Emtricitabine and Tenofovir Alafenamide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Descovy: Emtricitabine 200 mg and tenofovir alafenamide 25 mg [contains fd&c blue #2 aluminum lake]

Pharmacology

Mechanism of Action

Nucleoside and nucleotide reverse transcriptase inhibitor combination; emtricitabine is a cytosine analogue while tenofovir alafenamide fumarate (TAF) is an analog of adenosine 5'-monophosphate. Each drug interferes with HIV viral RNA dependent DNA polymerase activities resulting in inhibition of viral replication.

Pharmacokinetics/Pharmacodynamics

Metabolism

Emtricitabine: Not significantly metabolized; TAF: Primarily intracellular metabolism; minimal extent by CYP3A

Excretion

Emtricitabine: Urine (70%); feces (13.7%); TAF: Urine (<1%), feces 31.7%)

Clearance: Emtricitabine and tenofovir may be eliminated by both glomerular filtration and active tubular secretion

Half-Life Elimination

Emtricitabine: 10 hours; TAF: 0.51 hours

Protein Binding

Emtricitabine: <4%; TAF: ~80%

Use: Labeled Indications

HIV-1 infection, treatment: Treatment of HIV-1 infection in combination with other antiretroviral agents in adults and pediatric patients weighing ≥35 kg; in combination with other antiretroviral agents (other than protease inhibitors that require a CYP3A inhibitor) in pediatric patients weighing ≥25 kg and <35 kg.

HIV-1 infection, preexposure prophylaxis: Preexposure prophylaxis to reduce the risk of sexually acquired HIV-1 infection in at-risk adults and adolescents weighing ≥35 kg.

Limitations of use: Not indicated for individuals at risk from receptive vaginal sex.

Contraindications

As preexposure prophylaxis in patients with unknown or HIV-1 positive status.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to emtricitabine, tenofovir alafenamide, or any component of the formulation.

Dosage and Administration

Dosing: Adult

HIV-1 infection, treatment: Oral: One tablet (emtricitabine 200 mg/tenofovir alafenamide 25 mg) once daily, in combination with other antiretroviral agents.

HIV-1 infection, preexposure prophylaxis: Oral: One tablet (emtricitabine 200 mg/tenofovir alafenamide 25 mg) once daily.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Product is a fixed-dose combination; use not recommended in other weight groups.

HIV-1 infection, treatment: Note: Gene mutation and antiretroviral resistance patterns should be evaluated (refer to https://www.iasusa.org for more information) when necessary.

Children and Adolescents weighing ≥25 kg: Oral: Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg per tablet): One tablet once daily; in clinical trials, the youngest patients were 6 years of age; Note: In patients weighing <35 kg, efficacy has not been established for coadministration with an HIV protease inhibitor administered with either ritonavir or cobicistat.

HIV-1 infection, preexposure prophylaxis (PrEP) in uninfected high-risk individuals: Note: Patients should be confirmed HIV-negative immediately prior to initiation of therapy and screened again at least once every 3 months and upon diagnosis of any other sexually transmitted infections; adherence should also be closely monitored (CDC 2018; USPSTF 2019).

Adolescents weighing ≥35 kg: Oral: Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg per tablet): One tablet once daily.

Administration

Oral: Administer with or without food.

Storage

Store below 30°C (86°F). Dispense in original container.

Drug Interactions

Acyclovir-Valacyclovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Monitor therapy

Adefovir: May diminish the therapeutic effect of Tenofovir Products. Adefovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Adefovir. Avoid combination

Aminoglycosides: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Monitor therapy

Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Cidofovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Cidofovir. Monitor therapy

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Avoid combination

Cobicistat: May enhance the adverse/toxic effect of Tenofovir Products. More specifically, cobicistat may impair proper tenofovir monitoring and dosing. Monitor therapy

Diclofenac (Systemic): May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to this combination whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification

Fosphenytoin-Phenytoin: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Ganciclovir-Valganciclovir: Tenofovir Products may increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Tenofovir Products. Monitor therapy

LamiVUDine: May enhance the adverse/toxic effect of Emtricitabine. Avoid combination

Nonsteroidal Anti-Inflammatory Agents: May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy

OXcarbazepine: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

PHENobarbital: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Primidone: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Rifabutin: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

RifAMPin: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Rifapentine: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Sofosbuvir: May increase the serum concentration of Tenofovir Alafenamide. Monitor therapy

St John's Wort: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Tipranavir: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Adverse Reactions

Also see individual agents.

1% to 10%:

Central nervous system: Headache (2%)

Gastrointestinal: Diarrhea (5%), nausea (4%), abdominal pain (2%), fatigue (2%)

Neuromuscular & skeletal: Decreased bone mineral density (≥5% decrease at lumbar spine: 4%; ≥7% decrease at femoral neck: 1%)

Frequency not defined:

Endocrine & metabolic: Increased serum triglycerides

Hepatic: Exacerbation of hepatitis B

Postmarketing: Angioedema, skin rash, urticaria

Warnings/Precautions

Concerns related to adverse effects:

• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) later in therapy; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal, have been reported with use of nucleoside analogues, alone or in combination with other antiretrovirals. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (marked transaminase elevation may/may not accompany hepatomegaly and steatosis).
• Renal toxicity: Cases of acute renal failure and/or Fanconi syndrome have been reported with use of tenofovir prodrugs; patients with preexisting renal impairment and those taking nephrotoxic agents (including nonsteroidal anti-inflammatory drugs) are at increased risk. Assess serum creatinine, estimated CrCl, urine protein, and urine glucose prior to or when initiating therapy and during therapy. Monitor serum phosphorus in patients with chronic kidney disease. Discontinue therapy in patients that develop clinically significant decreases in renal function or evidence of Fanconi syndrome.

Disease-related concerns:

• Chronic hepatitis B: [US Boxed Warning]: Acute, severe exacerbations of hepatitis B virus (HBV) have been reported in HBV-infected patients following discontinuation of antiretroviral therapy. Closely monitor hepatic function with clinical and laboratory follow-up for at least several months in patients infected with HBV who discontinue this therapy. If appropriate, anti-HBV therapy may be warranted, especially in patients with advanced hepatic disease or cirrhosis (post-treatment HBV exacerbations may lead to hepatic decompensation and liver failure). All patients with HIV should be tested for HBV prior to or when initiating treatment; HBV-uninfected patients should be offered vaccination.
• Comprehensive prevention program: Preexposure prophylaxis (PrEP) should be accompanied by a comprehensive HIV-1 prevention program (eg, risk reduction counseling, consistent and correct condom use, regular sexually transmitted infection testing), with particular emphasis on medication adherence.
• Renal impairment: Use is not recommended in patients with CrCl <30 mL/minute (unless receiving hemodialysis). Safety and efficacy of concurrent administration with an HIV-1 protease inhibitor plus ritonavir or cobicistat has not been established in patients with CrCl <15 mL/minute (with or without hemodialysis).
• Resistance risk with preexposure prophylaxis: [US Boxed Warning]: Confirm HIV-1 negative status immediately before and at least every 3 months during therapy, and upon diagnosis of any other sexually transmitted infection. Do not start PrEP if signs or symptoms of acute HIV-1 infection are present unless HIV-1 negative status is confirmed by a test approved by the Food and Drug Administration (FDA) as an aid to detect HIV-1 infection (including acute or primary infection). Risk of drug resistant HIV-1 variants with PrEP use if patient had undetected acute HIV-1 infection: Some HIV-1 tests do not detect acute HIV-1 infection. Screen PrEP candidates for signs/symptoms of acute HIV-1 infection and potential exposure events within 1 month of starting PrEP. If signs/symptoms or potential exposure events exist, use a test approved by the FDA for diagnosing acute or primary HIV-1 infection before initiating PrEP. During use of PrEP, if a screening test indicates possible HIV-1 infection or if symptoms of acute HIV-1 infection develop after a potential exposure, convert the HIV-1 PrEP regimen to an HIV-1 treatment regimen until negative infection status is confirmed.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

CD4 count, HIV RNA plasma levels; serum creatinine, urine glucose, urine protein (prior to or when initiating therapy and as clinically indicated during therapy); serum phosphorus (in patients with chronic kidney disease); hepatic function tests; testing for hepatitis B virus (HBV) is recommended prior to or when initiating antiretroviral therapy. Patients with HIV and HBV coinfection should be monitored for several months following therapy discontinuation.

HIV-1 preexposure prophylaxis (CDC 2011; CDC 2013): Pregnancy test for women receiving preexposure prophylaxis (PrEP) (every visit); documented negative HIV test (immediately prior to use, every 2 to 3 months, and following discontinuation of PrEP); assess risk behaviors and symptoms of sexually-transmitted infections (STIs) or acute HIV-1 infection and provide condoms (immediately prior to use, then every 2 to 3 months during therapy); BUN and serum creatinine (prior to initiation, 3 months after initiation, then every 6 months); urine glucose and urine protein (in patients at risk for renal impairment); serum phosphorus in patients with chronic kidney disease, testing for HBV (prior to initiation) and STIs (prior to initiation, then at least every 6 months, even if asymptomatic).

Pregnancy

Pregnancy Considerations

The Health and Human Services perinatal HIV guidelines note there are insufficient data to recommend use of this fixed dose combination product as an initial regimen in antiretroviral-naive pregnant females.

In general, females who become pregnant on a stable antiretroviral therapy (ART) regimen may continue that regimen if viral suppression is effective, appropriate drug exposure can be achieved, contraindications for use in pregnancy are not present, and the regimen is well tolerated (HHS [perinatal] 2019).

Refer to individual monographs for additional information.

Patient Education

What is this drug used for?

• It is used to treat HIV infection.

Frequently reported side effects of this drug

• Nausea
• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection
• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin
• Lactic acidosis like fast breathing, fast heartbeat, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, or severe dizziness, feeling cold, or muscle pain or cramps
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.