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ALYFTREK vanzacaftor, tezacaftor, and deutivacaftor 10 mg; 50 mg; 125 mg Tablet, Film Coated — NDC 51167-0121-01 package photo

ALYFTREK vanzacaftor, tezacaftor, and deutivacaftor 10 mg; 50 mg; 125 mg Tablet, Film Coated

by Vertex Pharmaceuticals Incorporated · 4 BLISTER PACK in 1 CARTON (51167-121-01) / 14 TABLET, FILM COATED in 1 BLISTER PACK
NDC 51167-0121-01
🏷️ FDA NDC (as labeled) 51167-121-01 billing pads the product segment with a zero
Rx only Brand On market Non-controlled
🗂️ Data synced Sep 17, 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

🆔 Identity & classification

FDA NDC (as labeled) 51167-121-01
Product NDC 51167-121
11-digit billing NDC 51167012101
NCPDP billing unit EA — each (per item)
RxCUI 2701438, 2701444, 2701448, 2701450
UNII SHA6U5FJZL, COM1POP492, 8RW88Y506K
Application # NDA218730
SPL Set ID 7e635909-c6fd-4f0d-ae77-cdff03653a20
Established class (EPC) Cystic Fibrosis Transmembrane Conductance Regulator Potentiator
Mechanism of action Chloride Channel Activation Potentiators; Cytochrome P450 2C9 Inhibitors; P-Glycoprotein Inhibitors; Breast Cancer Resistance Protein Inhibitors
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2024-12-20
Route ORAL
Dosage form TABLET, FILM COATED
Substance VANZACAFTOR; TEZACAFTOR; DEUTIVACAFTOR
GCN Seq No 086964
GCN 56769
HICL code 050120
Ingredient (HICL) Vanzacaftor/Tezacaf/Deutivacaf
HIC1 code B
Therapeutic class — broad (HIC1) Respiratory System
HIC2 code B0
Therapeutic class — intermediate (HIC2) Effect Entire Respiratory System
HIC3 code B0F
Therapeutic class — specific (HIC3) Cystic Fibrosis-Cftr Potentiator-Corrector Combin.
AHFS code 48:14.04.00
AHFS class Cystic Fibrosis (Cftr) Correctors
FDB label name ALYFTREK 10-50-125 MG TABLET
FDB brand name Alyftrek
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 51167-121-01 — a 5-3-2 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 product segment → 51167-0121-01. 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 Other respiratory system products class.

Drug family (ATC) Other respiratory system products
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.

🏭 Manufacturer & labeler

LabelerVertex Pharmaceuticals Incorporated
Application holderVERTEX PHARMACEUTICALS INC
FDA applicationNDA218730 (NDA)
Labeler code51167
First marketedDec 2024
Product typeHuman Prescription Drug
Portfolio21 products on file
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.

🩺 Clinical

Label name ALYFTREK 10-50-125 MG TABLET Ingredient Vanzacaftor/Tezacaf/Deutivacaf
📖 What it is MedlinePlus · NLM

Vanzacaftor, tezacaftor, and deutivacaftor is used to treat certain types of cystic fibrosis (CF; an inherited condition that affects the lungs and other parts of the body). Vanzacaftor and tezacaftor are in a class of medications called cystic fibrosis transmembrane conductance regulator (CFTR) correctors. Deutivacaftor is in a class of medications called cystic fibrosis transmembrane conductance regulator (CFTR) potentiators. These medications work together to improve the function of a protein in the body to help decrease the build-up of thick mucus in the lungs and manage other CF symptoms...

Read the full MedlinePlus article ↗

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.

💊 What it looks like

Color Purple
ShapeOval
ImprintV10
Size15 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 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 H3R47K3TBD
    FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
  • UNII 1K09F3G675
    Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
  • UNII 9XZ8H6N6OH
    A plant-based cellulose derivative used as a binder to hold tablet ingredients together, a thickener in liquids, and a coating agent to control how fast the medicine dissolves.
  • UNII 36SFW2JZ0W
    Hypromellose 2910 is a plant-based thickening agent derived from cellulose. In medicines, it forms a protective coating on tablets or capsules and controls how quickly the drug dissolves and releases into your body.
  • UNII 6N003M473W
    Hypromellose acetate succinate is a modified cellulose polymer that dissolves in the small intestine. It's used as a coating material to protect the medicine from stomach acid and control where and when the drug is released in the digestive tract.
  • UNII 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
  • 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 368GB5141J
    A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
  • 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.

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.

💲 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 eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $499.98 $27,998.93 / 56 tablets
Medicare drug plans payPart D · Q2 2026 $514.98 $28,839.01 / 56 tablets
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.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Alyftrek 10 mg/1; 50 mg/1; 125 mgthis 51167-0121-01 Vertex 14 tablets — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
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

🏛️
2024
First FDA approval
Dec 2024
📍
2026
Currently FDA-listed
2 years listed
🛡️
2043
Latest patent/protection listed
not a guaranteed launch date
🔒No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Jan 2043. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Dec 20, 2024 RLD RS ⏳ ~16.3 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.

Patents & exclusivity — FDA Orange Book
US 9670163 — method of use (U-4080)
US 9670163 — method of use (U-4080)
US 10022352 — method of use (U-4081)
US 10022352 — method of use (U-4081)
US 9974781 — method of use (U-4082)
US 9974781 — method of use (U-4082)
US 11873300 — drug substance (U-4083)
US 11873300 — drug substance (U-4083)
US 8415387 — method of use (U-4082)
US 8415387 — method of use (U-4082)
US 10081621 — method of use (U-4087)
US 10081621 — method of use (U-4087)
US 12186306 — method of use (U-4088)
US 11951212 — method of use (U-4089)
US 11866450 — method of use (U-4082)
US 11866450 — method of use (U-4082)
US 8598181 — method of use (U-4090)
US 8598181 — method of use (U-4090)
US 8354427 — method of use (U-4091)
US 8354427 — method of use (U-4091)
US 10206877 — method of use (U-4092)
US 9181192 — drug substance (U-4094)
US 9181192 — drug substance (U-4094)
US 8324242 — method of use (U-4090)
US 8324242 — method of use (U-4090)
US 10239867 — drug substance (U-4090)
US 10239867 — drug substance (U-4090)
US 11564916 — method of use (U-4095)
US 11564916 — method of use (U-4095)
US 11639347 — drug substance (U-4090)
US 11639347 — drug substance (U-4090)
US 11578062 — method of use (U-4096)
US 11578062 — method of use (U-4096)
US 9012496 — method of use (U-4097)
US 9512079 — drug substance (U-4098)
US 9512079 — drug substance (U-4098)
US 9931334 — method of use (U-4080)
US 9931334 — method of use (U-4080)
US 10058546 — method of use (U-4218)
US 11873300 — drug substance (U-4462)
US 11873300 — drug substance (U-4462)
US 11866450 — method of use (U-4463)
US 11866450 — method of use (U-4463)
US 11639347 — drug substance (U-4464)
US 11639347 — drug substance (U-4464)
US 11578062 — method of use (U-4465)
US 11578062 — method of use (U-4465)
US 11564916 — method of use (U-4466)
US 11564916 — method of use (U-4466)
US 10239867 — drug substance (U-4464)
US 10239867 — drug substance (U-4464)
US 10206877 — method of use (U-4467)
US 10081621 — method of use (U-4468)
US 10081621 — method of use (U-4468)
US 9974781 — method of use (U-4463)
US 9974781 — method of use (U-4463)
US 9931334 — method of use (U-4469)
US 9931334 — method of use (U-4469)
US 9670163 — method of use (U-4470)
US 9670163 — method of use (U-4470)
US 9512079 — drug substance (U-4471)
US 9512079 — drug substance (U-4471)
US 9181192 — drug substance (U-4472)
US 9181192 — drug substance (U-4472)
US 8598181 — method of use (U-4463)
US 8598181 — method of use (U-4463)
US 8415387 — method of use (U-4463)
US 8415387 — method of use (U-4463)
US 8324242 — method of use (U-4464)
US 8324242 — method of use (U-4464)
US 12186306 — method of use (U-4460)
US 11951212 — method of use (U-4461)
US 10646481 — drug product
US 8623905 — drug substance
US 11066417 — drug substance
US 8865902 — drug substance
US 8754224 — drug substance
US 7776905 — drug substance
US RE50453 — drug substance
US 7776905 — drug substance
US 7645789 — drug substance
US 7495103 — drug substance
US 7645789 — drug substance
US 8623905 — drug substance
US 10646481 — drug product
US 10047053 — drug substance
US 8865902 — drug substance
US 11066417 — drug substance
US 10047053 — drug substance
US 8410274 — drug product
US 7495103 — drug substance
US RE50453 — drug substance
US 8754224 — drug substance
US 8410274 — drug product
Exclusivity NCE
Exclusivity ODE-526
Exclusivity ODE-536
Exclusivity NCE
Exclusivity ODE-526
Exclusivity ODE-536
2024 2026 2028 2030 2032 2034 2036 2038 2040 2042
Today
LOE
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 (94)
PatentTypeUse codeExpires
US 9670163 ↗ Method of use U-4080 Dec 28, 2026
US 9670163 ↗ Method of use U-4080 Dec 28, 2026
US 10022352 ↗ Method of use U-4081 Apr 9, 2027
US 10022352 ↗ Method of use U-4081 Apr 9, 2027
US 9974781 ↗ Method of use U-4082 Apr 9, 2027
US 9974781 ↗ Method of use U-4082 Apr 9, 2027
US 11873300 ↗ Drug substance U-4083 Aug 13, 2040
US 11873300 ↗ Drug substance U-4083 Aug 13, 2040
US 8415387 ↗ Method of use U-4082 Nov 12, 2027
US 8415387 ↗ Method of use U-4082 Nov 12, 2027
US 10081621 ↗ Method of use U-4087 Mar 25, 2031
US 10081621 ↗ Method of use U-4087 Mar 25, 2031
US 12186306 ↗ Method of use U-4088 Jan 10, 2043
US 11951212 ↗ Method of use U-4089 Apr 14, 2035
US 11866450 ↗ Method of use U-4082 Feb 14, 2039
US 11866450 ↗ Method of use U-4082 Feb 14, 2039
US 8598181 ↗ Method of use U-4090 May 1, 2027
US 8598181 ↗ Method of use U-4090 May 1, 2027
US 8354427 ↗ Method of use U-4091 Jul 6, 2026
US 8354427 ↗ Method of use U-4091 Jul 6, 2026
US 10206877 ↗ Method of use U-4092 Apr 14, 2035
US 9181192 ↗ Drug substance U-4094 May 17, 2032
US 9181192 ↗ Drug substance U-4094 May 17, 2032
US 8324242 ↗ Method of use U-4090 Aug 5, 2027
US 8324242 ↗ Method of use U-4090 Aug 5, 2027
US 10239867 ↗ Drug substance U-4090 Apr 9, 2027
US 10239867 ↗ Drug substance U-4090 Apr 9, 2027
US 11564916 ↗ Method of use U-4095 Aug 13, 2029
US 11564916 ↗ Method of use U-4095 Aug 13, 2029
US 11639347 ↗ Drug substance U-4090 Apr 9, 2027
US 11639347 ↗ Drug substance U-4090 Apr 9, 2027
US 11578062 ↗ Method of use U-4096 Mar 25, 2031
US 11578062 ↗ Method of use U-4096 Mar 25, 2031
US 9012496 ↗ Method of use U-4097 Jul 15, 2033
US 9512079 ↗ Drug substance U-4098 May 17, 2032
US 9512079 ↗ Drug substance U-4098 May 17, 2032
US 9931334 ↗ Method of use U-4080 Dec 28, 2026
US 9931334 ↗ Method of use U-4080 Dec 28, 2026
US 10058546 ↗ Method of use U-4218 Jul 15, 2033
US 11873300 ↗ Drug substance U-4462 Aug 13, 2040
US 11873300 ↗ Drug substance U-4462 Aug 13, 2040
US 11866450 ↗ Method of use U-4463 Feb 14, 2039
US 11866450 ↗ Method of use U-4463 Feb 14, 2039
US 11639347 ↗ Drug substance U-4464 Apr 9, 2027
US 11639347 ↗ Drug substance U-4464 Apr 9, 2027
US 11578062 ↗ Method of use U-4465 Mar 25, 2031
US 11578062 ↗ Method of use U-4465 Mar 25, 2031
US 11564916 ↗ Method of use U-4466 Aug 13, 2029
US 11564916 ↗ Method of use U-4466 Aug 13, 2029
US 10239867 ↗ Drug substance U-4464 Apr 9, 2027
US 10239867 ↗ Drug substance U-4464 Apr 9, 2027
US 10206877 ↗ Method of use U-4467 Apr 14, 2035
US 10081621 ↗ Method of use U-4468 Mar 25, 2031
US 10081621 ↗ Method of use U-4468 Mar 25, 2031
US 9974781 ↗ Method of use U-4463 Apr 9, 2027
US 9974781 ↗ Method of use U-4463 Apr 9, 2027
US 9931334 ↗ Method of use U-4469 Dec 28, 2026
US 9931334 ↗ Method of use U-4469 Dec 28, 2026
US 9670163 ↗ Method of use U-4470 Dec 28, 2026
US 9670163 ↗ Method of use U-4470 Dec 28, 2026
US 9512079 ↗ Drug substance U-4471 May 17, 2032
US 9512079 ↗ Drug substance U-4471 May 17, 2032
US 9181192 ↗ Drug substance U-4472 May 17, 2032
US 9181192 ↗ Drug substance U-4472 May 17, 2032
US 8598181 ↗ Method of use U-4463 May 1, 2027
US 8598181 ↗ Method of use U-4463 May 1, 2027
US 8415387 ↗ Method of use U-4463 Nov 12, 2027
US 8415387 ↗ Method of use U-4463 Nov 12, 2027
US 8324242 ↗ Method of use U-4464 Aug 5, 2027
US 8324242 ↗ Method of use U-4464 Aug 5, 2027
US 12186306 ↗ Method of use U-4460 Jan 10, 2043
US 11951212 ↗ Method of use U-4461 Apr 14, 2035
US 10646481 ↗ Drug product — Aug 13, 2029
US 8623905 ↗ Drug substance — May 1, 2027
US 11066417 ↗ Drug substance — Feb 14, 2039
US 8865902 ↗ Drug substance — May 17, 2032
US 8754224 ↗ Drug substance — Dec 28, 2026
US 7776905 ↗ Drug substance — Jun 3, 2027
US RE50453 ↗ Drug substance — Jul 10, 2031
US 7776905 ↗ Drug substance — Jun 3, 2027
US 7645789 ↗ Drug substance — May 1, 2027
US 7495103 ↗ Drug substance — May 20, 2027
US 7645789 ↗ Drug substance — May 1, 2027
US 8623905 ↗ Drug substance — May 1, 2027
US 10646481 ↗ Drug product — Aug 13, 2029
US 10047053 ↗ Drug substance — May 17, 2032
US 8865902 ↗ Drug substance — May 17, 2032
US 11066417 ↗ Drug substance — Feb 14, 2039
US 10047053 ↗ Drug substance — May 17, 2032
US 8410274 ↗ Drug product — Dec 28, 2026
US 7495103 ↗ Drug substance — May 20, 2027
US RE50453 ↗ Drug substance — Jul 10, 2031
US 8754224 ↗ Drug substance — Dec 28, 2026
US 8410274 ↗ Drug product — Dec 28, 2026
FDA exclusivity
CodeWhat it grantsExpires
NCENew Chemical Entity (5-year)Dec 20, 2029
ODE-526Orphan Drug Exclusivity (7-year)Dec 20, 2031
ODE-536Orphan Drug Exclusivity (7-year)Mar 27, 2033
NCENew Chemical Entity (5-year)Dec 20, 2029
ODE-526Orphan Drug Exclusivity (7-year)Dec 20, 2031
ODE-536Orphan Drug Exclusivity (7-year)Mar 27, 2033
Common questions
Is there a generic version of ALYFTREK 10-50-125 MG TABLET?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for ALYFTREK 10-50-125 MG TABLET. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Jan 2043 — an estimate, not a guaranteed launch date.
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.

🗺️ 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 51167-0121-01, 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 – Q4 2025 · 4 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
3.9K
Units reimbursed last 4 qtrs
216.3K
Gross reimbursed last 4 qtrs
$108.15M
Avg / prescription
$27,560.11
Avg / unit
$499.98
Latest quarter Q4 2025
1.6KRx
Fee-for-service vs managed care ⓘ
51% FFS 49% MCO
Fee-for-service · 2,006 Rx Managed care · 1,918 Rx
State Medicaid map
Alaska: 1,512 units · 206 per 100k residents AK Maine: 3,136 units · 225 per 100k residents ME Washington: 8,008 units · 103 per 100k residents WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: 2,296 units · 40.0 per 100k residents MN Wisconsin: 7,084 units · 120 per 100k residents WI Michigan: 4,592 units · 45.8 per 100k residents MI New York: 10,976 units · 56.1 per 100k residents NY Vermont: no data reported VT New Hampshire: 1,680 units · 120 per 100k residents NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: 2,072 units · 64.6 per 100k residents IA Illinois: 6,440 units · 51.3 per 100k residents IL Indiana: 10,584 units · 154 per 100k residents IN Ohio: 7,532 units · 63.9 per 100k residents OH Pennsylvania: 21,112 units · 163 per 100k residents PA New Jersey: 3,752 units · 40.4 per 100k residents NJ Massachusetts: 3,472 units · 49.6 per 100k residents MA California: 16,912 units · 43.4 per 100k residents CA Utah: no data reported UT Colorado: 19,432 units · 331 per 100k residents CO Nebraska: 784 units · 39.6 per 100k residents NE Missouri: 616 units · 9.9 per 100k residents MO Kentucky: 2,688 units · 59.4 per 100k residents KY West Virginia: 1,960 units · 111 per 100k residents WV Virginia: 2,352 units · 27.0 per 100k residents VA Maryland: 4,256 units · 68.9 per 100k residents MD Connecticut: 6,104 units · 169 per 100k residents CT Rhode Island: no data reported RI Arizona: 1,680 units · 22.6 per 100k residents AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: 3,416 units · 47.9 per 100k residents TN North Carolina: 5,152 units · 47.5 per 100k residents NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: 2,688 units · 66.3 per 100k residents OK Louisiana: 8,232 units · 180 per 100k residents LA Mississippi: no data reported MS Alabama: 7,392 units · 145 per 100k residents AL Georgia: 1,988 units · 18.0 per 100k residents GA D.C.: no data reported DC Hawaii: no data reported HI Texas: 13,776 units · 45.2 per 100k residents TX Florida: 22,624 units · 100 per 100k residents FL
Units reimbursed · per 100k residents
9.9331
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 Colorado 331 /100k
2 Maine 225 /100k
3 Alaska 206 /100k
4 Louisiana 180 /100k
5 Connecticut 169 /100k
6 Pennsylvania 163 /100k
7 Indiana 154 /100k
8 Alabama 145 /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 Alyftrek — 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 Alyftrek. 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
$46.14M
Claims incl. refills
1.6K
Beneficiaries
646
Spend / beneficiary
$71,426.10
Spend / claim
$28,015.34
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.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for ALYFTREK (this brand).

Top reported reactions

Hospitalisation47
Rash43
Headache42
Anxiety40
Fatigue39
Dyspnoea35
Diarrhoea31

Age at onset

Child9
Adolescent19
Adult127
Elderly4

Reporter sex

666 reports
Male · 34%
Female · 66%

Serious outcomes

Hospitalization162
Reports over time (by year) — tap or hover for the count & year
2024 2025 2026 344 2
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
51167-0121-01 You're viewing this 4 BLISTER PACK in 1 CARTON (51167-121-01) / 14 TABLET, FILM COATED in 1 BLISTER PACK 2024-12-20 Active

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) ✓ Available
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 51167-121-01, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 51167-0121-01, written without dashes as 51167012101. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 51167-0121-01, the first segment (51167) is the labeler code FDA assigned to Vertex Pharmaceuticals Incorporated; the middle segment (0121) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (01) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Vertex Pharmaceuticals Incorporated. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Vertex Pharmaceuticals Incorporated is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. 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 💬 Medication Guide
🚨 Boxed Warning ~2 min read ▾

WARNING: DRUG-INDUCED LIVER INJURY AND LIVER FAILURE Elevated transaminases have been observed in patients treated with ALYFTREK. Cases of serious and potentially fatal drug-induced liver injury and liver failure were reported in patients who were taking a fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor, which contains the same or similar active ingredients as ALYFTREK. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of elexacaftor/tezacaftor/ivacaftor [see Warnings and Precautions (5.1) and Adverse Reactions (6) ].

Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating ALYFTREK, every month during the first 6 months of treatment, then every 3 months for the next 12 months, then at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or elevated liver function tests at baseline [see Dosage and Administration (2.1) , Warnings and Precautions (5.1) , Adverse Reactions (6) , and Use in Specific Populations (8.7) ] . Interrupt ALYFTREK for significant elevations in liver function tests or in the event of signs or symptoms of liver injury.

Consider referral to a hepatologist. Follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If abnormalities resolve, resume treatment only if the benefit is expected to outweigh the risk.

Closer monitoring is advised after resuming ALYFTREK [see Warnings and Precautions (5.1) ] . ALYFTREK should not be used in patients with severe hepatic impairment (Child-Pugh Class C). ALYFTREK is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B) and should only be considered when there is a clear medical need, and the benefit outweighs the risk.

If used, monitor patients closely [see Dosage and Administration (2.4) , Warnings and Precautions (5.1) , Adverse Reactions (6) , Use in Specific Populations (8.7) , and Clinical Pharmacology (12.3) ] . WARNING: DRUG-INDUCED LIVER INJURY AND LIVER FAILURE See full prescribing information for complete boxed warning. Elevated transaminases have been observed in patients treated with ALYFTREK ( 5.1 , 6 ).

Cases of serious and potentially fatal drug-induced liver injury and liver failure leading to transplantation and death were reported in patients who were taking ELX/TEZ/IVA, a drug containing the same or similar active ingredients as ALYFTREK ( 5.1 ). Assess liver function tests (ALT, AST, alkaline phosphatase, bilirubin) in all patients prior to initiating ALYFTREK, every month for first 6 months, every 3 months for next 12 months, then at least annually ( 2.1 , 5.1 ). Interrupt ALYFTREK for significant elevations in LFTs or signs or symptoms of liver injury.

Follow patients closely with clinical and laboratory monitoring until abnormalities resolve ( 5.1 ). Resume ALYFTREK if abnormalities resolve and only if the benefit is expected to outweigh the risk ( 5.1 ). ALYFTREK should not be used in patients with severe hepatic impairment (Child-Pugh Class C).

ALYFTREK is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B) ( 2.4 , 5.1 , 8.7 , 12.3 ).

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE ALYFTREK is indicated for the treatment of cystic fibrosis (CF) in adult and pediatric patients 6 years of age and older who have a clinical diagnosis of CF and who have at least one variant in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene that is either responsive based on clinical and/or in vitro data (see Table 5 ) or results in production of CFTR protein [see Clinical Pharmacology (12.1) ]. If the patient's genotype is unknown, an FDA-cleared CF genetic test should be used to confirm the presence of at least one variant in the CFTR gene that is either responsive based on clinical and/or in vitro data or results in production of CFTR protein.

ALYFTREK is a combination of deutivacaftor, a CFTR potentiator, tezacaftor, and vanzacaftor indicated for the treatment of cystic fibrosis (CF) in adult and pediatric patients aged 6 years and older who have a clinical diagnosis of CF and who have at least one variant in the CFTR gene that is either responsive based on clinical and/or in vitro data or results in production of CFTR protein. ( 1 , 12.1 ) If the patient's genotype is unknown, an FDA-cleared CF genetic test should be used to confirm the presence of at least one variant in the CFTR gene that is either responsive based on clinical and/or in vitro data or results in production of CFTR protein.

( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Prior to initiating ALYFTREK obtain liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients. Monitor liver function tests every month during the first 6 months of treatment, then every 3 months during the next 12 months, then at least annually thereafter. ( 2.1 , 5.1 ) Recommended Dosage for Adult and Pediatric Patients Aged 6 Years and Older (with fat-containing food) ( 2.2 ) Age Weight Once Daily Oral Dosage 6 to less than 12 years old Less than 40 kg Three tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg Greater than or equal to 40 kg Two tablets of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg 12 years and older Any Weight Two tablets of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg Should not be used in patients with severe hepatic impairment.

Use not recommended in patients with moderate hepatic impairment unless the benefit outweighs the risk. If used, no dose adjustment is recommended. Liver function tests should be closely monitored.

( 2.4 , 5.1 , 6.1 , 8.7 ) See full prescribing information for dosage modifications for concomitant use of ALYFTREK with strong or moderate CYP3A inhibitors. ( 2.3 , 5.7 , 7.1 )

2.1Recommended Laboratory Testing Prior to ALYFTREK Initiation and During Treatment Prior to initiating ALYFTREK, obtain liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) for all patients. Monitor liver function tests every month during the first 6 months of treatment, then every 3 months for the next 12 months, then at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease, elevated liver function tests at baseline, or a history of elevated liver function tests with drugs containing elexacaftor, tezacaftor, and/or ivacaftor [see Warnings and Precautions (5.1) and Use in Specific Populations (8.7) ].

2.2Recommended Dosage The recommended ALYFTREK dosage in adult and pediatric patients aged 6 years and older is provided in Table 1. Administer ALYFTREK orally (swallow the tablets whole) with fat-containing food, once daily, at approximately the same time each day [see Clinical Pharmacology (12.3) ]. Examples of meals or snacks that contain fat are those prepared with butter or oils or those containing eggs, peanut butter, cheeses, nuts, whole milk, or meats.

Table 1: Recommended Dosage of ALYFTREK in Adult and Pediatric Patients Aged 6 Years and Older Age Weight Once Daily Oral Dosage 6 to less than 12 years old Less than 40 kg Three tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg (total dose of vanzacaftor 12 mg/tezacaftor 60 mg/ deutivacaftor 150 mg) Greater than or equal to 40 kg Two tablets of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg (total dose of vanzacaftor 20 mg/tezacaftor 100 mg/ deutivacaftor 250 mg) 12 years and older Any weight Two tablets of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg (total dose of vanzacaftor 20 mg/tezacaftor 100 mg/ deutivacaftor 250 mg)

2.3Dosage Modification for Strong or Moderate CYP3A Inhibitors Table 2 describes the recommended dosage modification for ALYFTREK when used concomitantly with strong or moderate CYP3A inhibitors [see Warnings and Precautions (5.7) ] . Administer ALYFTREK orally (swallow the tablets whole) with fat-containing food, once daily, at approximately the same time each day [see Clinical Pharmacology (12.3) ]. Table 2: Dosage Modification for Concomitant Use of ALYFTREK with Strong or Moderate CYP3A Inhibitors in Adult and Pediatric Patients Aged 6 Years and Older Age Weight Moderate CYP3A Inhibitors Strong CYP3A Inhibitors 6 to less than 12 years old Less than 40 kg Two tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg every other day (total dose of vanzacaftor 8 mg/tezacaftor 40 mg/deutivacaftor 100 mg) Two tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg once a week (total dose of vanzacaftor 8 mg/tezacaftor 40 mg/deuti…

💊 Dosage Forms and Strengths 115 words ▾

3 DOSAGE FORMS AND STRENGTHS Tablets: Fixed-dose combination containing vanzacaftor 4 mg, tezacaftor 20 mg, and deutivacaftor 50 mg. ( 3 ) Fixed-dose combination containing vanzacaftor 10 mg, tezacaftor 50 mg, and deutivacaftor 125 mg. ( 3 ) Tablets: Fixed-dose combination containing vanzacaftor 4 mg (equivalent to 4.24 mg of vanzacaftor calcium dihydrate), tezacaftor 20 mg, and deutivacaftor 50 mg.

Each tablet is purple, round-shaped, film-coated, debossed with "V4" on one side and plain on the other. Fixed-dose combination containing vanzacaftor 10 mg (equivalent to 10.6 mg of vanzacaftor calcium dihydrate), tezacaftor 50 mg, and deutivacaftor 125 mg. Each tablet is purple, oblong-shaped, film-coated, debossed with "V10" on one side and plain on the other.

⛔ Contraindications 7 words ▾

4 CONTRAINDICATIONS None. None. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Drug-Induced Liver Injury and Liver Failure : Elevated transaminases have been observed in patients treated with ALYFTREK. Cases of serious and potentially fatal drug-induced liver injury and liver failure have been reported with a drug that contains the same or similar active ingredients as ALYFTREK. Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating and throughout treatment with ALYFTREK.

Interrupt ALYFTREK in the event of significant elevations in liver function tests or signs or symptoms of liver injury. ALYFTREK should not be used in patients with severe hepatic impairment (Child-Pugh Class C). ALYFTREK is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B).

( 2.4 , 5.1 , 8.7 ) Hypersensitivity Reactions : Hypersensitivity reactions, including anaphylaxis, have been reported in the postmarketing setting for drugs containing elexacaftor, tezacaftor, and/or ivacaftor. If signs or symptoms of serious hypersensitivity reactions develop during ALYFTREK treatment, discontinue ALYFTREK and initiate appropriate therapy. ( 5.2 ) Patients Who Discontinued or Interrupted Elexacaftor-, Tezacaftor-, or Ivacaftor-Containing Drugs Due to Adverse Reactions : Consider benefits and risks before using ALYFTREK in patients who discontinued or interrupted elexacaftor-, tezacaftor-, or ivacaftor-containing drugs due to adverse reactions.

If ALYFTREK is used, closely monitor for adverse reactions as clinically appropriate. ( 5.3 ) Intracranial Hypertension : Intracranial hypertension (IH) has been reported in the postmarketing setting with use of drugs containing the same or similar active ingredients as ALYFTREK. If an unusual headache or visual disturbances occur during treatment, and IH is suspected, interrupt ALYFTREK and refer for prompt medical evaluation.

( 5.4 ) Neuropsychiatric Events, Including Suicidal Thoughts and Behaviors: Serious neuropsychiatric events, including symptoms of anxiety, depression, suicidal ideation and behavior, and sleep disturbances, have been reported in the postmarketing setting for ALYFTREK or drugs containing the same or similar active ingredients. Monitor patients closely for new or worsening symptoms. Consider the risks and benefits for the individual patient to determine if therapy with ALYFTREK should be interrupted at the occurrence of neuropsychiatric symptoms.

( 5.5 ) Reduced Effectiveness in Patients with Concomitant Use with CYP3A Inducers : Concomitant use with strong and moderate CYP3A inducers decreased vanzacaftor, tezacaftor, and deutivacaftor exposure, which may reduce ALYFTREK efficacy. Therefore, concomitant use is not recommended. ( 5.6 , 7.1 ) Adverse Reactions with Concomitant Use with CYP3A Inhibitors : Concomitant use with strong or moderate CYP3A inhibitors increased vanzacaftor, tezacaftor, and deutivacaftor exposure, which may increase the risk of ALYFTREK associated adverse reactions.

Reduce the ALYFTREK dosage with concomitant use. ( 2.3 , 5.7 , 7.1 ) Cataracts : Non-congenital lens opacities/cataracts have been reported in patients with CF aged 18 years or less treated with drugs containing ivacaftor. Baseline and follow up ophthalmological examinations are recommended in pediatric patients treated with ALYFTREK.

( 5.8 , 8.4 )

5.1Drug-Induced Liver Injury and Liver Failure Elevated transaminases have been observed in patients treated with ALYFTREK [see Adverse Reactions (6.1) ] . Cases of serious and potentially fatal drug-induced liver injury and liver failure have been reported in patients with and without a history of liver disease who were taking a fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor (ELX/TEZ/IVA), which contains the same or similar active ingredients as ALYFTREK. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of ELX/TEZ/IVA.

Assess liver function tests (ALT, A…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Drug-Induced Liver Injury and Liver Failure [see Warnings and Precautions (5.1) ] Hypersensitivity Reactions, Including Anaphylaxis [see Warnings and Precautions (5.2) ] Patients Who Discontinued or Interrupted Elexacaftor-, Tezacaftor-, or Ivacaftor-Containing Drugs Due to Adverse Reactions [see Warnings and Precautions (5.3) ] Intracranial Hypertension [see Warnings and Precautions (5.4) ] Neuropsychiatric Events, Including Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.5) ] Cataracts [see Warnings and Precautions (5.8) ] Most common adverse reactions to ALYFTREK (≥5% of patients and at a frequency higher than ELX/TEZ/IVA by ≥1%) were cough, nasopharyngitis, upper respiratory tract infection, headache, oropharyngeal pain, influenza, fatigue, increased ALT, rash, increased AST, and sinus congestion.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Vertex Pharmaceuticals Incorporated at 1-877-634-8789 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 cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The adverse reactions data below are from clinical trials of ALYFTREK in patients 6 years of age and older with CF with at least one responsive CFTR variant who were able to tolerate ELX/TEZ/IVA. Adverse reactions data in patients who previously discontinued or interrupted ELX/TEZ/IVA due to adverse reactions are not available .

Adverse Reactions in Patients Aged 12 Years and Older with CF The safety of ALYFTREK is based on 480 patients with CF aged 12 years and older who have at least one F508del variant or another responsive variant in the CFTR gene in two, 52-week, active-controlled trials (Trials 1 and 2) [see Clinical Studies (14) ]. In both trials, patients received a fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor (ELX/TEZ/IVA) in a 4-week run-in period and then were subsequently randomized to continue ELX/TEZ/IVA (elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg in the morning and ivacaftor 150 mg in the evening) or receive ALYFTREK (vanzacaftor 20 mg/tezacaftor 100 mg/deutivacaftor 250 mg) once daily.

Patients with a history of prior intolerance to ELX/TEZ/IVA (i.e., patients who discontinued or interrupted treatment due to adverse reactions) were excluded. Trials 1 and 2 were not designed to evaluate meaningful comparisons of the incidence of adverse reactions between the ALYFTREK and ELX/TEZ/IVA treatment groups. For additional information regarding ELX/TEZ/IVA adverse reactions, refer to ELX/TEZ/IVA Prescribing Information.

In Trial 1 and Trial 2 combined, the proportion of patients who discontinued treatment prematurely due to adverse reactions were 3.8% and 3.7% in ALYFTREK and ELX/TEZ/IVA treatment groups, respectively. Serious adverse reactions that occurred more frequently with ALYFTREK treatment than with ELX/TEZ/IVA treatment that occurred in 2 or more patients (≥0.4%) were influenza (1.5%), increased AST (0.4%), increased GGT (0.4%), depression (0.4%), and syncope (0.4%). Table 3: Adverse Reactions Occurring in ≥5% of ALYFTREK-Treated Patients and ≥1% Higher than ELX/TEZ/IVA-Treated Patients Aged 12 Years and Older with CF Who Had at Least One F508del Variant or Responsive Variant in the CFTR Gene (Trials 1 and 2) Adverse Reactions ALYFTREK N=480 ELX/TEZ/IVA N=491 Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ELX, elexacaftor; IVA, ivacaftor; TEZ, tezacaftor Cough Cough is composed of several similar terms including productive cough.

120 (25%) 116 (24%) Nasopharyngitis 102 (21%) 95 (19%) Upper respiratory tract infection Upper respir…

🔄 Drug Interactions ~3 min read ▾

7 DRUG INTERACTIONS Strong or moderate CYP3A inducers : Concomitant use with ALYFTREK is not recommended. ( 5.6 , 7.1 ) Strong or moderate CYP3A inhibitors : Reduce ALYFTREK dosage with concomitant use. Avoid food or drink containing grapefruit. ( 2.3 , 5.7 , 7.1 )

7.1Effect of Other Drugs and Grapefruit on ALYFTREK Strong or Moderate CYP3A Inducers Concomitant use of ALYFTREK with strong or moderate CYP3A inducers is not recommended. Vanzacaftor, tezacaftor, and deutivacaftor are substrates of CYP3A. Concomitant use of ALYFTREK with a strong or moderate CYP3A inducer decreases vanzacaftor, tezacaftor, and deutivacaftor exposure [see Clinical Pharmacology (12.3) ] which may reduce ALYFTREK effectiveness [see Warnings and Precautions (5.6) ] .

Strong or Moderate CYP3A Inhibitors Reduce the ALYFTREK dosage when used concomitantly with a strong or moderate CYP3A inhibitor [see Dosage and Administration (2.3) ] . Vanzacaftor, tezacaftor, and deutivacaftor are CYP3A substrates. Concomitant use with a strong CYP3A inhibitor increases vanzacaftor, tezacaftor, and deutivacaftor exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of ALYFTREK adverse reactions [see Warnings and Precautions (5.7) ].

Concomitant use with a moderate CYP3A inhibitor is predicted to increase vanzacaftor, tezacaftor, and deutivacaftor exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of ALYFTREK adverse reactions [see Warnings and Precautions (5.7) ]. Grapefruit Food or drink containing grapefruit should be avoided during treatment with ALYFTREK. Concomitant use of ALYFTREK with grapefruit juice which contains one or more components that moderately inhibit CYP3A may increase exposure of vanzacaftor, tezacaftor and deutivacaftor.

7.2Effect of ALYFTREK on Other Drugs P-glycoprotein (P-gp) Substrates Unless otherwise recommended in the P-gp substrate Prescribing Information, monitor more frequently for adverse reactions with concomitant use of ALYFTREK with P-gp substrates where minimal concentration changes may lead to serious adverse reactions related to P-gp substrates. Tezacaftor and deutivacaftor (components of ALYFTREK) are P-gp inhibitors. Administration of tezacaftor/ivacaftor increases exposure of P-gp substrates [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions related to these substrates.

Breast Cancer Resistance Protein (BCRP) Substrates Unless otherwise recommended in the BCRP substrate Prescribing Information, monitor more frequently for adverse reactions with concomitant use of ALYFTREK with BCRP substrates where minimal concentration changes may lead to serious adverse reactions related to BCRP substrates. Vanzacaftor (VNZ) and deutivacaftor (D-IVA) (components of ALYFTREK) are inhibitors of BCRP in vitro. Concomitant use of ALYFTREK with BCRP substrates may increase exposure of these substrates; however, this has not been studied clinically [see Clinical Pharmacology (12.3) ].

CYP2C9 Substrates Use caution when ALYFTREK is used concomitantly with CYP2C9 substrates. Monitor the international normalized ratio (INR) more frequently with concomitant use of ALYFTREK with warfarin. This recommendation is based upon a mechanistic understanding of deutivacaftor pharmacokinetics (it is an inhibitor of CYP2C9 in vitro) [see Clinical Pharmacology (12.3) ] .

Concomitant use of ALYFTREK with CYP2C9 substrates may increase exposure of these substrates; however, this has not been studied clinically.

7.3Drugs with No Clinically Significant Interactions with ALYFTREK Ciprofloxacin No clinically relevant effect on the exposure of tezacaftor was observed when tezacaftor/ivacaftor was used concomitantly with ciprofloxacin [see Clinical Pharmacology (12.3) ] . Hormonal Contraceptives No clinically significant differences in the pharmacokinetics of ethinyl estradiol/norethindrone containing hormonal contraceptives were observed when used concomitantly with tezacaftor in combinatio…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary There are no available data on ALYFTREK use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Although there are no animal reproduction studies with the concomitant administration of vanzacaftor, tezacaftor, and deutivacaftor, separate reproductive and developmental studies were conducted with vanzacaftor and tezacaftor in pregnant rats and rabbits. Deutivacaftor is a deuterated isotopologue of ivacaftor with a toxicity profile similar to ivacaftor.

Reproductive and development studies were conducted with ivacaftor in pregnant rats and rabbits. In animal embryo fetal development (EFD) studies, oral administration of vanzacaftor to pregnant rats and rabbits during organogenesis demonstrated no adverse developmental effects at doses that produced maternal exposures up to approximately 30 times the exposure at the maximum recommended human dose (MRHD) in rats and 22 times the MRHD in rabbits. Oral administration of tezacaftor to pregnant rats and rabbits during organogenesis demonstrated no adverse developmental effects at doses that produced maternal exposures up to approximately 3 times the exposure at the MRHD in rats and 0.2 times the MRHD in rabbits (based on summed AUCs of tezacaftor and the metabolite M1-TEZ).

Oral administration of ivacaftor to pregnant rats and rabbits during organogenesis demonstrated no adverse developmental effects at doses that produced maternal exposures up to approximately 8 and 9 times the exposure at the MRHD, respectively (based on AUC of ivacaftor for rats and rabbits). No adverse developmental effects were observed after oral administration of vanzacaftor, tezacaftor, or ivacaftor to pregnant rats from the period of organogenesis through lactation at doses that produced maternal exposures approximately 18 times, 1 time, and 8 times the exposures at the MRHD, respectively (based on AUCs of vanzacaftor, tezacaftor and M1-TEZ, and ivacaftor) ( see Data ).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal Data Vanzacaftor : In an EFD study, pregnant rats were administered vanzacaftor at oral doses of 2.5, 5, and 10 mg/kg/day during the period of organogenesis from gestation Days 6-17. Vanzacaftor did not cause adverse effects to the fetus at exposures up to 30 times the MRHD (based on AUC for vanzacaftor at maternal doses up to 10 mg/kg/day). In an EFD study, pregnant rabbits were administered vanzacaftor at oral doses of 10, 40, and 70 mg/kg/day during the period of organogenesis from gestation Days 7-20.

Vanzacaftor did not cause adverse effects to the fetus at exposures up to 22 times the MRHD (based on AUC of vanzacaftor at maternal doses up to 40 mg/kg/day). The high dose of 70 mg/kg/day (71 times the exposure at the MRHD) produced maternal toxicity (i.e., mortality, abortion, decreased mean body weight or body weight gains) and was associated with findings of increased post-implantation loss, decreased live fetuses, decreased fetal body weight, and increased kidney malformations. In a pre- and postnatal development (PPND) study in pregnant rats administered vanzacaftor at oral doses of 2.5, 5, and 10 mg/kg/day from gestation Day 6 through lactation Day 18, vanzacaftor did not cause adverse developmental effects in pups at maternal doses up to 10 mg/kg/day (approximately 18 times the exposure at the MRHD).

Placental transfer of vanzacaftor was observed in pregnant rats. Tezacaftor: In an EFD study, pregnant rats were administered tezacaftor at oral doses of 25, 50, and 100 mg/kg/day during the period of organogenes…

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary There are no available data on ALYFTREK use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Although there are no animal reproduction studies with the concomitant administration of vanzacaftor, tezacaftor, and deutivacaftor, separate reproductive and developmental studies were conducted with vanzacaftor and tezacaftor in pregnant rats and rabbits. Deutivacaftor is a deuterated isotopologue of ivacaftor with a toxicity profile similar to ivacaftor.

Reproductive and development studies were conducted with ivacaftor in pregnant rats and rabbits. In animal embryo fetal development (EFD) studies, oral administration of vanzacaftor to pregnant rats and rabbits during organogenesis demonstrated no adverse developmental effects at doses that produced maternal exposures up to approximately 30 times the exposure at the maximum recommended human dose (MRHD) in rats and 22 times the MRHD in rabbits. Oral administration of tezacaftor to pregnant rats and rabbits during organogenesis demonstrated no adverse developmental effects at doses that produced maternal exposures up to approximately 3 times the exposure at the MRHD in rats and 0.2 times the MRHD in rabbits (based on summed AUCs of tezacaftor and the metabolite M1-TEZ).

Oral administration of ivacaftor to pregnant rats and rabbits during organogenesis demonstrated no adverse developmental effects at doses that produced maternal exposures up to approximately 8 and 9 times the exposure at the MRHD, respectively (based on AUC of ivacaftor for rats and rabbits). No adverse developmental effects were observed after oral administration of vanzacaftor, tezacaftor, or ivacaftor to pregnant rats from the period of organogenesis through lactation at doses that produced maternal exposures approximately 18 times, 1 time, and 8 times the exposures at the MRHD, respectively (based on AUCs of vanzacaftor, tezacaftor and M1-TEZ, and ivacaftor) ( see Data ).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal Data Vanzacaftor : In an EFD study, pregnant rats were administered vanzacaftor at oral doses of 2.5, 5, and 10 mg/kg/day during the period of organogenesis from gestation Days 6-17. Vanzacaftor did not cause adverse effects to the fetus at exposures up to 30 times the MRHD (based on AUC for vanzacaftor at maternal doses up to 10 mg/kg/day). In an EFD study, pregnant rabbits were administered vanzacaftor at oral doses of 10, 40, and 70 mg/kg/day during the period of organogenesis from gestation Days 7-20.

Vanzacaftor did not cause adverse effects to the fetus at exposures up to 22 times the MRHD (based on AUC of vanzacaftor at maternal doses up to 40 mg/kg/day). The high dose of 70 mg/kg/day (71 times the exposure at the MRHD) produced maternal toxicity (i.e., mortality, abortion, decreased mean body weight or body weight gains) and was associated with findings of increased post-implantation loss, decreased live fetuses, decreased fetal body weight, and increased kidney malformations. In a pre- and postnatal development (PPND) study in pregnant rats administered vanzacaftor at oral doses of 2.5, 5, and 10 mg/kg/day from gestation Day 6 through lactation Day 18, vanzacaftor did not cause adverse developmental effects in pups at maternal doses up to 10 mg/kg/day (approximately 18 times the exposure at the MRHD).

Placental transfer of vanzacaftor was observed in pregnant rats. Tezacaftor: In an EFD study, pregnant rats were administered tezacaftor at oral doses of 25, 50, and 100 mg/kg/day during the period of organogenesis from gestation Days 6-17. T…

🧒 Pediatric Use ~3 min read ▾

8.4Pediatric Use The safety and effectiveness of ALYFTREK for the treatment of CF have been established in pediatric patients aged 6 years and older who have a clinical diagnosis of CF and who have at least one variant in the CFTR gene that is either responsive based on clinical and/or in vitro data or results in production of CFTR protein. Use of ALYFTREK for this indication was supported by evidence from two adequate and well-controlled trials (Trials 1 and 2) in patients with CF aged 12 years and older who had at least one F508del variant or another responsive variant in the CFTR gene and additional pharmacokinetic and safety data in pediatric patients with CF aged 6 to less than 12 years who had at least one F508del variant or another responsive variant in the CFTR gene (Trial 3).

In these trials, a total of 145 patients with CF aged 6 to less than 18 years received ALYFTREK including: In Trial 1, 26 adolescents aged 12 to less than 18 years who were heterozygous for F508del and a CFTR variant that is not responsive to ivacaftor or tezacaftor/ivacaftor (minimal function variant) [see Adverse Reactions (6.1) and Clinical Studies (14) ]. In Trial 2, 41 adolescents aged 12 to less than 18 years who were homozygous for F508del variant, heterozygous for F508del variant and either a gating or a residual function variant, or with at least one variant responsive to ELX/TEZ/IVA with no F508del variant [see Adverse Reactions (6.1) and Clinical Studies (14) ].

In Trial 3, 78 pediatric patients with CF aged 6 to less than 12 years (mean age 9.1 years) with at least one variant that is responsive to ELX/TEZ/IVA [see Adverse Reactions (6.1) ] . In Trial 3, patients who weighed less than 40 kg patients received ALYFTREK (vanzacaftor 12 mg/tezacaftor 60 mg/deutivacaftor 150 mg once daily) and patients who weighed 40 kg or more received ALYFTREK (vanzacaftor 20 mg/tezacaftor 100 mg/deutivacaftor 250 mg once daily). The efficacy of ALYFTREK in patients aged 6 to less than 12 years for this indication was extrapolated from patients aged 12 years and older with support from population pharmacokinetic analyses showing vanzacaftor, tezacaftor, and deutivacaftor exposure levels in patients aged 6 to less than 12 years to be within the range of exposures observed in patients aged 12 years and older [see Clinical Pharmacology (12.3) ] .

Safety of ALYFTREK in patients aged 6 to less than 12 years for this indication was based on Trial 3. The overall safety profile of patients in Trial 3 was generally similar to the safety data in adult and pediatric patients 12 years of age and older observed in Trials 1 and 2 [see Adverse Reactions (6.1) ]. There is a risk of cataracts in pediatric patients treated with ALYFTREK.

Perform baseline and follow-up ophthalmological examination in pediatric patients prior to and during treatment with ALYFTREK [see Warnings and Precautions (5.8) ]. The safety and effectiveness of ALYFTREK in patients younger than 6 years of age have not been established. Juvenile Animal Toxicity Data Findings of cataracts were observed in juvenile rats dosed from postnatal Day 7 through 35 with ivacaftor dose levels of 10 mg/kg/day and higher (0.21 times the MRHD based on systemic exposure of ivacaftor and its metabolites).

This finding has not been observed in older animals [see Warnings and Precautions (5.8) ]. Studies were conducted with tezacaftor in juvenile rats starting at postnatal day (PND) 21 and ranging up to PNDs 35 to 49. Findings of convulsions and death were observed in juvenile rats that received a tezacaftor dose level of 100 mg/kg/day (approximately equivalent to 1.9 times the MRHD based on summed AUCs of tezacaftor and its metabolite, M1-TEZ).

A no effect dose level was identified at 30 mg/kg/day (approximately equivalent to 0.8 times the MRHD based on summed AUCs of tezacaftor and its metabolite, M1-TEZ). Findings were dose related and generally more severe when dosing with tezacaftor was initiated earlier in the pos…

🧓 Geriatric Use 46 words ▾

8.5Geriatric Use Clinical studies of ALYFTREK did not include a sufficient number of patients with CF aged 65 years and older (n=2, 0.4% of patients treated with ALYFTREK in Trials 1 and 2) to determine whether they respond differently from younger adult patients with CF.

🆘 Overdosage 21 words ▾

10 OVERDOSAGE Treatment of overdosage consists of general supportive measures including monitoring of vital signs and observation of the clinical status.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Vanzacaftor and tezacaftor bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of select mutant forms of CFTR (including F508del- CFTR) to increase the amount of CFTR protein delivered to the cell surface compared to either molecule alone. Deutivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface. The combined effect of vanzacaftor, tezacaftor and deutivacaftor is increased quantity and function of CFTR at the cell surface, resulting in increased CFTR activity as measured both by CFTR-mediated chloride transport in vitro and by sweat chloride in patients with CF.

CFTR Chloride Transport Assay in Fischer Rat Thyroid Cells Expressing Mutant CFTR Protein Effects of vanzacaftor/tezacaftor/deutivacaftor on chloride transport for mutant CFTR protein was determined in Ussing chamber electrophysiology studies using a panel of Fischer Rat Thyroid (FRT) cell lines stably expressing CFTR protein from individual variants. Vanzacaftor/tezacaftor/deutivacaftor increased chloride transport in FRT cells expressing select CFTR variants, as identified in Table 5. The threshold that the treatment-induced increase in chloride transport must exceed for the mutant CFTR protein to be considered responsive is ≥10% of normal over baseline.

This threshold was used because it is expected to predict clinical benefit. For individual variants, the magnitude of the net change over baseline in CFTR-mediated chloride transport in vitro is not correlated with the magnitude of clinical response. CFTR Chloride Transport Assay in Human Bronchial Epithelial Cells Expressing Mutant CFTR Protein Homozygous and heterozygous N1303K- Human Bronchial Epithelial (HBE) cells showed greater chloride transport in the presence of vanzacaftor/tezacaftor/deutivacaftor than F508del/F508del- HBE cells treated with tezacaftor/ivacaftor which has shown clinical benefit in people homozygous for F508del .

Patient Selection Select adult and pediatric patients 6 years of age and older for the treatment of CF with ALYFTREK based on a clinical diagnosis of CF and the presence of at least one variant in the CFTR gene that is either responsive based on clinical and/or in vitro data or results in production of CFTR protein [see Indications and Usage (1) ]. ALYFTREK should only be used in patients with a clinical diagnosis of CF. The presence of eligible CFTR variant(s) should not be the sole determinant for using ALYFTREK.

Table 5 lists CFTR variants responsive to ALYFTREK based on clinical and/or in vitro data in FRT or HBE cells [see Clinical Studies (14) ]. Table 5: List of CFTR Gene Variants Responsive to ALYFTREK The list of responsive CFTR variants is non-exhaustive. There may be protein-producing CFTR variants not listed that respond to treatment with ALYFTREK.

Based on Clinical Data Clinical data is obtained from Trials 1 and 2. A455E G551D This variant is also predicted to be responsive by FRT assay with ALYFTREK. L1077P R352Q S1251N S945L W1098C D1152H G85E L206W R75Q S549N V562I W1282R F508del H1054D M1101K S1159F S549R V754M Y563N G1244E I336K R1066H Based on in vitro Data The N1303K variant is predicted to be responsive only by HBE assay.

All other variants predicted to be responsive with in vitro data are supported by FRT assay. 1140-1151dup D443Y G1265V I1398S M150R R1283M S977F 1461insGAT D443Y;G576A;R668C Complex/compound variants where a single allele of the CFTR gene has multiple variants; these exist independent of the presence of variants on the other allele. G126D I148L M152L R1283S S977F;R1438W 1507_1515del9 D513G G1298V I148N M152V R1438W T1036N 2055del9 D529G G1349D I148T M265R R170H T1053I 2183A→G D565G G149R I148T;H609R M348K R248K T1057R 2851A/G D567N G149R;G576A;R668C I175V M394L R258G T1086A 293A→G D572N G178E I331N M469V R297Q T1086I 3007del6 D579G G178R I336L M498I R31C T1246I 3131del15…

🧬 Mechanism of Action ~3 min read ▾

12.1Mechanism of Action Vanzacaftor and tezacaftor bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of select mutant forms of CFTR (including F508del- CFTR) to increase the amount of CFTR protein delivered to the cell surface compared to either molecule alone. Deutivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface. The combined effect of vanzacaftor, tezacaftor and deutivacaftor is increased quantity and function of CFTR at the cell surface, resulting in increased CFTR activity as measured both by CFTR-mediated chloride transport in vitro and by sweat chloride in patients with CF.

CFTR Chloride Transport Assay in Fischer Rat Thyroid Cells Expressing Mutant CFTR Protein Effects of vanzacaftor/tezacaftor/deutivacaftor on chloride transport for mutant CFTR protein was determined in Ussing chamber electrophysiology studies using a panel of Fischer Rat Thyroid (FRT) cell lines stably expressing CFTR protein from individual variants. Vanzacaftor/tezacaftor/deutivacaftor increased chloride transport in FRT cells expressing select CFTR variants, as identified in Table 5. The threshold that the treatment-induced increase in chloride transport must exceed for the mutant CFTR protein to be considered responsive is ≥10% of normal over baseline.

This threshold was used because it is expected to predict clinical benefit. For individual variants, the magnitude of the net change over baseline in CFTR-mediated chloride transport in vitro is not correlated with the magnitude of clinical response. CFTR Chloride Transport Assay in Human Bronchial Epithelial Cells Expressing Mutant CFTR Protein Homozygous and heterozygous N1303K- Human Bronchial Epithelial (HBE) cells showed greater chloride transport in the presence of vanzacaftor/tezacaftor/deutivacaftor than F508del/F508del- HBE cells treated with tezacaftor/ivacaftor which has shown clinical benefit in people homozygous for F508del .

Patient Selection Select adult and pediatric patients 6 years of age and older for the treatment of CF with ALYFTREK based on a clinical diagnosis of CF and the presence of at least one variant in the CFTR gene that is either responsive based on clinical and/or in vitro data or results in production of CFTR protein [see Indications and Usage (1) ]. ALYFTREK should only be used in patients with a clinical diagnosis of CF. The presence of eligible CFTR variant(s) should not be the sole determinant for using ALYFTREK.

Table 5 lists CFTR variants responsive to ALYFTREK based on clinical and/or in vitro data in FRT or HBE cells [see Clinical Studies (14) ]. Table 5: List of CFTR Gene Variants Responsive to ALYFTREK The list of responsive CFTR variants is non-exhaustive. There may be protein-producing CFTR variants not listed that respond to treatment with ALYFTREK.

Based on Clinical Data Clinical data is obtained from Trials 1 and 2. A455E G551D This variant is also predicted to be responsive by FRT assay with ALYFTREK. L1077P R352Q S1251N S945L W1098C D1152H G85E L206W R75Q S549N V562I W1282R F508del H1054D M1101K S1159F S549R V754M Y563N G1244E I336K R1066H Based on in vitro Data The N1303K variant is predicted to be responsive only by HBE assay.

All other variants predicted to be responsive with in vitro data are supported by FRT assay. 1140-1151dup D443Y G1265V I1398S M150R R1283M S977F 1461insGAT D443Y;G576A;R668C Complex/compound variants where a single allele of the CFTR gene has multiple variants; these exist independent of the presence of variants on the other allele. G126D I148L M152L R1283S S977F;R1438W 1507_1515del9 D513G G1298V I148N M152V R1438W T1036N 2055del9 D529G G1349D I148T M265R R170H T1053I 2183A→G D565G G149R I148T;H609R M348K R248K T1057R 2851A/G D567N G149R;G576A;R668C I175V M394L R258G T1086A 293A→G D572N G178E I331N M469V R297Q T1086I 3007del6 D579G G178R I336L M498I R31C T1246I 3131del15 D58H G194R I444S M952I R…

📦 How Supplied / Storage and Handling 134 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING ALYFTREK (vanzacaftor, tezacaftor, and deutivacaftor) tablets are supplied as follows: Table 10: ALYFTREK Tablets and Package Configuration Strengths Tablet Description Package Configuration NDC 4 mg of vanzacaftor/ 20 mg of tezacaftor / 50 mg of deutivacaftor purple, round-shaped, film-coated, debossed with "V4" on one side and plain on the other 84-count carton containing 4 wallets, each wallet containing 21 tablets in blister packs NDC 51167-135-01 10 mg of vanzacaftor/ 50 mg of tezacaftor / 125 mg of deutivacaftor purple, oblong-shaped, film-coated, debossed with "V10" on one side and plain on the other 56-count carton containing 4 wallets, each wallet containing 14 tablets in blister packs NDC 51167-121-01 Store at 20°C - 25°C (68°F - 77°F); excursions permitted to 15°C - 30°C (59°F - 86°F) [see USP Controlled Room Temperature].

📦 Storage and Handling 22 words ▾

Store at 20°C - 25°C (68°F - 77°F); excursions permitted to 15°C - 30°C (59°F - 86°F) [see USP Controlled Room Temperature].

📋 Description ~1 min read ▾

11 DESCRIPTION ALYFTREK (vanzacaftor, tezacaftor, and deutivacaftor tablets) are fixed-dose combination tablets for oral use available as: 10 mg of vanzacaftor (equivalent to 10.6 mg of vanzacaftor calcium dihydrate), 50 mg of tezacaftor, 125 mg of deutivacaftor or 4 mg of vanzacaftor (equivalent to 4.24 mg of vanzacaftor calcium dihydrate), 20 mg of tezacaftor, 50 mg of deutivacaftor. The tablets contain the following inactive ingredients: croscarmellose sodium, hypromellose, hypromellose acetate succinate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate.

The tablet film coating contains Brilliant Blue FCF aluminum lake/FD&C Blue #1, carmine, hydroxypropyl cellulose, hypromellose, iron oxide red, talc, and titanium dioxide. The active ingredients of ALYFTREK are described below: Vanzacaftor Vanzacaftor is provided as a calcium salt. Vanzacaftor calcium dihydrate is a white solid that is practically insoluble in water (< 0.1 mg/mL).

Its chemical name is calcium bis((14 S )-8-[3-(2-{dispiro[2.0.2 4 .1 3 ]heptan-7-yl}ethoxy)pyrazol-1-yl]-12,12-dimethyl-2,2,4-trioxo-2λ 6 -thia-3,9,11,18,23-pentaazatetracyclo[17.3.1.1 11,14 .0 5,10 ]tetracosa-1(23),5,7,9,19,21-hexaen-3-ide) dihydrate. Its molecular formula is C 32 H 38 N 7 O 4 S∙Ca 0.5 ∙H 2 O and its molecular weight is 654.82. Vanzacaftor calcium dihydrate has the following structural formula: Chemical Structure Tezacaftor Tezacaftor is a white to off-white solid that is practically insoluble in water (< 5 microgram/mL).

Its chemical name is 1-(2,2-difluoro-2H-1,3-benzodioxol-5-yl)-N-{1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl}cyclopropane-1-carboxamide. Its molecular formula is C 26 H 27 N 2 F 3 O 6 and its molecular weight is 520.50. Tezacaftor has the following structural formula: Chemical Structure Deutivacaftor Deutivacaftor is a white to off-white solid that is practically insoluble in water (< 0.1 mg/mL).

Pharmacologically, it is a CFTR potentiator. Its chemical name is N -(2-( tert -butyl)-5-hydroxy-4-(2-(methyl- d 3 )propan-2-yl-1,1,1,3,3,3- d 6 )phenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide. Its molecular formula is C 24 H 19 D 9 N 2 O 3 and its molecular weight is 401.55.

Deutivacaftor has the following structural formula: Chemical Structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Drug-Induced Liver Injury and Liver Failure Inform patients that elevations of transaminases have occurred in patients with CF treated with ALYFTREK and that cases of drug-induced liver injury and failure have been observed with fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor, which contains the same or similar active ingredients as ALYFTREK. Advise all patients that liver function tests should be assessed prior to initiating ALYFTREK, and then assessed every month during the first 6 months of treatment, then every 3 months for the next 12 months, then at least annually thereafter.

Inform patients with a history of liver disease or liver function test elevations at baseline that more frequent monitoring may be necessary. Instruct patients to interrupt treatment with ALYFTREK if symptoms of liver injury occur (e.g., jaundice, right upper quadrant pain, nausea, vomiting, altered mental status, ascites) and notify their healthcare provider immediately [see Dosage and Administration (2.1) , Warnings and Precautions (5.1) , Adverse Reactions (6.1) , Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ] .

Hypersensitivity Reactions, Including Anaphylaxis Inform patients that hypersensitivity reactions including anaphylaxis have been reported in patients who received drugs containing elexacaftor, tezacaftor, and/or ivacaftor (the same or similar active ingredients as ALYFTREK). Instruct patients to discontinue ALYFTREK and notify their healthcare provider if they experience signs and symptoms of a hypersensitivity reaction, including rash, hives, itching, facial swelling, tightness of the chest and wheezing [see Warnings and Precautions (5.2) ] .

Patients Who Discontinued or Interrupted Elexacaftor-, Tezacaftor-, or Ivacaftor-Containing Drugs Due to Adverse Reactions Inform patients that there is no available safety data for ALYFTREK in patients who previously discontinued or interrupted treatment with elexacaftor-, tezacaftor-, or ivacaftor-containing drugs due to adverse reactions. These patients who start treatment with ALYFTREK may require closer and more frequent monitoring [see Warnings and Precautions (5.3) ] . Intracranial Hypertension Inform patients that intracranial hypertension has occurred in patients who received drugs containing the same or similar active ingredients as ALYFTREK.

Instruct patients to notify their healthcare provider right away if they experience signs and symptoms of intracranial hypertension, including headache, blurred vision, diplopia, and vision loss [see Warnings and Precautions (5.4) ] . Neuropsychiatric Events, Including Suicidal Thoughts and Behaviors Inform patients that neuropsychiatric symptoms, including anxiety, depression, suicidal thoughts and behaviors, and sleep disturbances (e.g., insomnia), have been reported with the use of ALYFTREK or drugs containing the same or similar active ingredients as ALYFTREK.

The symptoms have been observed in patients with and without a history of similar symptoms and may occur within three months of ALYFTREK initiation. Instruct patients to contact their healthcare provider immediately if changes in behavior or thinking that are not typical for the patient occur, or if the patient develops suicidal ideation or behavior [see Warnings and Precautions (5.5) ] . Drug Interactions with CYP3A Inducers and Inhibitors Inform patients that certain medications, herbal supplements, or vitamins, when used concomitantly with ALYFTREK, may reduce the effectiveness of ALYFTREK or increase the risk of adverse reactions associated with ALYFTREK.

Instruct patients to report all concomitant medications, herbal supplements, or vitamins, to their healthcare providers while taking ALYFTREK [see Dosage and Administration (2.3) , Warnings and Precautions (5.6 , 5.7) and Drug Interactions (7.1) ] . Instruct patients to a…

💬 Medication Guide ~3 min read ▾

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 03/2026 MEDICATION GUIDE ALYFTREK™ (ah-LIF-trek) (vanzacaftor, tezacaftor, and deutivacaftor tablets), tablets for oral use What is the most important information I should know about ALYFTREK?

Elevated liver enzymes have been observed in patients taking ALYFTREK . Cases of serious liver damage and liver failure leading to transplantation and death have been seen in some people with or without a history of liver problems taking elexacaftor/tezacaftor/ivacaftor (TRIKAFTA), a medicine which has the same or similar active ingredients as ALYFTREK. Your healthcare provider will do blood tests to check your liver: before you start ALYFTREK every month during your first 6 months of taking ALYFTREK then every 3 months during the next 12 months of taking ALYFTREK then at least every year while you are taking ALYFTREK Your healthcare provider may do blood tests to check the liver more often if you have had high liver enzymes in your blood in the past or are experiencing signs or symptoms of liver injury.

Stop taking ALYFTREK and call your healthcare provider right away if you have any of the following symptoms of liver problems: pain, swelling, or discomfort in the upper right stomach (abdominal) area yellowing of your skin or the white part of your eyes mental changes nausea or vomiting dark, amber-colored urine loss of appetite have fluid in your stomach area (ascites) What is ALYFTREK? ALYFTREK is a prescription medicine for people aged 6 years and older who have a diagnosis of cystic fibrosis (CF) and who have at least one genetic change (variant) in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene that is either responsive to ALYFTREK or results in the production of protein.

Talk to your healthcare provider to learn if you have an indicated CF gene variant. It is not known if ALYFTREK is safe and effective in children under 6 years of age. What should I tell my healthcare provider before taking ALYFTREK?

Before taking ALYFTREK, tell your healthcare provider about all of your medical conditions, including if you: have or have had liver problems. are allergic to ALYFTREK or any ingredients in ALYFTREK. See the end of this medication guide for a complete list of ingredients in ALYFTREK. have taken another medicine with elexacaftor, tezacaftor, or ivacaftor before and temporarily or permanently stopped because of side effects. Your healthcare provider may want to see you more often. have kidney problems. have or have had mental health problems. are pregnant or plan to become pregnant.

It is not known if ALYFTREK will harm your unborn baby. You and your healthcare provider should decide if you will take ALYFTREK while you are pregnant. are breastfeeding or planning to breastfeed. It is not known if ALYFTREK passes into your breast milk.

You and your healthcare provider should decide if you will take ALYFTREK while you are breastfeeding. Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. ALYFTREK may affect the way other medicines work and other medicines may affect how ALYFTREK works.

The dose of ALYFTREK may need to be adjusted when taken with certain medicines. Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure. Know the medicines you take.

Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I take ALYFTREK? Take ALYFTREK exactly as your healthcare provider tells you to take it.

Take ALYFTREK by mouth only. Always take ALYFTREK tablets with food that contains fat . Examples of fat-containing foods include butter, oil, eggs, peanut butter, nuts, meat, and whole-milk dairy products such as whole milk, cheese, and yogurt.

ALYFTREK tablets (age 6 to less than 12 years weighing less than 88 pounds (40 kg)): The purple round-shaped ta…

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