Dosing & Uses
Dosage Forms & Strengths
bictegravir/emtricitabine/tenofovir AF
tablet
- 50mg/200mg/25mg
Human Immunodeficiency Virus Infection
Indicated as a complete regimen for patients with human immunodeficiency virus type 1 (HIV-1)
- Who have no antiretroviral therapy (ART) treatment history or
- To replace current ART regimen in virologically suppressed patients (HIV-1 RNA <50 copies/mL) on a stable ART regimen with no known or suspected substitution associated with resistance to bictegravir or tenofovir
1 tablet PO qDay
Dosage Modifications
Hepatic impairment
- Mild-to-moderate (Child-Pugh class A or B): No dosage adjustment necessary
- Severe (Child-Pugh class C): Not studied; use not recommended
Renal impairment
- CrCl ≥30 mL/min: No dosage adjustment necessary
- Virologically suppressed adults with ESRD (CrCl <15 mL/min) on chronic hemodialysis: On hemodialysis days, administer daily dose after completing hemodialysis
-
Severe
- Not recommended for
- CrCl 15 to <30 mL/min
- ESRD not on hemodialysis
- No ART history and ESRD in patients who are receiving chronic hemodialysis
Dosing Considerations
Testing when initiating and during treatment
- Before or when initiating therapy: Test patients for hepatitis B virus infection
- Before or when initiating and during treatment: Assess serum creatinine, estimated CrCl, urine glucose, and urine protein in all patients as clinically appropriate; in patients with chronic kidney disease, also assess serum phosphorus
Dosage Forms & Strengths
bictegravir/emtricitabine/tenofovir AF
tablet
- 30mg/120mg/15mg
- 50mg/200mg/25mg
Human Immunodeficiency Virus Infection
Indicated as a complete regimen for human immunodeficiency virus type 1 (HIV-1) in pediatric patients weighing ≥14 kg
- Who have no antiretroviral therapy (ART) treatment history or
- To replace current ART regimen in virologically suppressed patients (HIV-1 RNA <50 copies/mL) on a stable ART regimen with no known or suspected substitution associated with resistance to bictegravir or tenofovir
Dosage
- <14 kg: Safety and efficacy not established
- ≥14 to 25 kg: 1 tablet (30mg/120mg/15mg) PO qDay
- ≥25 kg: 1 tablet (50mg/200mg/25mg) PO qDay
Dosage Modifications
Hepatic impairment
- Mild-to-moderate (Child-Pugh class A or B): No dosage adjustment necessary
- Severe (Child-Pugh class C): Not studied; use not recommended
Renal impairment
- CrCl ≥30 mL/min: No dosage adjustment necessary
-
Severe
- Not recommended for
- CrCl 15 to <30 mL/min
- ESRD (CrCl <15 mL/min) with or without hemodialysis
- No ART history and ESRD in patients who are receiving chronic hemodialysis
Dosing Considerations
Testing when initiating and during treatment
- Before or when initiating therapy: Test patients patients for hepatitis B virus infection
- Before or when initiating and during treatment: Assess serum creatinine, estimated CrCl, urine glucose, and urine protein in all patients as clinically appropriate; in patients with chronic kidney disease, also assess serum phosphorus
Interactions
Interaction Checker
No Results
Contraindicated
Serious
Significant - Monitor Closely
Minor
Contraindicated (2)
- dofetilide
bictegravir will increase the level or effect of dofetilide by decreasing renal clearance. Contraindicated. Bictegravir inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE1) in vitro. Coadministration with OCT2 and MATE1 substrates may increase their plasma concentrations.
- rifampin
rifampin will decrease the level or effect of bictegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of strong CYP3A and UGT1A1 inducers can substantially decrease bictegravir plasma concentrations. This may result in the loss of therapeutic effect and development of resistance to bictegravir. Coadministration with rifampin is contraindicated.
Serious (15)
- atidarsagene autotemcel
bictegravir, atidarsagene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Antiretroviral (ART) medications may interfere with the manufacturing of atidarsagene autotemcel. Do not take ARTs for at least 1 month before cell mobilization or the expected duration for elimination of the medications.
- betibeglogene autotemcel
bictegravir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- carbamazepine
carbamazepine will decrease the level or effect of bictegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of strong CYP3A and UGT1A1 inducers can substantially decrease bictegravir plasma concentrations. This may result in the loss of therapeutic effect and development of resistance to bictegravir. Coadministration with another anticonvulsant should be considered.
- elivaldogene autotemcel
elivaldogene autotemcel, bictegravir. Either decreases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Patients should not take antiretroviral medications for at least 1 month before initiating medications for stem cell mobilization, for the duration of the medications? elimination, and until all cycles of apheresis are completed.
- enasidenib
enasidenib will increase the level or effect of tenofovir AF by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of enasidenib with sensitive OATP1B1, OATP1B3, or BCRP substrates, for which minimal concentration changes may lead to serious toxicities. If unavoidable, decrease the substrate(s) dosage in accordance with their Prescribing Information.
- leniolisib
leniolisib will increase the level or effect of tenofovir AF by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, a BCRP inhibitor, may increase systemic exposure of BCRP substrates
- letermovir
tenofovir AF will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.
- lovotibeglogene autotemcel
bictegravir, lovotibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Discontinue antiretrovirals (ARTs) at least 1 month before mobilization and until all apheresis cycles are completed. Some long-acting ARTs may require a longer duration of discontinuation for elimination. ARTs may interfere with lovotibeglogene autotemcel manufacturing.
- oxcarbazepine
oxcarbazepine will decrease the level or effect of bictegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of strong CYP3A and UGT1A1 inducers can substantially decrease bictegravir plasma concentrations. This may result in the loss of therapeutic effect and development of resistance to bictegravir. Coadministration with another anticonvulsant should be considered.
- phenobarbital
phenobarbital will decrease the level or effect of bictegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of strong CYP3A and UGT1A1 inducers can substantially decrease bictegravir plasma concentrations. This may result in the loss of therapeutic effect and development of resistance to bictegravir. Coadministration with another anticonvulsant should be considered.
- phenytoin
phenytoin will decrease the level or effect of bictegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of strong CYP3A and UGT1A1 inducers can substantially decrease bictegravir plasma concentrations. This may result in the loss of therapeutic effect and development of resistance to bictegravir. Coadministration with another anticonvulsant should be considered.
- rifabutin
rifabutin will decrease the level or effect of bictegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of strong CYP3A and UGT1A1 inducers can substantially decrease bictegravir plasma concentrations. This may result in the loss of therapeutic effect and development of resistance to bictegravir. Coadministration with rifabutin is not recommended.
- rifapentine
rifapentine will decrease the level or effect of bictegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of strong CYP3A and UGT1A1 inducers can substantially decrease bictegravir plasma concentrations. This may result in the loss of therapeutic effect and development of resistance to bictegravir. Coadministration with rifapentine is not recommended.
- St John's Wort
St John's Wort will decrease the level or effect of bictegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of strong CYP3A and UGT1A1 inducers can substantially decrease bictegravir plasma concentrations. This may result in the loss of therapeutic effect and development of resistance to bictegravir. Coadministration with St John's wort is not recommended.
- sotorasib
sotorasib will decrease the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.
Monitor Closely (53)
- acalabrutinib
acalabrutinib increases levels of tenofovir AF by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- aluminum hydroxide
aluminum hydroxide will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir can be taken under fasting conditions 2 hr before antacids containing Al, Mg, or Ca. Routine administration of bictegravir simultaneously with, or 2 hr after, antacids containing Al, Mg, or Ca is not recommended.
- aluminum hydroxide/magnesium carbonate
aluminum hydroxide/magnesium carbonate will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir can be taken under fasting conditions 2 hr before antacids containing Al, Mg, or Ca. Routine administration of bictegravir simultaneously with, or 2 hr after, antacids containing Al, Mg, or Ca is not recommended.
- apalutamide
apalutamide will decrease the level or effect of tenofovir AF by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces BCRP and may decrease systemic exposure of drugs that are BCRP substrates.
- berotralstat
berotralstat will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.
- cabozantinib
tenofovir AF will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity
- calcium acetate
calcium acetate will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir can be taken under fasting conditions 2 hr before antacids containing Al, Mg, or Ca. Routine administration of bictegravir simultaneously with, or 2 hr after, antacids containing Al, Mg, or Ca is not recommended.
- calcium carbonate
calcium carbonate will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir can be taken under fasting conditions 2 hr before antacids containing calcium. However, bictegravir and supplements containing calcium can be taken together with food. Routine administration of bictegravir (under fasting conditions) simultaneously with, or 2 hr after, calcium supplements or antacids containing calcium is not recommended.
- calcium citrate
calcium citrate will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir can be taken under fasting conditions 2 hr before antacids containing Al, Mg, or Ca. Routine administration of bictegravir simultaneously with, or 2 hr after, antacids containing Al, Mg, or Ca is not recommended.
- danicopan
danicopan will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Danicopan increases plasma concentrations of BCRP substrates; consider dose reduction of BCRP substrate according to its prescribing information.
danicopan will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Danicopan increases plasma concentrations of P-gp substrates; consider dose reduction of P-gp substrates where minimal concentration changes may lead to serious adverse reactions. - darolutamide
darolutamide will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- duvelisib
tenofovir AF will decrease the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- elagolix
elagolix will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- encorafenib
encorafenib will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.
- ferric maltol
ferric maltol will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir and supplements containing iron can be taken together with food. Routine administration of bictegravir (under fasting conditions) simultaneously with, or 2 hr after, supplements containing iron is not recommended.
- ferrous fumarate
ferrous fumarate will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir and supplements containing iron can be taken together with food. Routine administration of bictegravir (under fasting conditions) simultaneously with, or 2 hr after, supplements containing iron is not recommended.
- ferrous gluconate
ferrous gluconate will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir and supplements containing iron can be taken together with food. Routine administration of bictegravir (under fasting conditions) simultaneously with, or 2 hr after, supplements containing iron is not recommended.
- ferrous sulfate
ferrous sulfate will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir and supplements containing iron can be taken together with food. Routine administration of bictegravir (under fasting conditions) simultaneously with, or 2 hr after, supplements containing iron is not recommended.
- fostamatinib
fostamatinib will increase the level or effect of tenofovir AF by decreasing metabolism. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of BCRP substrate drugs. Monitor for toxicities of BCRP substrate drug that may require dosage reduction when given concurrently with fostamatinib.
- glecaprevir/pibrentasvir
glecaprevir/pibrentasvir will increase the level or effect of tenofovir AF by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.
- ifosfamide
ifosfamide, tenofovir AF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Monitor electrolytes and renal function.
- istradefylline
istradefylline will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.
- lonafarnib
lonafarnib will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.
- magnesium citrate
magnesium citrate will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir can be taken under fasting conditions 2 hr before antacids containing Al, Mg, or Ca. Routine administration of bictegravir simultaneously with, or 2 hr after, antacids containing Al, Mg, or Ca is not recommended.
- magnesium gluconate
magnesium gluconate will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir can be taken under fasting conditions 2 hr before antacids containing Al, Mg, or Ca. Routine administration of bictegravir simultaneously with, or 2 hr after, antacids containing Al, Mg, or Ca is not recommended.
- magnesium hydroxide
magnesium hydroxide will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir can be taken under fasting conditions 2 hr before antacids containing Al, Mg, or Ca. Routine administration of bictegravir simultaneously with, or 2 hr after, antacids containing Al, Mg, or Ca is not recommended.
- magnesium oxide
magnesium oxide will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir can be taken under fasting conditions 2 hr before antacids containing Al, Mg, or Ca. Routine administration of bictegravir simultaneously with, or 2 hr after, antacids containing Al, Mg, or Ca is not recommended.
- magnesium supplement
magnesium supplement will decrease the level or effect of bictegravir by Other (see comment). Modify Therapy/Monitor Closely. Drug may form a chelate with polyvalent cations; may decrease absorption by the intestinal tract; applies to oral forms; may administer under fasting conditions 2 hr before administering polyvalent cation or 6 hr after
- mavorixafor
mavorixafor will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Caution if mavorixafor (a P-gp inhibitor) is coadministered with a sensitive P-gp substrate where minimal substrate concentration changes may lead to serious adverse effects.
- metformin
bictegravir will increase the level or effect of metformin by decreasing renal clearance. Modify Therapy/Monitor Closely. Bictegravir inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE1) in vitro. Coadministration with OCT2 and MATE1 substrates may increase their plasma concentrations. Metformin dose reduction may be required.
- momelotinib
momelotinib increases toxicity of tenofovir AF by plasma protein binding competition. Modify Therapy/Monitor Closely. Momelotinib (BCRP inhibitor) may increase exposure of BCRP substrates, which may increase the risk of BCRP substrate adverse reactions. Dose adjustment of other BCRP substrates may necessary.
- multivitamins
multivitamins will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir and supplements containing iron can be taken together with food. Routine administration of bictegravir (under fasting conditions) simultaneously with, or 2 hr after, supplements containing iron is not recommended.
- multivitamins, vision
multivitamins, vision will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir and supplements containing iron can be taken together with food. Routine administration of bictegravir (under fasting conditions) simultaneously with, or 2 hr after, supplements containing iron is not recommended.
- nirmatrelvir
nirmatrelvir will increase the level or effect of bictegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration may increase bictegravir systemic exposures.
nirmatrelvir will increase the level or effect of tenofovir AF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration may increase tenofovir systemic exposures. - nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of tenofovir AF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration may increase tenofovir systemic exposures.
nirmatrelvir/ritonavir will increase the level or effect of bictegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration may increase bictegravir systemic exposures. - orlistat
orlistat will decrease the level or effect of tenofovir AF by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.
- selenium
selenium will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer bictegravir on an empty stomach at least 2 h before or 6 h after polyvalent cation containing drugs.
- oteseconazole
oteseconazole will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Otesezonale, a BCRP inhibitor, may increase the effects and risk of toxicities of BCRP substrates. Use lowest starting dose of BCRP substrate, or consider reducing BCRP substrate dose.
- regorafenib
regorafenib will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Regorafenib likely inhibits BCRP (ABCG2) transport. Coadministration with a BCRP substrate may increase systemic exposure to the substrate and related toxicity.
- safinamide
safinamide will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.
- sarecycline
sarecycline will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.
- sodium sulfate/?magnesium sulfate/potassium chloride
sodium sulfate/?magnesium sulfate/potassium chloride decreases levels of bictegravir by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Bictegravir sodium/emtricitabine/tenofovir alafenamide fumarate can be takenat least 2 hr before or 6 hr after taking a medication containing magnesium.
- sodium sulfate/potassium sulfate/magnesium sulfate
sodium sulfate/potassium sulfate/magnesium sulfate decreases levels of bictegravir by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Bictegravir sodium/emtricitabine/tenofovir alafenamide fumarate can be takenat least 2 hr before or 6 hr after taking a medication containing magnesium.
- stiripentol
stiripentol will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Stiripentol is a BCRP transport inhibitor. Consider dosage reduction for BCRP substrates if adverse effects are experienced when coadministered.
- sucralfate
sucralfate will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Bictegravir can be taken under fasting conditions 2 hr before antacids containing Al, Mg, or Ca. Routine administration of bictegravir simultaneously with, or 2 hr after, antacids containing Al, Mg, or Ca is not recommended.
- tafamidis
tafamidis will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.
- tafamidis meglumine
tafamidis meglumine will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.
- tucatinib
tucatinib will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.
- ublituximab
ublituximab decreases effects of bictegravir by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely.
- vadadustat
vadadustat will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Vadadustat may increase exposure of BCRP substrates. Monitor for signs of adverse effect of BCRP substrate and reduce substrate dose in accordance with their product labeling.
- voclosporin
voclosporin, tenofovir AF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.
- xanomeline/trospium
tenofovir AF, xanomeline/trospium. Either increases levels of the other by decreasing elimination. Use Caution/Monitor. Coadministration of trospium with other drugs eliminated by active tubular secretion may increase plasma concentrations of trospium and/or the concomitantly used drug owing to competition for this elimination pathway. Monitor for increased frequency and/or severity of adverse reactions.
- zinc
zinc will decrease the level or effect of bictegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer bictegravir/emtricitabine/tenofovir AF at least 2 hr before or 6 hr after these agents.
Minor (0)
Adverse Effects
1-10%
Adults
- Diarrhea (3-6%)
- Nausea (3-5%)
- Headache (4-5%)
- Creatine kinase ≥10x ULN (4%)
- Abnormal dreams (<3%)
- Fasting LDL-C >190 mg/dL (2-3%)
- Fatigue (2-3%)
- Dizziness (2%)
- Insomnia (2%)
- Neutrophil <750 mm³ (2%)
- Amylase >2x ULN (2%)
- ALT >5x ULN (1-2%)
- AST >5x ULN (1-2%)
Children
- Insomnia, grade 2
- Anxiety, grade 2
Frequency Not Defined
Children
- Abdominal pain
Postmarketing Reports
Angioedema, urticaria, Stevens-Johnson syndrome/toxic epidermal necrolysis
Acute renal failure, acute tubular necrosis, proximal renal tubulopathy, and Fanconi syndrome
Warnings
Black Box Warnings
Post-treatment acute exacerbation of hepatitis B
- Severe acute exacerbations of hepatitis B reported in patients coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF)
- Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients coinfected with HIV-1 and HBV who discontinue therapy
- If appropriate, antihepatitis B therapy may be warranted
Contraindications
Coadministration with dofetilide and/or rifampin
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 reported in patients treated with combination ART therapy; autoimmune disorders (eg, 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 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 nephrotoxic drug, including nonsteroidal anti-inflammatory drugs, owing to 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 bictegravir 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 inhibit 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-gp activity are 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 increasing concentrations of emtricitabine and tenofovir, thereby increase risk of adverse effects
Pregnancy
Pregnancy
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)
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 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 potential risk for postnatal transmission of HIV
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 published literature have not reported adverse effects of FTC or TAF on a breastfed child; there are no data on 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
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Three-drug combination of bictegravir (BIC), a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI); emtricitabine (FTC); and tenofovir alafenamide (TAF), both HIV-1 nucleoside analog reverse transcriptase inhibitors (NRTIs)
Bictegravir: HIV-1 integrase strand transfer inhibitor (INSTI); inhibits HIV-1 replication by blocking the strand transfer step of viral DNA integration into the host genome; novel INSTI since it can be dosed once daily without boosting
Emtricitabine: Nucleoside reverse transcriptase inhibitor (NRTI); cytosine analog phosphorylated to emtricitabine 5'-triphosphate causing inhibition of HIV and RNA dependent DNA polymerase
Tenofovir alafenamide (AF): NRTI prodrug of tenofovir; compared with tenofovir disoproxil fumarate (tenofovir DF, Viread), tenofovir alafenamide (AF) is a more targeted form of tenofovir that has demonstrated high antiviral efficacy at a dose that is 10 times lower than tenofovir DF, as well as an improved renal and bone safety profile; inhibits HIV-1 RT by competing with the natural substrate deoxyadenosine 5′-triphosphate and, after incorporation into DNA, by DNA chain termination
Absorption
Peak plasma time (adults): 2-4 hr (BIC); 1.5-2 hr (FTC); 0.5-2 hr (TAF)
Effect of high-fat meal
- AUC ratio: 1.24 (BIC); 0.96 (FTC); 1.63 (TAF)
- Peak plasma concentration ratio: 1.13 (BIC); 0.86 (FTC); 0.92 (TAF)
Peak plasma concentration
- Adults: 6.15 mcg/mL (BIC); 2.13 mcg/mL (FTC); 0.121 mcg/mL (TAF)
- Pediatric patients (6 to <12 years): 9.46 mcg/mL (BIC); 3.89 mcg/mL (FTC); 0.205 mcg/mL (TAF)
- Pediatric patients (12 to <18 years): 6.24 mcg/mL (BIC); 2.69 mcg/mL (FTC); 0.133 mcg/mL (TAF)
AUC
- Adults: 102 mcg·hr/mL (BIC); 12.3 mcg·hr/mL (FTC); 0.142 mcg·hr/mL (TAF)
- Pediatric patients (6 to <12 years): 128 mcg·hr/mL (BIC); 17.6 mcg·hr/mL (FTC); 0.278 mcg·hr/mL (TAF)
- Pediatric patients (12 to <18 years): 89.1 mcg·hr/mL (BIC); 13.6 mcg·hr/mL (FTC); 0.196 mcg·hr/mL (TAF)
Distribution
Protein binding: >99% (BIC); <4% (FTC); ~80% (TAF)
Blood-to-plasma ratio: 0.64 (BIC); 0.6 (FTC); 1 (TAF)
Metabolism
Bictegravir
- Metabolized by CYP3A4 and UGT1A1
Emtricitabine
- Not significantly metabolized
- Metabolized by oxidation
Tenofovir
- Tenofovir AF (TAF) is hydrolyzed within cells to form tenofovir (major metabolite), which is phosphorylated to the active metabolite, tenofovir diphosphate
- In vitro studies have shown that TAF is metabolized to tenofovir by cathepsin A in PBMCs and macrophages, and by CES1 in hepatocytes
- Upon coadministration with the moderate CYP3A inducer probe efavirenz, TAF exposure was unaffected
Excretion
Half-life: 17.3 hr (BIC); 10.4 hr (FTC); 0.51 hr (TAF)
Excretion, urine: 35% (BIC); 70% (FTC); <1% (TAF)
Excretion, feces: 60.3% (BIC); 13.7% (FTC); 31.7% (TAF)
Administration
Oral Administration
For oral use only
Take once daily with or without food
Storage
Tablets
- Store below 30°C (86°F)
- Keep container tightly closed
- Dispense only in original container
Images
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
