) together with certain other HIV- 1 medicines. Your healthcare provider will determine which other HIV-1 medicines may be used with DESCOVY.
for HIV-1 PrEP to reduce the risk of getting HIV-1 infection in adults and adolescents who weigh at least 77 pounds (35 kg). It is not known if DESCOVY is effective in reducing the risk of getting HIV-1 from certain types of sex.

DESCOVY for PrEP is not for use in people born female (assigned female at birth) who are at risk of getting HIV- 1 infection from vaginal sex, because its effectiveness has not been studied.

HIV-1 is the virus that causes Acquired Immune Deficiency Syndrome (AIDS). DESCOVY contains the prescription medicines emtricitabine and tenofovir alafenamide.

It is not known if DESCOVY for treatment of HIV-1 infection is safe and effective in children who weigh less than 31 pounds (14 kg).

It is not known if DESCOVY is safe and effective in reducing the risk of HIV-1 infection in people who weigh less than 77 pounds (35 kg).

…

09/15/2021 (SUPPL-19)

Approved Drug Label (PDF)

8 Use in Specific Populations

Pregnancy

(Additions and/or revisions underlined)

Risk Summary

Available data from the APR show no statistically significant difference in the overall risk of major birth defects for emtricitabine (FTC) or tenofovir alafenamide (TAF) compared with the background rate for major birth defects of 2.7% in a

U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) (see Data). The rate of miscarriage for individual drugs is not reported in the APR. The estimated background rate of miscarriage in the clinically recognized pregnancies in the U.S. general population is 15?20%.

In animal studies, no adverse developmental effects were observed when the components of DESCOVY were administered separately during the period of organogenesis at exposures 60 and 108 times (mice and rabbits, respectively) the FTC exposure and at exposure equal to or 53 times (rats and rabbits, respectively) the TAF exposure at the recommended daily dose of DESCOVY (see Data). Likewise, no adverse developmental effects were seen when FTC was administered to mice through lactation at exposures up to approximately 60 times the exposure at the recommended daily dose of DESCOVY. No adverse effects were observed in the offspring when TDF was administered through lactation at tenofovir exposures of approximately 14 times the exposure at the recommended daily dosage of DESCOVY.

Data

Human Data

Emtricitabine (FTC):

Based on prospective reports to the APR of over 5,400 exposures to FTC- containing regimens during pregnancy resulting in live births (including over 3,900 exposed in the first trimester and over 1,500 exposed in the second/third trimester), the prevalence of birth defects in live births was 2.6% (95% CI: 2.2% to 3.2%) and 2.7 % (95% CI: 1.9 % to 3.7 %) following first and second/third trimester exposure, respectively, to FTC-containing regimens.

Tenofovir Alafenamide (TAF):

Based on prospective reports to the APR of over 660 exposures to TAF- containing regimens during pregnancy resulting in live births (including over 520 exposed in the first trimester and over 130 exposed in the second/third trimester), the prevalence of birth defects in live births was 4.2 % (95% CI: 2.6 % to 6.3 %) and 3.0% (95% CI: 0.8% to 7.5 %) following first and second/third trimester exposure, respectively, to TAF-containing regimens.

03/04/2021 (SUPPL-17)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.4 New Onset or Worsening Renal Impairment

Additions and/or revisions underlined

Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with TAF- containing products; while most of these cases were characterized by potential confounders that may have contributed to the reported renal events, it is also possible these factors may have predisposed patients to tenofovir-related adverse events [see Adverse Reactions (6.1, 6.2)].

…

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions underlined

Renal Laboratory Tests

… Across these trials, renal serious adverse events or discontinuations due to renal adverse reactions were encountered in less than 1% of participants treated with FTC+TAF with EVG+COBI.

In a 24-week trial in adults with renal impairment (baseline eGFR 30 to 69 mL per minute) who received FTC+TAF with EVG+COBI (N=248), mean serum creatinine was 1.5 mg per dL at both baseline and Week 24. Median UPCR was 161 mg per gram at baseline and 93 mg per gram at Week 24. FTC+TAF with EVG+COBI was permanently discontinued due to worsening renal function in two of 80 (3%) subjects.

…

6.2 Postmarketing Experience

Additions underlined

…

Renal and Urinary Disorders

Acute renal failure, acute tubular necrosis, proximal renal tubulopathy, and Fanconi syndrome

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions underlined

…

What is the most important information I should know about DESCOVY?

…

If you stop taking DESCOVY, your healthcare provider will need to check your health often and do blood tests regularly for several months to check your liver, and may give you a medicine to treat hepatitis B. Tell your healthcare provider about any new or unusual symptoms you may have after you stop taking DESCOVY.
…

PATIENT COUNSELING INFORMATION

Additions underlined

…

New Onset or Worsening Renal Impairment

Advise HIV-1 infected patients and uninfected individuals to avoid taking DESCOVY with concurrent or recent use of nephrotoxic agents. Postmarketing cases of renal impairment, including acute renal failure, have been reported [see Warnings and Precautions (5.4)].

…

12/03/2019 (SUPPL-11)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.4 New Onset or Worsening Renal Impairment

(additions underlined)

…

DESCOVY is not recommended in individuals with estimated creatinine clearance of 15 to below 30 mL per minute, or in individuals with estimated creatinine clearance below 15 mL per minute who are not receiving chronic hemodialysis.

…

6 Adverse Reactions

6.1 Clinical Trials Experience

(additions underlined)

…

Adverse Reactions in a Clinical Trial of FTC+TAF with EVG+COBI in Virologically-Suppressed Adults with End Stage Renal Disease (ESRD) Receiving Chronic Hemodialysis

In a 48-week trial of virologically-suppressed HIV-1 infected adult subjects with end stage renal disease (ESRD) (estimated creatinine clearance of less than 15 mL/min) on chronic hemodialysis treated with FTC+TAF with EVG+COBI (N=55), the most commonly reported adverse reaction (adverse event assessed as causally related by investigator and all grades) was nausea (7%). Serious adverse events were reported in 53% of subjects and the most common serious adverse events were pneumonia (13%), fluid overload (7%), hyperkalemia (7%) and osteomyelitis (7%). Overall 5% of subjects permanently discontinued treatment due to an adverse event.

…

8 Use in Specific Populations

8.6 Renal Impairment

(additions underlined)

dosage adjustment of DESCOVY is recommended in individuals with estimated creatinine clearance greater than or equal to 30 mL per minute, or in adults with ESRD (estimated creatinine clearance below 15 mL per minute) who are receiving chronic hemodialysis. On days of hemodialysis, administer the daily dose of DESCOVY after completion of hemodialysis treatment.

Safety and effectiveness of DESCOVY coadministered with an HIV-1 protease inhibitor that is administered with either ritonavir or cobicistat have not been established in patients with ESRD.

DESCOVY is not recommended in individuals with severe renal impairment (estimated creatinine clearance of 15 to below 30 mL per minute), or in individuals with ESRD who are not receiving chronic hemodialysis, as the safety of DESCOVY has not been established in these populations.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

(additions underlined)

…

How should I take DESCOVY?

…

If you are on dialysis, take your daily dose of DESCOVY following dialysis.

…

10/03/2019 (SUPPL-12)

Approved Drug Label (PDF)

Boxed Warning

(additions and/or revisions are underlined)

WARNING: POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B and RISK OF DRUG RESISTANCE WITH USE OF DESCOVY FOR HIV-1

PRE-EXPOSURE PROPHYLAXIS (PrEP) IN UNDIAGNOSED EARLY HIV-1 INFECTION

Severe acute exacerbations of hepatitis B (HBV) have been reported in HBV-infected individuals who have discontinued products containing

emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF) and may occur with discontinuation of DESCOVY.

Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in individuals who are infected with HBV and discontinue DESCOVY. If appropriate, anti-hepatitis B therapy may be warranted.

DESCOVY used for HIV-1 PrEP must only be prescribed to individuals confirmed to be HIV-negative immediately prior to initiating and at least every 3 months during use. Drug-resistant HIV-1 variants have been identified with use of FTC/TDF for HIV-1 PrEP following undetected acute HIV-1 infection. Do not initiate DESCOVY for HIV-1 PrEP if signs or symptoms of acute HIV-1 infection are present unless negative infection status is confirmed.

4 Contraindications

(additions and/or revisions are underlined)

DESCOVY for HIV-1 PrEP is contraindicated in individuals with unknown or positive HIV-1 status.

5 Warnings and Precautions

5.1 Severe Acute Exacerbation of Hepatitis B in Individuals with HBV Infection

(additions and/or revisions are underlined)

All individuals should be tested for the presence of hepatitis B virus (HBV) before or when initiating DESCOVY.

Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in HBV-infected individuals who have discontinued products containing FTC and/or tenofovir disoproxil fumarate (TDF) and may occur with discontinuation of DESCOVY. Individuals infected with HBV who discontinue DESCOVY should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, anti-hepatitis B therapy may be warranted, especially in individuals with advanced liver disease or cirrhosis, since post-treatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure. HBV-uninfected individuals should be offered vaccination.

5.2 Comprehensive Management to Reduce the Risk of Sexually Transmitted Infections, Including HIV-1, and Development of HIV-1 Resistance When DESCOVY Is Used for HIV-1 PrEP

(newly added subsection)

Use DESCOVY for HIV-1 PrEP to reduce the risk of HIV-1 infection as part of a comprehensive prevention strategy, including adherence to daily administration and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). The time from initiation of DESCOVY for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown.

Risk for HIV-1 acquisition includes behavioral, biological, or epidemiologic factors including but not limited to condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network.

Counsel individuals on the use of other prevention measures (e.g., consistent and correct condom use, knowledge of partner(s)’ HIV-1 status, including viral suppression status, regular testing for STIs that can facilitate HIV-1 transmission). Inform uninfected individuals about and support their efforts in reducing sexual risk behavior.

Use DESCOVY to reduce the risk of acquiring HIV-1 only in individuals confirmed to be HIV-1 negative. HIV-1 resistance substitutions may emerge in individuals with undetected HIV-1 infection who are taking only DESCOVY, because DESCOVY alone does not constitute a complete regimen for HIV-1 treatment; therefore, care should be taken to minimize the risk of initiating or continuing DESCOVY before confirming the individual is HIV-1 negative.

Some HIV-1 tests only detect anti-HIV antibodies and may not identify HIV-1 during the acute stage of infection. Prior to initiating DESCOVY for HIV-1 PrEP, ask seronegative individuals about recent (in past month) potential exposure events (e.g., condomless sex or condom breaking during sex with a partner of unknown HIV-1 status or unknown viremic status, or a recent STI), and evaluate for current or recent signs or symptoms consistent with acute HIV-1 infection (e.g., fever, fatigue, myalgia, skin rash).

If recent (<1 month) exposures to HIV-1 are suspected or clinical symptoms consistent with acute HIV-1 infection are present, use a test approved or cleared by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection.

While using DESCOVY for HIV-1 PrEP, HIV-1 testing should be repeated at least every 3 months, and upon diagnosis of any other STIs.

If an HIV-1 test indicates possible HIV-1 infection, or if symptoms consistent with acute HIV-1 infection develop following a potential exposure event, convert the HIV-1 PrEP regimen to an HIV treatment regimen until negative infection status is confirmed using a test approved or cleared by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection.

Counsel HIV-1 uninfected individuals to strictly adhere to the once daily DESCOVY dosing schedule. The effectiveness of DESCOVY in reducing the risk of acquiring HIV-1 is strongly correlated with adherence, as demonstrated by measurable drug levels in a clinical trial of DESCOVY for HIV-1 PrEP. Some individuals, such as adolescents, may benefit from more frequent visits and counseling to support adherence.

5.3 Immune Reconstitution Syndrome

(additions and/or revisions are underlined)

Immune reconstitution syndrome has been reported in HIV-1 infected patients treated with combination antiretroviral therapy, including FTC, a component of DESCOVY. During the initial phase of combination antiretroviral treatment, HIV-1 infected patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves’ disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

5.4 New Onset or Worsening Renal Impairment

(additions and/or revisions are underlined)

Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir prodrugs in both animal toxicology studies and human trials. In clinical trials of FTC+TAF with cobicistat (COBI) plus elvitegravir (EVG) in HIV-1 infected patients there have been no cases of Fanconi syndrome or Proximal Renal Tubulopathy (PRT). In clinical trials of FTC+TAF with EVG+COBI in treatment-naïve subjects and in virally suppressed subjects switched to FTC+TAF with EVG+COBI with estimated creatinine clearance greater than 50 mL per minute, renal serious adverse events or discontinuations due to renal adverse reactions were encountered in less than 1% of participants treated with FTC+TAF with EVG+COBI. In a study of virally suppressed subjects with baseline estimated creatinine clearance between 30 and 69 mL per minute treated with FTC+TAF with EVG+COBI for a median duration of 43 weeks, FTC+TAF with EVG+COBI was permanently discontinued due to worsening renal function in two of 80 (3%) subjects with a baseline estimated creatinine clearance between 30 and 50 mL per minute. DESCOVY is not recommended in individuals with estimated creatinine clearance below 30 mL per minute because data in this population are insufficient.

Individuals taking tenofovir prodrugs who have impaired renal function and those taking nephrotoxic agents including non-steroidal anti-inflammatory drugs are at increased risk of developing renal-related adverse reactions.

Prior to or when initiating DESCOVY, and during treatment with DESCOVY on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all individuals. In individuals with chronic kidney disease, also assess serum phosphorus. Discontinue DESCOVY in individuals who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.

5.5 Lactic Acidosis/Severe Hepatomegaly with Steatosis

(additions and/or revisions are underlined)

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including emtricitabine, a component of DESCOVY, and tenofovir DF, another prodrug of tenofovir, alone or in combination with other antiretrovirals. Treatment with DESCOVY should be suspended in any individual who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

6 Adverse Reactions

6.1 Clinical Trials Experience

(extensive revisions; please refer to labeling for complete information)

6.2 Postmarketing Experience

(newly added subsection)

The following reactions have been identified during postapproval use of products containing TAF. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and Subcutaneous Tissue Disorders

Angioedema, urticaria, and rash

7 Drug Interactions

7.3 Established and Other Potentially Significant Interactions

(additions and/or revisions are underlined)

Table 5 provides a listing of established or potentially clinically significant drug interactions with recommended steps to prevent or manage the drug interaction (the table is not all inclusive). The drug interactions described are based on studies conducted with either DESCOVY, the components of DESCOVY (emtricitabine and tenofovir alafenamide) as individual agents, or are predicted drug interactions that may occur with DESCOVY. For magnitude of interaction, see Clinical Pharmacology (12.3).

Table 5 Established and Other Potentially Significant Drug Interactions

...

8 Use in Specific Populations

8.1 Pregnancy

(additions and/or revisions are underlined)

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to DESCOVY during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.

Risk Summary

Available data from the APR show no increase in the risk of overall major birth defects for emtricitabine (FTC) compared with the background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). There are insufficient tenofovir alafenamide (TAF) data from the APR to adequately assess the risk of major birth defects. The rate of miscarriage for individual drugs is not reported in the APR. The estimated background rate of miscarriage in the clinically recognized pregnancies in the U.S. general population is 15?20%.

Likewise, no adverse developmental effects were seen when FTC was administered to mice through lactation at exposures up to approximately 60 times the exposure at the recommended daily dose of DESCOVY. No adverse effects were observed in the offspring when TDF was administered through lactation at tenofovir exposures of approximately 14 times the exposure at the recommended daily dosage of DESCOVY.

Data

Human Data

Emtricitabine: Based on prospective reports to the APR through January 2019 of over 4,450 exposures to FTC-containing regimens during pregnancy (including over 3,150 exposed in the first trimester and over 1,300 exposed in the second/third trimester), there was no difference between FTC and overall birth defects compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP. The prevalence of birth defects in live births was 2.4% (95% CI: 1.9% to 3.0%) with first trimester exposure to FTC-containing regimens and 2.3% (95% CI: 1.5% to 3.2%) with the second/third trimester exposure to FTC-containing regimens.

Tenofovir Alafenamide: Based on prospective reports to the APR of over 220 exposures to TAF-containing regimens during pregnancy (including over 160 exposed in the first trimester and over 60 exposed in the second/third trimester), there have been 6 birth defects with first trimester exposure to TAF-containing regimens.

Methodologic limitations of the APR include the use of MACDP as the external comparator group. The MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at <20 weeks gestation.

Additionally, published observational studies on emtricitabine and tenofovir exposure in pregnancy have not shown an increased risk for major malformations.

Animal Data

Emtricitabine: FTC was administered orally to pregnant mice (250, 500, or 1000 mg/kg/day) and rabbits (100, 300, or 1000 mg/kg/day) through organogenesis (on gestation days 6 through 15, and 7 through 19, respectively). No significant toxicological effects were observed in embryo-fetal toxicity studies performed with FTC in mice at exposures (area under the curve [AUC]) approximately 60 times higher and in rabbits at approximately 108 times higher than human exposures at the recommended daily dose. In a pre/postnatal development study with FTC, mice were administered doses up to 1000 mg/kg/day; no significant adverse effects directly related to drug were observed in the offspring exposed daily from before birth (in utero) through sexual maturity at daily exposures (AUC) of approximately 60-fold higher than human exposures at the recommended daily dose.

Tenofovir Alafenamide: TAF was administered orally to pregnant rats (25, 100, or 250 mg/kg/day) and rabbits (10, 30, or 100 mg/kg/day) through organogenesis (on gestation days 6 through 17, and 7 through 20, respectively). No adverse embryo-fetal effects were observed in rats and rabbits at TAF exposures approximately similar to (rats) and 53 (rabbits) times higher than the exposure in humans at the recommended daily dose of DESCOVY. TAF is rapidly converted to tenofovir; the observed tenofovir exposures in rats and rabbits were 59 (rats) and 93 (rabbits) times higher than human tenofovir exposures at the recommended daily dose. Since TAF is rapidly converted to tenofovir and a lower tenofovir exposure in rats and mice was observed after TAF administration compared to tenofovir disoproxil fumarate (TDF, another prodrug for tenofovir) administration, a pre/postnatal development study in rats was conducted only with TDF. Doses up to 600 mg/kg/day were administered through lactation; no adverse effects were observed in the offspring on gestation day 7 (and lactation day 20) at tenofovir exposures of approximately 14 (21) times higher than the exposures in humans at the recommended daily dose of DESCOVY.

8.2 Lactation

(additions and/or revisions are underlined)

Risk Summary

The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants, to avoid risking postnatal transmission of HIV-1.

Based on limited data, FTC has been shown to be present in human breast milk; it is not known if TAF is present in human breast milk. Tenofovir has been shown to be present in the milk of lactating rats and rhesus monkeys after administration of TDF. It is not known if TAF is present in animal milk.

It is not known if DESCOVY affects milk production or has effects on the breastfed child.

Because of the potential for: 1) HIV transmission (in HIV-negative infants); 2) developing viral resistance (in HIV-positive infants); and 3) adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed if they are taking DESCOVY for the treatment of HIV-1.

Data

Animal Data

Tenofovir Alafenamide: Studies in rats and monkeys have demonstrated that tenofovir is secreted in milk. Tenofovir was excreted into the milk of lactating rats following oral administration of TDF (up to 600 mg/kg/day) at up to approximately 24% of the median plasma concentration in the highest dosed animals at lactation day 11. Tenofovir was excreted into the milk of lactating monkeys following a single subcutaneous (30 mg/kg) dose of tenofovir at concentrations up to approximately 4% of plasma concentration, resulting in exposure (AUC) of approximately 20% of plasma exposure.

8.4 Pediatric Use

(additions and/or revisions are underlined)

Treatment of HIV-1 Infection

Use of DESCOVY in pediatric patients between the ages of 12 to less than 18 years weighing at least 35 kg is supported by adequate and well controlled studies of FTC+TAF with EVG+COBI in adults and by an open-label trial in antiretroviral treatment-naïve HIV-1 infected pediatric subjects ages 12 to less than 18 years and weighing at least 35 kg (N=50; cohort 1). The safety and efficacy of FTC+TAF with EVG+COBI in these pediatric subjects was similar to that of HIV-1 infected adults on this regimen.

Use of DESCOVY in pediatric patients weighing at least 25 kg is supported by adequate and well controlled studies of FTC+TAF with EVG+COBI in adults and by an open-label trial in virologically-suppressed pediatric subjects between the ages of 6 to less than 12 years weighing at least 25 kg, in which subjects were switched from their antiretroviral regimen to FTC+TAF with EVG+COBI (N=23; cohort 2). The safety in these subjects through 24 weeks of FTC+TAF with EVG+COBI was similar to that of HIV-1 infected adults on this regimen, with the exception of a decrease in mean change from baseline in CD4+ cell count.

Safety and effectiveness of DESCOVY for treatment of HIV-1 infection in pediatric patients less than 25 kg have not been established.

HIV-1 PrEP

Safety and effectiveness of DESCOVY for HIV-1 PrEP in pediatric patients less than 35 kg have not been established.

8.5 Geriatric Use

(additions and/or revisions are underlined)

In clinical trials of an FTC+TAF-containing regimen for treatment of HIV-1, 80 of the 97 subjects enrolled aged 65 years and over received FTC+TAF and EVG+COBI. No differences in safety or efficacy have been observed between elderly subjects and adults between 18 and less than 65 years of age.

8.6 Renal Impairment

(additions and/or revisions are underlined)

DESCOVY is not recommended in individuals with severe renal impairment (estimated creatinine clearance below 30 mL per minute). No dosage adjustment of DESCOVY is recommended in individuals with estimated creatinine clearance greater than or equal to 30 mL per minute.

8.7 Hepatic Impairment

(additions and/or revisions are underlined)

No dosage adjustment of DESCOVY is recommended in individuals with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. DESCOVY has not been studied in individuals with severe hepatic impairment.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

(addition of medication guide; please refer to labeling for complete information)

PATIENT COUNSELING INFORMATION

(additions and/or revisions are underlined)

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Important Information for Uninfected Individuals Taking DESCOVY for HIV-1 PrEP

Advise HIV-1 uninfected individuals about the following:

The need to confirm that they are HIV-negative before starting to take DESCOVY to reduce the risk of acquiring HIV-1.

That HIV-1 resistance substitutions may emerge in individuals with undetected HIV-1 infection who are taking DESCOVY, because DESCOVY alone does not constitute a complete regimen for HIV-1 treatment.

The importance of taking DESCOVY on a regular dosing schedule and strict adherence to the recommended dosing schedule to reduce the risk of acquiring HIV-1. Uninfected individuals who miss doses are at greater risk of acquiring HIV-1 than those who do not miss doses.

That DESCOVY does not prevent other sexually acquired infections and should be used as part of a complete prevention strategy including other prevention measures.

To use condoms consistently and correctly to lower the chances of sexual contact with any body fluids such as semen, vaginal secretions, or blood.

The importance of knowing their HIV-1 status and the HIV-1 status of their partner(s).

The importance of virologic suppression in their partner(s) with HIV-1.

The need to get tested regularly for HIV-1 (at least every 3 months, or more frequently for some individuals such as adolescents) and to ask their partner(s) to get tested as well.

To report any symptoms of acute HIV-1 infection (flu-like symptoms) to their healthcare provider immediately.

That the signs and symptoms of acute infection include fever, headache, fatigue, arthralgia, vomiting, myalgia, diarrhea, pharyngitis, rash, night sweats, and adenopathy (cervical and inguinal).

To get tested for other sexually transmitted infections, such as syphilis, chlamydia, and gonorrhea, that may facilitate HIV-1 transmission.

To assess their sexual risk behavior and get support to help reduce sexual risk behavior.

Post-treatment Acute Exacerbation of Hepatitis B in Patients with HBV Infection

Inform individuals that severe acute exacerbations of hepatitis B have been reported in patients who are infected with HBV and have discontinued products containing FTC and/or TDF and may likewise occur with discontinuation of DESCOVY. Advise HBV-infected individuals to not discontinue DESCOVY without first informing their healthcare provider.

Immune Reconstitution Syndrome

Advise HIV-1 infected patients to inform their healthcare provider immediately of any symptoms of infection. In some patients with advanced HIV infection (AIDS), signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started.

New Onset or Worsening Renal Impairment

Advise HIV-1 infected patients and uninfected individuals to avoid taking DESCOVY with concurrent or recent use of nephrotoxic agents. Renal impairment, including cases of acute renal failure, has been reported in association with the use of tenofovir prodrugs.

Lactic Acidosis and Severe Hepatomegaly

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with use of drugs similar to DESCOVY. Advise HIV-1 infected patients and uninfected individuals that they should stop DESCOVY if they develop clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity.

Dosage Recommendations for Treatment of HIV-1 Infection

Inform HIV-1 infected patients that it is important to take DESCOVY with other antiretroviral drugs for the treatment of HIV-1 on a regular dosing schedule with or without food and to avoid missing doses as it can result in development of resistance.

Pregnancy Registry

Inform individuals using DESCOVY that there is an antiretroviral pregnancy registry to monitor fetal outcomes of pregnant women exposed to DESCOVY.

Lactation

Instruct mothers with HIV-1 infection not to breastfeed because of the risk of passing the HIV-1 virus to the baby.

09/29/2017 (SUPPL-5)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

(subsection revised, additions and revisions underlined)

…

Adverse Reactions in Clinical Trials in Pediatric Subjects with HIV-1 Infection

In an open-label trial of antiretroviral treatment-naïve HIV-1 infected pediatric subjects between the ages of 12 to less than 18 years weighing at least 35 kg through 48 weeks (N=50; cohort 1) and virologically-suppressed subjects between the ages of 6 to less than 12 years weighing at least 25 kg (N=23; cohort 2) who received FTC+TAF with EVG+COBI through 24 weeks, with the exception of a decrease in the mean CD4+ cell count observed in cohort 2, the safety of this combination was similar to that of adults.

Bone Mineral Density Effects

Cohort 1: Treatment-naïve adolescents (12 to less than 18 years; at least 35 kg)

Among the subjects in cohort 1 receiving FTC+TAF with EVG+COBI, mean BMD increased from baseline to Week 48, +4.2% at the lumbar spine and +1.3% for the total body less head (TBLH). Mean changes from baseline BMD Z-scores were minus 0.07 for lumbar spine and minus 0.20 for TBLH at Week 48. One subject had significant (at least 4%) lumbar spine BMD loss at Week 48.

Cohort 2: Virologically-suppressed children (6 to less than 12 years; at least 25 kg)

Among the subjects in cohort 2 receiving FTC+TAF with EVG+COBI, mean BMD increased from baseline to Week 24, +2.9% at the lumbar spine and +1.7% for TBLH. Mean changes from baseline BMD Z-scores were -0.06 for lumbar spine and -0.18 for TBLH at Week 24. Two subjects had significant (at least 4%) lumbar spine BMD loss at Week 24.

Change from Baseline in CD4+ cell counts

Cohort 2: Virologically-suppressed children (6 to less than 12 years; at least 25 kg)

Cohort 2 evaluated pediatric subjects (N=23) who were virologically-suppressed and who switched from their antiretroviral regimen to FTC+TAF with EVG+COBI. Although all subjects had HIV-1 RNA < 50 copies/mL, there was a decrease from baseline in CD4+ cell count at Week 24. The mean baseline and mean change from baseline in CD4+ cell count and in CD4% from Week 2 to Week 24 are presented in Table 1. All subjects maintained their CD4+ cell counts above 400 cells/mm3.

Table 1 Mean Change in CD4+ Count and Percentage from Baseline to Week 24 in Virologically-Suppressed Pediatric Patients from 6 to <12 Years Who Switched to FTC+TAF with EVG+COBI

(please refer to label to view Table 1)

8 Use in Specific Populations

8.4 Pediatric Use

(additions underlined)

Safety and effectiveness of DESCOVY coadminstered with an HIV-1 protease inhibitor that is administered with either ritonavir or cobicistat have not been established in pediatric subjects weighing less than 35 kg.

Safety and effectiveness of DESCOVY in pediatric patients less than 25 kg have not been established.

8.5 Geriatric Use

(additions underlined)

In clinical trials, 80 of the 97 subjects enrolled aged 65 years and over received FTC+TAF and EVG+COBI. No differences in safety or efficacy have been observed between elderly subjects and adults between 18 and less than 65 years of age.

04/07/2017 (SUPPL-1)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.4 Lactic Acidosis/Severe Hepatomegaly with Steatosis

(Additions and/or revisions are underlined)

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

(Additions and/or revisions are underlined)

Lactic Acidosis and Severe Hepatomegaly

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported…

Patient Information

(Additions and/or revisions are underlined)

What are the possible side effects of DESCOVY?

DESCOVY may cause serious side effects, including:

Too much lactic acid in your blood (lactic acidosis). Too much lactic acid is a serious but rare medical emergency that can lead to death. Tell your healthcare provider right away if you get these symptoms: weakness or being more tired than usual, unusual muscle pain, being short of breath or fast breathing, stomach pain with nausea and vomiting, cold or blue hands and feet, feel dizzy or lightheaded, or a fast or abnormal heartbeat.
Severe liver problems. In rare cases, severe liver problems can happen that can lead to death. Tell your healthcare provider right away if you get these symptoms: skin or the white part of your eyes turns yellow, dark “tea-colored” urine, light-colored stools, loss of appetite for several days or longer, nausea, or stomach-area pain.