Version May 2024
Severe acute exacerbations of hepatitis B (HBV) have been reported in HBV-infected individuals who have discontinued products containing emtricitabine and/or tenofovir disoproxil fumarate, and may occur with discontinuation of emtricitabine/tenofovir alafenamide. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in individuals who are infected with HBV and discontinue emtricitabine/tenofovir alafenamide. If appropriate, anti-HBV therapy may be warranted.
Emtricitabine/tenofovir alafenamide used for HIV-1 preexposure prophylaxis (PrEP) must only be prescribed to individuals confirmed to be HIV-negative immediately prior to initiating and at least every 3 months during use. Drug-resistant HIV-1 variants have been identified with the use of emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP following undetected acute HIV-1 infection. Do not initiate emtricitabine/tenofovir alafenamide for HIV-1 PrEP if signs or symptoms of acute HIV-1 infection are present unless negative infection status is confirmed.
HIV-1/hepatitis B co-infection, treatment (off-label use): Oral: One tablet (emtricitabine 200 mg/tenofovir alafenamide 25 mg) once daily in combination with other antiretroviral agents (Ref).
HIV-1 infection, treatment: Oral: One tablet (emtricitabine 200 mg/tenofovir alafenamide 25 mg) once daily, in combination with other antiretroviral agents.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Dose adjustments for altered kidney function prior to treatment initiation :
Note: Kidney function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes. Although the manufacturer’s labeling of individual agent emtricitabine suggests adjustments to the dosing interval when CrCl <50 mL/minute, clinical and pharmacokinetic studies suggest that it can be used at usual recommended doses/intervals when CrCl ≥30 mL/minute and in patients receiving hemodialysis; monitor for GI (eg, nausea) and CNS-related adverse effects (Ref).
Altered kidney function: Oral:
CrCl ≥30 mL/minute: No dosage adjustment necessary (Ref).
CrCl <30 mL/minute: Use is not recommended (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
Oral: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Emtricitabine (~30% removed over 3 hours); tenofovir alafenamide (no data on % removed):
Oral: No dosage adjustment necessary. When a scheduled dose falls on a hemodialysis day, administer after hemodialysis (Ref).
Peritoneal dialysis: Oral: Use not recommended (has not been studied) (Ref).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations. Close monitoring of response and adverse reactions due to drug accumulation is important.
Oral: There are no data available in patients on CRRT (has not been studied). Although some removal of emtricitabine and tenofovir are expected based on physicochemical characteristics, no dosage adjustment is likely to be necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations. Close monitoring of response and adverse reactions due to drug accumulation is important.
Oral: There are no data available in patients on PIRRT (has not been studied). Although some removal of emtricitabine and tenofovir are expected based on physicochemical characteristics, no dosage adjustment is likely to be necessary. When a scheduled dose falls on a PIRRT day, administer after PIRRT session (Ref).
Nephrotoxicity during treatment:
Tenofovir alafenamide has been associated with acute kidney injury, proximal tubular nephropathy, and Fanconi syndrome. Although kidney injury is less common with tenofovir alafenamide than tenofovir disoproxil fumarate, discontinue use in patients who develop clinically significant decreases in kidney function or evidence of Fanconi syndrome (Ref).
Mild-to-moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
(For additional information see "Tenofovir alafenamide and emtricitabine: Pediatric drug information")
Note: Multiple tablet strengths are available and contain different amounts of each component; use caution.
HIV-1 infection, treatment: Note: In patients weighing <35 kg, efficacy has not been established for coadministration with an HIV protease inhibitor administered with either ritonavir or cobicistat. Gene mutation and antiretroviral resistance patterns should be evaluated (refer to https://www.iasusa.org for more information) when necessary.
Children weighing 14 to <25 kg: Oral: Emtricitabine 120 mg and tenofovir alafenamide 15 mg per tablet: One tablet once daily.
Children and Adolescents weighing ≥25 kg: Oral: Emtricitabine 200 mg and tenofovir alafenamide 25 mg per tablet: One tablet once daily.
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 (Ref).
Adolescents weighing ≥35 kg: Oral: Emtricitabine 200 mg and tenofovir alafenamide 25 mg per tablet: One tablet once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children and Adolescents weighing ≥14 kg:
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: Use is not recommended.
Children and Adolescents weighing ≥14 kg:
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: There are no dosage recommendations in the manufacturer's labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for HIV-1 preexposure prophylaxis in adults. Also see individual agents.
1% to 10%:
Gastrointestinal: Abdominal pain (2%), diarrhea (5%), nausea (4%)
Nervous system: Fatigue (2%), headache (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:
Dermatologic: Skin rash, urticaria
Endocrine & metabolic: Fanconi’s syndrome
Genitourinary: Proximal tubular nephropathy
Hypersensitivity: Angioedema
Renal: Acute kidney injury, renal tubular necrosis
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.
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: Renal toxicity (acute renal failure, Fanconi syndrome, and/or proximal renal tubulopathy) has been reported with use of tenofovir prodrugs; patients with impaired renal function and those with concurrent or recent nephrotoxic therapy (including nonsteroidal anti-inflammatory drug use) are at an increased risk. Discontinue use in patients who 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.
Emtricitabine-associated hyperpigmentation may occur at a higher frequency in pediatric patients compared to adults (children: 32%; adults: 2% to 6%).
Through disruption in vitamin D metabolism, decreases in bone mineral density (BMD) have been observed with tenofovir alafenamide (TAF) after 48 weeks of treatment; however, the incidence and negative impact on BMD is less than that observed with tenofovir disoproxil fumarate (TDF). Additionally, TAF is associated with less renal toxicity than TDF but equal antiviral efficacy. A higher incidence of dyslipidemia has been reported with TAF than TDF. TAF is preferred over TDF whenever possible; do not use TAF and TDF concomitantly (HHS [pediatric] 2019).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Descovy: Emtricitabine 120 mg and tenofovir alafenamide 15 mg
Descovy: Emtricitabine 200 mg and tenofovir alafenamide 25 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
No
Tablets (Descovy Oral)
120-15 mg (per each): $88.09
200-25 mg (per each): $88.09
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Descovy: Emtricitabine 200 mg and tenofovir alafenamide 10 mg
Descovy: Emtricitabine 200 mg and tenofovir alafenamide 25 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Oral: Administer with or without food.
Oral: Administer with or without food.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Descovy: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208215s019lbl.pdf#page=37
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 ≥14 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.
HIV-1/hepatitis B co-infection, treatment
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acyclovir-Valacyclovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Risk C: 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. Risk X: Avoid combination
Aminoglycosides: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Risk C: Monitor therapy
Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination
Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
CarBAMazepine: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Cidofovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Cidofovir. Risk C: Monitor therapy
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Cobicistat: May increase the serum concentration of Tenofovir Alafenamide. Risk C: Monitor therapy
Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid combination
Fosphenytoin-Phenytoin: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Ganciclovir-Valganciclovir: Tenofovir Products may increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Tenofovir Products. Risk C: Monitor therapy
Lovotibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
Lumacaftor and Ivacaftor: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may decrease the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: May increase the serum concentration of Tenofovir Alafenamide. Risk C: Monitor therapy
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 due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the nephrotoxic effect of Tenofovir Products. Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
OXcarbazepine: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Tenofovir Alafenamide. Management: Consider alternatives to the use of P-gp inducers with tenofovir alafenamide. If combined, monitor for reduced tenofovir alafenamide concentrations and efficacy, and for the development of resistance. Risk D: Consider therapy modification
PHENobarbital: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Primidone: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Rifabutin: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
RifAMPin: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Rifapentine: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Ritonavir: May increase the serum concentration of Tenofovir Alafenamide. Risk C: Monitor therapy
St John's Wort: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Tacrolimus (Systemic): Tenofovir Products may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Tipranavir: May decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
The Health and Human Services (HHS) perinatal HIV guidelines consider emtricitabine and tenofovir alafenamide preferred agents for use in patients with HIV who are not yet pregnant but are trying to conceive (HHS [perinatal] 2023).
Refer to individual monographs for additional information.
The Health and Human Services (HHS) perinatal HIV guidelines consider this combination to be a preferred nucleoside reverse transcriptase inhibitor backbone for initial therapy in antiretroviral-naive pregnant patients. In addition, this combination is preferred for use in pregnant patients with HIV who have had antiretroviral therapy (ART) in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). Patients who become pregnant while taking this combination may continue if viral suppression is effective and the regimen is well tolerated.
Emtricitabine and tenofovir alafenamide are recommended as part of a preferred regimen when early (acute/recent) HIV infection is detected during pregnancy; genotyping may be required if the person had prior use of long acting cabotegravir for pre-exposure prophylaxis (PrEP).
The HHS perinatal guidelines also recommend emtricitabine plus tenofovir alafenamide as a component of regimens for HIV/hepatitis B virus–coinfected patients who are pregnant (HHS [perinatal] 2023).
Refer to individual monographs for additional information.
Emtricitabine and tenofovir alafenamide are present in breast milk (HHS [perinatal] 2023).
Refer to individual monographs for additional information.
CD4 count, HIV RNA plasma levels; serum creatinine, estimated CrCl, 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 2021): Documented negative HIV test (≤1 week before initiating or reinitiating PrEP, at least every 3 months while taking PrEP, and following discontinuation of PrEP); assess symptoms of side effects and acute HIV infection (every 3 months); testing for HBV (prior to initiation); lipid panel (prior to initiation, then every 12 months).
Nucleoside and nucleotide reverse transcriptase inhibitor combination; emtricitabine is a cytidine 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.
Protein binding: Emtricitabine: <4%; TAF: ~80%
Metabolism: Emtricitabine: Not significantly metabolized; TAF: Primarily intracellular metabolism; minimal extent by CYP3A
Half-life elimination: Emtricitabine: 10 hours; TAF: 0.51 hours
Time to peak, plasma: Emtricitabine: 3 hours; TAF: 1 hour
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
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