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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.
BIKTARVY (NDA-210251)
(BICTEGRAVIR SODIUM; EMTRICITABINE; TENOFOVIR ALAFENAMIDE FUMARATE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
07/30/2025 (SUPPL-23)
8 Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
The safety and effectiveness of BIKTARVY have been established as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in pediatric patients weighing at least 14 kg:
who have no antiretroviral treatment history, or
with an antiretroviral treatment history and not virologically suppressed, with no known or suspected substitutions associated with resistance to the integrase strand inhibitor class, emtricitabine, or tenofovir, or
. . .
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
Additions and/or revisions underlined:
. . .
What is BIKTARVY?
BIKTARVY is a prescription medicine that is used without other human immunodeficiency virus-1 (HIV-1) medicines to treat HIV-1 in adults and children who weigh at least 31 pounds (14 kg):
who have not received HIV-1 medicines in the past, or
who have received HIV-1 medicines in the past, or to replace their current HIV-1 medicines, and whose healthcare provider determines that they meet certain requirements.
. . .
04/24/2024 (SUPPL-19)
7 Drug Interactions
7.5 Established and Potentially Significant Drug Interactions
Addition of clinical comments to the Oral medications or supplements containing polyvalent cations (e.g. Mg, Al, Ca, Fe) section of table 3; please refer to label for complete information
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 BIKTARVY 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 observational studies and the APR with BIC, FTC and TAF use during pregnancy have not established a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Reports of pregnant individuals treated with products containing BIC, FTC, or TAF contribute to APR’s overall risk assessment for these components. Available data from the APR show no statistically significant difference in the overall risk of major birth defects for BIC, FTC, or 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 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%.
BIKTARVY safety has also been evaluated in an open-label trial that demonstrated safety findings that were consistent with other trials in adults (see Data).
…
Data
Human Data
BIKTARVY was evaluated in an open-label clinical trial of 33 virologically- suppressed (HIV-1 RNA < 50 copies/mL) pregnant adults with HIV-1 and no known substitutions associated with resistance to BIC, FTC, or TAF. Pregnant adults were administered BIKTARVY (containing 50 mg of BIC, 200 mg of FTC and 25 mg of TAF) once daily from the second or third trimester through postpartum. Exposures of BIC, FTC, and TAF were lower during pregnancy as compared to postpartum [see Clinical Pharmacology (12.3)]. All 32 adult participants who completed the study maintained viral suppression during pregnancy, at delivery, and through Week 18 postpartum. The median CD4+ cell count at baseline was 558 cells/microliter, and the median change in CD4+ cell count from baseline to Week 12 postpartum was 159 cells/microliter. All 29 neonate participants had negative/nondetectable HIV-1 PCR results at birth and/or at 4 to 8 weeks post-birth. The safety findings in this trial were consistent with other trials in adults.
BIKTARVY was only studied in pregnant individuals who were virologically- suppressed, and lower plasma exposures of BIKTARVY were observed during pregnancy compared to post-partum. Therefore, BIKTARVY is recommended in pregnant individuals who are virologically-suppressed on a stable antiretroviral regimen with no known substitutions associated with resistance to any of the individual components of BIKTARVY.
Bictegravir (BIC):
Based on prospective reports to the APR of over 500 exposures to a BIC-containing regimen during pregnancy resulting in live births (including 423 exposed in the first trimester and 113 exposed in the second/third trimester), the prevalence of birth defects in live births was 4.3% (95% CI: 2.5% to 6.6%) and 1.8% (0.2%, 6.2%) following first and second/third trimester exposure, respectively, to a BIC-containing regimen.
Emtricitabine (FTC):
Based on prospective reports to the APR of over 6,500 exposures to FTC-containing regimens during pregnancy resulting in live births (including over 4,800 exposed in the first trimester and over 1,700 exposed in the second/third trimester), the prevalence of birth defects in live births was 2.9% (95% CI: 2.5% to 3.4%) and 2.8% (95% CI: 2.1% 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 1,200 exposures to TAF-containing regimens during pregnancy resulting in live births (including over 1000 exposed in the first trimester and over 200 exposed in the second/third trimester), the prevalence of birth defects in live births was 3.9% (95% CI: 2.8% to 5.2%) and 4.8% (95% CI: 2.5% to 8.3%) following first and second/third trimester exposure, respectively, to TAF-containing regimens.
Methodological limitations of the APR include the use of MACDP as the external comparator group. The MACDP population is not disease-specific, evaluatesindividuals and infants from a limited geographic area, and does not include outcomes for births that occurred at less than 20 weeks gestation.
8.2 Lactation
Additions and/or revisions underlined:
Risk Summary
Data from the published literature report the presence of BIC, FTC, TAF, and tenofovir in human milk. There are no data on the effects of BIC on the breastfed child. 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 BIC, FTC or TAF on milk production.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
Additions and/or revisions underlined:
How should I take BIKTARVY?
…
- If you are pregnant and take supplements or antacids that contain aluminum, magnesium, iron or calcium, talk to your healthcare provider about how to take BIKTARVY along with these supplements or antacids.
02/23/2024 (SUPPL-18)
6 Adverse Reactions
6.1 Clinical Trials Experience
…
Clinical Trials in Virologically Suppressed Adults
(Additions and/or revisions underlined)
The safety of BIKTARVY in virologically-suppressed adults was based on Week 48 data from 282 subjects in a randomized, double-blind, active-controlled trial (Trial 1844) in which virologically-suppressed subjects were switched from either DTG + ABC/3TC or ABC/DTG/3TC to BIKTARVY; Week 48 data from 290 subjects in an open-label, active- controlled trial in which virologically-suppressed subjects were switched from a regimen containing atazanavir (ATV) (given with cobicistat or ritonavir) or darunavir (DRV) (given with cobicistat or ritonavir) plus either FTC/TDF or ABC/3TC, to BIKTARVY (Trial 1878); and Week 48 data from a randomized, double-blind active-controlled trial in which 284 virologically-suppressed subjects were switched from DTG plus either FTC/TAF or FTC/TDF, to BIKTARVY (Trial 4030). Overall, the safety profile in virologically- suppressed adult subjects in Trials 1844, 1878, and 4030 was similar to that in subjects with no antiretroviral treatment history [see Clinical Studies (14.3)].
…
6.2 Postmarketing Experience
(Additions and/or revisions underlined)
The following events have been identified during post approval use of BIKTARVY or 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.
Renal and Urinary Disorders
Acute renal failure, acute tubular necrosis, proximal renal tubulopathy, and Fanconi syndrome
Skin and Subcutaneous Tissue Disorders
Angioedema, Stevens-Johnson syndrome/toxic epidermal necrolysis, and urticaria
Investigations
Weight increased
8 Use in Specific Populations
8.2 Lactation
Risk Summary
(Additions and/or revisions underlined)
It is not known whether BIKTARVY or all of the components of BIKTARVY are present in human breast milk, affects human milk production, or has effects on the breastfed infant. Based on published data, FTC has been shown to be present in human breast milk. BIC was detected in the plasma of nursing rat pups likely due to the presence of BIC in milk, and tenofovir has been shown to be present in the milk of lactating rats and rhesus monkeys after administration of TDF (see Data). It is unknown if TAF is present in animal milk.
Potential risks of breastfeeding include: (1) HIV-1 transmission to HIV-1 negative infants; (2) developing viral resistance in HIV-1 positive infants; and (3) adverse reactions in a breastfed infant similar to those seen in adults.
8.4 Pediatric Use
(Additions and/or revisions underlined)
The safety and effectiveness of BIKTARVY have been established as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in pediatric patients weighing at least 14 kg :
· who have no antiretroviral treatment history or
· to replace the current antiretroviral regimen in those who are virologically- suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no known or suspected resistance to bictegravir or tenofovir [see Indications and Usage (1), and Dosage and Administration (2.2, 2.3)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
Lactation
(Additions and/or revisions underlined)
Inform individuals with HIV-1 infection that the potential risks of breastfeeding include: (1) HIV-1 transmission to HIV-1–negative infants, (2) developing viral resistance in HIV-1–positive infants, and (3) adverse reactions in a breastfed infant similar to those seen in adults [see Use in Specific Populations (8.2)].
Patient Information BIKTARVY (bik-TAR-vee) (bictegravir, emtricitabine, and tenofovir alafenamide) tablets
(Additions and/or revisions underlined)
What should I tell my healthcare provider before taking BIKTARVY?
Before taking BIKTARVY, tell your healthcare provider about all your medical conditions, including if you:
· have liver problems, including HBV infection
· have kidney problems
· are pregnant or plan to become pregnant. It is not known if BIKTARVY can harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with BIKTARVY.
Pregnancy Registry: There is a pregnancy registry for women who take BIKTARVY during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk with your healthcare provider about how you can take part in this registry.
· are breastfeeding or plan to breastfeed. At least one of the medicines in BIKTARVY can pass to your baby in your breast milk. It is not known if the other medicines in BIKTARVY can pass into your breast milk.
· Talk to your healthcare provider about the following risks of breastfeeding during treatment with BIKTARVY:
o The HIV-1 virus may pass to your baby if your baby does not have the HIV-1 infection
o The HIV-1 virus may become harder to treat if your baby has HIV-1 infection.
o Your baby may get side effects from BIKTARVY.
10/14/2022 (SUPPL-15)
6 Adverse Reactions
6.1 Clinical Trials ExperienceExtensive changes to add Week 144 efficacy and safety data; please refer to label
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Patient InformationNewly added information:
BIKTARVY contains a desiccant packet to help keep your medicine dry (protect it from moisture). Keep the desiccant packet in the bottle. Do not eat the desiccant packet.
10/07/2021 (SUPPL-14)
6 Adverse Reactions
6.1 Clinical Trials ExperienceAdditions and/or revisions underlined
…
Clinical Trials in Pediatric Subjects
The safety of BIKTARVY was evaluated in HIV-1 infected virologically-suppressed subjects between the ages of 12 to less than 18 years and weighing at least 35 kg (N=50) through Week 48 (cohort 1), in virologically-suppressed subjects between the ages of 6 to less than 12 years and weighing at least 25 kg (N=50) through Week 24 (cohort 2), and in virologically suppressed subjects at least 2 years of age and weighing at least 14 to less than 25 kg (N=22) through Week 24 (cohort 3) in an open label clinical trial (Trial 1474) [see Clinical Studies (14.4)]. No new adverse reactions or laboratory abnormalities were identified compared to those observed in adults. Adverse reactions were reported in 11% of pediatric subjects. The majority (76%) of adverse reactions were Grade 1. No Grade 3 or 4 adverse reactions were reported. The adverse reaction reported by more than one subject (regardless of severity) was abdominal discomfort (n=2). One subject (1%) had Grade 2 adverse reactions of insomnia and anxiety that led to discontinuation of BIKTARVY. The other adverse reactions that occurred in single subjects were similar to those seen in adults.
8 Use in Specific Populations
8.4 Pediatric UseAdditions and/or revisions underlined
The safety and effectiveness of BIKTARVY have been established as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in pediatric patients weighing at least 14 kg who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of BIKTARVY [see Indications and Usage (1) and Dosage and Administration (2.2, 2.3)].
Use of BIKTARVY in pediatric patients weighing at least 14 kg is supported by the following:
trials in adults [see Clinical Studies (14.1)]
an open-label trial in three age-based cohorts of virologically-suppressed pediatric subjects [see Clinical Studies (14.4)]
Cohort 1: 12 to less than 18 years of age and weighing at least 35 kgreceiving BIKTARVY through Week 48 (N=50),
Cohort 2: 6 to less than 12 years of age and weighing at least 25 kg receiving BIKTARVY through Week 24 (N=50), and
Cohort 3: at least 2 years of age and weighing at least 14 to less than 25 kg through Week 24 (N=22). No pediatric subjects 2 years of age were enrolled; of the 6 pediatric subjects who were 3 years of age at enrollment, 3 subjects weighed between 14 to less than 15 kg.
The safety and efficacy of BIKTARVY in these pediatric subjects were similar to that in adults, and there was no clinically significant change in exposure for the components of BIKTARVY [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.4)].
Safety and effectiveness of BIKTARVY in pediatric patients weighing less than 14 kg have not been established.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATIONAdditions underlined
…
Tablet Splitting
Advise caregivers that, for children unable to swallow a whole tablet, the tablet can be split and each part taken separately as long as all parts are ingested within approximately 10 minutes [see Dosage and Administration (2.3)].
…
Additions and/or revisions underlined
…
What is BIKTARVY?
BIKTARVY is a prescription medicine that is used without other human immunodeficiency virus-1 (HIV-1) medicines to treat HIV-1 infection in adults and children who weigh at least 31 pounds (14 kg):
who have not received HIV-1 medicines in the past, or
to replace their current HIV-1 medicines for people whose healthcare provider determines that they meet certain requirements.
HIV-1 is the virus that causes Acquired Immune Deficiency Syndrome (AIDS). BIKTARVY contains the medicines bictegravir, emtricitabine, and tenofovir alafenamide.
It is not known if BIKTARVY is safe and effective in children who weigh less than 31 pounds (14 kg).
…
How should I take BIKTARVY?
…
For children unable to swallow a whole tablet, the tablet can be split and each part taken separately as long as all parts are swallowed within about 10 minutes.
…
How should I store BIKTARVY?
Store BIKTARVY bottle below 86 °F (30 °C).
Keep the bottle tightly closed.
Store BIKTARVY blister pack at room temperature between 68 °F to 77 °F (20 °C to 25 °C).
Keep BIKTARVY in its original bottle or blister pack.
BIKTARVY comes in a child-resistant package.
…
09/10/2021 (SUPPL-13)
8 Use in Specific Populations
8.1 Pregnancy
(Additions and/or revisions are underlined)
Risk Summary
There are insufficient human data on the use of BIKTARVY during pregnancy to inform a drug-associated risk of birth defects and miscarriage. Dolutegravir, another integrase inhibitor, has been associated with neural tube defects (NTDs) (see Data). Discuss the benefit-risk of using BIKTARVY with individuals of childbearing potential, particularly if pregnancy is being planned. BIKTARVY use during pregnancy has been evaluated in a limited number of women reported to the APR; consequently, there are insufficient BIC data from the APR to adequately assess the risk of major birth defects. Reports of pregnant individuals treated with other drug products containing TAF or FTC contribute to APR’s overall risk assessment for these components. Available data from the APR show no statistically significant difference in the overall risk of major birth defects for FTC or 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 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%.
Data
Human Data
Prospective reports from the APR of overall major birth defects in pregnancies exposed to the components of BIKTARVY 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.
Bictegravir (BIC):
Data from an observational study in Botswana showed that dolutegravir, another integrase inhibitor, was associated with increased risk of neural tube defects when administered at the time of conception and in early pregnancy. Data available to date from other sources including the APR, clinical trials, and postmarketing data are insufficient to address this risk with BIC.
There are an insufficient number of reports to the APR to adequately assess the risk of major birth defects associated with BIC exposure. The APR has received prospective reports of 3 birth defects among 100 (3.0%) first trimester exposures to BIC-containing regimens during pregnancy resulting in live births. No birth defects were reported among 40 exposures during the second/third trimester.
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-10)
5 Warnings and Precautions
5.4 New Onset or Worsening Renal ImpairmentAdditions 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.
…
6 Adverse Reactions
6.1 Clinical Trials Experience
Additions underlined
…
Changes in Serum Creatinine:… There were no discontinuations due to renal adverse events and renal serious adverse events were encountered in less than 1% of participants treated with BIKTARVY through Week 48 in clinical trials.
…
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)
PATIENT COUNSELING INFORMATIONAdditions underlined
…
Renal Impairment
Advise patients to avoid taking BIKTARVY 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)].
…
02/24/2021 (SUPPL-8)
8 Use in Specific Populations
8.5 Geriatric Use(Additions and/or revisions underlined)
Clinical trials in virologically-suppressed subjects (Trials 4449, 1844, and 1878) included 111 subjects aged 65 years and over who received BIKTARVY, including 86 patients from an open-label, single-arm trial of subjects aged 65 years and over who were switched from their previous antiretroviral regimen to BIKTARVY [see Clinical Studies (14.3)]. Of the total number of BIKTARVY-treated patients in these trials, 100 (90%) were 65 to 74 years of age, and 11 (10%) were 75 to 84 years of age. No overall differences in safety or effectiveness were observed between elderly subjects and adults between 18 and less than 65 years of age, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
02/11/2021 (SUPPL-9)
6 Adverse Reactions
6.2 Postmarketing Experience
(Additions and/or revisions underlined)
The following events have been identified during post approval use of BIKTARVY or 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, Stevens-Johnson syndrome/toxic epidermal necrolysis, and urticaria
02/05/2021 (SUPPL-7)
5 Warnings and Precautions
5.4 New Onset or Worsening Renal Impairment(Additions and/or revisions underlined)
BIKTARVY is not recommended in patients with severe renal impairment (estimated creatinine clearance of 15 to below 30 mL per minute), or patients with ESRD (estimated creatinine clearance below 15 mL per minute) who are not receiving chronic hemodialysis, or patients with no antiretroviral treatment history and ESRD who are receiving chronic hemodialysis [see Dosage and Administration (2.3), Use in Specific Populations (8.6)].
6 Adverse Reactions
6.1 Clinical Trials Experience(Newly added information)
Clinical Trial in Adults with End Stage Renal Disease (ESRD) Receiving Chronic Hemodialysis
The safety of FTC and TAF (components of BIKTARVY) was evaluated in a single arm, open-label trial (Trial 1825) in virologically-suppressed adults with ESRD (estimated creatinine clearance of less than 15 mL/min) on chronic hemodialysis treated with FTC+TAF in combination with elvitegravir and cobicistat as a fixed-dose combination tablet for 96 weeks (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 65% of subjects and the most common serious adverse events were pneumonia (15%), fluid overload (7%), hyperkalemia (11%) and osteomyelitis (7%). Overall 7% of subjects permanently discontinued treatment due to an adverse event. In an extension phase of Trial 1825 in which 10 subjects switched to BIKTARVY for 48 weeks, the safety findings were similar to those in the initial phase of the open-label trial [see Use in Specific Populations (8.6), Clinical Studies (14.3)].
8 Use in Specific Populations
8.4 Renal Impairment(Additions and/or revisions underlined)
The pharmacokinetics, safety, virologic and immunologic responses of FTC and TAF (components of BIKTARVY) were evaluated in a single arm, open-label trial (Trial 1825) in virologically-suppressed adults with ESRD (estimated creatinine clearance of less than 15 mL/min) on chronic hemodialysis treated with FTC+TAF in combination with elvitegravir and cobicistat as a fixed-dose combination tablet for 96 weeks (N=55). In an extension phase of Trial 1825, 10 virologically-suppressed subjects switched to BIKTARVY and all remained virologically suppressed for 48 weeks [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.3)].
No dosage adjustment of BIKTARVY is recommended in patients with estimated creatinine clearance greater than or equal to 30 mL per minute, or in virologically- suppressed 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 BIKTARVY after completion of hemodialysis treatment [see Dosage and Administration (2.3)]
BIKTARVY is not recommended in patients with severe renal impairment (estimated creatinine clearance of 15 to below 30 mL per minute, by Cockcroft-Gault), or patients with ESRD (estimated creatinine clearance below 15 mL per minute) who are not receiving chronic hemodialysis, or patients with no antiretroviral treatment history and ESRD who are receiving chronic hemodialysis, as the safety and/or efficacy of BIKTARVY has not been established in these populations [see Dosage and Administration (2.3), Warnings and Precautions (5.4) and Clinical Pharmacology (12.3)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Patient Information(Newly added section)
08/02/2019 (SUPPL-6)
8 Use in Specific Populations
8.1 Pregnancy(additions underlined)
…
Risk Summary
There are insufficient human data on the use of BIKTARVY during pregnancy to inform a drug-associated risk of birth defects and miscarriage. Dolutegravir, another integrase inhibitor, has been associated with neural tube defects (NTDs) (see Data). Discuss the benefit-risk of using BIKTARVY with individuals of childbearing potential, particularly if pregnancy is being planned.
…
Data
Human Data
Bictegravir: Data from an observational study in Botswana showed that dolutegravir, another integrase inhibitor, was associated with increased risk of neural tube defects when administered at the time of conception and in early pregnancy. Data available to date from other sources including the APR, clinical trials, and postmarketing data are insufficient to address this risk with BIC.
...
06/18/2019 (SUPPL-5)
5 Warnings and Precautions
5.3 Immune Reconstitution Syndrome(Additions and/or revisions underlined)
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.
6 Adverse Reactions
6.1 Clinical Trials Experience(Additions and/or revisions underlined)
Clinical Trials in Pediatric Subjects
The safety of BIKTARVY was evaluated in HIV-1 infected virologically-suppressed subjects between the ages of 12 to less than 18 years and weighing at least 35 kg (N=50) through Week 48 (cohort 1), and in virologically-suppressed subjects between the ages of 6 to less than 12 years and weighing at least 25 kg (N=50) through Week 24 (cohort 2) in an open label clinical trial (Trial 1474). No new adverse reactions or laboratory abnormalities were identified compared to those
observed in adults. Adverse reactions were reported in 10% of pediatric subjects. The majority (85%) of adverse reactions were Grade 1. No Grade 3 or 4 adverse reactions were reported. The adverse reaction reported by more than one subject (regardless of severity) was abdominal pain (n=2). One subject (1%) had Grade 2 adverse reactions of insomnia and anxiety that led to discontinuation of BIKTARVY. The other adverse reactions that occurred in single subjects were similar to those seen in adults.
(Newly Added Subsection)
The following events have been identified during post approval 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 and urticaria
8 Use in Specific Populations
8.4 Pediatric Use(Additions and/or revisions underlined)
The safety and effectiveness of BIKTARVY for the treatment of HIV-1 infection was established in pediatric patients with body weight greater than or equal to 25 kg.
Use of BIKTARVY in pediatric patients between the ages of 6 to less than 18 years and weighing at least 25 kg is supported by trials in adults and by an open-label trial in virologically-suppressed pediatric subjects aged 12 to less than 18 years and weighing at least 35 kg receiving BIKTARVY through Week 48 (cohort 1 of Trial 1474, N=50) and in virologically-suppressed pediatric subjects aged 6 to less than 12 years and weighing at least 25 kg receiving BIKTARVY through Week 24 (cohort 2 of Trial 1474, N=50). The safety and efficacy of BIKTARVY in these pediatric subjects was similar to that in adults, and there was no clinically significant change in exposure for the components of BIKTARVY.
Safety and effectiveness of BIKTARVY in pediatric patients weighing less than 25 kg have not been established.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION(Additions and/or revisions underlined)
What is BIKTARVY?
BIKTARVY is a prescription medicine that is used without other anti-HIV-1 medicines to treat Human Immunodeficiency Virus-1 (HIV-1) in adults and children who weigh at least 55 pounds (25 kg):
• who have not received anti-HIV-1 medicines in the past, or
• to replace their current anti-HIV-1 medicines for people whose healthcare provider determines that they meet certain requirements.
HIV-1 is the virus that causes (Acquired Immune Deficiency Syndrome (AIDS).
BIKTARVY contains the medicines bictegravir, emtricitabine, and tenofovir alafenamide.
It is not known if BIKTARVY is safe and effective in children who weigh less than 55 pounds (25 kg).
How should I take BIKTARVY?
• Take BIKTARVY exactly as your healthcare provider tells you to take it. BIKTARVY is taken by itself (not with other HIV-1 medicines) to treat HIV-1 infection.
• Take BIKTARVY 1 time each day with or without food.
• Do not change your dose or stop taking BIKTARVY without first talking with your healthcare provider. Stay under a healthcare provider’s care during treatment with BIKTARVY.
• If you take antacids that contain aluminum or magnesium, take BIKTARVY at least 2 hours before or 6 hours after you take these antacids.
• If you take supplements or antacids that contain iron or calcium, take BIKTARVY with food at the same time that you take these supplements or antacids.
• Do not miss a dose of BIKTARVY.
• If you take too much BIKTARVY, call your healthcare provider or go to the nearest hospital emergency room right away.
• When your BIKTARVY supply starts to run low, get more from your healthcare provider or pharmacy. This is very important because the amount of virus in your blood may increase if the medicine is stopped for even a short time. The virus may develop resistance to BIKTARVY and become harder to treat.