Bictegravir-Emtricitabine-Tenofovir AF

Bictegravir-Emtricitabine-Tenofovir AF is a combination medication used to treat the symptoms of Human Immunodeficiency Virus Infection. 

• Bictegravir/emtricitabine/tenofovir AF is a prescription medication indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing  at least 14 kg:
• with 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
• 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 substitutions associated with resistance to bictegravir or tenofovir

Bictegravir-Emtricitabine-Tenofovir AF is available under the following different brand names: Biktarvy

Common side effects of Bictegravir/emtricitabine/tenofovir AF include:

• diarrhea 
• nausea
• headache

Serious side effects of Bictegravir/emtricitabine/tenofovir AF include:

• worsening of hepatitis B virus (HBV)
• immune reconstitution syndrome
• new or worsening kidney problems, including kidney failure
• symptoms of lactic acidosis may include weakness or tiredness, muscle pain, trouble breathing, abdominal pain with nausea and vomiting, cold or blue hands and feet, dizziness,  or a fast or abnormal heartbeat 
• symptoms of severe liver problems may include skin or the white part of the eyes turning yellow, dark (tea-colored) urine, light-colored stools, loss of appetite for several days or longer, nausea, or abdominal pain

Rare side effects of Bictegravir-Emtricitabine-Tenofovir AF include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet

• 50 mg/200 mg/25 mg
• 30 mg/120 mg/15 mg

Human Immunodeficiency Virus Infection

Adult dosage

• 1 tablet orally once a day

Pediatric dosage

• Children below 14 kg: Safety and efficacy not established
• Children above 14 to 25 kg: 1 tablet (30 mg/120 mg/15 mg) orally once a day
• Children above 25 kg: 1 tablet (50 mg/200 mg/25 mg) orally once a day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Drug interactions overview
  • Bictegravir inhibits OCT2 and MATE1; coadministration with drugs that are OCT2 and MATE1 substrates may increase their plasma concentrations
  • Strong CYP3A inducers that also induce UGT1A1 can substantially decrease bictegravir plasma concentrations, which may lead to loss of therapeutic effect of bictegravir/emtricitabine/tenofovir AF and development of resistance
  • Strong CYP3A4 inhibitors that also inhibit UGT1A1 may significantly increase bictegravir plasma concentrations
  • Coadministration of drugs that inhibit P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may increase the absorption and plasma concentrations of tenofovir AF
  • Coadministration of drugs that induce P-gp activity is expected to decrease the absorption of tenofovir AF, resulting in decreased plasma concentration of tenofovir AF, which may lead to loss of therapeutic effect of treatment and development of resistance
  • Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of emtricitabine and tenofovir, thereby increasing the risk of adverse

Contraindications

• Coadministration with dofetilide and/or rifampin

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Bictegravir-Emtricitabine-Tenofovir AF?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Bictegravir-Emtricitabine-Tenofovir AF?”

Cautions

• Patients with HIV-1 infection should be tested for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy (ART); not approved for the treatment of chronic HBV infection (see Black Box Warnings)
• Immune reconstitution syndrome is reported in patients treated with combination ART therapy; autoimmune disorders (.g, Graves’ disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) may occur in the setting of immune reconstitution; time to onset varies and can occur many months after initiation of treatment
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with use; suspend treatment if a patient develops signs or symptoms of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis, even in absence of marked transaminase elevations)
• New-onset or worsening renal impairment
  • Cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia) reported with the use of tenofovir prodrugs
  • Discontinue drug if clinically significant decreases in renal function or evidence of Fanconi syndrome develop
  • Avoid concurrent or recent use of the nephrotoxic drug, including nonsteroidal anti-inflammatory drugs, owing to the increased risk of developing renal-related adverse reactions
• Drug interactions overview
  • Bictegravir inhibits OCT2 and MATE1; coadministration with drugs that are OCT2 and MATE1 substrates may increase their plasma concentrations (also see Contraindications)
  • Strong CYP3A inducers that also induce UGT1A1 can substantially decrease raltegravir plasma concentrations, which may lead to loss of therapeutic effect of Bictegravir-Emtricitabine-Tenofovir AF and development of resistance (also see Contraindications)
  • Strong CYP3A4 inhibitors that also inhibit UGT1A1 may significantly increase bictegravir plasma concentrations
  • Coadministration of drugs that bit of P-glycoprotein (P-GP) and breast cancer resistance protein (BCRP) may increase the absorption and plasma concentrations of tenofovir AF
  • Coadministration of drugs that induce P-positivity is expected to decrease the absorption of tenofovir AF, resulting in reduced plasma concentration of tenofovir AF, which may lead to loss of therapeutic effect of treatment and development of resistance
  • Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of emtricitabine and tenofovir, thereby increasing the risk of adverse effects

Pregnancy and Lactation

• There is insufficient human data on the use of Bictegravir-Emtricitabine-Tenofovir AF during pregnancy to inform a drug-associated risk of birth defects and miscarriage
• Bictegravir: Data from an observational study in Botswana showed that dolutegravir, another integrase inhibitor, was associated with an 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 pregnancy registry, clinical trials, and postmarketing data are insufficient to address this risk with raltegravir
• Bictegravir and tenofovir AF use in women during pregnancy has not been evaluated
• Emtricitabine (FTC) use during pregnancy in a limited number of women reported to the APR showed no difference in the overall risk of major birth defects for FTC compared with the background rate for major birth defects
• Pregnancy registry
  • Registry monitors pregnancy outcomes in women exposed to Bictegravir-Emtricitabine-Tenofovir AF during pregnancy
  • Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263
• Lactation
  • The Centers for Disease Control and Prevention do not recommend HIV-infected mothers breastfeed their infants owing to the potential risk for postnatal transmission of HIV
  • Data from the published literature reports on the presence of BIC, FTC, TAF, and tenofovir in human milk; there is no data on the effects of BIC on the breastfed child
  • Data from published literature have not reported adverse effects of FTC or TAF on a breastfed child; there is no data on the effects of BIC, FTC, or TAF on milk production
  • Owing to the potential for HIV transmission (in HIV-negative infants), developing viral resistance (in HIV-positive infants), and adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed while taking this medication