INDICATION
BIKTARVY® is indicated as a complete regimen for the treatment of HIV-1 infection in adult and pediatric patients weighing ≥25 kg who have no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of BIKTARVY.
Please see below for Important Safety Information for BIKTARVY.
Few Contraindications and Drug-Drug Interactions1
BIKTARVY® is contraindicated with two medications: dofetilide and rifampin
Established and Potentially Significant* Drug Interactions:
Alteration in Regimen May Be Recommended
| Concomitant Drug Class: Drug Name | Clinical Comment | ||||||||||||
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- For an aging patient population, which may have comorbidities, the safety profile and drug-drug interactions of a treatment are important considerations when choosing a therapy2
*Table is not all-inclusive.
†Drug-drug interaction study was conducted with either BIKTARVY or its components as individual agents.
‡Strong inducer of CYP3A and P-gp, and inducer of UGT1A1.
§The induction potency of St. John's wort may vary widely based on preparation.
No Known Dose Adjustments When BIKTARVY Is Coadministered With These Medications1
Drugs With No Clinically Significant Interactions With BIKTARVY
| Drug Class | Drug Within Class | ||||||||
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Warnings and Precautions1
| Drug interactions: See Contraindications and Drug Interactions sections. Consider the potential for drug interactions prior to and during BIKTARVY therapy and monitor for adverse reactions. |
| Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported. |
|
New onset or worsening renal impairment: Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with tenofovir alafenamide (TAF)—containing products. Do not initiate BIKTARVY in patients with estimated creatinine clearance (CrCl) <30 mL/min except in virologically suppressed adults <15 mL/min who are receiving chronic hemodialysis. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue BIKTARVY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
Renal monitoring: Prior to or when initiating BIKTARVY and during therapy, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, assess serum phosphorus. |
| Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue BIKTARVY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations. |
Established Safety Profile.
Demonstrated Long-Term Safety and Tolerability Profile in Treatment-Naïve Adults Through Week 1443,4
|
Study 1489 |
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| Adverse Reactions (ARs) (All Grades) Reported in ≥2% of Adults Who Received BIKTARVY |
BIKTARVY(n=314)
ABC/
DTG/3TC(n=315) |
Study 1490 BIKTARVY(n=320)
FTC/TAF
+DTG(n=325) |
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Frequencies of ARs are based on all adverse events attributed to trial drugs by the investigator. No ARs of Grade 2 or higher occurred in >1% of subjects treated with BIKTARVY.
In Study 1490, no adults discontinued BIKTARVY due to weight-related AEs through Week 144 and within the OLE through Week 1923-5
- In Study 1490, an AE of weight increase was reported for BIKTARVY (2.5%), FTC/TAF+DTG (3.1%), and weight decrease for BIKTARVY (0.9%), FTC/TAF+DTG (0.9%)
IMPORTANT SAFETY INFORMATION
Contraindications
- Coadministration: Do not use BIKTARVY with dofetilide or rifampin.
AE, adverse event; DTG, dolutegravir; FTC, emtricitabine; TAF, tenofovir alafenamide.
In Study 1489, no adults discontinued BIKTARVY due to weight-related AEs through Week 144 and within the OLE through Week 1923-5
- In Study 1489, an AE of weight increase was reported for BIKTARVY (2.9%), ABC/DTG/3TC (4.1%), and weight decrease for BIKTARVY (1.9%), ABC/DTG/3TC (1.6%)
IMPORTANT SAFETY INFORMATION
Contraindications
- Coadministration: Do not use BIKTARVY with dofetilide or rifampin.
3TC, lamivudine; ABC, abacavir; AE, adverse event; DTG, dolutegravir.
The majority (84%) of AEs associated with BIKTARVY were Grade 13
Demonstrated Safety and Tolerability Profile in Virologically Suppressed Adults Through Week 481,3,6,7
| Adverse Reactions (ARs) (All Grades) Reported in ≥2% of Adults Who Switched to BIKTARVY |
Study 1844 BIKTARVY(n=282)
ABC/
DTG/3TC(n=281) |
Study 1878 BIKTARVY(n=290)
ATV- or DRV-Based Regimen(n=287)
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Frequencies of ARs are based on all adverse events attributed to trial drugs by the investigator. No ARs of Grade 2 or higher occurred in ≥1% of subjects treated with BIKTARVY.
- The majority of adverse events associated with BIKTARVY were Grade 1 in Study 1878 (76%) and in Study 1844 (58%)
- The most common ARs (incidence ≥5%; all grades) in clinical trials of treatment-naïve adults who received BIKTARVY were diarrhea, nausea, and headache
- Overall, the safety profile of BIKTARVY in virologically suppressed adults was similar to that of treatment-naïve adults
Demonstrated Safety and Tolerability Profile in Virologically Suppressed Adult Women Through Week 483
| Adverse Reactions (ARs) (All Grades) Reported in ≥0.5% of Adult Women Who Switched to BIKTARVY |
Study 1961 BIKTARVY(n=234)
INSTI- or PI-
Based Regimen(n=236) |
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Through Week 48, no adult women discontinued due to AEs in either treatment arm8
Overall, 1% of Treatment-Naïve Adults Discontinued BIKTARVY Due to AEs Through Week 1443,4
Discontinuation Rates Due to AEs
BIKTARVY(n=314) |
ABC/DTG/3TC(n=315) |
0.0% |
1.6% |
Study 1489 Treatment-Naïve Adults |
|
BIKTARVY(n=320) |
FTC/TAF+DTG(n=325) |
1.9% |
1.8% |
Study 1490 Treatment-Naïve Adults |
|
No adults discontinued BIKTARVY due to renal-, hepatic-, bone-, or weight-related adverse events4
- BIKTARVY is not recommended in patients with severe hepatic impairment (Child-Pugh Class C), and is not recommended in patients with severe renal impairment (estimated CrCl <30 mL/min) except in virologically suppressed patients with CrCl <15 mL/min on chronic hemodialysis
Overall, 1% of Virologically Suppressed Adults Discontinued BIKTARVY Due to AEs Through Week 483,6-8
Discontinuation Rates Due to AEs
| BIKTARVY(n=282) | ABC/DTG/3TC(n=281) |
2.1% |
0.7% |
Study 1844 Virologically Suppressed Adults |
|
|
ATV- or DRV- Based Regimen (n=287) |
0.7% |
0.3% |
Study 1878 Virologically Suppressed Adults |
|
|
INSTI- or PI- Based Regimen (n=236) |
0.0% |
0.0% |
Study 1961 Virologically Suppressed Adult Women |
|
No adults discontinued BIKTARVY due to renal-, hepatic-, or bone-related adverse events3,6-8
- Prior to or when initiating BIKTARVY and during therapy, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, assess serum phosphorus
Please see below for Important Safety Information for BIKTARVY.
INDICATION
BIKTARVY® is indicated as a complete regimen for the treatment of HIV-1 infection in adult and pediatric patients weighing ≥25 kg who have no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of BIKTARVY.
Please see below for Important Safety Information for BIKTARVY.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
- Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of BIKTARVY. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue BIKTARVY. If appropriate, anti-hepatitis B therapy may be warranted.
Contraindications
- Coadministration: Do not use BIKTARVY with dofetilide or rifampin.
Warnings and precautions
- Drug interactions: See Contraindications and Drug Interactions sections. Consider the potential for drug interactions prior to and during BIKTARVY therapy and monitor for adverse reactions.
- Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported.
- New onset or worsening renal impairment: Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with tenofovir alafenamide (TAF)–containing products. Do not initiate BIKTARVY in patients with estimated creatinine clearance (CrCl) <30 mL/min except in virologically suppressed adults <15 mL/min who are receiving chronic hemodialysis. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue BIKTARVY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
Renal monitoring: Prior to or when initiating BIKTARVY and during therapy, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, assess serum phosphorus. - Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue BIKTARVY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.
Adverse reactions
- Most common adverse reactions (incidence ≥5%; all grades) in clinical studies through week 144 were diarrhea (6%), nausea (6%), and headache (5%).
Drug interactions
- Prescribing information: Consult the full prescribing information for BIKTARVY for more information on Contraindications, Warnings, and potentially significant drug interactions, including clinical comments.
- Enzymes/transporters: Drugs that induce P-gp or induce both CYP3A and UGT1A1 can substantially decrease the concentration of components of BIKTARVY. Drugs that inhibit P-gp, BCRP, or inhibit both CYP3A and UGT1A1 may significantly increase the concentrations of components of BIKTARVY. BIKTARVY can increase the concentration of drugs that are substrates of OCT2 or MATE1.
- Drugs affecting renal function: Coadministration of BIKTARVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC and tenofovir and the risk of adverse reactions.
Dosage and administration
- Dosage: Patients weighing ≥25 kg: 1 tablet taken once daily with or without food.
- Renal impairment: Not recommended in patients with CrCl 15 to <30 mL/min, or <15 mL/min who are not receiving chronic hemodialysis, or <15 mL/min who are receiving chronic hemodialysis and have no antiretroviral treatment history.
- Hepatic impairment: Not recommended in patients with severe hepatic impairment.
- Prior to or when initiating: Test patients for HBV infection.
- Prior to or when initiating, and during treatment: As clinically appropriate, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus.
Pregnancy and lactation
- Pregnancy: There is insufficient human data on the use of BIKTARVY during pregnancy. Dolutegravir, another integrase inhibitor, has been associated with neural tube defects. Discuss the benefit-risk of using BIKTARVY during pregnancy and conception. An Antiretroviral Pregnancy Registry (APR) has been established. Available data from the APR for FTC shows no difference in the rates of birth defects compared with a US reference population.
- Lactation: Women infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission.
Please see full Prescribing Information for BIKTARVY® and DESCOVY®, including BOXED WARNINGS.
3TC, lamivudine; ABC, abacavir; AE, adverse event; Al, aluminum; ATV, atazanavir; BIC, bictegravir; Ca, calcium; CrCl, creatinine clearance; DRV, darunavir; DTG, dolutegravir; Fe, iron; FTC, emtricitabine; HCV, hepatitis C virus; INSTI, integrase strand transfer inhibitor; Mg, magnesium; NSAIDs, nonsteroidal anti-inflammatory drugs; PI, protease inhibitor; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.
References: 1. BIKTARVY. Package insert. Gilead Sciences, Inc.; 2021. 2. Burgess MJ, Zeuli JD, Kasten MJ. Management of HIV/AIDS in older patients-drug/drug interactions and adherence to antiretroviral therapy. HIV/AIDS (Auckl). 2015;7:251-264. 3. Data on file. Gliead Sciences, Inc. 4. Orkin C, DeJesus E, Sax PE, et al. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV. 2020;7(6):e389-e400. 5. Workowski K, Orkin C, Sax P, et al. Four-year outcomes of B/F/TAF in treatment-naïve adults. Presented at: 28th Conference on Retroviruses and Opportunistic Infections; March 6-10, 2021; Virtual. Abstract 415. 6. Molina JM, Ward D, Brar I, et al. Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet HIV. 2018;5(7):e357-e365. 7. Daar ES, DeJesus E, Ruane P, et al. Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2018;5(7):e347-e356. 8. Kityo C, Hagins D, Koenig E, et al. Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) in virologically suppressed HIV-1 infected women: a randomized, open-label, multicenter, active-controlled, phase 3, noninferiority trial. J Acquir Immune Defic Syndr. 2019;82(3):321-328.