Descovy 200 MG / 25 MG Oral Tablet
DRUG INTERACTIONS
7 Consult the Full Prescribing Information prior to and during treatment for potential drug interactions.
(7, 12.3) 7.1 Potential for Other Drugs to Affect One or More Components of DESCOVY TAF, a component of DESCOVY, is a substrate of P-gp, BCRP, OATP1B1, and OATP1B3.
Drugs that strongly affect P-gp and BCRP activity may lead to changes in TAF absorption (see Table 2).
Drugs that induce P-gp activity are expected to decrease the absorption of TAF, resulting in decreased plasma concentration of TAF, which may lead to loss of therapeutic effect of DESCOVY and development of resistance.
Coadministration of DESCOVY with other drugs that inhibit P-gp and BCRP may increase the absorption and plasma concentration of TAF.
TAF is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or UGT1A1.
TAF is a weak inhibitor of CYP3A in vitro.
TAF is not an inhibitor or inducer of CYP3A in vivo.
7.2 Drugs Affecting Renal Function Because FTC and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of DESCOVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC, tenofovir, and other renally eliminated drugs and this may increase the risk of adverse reactions.
Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.3)].
7.3 Established and Other Potentially Significant Interactions Table 2 provides a listing of established or potentially clinically significant drug interactions with recommended steps to prevent or manage the drug interaction (the table is not all inclusive).
The drug interactions described are based on studies conducted with either DESCOVY, the components of DESCOVY (emtricitabine and tenofovir alafenamide) as individual agents, or are predicted drug interactions that may occur with DESCOVY.
For magnitude of interaction, see Clinical Pharmacology (12.3) .
Table 2 Established and Other Potentially SignificantThis table is not all inclusive.
Drug Interactions Concomitant Drug Class: Drug Name Effect on Concentration↓=Decrease Clinical Comment Antiretroviral Agents: Protease Inhibitors (PI) tipranavir/ritonavir ↓ TAF Coadministration with DESCOVY is not recommended.
Other Agents Anticonvulsants: carbamazepine oxcarbazepine phenobarbital phenytoin ↓ TAF Consider alternative anticonvulsant.
Antimycobacterials: rifabutin rifampin rifapentine ↓ TAF Coadministration of DESCOVY with rifabutin, rifampin, or rifapentine is not recommended.
Herbal Products: St.
John’s wort (Hypericum perforatum) ↓ TAF Coadministration of DESCOVY with St.
John’s wort is not recommended.
7.4 Drugs without Clinically Significant Interactions with DESCOVY Based on drug interaction studies conducted with the components of DESCOVY, no clinically significant drug interactions have been either observed or are expected when DESCOVY is combined with the following antiretroviral agents: atazanavir with ritonavir or cobicistat, darunavir with ritonavir or cobicistat, dolutegravir, efavirenz, ledipasvir, lopinavir/ritonavir, maraviroc, nevirapine, raltegravir, rilpivirine, and sofosbuvir.
No clinically significant drug interactions have been either observed or are expected when DESCOVY is combined with the following drugs: buprenorphine, itraconazole, ketoconazole, lorazepam, methadone, midazolam, naloxone, norbuprenorphine, norgestimate/ethinyl estradiol, and sertraline.
OVERDOSAGE
10 No data are available on overdose of DESCOVY in patients.
If overdose occurs, monitor the patient for evidence of toxicity.
Treatment of overdose with DESCOVY consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient.
Emtricitabine (FTC): Limited clinical experience is available at doses higher than the recommended dose of FTC in DESCOVY.
In one clinical pharmacology study, single doses of FTC 1200 mg (6 times the FTC dose in DESCOVY) were administered to 11 subjects.
No severe adverse reactions were reported.
The effects of higher doses are not known.
Hemodialysis treatment removes approximately 30% of the FTC dose over a 3-hour dialysis period starting within 1.5 hours of FTC dosing (blood flow rate of 400 mL per minute and a dialysate flow rate of 600 mL per minute).
It is not known whether FTC can be removed by peritoneal dialysis.
Tenofovir alafenamide (TAF): Limited clinical experience is available at doses higher than the recommended dose of TAF.
A single dose of 125 mg TAF (5 times the TAF dose in 200/25 mg DESCOVY) was administered to 48 healthy subjects; no serious adverse reactions were reported.
The effects of higher doses are unknown.
Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%.
DESCRIPTION
11 DESCOVY (emtricitabine and tenofovir alafenamide) is a fixed dose combination tablet containing emtricitabine (FTC) and tenofovir alafenamide (TAF) for oral administration.
FTC, a synthetic nucleoside analog of cytidine, is an HIV nucleoside analog reverse transcriptase inhibitor (HIV NRTI).
TAF, an HIV NRTI, is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5′-monophosphate.
Each 200/25 mg tablet contains 200 mg of FTC and 25 mg of TAF (equivalent to 28 mg of tenofovir alafenamide fumarate) and the following inactive ingredients: croscarmellose sodium, magnesium stearate, and microcrystalline cellulose.
The tablets are film-coated with a coating material containing indigo carmine aluminum lake, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.
Emtricitabine: The chemical name of FTC is 4-amino-5-fluoro-1-(2R-hydroxymethyl-1,3-oxathiolan-5S-yl)-(1H)-pyrimidin-2-one.
FTC is the (-)enantiomer of a thio analog of cytidine, which differs from other cytidine analogs in that it has a fluorine in the 5 position.
FTC has a molecular formula of C8H10FN3O3S and a molecular weight of 247.24 and has the following structural formula: FTC is a white to off-white powder with a solubility of approximately 112 mg per mL in water at 25 °C.
Tenofovir alafenamide: The chemical name of tenofovir alafenamide fumarate drug substance is L-alanine, N-[(S)-[[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphinyl]-, 1-methylethyl ester, (2E)-2-butenedioate (2:1).
Tenofovir alafenamide fumarate has an empirical formula of C21H29O5N6P∙½(C4H4O4) and a formula weight of 534.50 and has the following structural formula: Tenofovir alafenamide fumarate is a white to off-white or tan powder with a solubility of 4.7 mg per mL in water at 20 °C.
Chemical Structure Chemical Structure
CLINICAL STUDIES
14 In trials of FTC+TAF with EVG+COBI in HIV-1 infected adults as initial therapy in those with no antiretroviral treatment history (N=866) and to replace a stable antiretroviral regimen in those who were virologically-suppressed for at least 6 months with no known resistance substitutions (N=799), 92% and 96% of patients in the two populations, respectively, had HIV-1 RNA less than 50 copies per mL at Week 48.
An open-label, single arm trial of FTC+TAF with EVG+COBI enrolled 50 treatment-naïve HIV-1 infected adolescents aged 12 to less than 18 years weighing at least 35 kg (cohort 1) and 23 virologically suppressed children aged 6 to less than 12 years weighing at least 25 kg (cohort 2).
In cohort 1, the virologic response rate (i.e., HIV-1 RNA less than 50 copies per mL) was 92% (46/50) and the mean increase from baseline in CD4+ cell count was 224 cells per mm3 at Week 48.
In cohort 2, 100% of subjects remained virologically suppressed at Week 24.
From a mean (SD) baseline CD4+ cell count of 966 (201.7), the mean change from baseline in CD4+ cell count was -150 cells/mm3 and the mean (SD) change in CD4% was -1.5% (3.7%) at Week 24.
All subjects maintained CD4+ cell counts above 400 cells/mm3 [see Adverse Reactions (6.1) and Use in Specific Populations (8.4)].
In a trial in 248 HIV-1 infected adult patients with estimated creatinine clearance greater than 30 mL per minute but less than 70 mL per minute, 95% (235/248) of the combined population of treatment-naïve subjects (N=6) began on FTC+TAF with EVG+COBI and those previously virologically-suppressed on other regimens (N=242) and switched to FTC+TAF with EVG+COBI had HIV-1 RNA less than 50 copies per mL at Week 24.
HOW SUPPLIED
16 /STORAGE AND HANDLING DESCOVY 200 mg/25 mg tablets are blue, rectangular-shaped, and film-coated with “GSI” debossed on one side and “225” on the other side.
Each bottle contains 30 tablets (NDC 61958-2002-1), a silica gel desiccant, polyester coil, and is closed with a child-resistant closure.
Store below 30 °C (86 °F).
Keep container tightly closed.
Dispense only in original container.
RECENT MAJOR CHANGES
Indications and Usage (1) 09/2017 Dosage and Administration, Recommended Dosage (2.2) 09/2017 Warnings and Precautions, Bone Loss and Mineralization Defects [removed] 09/2017 Boxed Warning, Lactic Acidosis/Severe Hepatomegaly with Steatosis [removed] 04/2017 Warnings and Precautions, Lactic Acidosis/Severe Hepatomegaly with Steatosis (5.4) 04/2017 Warnings and Precautions, Fat Redistribution [removed] 04/2017
GERIATRIC USE
8.5 Geriatric Use In clinical trials, 80 of the 97 subjects enrolled aged 65 years and over received FTC+TAF and EVG+COBI.
No differences in safety or efficacy have been observed between elderly subjects and adults between 18 and less than 65 years of age.
DOSAGE FORMS AND STRENGTHS
3 Each DESCOVY tablet contains 200 mg of emtricitabine (FTC) and 25 mg of tenofovir alafenamide (TAF) (equivalent to 28 mg of tenofovir alafenamide fumarate).
The tablets are blue, rectangular-shaped, film-coated, debossed with “GSI” on one side and “225” on the other side.
Tablets: 200 mg of FTC and 25 mg of TAF (3)
MECHANISM OF ACTION
12.1 Mechanism of Action DESCOVY is a fixed dose combination of antiretroviral drugs emtricitabine (FTC) and tenofovir alafenamide (TAF) [see Microbiology (12.4)].
INDICATIONS AND USAGE
1 DESCOVY is indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg.
DESCOVY is also indicated, in combination with other antiretroviral agents other than protease inhibitors that require a CYP3A inhibitor, for the treatment of HIV-1 infection in pediatric patients weighing at least 25 kg and less than 35 kg.
DESCOVY is a two-drug combination of emtricitabine (FTC) and tenofovir alafenamide (TAF), both HIV nucleoside analog reverse transcriptase inhibitors (NRTIs), and is indicated: in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35kg.
in combination with other antiretroviral agents other than protease inhibitors that require a CYP3A inhibitor for the treatment of HIV-1 infection in pediatric patients weighing at least 25 kg and less than 35 kg.
(1) Limitations of Use: DESCOVY is not indicated for use as pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults at high risk.
Limitations of Use: DESCOVY is not indicated for use as pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults at high risk.
PEDIATRIC USE
8.4 Pediatric Use The safety and effectiveness of DESCOVY, in combination with other antiretroviral agents, for the treatment of HIV-1 infection was established in pediatric patients with body weight greater than or equal to 25 kg [see Indication and Usage (1) and Dosage and Administration (2.2)].
Use of DESCOVY in pediatric patients between the ages of 12 to less than 18 years weighing at least 35 kg is supported by adequate and well controlled studies of FTC+TAF with EVG+COBI in adults and by an open-label trial in antiretroviral treatment-naïve HIV-1 infected pediatric subjects ages 12 to less than 18 years and weighing at least 35 kg (N=50; cohort 1).
The safety and efficacy of FTC+TAF with EVG+COBI in these pediatric subjects was similar to that of HIV-1 infected adults on this regimen [see Clinical Pharmacology (12.3) and Clinical Studies (14)].
Use of DESCOVY in pediatric patients weighing at least 25 kg is supported by adequate and well controlled studies of FTC+TAF with EVG+COBI in adults and by an open-label trial in virologically-suppressed pediatric subjects between the ages of 6 to less than 12 years weighing at least 25 kg, in which subjects were switched from their antiretroviral regimen to FTC+TAF with EVG+COBI (N=23; cohort 2).
The safety in these subjects through 24 weeks of FTC+TAF with EVG+COBI was similar to that of HIV-1 infected adults on this regimen, with the exception of a decrease in mean change from baseline in CD4+ cell count [see Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14)].
Safety and effectiveness of DESCOVY coadminstered with an HIV-1 protease inhibitor that is administered with either ritonavir or cobicistat have not been established in pediatric subjects weighing less than 35 kg [see Dosage and Administration (2.2)].
Safety and effectiveness of DESCOVY in pediatric patients less than 25 kg have not been established.
PREGNANCY
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to DESCOVY during pregnancy.
Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.
Risk Summary There are insufficient human data on the use of DESCOVY during pregnancy to inform a drug-associated risk of birth defects and miscarriage.
Tenofovir alafenamide (TAF) use in women during pregnancy has not been evaluated; however, emtricitabine (FTC) use during pregnancy has been evaluated in a limited number of women reported to the APR.
Available data from the APR show no difference in the risk of overall major birth defects for FTC (2.4%) compared with the background rate for major birth defects of 2.7% in a U.S.
reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP).
The rate of miscarriage is not reported in the APR.
The estimated background rate of miscarriage in the clinically recognized pregnancies in the U.S.
general population is 15−20%.
In animal studies, no adverse developmental effects were observed when the components of DESCOVY were administered separately during the period of organogenesis at exposures 60 and 108 times (mice and rabbits, respectively) the FTC exposure and at exposure equal to or 53 times (rats and rabbits, respectively) the TAF exposure at the recommended daily dose of DESCOVY [see Data (8.1)].
Likewise, no adverse developmental effects were seen when FTC was administered to mice through lactation at exposures up to approximately 60 times the exposure at the recommended daily dose of DESCOVY.
No adverse effects were observed in the offspring when TDF was administered through lactation at tenofovir exposures of approximately 14 times the exposure at the recommended daily dosage of DESCOVY.
Data Human Data Emtricitabine: Based on prospective reports to the APR through July 2015 of 2933 exposures to FTC-containing regimens during pregnancy (including 1984 exposed in the first trimester and 949 exposed in the second/third trimester), there was no difference between FTC and overall birth defects compared with the background birth defect rate of 2.7% in the U.S.
reference population of the MACDP.
The prevalence of birth defects in live births was 2.4% (95% CI: 1.7% to 3.1%) with first trimester exposure to FTC-containing regimens and 2.1% (95% CI: 1.3% to 3.2%) with the second/third trimester exposure to FTC-containing regimens.
Animal Data Emtricitabine: FTC was administered orally to pregnant mice (250, 500, or 1000 mg/kg/day) and rabbits (100, 300, or 1000 mg/kg/day) through organogenesis (on gestation days 6 through 15, and 7 through 19, respectively).
No significant toxicological effects were observed in embryo-fetal toxicity studies performed with FTC in mice at exposures (area under the curve [AUC]) approximately 60 times higher and in rabbits at approximately 108 times higher than human exposures at the recommended daily dose.
In a pre/postnatal development study with FTC, mice were administered doses up to 1000 mg/kg/day; no significant adverse effects directly related to drug were observed in the offspring exposed daily from before birth (in utero) through sexual maturity at daily exposures (AUC) of approximately 60-fold higher than human exposures at the recommended daily dose.
Tenofovir Alafenamide: TAF was administered orally to pregnant rats (25, 100, or 250 mg/kg/day) and rabbits (10, 30, or 100 mg/kg/day) through organogenesis (on gestation days 6 through 17, and 7 through 20, respectively).
No adverse embryo-fetal effects were observed in rats and rabbits at TAF exposures approximately similar to (rats) and 53 (rabbits) times higher than the exposure in humans at the recommended daily dose of DESCOVY.
TAF is rapidly converted to tenofovir; the observed tenofovir exposures in rats and rabbits were 59 (rats) and 93 (rabbits) times higher than human tenofovir exposures at the recommended daily dose.
Since TAF is rapidly converted to tenofovir and a lower tenofovir exposure in rats and mice was observed after TAF administration compared to tenofovir disoproxil fumarate (TDF, another prodrug for tenofovir) administration, a pre/postnatal development study in rats was conducted only with TDF.
Doses up to 600 mg/kg/day were administered through lactation; no adverse effects were observed in the offspring on gestation day 7 [and lactation day 20] at tenofovir exposures of approximately 14 [21] times higher than the exposures in humans at the recommended daily dose of DESCOVY.
BOXED WARNING
WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B DESCOVY is not approved for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy of DESCOVY have not been established in patients coinfected with human immunodeficiency virus-1 (HIV-1) and HBV.
Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of DESCOVY.
Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue DESCOVY.
If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.1)].
WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B See full prescribing information for complete boxed warning.
DESCOVY is not approved for the treatment of chronic hepatitis B virus (HBV) infection.
Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of DESCOVY.
Hepatic function should be monitored closely in these patients.
If appropriate, initiation of anti-hepatitis B therapy may be warranted.
(5.1)
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS Immune reconstitution syndrome: May necessitate further evaluation and treatment.(5.2) New onset or worsening renal impairment: Assess creatinine clearance, urine glucose, and urine protein in all patients before initiating DESCOVY therapy and monitor during therapy.
Monitor serum phosphorus in patients with chronic kidney disease.
(5.3) Lactic acidosis/severe hepatomegaly with steatosis: Discontinue treatment in patients who develop symptoms or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.
(5.4) 5.1 Severe Acute Exacerbation of Hepatitis B in Patients Coinfected with HIV-1 and HBV Patients with HIV-1 should be tested for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy [see Dosage and Administration (2.1)].
DESCOVY is not approved for the treatment of chronic HBV infection, and the safety and efficacy of DESCOVY have not been established in patients coinfected with HIV-1 and HBV.
Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing FTC and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of DESCOVY.
Patients coinfected with HIV-1 and HBV who discontinue DESCOVY should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.
If appropriate, initiation of anti-hepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since post-treatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.
5.2 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including FTC, a component of DESCOVY.
During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis], which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.
5.3 New Onset or Worsening Renal Impairment Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir prodrugs in both animal toxicology studies and human trials.
In clinical trials of FTC+TAF with cobicistat (COBI) plus elvitegravir (EVG), there have been no cases of Fanconi syndrome or Proximal Renal Tubulopathy (PRT).
In clinical trials of FTC+TAF with EVG+COBI in treatment-naïve subjects and in virally suppressed subjects switched to FTC+TAF with EVG+COBI with eGFRs greater than 50 mL per minute, renal serious adverse events or discontinuations due to renal adverse reactions were encountered in less than 1% of participants treated with FTC+TAF with EVG+COBI.
In a study of virally suppressed subjects with baseline eGFRs between 30 and 69 mL per minute treated with FTC+TAF with EVG+COBI for a median duration of 43 weeks, FTC+TAF with EVG+COBI was permanently discontinued due to worsening renal function in two of 80 (3%) subjects with a baseline eGFR between 30 and 50 mL per minute [see Adverse Reactions (6.1)].
DESCOVY is not recommended in patients with estimated creatinine clearance below 30 mL per minute because data in this population are insufficient.
Patients taking tenofovir prodrugs who have impaired renal function and those taking nephrotoxic agents including non-steroidal anti-inflammatory drugs are at increased risk of developing renal-related adverse reactions.
Estimated creatinine clearance, urine glucose, and urine protein should be assessed before initiating DESCOVY therapy and should be monitored during therapy in all patients.
Serum phosphorus should be monitored in patients with chronic kidney disease because these patients are at greater risk of developing Fanconi syndrome on tenofovir prodrugs.
Discontinue DESCOVY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
5.4 Lactic Acidosis/Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including emtricitabine, a component of DESCOVY, and tenofovir DF, another prodrug of tenofovir, alone or in combination with other antiretrovirals.
Treatment with DESCOVY should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information).
Post-treatment Acute Exacerbation of Hepatitis B in Patients with HBV Coinfection Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued products containing FTC and/or TDF, and may likewise occur with discontinuation of DESCOVY [see Warnings and Precautions (5.1)].
Advise the patient to not discontinue DESCOVY without first informing their healthcare provider.
Immune Reconstitution Syndrome Advise patients to inform their healthcare provider immediately of any symptoms of infection, as in some patients with advanced HIV infection (AIDS), signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started [see Warnings and Precautions (5.2)].
New Onset or Worsening Renal Impairment Advise patients to avoid taking DESCOVY with concurrent or recent use of nephrotoxic agents.
Renal impairment, including cases of acute renal failure, has been reported in association with the use of tenofovir prodrugs [see Warnings and Precautions (5.3)].
Lactic Acidosis and Severe Hepatomegaly Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with use of drugs similar to DESCOVY.
Advise patients that they should stop DESCOVY if they develop clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity [see Warnings and Precautions (5.4)].
Missed Dosage Inform patients that it is important to take DESCOVY on a regular dosing schedule with or without food and to avoid missing doses as it can result in development of resistance [see Dosage and Administration (2.2)].
Pregnancy Registry Inform patients that there is an antiretroviral pregnancy registry to monitor fetal outcomes of pregnant women exposed to DESCOVY [see Use in Specific Populations (8.1)].
Lactation Instruct women with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in breast milk [see Use in Specific Populations (8.2)].
DOSAGE AND ADMINISTRATION
2 Testing: Prior to initiation of DESCOVY, patients should be tested for hepatitis B virus infection, and estimated creatinine clearance, urine glucose and urine protein should be obtained.
(2.1) Recommended dosage: One tablet taken once daily with or without food in patients with body weight at least 25 kg and a creatinine clearance greater than or equal to 30 mL per minute.
(2.2) Renal impairment: DESCOVY is not recommended in patients with estimated creatinine clearance below 30 mL per minute.
(2.3) 2.1 Testing Prior to Initiation of DESCOVY Prior to initiation of DESCOVY, patients should be tested for hepatitis B virus infection [see Warnings and Precautions (5.1)].
Estimated creatinine clearance, urine glucose, and urine protein should be assessed before initiating DESCOVY therapy and should be monitored during therapy in all patients [see Warnings and Precautions (5.3)].
2.2 Recommended Dosage DESCOVY is a two-drug fixed dose combination product containing 200 mg of emtricitabine (FTC) and 25 mg of tenofovir alafenamide (TAF).
The recommended dosage of DESCOVY is one tablet taken orally once daily with or without food in adults and pediatric patients with body weight at least 25 kg and creatinine clearance greater than or equal to 30 mL per minute [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
For specific dosing recommendations for coadministered third agents, refer to their respective prescribing information [see Drug Interactions (7)].
The safety and effectiveness of DESCOVY coadminstered with an HIV-1 protease inhibitor that is administered with either ritonavir or cobicistat have not been established in pediatric subjects weighing less than 35 kg.
2.3 Not Recommended in Patients with Severe Renal Impairment DESCOVY is not recommended in patients with estimated creatinine clearance below 30 mL per minute [see Warnings and Precautions (5.3) and Use in Specific Populations (8.6)].