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Drug overview for BIKTARVY (bictegravir sodium/emtricitabine/tenofovir alafenamide fumar):
Generic name: bictegravir sodium/emtricitabine/tenofovir alafenamide fumar (bik-TEG-ra-vir/EM-trye-SYE-ta-been/ten-OF-oh-vir AL-a-FEN-a-mide)
Drug class: Tenofovir
Therapeutic class: Anti-Infective Agents
Bictegravir sodium, emtricitabine, and tenofovir alafenamide fumarate (BIC/FTC/TAF) is a fixed-combination antiretroviral agent containing bictegravir (human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor), emtricitabine (HIV-1 nucleoside reverse transcriptase inhibitor), and tenofovir alafenamide (HIV-1 nucleotide reverse transcriptase inhibitor).
No enhanced Uses information available for this drug.
Generic name: bictegravir sodium/emtricitabine/tenofovir alafenamide fumar (bik-TEG-ra-vir/EM-trye-SYE-ta-been/ten-OF-oh-vir AL-a-FEN-a-mide)
Drug class: Tenofovir
Therapeutic class: Anti-Infective Agents
Bictegravir sodium, emtricitabine, and tenofovir alafenamide fumarate (BIC/FTC/TAF) is a fixed-combination antiretroviral agent containing bictegravir (human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor), emtricitabine (HIV-1 nucleoside reverse transcriptase inhibitor), and tenofovir alafenamide (HIV-1 nucleotide reverse transcriptase inhibitor).
No enhanced Uses information available for this drug.
DRUG IMAGES
BIKTARVY 50-200-25 MG TABLET
BIKTARVY 30-120-15 MG TABLET
The following indications for BIKTARVY (bictegravir sodium/emtricitabine/tenofovir alafenamide fumar) have been approved by the FDA:
Indications:
HIV infection
Professional Synonyms:
Human immunodeficiency virus disease
Human immunodeficiency virus infection
Indications:
HIV infection
Professional Synonyms:
Human immunodeficiency virus disease
Human immunodeficiency virus infection
The following dosing information is available for BIKTARVY (bictegravir sodium/emtricitabine/tenofovir alafenamide fumar):
Fixed combination tablets of BIC/FTC/TAF contain bictegravir sodium, emtricitabine, and tenofovir alafenamide fumarate; dosage of bictegravir sodium is expressed in terms of bictegravir and dosage of tenofovir alafenamide fumarate is expressed in terms of tenofovir alafenamide.
Fixed-combination tablets of BIC/FTC/TAF are available in 2 different strengths: bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, and bictegravir 30 mg, emtricitabine 120 mg, and tenofovir alafenamide 15 mg.
Fixed-combination tablets of BIC/FTC/TAF are available in 2 different strengths: bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, and bictegravir 30 mg, emtricitabine 120 mg, and tenofovir alafenamide 15 mg.
The fixed combination BIC/FTC/TAF is administered orally once daily without regard to food. In children unable to swallow the whole fixed combination tablet of BIC/FTC/TAF, the tablet can be split, and each part swallowed separately; the full dose must be consumed within approximately 10 minutes. Store bottles below 30oC. Store blister packs at 25oC (excursions permitted between 15-30oC).
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| BIKTARVY 50-200-25 MG TABLET | Maintenance | Adults take 1 tablet by oral route once daily |
No generic dosing information available.
The following drug interaction information is available for BIKTARVY (bictegravir sodium/emtricitabine/tenofovir alafenamide fumar):
There are 5 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Selected Nephrotoxic Agents/Cidofovir SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Cidofovir is nephrotoxic. Concurrent administration of other nephrotoxic agents may result in additive or synergistic effects on renal function.(1-3) CLINICAL EFFECTS: Concurrent use of cidofovir with nephrotoxic agents such as adefovir, intravenous aminoglycosides, amphotericin B, foscarnet, intravenous pentamidine, tenofovir, vancomycin, voclosporin and non-steroidal anti-inflammatory agents may result in renal toxicity.(1-3) Other nephrotoxic agents include capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, and streptozocin. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The Australian,(1) UK,(2) and US(3) manufacturers of cidofovir state that concurrent administration of potentially nephrotoxic agents such as adefovir, intravenous aminoglycosides, amphotericin B, foscarnet, intravenous pentamidine, tenofovir, vancomycin, voclosporin and non-steroidal anti-inflammatory agents may result in renal toxicity.(1-3) Other nephrotoxic agents include capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, and streptozocin. These agents should be discontinued at least 7 days before the administration of cidofovir. DISCUSSION: The safety of cidofovir has not been studied in patients receiving other known potentially nephrotoxic agents. Renal impairment is the major toxicity of cidofovir.(1-3) |
CIDOFOVIR |
| Adefovir/Tenofovir SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: The mechanism involves competition for active tubular secretion sites in the kidney.(1-4) CLINICAL EFFECTS: Concurrent use of adefovir and tenofovir in the treatment of hepatitis B may result in elevated levels of tenofovir or adefovir. PREDISPOSING FACTORS: Renal impairment or use of concurrent renally excreted drugs. PATIENT MANAGEMENT: The US manufacturer of adefovir(1) and the UK(2) and US(3) manufacturers of tenofovir state that adefovir and tenofovir should be not be administered together. DISCUSSION: Tenofovir is eliminated principally by renal tubular secretion and any competitive inhibition of excretion of tenofovir by adefovir increases the likelihood of increased serum concentrations of tenofovir and resultant toxicity.(1-4) |
ADEFOVIR DIPIVOXIL, HEPSERA |
| Dofetilide/Bictegravir SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Dofetilide is primarily excreted in the urine via both glomerular filtration and active tubular secretion via the cation transport system. Bictegravir is believed to inhibit the cation transport system (OCT2) and thus may inhibit the active tubular secretion of dofetilide.(1) CLINICAL EFFECTS: The concurrent administration of dofetilide with bictegravir may result in elevated levels and increased effects of dofetilide, including torsades de pointes.(1) PREDISPOSING FACTORS: Renal impairment may increase risk for excessive QTc prolongation as dofetilide is primarily renally eliminated. To prevent increased serum levels and risk for ventricular arrhythmias, dofetilide must be dose adjusted for creatinine clearance < or = to 60 mL/min.(1) The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: The manufacturer of bictegravir states that the concurrent administration of dofetilide with bictegravir is contraindicated. If dofetilide is to be discontinued, a washout of at least 2 days is recommended prior to starting bictegravir.(1) If alternatives are not available and concurrent therapy is deemed medically necessary, obtain serum calcium, magnesium, and potassium levels and monitor ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: The concurrent administration of dofetilide and bictegravir is expected to increase dofetilide plasma concentrations. Bictegravir is an inhibitor of organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE1) in vitro.(1) |
DOFETILIDE, TIKOSYN |
| Bictegravir/Rifampin SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Rifampin may induce the metabolism of bictegravir via CYP3A4 and UGT1A1.(1) CLINICAL EFFECTS: The concurrent use of bictegravir and rifampin may lead to decreased levels of bictegravir, which may result in the loss of therapeutic effect and development of resistance to bictegravir.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of bictegravir and rifampin is contraindicated.(1) DISCUSSION: In a single dose study, rifampin decreased the maximum concentration (Cmax) and area-under-curve (AUC) levels of bictegravir by 28% and 75%, respectively.(1) |
RIFADIN, RIFAMPIN |
| Selected Nephrotoxic Agents/Bacitracin SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Bacitracin may cause renal failure due to glomerular and tubular necrosis. Concurrent administration of other nephrotoxic agents may result in additive renal toxicity.(1-3) CLINICAL EFFECTS: Concurrent use of bacitracin with other potentially nephrotoxic agents may result in renal toxicity.(1-3) PREDISPOSING FACTORS: Dehydration and high-dose bacitracin may predispose to adverse renal effects.(1) PATIENT MANAGEMENT: Health Canada states that bacitracin is contraindicated in patients with renal impairment, including those taking other nephrotoxic drugs.(1) The Canadian and US manufacturers of bacitracin state that concomitant use of bacitracin with other potentially nephrotoxic agents should be avoided.(2,3) DISCUSSION: Renal impairment is a major toxicity of bacitracin. Cases of nephrotoxicity have been reported when bacitracin was used off-label.(1-3) |
BACITRACIN, BACITRACIN MICRONIZED, BACITRACIN ZINC |
There are 13 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Colistimethate/Selected Nephrotoxic Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Colistimethate can cause nephrotoxicity.(1,2) Concurrent administration of other nephrotoxic agents may result in an increased risk of nephrotoxicity.(1) It is suspected that cephalothin interferes with the excretion of colistimethate resulting in enhanced nephrotoxicity.(2,3) CLINICAL EFFECTS: Concurrent use of colistimethate with other nephrotoxic agents may result in additive nephrotoxic effects. PREDISPOSING FACTORS: Factors predisposing to nephrotoxicity include higher cumulative doses of colistimethate, longer treatment duration, hypovolemia, and critical illness. PATIENT MANAGEMENT: Concurrent use of potentially nephrotoxic agents with colistimethate should be avoided.(1,2) If concurrent use is necessary, it should be undertaken with great caution.(1) DISCUSSION: In a case control study of 42 patients on intravenous colistimethate sodium, NSAIDs were identified as an independent risk factor for nephrotoxicity (OR 40.105, p=0.044).(4) In 4 case reports, patients developed elevated serum creatinine and blood urea nitrogen following concurrent colistimethate and cephalothin (3 patients) or when colistimethate followed cephalothin therapy (1 patient).(3) A literature review found that individual nephrotoxic agents, including aminoglycosides, vancomycin, amphotericin, IV contrast, diuretics, ACE inhibitors, ARBs, NSAIDs, and calcineurin inhibitors, were not consistently associated with additive nephrotoxicity when used with colistimethate. However, when multiple agents (at least 2 additional potential nephrotoxins) were used concurrently, there was a significant correlation to colistimethate nephrotoxicity.(5) |
COLISTIMETHATE, COLISTIMETHATE SODIUM, COLY-MYCIN M PARENTERAL |
| Selected Nephrotoxic Agents/Foscarnet SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Foscarnet is nephrotoxic. Concurrent administration of other nephrotoxic agents may result in additive or synergistic effects on renal function.(1) Concurrent intravenous pentamidine may also result in hypocalcemia.(1) CLINICAL EFFECTS: Concurrent use of foscarnet with nephrotoxic agents such as acyclovir, adefovir, intravenous aminoglycosides, amphotericin B, cyclosporine, methotrexate, non-steroidal anti-inflammatory agents, intravenous pentamidine, tacrolimus, tenofovir, vancomycin and voclosporin may result in renal toxicity.(1) Other nephrotoxic agents include capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, and streptozocin. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of foscarnet state that concurrent administration of potentially nephrotoxic agents such as acyclovir, intravenous aminoglycosides, amphotericin B, cyclosporine, methotrexate, tacrolimus, and intravenous pentamidine should be avoided.(1) Other nephrotoxic agents include adefovir, capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, non-steroidal anti-inflammatory agents, streptozocin, tenofovir, vancomycin and voclosporin. If concurrent therapy is warranted, monitor renal function closely. In patients receiving concurrent foscarnet and pentamidine, also monitor serum calcium levels and instruct patients to report severe muscle spasms, mental/mood changes, and/or seizures.(1) DISCUSSION: The safety of foscarnet has not been studied in patients receiving other known potentially nephrotoxic agents. Renal impairment is the major toxicity of foscarnet.(1) |
FOSCARNET SODIUM, FOSCAVIR |
| Orlistat/Selected Antiretrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. Orlistat may reduce the absorption of lipophilic antiretroviral HIV drugs by retention in the gastrointestinal tract or reduced gastrointestinal tract transit time. CLINICAL EFFECTS: The concurrent administration of orlistat and atazanavir, efavirenz, emtricitabine, maraviroc, ritonavir, or tenofovir may result in a decrease in the levels and clinical effects of the antiretroviral, including loss of virological control.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: HIV RNA levels should be frequently monitored in patients taking orlistat while being treated for HIV infection. If there is a confirmed increase in HIV viral load, orlistat should be discontinued.(1) DISCUSSION: Loss of virological control has been reported in HIV-infected patients taking orlistat concomitantly with lipophilic antiretroviral drugs.(1) There are three case reports of patients having an increased HIV viral load after taking orlistat concomitantly with their HIV therapy.(2-4) Antiretrovirals included in this monograph are atazanavir, efavirenz, emtricitabine, maraviroc, ritonavir, and tenofovir. |
ORLISTAT, XENICAL |
| Deoxycytidine Kinase Substrates/Cladribine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine and zalcitabine may inhibit the intracellular phosphorylation of cladribine by deoxycytidine kinase (dCK). CLINICAL EFFECTS: Concurrent administration of clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine, or zalcitabine with cladribine may result in decreased clinical efficacy of cladribine. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of lamivudine states that the concurrent use of lamivudine and cladribine is not recommended.(1) The manufacturer of cladribine states that concurrent use of compounds that require activation by intracellular phosphorylation should be avoided.(2) DISCUSSION: Cladribine undergoes a series of phosphorylations to its active metabolites. In a case report, a patient on lamivudine who received cladribine concurrently did not experience a decrease in his lymphocyte count. After discontinuation of lamivudine and readministration of cladribine, his lymphocytes dropped as expected.(3) It is expected that other compounds phosphorylated by dCK would also decrease cladribine's efficacy.(4) Compounds phosphorylated by dCK include: clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine and zalcitabine. |
CLADRIBINE, MAVENCLAD |
| Bictegravir-Emtricitabine-Tenofovir Alafenamide/Selected Strong CYP3A4 Inducers; Oxcarbazepine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong CYP3A4 inducers and oxcarbazepine may induce the metabolism of bictegravir.(1,2) CLINICAL EFFECTS: Concurrent use of bictegravir with strong CYP3A4 inducers or oxcarbazepine may result in decreased levels of bictegravir, virologic failure, and development of resistance.(1,2) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of bictegravir recommends considering alternatives to oxcarbazepine.(1) The National Institute of Health HIV guidelines do not recommend coadministration of oxcarbazepine with bictegravir.(2) Other CYP3A4 inducers should not be coadministered with bictegravir.(1,2) DISCUSSION: Coadministration of rifampin (600 mg daily, a strong CYP3A4 inducer) decreased bictegravir area-under-curve (AUC) by 75% and maximum concentration (Cmax) by 28%.(1) Although the other CYP3A4 inducers linked to this monograph have not been studied with bictegravir, a similar effect is expected. Coadministration of rifabutin (300 mg daily) with bictegravir decreased bictegravir AUC and Cmax by 38% and 20%, respectively.(1) CYP3A4 inducers linked to this monograph include: barbiturates, encorafenib, enzalutamide, ivosidenib, mitotane, or oxcarbazepine.(1-3) |
ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, BRAFTOVI, BUTALB-ACETAMINOPH-CAFF-CODEIN, BUTALBITAL, BUTALBITAL-ACETAMINOPHEN, BUTALBITAL-ACETAMINOPHEN-CAFFE, BUTALBITAL-ASPIRIN-CAFFEINE, FIORICET, FIORICET WITH CODEINE, LYSODREN, MITOTANE, OXCARBAZEPINE, OXCARBAZEPINE ER, OXTELLAR XR, PENTOBARBITAL SODIUM, TENCON, TIBSOVO, TRILEPTAL, XTANDI |
| Chloroquine; Hydroxychloroquine/MATE Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of the Multidrug and Toxin Extrusion (MATE) protein transporters in the kidneys may inhibit the renal tubular secretion of chloroquine or hydroxychloroquine via the MATE1 transporter.(1,2) CLINICAL EFFECTS: Concurrent use of MATE inhibitors may result in increased levels of and toxicity from chloroquine or hydroxychloroquine, including irreversible retinopathy, potentially life-threatening cardiac arrhythmias like torsades de pointes (TdP), hypoglycemia, or myopathy.(1,2) PREDISPOSING FACTORS: In general, the risk of QT prolongation or torsade de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsade de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(3) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsade de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(3) PATIENT MANAGEMENT: The manufacturers of chloroquine and hydroxychloroquine state that concomitant use of MATE inhibitors should be avoided.(1,2) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: In a study of healthy volunteers, cimetidine (400 mg daily for 4 days) decreased the clearance of single-dose chloroquine (300 mg) by 53% and half-life by 49%, compared to subjects not on cimetidine.(4) MATE inhibitors linked to this monograph include: bictegravir, cimetidine, isavuconazole, pyrimethamine, risdiplam, trimethoprim, and tucatinib.(5) |
CHLOROQUINE PHOSPHATE, HYDROXYCHLOROQUINE SULFATE, PLAQUENIL, SOVUNA |
| Betibeglogene Autotemcel/Anti-Retrovirals; Hydroxyurea SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Betibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. Hydroxyurea may interfere with hematopoietic stem cell (HSC) mobilization of CD34+ cells.(1) CLINICAL EFFECTS: Use of hydroxyurea before mobilization may result in unsuccessful stem cell mobilization. Use of antiretrovirals before mobilization and apheresis may interfere with the production of betibeglogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals and hydroxyurea for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications and hydroxyurea may interfere with the manufacturing of betibeglogene autotemcel therapy.(1) |
ZYNTEGLO |
| Elivaldogene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Elivaldogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of elivaldogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications may interfere with the manufacturing of elivaldogene autotemcel therapy.(1) |
SKYSONA |
| Lovotibeglogene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Lovotibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of lovotibeglogene autotemcel.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed.(1) There are some long-acting antiretroviral medications that may require a longer duration of discontinuation for elimination of the medication. If a patient is taking anti-retrovirals for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.(1) DISCUSSION: Antiretroviral medications may interfere with the manufacturing of lovotibeglogene autotemcel therapy.(1) |
LYFGENIA |
| Atidarsagene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Atidarsagene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of atidarsagene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization (or the expected duration of time needed for elimination of the medication) until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications may interfere with the manufacturing of atidarsagene autotemcel therapy.(1) |
LENMELDY |
| Bictegravir-Emtricitabine-Tenofovir Alafenamide/Strong CYP3A4 and P-gp Inducers; Rifabutin SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Bictegravir is a CYP3A4 substrate and tenofovir alafenamide (TAF) is a substrate of the intestinal efflux transporter P-glycoprotein (P-gp). Concurrent use of agents that are both CYP3A4 and P-gp inducers may induce the metabolism of bictegravir and decrease systemic absorption of TAF.(1) Phenobarbital may also induce the metabolism of TAF.(1) Primidone is metabolized to phenobarbital. CLINICAL EFFECTS: Concurrent or recent use of strong CYP3A4 and P-gp inducers, phenobarbital, primidone, or rifabutin may result in decreased systemic levels of bictegravir and tenofovir alafenamide, virologic failure, and development of resistance.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of bictegravir recommends considering alternatives to carbamazepine, phenobarbital, and phenytoin for patients on bictegravir.(1) The National Institute of Health HIV guidelines do not recommend coadministration of carbamazepine, phenobarbital or phenytoin with bictegravir.(2) Fosphenytoin and primidone are metabolized to phenytoin and phenobarbital, respectively. Other CYP3A4 inducers are not recommended to be coadministered with bictegravir.(1,2) DISCUSSION: Coadministration of rifampin (600 mg daily, a strong CYP3A4 inducer) decreased bictegravir area-under-curve (AUC) by 75% and maximum concentration (Cmax) by 28%.(1) Although the other strong CYP3A4 inducers linked to this monograph have not been studied with bictegravir, a similar effect is expected. Coadministration of rifabutin (300 mg daily) with bictegravir decreased bictegravir AUC and Cmax by 38% and 20%, respectively.(1) When tenofovir alafenamide (TAF) was coadministered with carbamazepine, the maximum concentration (Cmax) and area-under-curve (AUC) were decreased 57% and 55%, respectively.(1-4) A subsequent study suggests that this interaction may not have clinically significant effects on intracellular levels of tenofovir diphosphate, the active metabolite of tenofovir alafenamide. In a study of 23 healthy volunteers, the intracellular Cmax and AUC of tenofovir diphosphate were 38% and 36% lower, respectively, when tenofovir alafenamide was coadministered with rifampin than without rifampin. However, these levels of tenofovir diphosphate were 4.4- and 4.21-fold higher, respectively, than levels obtained from tenofovir disoproxil 300 mg daily without rifampin.(3) CYP3A4 and P-gp inducers linked to this monograph include: apalutamide, carbamazepine, fosphenytoin, phenytoin, rifabutin, rifapentine, and St. John's wort.(1,4) Phenobarbital and primidone are known strong CYP3A4 inducers (4) and the manufacturer of bictegravir also classifies phenobarbital as a P-gp inducer.(1) |
CARBAMAZEPINE, CARBAMAZEPINE ER, CARBATROL, CEREBYX, DILANTIN, DILANTIN-125, DONNATAL, EPITOL, EQUETRO, ERLEADA, FOSPHENYTOIN SODIUM, MYSOLINE, PHENOBARBITAL, PHENOBARBITAL SODIUM, PHENOBARBITAL-BELLADONNA, PHENOBARBITAL-HYOSC-ATROP-SCOP, PHENOHYTRO, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED, PRIFTIN, PRIMIDONE, RIFABUTIN, SEZABY, TALICIA, TEGRETOL, TEGRETOL XR |
| Bictegravir/Efavirenz; Etravirine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Efavirenz and etravirine may induce the metabolism of bictegravir via CYP3A4 and UGT1A1.(1-3) Efavirenz and etravirine are moderate CYP3A4 and UGT1A1 inducers.(2) CLINICAL EFFECTS: The concurrent use of bictegravir and efavirenz or etravirine may lead to decreased levels of bictegravir, which may result in the loss of therapeutic effect and development of resistance to bictegravir.(1-4) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The HIV guidelines state that bictegravir and efavirenz or etravirine should not be coadministered.(3) DISCUSSION: In a single dose study, rifampin (a strong CYP3A4 and UGT1A1 inducer) decreased the maximum concentration (Cmax) and area-under-curve (AUC) levels of bictegravir by 28% and 75%, respectively.(1) |
EFAVIRENZ, EFAVIRENZ-EMTRIC-TENOFOV DISOP, EFAVIRENZ-LAMIVU-TENOFOV DISOP, ETRAVIRINE, INTELENCE, SYMFI, SYMFI LO |
| Bictegravir/Atazanavir SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Atazanavir may inhibit the metabolism of bictegravir via CYP3A4 and UGT1A1.(1,2) CLINICAL EFFECTS: The concurrent use of bictegravir and atazanavir may lead to increased levels of bictegravir.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The HIV guidelines state that bictegravir and atazanavir should not be coadministered.(3) DISCUSSION: In a pharmacokinetic study, atazanavir (400 mg daily for 8 days) increased the area-under-curve (AUC) of bictegravir by 4.15-fold.(1) In a pharmacokinetic study, atazanavir/cobicistat increased the AUC of bictegravir by 306%.(3) |
ATAZANAVIR SULFATE, EVOTAZ, REYATAZ |
There are 13 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Tenofovir/Selected Nephrotoxic Agents SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tenofovir and other nephrotoxic agents may result in additive or synergistic effects on renal function and increase nephrotoxicity risk.(1) CLINICAL EFFECTS: Concurrent use of tenofovir and other nephrotoxic agents may result in renal toxicity and acute renal failure.(1) Reports of acute renal failure and Fanconi syndrome have been reported with tenofovir use.(2,3) However, this has been reported in 3 case reports and the renal failure may have been complicated by other pre-existing conditions.(2) PREDISPOSING FACTORS: Pre-existing renal dysfunction, long duration of use, low body weight, concomitant use of drugs that may increase tenofovir levels may increase the risk of nephrotoxicity.(1) PATIENT MANAGEMENT: The US prescribing information for tenofovir recommends avoiding concurrent or recent use of a nephrotoxic agent.(3) Evaluate renal function prior to initiation of concurrent therapy and continue renal function monitoring during therapy. Dose adjustments may be required for impaired renal function. Tenofovir should be avoided with high-dose or multiple NSAIDs. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction.(3) Patients receiving concurrent NSAIDs with tenofovir should be monitored for possible renal toxicity.(1,2) The dosing interval should be adjusted in patients with a baseline creatinine clearance of less than 50 ml/min.(1-3) DISCUSSION: From March 18, 2003 to December 1, 2005, Health Canada received 10 reports of nephrotoxic reactions with tenofovir. Three of these occurred following the addition of a NSAID to tenofovir therapy. In the first report, a patient maintained on tenofovir for 29 months developed acute renal failure and acute tubular necrosis requiring dialysis 5 days after beginning indomethacin (100 mg rectally twice daily). In the second report, a patient maintained on tenofovir for 7 months developed acute renal failure and acute tubular necrosis after taking 90 tablets of naproxen (375 mg) over 2 months. The patient died. In the third report, a patient maintained on tenofovir for over a year developed acute renal failure and nephrotic syndrome after 2 months of valdecoxib (20 mg daily) therapy. Symptoms subsided following discontinuation of valdecoxib.(1) |
ABELCET, ACYCLOVIR, ACYCLOVIR SODIUM, ACYCLOVIR SODIUM-0.9% NACL, AFINITOR, AFINITOR DISPERZ, AMBISOME, AMIKACIN SULFATE, AMPHOTERICIN B, AMPHOTERICIN B LIPOSOME, ANAPROX DS, ANJESO, ARTHROTEC 50, ARTHROTEC 75, ASTAGRAF XL, BROMFENAC SODIUM, BUPIVACAINE-KETOROLAC-KETAMINE, CALDOLOR, CAMBIA, CELEBREX, CELECOXIB, CISPLATIN, COMBOGESIC, COMBOGESIC IV, CONSENSI, COXANTO, CYCLOSPORINE, CYCLOSPORINE MODIFIED, DAYPRO, DICLOFENAC, DICLOFENAC POTASSIUM, DICLOFENAC SODIUM, DICLOFENAC SODIUM ER, DICLOFENAC SODIUM MICRONIZED, DICLOFENAC SODIUM-MISOPROSTOL, EC-NAPROSYN, ELYXYB, ENVARSUS XR, ETODOLAC, ETODOLAC ER, EVEROLIMUS, FELDENE, FENOPROFEN CALCIUM, FENOPRON, FLURBIPROFEN, FYARRO, GANCICLOVIR SODIUM, GENGRAF, GENTAMICIN SULFATE, GENTAMICIN SULFATE IN NS, HYDROCODONE-IBUPROFEN, IBU, IBUPAK, IBUPROFEN, IBUPROFEN LYSINE, IBUPROFEN-FAMOTIDINE, INDOCIN, INDOMETHACIN, INDOMETHACIN ER, INFLAMMACIN, INFLATHERM(DICLOFENAC-MENTHOL), KANAMYCIN SULFATE, KEMOPLAT, KETOPROFEN, KETOPROFEN MICRONIZED, KETOROLAC TROMETHAMINE, KIPROFEN, LODINE, LOFENA, LUPKYNIS, LURBIPR, MECLOFENAMATE SODIUM, MEFENAMIC ACID, MELOXICAM, METHOTREXATE, METHOTREXATE SODIUM, NABUMETONE, NABUMETONE MICRONIZED, NALFON, NAPRELAN, NAPROSYN, NAPROTIN, NAPROXEN, NAPROXEN SODIUM, NAPROXEN SODIUM CR, NAPROXEN SODIUM ER, NAPROXEN-ESOMEPRAZOLE MAG, NEOMYCIN SULFATE, NEOPROFEN, NEORAL, OXAPROZIN, PENTAM 300, PENTAMIDINE ISETHIONATE, PHENYLBUTAZONE, PIROXICAM, PROGRAF, R.E.C.K.(ROPIV-EPI-CLON-KETOR), RELAFEN DS, ROPIVACAINE-CLONIDINE-KETOROLC, ROPIVACAINE-KETOROLAC-KETAMINE, SANDIMMUNE, SIROLIMUS, SPRIX, STREPTOMYCIN SULFATE, SULINDAC, SUMATRIPTAN SUCC-NAPROXEN SOD, SYMBRAVO, TACROLIMUS, TACROLIMUS XL, TEMSIROLIMUS, TOBRAMYCIN, TOBRAMYCIN SULFATE, TOLECTIN 600, TOLMETIN SODIUM, TORISEL, TORONOVA II SUIK, TORONOVA SUIK, TORPENZ, TOXICOLOGY SALIVA COLLECTION, TRESNI, TREXIMET, VALACYCLOVIR, VALACYCLOVIR HCL, VALCYTE, VALGANCICLOVIR HCL, VALTREX, VANCOMYCIN, VANCOMYCIN HCL, VANCOMYCIN HCL-0.9% NACL, VANCOMYCIN HCL-D5W, VIMOVO, VIVLODEX, ZIPSOR, ZORTRESS, ZORVOLEX, ZOVIRAX, ZYNRELEF |
| Cobicistat; Ritonavir/Tenofovir Alafenamide (> 10 mg) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tenofovir alafenamide (AF) is a substrate of P-glycoprotein (P-gp) and BCRP, which may be inhibited by cobicistat or ritonavir.(1-6) Ritonavir coadministered with tipranavir has a net inductive effect on P-gp.(7) CLINICAL EFFECTS: Cobicistat or ritonavir in combination with tenofovir alafenamide (AF) may increase the concentration of tenofovir AF and the risk of renal or other toxicities in some patients.(1-6,8-9) Ritonavir-boosted tipranavir may decrease the levels of tenofovir AF.(4-6,8) PREDISPOSING FACTORS: Patients with baseline impairment of renal function and/or receiving commitant nephrotoxic agents are at increased risk of renal-related adverse events.(1-6,8-9) PATIENT MANAGEMENT: Regulatory agencies in different countries differ with regard to recommendations for the coadministration of cobicistat or ritonavir and tenofovir alafenamide (AF). The US National Institute of Health HIV guidelines state that no dose adjustment is necessary when using tenofovir AF 25 mg concurrently with cobicistat or ritonavir boosted atazanavir, darunavir, or lopinavir.(8) The US manufacturer of emtricitabine-tenofovir AF states that there are no clinically significant interactions with cobicistat or ritonavir boosted atazanavir, darunavir, or lopinavir. Coadministration with tipranavir-ritonavir is not recommended.(4,8) Note that other countries have different recommendations. The Canadian and European manufacturers of emtricitabine-tenofovir alafenamide that that the dose of tenofovir alafenamide should be 10 mg when coadministered with cobicistat or ritonavir boosted atazanavir, darunavir, or lopinavir. Coadministration with tipranavir-ritonavir is not recommended. There are no data to make recommendations for use of tenofovir AF with other protease inhibitors.(5-6) In patients receiving concurrent therapy, check glucose and urine protein at baseline and routinely monitor CrCl, urine glucose, urine protein, and serum phosphorus. Discontinue concurrent therapy if CrCL decreases below 30 ml/min.(4-6) DISCUSSION: In clinical trials, cobicistat 150 mg daily increased the area-under-curve (AUC) and maximal concentration (Cmax) of tenofovir alafenamide (AF) by 2.65-fold and 2.83-fold, respectively. Atazanavir 300 mg daily with ritonavir 100 mg daily increased the AUC and Cmax of tenofovir AF by 1.91-fold and 1.77-fold, respectively, whereas cobicistat-boosted atazanavir caused 1.75-fold and 1.8-fold increases in tenofovir AF AUC and Cmax. Darunavir 800 mg daily with cobicistat 150 mg daily did not affect the pharmacokinetics of tenofovir AF, but increased tenofovir AUC and Cmax by 3.24-fold and 3.16-fold, respectively. Similarly, darunavir 800 mg daily with ritonavir 100 mg daily did not affect the levels of tenofovir AF, but increased AUC and Cmax of tenofovir by 2.05-fold and 2.42-fold, respectively. Lopinavir 800 mg daily with ritonavir 200 mg daily increased AUC and Cmax of tenofovir AF by 1.47-fold and 2.19-fold, respectively.(4,6) Renal toxicity, including proximal renal tubulopathy and Fanconi syndrome, has been documented with coadministration of cobicistat with tenofovir disoproxil fumarate (DF) but not tenofovir alafenamide (AF). Monitoring of renal function is prudent and discontinuation is recommended when CrCl decreases below 30 ml/min to avoid renal impairment.(1-6,8-9) In a phase 3 trial of tenofovir AF versus tenofovir DF coformulated with elvitegravir, cobicistat, and emtricitabine, at 48 weeks patients in the tenofovir AF group had significantly smaller mean serum creatinine increases(0.08 vs 0.12 mg/dL; p<0.0001) and significantly less proteinuria (median % change -3 vs 20; p<0.0001).(9) Tenofovir AF strengths less than or equal to 10 mg are excluded from this interaction. In a pre-approval drug-drug interaction study, concurrent cobicistat (150 mg daily) increased tenofovir AF exposure (area-under-curve, AUC) 2.5-fold. Due to this interaction, the tenofovir AF strength in the cobicistat-elvitegravir-emtricitabine-tenofovir AF combination product was reduced from the originally proposed 25 mg to 10 mg.(10) |
EVOTAZ, KALETRA, LOPINAVIR-RITONAVIR, NORVIR, PREZCOBIX, RITONAVIR, TYBOST |
| Selected Nephrotoxic Agents/Immune Globulin IV (IGIV) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Immune Globulin Intravenous (IGIV) products, particularly those containing sucrose, can cause renal dysfunction, acute renal failure, osmotic nephrosis, and/or death. Concurrent administration of other nephrotoxic agents may result in additive or synergistic effects on renal function.(1-4) CLINICAL EFFECTS: Concurrent use of Immune Globulin Intravenous (IGIV) products with nephrotoxic agents such as adefovir, intravenous aminoglycosides, amphotericin B, non-steroidal anti-inflammatory agents, tenofovir, and vancomycin may result in renal toxicity.(1-4) Other nephrotoxic agents include capreomycin, gallium nitrate, and streptozocin. PREDISPOSING FACTORS: Patients at risk of acute renal failure include those with any degree of pre-existing renal insufficiency, diabetes mellitus, advanced age (above 65 years of age), volume depletion, sepsis, paraproteinemia, or receiving known nephrotoxic drugs.(1-4) Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose.(3-4) PATIENT MANAGEMENT: For patients at risk of renal dysfunction or renal failure, the US manufacturers of Immune Globulin Intravenous (IGIV) products recommends administration at the minimum dose and infusion rate practicable; ensure adequate hydration in patients before administration; and monitor renal function and urine output with assessment of blood urea nitrogen (BUN) and serum creatinine before initial infusion and at regular intervals during therapy.(1-3) Concurrent administration of potentially nephrotoxic agents should be avoided.(1) Review prescribing information for IGIV product to be administered for sucrose content. If concurrent therapy is warranted, monitor renal function closely. In high risk patients, consider selecting an IGIV product that does not contain sucrose. DISCUSSION: The safety of Immune Globulin Intravenous (IGIV) has not been studied in patients receiving other known potentially nephrotoxic agents. Renal impairment is a major toxicity of IGIV products.(1-3) A review of the FDA renal adverse events (RAEs) (i.e. acute renal failure or insufficiency) from June 1985 to November 1998 identified 120 reports worldwide associated with IGIV administration. In the US, the FDA received 88 reports of cases with clinical and/or laboratory findings consistent with RAE (i.e. increased serum creatinine, oliguria, and acute renal failure). Patient cases involved a median age of 60.5 years and 55% were male. Of the 54 patients who developed acute renal failure, 65% were greater than 65 years, 56% had diabetes, and 26% had prior renal insufficiency; 59% had one, 35% had two, and 6% had three of these conditions. Upon review of the IGIV product received, 90% of cases received sucrose-containing IGIV products with the remaining patients receiving either maltose- or glucose-containing products. Approximately 40% of affected patients required dialysis and RAE may have contributed to death in 15% of patients.(4) |
ALYGLO, BIVIGAM, CUTAQUIG, CUVITRU, FLEBOGAMMA DIF, GAMMAGARD LIQUID, GAMMAGARD S-D, GAMMAKED, GAMMAPLEX, GAMUNEX-C, HIZENTRA, HYQVIA, HYQVIA IG COMPONENT, OCTAGAM, PANZYGA, PRIVIGEN, XEMBIFY |
| Metformin/Bictegravir SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Metformin renal clearance is mediated by OCT2 and MATE1 transport. Bictegravir inhibits elimination by these pathways.(1,2) CLINICAL EFFECTS: Use of bictegravir may increase levels of metformin, which may result in lactic acidosis. PREDISPOSING FACTORS: Risk factors for metformin associated lactic acidosis include renal impairment,sepsis, dehydration, excessive alcohol intake, acute or chronic metabolic acidosis, hepatic insufficiency, acute heart failure, metformin plasma levels > 5 micrograms/mL, and conditions which may lead to tissue hypoxia. Geriatric patients may also be at higher risk due to slower metformin clearance and increased half-life in this population. PATIENT MANAGEMENT: The US labeling for metformin recommends the dose of metformin be adjusted as needed.(1) Evaluate patient's renal function and consider discontinuation of one or both agents in patients with renal impairment. Monitor for signs and symptoms of metformin toxicity (lactic acidosis) such as malaise, myalgias, increasing somnolence, and respiratory distress. Laboratory results which may signal lactic acidosis include: elevated blood lactate levels (greater than 5 mmol/L), low pH, an increased anion gap, and increased lactate to pyruvate ratio. DISCUSSION: Bictegravir is an inhibitor of OCT2 and MATE1.(2) Trimethoprim, an inhibitor of OCT2 and MATE1, was found to cause significant inhibition of net transcellular chloroquine transport in canine kidney-OCT2-MATE1 cells. Chloroquine is eliminated by renal tubular secretion involving multidrug and toxin extrusion protein 1 (MATE1). Trimethoprim caused concentration-dependent inhibition of net metformin intake in HEK293-MATE1 cells (human embryonic kidney).(3) A randomized, open-label, two-phase crossover study found that trimethoprim inhibited OCT2, MATE1, and MATE2-K-dependent transport of metformin. Trimethoprim increased metformin area-under-curve (AUC) by 29.4% and decreased metformin renal clearance by 26.4%.(4) In a study in 24 healthy volunteers received metformin 500 mg three times daily for ten days and trimethoprim 200 mg twice daily from days 5-10. Trimethoprim significantly reduced the apparent systemic metformin clearance (CL/F) from 74 to 54 l/h and renal metformin clearance from 31 to 21 l/h. Metformin half-life was prolonged from 2.7 to 3.6h. The metformin plasma concentration (Cmax) increased 38% and the AUC by 37%. Trimethoprim was also associated with a decrease in creatinine clearance and an increase in plasma lactate. (5) |
ACTOPLUS MET, ALOGLIPTIN-METFORMIN, DAPAGLIFLOZIN-METFORMIN ER, GLIPIZIDE-METFORMIN, GLYBURIDE-METFORMIN HCL, INVOKAMET, INVOKAMET XR, JANUMET, JANUMET XR, JENTADUETO, JENTADUETO XR, KAZANO, METFORMIN ER GASTRIC, METFORMIN ER OSMOTIC, METFORMIN HCL, METFORMIN HCL ER, PIOGLITAZONE-METFORMIN, RIOMET, SAXAGLIPTIN-METFORMIN ER, SEGLUROMET, SITAGLIPTIN-METFORMIN, SYNJARDY, SYNJARDY XR, TRIJARDY XR, XIGDUO XR, ZITUVIMET, ZITUVIMET XR |
| Bictegravir/Polyvalent Cations; Sucralfate SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Polyvalent cations and sucralfate may bind to bictegravir in the GI tract, preventing its absorption.(1) CLINICAL EFFECTS: Polyvalent cations and sucralfate may reduce levels and clinical effectiveness of bictegravir.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Bictegravir must be taken 2 hours before or 6 hours after polyvalent cations or sucralfate. Medicines containing calcium can be taken together with bictegravir if taken with food.(1) Some vitamin preparations may contain sufficient quantities of polyvalent cations to interact as well. DISCUSSION: Simultaneous administration of aluminum and magnesium hydroxide (20 ml) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir maximum concentration (Cmax) and area-under-curve (AUC) by 80% and 79%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 2 hours after bictegravir (50 mg single dose) in a fasted state decreased bictegravir Cmax and AUC by 7% and 13%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 2 hours before bictegravir (50 mg single dose) in a fasted state decreased bictegravir Cmax and AUC by 58% and 52%, respectively.(1) Simultaneous administration of aluminum and magnesium hydroxide (20 ml) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 49% and 47%, respectively.(1) Simultaneous administration of calcium carbonate (1200 mg single dose) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 42% and 33%, respectively.(1) Simultaneous administration of calcium carbonate (1200 mg single dose) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax by 10% and increased AUC 3%, respectively.(1) Simultaneous administration of ferrous fumarate (324 mg single dose) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 71% and 63%, respectively.(1) Simultaneous administration of ferrous fumarate (324 mg single dose) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 25% and 16%, respectively.(1) |
ALUMINUM HYDROXIDE, CARAFATE, CLENPIQ, GALZIN, MAGNESIUM CHLORIDE, MAGNESIUM OXIDE, MAGNESIUM SULFATE, MANGANESE CHLORIDE, MANGANESE GLUCONATE, MANGANESE SULFATE, SUCRALFATE, WILZIN, ZINC ACETATE, ZINC CHLORIDE, ZINC SULFATE |
| Bictegravir/Calcium & Iron Containing Supplements SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Calcium or iron containing supplements may bind to bictegravir in the GI tract, preventing its absorption.(1) CLINICAL EFFECTS: Calcium or iron containing supplements may reduce levels and clinical effectiveness of bictegravir.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Bictegravir and calcium or iron containing supplements may be taken together with food. Routine administration of bictegravir under fasting conditions simultaneously with, or within 2 hours after, calcium or iron containing supplements is not recommended.(1) In pregnant patients, if bictegravir is taken on an empty stomach, take bictegravir at least 2 hours before or 6 hours after calcium or iron containing supplements.(1) DISCUSSION: Simultaneous administration of aluminum and magnesium hydroxide (20 ml) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir maximum concentration (Cmax) and area-under-curve (AUC) by 80% and 79%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 2 hours after bictegravir (50 mg single dose) in a fasted state decreased bictegravir Cmax and AUC by 7% and 13%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 2 hours before bictegravir (50 mg single dose) in a fasted state decreased bictegravir Cmax and AUC by 58% and 52%, respectively.(1) Simultaneous administration of aluminum and magnesium hydroxide (20 ml) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 49% and 47%, respectively.(1) Simultaneous administration of calcium carbonate (1200 mg single dose) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 42% and 33%, respectively.(1) Simultaneous administration of calcium carbonate (1200 mg single dose) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax by 10% and increased AUC 3%, respectively.(1) Simultaneous administration of ferrous fumarate (324 mg single dose) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 71% and 63%, respectively.(1) Simultaneous administration of ferrous fumarate (324 mg single dose) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 25% and 16%, respectively.(1) |
ACCRUFER, AUROVELA 24 FE, AUROVELA FE, AURYXIA, BALCOLTRA, BLISOVI 24 FE, BLISOVI FE, CALCIUM ACETATE, CALCIUM CHLORIDE, CALCIUM GLUCONATE, CALCIUM GLUCONATE MONOHYDRATE, CHARLOTTE 24 FE, DILUENT FOR ROTARIX, FEIRZA, FERRIC CITRATE, FINZALA, GEMMILY, HAILEY 24 FE, HAILEY FE, JOYEAUX, JUNEL FE, JUNEL FE 24, KAITLIB FE, LARIN 24 FE, LARIN FE, LAYOLIS FE, LEVONORG-ETH ESTRAD-FE BISGLYC, LO LOESTRIN FE, LOESTRIN FE, MERZEE, MIBELAS 24 FE, MICROGESTIN FE, MINZOYA, NORETHIN-ETH ESTRA-FERROUS FUM, NORETHINDRONE-E.ESTRADIOL-IRON, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TAYTULLA, TILIA FE, TRI-LEGEST FE, VELPHORO, WYMZYA FE, XARAH FE, XELRIA FE |
| Flecainide/MATE Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Inhibitors of the Multidrug and Toxin Extrusion (MATE) protein transporters in the kidneys may interfere with the renal elimination of flecainide.(1) CLINICAL EFFECTS: Concurrent use of MATE renal transporter inhibitors may result in increased levels of and toxicity from flecainide.(1) PREDISPOSING FACTORS: Risk factors for QT prolongation include: cardiovascular disease (e.g. heart failure, recent myocardial infarction, history of torsades de pointes, congenital long QT syndrome), female sex, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, advanced age, and concurrent use of agents known to cause QT prolongation.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: Monitor serum flecainide concentrations and observe the patients for signs of toxicity. If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: In a pharmacokinetic study, concurrent use of cimetidine (1 gram daily) increased flecainide levels by 30% and increased half-life by 10%.(1) MATE inhibitors linked include: abemaciclib, bictegravir, cimetidine, isavuconazole, pyrimethamine, risdiplam, trimethoprim, and tucatinib.(4,5) |
FLECAINIDE ACETATE |
| Oxaliplatin/MATE Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Inhibitors of the Multidrug and Toxin Extrusion (MATE) protein transporters in the kidneys may inhibit the renal transport of oxaliplatin.(1) Oxaliplatin is a MATE substrate.(2,3) CLINICAL EFFECTS: Concurrent use of MATE renal transporter inhibitors may result in increased levels of and toxicity from oxaliplatin, including QT prolongation and neutropenia.(1) PREDISPOSING FACTORS: Risk factors for QT prolongation include: cardiovascular disease (e.g. heart failure, recent myocardial infarction, history of torsades de pointes, congenital long QT syndrome), female sex, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, advanced age, and concurrent use of agents known to cause QT prolongation.(4) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(4) PATIENT MANAGEMENT: Concurrent use of oxaliplatin with MATE renal transporter inhibitors should be approached with caution and monitored closely. If concurrent use is warranted, monitor for toxicities of oxaliplatin and consider dosage reduction based on toxicity dose recommendations.(1) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: Oxaliplatin is a MATE substrate.(2,3) MATE inhibitors include: abemaciclib, bictegravir, cimetidine, isavuconazole, pyrimethamine, risdiplam, trimethoprim, and tucatinib.(6,7) |
OXALIPLATIN |
| Dalfampridine/OCT2 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Agents that inhibit the organic cation transporter 2 (OCT2) may inhibit the excretion of dalfampridine by OCT2 in the kidneys.(1,2) CLINICAL EFFECTS: Concurrent use of OCT2 renal transport inhibitors may result in increased levels of and toxicity from dalfampridine.(1,2) PREDISPOSING FACTORS: The risk of seizures from dalfampridine may be increased in patients with a history of head trauma or prior seizure; CNS tumor; CNS infections; severe hepatic cirrhosis; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; diabetics treated with oral hypoglycemics or insulin; or with concomitant medications known to lower seizure threshold (antidepressants, theophylline, systemic steroids). PATIENT MANAGEMENT: Consider the potential benefits against the risks of concurrent use of dalfampridine with OCT2 renal transport inhibitors. If concurrent use is appropriate, monitor for toxicities of dalfampridine and consider dosage reduction of dalfampridine.(1,2) DISCUSSION: In a study, givinostat increased the levels of creatinine (OCT2 substrate) by 4.76 umol/L from baseline.(1) In a study, trilaciclib increased the area-under-curve (AUC) and maximum concentration (Cmax) of metformin (an OCT2, MATE1, and MATE-2K substrate) by approximately 65% and 81%, respectively. Renal clearance of metformin was decreased by 37%. Trilaciclib did not cause significant changes in the pharmacokinetics of topotecan (a MATE1 and MATE-2K substrate).(2) OCT2 inhibitors linked to this monograph include: abemaciclib, arimoclomol, bictegravir, givinostat, isavuconazole, ranolazine, trilaciclib, trimethoprim, tucatinib, and vimseltinib.(3) |
4-AMINOPYRIDINE, AMPYRA, DALFAMPRIDINE, DALFAMPRIDINE ER |
| Cisplatin/OCT2 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Agents that inhibit the organic cation transporter 2 (OCT2) may inhibit the excretion of cisplatin by OCT2 in the kidneys.(1,2) CLINICAL EFFECTS: Concurrent use of OCT2 renal transport inhibitors may result in increased levels of and toxicities from cisplatin, including nephrotoxicity, ototoxicity, neuropathy, and myelosuppression.(1,2) PREDISPOSING FACTORS: Pre-existing renal insufficiency, advanced age, and dehydration may increase the risk of nephrotoxicity. PATIENT MANAGEMENT: Consider the potential benefits against the risks of concurrent use of cisplatin with OCT2 renal transport inhibitors. If concurrent use is appropriate, monitor closely for toxicities of cisplatin and consider dosage reduction of cisplatin.(1,2) DISCUSSION: In a study, givinostat increased the levels of creatinine (OCT2 substrate) by 4.76 umol/L from baseline.(1) In a study, trilaciclib increased the area-under-curve (AUC) and maximum concentration (Cmax) of metformin (an OCT2, MATE1, and MATE-2K substrate) by approximately 65% and 81%, respectively. Renal clearance of metformin was decreased by 37%. Trilaciclib did not cause significant changes in the pharmacokinetics of topotecan (a MATE1 and MATE-2K substrate).(2) OCT2 inhibitors linked to this monograph include: abemaciclib, arimoclomol, bictegravir, dolutegravir, givinostat, isavuconazole, ranolazine, trilaciclib, trimethoprim, tucatinib, and vimseltinib.(3) |
CISPLATIN, KEMOPLAT |
| Clofarabine/OCT2 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Agents that inhibit the organic cation transporter 2 (OCT2) may inhibit the excretion of clofarabine by OCT2 in the kidneys.(1,2) CLINICAL EFFECTS: Concurrent use of OCT2 renal transport inhibitors may result in increased levels of and toxicity from clofarabine, including myelosuppression, serious hemorrhages, enterocolitis, nephrotoxicity, and hepatotoxicity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Consider the potential benefits against the risks of concurrent use of clofarabine with OCT2 renal transport inhibitors. If concurrent use is appropriate, monitor for toxicities of the clofarabine and consider dosage reduction of clofarabine.(1) DISCUSSION: In an animal study, cimetidine, an OCT2 inhibitor, decreased the clearance of clofarabine in rats by 61%. The clinical implications of this finding are unclear.(1,2) In a study, givinostat increased the levels of creatinine (OCT2 substrate) by 4.76 umol/L from baseline.(3) In a study, trilaciclib increased the area-under-curve (AUC) and maximum concentration (Cmax) of metformin (an OCT2, MATE1, and MATE-2K substrate) by approximately 65% and 81%, respectively. Renal clearance of metformin was decreased by 37%. Trilaciclib did not cause significant changes in the pharmacokinetics of topotecan (a MATE1 and MATE-2K substrate).(4) OCT2 inhibitors linked to this monograph include: abemaciclib, arimoclomol, bictegravir, cimetidine, dolutegravir, givinostat, isavuconazole, ranolazine, trilaciclib, trimethoprim, tucatinib, and vimseltinib.(5) |
CLOFARABINE |
| Procainamide/OCT2 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Agents that inhibit the organic cation transporter 2 (OCT2) may inhibit the excretion of procainamide by OCT2 in the kidneys.(1,2) CLINICAL EFFECTS: Concurrent use of OCT2 renal transport inhibitors may result in increased levels of and toxicities of procainamide,(1,2) including potentially life-threatening cardiac arrhythmias, like torsades de pointes (TdP).(3) PREDISPOSING FACTORS: Risk factors for QT prolongation include: cardiovascular disease (e.g. heart failure, recent myocardial infarction, history of torsades de pointes, congenital long QT syndrome), female sex, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, advanced age, and concurrent use of agents known to cause QT prolongation.(3) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(3) PATIENT MANAGEMENT: Consider the potential benefits against the risks of concurrent use of procainamide with OCT2 renal transport inhibitors. If concurrent use is appropriate, monitor for toxicities of procainamide and consider dosage reduction of procainamide.(1) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: In a study, givinostat increased the levels of creatinine (OCT2 substrate) by 4.76 umol/L from baseline.(1) In a study, trilaciclib increased the area-under-curve (AUC) and maximum concentration (Cmax) of metformin (an OCT2, MATE1, and MATE-2K substrate) by approximately 65% and 81%, respectively. Renal clearance of metformin was decreased by 37%. Trilaciclib did not cause significant changes in the pharmacokinetics of topotecan (a MATE1 and MATE-2K substrate).(2) OCT2 inhibitors linked to this monograph include: abemaciclib, arimoclomol, bictegravir, cimetidine, dolutegravir, givinostat, isavuconazole, trilaciclib, tucatinib, and vimseltinib.(4) |
PROCAINAMIDE HCL |
| Bictegravir-Emtricitabine-Tenofovir Alafenamide/Selected P-gp Inducers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tenofovir alafenamide (TAF) is a substrate of the intestinal efflux transporter P-glycoprotein (P-gp). Inducers of P-gp may decrease systemic absorption of TAF.(1-2) CLINICAL EFFECTS: Concurrent or recent use of P-gp inducers may result in decreased systemic levels and effectiveness of tenofovir alafenamide.(1-2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of bictegravir-emtricitabine-TAF states that concurrent use with rifabutin or rifapentine (P-gp inducers) is not recommended.(1) It may be prudent to use alternatives to other P-gp inducers as well. DISCUSSION: When tenofovir alafenamide (TAF) was coadministered with carbamazepine, the maximum concentration (Cmax) and area-under-curve (AUC) were decreased 57% and 55%, respectively.(2) A subsequent study suggests that this interaction may not have clinically significant effects on intracellular levels of tenofovir diphosphate, the active metabolite of tenofovir alafenamide. In a study of 23 healthy volunteers, the intracellular Cmax and AUC of tenofovir diphosphate were 38% and 36% lower, respectively, when tenofovir alafenamide was coadministered with rifampin than without rifampin. However, these levels of tenofovir diphosphate were 4.4- and 4.21-fold higher, respectively, than levels obtained from tenofovir disoproxil 300 mg daily without rifampin.(3) Selected P-gp inducers linked to this monograph include: lorlatinib.(4) |
LORBRENA |
The following contraindication information is available for BIKTARVY (bictegravir sodium/emtricitabine/tenofovir alafenamide fumar):
Drug contraindication overview.
*Concomitant use of dofetilide since serious and/or life-threatening adverse effects due to possible increased dofetilide plasma concentrations may occur. *Concomitant use of rifampin since substantially decreased plasma bictegravir concentrations may occur and result in loss of virologic response and development of resistance.
*Concomitant use of dofetilide since serious and/or life-threatening adverse effects due to possible increased dofetilide plasma concentrations may occur. *Concomitant use of rifampin since substantially decreased plasma bictegravir concentrations may occur and result in loss of virologic response and development of resistance.
There are 2 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Lactation |
| Lactic acidosis |
There are 1 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
There are 2 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Kidney disease with likely reduction in glomerular filtration rate (GFr) |
| Viral hepatitis B |
The following adverse reaction information is available for BIKTARVY (bictegravir sodium/emtricitabine/tenofovir alafenamide fumar):
Adverse reaction overview.
The most common adverse effects (>=5% incidence) in patients receiving BIC/FTC/TAF include diarrhea, nausea, and headache.
The most common adverse effects (>=5% incidence) in patients receiving BIC/FTC/TAF include diarrhea, nausea, and headache.
There are 22 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. |
Elevated serum amylase Increased alanine transaminase Increased aspartate transaminase Kidney disease with reduction in glomerular filtration rate (GFr) |
| Rare/Very Rare |
|---|
|
Abnormal hepatic function tests Acute renal failure Angioedema Autoimmune hepatitis Fanconi syndrome Graves' disease Guillain-barre syndrome Hypophosphatemia Lactic acidosis Pancreatitis Polymyositis Steatosis of liver Stevens-johnson syndrome Suicidal Suicidal ideation Thrombocytopenic disorder Toxic epidermal necrolysis Urticaria |
There are 16 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Diarrhea Headache disorder Hyperbilirubinemia Nausea |
Acute abdominal pain Dizziness Dream disorder Fatigue Flatulence Insomnia Skin rash Vomiting |
| Rare/Very Rare |
|---|
|
Depression Dyspepsia Fever Weight gain |
The following precautions are available for BIKTARVY (bictegravir sodium/emtricitabine/tenofovir alafenamide fumar):
Safety and efficacy of BIC/FTC/TAF have not been established in pediatric patients weighing <14 kg. Safety and efficacy of BIC/FTC/TAF have been established for the treatment of HIV-1 infection in pediatric patients weighing 14 kg or more. Use of BIC/FTC/TAF in pediatric patients 2 to <18 years of age weighing at least 14 kg is supported by results of clinical trials in adults, and by results of an open-label study in 3 age-based cohorts of pediatric patients.
Patients in these cohorts were virologically suppressed, and received BIC/FTC/TAF for a treatment duration of 24 or 48 weeks. No patients 2 years of age were enrolled in these clinical studies of BIC/FTC/TAF; the youngest patient was 3 years of age at enrollment and weighed at least 14 kg. Safety and efficacy of BIC/FTC/TAF in these pediatric patients were similar to that in adults, and there was no clinically important difference in exposures of the components of BIC/FTC/TAF in these pediatric patients compared with adults. Adverse effects reported in pediatric patients receiving BIC/FTC/TAF are similar to those reported in adults receiving the drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Patients in these cohorts were virologically suppressed, and received BIC/FTC/TAF for a treatment duration of 24 or 48 weeks. No patients 2 years of age were enrolled in these clinical studies of BIC/FTC/TAF; the youngest patient was 3 years of age at enrollment and weighed at least 14 kg. Safety and efficacy of BIC/FTC/TAF in these pediatric patients were similar to that in adults, and there was no clinically important difference in exposures of the components of BIC/FTC/TAF in these pediatric patients compared with adults. Adverse effects reported in pediatric patients receiving BIC/FTC/TAF are similar to those reported in adults receiving the drug.
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
In pregnant individuals who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no known substitutions associated with resistance to the individual components of the drug, the recommended dosage of BIC/FTC/TAF is 1 tablet containing 50 mg of bictegravir, 200 mg of emtricitabine, and 25 mg of tenofovir alafenamide once daily. Reduced drug exposures have been observed with use of BIC/FTC/TAF in pregnancy. Viral load should be monitored closely.
The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to BIC/FTC/TAF during pregnancy. Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting https://www.apregistry.com/.
The manufacturer states that data regarding use of BIC, FTC, and TAF in pregnant women have not established a drug-associated risk of birth defects, miscarriage, or other adverse maternal or fetal outcomes. Prospective reports to the APR reveal that of over 500 BIC exposures during pregnancy resulting in live births, the prevalence of birth defects was 4.3% following first trimester exposure and 1.8%
following second-/third-trimester exposure. Of over 6500 FTC exposures during pregnancy resulting in live births, the prevalence of birth defects was 2.9% following first trimester exposure and 2.8%
following second-/third-trimester exposure. Of over 1200 TAF exposures during pregnancy resulting in live births, the prevalence of birth defects was 3.9% following first trimester exposure and 4.8%
following second-/third-trimester exposure. In an open-label, multicenter, single-arm, phase 1b study, the pharmacokinetics, safety, and efficacy of BIC/FTC/TAF during pregnancy were evaluated. The trial included 33 virologically suppressed (HIV-1 RNA <50 copies/mL) pregnant adult women with no known substitutions associated with resistance to BIC, FTC, or TAF.
The patients were administered BIC/FTC/TAF (containing 50 mg of bictegravir, 200 mg of emtricitabine, and 25 mg of tenofovir alafenamide) once daily from the second or third trimester through postpartum. Of the 32 patients who completed the study, 100% maintained viral suppression during pregnancy, at delivery, and through Week 18 postpartum. The baseline median CD4+ cell count for evaluable patients was 558 cells/mcL; median change in CD4+ cell count from baseline to Week 12 postpartum was 159 cells/microL.
Of the 29 neonates assessed, all had a negative/nondetectable HIV-1 polymerase chain reaction result at birth and/or at 4 to 8 weeks post-birth. Safety findings were consistent with those observed in other adult trials involving BIC/FTC/TAF.
The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to BIC/FTC/TAF during pregnancy. Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting https://www.apregistry.com/.
The manufacturer states that data regarding use of BIC, FTC, and TAF in pregnant women have not established a drug-associated risk of birth defects, miscarriage, or other adverse maternal or fetal outcomes. Prospective reports to the APR reveal that of over 500 BIC exposures during pregnancy resulting in live births, the prevalence of birth defects was 4.3% following first trimester exposure and 1.8%
following second-/third-trimester exposure. Of over 6500 FTC exposures during pregnancy resulting in live births, the prevalence of birth defects was 2.9% following first trimester exposure and 2.8%
following second-/third-trimester exposure. Of over 1200 TAF exposures during pregnancy resulting in live births, the prevalence of birth defects was 3.9% following first trimester exposure and 4.8%
following second-/third-trimester exposure. In an open-label, multicenter, single-arm, phase 1b study, the pharmacokinetics, safety, and efficacy of BIC/FTC/TAF during pregnancy were evaluated. The trial included 33 virologically suppressed (HIV-1 RNA <50 copies/mL) pregnant adult women with no known substitutions associated with resistance to BIC, FTC, or TAF.
The patients were administered BIC/FTC/TAF (containing 50 mg of bictegravir, 200 mg of emtricitabine, and 25 mg of tenofovir alafenamide) once daily from the second or third trimester through postpartum. Of the 32 patients who completed the study, 100% maintained viral suppression during pregnancy, at delivery, and through Week 18 postpartum. The baseline median CD4+ cell count for evaluable patients was 558 cells/mcL; median change in CD4+ cell count from baseline to Week 12 postpartum was 159 cells/microL.
Of the 29 neonates assessed, all had a negative/nondetectable HIV-1 polymerase chain reaction result at birth and/or at 4 to 8 weeks post-birth. Safety findings were consistent with those observed in other adult trials involving BIC/FTC/TAF.
Published literature demonstrate that BIC, FTC, and TAF are present in human milk. There are no reported adverse effects of FTC or TAF on the breastfed child; no data exist on the effects of BIC on breastfed children. It is not known whether BIC/FTC/TAF affects human milk production.
The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant.
Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV arenot on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant.
Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV arenot on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
The manufacturer does not provide recommendations on dosage adjustments in geriatric patients; however, increased sensitivity to BIC/FTC/TAF in some older individuals cannot be ruled out. In studies of virologically-suppressed patients 65 years of age and older receiving BIC/FTC/TAF, 90% of 111 subjects were 65-74 years of age, and 10% were 75-84 years of age. These studies identified no overall differences in response based on safety or efficacy between older adults and younger adult subjects, although greater sensitivity of some older individuals cannot be ruled out.
The following prioritized warning is available for BIKTARVY (bictegravir sodium/emtricitabine/tenofovir alafenamide fumar):
WARNING: If you have hepatitis B infection as well as HIV, your hepatitis symptoms may get worse or become very serious if you stop taking this medication. Talk with your doctor before stopping this medication. Your doctor will check your liver function tests for several months after you stop. Tell your doctor right away if you develop symptoms of worsening liver problems.
WARNING: If you have hepatitis B infection as well as HIV, your hepatitis symptoms may get worse or become very serious if you stop taking this medication. Talk with your doctor before stopping this medication. Your doctor will check your liver function tests for several months after you stop. Tell your doctor right away if you develop symptoms of worsening liver problems.
The following icd codes are available for BIKTARVY (bictegravir sodium/emtricitabine/tenofovir alafenamide fumar)'s list of indications:
| HIV infection | |
| B20 | Human immunodeficiency virus [HIv] disease |
| B97.35 | Human immunodeficiency virus, type 2 [HIV 2] as the cause of diseases classified elsewhere |
| O98.7 | Human immunodeficiency virus [HIv] disease complicating pregnancy, childbirth and the puerperium |
| O98.71 | Human immunodeficiency virus [HIv] disease complicating pregnancy |
| O98.711 | Human immunodeficiency virus [HIv] disease complicating pregnancy, first trimester |
| O98.712 | Human immunodeficiency virus [HIv] disease complicating pregnancy, second trimester |
| O98.713 | Human immunodeficiency virus [HIv] disease complicating pregnancy, third trimester |
| O98.719 | Human immunodeficiency virus [HIv] disease complicating pregnancy, unspecified trimester |
| O98.72 | Human immunodeficiency virus [HIv] disease complicating childbirth |
| O98.73 | Human immunodeficiency virus [HIv] disease complicating the puerperium |
| Z21 | Asymptomatic human immunodeficiency virus [HIv] infection status |
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