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Odefsey emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide 200 mg; 25 mg; 25 mg Tablet, 30-count — NDC 61958-2101-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Odefsey emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide 200 mg; 25 mg; 25 mg Tablet, 30-count — NDC 61958-2101-1 (Billing 61958-2101-01)

by Gilead Sciences, Inc. · 30 TABLET in 1 BOTTLE, PLASTIC

This is a package of 30 tablets of Odefsey emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide 200 mg; 25 mg; 25 mg Tablet from Gilead Sciences, Inc., marketed since Mar 2016 and currently FDA-listed; retail pharmacies pay about $130.49 per tablet (NADAC). It is this product's only package size.

NDC 61958-2101-01
🏷️ FDA NDC (as labeled) 61958-2101-1 billing pads the package segment with a zero
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Oct 8, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 61958-2101-1 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
61958 labeler · 2101 product · 1 package
Package marketed since
Mar 1, 2016
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Billing quantity
30 EA per package
Barcode (UPC-A, from the NDC)
3 6195821011 9
Medicaid fills, this package
43,465 prescriptions in the last four reported quarters
FDA record last changed
Oct 8, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 61958-2101-1
Product NDC 61958-2101
11-digit billing NDC 61958210101
NCPDP billing unit EA — each (per item)
RxCUI 1741733, 1741739
UNII G70B4ETF4S, 212WAX8KDD, FWF6Q91TZO
Application # NDA208351
SPL Set ID ea3b9ec8-e04a-412c-8b3f-e5cbc7e641d5
Established class (EPC) Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor
Mechanism of action Nucleoside Reverse Transcriptase Inhibitors
Chemical class Nucleosides
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2016-03-01
Route ORAL
Dosage form TABLET
Substance EMTRICITABINE; RILPIVIRINE HYDROCHLORIDE; TENOFOVIR ALAFENAMIDE FUMARATE

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 12109903390320
GPI class Odefsey
GCN Seq No 075634
GCN 37633
HICL code 043121
Ingredient (HICL) Emtricitab/Rilpiviri/Tenof Ala
HIC1 code W
Therapeutic class — broad (HIC1) Anti-Infecting Agents
HIC2 code W5
Therapeutic class — intermediate (HIC2) Antiviral Agents
HIC3 code W5Q
Therapeutic class — specific (HIC3) Artv Nucleoside,Nucleotide,Non-Nucleoside Rti Comb
AHFS code 08:18.08.16
AHFS class Hiv Nonnucleoside Rev.transcrip. Inhib.
FDB label name ODEFSEY TABLET
FDB brand name Odefsey
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 075634
  • GCN: 37633
  • GPI-14 (Medi-Span): 12109903390320
  • HICL (First Databank): 043121
  • AHFS class code: 08:18.08.16
  • RxCUI (RxNorm): 1741733
Why two NDCs? The FDA registers this code as 61958-2101-1 — a 5-4-1 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the package segment → 61958-2101-01. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor class.

Pharmacologic class Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor
Drug family (ATC) Non-nucleoside reverse transcriptase inhibitors
How it works Non-Nucleoside Reverse Transcriptase Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name ODEFSEY TABLET Ingredient Emtricitab/Rilpiviri/Tenof Ala

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eaPer package
Retail pharmacies payNADAC · weekly $130.492 $3,914.76 / 30 tablets
Medicaid paysCMS SDUD · 12 mo $124.81 $3,744.17 / 30 tablets
Medicare drug plans payPart D · Q2 2026 $129.29 $3,878.58 / 30 tablets
NADAC price history (per ea) — tap or hover for the price & month
Oct 2021 Jan 2024 May 2026 Sep 2026 $130.492 $100.173
▲ Up 30% over the last 11 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
61958-2101-01 You're viewing this Main listing 30 TABLET in 1 BOTTLE, PLASTIC 2016-03-01 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Odefsey 200 mg/1; 25 mg/1; 25 mgthis 61958-2101-01 Gilead 30 tablets $130.492 — Availability likely —
About this product: this is the brand-name version. Some generic versions are approved by the FDA, but we could not confirm current pharmacy availability from our pricing/market data.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2016
First FDA approval
Mar 2016
📍
2026
Currently FDA-listed
10 years listed
🛡️
2033
Latest patent/protection listed
not a guaranteed launch date
🔒Generic approved by FDA, but pharmacy availability is not confirmed

The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Feb 2033. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Mar 1, 2016 RLD RS ⏳ ~6.4 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

When could a generic Odefsey arrive?

Our estimate: January 2032 about 5.5 years away

How sure: Very likely. Few things could still move it, but a court ruling or a new deal can.

Why then: The brand company and a generic maker settled their patent fight and agreed on when a generic can launch.

That is before the February 2033 date above, which is common: a court ruling or a deal with the brand’s maker often lets a generic in before the last patent runs out.

See the full forecast for generic Odefsey →
Patents & exclusivity — FDA Orange Book
US 9296769 — drug substance (U-257)
US 8754065 — drug substance (U-257)
US 8754065*PED — drug product
US 9296769*PED — drug product
2016 2018 2020 2022 2024 2026 2028 2030 2032
Today
LOE
Expected generic
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (4)
PatentTypeUse codeExpires
US 9296769 ↗ Drug substance U-257 Aug 15, 2032
US 8754065 ↗ Drug substance U-257 Aug 15, 2032
US 8754065*PED ↗ Drug product — Feb 15, 2033
US 9296769*PED ↗ Drug product — Feb 15, 2033
Common questions
Is there a generic version of ODEFSEY TABLET?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for ODEFSEY TABLET. See the alternatives section for substitutable, lower-cost products. An approval does not always mean it is on pharmacy shelves yet: we expect the first generic Odefsey in January 2032, about 5.5 years away. See the forecast.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII M28OL1HH48
    Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
  • UNII XM0M87F357
    A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
  • UNII EWQ57Q8I5X
    Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII 3WJQ0SDW1A
    Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
  • UNII 7T1F30V5YH
    A synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together and keeps them from separating in liquid formulations.
  • UNII 532B59J990
    Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
  • UNII FZ989GH94E
    Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
  • UNII 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

12 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerGilead Sciences, Inc.
Application holderGILEAD SCIENCES INC
FDA applicationNDA208351 (NDA)
Labeler code61958
First marketedMar 2016
Product typeHuman Prescription Drug
Portfolio42 products on file

More NDCs from Gilead Sciences, Inc. labeler code 61958

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 153 words ▾

WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B Severe acute exacerbations of hepatitis B have been reported in patients with HIV-1 and HBV who have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of ODEFSEY. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients with HIV-1 and HBV who discontinue ODEFSEY. If appropriate, 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. Severe acute exacerbations of hepatitis B have been reported in patients with HIV-1 and HBV who have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of ODEFSEY. Hepatic function should be monitored closely in these patients.

If appropriate, anti-hepatitis B therapy may be warranted. ( 5.1 )

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE ODEFSEY is indicated as a complete regimen for the treatment of HIV-1 infection in adult and pediatric patients weighing at least 25 kg: as initial therapy in those with no antiretroviral treatment history with HIV-1 RNA less than or equal to 100,000 copies/mL or to replace a stable antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies/mL) for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of ODEFSEY [see Microbiology (12.4) and Clinical Studies (14) ].

ODEFSEY is a three-drug combination of emtricitabine (FTC) and tenofovir alafenamide (TAF), both HIV nucleoside analog reverse transcriptase inhibitors (NRTIs), and rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), and is indicated as a complete regimen for the treatment of HIV-1 infection in adult and pediatric patients weighing at least 25kg: as initial therapy in those with no antiretroviral treatment history with HIV-1 RNA less than or equal to 100,000 copies/mL; or to replace a stable antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies/mL) for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of ODEFSEY.

( 1 ) Limitations of Use : More rilpivirine-treated participants with HIV-1 RNA greater than 100,000 copies/mL at the start of therapy experienced virologic failure (HIV-1 RNA ≥ 50 copies/mL) compared to rilpivirine-treated participants with HIV-1 RNA less than or equal to 100,000 copies/mL. ( 14.2 , 14.3 ) Limitations of Use: More rilpivirine-treated participants with no antiretroviral treatment history with HIV-1 RNA greater than 100,000 copies/mL at the start of therapy experienced virologic failure (HIV-1 RNA ≥ 50 copies/mL) compared to rilpivirine-treated participants with HIV-1 RNA less than or equal to 100,000 copies/mL [see Clinical Studies (14.2 , 14.3) ].

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION Testing: Prior to or when initiating ODEFSEY, test for hepatitis B virus infection. Prior to or when initiating ODEFSEY, and during treatment on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus ( 2.1 ) Recommended dosage: one tablet taken orally once daily with a meal.

( 2.2 ) For pregnant patients who are already on ODEFSEY prior to pregnancy and who are virologically suppressed (HIV-1 RNA less than 50 copies per mL), one tablet taken once daily may be continued. Lower exposures of rilpivirine were observed during pregnancy, therefore viral load should be monitored closely. ( 2.3 ) Renal impairment: ODEFSEY is not recommended in patients with estimated creatinine clearance of 15 to below 30 mL per minute, or below 15 mL per minute who are not receiving chronic hemodialysis.

( 2.4 )

2.1Testing Prior to Initiation and During Treatment with ODEFSEY Prior to or when initiating ODEFSEY, test patients for hepatitis B virus infection [see Warnings and Precautions (5.1) ] . Prior to or when initiating ODEFSEY, and during treatment with ODEFSEY, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus [see Warnings and Precautions (5.5) ].

2.2Recommended Dosage in Adult and Pediatric Patients Weighing at Least 25 kg ODEFSEY is a three-drug fixed dose combination product containing 200 mg of emtricitabine (FTC), 25 mg of rilpivirine (RPV), and 25 mg of tenofovir alafenamide (TAF). The recommended dosage of ODEFSEY is one tablet taken orally once daily with a meal 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) ].

2.3Recommended Dosage During Pregnancy For pregnant patients who are already on ODEFSEY prior to pregnancy and are virologically suppressed (HIV-1 RNA less than 50 copies per mL), one tablet of ODEFSEY taken once daily may be continued. Lower exposures of rilpivirine, a component of ODEFSEY, were observed during pregnancy, therefore viral load should be monitored closely [see Use in Specific Populations (8.1) and Clinical Pharmacology (12.3) ] .

2.4Not Recommended in Patients with Severe Renal Impairment ODEFSEY is not recommended in patients with: severe renal impairment (estimated creatinine clearance of 15 to below 30 mL per minute); or end stage renal disease (ESRD; estimated creatinine clearance below 15 mL per minute) who are not receiving chronic hemodialysis [see Dosage and Administration (2.2) , Warnings and Precautions (5.5) , and Use in Specific Populations (8.6) ].

💊 Dosage Forms and Strengths 77 words ▾

3 DOSAGE FORMS AND STRENGTHS Each ODEFSEY tablet contains 200 mg of emtricitabine (FTC), 25 mg of rilpivirine (RPV) (equivalent to 27.5 mg of rilpivirine hydrochloride), and 25 mg of tenofovir alafenamide (TAF) (equivalent to 28 mg of tenofovir alafenamide fumarate). The tablets are gray, capsule-shaped, film-coated and debossed with "GSI" on one side and "255" on the other side. Tablets: 200 mg of FTC, 25 mg of RPV and 25 mg of TAF. ( 3 )

⛔ Contraindications 108 words ▾

4 CONTRAINDICATIONS ODEFSEY is contraindicated when coadministered with the following drugs; coadministration may result in loss of virologic response and possible resistance to ODEFSEY or to the class of NNRTIs [see Warnings and Precautions (5.6) , Drug Interactions (7) and Clinical Pharmacology (12.3) ]: Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin Antimycobacterials: rifampin, rifapentine Glucocorticoid (systemic): dexamethasone (more than a single-dose) Herbal Products: St. John's wort (Hypericum perforatum) Proton Pump Inhibitors: e.g., dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole ODEFSEY is contraindicated when coadministered with drugs where significant decreases in RPV plasma concentrations may occur, which may result in loss of virologic response and possible resistance and cross-resistance.

( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Skin and Hypersensitivity Reactions: Severe skin and hypersensitivity reactions have been reported during postmarketing experience with RPV-containing regimens, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Immediately discontinue treatment if hypersensitivity or rash with systemic symptoms or elevations in hepatic serum biochemistries develops and closely monitor clinical status, including hepatic serum biochemistries. ( 5.2 ) Hepatotoxicity: Hepatic adverse events have been reported in patients receiving an RPV-containing regimen.

Monitor liver-associated tests before and during treatment with ODEFSEY in patients with underlying hepatic disease or marked elevations in liver-associated tests. Also consider monitoring liver-associated tests in patients without risk factors. ( 5.3 ) Depressive disorders: Severe depressive disorders have been reported.

Immediate medical evaluation is recommended for severe depressive disorders. ( 5.4 ) New onset or worsening renal impairment: Assessment of serum creatinine, estimated creatinine clearance, urine glucose, and urine protein when initiating ODEFSEY and during therapy on a clinically appropriate schedule in all patients. Also assess serum phosphorus in patients with chronic kidney disease.

( 5.5 ) Concomitant use of ODEFSEY with drugs with a known risk to prolong the QTc interval of the electrocardiogram may increase the risk of Torsade de Pointes. ( 5.6 ) Lactic acidosis/severe hepatomegaly with steatosis: Discontinue treatment in patients who develop symptoms or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity. ( 5.7 ) Immune reconstitution syndrome: May necessitate further evaluation and treatment.

( 5.8 )

5.1Severe Acute Exacerbation of Hepatitis B in Patients with HIV-1 and HBV Test patients with HIV-1 for the presence of hepatitis B virus (HBV) before or when initiating antiretroviral therapy [see Dosage and Administration (2.1) ] . Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in patients with HIV-1 and HBV who have discontinued products containing FTC and/or TDF, and may occur with discontinuation of ODEFSEY. Patients with HIV-1 and HBV who discontinue ODEFSEY should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment with ODEFSEY.

If appropriate, 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.

5.2Skin and Hypersensitivity Reactions Severe skin and hypersensitivity reactions, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported during postmarketing experience with RPV-containing regimens. While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunction, including elevations in hepatic serum biochemistries. During Phase 3 clinical trials of RPV, treatment-related rashes with at least Grade 2 severity were reported in 1% of participants.

Overall, most rashes were Grade 1 or 2 and occurred in the first four to six weeks of therapy [see Adverse Reactions (6.2) ] . Discontinue ODEFSEY immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, including but not limited to, severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis, or eosinophilia. Clinical status including laboratory parameters should be monitored and appropriate therapy should be initiated.

5.3Hepatotoxicity Hepatic adverse events have been reported in patients receiving an RPV-containing regimen. Patients with underlying hepatitis B or C virus infection, or marked elevations in liver-associated tests prior to treatme… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Severe Acute Exacerbations of Hepatitis B [see Warnings and Precautions (5.1) ] Skin and Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] Hepatotoxicity [see Warnings and Precautions (5.3) ] Depressive Disorders [see Warnings and Precautions (5.4) ] New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.5) ] Lactic Acidosis/Severe Hepatomegaly with Steatosis [see Warnings and Precautions (5.7) ] Immune Reconstitution Syndrome [see Warnings and Precautions (5.8) ] Most common adverse reactions (incidence greater than or equal to 2%, all grades) are headache and sleep disturbances.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug (or a drug given in various combinations with other concomitant therapy) cannot be directly compared to rates in the clinical trials of another drug (or drug given in the same or different combination therapy) and may not reflect the rates observed in practice. Adverse Reactions in Clinical Trials of ODEFSEY in Virologically-Suppressed Adult Participants with HIV-1 The safety of ODEFSEY in virologically-suppressed adults is based on Week 48 data from two randomized, double-blinded, active-controlled clinical trials, 1160 and 1216, that enrolled 1505 adult participants with HIV-1 who were virologically-suppressed for at least 6 months.

Both trials were designed to compare switching to ODEFSEY to maintaining efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) or emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) in Trials 1160 and 1216, respectively. A total of 754 participants received one tablet of ODEFSEY daily [see Clinical Studies (14.1) ]. The most common adverse reactions (all Grades) reported in at least 2% of participants in the ODEFSEY group across Trials 1216 and 1160 were headache and sleep disturbances (Table 1).

Over 98% of the adverse reactions in the ODEFSEY group were of mild to moderate intensity. The proportion of participants who discontinued treatment with ODEFSEY due to adverse events, regardless of severity, was 2% compared to 1% for FTC/RPV/TDF and 2% for EFV/FTC/TDF. Table 1 Adverse Reactions Frequencies of adverse reactions are based on all adverse events attributed to study drugs by the investigator.

(All Grades) Reported in ≥1% of Virologically-Suppressed Adults with HIV-1 in Trial 1160 or Trial 1216 (Week 48 analysis) Adverse Reaction Trial 1160 Trial 1216 ODEFSEY (N=438) EFV/FTC/TDF (N=437) Data from Trials 1160 and 1216 do not provide an adequate basis for comparison of adverse reaction incidences between ODEFSEY and the FTC/RPV/TDF and EFV/FTC/TDF groups. ODEFSEY (N=316) FTC/RPV/TDF (N=313) Headache 2% 1% 0 1% Sleep Disturbances 2% 1% 0 <1% Flatulence 1% <1% <1% 1% Abnormal Dreams 1% 1% 0 2% Diarrhea 1% 3% 1% 2% Nausea 1% 1% 1% 1% Renal Laboratory Tests In Trial 1216, the median baseline eGFR was 104 mL per minute for participants who switched to ODEFSEY from FTC/RPV/TDF (N=316) and the mean serum creatinine decreased by 0.02 mg per dL from baseline to Week 48.

In Trial 1160, the median baseline eGFR was 110 mL per minute for participants who switched to ODEFSEY from EFV/FTC/TDF (N=438), and the mean serum creatinine increased by 0.1 mg per dL from baseline to Week 48. Bone Mineral Density Effects Changes in BMD from baseline to Week 48 were assessed by dual-energy X-ray absorptiometry (DXA) in Trials 1216 and 1160. In Trial 1216, mean bone mineral density (BMD) increased in participants who switched to ODEFSEY (1.61% lumbar spine, 1.04% total hip) and remained stable or decreased in participants who remained on FTC/RPV/TDF (0.08% lumbar spine, −0.2… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~3 min read ▾

7 DRUG INTERACTIONS ODEFSEY is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended. ( 7.1 ) Consult the Full Prescribing Information prior to and during treatment for important drug interactions. ( 4 , 5.6 , 7 )

7.1Not Recommended with Other Antiretroviral Medications Because ODEFSEY is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended.

7.2Drugs Inducing or Inhibiting CYP3A Enzymes RPV is primarily metabolized by CYP3A, and drugs that induce or inhibit CYP3A may affect the clearance of RPV [see Clinical Pharmacology (12.3) ] . Coadministration of RPV and drugs that induce CYP3A may result in decreased plasma concentrations of RPV and loss of virologic response and possible resistance to RPV or to the class of NNRTIs [see Contraindications (4) , Warnings and Precautions (5.6) , and Table 4 ] . Coadministration of RPV and drugs that inhibit CYP3A may result in increased plasma concentrations of RPV and possible adverse events.

7.3Drugs Inducing or Inhibiting P-glycoprotein TAF, a component of ODEFSEY, 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 4 ) . 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 ODEFSEY and development of resistance.

Coadministration of ODEFSEY with other drugs that inhibit P-gp and BCRP may increase the absorption and plasma concentration of TAF.

7.4Drugs Increasing Gastric pH Coadministration of RPV with drugs that increase gastric pH may decrease plasma concentrations of RPV and lead to loss of virologic response and possible resistance to RPV or to the class of NNRTIs. Use of RPV with proton pump inhibitors is contraindicated and use of RPV with H 2 -receptor antagonists requires staggered administration [see Contraindications (4) and Table 4 ].

7.5QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between RPV and drugs that prolong the QTc interval. In a study of healthy participants, higher than recommended doses of RPV, 75 mg once daily and 300 mg once daily (3 times and 12 times recommended daily dose in ODEFSEY) prolonged the QTc interval [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.2) ] . Consider alternative medications to ODEFSEY in patients taking a drug with a known risk of Torsade de Pointes.

7.6Drugs 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 ODEFSEY 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 (5.5) ] .

7.7Significant Drug Interactions Table 4 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 ODEFSEY, the components of ODEFSEY (FTC, RPV and TAF) as individual agents, or are predicted drug interactions that may occur with ODEFSEY [see Clinical Pharmacology (12.3) , Tables 9–12]. For list of contraindicated drugs, [see Contraindications (4) ].

Table 4 Significant This table is not all inclusive. Dru… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy: Total rilpivirine exposures were generally lower during pregnancy compared to the postpartum period. ( 2.3 , 8.1 , 12.3 ). Pediatrics: Not recommended for patients weighing less than 25 kg. ( 8.4 )

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to ODEFSEY during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Available data from the APR show no statistically significant difference in the overall risk of major birth defects for emtricitabine (FTC), rilpivirine (RPV) or tenofovir alafenamide (TAF) compared with the background rate for major birth defects of 2.7% in a US reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) (see Data ) .

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%. Based on the experience of pregnant individuals with HIV-1 who completed a clinical trial through the postpartum period with an RPV-based regimen, no dose adjustments are required for pregnant patients who are already on a stable RPV-containing regimen prior to pregnancy and who are virologically suppressed (HIV-1 RNA less than 50 copies per mL).

Lower exposures of RPV were observed during pregnancy compared to the postpartum period. Therefore, viral load should be monitored closely [see Data and Clinical Pharmacology (12.3) ] . In animal studies, no adverse developmental effects were observed when the components of ODEFSEY were administered separately during the period of organogenesis at exposures up to 60 and 108 times (mice and rabbits, respectively; FTC), 15 and 70 times (rats and rabbits, respectively; RPV) and equal to and 53 times (rats and rabbits, respectively; TAF) the exposure at the recommended daily dose of these components in ODEFSEY (see Data ) .

Likewise, no adverse developmental effects were seen when FTC was administered to mice and RPV was administered to rats through lactation at exposures up to approximately 60 and 63 times, respectively, the exposure at the recommended daily dose of these components in ODEFSEY. 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 ODEFSEY. Data Human Data Prospective reports from the APR of overall major birth defects in pregnancies exposed to drug components of ODEFSEY are compared with a U.S. background major birth defect rate.

Methodological limitations of the APR include the use of MACDP as the external comparator group. The MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at less than 20 weeks gestation. Emtricitabine (FTC): Based on prospective reports to the APR of over 5,400 exposures to FTC-containing regimens during pregnancy resulting in live births (including over 3,900 exposed in the first trimester and over 1,500 exposed in the second/third trimester), the prevalence of birth defects in live births was 2.6% (95% CI: 2.2% to 3.2%) and 2.7% (95% CI: 1.9% to 3.7%) following first and second/third trimester exposure, respectively, to FTC-containing regimens.

Rilpivirine (RPV): RPV in combination with a background regimen was evaluated in a clinical trial of 19 pregnant participants with HIV-1 during the second and third trimesters and postpartum. Each of the subjects were on an RPV-based regimen at the time of enrollment. Twelve participants completed the trial through the postpartum period (6–12 weeks after delivery) and pregnancy outcomes are missing for six participants.

The exposure (C 0h and AUC) of total RPV was approximately 30 to 40% lower dur… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to ODEFSEY during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Available data from the APR show no statistically significant difference in the overall risk of major birth defects for emtricitabine (FTC), rilpivirine (RPV) or tenofovir alafenamide (TAF) compared with the background rate for major birth defects of 2.7% in a US reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) (see Data ) .

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%. Based on the experience of pregnant individuals with HIV-1 who completed a clinical trial through the postpartum period with an RPV-based regimen, no dose adjustments are required for pregnant patients who are already on a stable RPV-containing regimen prior to pregnancy and who are virologically suppressed (HIV-1 RNA less than 50 copies per mL).

Lower exposures of RPV were observed during pregnancy compared to the postpartum period. Therefore, viral load should be monitored closely [see Data and Clinical Pharmacology (12.3) ] . In animal studies, no adverse developmental effects were observed when the components of ODEFSEY were administered separately during the period of organogenesis at exposures up to 60 and 108 times (mice and rabbits, respectively; FTC), 15 and 70 times (rats and rabbits, respectively; RPV) and equal to and 53 times (rats and rabbits, respectively; TAF) the exposure at the recommended daily dose of these components in ODEFSEY (see Data ) .

Likewise, no adverse developmental effects were seen when FTC was administered to mice and RPV was administered to rats through lactation at exposures up to approximately 60 and 63 times, respectively, the exposure at the recommended daily dose of these components in ODEFSEY. 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 ODEFSEY. Data Human Data Prospective reports from the APR of overall major birth defects in pregnancies exposed to drug components of ODEFSEY are compared with a U.S. background major birth defect rate.

Methodological limitations of the APR include the use of MACDP as the external comparator group. The MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at less than 20 weeks gestation. Emtricitabine (FTC): Based on prospective reports to the APR of over 5,400 exposures to FTC-containing regimens during pregnancy resulting in live births (including over 3,900 exposed in the first trimester and over 1,500 exposed in the second/third trimester), the prevalence of birth defects in live births was 2.6% (95% CI: 2.2% to 3.2%) and 2.7% (95% CI: 1.9% to 3.7%) following first and second/third trimester exposure, respectively, to FTC-containing regimens.

Rilpivirine (RPV): RPV in combination with a background regimen was evaluated in a clinical trial of 19 pregnant participants with HIV-1 during the second and third trimesters and postpartum. Each of the subjects were on an RPV-based regimen at the time of enrollment. Twelve participants completed the trial through the postpartum period (6–12 weeks after delivery) and pregnancy outcomes are missing for six participants.

The exposure (C 0h and AUC) of total RPV was approximately 30 to 40% lower during pregnancy compared with postpartum (6 to 12 weeks). The protein binding of RPV was similar (>99%) during second trimester, third trimester, and postpartum period [see Clinical Pharmacology (12.3) ] . One participant discontinued the tr… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use ~2 min read ▾

8.4Pediatric Use The efficacy and safety of ODEFSEY as a complete regimen for the treatment of HIV-1 was established in pediatric patients 6 years of age and older with body weight greater than or equal to 25 kg [see Dosage and Administration (2.2) ]. No pediatric clinical trials were conducted with ODEFSEY . Use of ODEFSEY in this age group is supported by adequate and well-controlled studies of RPV+FTC+TDF in adults with HIV-1 infection, adequate and well-controlled studies of FTC+TAF with EVG+COBI in adults with HIV-1, and by the following pediatric studies conducted using the components of ODEFSEY [see Clinical Studies (14) ]: 48-week open-label trials of antiretroviral treatment-naïve pediatric participants with HIV-1 aged 12 to less than 18 years and weighing at least 32 kg (N=36) and aged 6 to less than 12 years weighing at least 17 kg (N=18) treated with RPV and other antiretrovirals.

The safety and efficacy of RPV administered with other antiretrovirals were similar to that in antiretroviral treatment-naïve adults with HIV-1 on this regimen [see Adverse Reactions (6.1) and Clinical Studies (14) ]. 48-week open-label trial of 26 virologically-suppressed pediatric participants with HIV-1 aged less than 12 years old and weighing at least 16 kg (N=26) treated with RPV and other antiretrovirals. The safety and efficacy of RPV administered with other antiretrovirals were similar to that in virologically-suppressed adults with HIV-1 on this regimen [see Adverse Reactions (6.1) ] 48-week open-label trials of antiretroviral treatment-naïve pediatric participants with HIV-1 aged 12 to less than 18 years and weighing at least 35 kg (N=50) and virologically-suppressed pediatric participants between the ages of 6 to less than 12 years weighing at least 25 kg (N=52) treated with FTC+TAF with EVG+COBI.

The safety and efficacy of FTC+TAF with EVG+COBI were similar to that in adults with HIV-1 on this regimen, with the exception of a decrease from baseline in CD4+ cell counts in participants 6 to less than 12 years of age weighing at least 25 kg [see Adverse Reactions (6.1) and Clinical Studies (14) ]. Because it is a fixed-dose combination tablet, the dose of ODEFSEY cannot be adjusted for patients of lower age and weight. The safety and efficacy of ODEFSEY have not been established in pediatric patients weighing less than 25 kg [see Clinical Pharmacology (12.3) and Clinical Studies (14) ] .

🧓 Geriatric Use 74 words ▾

8.5Geriatric Use In clinical trials, 80 of the 97 participants enrolled aged 65 years and over received FTC+TAF with EVG+COBI. No differences in safety or efficacy have been observed between elderly participants and those between 12 and less than 65 years of age. Clinical trials of RPV did not include sufficient numbers of participants aged 65 years and over to determine whether they respond differently from younger participants [see Clinical Pharmacology (12.3) ].

🆘 Overdosage 161 words ▾

10 OVERDOSAGE Limited data are available on overdose of the components of ODEFSEY in patients. If overdose occurs, monitor the patient for evidence of toxicity. Treatment of overdose with ODEFSEY consists of general supportive measures including monitoring of vital signs and ECG (QT interval) as well as observation of the clinical status of the patient.

Emtricitabine (FTC): 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. Rilpivirine (RPV): Human experience of overdose with RPV is limited.

There is no specific antidote for overdose with RPV. Since RPV is highly bound to plasma protein, dialysis is unlikely to result in significant removal of RPV. Tenofovir Alafenamide (TAF): Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action ODEFSEY is a fixed dose combination of antiretroviral drugs emtricitabine, rilpivirine, and tenofovir alafenamide [see Microbiology (12.4) ] .

12.2Pharmacodynamics Cardiac Electrophysiology When higher than recommended RPV doses of 75 mg (3 times the recommended dosage in ODEFSEY) once daily and 300 mg (12 times the recommended dosage in ODEFSEY) once daily were studied in healthy adults, the maximum mean time-matched (95% upper confidence bound) differences in QTcF interval from placebo after baseline correction were 10.7 (15.3) and 23.3 (28.4) milliseconds, respectively. Steady-state administration of RPV 75 mg once daily and 300 mg once daily resulted in a mean steady-state C max approximately 2.6 times and 6.7 times, respectively, higher than the mean C max observed with the recommended 25 mg once daily dose of RPV [see Warnings and Precautions (5.6) ] .

The effect of RPV at the recommended dose of 25 mg once daily on the QTcF interval was evaluated in a randomized, placebo-, and active- (moxifloxacin 400 mg once daily) controlled crossover study in 60 healthy adults, with 13 measurements over 24 hours at steady state. The maximum mean time-matched (95% upper confidence bound) differences in QTcF interval from placebo after baseline correction was 2 (5) milliseconds (i.e., below the threshold of clinical concern). In a thorough QT/QTc study in 48 healthy participants, TAF at the recommended dose and at a dose approximately 5 times the recommended dose, did not affect the QT/QTc interval and did not prolong the PR interval.

The effect of FTC on the QT interval is not known.

12.3Pharmacokinetics Absorption, Distribution, Metabolism, and Excretion The pharmacokinetic properties of the components of ODEFSEY are provided in Table 5. The multiple dose pharmacokinetic parameters of FTC, RPV and TAF and its metabolite tenofovir are provided in Table 6. Table 5 Pharmacokinetic Properties of the Components of ODEFSEY Rilpivirine Emtricitabine Tenofovir Alafenamide PBMCs = peripheral blood mononuclear cells; CES1 = carboxylesterase 1.

Absorption T max (h) 4 3 1 Effect of moderate fat meal (relative to fasting) Values refer to geometric mean ratio [fed/ fasted] in PK parameters and (90% confidence interval). High-calorie/high-fat meal = ~800 kcal, 50% fat. Moderate-fat meal = ~600 kcal, 27% fat.

AUC Ratio = 1.13 (1.03, 1.23) AUC Ratio = 0.91 (0.89, 0.93) AUC Ratio = 1.45 (1.33, 1.58) Effect of high fat meal (relative to fasting) AUC Ratio = 1.72 (1.49, 1.99) AUC Ratio = 0.88 (0.85, 0.90) AUC Ratio = 1.53 (1.39, 1.69) Distribution % Bound to human plasma proteins ~99 <4 ~80 Source of protein binding data In vitro In vitro Ex vivo Blood-to-plasma ratio 0.7 0.6

1.0Metabolism Metabolism CYP3A Not significantly metabolized Cathepsin A In vivo, TAF is hydrolyzed within cells to form tenofovir (major metabolite), which is phosphorylated to the active metabolite, tenofovir diphosphate. In vitro studies have shown that TAF is metabolized to tenofovir by cathepsin A in PBMCs and macrophages; and by CES1 in hepatocytes. Upon coadministration with the moderate CYP3A inducer probe efavirenz, TAF exposure was unaffected.

(PBMCs) CES1 (hepatocytes) CYP3A (minimal) Elimination Major route of elimination Metabolism Glomerular filtration and active tubular secretion Metabolism (>80% of oral dose) t 1/2 (h) t 1/2 values refer to median terminal plasma half-life. Note that the pharmacologically active metabolite, tenofovir diphosphate, has a half-life of 150–180 hours within PBMCs. 50 10 0.51 % Of dose excreted in urine Dosing in mass balance studies: FTC (single dose administration of [ 14 C] emtricitabine after multiple dosing of emtricitabine for ten days); TAF (single dose administration of [ 14 C] tenofovir alafenamide).

6 70 <1 % Of dose excreted in feces 85 13.7

31.7Table 6 Multiple Dose Pharmacokinetic Parameters of Emtricitabine, Rilpivirine, Tenofovir Alafenamide and its Metabolite Tenofovir… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 23 words ▾

12.1Mechanism of Action ODEFSEY is a fixed dose combination of antiretroviral drugs emtricitabine, rilpivirine, and tenofovir alafenamide [see Microbiology (12.4) ] .

📦 How Supplied / Storage and Handling 60 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING ODEFSEY tablets are gray, capsule-shaped, and film coated with "GSI" debossed on one side and "255" on the other side. Each bottle contains 30 tablets (NDC 61958-2101-1), a silica gel desiccant, and a 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.

📦 Storage and Handling 13 words ▾

Store below 30°C (86°F). Keep container tightly closed. Dispense only in original container.

📋 Description ~2 min read ▾

11 DESCRIPTION ODEFSEY (emtricitabine, rilpivirine, and tenofovir alafenamide) is a fixed-dose combination tablet containing emtricitabine (FTC), rilpivirine (RPV), and tenofovir alafenamide (TAF) for oral administration. FTC, a synthetic nucleoside analog of cytidine, is an HIV-1 nucleoside analog reverse transcriptase inhibitor (HIV-1 NRTI). RPV is an HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI).

TAF, an HIV-1 NRTI, is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5′-monophosphate. Each tablet contains 200 mg of FTC, 25 mg of RPV (equivalent to 27.5 of rilpivirine hydrochloride) and 25 mg of TAF (equivalent to 28 mg of tenofovir alafenamide fumarate) and the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polysorbate 20, and povidone. The tablets are film-coated with a coating material containing iron oxide black, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.

Emtricitabine: The chemical name of FTC is 4-amino-5-fluoro-1-(2 R -hydroxymethyl-1,3-oxathiolan-5 S -yl)-(1 H )-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 C 8 H 10 FN 3 O 3 S 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.

Rilpivirine: The chemical name of rilpivirine hydrochloride drug substance is 4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile monohydrochloride. Its molecular formula is C 22 H 18 N 6 ∙ HCl and its molecular weight is 402.88. Rilpivirine hydrochloride has the following structural formula: Rilpivirine hydrochloride is a white to almost white powder.

Rilpivirine hydrochloride is practically insoluble in water over a wide pH range. Tenofovir Alafenamide: The chemical name of tenofovir alafenamide fumarate drug substance is L-alanine, N -[( S )-[[(1 R )-2-(6-amino-9 H -purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphinyl]-, 1-methylethyl ester, (2 E )-2-butenedioate (2:1). Tenofovir alafenamide fumarate has an empirical formula of C 21 H 29 O 5 N 6 P∙½(C 4 H 4 O 4 ) 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 Chemical Structure

💬 Information for Patients ~3 min read ▾

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 with HBV and HIV-1 who have discontinued products containing FTC and/or TDF, and may likewise occur with discontinuation of ODEFSEY [see Warnings and Precautions (5.1) ] . Advise the patient to not discontinue ODEFSEY without first informing their healthcare provider.

Severe Skin Reactions and Hypersensitivity Inform patients that skin reactions ranging from mild to severe, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported with RPV-containing products. Instruct patients to immediately stop taking ODEFSEY and seek medical attention if they develop a rash associated with any of the following symptoms: fever, blisters, mucosal involvement, eye inflammation (conjunctivitis), severe allergic reaction causing swelling of the face, eyes, lips, mouth, tongue or throat which may lead to difficulty swallowing or breathing, and any signs and symptoms of liver problems, as they may be a sign of a more serious reaction.

Patients should understand that if severe rash occurs, they will be closely monitored, laboratory tests will be performed and appropriate therapy will be initiated [see Warnings and Precautions (5.2) ]. Hepatotoxicity Inform patients that hepatotoxicity has been reported with RPV, therefore, it is important to inform the healthcare professional if patients have underlying hepatitis B or C or elevations in liver-associated tests prior to treatment [see Dosage and Administration (2.1) and Warnings and Precautions (5.3) ] .

Depressive Disorders Inform patients that depressive disorders (depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) have been reported with RPV. Inform patients to seek immediate medical evaluation if they experience depressive symptoms [see Warnings and Precautions (5.4) ]. New Onset or Worsening Renal Impairment Advise patients to avoid taking ODEFSEY with concurrent or recent use of nephrotoxic agents.

Postmarketing cases of renal impairment, including acute renal failure, have been reported [see Warnings and Precautions (5.5) ]. Drug Interactions ODEFSEY may interact with many drugs and is not recommended to be coadministered with numerous drugs. Advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products, including St.

John's wort [see Contraindications (4) , Warnings and Precautions (5.6) and Drug Interactions (7) ] . Lactic Acidosis and Severe Hepatomegaly Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with use of drugs similar to ODEFSEY. Advise patients to stop taking ODEFSEY if they develop clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity [see Warnings and Precautions (5.7) ] .

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 (5.8) ]. Missed Dosage Inform patients that it is important to take ODEFSEY on a regular dosing schedule with a meal 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 in those exposed to ODEFSEY during pregnancy [see Use in Specific Populations (8.1) ]. Lactation Instruct patients with HIV-1 that the potential risks of breastfeeding include: (1) HIV-1 transmission to infants without HIV-1, (2) devel… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption, Distribution, Metabolism, and Excretion The pharmacokinetic properties of the components of ODEFSEY are provided in Table 5. The multiple dose pharmacokinetic parameters of FTC, RPV and TAF and its metabolite tenofovir are provided in Table 6. Table 5 Pharmacokinetic Properties of the Components of ODEFSEY Rilpivirine Emtricitabine Tenofovir Alafenamide PBMCs = peripheral blood mononuclear cells; CES1 = carboxylesterase 1.

Absorption T max (h) 4 3 1 Effect of moderate fat meal (relative to fasting) Values refer to geometric mean ratio [fed/ fasted] in PK parameters and (90% confidence interval). High-calorie/high-fat meal = ~800 kcal, 50% fat. Moderate-fat meal = ~600 kcal, 27% fat.

AUC Ratio = 1.13 (1.03, 1.23) AUC Ratio = 0.91 (0.89, 0.93) AUC Ratio = 1.45 (1.33, 1.58) Effect of high fat meal (relative to fasting) AUC Ratio = 1.72 (1.49, 1.99) AUC Ratio = 0.88 (0.85, 0.90) AUC Ratio = 1.53 (1.39, 1.69) Distribution % Bound to human plasma proteins ~99 <4 ~80 Source of protein binding data In vitro In vitro Ex vivo Blood-to-plasma ratio 0.7 0.6

1.0Metabolism Metabolism CYP3A Not significantly metabolized Cathepsin A In vivo, TAF is hydrolyzed within cells to form tenofovir (major metabolite), which is phosphorylated to the active metabolite, tenofovir diphosphate. In vitro studies have shown that TAF is metabolized to tenofovir by cathepsin A in PBMCs and macrophages; and by CES1 in hepatocytes. Upon coadministration with the moderate CYP3A inducer probe efavirenz, TAF exposure was unaffected.

(PBMCs) CES1 (hepatocytes) CYP3A (minimal) Elimination Major route of elimination Metabolism Glomerular filtration and active tubular secretion Metabolism (>80% of oral dose) t 1/2 (h) t 1/2 values refer to median terminal plasma half-life. Note that the pharmacologically active metabolite, tenofovir diphosphate, has a half-life of 150–180 hours within PBMCs. 50 10 0.51 % Of dose excreted in urine Dosing in mass balance studies: FTC (single dose administration of [ 14 C] emtricitabine after multiple dosing of emtricitabine for ten days); TAF (single dose administration of [ 14 C] tenofovir alafenamide).

6 70 <1 % Of dose excreted in feces 85 13.7

31.7Table 6 Multiple Dose Pharmacokinetic Parameters of Emtricitabine, Rilpivirine, Tenofovir Alafenamide and its Metabolite Tenofovir Following Oral Administration with a Meal in Adults with HIV-1 Parameter Mean (CV%) Emtricitabine From Intensive PK analysis in a phase 2 trial in adults with HIV-1 treated with FTC+TAF with EVG+COBI (n=19). Rilpivirine From Population PK analysis in a trial of treatment-naïve adults with HIV-1 treated with RPV (n=679). Tenofovir Alafenamide From Population PK analysis in two trials of treatment-naïve adults with HIV-1 treated within EVG+COBI+FTC+TAF (n=539).

Tenofovir From Population PK analysis in two trials of treatment-naïve adults with HIV-1 treated with EVG+COBI+FTC+TAF (n=841). CV = Coefficient of Variation; NA = Not Applicable C max (microgram per mL) 2.1 (20.2) NA 0.16 (51.1) 0.02 (26.1) AUC tau (microgram∙hour per mL) 11.7 (16.6) 2.2 (38.1) 0.21 (71.8) 0.29 (27.4) C trough (microgram per mL) 0.10 (46.7) 0.08 (44.3) NA 0.01 (28.5) Specific Populations Geriatric Patients The pharmacokinetics of FTC and TAF have not been fully evaluated in the elderly (65 years of age and older).

Population pharmacokinetics analysis of participants with HIV-1 in Phase 2 and Phase 3 trials of FTC+TAF with EVG+COBI showed that age did not have a clinically relevant effect on exposures of TAF up to 75 years of age. The pharmacokinetics of RPV have not been fully evaluated in the elderly (65 years of age and older) [see Use in Specific Populations (8.5) ]. Pediatric Patients Exposures of TAF in 24 pediatric participants with HIV-1 aged 12 to less than 18 years who received FTC+TAF with EVG+COBI were decreased (23% for TAF AUC) compared to exposures achieved in treatment-naïve adults following administration of FTC+TAF with EVG+COBI.

These e… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics ~1 min read ▾

12.2Pharmacodynamics Cardiac Electrophysiology When higher than recommended RPV doses of 75 mg (3 times the recommended dosage in ODEFSEY) once daily and 300 mg (12 times the recommended dosage in ODEFSEY) once daily were studied in healthy adults, the maximum mean time-matched (95% upper confidence bound) differences in QTcF interval from placebo after baseline correction were 10.7 (15.3) and 23.3 (28.4) milliseconds, respectively. Steady-state administration of RPV 75 mg once daily and 300 mg once daily resulted in a mean steady-state C max approximately 2.6 times and 6.7 times, respectively, higher than the mean C max observed with the recommended 25 mg once daily dose of RPV [see Warnings and Precautions (5.6) ] .

The effect of RPV at the recommended dose of 25 mg once daily on the QTcF interval was evaluated in a randomized, placebo-, and active- (moxifloxacin 400 mg once daily) controlled crossover study in 60 healthy adults, with 13 measurements over 24 hours at steady state. The maximum mean time-matched (95% upper confidence bound) differences in QTcF interval from placebo after baseline correction was 2 (5) milliseconds (i.e., below the threshold of clinical concern). In a thorough QT/QTc study in 48 healthy participants, TAF at the recommended dose and at a dose approximately 5 times the recommended dose, did not affect the QT/QTc interval and did not prolong the PR interval.

The effect of FTC on the QT interval is not known.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Clinical Trial Results in HIV-1 Virologically-Suppressed Subjects Who Switched to ODEFSEY In Trial 1216, the efficacy and safety of switching from emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) to ODEFSEY were evaluated in a randomized, double-blind study of virologically-suppressed adults with HIV-1. Participants were suppressed (HIV-1 RNA <50 copies/mL) on their baseline regimen of FTC/RPV/TDF for at least 6 months and had no documented resistance mutations to FTC, TAF, or RPV prior to study entry.

Participants were randomized in a 1:1 ratio to either switch to ODEFSEY (N=316) once daily or stay on FTC/RPV/TDF (N=314) once daily. Participants had a mean age of 45 years (range: 23–72), 90% were male, 75% were White, and 19% were Black. The mean baseline CD4+ cell count was 709 cells/mm 3 (range: 104–2527).

In Trial 1160, the efficacy and safety of switching from efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) to ODEFSEY were evaluated in a randomized, double-blind study of virologically-suppressed adults with HIV-1. Participants were stably suppressed (HIV-1 RNA <50 copies/mL) on their baseline regimen of EFV/FTC/TDF for at least 6 months and had no documented resistance mutations to FTC, TAF, or RPV prior to study entry. Participants were randomized in a 1:1 ratio to either switch to ODEFSEY (N=438) once daily or stay on EFV/FTC/TDF (N=437) once daily.

Participants had a mean age of 48 years (range: 19–76), 87% were male, 67% were White, and 27% were Black. The mean baseline CD4+ cell count was 700 cells/mm 3 (range: 140–1862). Treatment outcomes of Trials 1216 and 1160 are presented in Table 13.

Table 13 Virologic Outcomes of Trials 1216 and 1160 at Week 48 Week 48 window was between Day 295 and 378 (inclusive). in Virologically-Suppressed Participants who Switched to ODEFSEY Study 1216 Study 1160 ODEFSEY (N=316) FTC/RPV/TDF (N=313) One subject who was not on FTC/RPV/TDF prior to screening was excluded from the efficacy analysis. ODEFSEY (N=438) EFV/FTC/TDF (N=437) HIV-1 RNA <50 copies/mL 94% 94% 90% 92% HIV-1 RNA ≥50 copies/mL Included participants who had HIV-1 RNA ≥50 copies/mL in the Week 48 window; participants who discontinued early due to lack or loss of efficacy; participants who discontinued for reasons other than lack or loss of efficacy and at the time of discontinuation had a viral value of ≥50 copies/mL.

1% 0% 1% 1% No Virologic Data at Week 48 Window 6% 6% 9% 7% Discontinued Study Drug Due to AE or Death and Last Available HIV-1 RNA <50 copies/mL 2% 1% 3% 1% Discontinued Study Drug Due to Other Reasons and Last Available HIV-1 RNA <50 copies/mL Includes participants who discontinued for reasons other than an AE, death, or lack or loss of efficacy; e.g., withdrew consent, loss to follow-up, etc. 4% 4% 5% 5% Missing Data During Window but on Study Drug <1% 1% 1% 1%

14.2Clinical Trial Results for Adult Participants with no Antiretroviral Treatment History and Adults with Renal Impairment for Components of ODEFSEY The efficacy of RPV, FTC, and TAF in the treatment of HIV-1 infection in adults as initial therapy in those with no antiretroviral treatment history [see Indications and Usage (1) ] was established in trials of: RPV+FTC/TDF in adults with HIV-1 as initial therapy in those with no antiretroviral treatment history (n=550). The virologic response rate (i.e., HIV-1 RNA less than 50 copies per mL) was 77% at Week 96.

The virologic response rate at 96 weeks was 83% in participants with baseline HIV-1 RNA less than or equal to 100,000 copies per mL and 71% in participants with baseline HIV-1 RNA greater than 100,000 copies per mL. Further, the virologic response rate at 96 weeks among participants with baseline CD4+ cell counts less than 200 and greater than or equal to 200 cells/mm 3 were 68% and 82%, respectively. FTC+TAF with EVG+COBI in adults with HIV-1 as initial therapy in those with no antiretroviral treatment history (n=866).

The viro… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~3 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Emtricitabine: In long-term carcinogenicity studies of FTC, no drug-related increases in tumor incidence were found in mice at doses up to 750 mg per kg per day (23 times the human systemic exposure at the recommended dose of 200 mg per day in ODEFSEY) or in rats at doses up to 600 mg per kg per day (28 times the human systemic exposure at the recommended dose in ODEFSEY). FTC was not genotoxic in the reverse mutation bacterial test (Ames test), mouse lymphoma or mouse micronucleus assays.

FTC did not affect fertility in male rats at approximately 140 times or in male and female mice at approximately 60 times higher exposures (AUC) than in humans given the recommended 200 mg daily dose in ODEFSEY. Fertility was normal in the offspring of mice exposed daily from before birth (in utero) through sexual maturity at daily exposures (AUC) of approximately 60 times higher than human exposures at the recommended 200 mg daily dose in ODEFSEY. Rilpivirine: RPV was evaluated for carcinogenic potential by oral gavage administration to mice and rats up to 104 weeks.

Daily doses of 20, 60, and 160 mg per kg per day were administered to mice and doses of 40, 200, 500, and 1500 mg per kg per day were administered to rats. In rats, there were no drug-related neoplasms. In mice, RPV was positive for hepatocellular neoplasms in both males and females.

The observed hepatocellular findings in mice may be rodent-specific. At the lowest tested doses in the carcinogenicity studies, the systemic exposures (based on AUC) to RPV were 21 times (mice) and 3 times (rats) relative to those observed in humans at the recommended dose (25 mg once daily) in ODEFSEY. RPV has tested negative in the absence and presence of a metabolic activation system, in the in vitro Ames reverse mutation assay and in vitro clastogenicity mouse lymphoma assay.

RPV did not induce chromosomal damage in the in vivo micronucleus test in mice . In a study conducted in rats, there were no effects on mating or fertility with RPV up to 400 mg per kg per day, a dose of RPV that showed maternal toxicity. This dose is associated with an exposure that is approximately 40 times higher than the exposure in humans at the recommended dose of 25 mg once daily in ODEFSEY.

Tenofovir Alafenamide: Since TAF is rapidly converted to tenofovir and a lower tenofovir exposure in rats and mice was observed after TAF administration compared to TDF administration, carcinogenicity studies were conducted only with TDF. Long-term oral carcinogenicity studies of TDF in mice and rats were carried out at exposures up to approximately 10 times (mice) and 4 times (rats) those observed in humans at the recommended dose of TDF (300 mg) for HIV-1 infection. The tenofovir exposure in these studies was approximately 167 times (mice) and 55 times (rat) those observed in humans after administration of the daily recommended dose of ODEFSEY.

At the high dose in female mice, liver adenomas were increased at tenofovir exposures approximately 10 times (300 mg TDF) and 167 times (ODEFSEY) the exposure observed in humans. In rats, the study was negative for carcinogenic findings. TAF was not genotoxic in the reverse mutation bacterial test (Ames test), mouse lymphoma or rat micronucleus assays.

There were no effects on fertility, mating performance or early embryonic development when TAF was administered to male rats at a dose equivalent to 62 times the human dose based on body surface area comparisons for 28 days prior to mating and to female rats for 14 days prior to mating through Day 7 of gestation.

13.2Animal Toxicology and/or Pharmacology Minimal to slight infiltration of mononuclear cells in the posterior uvea was observed in dogs with similar severity after three- and nine-month administration of TAF; reversibility was seen after a three-month recovery period. No eye toxicity was observed in the dog at systemic exposures of 5 (TAF) and 1… [Excerpted — this section continues on DailyMed.]

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~3 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Emtricitabine: In long-term carcinogenicity studies of FTC, no drug-related increases in tumor incidence were found in mice at doses up to 750 mg per kg per day (23 times the human systemic exposure at the recommended dose of 200 mg per day in ODEFSEY) or in rats at doses up to 600 mg per kg per day (28 times the human systemic exposure at the recommended dose in ODEFSEY). FTC was not genotoxic in the reverse mutation bacterial test (Ames test), mouse lymphoma or mouse micronucleus assays.

FTC did not affect fertility in male rats at approximately 140 times or in male and female mice at approximately 60 times higher exposures (AUC) than in humans given the recommended 200 mg daily dose in ODEFSEY. Fertility was normal in the offspring of mice exposed daily from before birth (in utero) through sexual maturity at daily exposures (AUC) of approximately 60 times higher than human exposures at the recommended 200 mg daily dose in ODEFSEY. Rilpivirine: RPV was evaluated for carcinogenic potential by oral gavage administration to mice and rats up to 104 weeks.

Daily doses of 20, 60, and 160 mg per kg per day were administered to mice and doses of 40, 200, 500, and 1500 mg per kg per day were administered to rats. In rats, there were no drug-related neoplasms. In mice, RPV was positive for hepatocellular neoplasms in both males and females.

The observed hepatocellular findings in mice may be rodent-specific. At the lowest tested doses in the carcinogenicity studies, the systemic exposures (based on AUC) to RPV were 21 times (mice) and 3 times (rats) relative to those observed in humans at the recommended dose (25 mg once daily) in ODEFSEY. RPV has tested negative in the absence and presence of a metabolic activation system, in the in vitro Ames reverse mutation assay and in vitro clastogenicity mouse lymphoma assay.

RPV did not induce chromosomal damage in the in vivo micronucleus test in mice . In a study conducted in rats, there were no effects on mating or fertility with RPV up to 400 mg per kg per day, a dose of RPV that showed maternal toxicity. This dose is associated with an exposure that is approximately 40 times higher than the exposure in humans at the recommended dose of 25 mg once daily in ODEFSEY.

Tenofovir Alafenamide: Since TAF is rapidly converted to tenofovir and a lower tenofovir exposure in rats and mice was observed after TAF administration compared to TDF administration, carcinogenicity studies were conducted only with TDF. Long-term oral carcinogenicity studies of TDF in mice and rats were carried out at exposures up to approximately 10 times (mice) and 4 times (rats) those observed in humans at the recommended dose of TDF (300 mg) for HIV-1 infection. The tenofovir exposure in these studies was approximately 167 times (mice) and 55 times (rat) those observed in humans after administration of the daily recommended dose of ODEFSEY.

At the high dose in female mice, liver adenomas were increased at tenofovir exposures approximately 10 times (300 mg TDF) and 167 times (ODEFSEY) the exposure observed in humans. In rats, the study was negative for carcinogenic findings. TAF was not genotoxic in the reverse mutation bacterial test (Ames test), mouse lymphoma or rat micronucleus assays.

There were no effects on fertility, mating performance or early embryonic development when TAF was administered to male rats at a dose equivalent to 62 times the human dose based on body surface area comparisons for 28 days prior to mating and to female rats for 14 days prior to mating through Day 7 of gestation.

📄 Patient Package Insert ~3 min read ▾

Patient Information ODEFSEY ® (oh-DEF-see) (emtricitabine, rilpivirine and tenofovir alafenamide) tablets This Patient Information has been approved by the U.S. Food and Drug Administration Revised: 02/2025 Important: Ask your healthcare provider or pharmacist about medicines that should not be taken with ODEFSEY. For more information, see " What should I tell my healthcare provider before taking ODEFSEY? " What is the most important information I should know about ODEFSEY?

ODEFSEY can cause serious side effects, including: Worsening of hepatitis B virus (HBV) infection. Your healthcare provider will test you for HBV before or when you start treatment with ODEFSEY. If you have HBV and take ODEFSEY, your HBV may get worse (flare-up) if you stop taking ODEFSEY.

A "flare-up" is when your HBV suddenly returns in a worse way than before. Do not run out of ODEFSEY. Refill your prescription or talk to your healthcare provider before your ODEFSEY is all gone.

Do not stop taking ODEFSEY without first talking to your healthcare provider. If you stop taking ODEFSEY, your healthcare provider will need to check your health often and do blood tests regularly for several months to check your liver, and may give you a medicine to treat hepatitis B. Tell your healthcare provider about any new or unusual symptoms you may have after you stop taking ODEFSEY.

For more information about side effects, see " What are the possible side effects of ODEFSEY? " What is ODEFSEY? ODEFSEY is a prescription medicine that is used to treat human immunodeficiency virus-1 (HIV-1) infection in adults and children who weigh at least 55 pounds (25 kg): who have not received HIV-1 medicines in the past and who have an amount of HIV-1 in their blood (this is called "viral load") that is no more than 100,000 copies/mL, or to replace their current HIV-1 medicines for people whose healthcare provider determines that they meet certain requirements.

HIV-1 is the virus that causes Acquired Immune Deficiency Syndrome (AIDS). ODEFSEY contains the prescription medicines emtricitabine, rilpivirine and tenofovir alafenamide. It is not known if ODEFSEY is safe and effective in children who weigh less than 55 pounds (25 kg).

Who should not take ODEFSEY? Do not take ODEFSEY if you also take a medicine that contains: carbamazepine dexamethasone dexlansoprazole esomeprazole lansoprazole omeprazole oxcarbazepine pantoprazole sodium phenobarbital phenytoin rabeprazole rifampin rifapentine St. John's wort ( Hypericum perforatum ) or a product that contains St.

John's wort What should I tell my healthcare provider before taking ODEFSEY? Before taking ODEFSEY, tell your healthcare provider about all of your medical conditions, including if you: have liver problems, including HBV or hepatitis C virus have kidney problems have a history of depression or suicidal thoughts are pregnant or plan to become pregnant. It is not known if ODEFSEY can harm your unborn baby.

Tell your healthcare provider if you become pregnant during treatment with ODEFSEY. Pregnancy Registry: There is a pregnancy registry for those who take ODEFSEY during pregnancy. The purpose of this registry is to collect information about the health of you and your baby.

Talk with your healthcare provider about how you can take part in this registry. are breastfeeding or plan to breastfeed. Two of the medicines in ODEFSEY can pass to your baby in your breast milk. It is not known if the other medicine in ODEFSEY can pass into your breast milk.

Talk to your healthcare provider about the following risks of breastfeeding during treatment with ODEFSEY: The HIV-1 virus may pass to your baby if your baby does not have HIV-1. The HIV-1 virus may become harder to treat if your baby has HIV-1. Your baby may get side effects from ODEFSEY.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines may interact with ODEFSEY. Keep a li… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 14 words ▾

Indications and Usage ( 1 ) 02/2025 Dosage and Administration ( 2.2 ) 02/2025

📄 Package Label / Principal Display Panel 51 words ▾

PRINCIPAL DISPLAY PANEL - 30 Tablet Bottle Label NDC 61958- 2101 -1 30 tablets Odefsey ® (emtricitabine, rilpivirine, and tenofovir alafenamide) Tablets 200 mg/25 mg/25 mg Note to pharmacist: Do not cover ALERT box with pharmacy label. ALERT: Find out about medicines that should NOT be taken with Odefsey ® odefsey-04.jpg

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
43.5K
Units reimbursed last 4 qtrs
1.5M
Gross reimbursed last 4 qtrs
$187.77M
Avg / prescription
$4,320.10
Avg / unit
$124.81
Latest quarter Q1 2026
9.5KRx
Medicaid pays / ea
$124.81
gross reimbursed
vs
NADAC / ea
$130.49
acquisition cost
=
Spread
−$5.6862
-4% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
55% FFS 45% MCO
Fee-for-service · 24,026 Rx Managed care · 19,439 Rx
State Medicaid map
Alaska: 840 units · 115 per 100k residents AK Maine: 4,620 units · 331 per 100k residents ME Washington: 18,900 units · 242 per 100k residents WA Idaho: no data reported ID Montana: 1,050 units · 92.8 per 100k residents MT North Dakota: no data reported ND Minnesota: 9,780 units · 170 per 100k residents MN Wisconsin: 6,968 units · 118 per 100k residents WI Michigan: 42,210 units · 421 per 100k residents MI New York: 433,309 units · 2,214 per 100k residents NY Vermont: 1,650 units · 255 per 100k residents VT New Hampshire: 3,584 units · 256 per 100k residents NH Oregon: 18,720 units · 442 per 100k residents OR Nevada: 8,850 units · 277 per 100k residents NV Wyoming: no data reported WY South Dakota: 750 units · 81.6 per 100k residents SD Iowa: 6,510 units · 203 per 100k residents IA Illinois: 44,610 units · 355 per 100k residents IL Indiana: 10,890 units · 159 per 100k residents IN Ohio: 27,367 units · 232 per 100k residents OH Pennsylvania: 83,404 units · 643 per 100k residents PA New Jersey: 45,930 units · 494 per 100k residents NJ Massachusetts: 41,068 units · 587 per 100k residents MA California: 212,274 units · 545 per 100k residents CA Utah: 1,290 units · 37.8 per 100k residents UT Colorado: 10,860 units · 185 per 100k residents CO Nebraska: 1,680 units · 84.9 per 100k residents NE Missouri: 26,010 units · 420 per 100k residents MO Kentucky: 3,302 units · 73.0 per 100k residents KY West Virginia: 3,540 units · 200 per 100k residents WV Virginia: 29,610 units · 340 per 100k residents VA Maryland: 51,630 units · 835 per 100k residents MD Connecticut: 32,310 units · 893 per 100k residents CT Rhode Island: 5,130 units · 468 per 100k residents RI Arizona: 16,934 units · 228 per 100k residents AZ New Mexico: 3,900 units · 184 per 100k residents NM Kansas: 1,140 units · 38.8 per 100k residents KS Arkansas: 1,110 units · 36.2 per 100k residents AR Tennessee: 12,660 units · 178 per 100k residents TN North Carolina: 59,040 units · 545 per 100k residents NC South Carolina: 5,850 units · 109 per 100k residents SC Delaware: 4,650 units · 451 per 100k residents DE Oklahoma: 6,210 units · 153 per 100k residents OK Louisiana: 30,570 units · 668 per 100k residents LA Mississippi: 4,710 units · 160 per 100k residents MS Alabama: 12,030 units · 236 per 100k residents AL Georgia: 16,065 units · 146 per 100k residents GA D.C.: 30,450 units · 4,485 per 100k residents DC Hawaii: 4,950 units · 345 per 100k residents HI Texas: 24,855 units · 81.5 per 100k residents TX Florida: 35,364 units · 156 per 100k residents FL
Units reimbursed · per 100k residents
36.24,485
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 D.C. 4,485 /100k
2 New York 2,214 /100k
3 Connecticut 893 /100k
4 Maryland 835 /100k
5 Louisiana 668 /100k
6 Pennsylvania 643 /100k
7 Massachusetts 587 /100k
8 North Carolina 545 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Odefsey — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Odefsey. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$93.11M
Claims incl. refills
22.4K
Beneficiaries
8.7K
Spend / beneficiary
$10,717.59
Spend / claim
$4,162.28
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.
← 61958-2005-01 · Gilead 61958-2201-01 · Gilead →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.