BIKTARVY® | Safety & Tolerability Profile in Treatment-Naive Adults

INDICATION

BIKTARVY^® is indicated as a complete regimen for the treatment of HIV-1 infection in adults 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 for ≥3 months with no history of treatment failure and no known resistance to any component of BIKTARVY.

DHHS RECOMMENDED
AS AN INITIAL REGIMEN FOR
ADULTS WITH HIV-1¹

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

Antiarrhythmics: Dofetilide	Coadministration is contraindicated due to the potential for serious and/or life-threatening events associated with dofetilide therapy.
Anticonvulsants: Carbamazepine^† Oxcarbazepine Phenobarbital Phenytoin	Coadministration with alternative anticonvulsants should be considered.
Antimycobacterials: Rifabutin^† Rifampin^†‡ Rifapentine	Coadministration with rifampin is contraindicated due to the effect of rifampin on the BIC component of BIKTARVY. Coadministration with rifabutin or rifapentine is not recommended.
Herbal products: St. John's wort^§	Coadministration with St. John's wort is not recommended.
Medications or oral supplements containing polyvalent cations (e.g., Mg, Al, Ca, Fe): Calcium or iron supplements^† Cation-containing antacids or laxatives^† Sucralfate Buffered medications	Antacids containing Al/Mg or Calcium: BIKTARVY can be taken under fasting conditions 2 hours before antacids containing Al/Mg or calcium. Routine administration of BIKTARVY simultaneously with, or 2 hours after, antacids containing Al/Mg or calcium is not recommended. Supplements containing Calcium or Iron: BIKTARVY and supplements containing calcium or iron can be taken together with food. Routine administration of BIKTARVY under fasting conditions simultaneously with, or 2 hours after, supplements containing calcium or iron is not recommended.
Metformin	Refer to the prescribing information of metformin for assessing the benefit and risk of concomitant use of BIKTARVY and metformin.

*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

Oral contraceptive	Ethinyl estradiol, norgestimate
HCV antiviral	Sofosbuvir, sofosbuvir/velpatasvir, ledipasvir/sofosbuvir, and sofosbuvir/velpatasvir/voxilaprevir
Benzodiazepine	Midazolam
Selective serotonin reuptake inhibitor	Sertraline

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: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. In clinical trials of BIKTARVY, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). Do not initiate BIKTARVY in patients with estimated creatinine clearance (CrCl) <30 mL/min. 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, also 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.

Demonstrated Safety and Tolerability Profile in Treatment-Naïve Adults Through Week 48¹

Adverse Reactions (ARs) (All Grades) Reported in ≥2% of Adults Who Received BIKTARVY

Study 1489

BIKTARVY(n=314)

ABC/
DTG/3TC(n=315)

Study 1490

BIKTARVY(n=320)

FTC/TAF
+DTG(n=325)

Diarrhea, %	6	4	3	3
Nausea, %	5	17	3	5
Headache, %	5	5	4	3
Fatigue, %	3	3	2	2
Abnormal dreams, %	3	3	<1	1
Dizziness, %	2	3	2	1
Insomnia, %	2	3	2	<1

Adverse Reactions (ARs) (All Grades) Reported in ≥2% of Adults Who Received BIKTARVY

Study 1490

BIKTARVY(n=320)

FTC/TAF
+DTG(n=325)

Diarrhea, %	3	3
Nausea, %	3	5
Headache, %	4	3
Fatigue, %	2	2
Abnormal dreams, %	<1	1
Dizziness, %	2	1
Insomnia, %	2	<1

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 (87%) of AEs associated with BIKTARVY were Grade 1

Overall, 1% of Treatment-Naïve Adults Discontinued BIKTARVY Due to AEs Through Week 48^1-3

Discontinuation Rates Due to AEs

	BIKTARVY(n=314)	ABC/DTG/ 3TC(n=315)
Study 1489 Treatment-Naïve Adults	0.0%	1.3%

	BIKTARVY(n=320)	FTC/TAF +DTG(n=325)
Study 1490 Treatment-Naïve Adults	1.6%	0.3%

No adults discontinued BIKTARVY due to renal or hepatic adverse events¹

Prior to or when initiating BIKTARVY, and during treatment with BIKTARVY, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, also assess serum phosphorus

INDICATION

DHHS RECOMMENDED
AS AN INITIAL REGIMEN FOR
ADULTS WITH HIV-1¹

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: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. In clinical trials of BIKTARVY, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). Do not initiate BIKTARVY in patients with estimated creatinine clearance (CrCl) <30 mL/min. 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, also 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 were diarrhea (6%), nausea (5%), 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: 1 tablet taken once daily with or without food.
Renal impairment: Not recommended in patients with CrCl <30 mL/min.
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. 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; Al, aluminum; BIC, bictegravir; Ca, calcium; DDIs, drug-drug interactions; DTG, dolutegravir; Fe, iron; FTC, emtricitabine; HCV, hepatitis C virus; Mg, magnesium; NSAIDs, nonsteroidal anti-inflammatory drugs; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.

References: 1. BIKTARVY [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2018. 2. Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017;390(10107):2063-2072. 3. Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet. 2017;390(10107):2073-2082.