Emtricitabine and tenofovir alafenamide fumarate (monograph)

Emtricitabine and tenofovir alafenamide fumarate (monograph)

Emtricitabine and tenofovir alafenamide fumarate (monograph)

warning

HBV-Infektion

• Severe, acute exacerbations of HBV have been reported following discontinuation of products containing emtricitabine (FTC) and/or the tenofovir prodrug tenofovir disoproxil fumarate (tenofovir DF; TDF) in patients infected with HBV; may occur in such patients even after discontinuation of emtricitabine and tenofovir alafenamide fumarate (emtricitabine/tenofovir alafenamide fumarate; FTC/TAF).

• Monitor liver function closely with clinical and laboratory assessments in HBV-infected patients for at least several months after discontinuation of FTC/TAF. If clinically appropriate, initiate HBV treatment.

HIV-1-Präexpositionsprophylaxe (PrEP)

• Only prescribe FTC/TAF for HIV-1 PrEP to individuals who were confirmed to be HIV-1 negative immediately prior to starting PrEP. Confirm HIV-1 negative status regularly (at least every 3 months) while on PrEP.

• Drug-resistant HIV-1 variants were identified when FTC/TDF PrEP was used after undetected acute HIV-1 infection. Do not initiate FTC/TAF PrEP if signs or symptoms of acute HIV-1 infection are present unless negative infection status is confirmed.

introduction

Uses for Emtricitabine and Tenofovir Alafenamide Fumarate

Treatment of HIV infection

Treatment of HIV-1 infection in adults, adolescents, and pediatric patients weighing ≥35 kg; must be used in conjunction with other antiretroviral drugs.

Treatment of HIV-1 infection in pediatric patients weighing ≥ 14 kg and < 35 kg in conjunction with other antiretroviral drugs, excluding protease inhibitors, which require a CYP3A inhibitor.

Dual NRTIs are used in conjunction with an HIV integrase strand transfer inhibitor (INSTI), an HIV nonnucleoside reverse transcriptase inhibitor (NNRTI), or an HIV protease inhibitor (PI) in INSTI, NNRTI, or PI-based regimens. Fixed combinations are used in certain patient populations to reduce pill burden and improve compliance.

Experts indicate that FTC/TAF is a recommended dual NRTI option for use in most INSTI, NNRTI, and PI-based regimens for the initial treatment of HIV-infected adults and adolescents.

For first-line treatment in antiretroviral-naive pediatric patients, experts indicate that FTC/TAF is a preferred dual NRTI option for first-line treatment regimens in antiretroviral-naïve children aged ≥ 6 years in early puberty (SMR 1-3) and weighing ≥ 25 kg who are part of NNRTI or INSTI-based therapy and in those Patients weighing ≥ 35 kg on PI, NNRTI or INSTI based therapy. These experts indicate that FTC/TAF is a preferred dual NRTI option in antiretroviral-naïve adolescents ≥ 12 years of age with SMR 4 or 5.

May also be used as part of combination antiretroviral therapy in previously treated patients; Select antiretroviral drugs in the new treatment regimen for patients experiencing treatment failure based on antiretroviral treatment history and results of current and previous resistance testing.

Since both drugs are active against both HIV and HBV, FTC/TAF is a preferred dual NRTI option for antiretroviral therapy in HIV-infected patients who are co-infected with HBV.

The most appropriate antiretroviral regimen cannot be defined for every clinical scenario; Select the treatment regimen based on information regarding antiretroviral efficacy, the potential rate of resistance development, known toxicities, the potential for pharmacokinetic interactions, and the patient's virologic, immunologic, and clinical characteristics. Guidelines for the treatment of HIV infection, including specific recommendations for initial treatment of antiretroviral-naïve patients and recommendations for modification of antiretroviral regimens, can be found at [Web].

Pre-exposure prophylaxis to prevent HIV-1 infection (PrEP)

FTC/TAF is used for PrEP in conjunction with safe sex practices to reduce the risk of sexually acquired HIV-1 infection (excluding receptive vaginal sex) in at-risk HIV-1 negative adults and adolescents weighing ≥35 kg.

Individuals must have a negative HIV-1 test immediately prior to starting FTC/TAF treatment for PrEP.

The effectiveness of FTC/TAF for HIV-1 PrEP in individuals at risk of HIV-1 acquisition through receptive vaginal sex has not been established.

Adults and adolescents at risk include those whose partners are known to be infected with HIV-1, or those who engage in sexual activity in a high-prevalence area or social network and have ≥1 of the following: inconsistent or no condom use, past or current sexually transmitted infections, illicit drug use, alcohol dependence, or partners with unknown HIV-1 status and any of these Risk factors.

PrEP with FTC/TAF is not always effective in preventing HIV-1 infection; must be used as part of a comprehensive prevention strategy that includes safe sex practices.

Dosage and administration of emtricitabine and tenofovir alafenamide fumarate

Generally

Pre-treatment screening

• Test patients for hepatitis B virus (HBV) infection before or during treatment with emtricitabine/tenofovir alafenamide fumarate (FTC/TAF).

• Before initiating FTC/TAF, all patients should have their Scr, estimated Clcr, urine glucose, and urine protein assessed. Also assess serum phosphate levels in patients with chronic kidney disease.

• Screening for HIV-1 infection immediately prior to initiating FTC/TAF therapy for HIV-1 pre-exposure prophylaxis (PrEP). If recent (<1 month) HIV-1 exposure is suspected or clinical symptoms suggestive of acute HIV-1 infection are present, use an FDA-cleared or approved test as an aid in the diagnosis of acute or primary HIV-1 infection.

Patient monitoring

• Monitor liver function closely with clinical and laboratory follow-up in HBV-infected patients for at least several months after discontinuation of FTC/TAF.

• Assess Scr, estimated Clcr, urine glucose, and urine protein in all patients on a clinically appropriate schedule. Also assess serum phosphate levels in patients with chronic kidney disease.

• For patients receiving FTC/TAF for PrEP, screen for HIV-1 infection at least every 3 months and when another sexually transmitted infection is diagnosed.

Administration

Oral administration

Administer a fixed combination of FTC/TAF orally once daily, regardless of food intake. Use in conjunction with other antiretroviral drugs to treat HIV-1; Use alone as a complete PrEP regimen to prevent sexually transmitted HIV-1.

dosage

FTC/TAF tablets contain emtricitabine and tenofovir alafenamide fumarate; Dosage of tenofovir alafenamide fumarate expressed in tenofovir alafenamide.

FTC/TAF fixed-dose tablets contain 200 mg emtricitabine and 25 mg tenofovir alafenamide or 120 mg emtricitabine and 15 mg tenofovir alafenamide.

Pediatric patients

Treatment of HIV infection

Orally

Pediatric patients ≥ 35 kg: 1 tablet FTC/TAF (emtricitabine 200 mg, tenofovir alafenamide 25 mg) once daily.

Pediatric patients 14 to <35 kg: base dose by weight; For people weighing <25 kg, use a low-dose fixed combination tablet (emtricitabine 120 mg, tenofovir alafenamide 15 mg). (See Table 1.)

Table 1. Dosage of emtricitabine/tenofovir alafenamide for the treatment of HIV-1 infection in children weighing ≥ 14 kg1

This dosing information applies to pediatric patients with an estimated Clcr ≥ 30 mL/minute who are not receiving an HIV protease inhibitor coadministered with ritonavir or cobicistat.

Safety and efficacy of concomitant use of FTC/TAF with an HIV-1 protease inhibitor administered with either ritonavir or cobicistat have not been established in pediatric patients weighing <35 kg.

Pre-exposure prophylaxis to prevent HIV-1 infection (PrEP)

HIV-1-negative at-risk adolescents

Orally

Adolescents weighing ≥ 35 kg and an estimated Clcr ≥ 30 mL/minute: 1 tablet of FTC/TAF (emtricitabine 200 mg, tenofovir alafenamide 25 mg) once daily.

Adult

Treatment of HIV infection

Orally

1 tablet FTC/TAF (emtricitabine 200 mg, tenofovir alafenamide 25 mg) once daily.

This dosage recommendation applies to adults weighing ≥ 35 kg whose estimated Clcr is greater than or equal to 30 mL/minute or whose Clcr is < 15 mL/minute and who are receiving chronic hemodialysis.

Pre-exposure prophylaxis to prevent HIV-1 infection (PrEP)

HIV-1 negative adults at risk

Orally

1 tablet FTC/TAF (emtricitabine 200 mg, tenofovir alafenamide 25 mg) once daily.

This dosage recommendation applies to adults weighing ≥ 35 kg whose estimated Clcr is greater than or equal to 30 mL/minute or whose Clcr is < 15 mL/minute and who are receiving chronic hemodialysis.

Special populations

Renal dysfunction

Treatment of HIV infection

Clcr ≥30 ml/minute: Use usual dosage.

Clcr 15 to <30 ml/minute: Use not recommended.

Clcr <15 mL/minute (adults receiving hemodialysis): Use usual dosage. Administer a daily dose of FTC/TAF on hemodialysis days following completion of hemodialysis.

Clcr <15 ml/minute (no hemodialysis): Use not recommended.

Pre-exposure prophylaxis to prevent HIV-1 infection (PrEP)

Clcr ≥30 ml/minute: Use usual dosage.

Clcr 15 to <30 ml/minute: Use not recommended.

Clcr <15 mL/minute (adults receiving hemodialysis): Use usual dosage.

Clcr <15 ml/minute (no hemodialysis): Use not recommended.

Liver dysfunction

Treatment of HIV infection

Mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment: Use the usual dosage.

Severe hepatic impairment (Child-Pugh Class C): Not studied.

Pre-exposure prophylaxis to prevent HIV-1 infection (PrEP)

Mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment: Use the usual dosage.

Severe hepatic impairment (Child-Pugh Class C): Not studied.

Geriatric patients

Specific dosage recommendations are not available.

Precautions for emtricitabine and tenofovir alafenamide fumarate

Contraindications

• Do not use for PrEP for HIV-1 infection in individuals with unknown or positive HIV-1 status.

Warnings/Precautions

Warnings

People with HBV infection

Test all patients for the presence of HBV before initiating FTC/TAF.

Severe acute HBV exacerbations have been reported in HBV-infected patients following discontinuation of FTC- and/or TDF-containing products. HBV exacerbations have been associated with liver decompensation and liver failure. Such reactions could occur with FTC/TAF.

Offer HBV vaccination to HBV-infected individuals.

Carefully monitor liver function in HBV-infected patients with clinical and laboratory assessments for at least several months after discontinuation of FTC/TAF. If clinically appropriate, initiate HBV treatment.

FTC/TAF is not indicated for the treatment of chronic HBV infection.

Precautions associated with HIV-1 pre-exposure prophylaxis

Use FTC/TAF for HIV-1 PrEP only in at-risk adults or adolescents (≥35 kg) who are HIV-1 negative. Confirm a negative HIV-1 test immediately before starting PrEP and screen for HIV-1 infection at least every three months and if another sexually transmitted infection is diagnosed while on PrEP.

When FTC/TAF PrEP is used in people with undetected acute HIV-1 infection, drug-resistant HIV-1 variants may emerge. Do not initiate FTC/TAF PrEP if signs or symptoms of acute HIV-1 infection are present unless negative infection status is confirmed.

Some HIV-1 tests only detect anti-HIV antibodies and may not identify HIV-1 in the acute stage of infection. Before starting PrEP, screen HIV-negative individuals for current or recent signs or symptoms suggestive of acute viral infections (e.g., fever, fatigue, myalgia, rash) and ask about possible exposure events within the past month (e.g., unprotected sex, condom broken during sex with a partner of unknown HIV-1 status, or unknown viremia status, a recent sexually transmitted infection).

If recent (<1 month) HIV-1 exposure is suspected or clinical symptoms suggestive of acute HIV-1 infection are present, use an FDA-cleared or approved test as an aid in the diagnosis of acute or primary HIV-1 infection.

Time from initiation of FTC/TAF for HIV-1 PrEP to maximum protection against HIV-1 infection unknown.

Advise uninfected individuals to strictly adhere to the recommended FTC/TAF dosing schedule. Effectiveness in reducing the risk of acquiring HIV-1 was highly correlated with treatment adherence. Some individuals (e.g., adolescents) may benefit from more frequent visits and counseling to support adherence.

Additional Warnings/Precautions

Immune reconstitution syndrome

Immune reconstitution syndrome has been reported in HIV-infected patients receiving multidrug antiretroviral therapy, including regimens containing FTC, a component of FTC/TAF.

During initial treatment, an inflammatory response to indolent or persistent opportunistic infections (e.g., Mycobacterium avium complex) may occur in HIV-infected patients who respond to antiretroviral therapy [MAC]M. tuberculosis, cytomegalovirus [CMV] Pneumocystis jirovecii [formerly P. carinii]); This may require further evaluation and treatment.

Autoimmune diseases (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) have also been reported in the setting of immune reconstitution; Time to onset is more variable and may occur many months after starting antiretroviral therapy.

Renal dysfunction

Renal dysfunction, including cases of acute renal failure, proximal renal tubulopathy and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), have been reported with the use of preparations containing TAF, a component of FTC/TAF. Most of these cases are characterized by potential confounding factors; However, these factors may have predisposed patients to tenofovir-related renal toxicity.

Individuals with impaired renal function and those receiving nephrotoxic agents (e.g., nonsteroidal anti-inflammatory agents [NSAIAs]) are at increased risk of developing kidney-related side effects.

Measure Scr, estimated Clcr, urine glucose, and urine protein prior to initiating FTC/TAF treatment and monitor during treatment in all patients as clinically appropriate. In patients with chronic kidney disease, also assess serum phosphate levels at baseline and during treatment as clinically appropriate.

Discontinue FTC/TAF in individuals who develop clinically significant deterioration in renal function or signs of Fanconi syndrome.

The use of FTC/TAF is not recommended in patients with an estimated Clcr of 15 to <30 mL/minute or in patients with an estimated Clcr <15 mL/minute who are not receiving chronic hemodialysis.

Lactic acidosis and severe hepatomegaly with steatosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) have been reported in patients receiving HIV NRTIs, including FTC and TDF, alone or in combination with other antiretroviral drugs.

Discontinue FTC/TAF treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or marked hepatotoxicity (signs of hepatotoxicity may include hepatomegaly and steatosis, even in the absence of marked increases in serum aminotransferase concentrations).

Using fixed combinations

Consider the cautions, cautions, contraindications, and interactions associated with each component of FTC/TAF. For each drug in the fixed-dose combination, consider warnings that apply to specific populations (e.g., pregnant or breast-feeding women, people with liver or kidney impairment, geriatric patients).

FTC/TAF is used in conjunction with other antiretroviral drugs to treat HIV-1 infection. FTC/TAF is used alone without other antiretroviral medications for PrEP to prevent HIV-1 infection.

Specific populations

pregnancy

Antiretroviral Pregnancy Registry (APR) at 800-258-4263 or [Web].

Available data from APR show no difference in the overall risk of major birth defects for FTC or TAF compared to the background rate of 2.7% for major birth defects in a US reference population from the Metropolitan Atlanta Congenital Defects Program. An incidence of major birth defects for first trimester exposure of 2.6 or 4.2% and for second or third trimester exposure of 2.7 or 3% reported for FTC and TAF, respectively. No congenital anomalies were reported in 117 infants exposed to TAF after 24 weeks' gestation from mothers with HBV.

Experts indicate that FTC/TAF is a preferred dual NRTI option for use in conjunction with an HIV-INSTI or HIV-PI for initial treatment of HIV-1 infection in antiretroviral-naïve pregnant women and a preferred dual NRTI option in pregnant women with HBV co-infection. These experts state that FTC/TAF in conjunction with an HIV NNRTI represents an alternative therapy to the initial treatment of HIV-1 infection in antiretroviral-naïve pregnant women.

Experts indicate that the dual NRTI option FTC/TAF in combination with lopinavir/ritonavir, dolutegravir, raltegravir or darunavir/ritonavir is among the preferred therapies for the treatment of HIV type 2 (HIV-2) infections† [off-label] in pregnant women.

FTC/TAF has not been shown to be effective for PrEP in people who are susceptible to vaginal exposure to HIV-1. In HIV-1 negative women at risk of HIV-1 infection, HIV-1 prevention methods should be considered, including initiation or continuation of FTC/TDF PrEP, taking into account the potential increased risk of HIV-1 infection during pregnancy and the increased risk of mother-to-child transmission during acute HIV-1 infection.

lactation

FTC is excreted in breast milk; It is not known whether TAF is excreted in breast milk. Tenofovir is excreted in breast milk following administration of TDF.

It is not known whether FTC/TAF affects milk production in humans or breast-fed infants.

Advise HIV-infected women not to breastfeed due to the risk of HIV transmission (in HIV-negative infants), the risk of developing viral resistance (in HIV-positive infants), and the risk of adverse effects in the infant.

Pediatric use

Safety and efficacy for the treatment of HIV-1 infection in pediatric patients weighing <14 kg have not been established; The safety and effectiveness of HIV-1 PrEP in pediatric patients weighing <35 kg have not been established.

Safety and efficacy of concomitant use of FTC/TAF with an HIV-1 protease inhibitor administered with ritonavir or cobicistat in pediatric patients weighing <35 kg have not been established.

In children aged 6 to <18 years weighing ≥25 kg who received FTC/TAF in clinical trials for the treatment of HIV-1 infection, adverse reactions similar to those reported in adults were reported, except for a decrease in mean CD4+ cell count, which occurred in virologically-suppressed subjects between the ages of 6 and <12 years.

Decreased adherence to daily oral PrEP therapy after switching from monthly to quarterly clinic visits has been reported in at-risk adolescents; Therefore, adolescents receiving FTC/TAF PrEP may benefit from more frequent visits and counseling.

Geriatric use

No differences in safety or effectiveness were observed in patients ≥ 65 years compared to younger adults.

Liver dysfunction

Not studied in patients with severe hepatic impairment.

No dosage adjustment is necessary in patients with mild or moderate hepatic impairment.

Renal dysfunction

Assess Scr, estimated Clcr, urine glucose, and urine protein prior to initiation of FTC/TAF and monitor routinely during treatment in all patients as clinically appropriate. In patients with chronic kidney disease, also assess serum phosphate levels at baseline and during treatment as clinically appropriate.

No dose adjustment is required in patients with Clcr ≥ 30 mL/minute.

No dose adjustment is required in adults with an estimated Clcr < 15 mL/minute (end-stage renal disease) receiving chronic hemodialysis. On hemodialysis days, administer the daily dose of FTC/TAF after completion of hemodialysis treatment.

Use is not recommended in patients with severe renal impairment (estimated Clcr of 15 to <30 ml/minute) or in patients with end-stage renal disease (estimated Clcr <15 ml/minute) who are not receiving hemodialysis.

The safety and efficacy of concomitant use of FTC/TAF with an HIV-1 protease inhibitor administered with either ritonavir or cobicistat have not been established in adults with Clcr <15 mL/minute, with or without hemodialysis.

Common side effects

HIV-infected patients (≥ 10% of patients): Nausea.

PrEP (≥5% of patients): diarrhea.

Interactions with other medications

Drugs that affect or are metabolized by hepatic microsomal enzymes

FTC is not a substrate of CYP isoenzymes and does not inhibit CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6 or 3A4.

TAF is minimally metabolized by CYP3A. TAF is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or UGT1A1; TAF is a weak inhibitor of CYP3A in vitro but is not an inhibitor or inducer of CYP3A in vivo.

Pharmacokinetic interactions between FTC/TAF and drugs that affect or are metabolized by liver microsomal enzymes are unlikely.

Drugs that affect or are affected by P-glycoprotein transport

TAF is a substrate of P-glycoprotein (P-gp). Changes in tenofovir absorption may occur when co-administered with drugs that have a strong effect on P-gp.

P-gp inhibitors: May increase the absorption and plasma concentrations of tenofovir.

Inducers of P-gp: May decrease the absorption of tenofovir, resulting in reduced plasma concentrations and possible loss of therapeutic effect and development of resistance.

Drugs that affect breast cancer resistance protein

TAF is a substrate of breast cancer resistance protein (BCRP). Changes in tenofovir absorption may occur when coadministered with drugs that strongly affect BCRP.

BCRP inhibitors: May increase the absorption and plasma concentrations of tenofovir.

Drugs that affect kidney function

FTC and tenofovir are eliminated primarily by the kidneys through a combination of glomerular filtration and active tubular secretion.

Drugs that impair renal function or compete for active tubular secretion: Possible increased concentrations of FTC, TAF and/or concomitant medications; possibly increased risk of side effects.

Nephrotoxic drugs: Avoid concurrent use.

Specific medications

Pharmacokinetics of emtricitabine and tenofovir alafenamide fumarate

absorption

Bioavailability

After oral administration of the individual components of FTC/TAF, maximum plasma concentrations of FTC and tenofovir are reached after 3 hours and 1 hour, respectively.

Eat

No clinically relevant effect of food on FTC or tenofovir absorption.

Compared to fasting, administration of FTC/TAF components with a high-fat meal (approximately 800 kcal, 50% fat) decreased the peak concentration and AUC of FTC by 26 and 9%, respectively, compared to administration in the fasting state; A 15% decrease in tenofovir peak concentration and a 75% increase in tenofovir AUC were observed.

distribution

extent

FTC: Excreted in breast milk.

TAF: It is not known whether it passes into breast milk. Tenofovir passes into breast milk following administration of TDF.

Plasma protein binding

FTC: <4%.

Tenofovir alafenamide: Approximately 80%.

Elimination

metabolism

FTC: Intracellularly phosphorylated and converted by cellular enzymes to the active metabolite emtricitabine 5′-triphosphate.

Tenofovir alafenamide: prodrug of tenofovir; hydrolyzed intracellularly in peripheral blood mononuclear cells (PBMCs) and macrophages by cathepsin A to form tenofovir; subsequently metabolized to the active metabolite (tenofovir diphosphate). In vitro studies indicate that tenofovir alafenamide is also converted to tenofovir by carboxylesterase 1 (CES1) in hepatocytes. After oral administration, metabolism accounts for more than 80% of elimination; minimally metabolized via CYP3A.

Elimination route

FTC: 70% in urine, 13.7% in feces. Eliminated by glomerular filtration and active tubular secretion. Removed by hemodialysis (approximately 30% of dose over a 3-hour dialysis period beginning within 1.5 hours of FTC dosing). [blood flow rate of 400 mL/minute and dialysate flow rate of 600 mL/minute]); It is not known whether it can be removed by peritoneal dialysis.

Tenofovir alafenamide: 31.7% in feces and minimal (<1%) in urine. Tenofovir is eliminated by glomerular filtration and active tubular secretion. Efficiently removed by hemodialysis with an extraction coefficient of approximately 54%.

Half-life

FTC: 10 hours.

Tenofovir alafenamide: 0.51 hours; The half-life of the active metabolite (tenofovir diphosphate) in PBMCs is 150-180 hours.

Special populations

Pediatric patients aged ≥ 6 years and weighing ≥ 25 kg: No clinically meaningful differences in pharmacokinetics were observed.

Geriatric patients: Pharmacokinetics of FTC and TAF not fully studied in patients ≥ 65 years; However, no clinically relevant effect of age on TAF exposure was observed in patients up to 75 years of age.

Renal Impairment: Clinically significant effects on the pharmacokinetics of FTC and TAF were not observed in patients with mild or moderate renal impairment.

Severe renal impairment: FTC/TAF is not recommended in subjects with severe renal impairment (estimated Clcr 15 to <30 mL/minute) or in subjects with end-stage renal disease not receiving chronic hemodialysis. Clinically significant effects on the pharmacokinetics of FTC and TAF were not observed in patients with end-stage renal disease (Clcr <15 ml/minute) receiving chronic hemodialysis.

Hepatic Impairment: The pharmacokinetics of FTC have not been studied in patients with hepatic impairment. clinically significant changes in metabolism are not to be expected. Clinically relevant changes in tenofovir pharmacokinetics were not observed in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. The pharmacokinetics of FTC/TAF in subjects infected with hepatitis B and/or C virus have not been fully studied.

Race/Gender: No clinically significant effects on pharmacokinetics based on population pharmacokinetic analyses.

stability

storage

Orally

Tablets

25°C (excursions up to 15–30°C permitted). Store in original container; keep tightly closed.

Actions and spectrum

• antiretroviral; fixed combination of FTC (an HIV NRTI) and TAF (an HIV nucleotide reverse transcriptase inhibitor).

• FTC is inactive until it is converted intracellularly into an active 5′-triphosphate metabolite.

• TAF is inactive until it undergoes cathepsin A hydrolysis to tenofovir in vivo and is subsequently phosphorylated by cellular kinases to the active metabolite (tenofovir diphosphate).

• FTC and TAF are active against HIV-1 and HIV-2 in vitro. Also have some activity against HBV.

• Inhibit HIV replication by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).

• HIV-1 with reduced susceptibility to FTC and TAF were produced in vitro and appeared during therapy.

• HIV resistant to FTC or TAF may be cross-resistant to some other NRTIs (e.g., lamivudine, abacavir, didanosine).

Advice for patients

• It is important to advise patients to read the FDA-approved patient labeling (Medication Guide).

• Adherence to therapy for HIV-1 infection is critical and it is important to remain under the care of a doctor. importance of prescribed intake; Do not change or stop antiretroviral therapy without consulting your doctor. It is important to inform patients that missing doses can lead to the development of resistance.

• Importance of using FTC/TAF in conjunction with other antiretroviral drugs to treat HIV-1 infection - not as monotherapy.

• Advise patients receiving FTC/TAF in conjunction with other antiretrovirals for the treatment of HIV-1 infection that early initiation of antiretroviral therapy and sustained declines in plasma HIV RNA are associated with a reduced risk of acquired immunodeficiency syndrome (AIDS) progression and death. Advise patients that effective antiretroviral therapies can reduce HIV concentrations in the blood and genital secretions and that strict adherence to such therapies, coupled with risk reduction measures, can reduce, but not completely eliminate, the risk of secondary transmission of HIV to others. It is important to continue practicing safe sex (e.g., using latex or polyurethane condoms to minimize sexual contact with bodily fluids) and reduce risky behavior (e.g., reusing or sharing needles).

• Educate HIV-negative people taking FTC/TAF for HIV-1 PrEP about the importance of confirming that they are HIV-1 negative before starting PrEP and the importance of regular HIV-1 testing (at least every 3 months, or more frequently for some people). [e.g., adolescents]) while on PrEP, the importance of strictly adhering to the recommended dosing schedule and not missing doses, and the importance of using a complete prevention strategy that also includes other measures (e.g., consistent condom use, testing for other sexually transmitted infections such as syphilis, chlamydia, and gonorrhea, which may facilitate transmission of HIV-1 and reduce sexual risk behavior). Advise uninfected individuals that PrEP does not protect everyone from infection with HIV-1, and report any symptoms of acute HIV-1 infection (e.g., fever, headache, fatigue, arthralgia, vomiting, myalgia, diarrhea, pharyngitis, rash, night sweats, cervical and inguinal adenopathy) to a healthcare professional immediately. Advise patients that HIV-1 resistance substitution may occur in individuals with undetected HIV-1 infection taking FTC/TAF because FTC/TAF alone is not a complete treatment regimen for HIV-1.

• Inform patients that testing for HBV infection is recommended before initiating antiretroviral therapy. Also advise patients that severe acute exacerbations of HBV infection have been reported following discontinuation of emtricitabine and/or tenofovir disoproxil fumarate in HIV-infected patients with HBV co-infection, which may occur upon discontinuation of FTC/TAF. Advise patients with HBV not to discontinue FTC/TAF without consulting their healthcare provider.

• Inform patients that some patients with advanced HIV infection may experience signs and symptoms of inflammation due to previous infections soon after starting antiretroviral therapy. These symptoms may be due to an improvement in the immune response, allowing the body to fight infections that may have occurred without obvious symptoms. Advise patients with HIV-1 infection to notify their healthcare provider immediately if symptoms of possible infection occur.

• Advise patients that cases of renal impairment, including acute renal failure, have been reported. Advise patients to avoid FTC/TAF with concurrent or recent use of nephrotoxic agents (e.g., high-dose or multiple NSAIAs).

• Advise patients that cases of lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported associated with the use of drugs similar to FTC/TAF. If symptoms suggestive of lactic acidosis or significant hepatotoxicity (e.g., unusual muscle pain, shortness of breath or rapid breathing, cold or blue hands and feet, dizziness or lightheadedness, fast or abnormal heartbeat, nausea, vomiting, unusual/unexpected stomach discomfort, weakness or unusual tiredness) occur.

• It is important to inform the doctor about existing or planned concomitant therapies, including prescription (e.g. other antivirals) and over-the-counter medicines, as well as dietary or herbal products (e.g. St. John's wort).

• It is important for women to tell doctors if they are pregnant, plan to become pregnant, or want to breastfeed. Inform patients about the pregnancy registry. Advise HIV-infected women not to breastfeed.

• It is important to inform patients of other important precautionary information. (See Precautions.)

Preparations

Excipients in commercial drug preparations may have clinically significant effects in some individuals; Details can be found on the respective product labeling.

For information about shortages of one or more of these drugs, visit the ASHP Drug Shortages Resource Center.

Emtricitabine and tenofovir alafenamide fumarate

AHFS DI Essentials™. © Copyright 2024, Selected changes April 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-Label: Use is not currently included in U.S. Food and Drug Administration-approved labeling.

Reload page with included references

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