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ORKAMBI lumacaftor and ivacaftor 75 mg; 94 mg Granule, 56-count — NDC 51167-0122-01 package photo

ORKAMBI lumacaftor and ivacaftor 75 mg; 94 mg Granule, 56-count

by Vertex Pharmaceuticals Incorporated · 56 PACKET in 1 CARTON (51167-122-01) / 1 GRANULE in 1 PACKET
NDC 51167-0122-01
🏷️ FDA NDC (as labeled) 51167-122-01 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) 51167-122-01
Product NDC 51167-122
11-digit billing NDC 51167012201
NCPDP billing unit EA — each (per item)
RxCUI 1655928, 1655934, 1812468, 1812470, 2053509, 2053512, 2053517, 2053519,
UNII 1Y740ILL1Z, EGP8L81APK
Application # NDA211358
SPL Set ID 3fc1c40e-cfac-47a1-9e1a-61ead3570600
Established class (EPC) Cystic Fibrosis Transmembrane Conductance Regulator Potentiator
Mechanism of action Chloride Channel Activation Potentiators; Cytochrome P450 2C9 Inhibitors; P-Glycoprotein Inhibitors; Cytochrome P450 3A Inhibitors; Cytochrome P450 3A Inducers; Cytochrome P450 2B6 Inducers; Cytochrome P450 2C8 Inducers; Cytochrome P450 2C9 Inducers; Cytochrome P450 2C19 Inducers; Cytochrome P450 2C8 Inhibitors; P-Glycoprotein Inducers
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2022-09-02
Route ORAL
Dosage form GRANULE
Substance LUMACAFTOR; IVACAFTOR
GPI-14 45309902303005
GCN Seq No 083804
GCN 52865
HICL code 042235
Ingredient (HICL) Lumacaftor/Ivacaftor
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 ORKAMBI 75-94 MG GRANULE PKT
FDB brand name Orkambi
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 51167-122-01 — 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 → 51167-0122-01. 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 Cystic Fibrosis Transmembrane Conductance Regulator Potentiator class.

Pharmacologic class Cystic Fibrosis Transmembrane Conductance Regulator Potentiator
Drug family (ATC) Other respiratory system products
How it works Chloride Channel Activation Potentiators, P-Glycoprotein Inhibitors, Cytochrome P450 2C9 Inhibitors, Cytochrome P450 3A Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerVertex Pharmaceuticals Incorporated
Application holderVERTEX PHARMACEUTICALS INC
FDA applicationNDA211358 (NDA)
Labeler code51167
First marketedSep 2022
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 ORKAMBI 75-94 MG GRANULE PKT Ingredient Lumacaftor/Ivacaftor
📗 Our plain-language guide HelloPharmacist
  • This is really important — fat in food dramatically increases how much of the medicine your body actually absorbs. Without it, lumacaftor absorption is cut roughly in half and ivac...
  • Why does my doctor want me to eat something fatty before taking Orkambi?
  • Yes — this is one of the most important things to know before starting Orkambi. The medication significantly reduces how well hormonal birth control works, including the pill, patc...
  • I use the birth control pill. Do I need to change anything while taking Orkambi?
📖 Read our full Lumacaftor and Ivacaftor guide →

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 Pink / White
ShapeOval
Imprint1V125
Size14 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 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 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 FZ989GH94E
    Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
  • UNII 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.

5 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 gPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $415.16 —
Medicare drug plans payPart D · Q2 2026 $424.05 —
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
Orkambi 75 mg/1; 94 mgthis 51167-0122-01 Vertex 56 granules — — 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

🏛️
2018
First FDA approval
Aug 2018
📍
2026
Currently FDA-listed
8 years listed
🛡️
2031
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 Jun 2031. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Aug 7, 2018 RLD RS ⏳ ~4.7 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 8324242 — method of use (U-2374)
US 7973038 — method of use (U-2374)
US 9931334 — method of use (U-2376)
US 8741933 — method of use (U-2374)
US 8716338 — method of use (U-2396)
US 8846718 — method of use (U-2375)
US 9150552 — method of use (U-2375)
US 9670163 — method of use (U-2376)
US 8716338 — method of use (U-2396)
US 9931334 — method of use (U-2376)
US 8741933 — method of use (U-2374)
US 9192606 — method of use (U-2397)
US 9192606 — method of use (U-2397)
US 12458635 — method of use (U-4335)
US 12458635 — method of use (U-4335)
US 12458635 — method of use (U-4335)
US 8324242 — method of use (U-3424)
US 7973038 — method of use (U-3424)
US 8716338 — method of use (U-3426)
US 8741933 — method of use (U-3424)
US 8846718 — method of use (U-3427)
US 9150552 — method of use (U-3427)
US 11564916 — method of use (U-3526)
US 11564916 — method of use (U-3526)
US 11564916 — method of use (U-3526)
US 10597384 — drug substance (U-2778)
US 10597384 — drug substance (U-2778)
US 7973038 — method of use (U-2374)
US 9150552 — method of use (U-2375)
US 8324242 — method of use (U-2374)
US 8846718 — method of use (U-2375)
US 12065432 — method of use (U-3983)
US 12065432 — method of use (U-3983)
US 12065432 — method of use (U-3983)
US 9670163 — method of use (U-2376)
US 9192606 — method of use (U-3428)
US 9670163 — method of use (U-3429)
US 9931334 — method of use (U-3429)
US 10597384 — drug substance (U-3430)
US 9216969 — drug product
US 8653103 — drug product
US 7495103 — drug substance
US 8653103 — drug product
US 8754224 — drug substance
US 7495103 — drug substance
US 10646481 — drug product
US 8410274 — drug product
US 7495103 — drug substance
US 8507534 — drug substance
US 8507534 — drug substance
US 8754224 — drug substance
US 8993600 — drug product
US 9216969 — drug product
US 9216969 — drug product
US 8507534 — drug substance
US 10646481 — drug product
US 8410274 — drug product
US 8653103 — drug product
US 8410274 — drug product
US 8754224 — drug substance
US 10646481 — drug product
US 8993600 — drug product
US 8993600 — drug product
US 8716338*PED — drug product
US 8716338*PED — drug product
US 7973038*PED — drug product
US 8410274*PED — drug product
US 8324242*PED — drug product
US 7495103*PED — drug product
US 7495103*PED — drug product
US 8324242*PED — drug product
US 7973038*PED — drug product
US 8410274*PED — drug product
US 8507534*PED — drug product
US 8653103*PED — drug product
US 8741933*PED — drug product
US 8653103*PED — drug product
US 8507534*PED — drug product
US 8741933*PED — drug product
US 9150552*PED — drug product
US 8754224*PED — drug product
US 8993600*PED — drug product
US 8846718*PED — drug product
US 8993600*PED — drug product
US 8754224*PED — drug product
US 8846718*PED — drug product
US 9150552*PED — drug product
US 9931334*PED — drug product
US 9670163*PED — drug product
US 9216969*PED — drug product
US 9670163*PED — drug product
US 9216969*PED — drug product
US 9931334*PED — drug product
US 9192606*PED — drug product
US 9192606*PED — drug product
US 10597384*PED — drug product
US 9192606*PED — drug product
US 9216969*PED — drug product
US 9670163*PED — drug product
US 9931334*PED — drug product
US 10646481*PED — drug product
US 12065432*PED — drug product
US 12065432*PED — drug product
US 12065432*PED — drug product
US 10597384*PED — drug product
US 10597384*PED — drug product
US 10646481*PED — drug product
US 10646481*PED — drug product
US 12458635*PED — drug product
US 12458635*PED — drug product
US 12458635*PED — drug product
US 7495103*PED — drug product
US 8324242*PED — drug product
US 7973038*PED — drug product
US 8410274*PED — drug product
US 8507534*PED — drug product
US 8653103*PED — drug product
US 8716338*PED — drug product
US 8741933*PED — drug product
US 8754224*PED — drug product
US 8846718*PED — drug product
US 8993600*PED — drug product
US 9150552*PED — drug product
US 11564916*PED — drug product
US 11564916*PED — drug product
US 11564916*PED — drug product
Exclusivity M-14
Exclusivity ODE-408
Exclusivity M-14
Exclusivity ODE-408
Exclusivity M-14
Exclusivity ODE-408
Exclusivity PED
Exclusivity PED
Exclusivity PED
Exclusivity PED
Exclusivity PED
Exclusivity PED
2018 2020 2022 2024 2026 2028 2030
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 (126)
PatentTypeUse codeExpires
US 8324242 ↗ Method of use U-2374 Aug 5, 2027
US 7973038 ↗ Method of use U-2374 Nov 8, 2026
US 9931334 ↗ Method of use U-2376 Dec 28, 2026
US 8741933 ↗ Method of use U-2374 Nov 8, 2026
US 8716338 ↗ Method of use U-2396 Sep 20, 2030
US 8846718 ↗ Method of use U-2375 Jul 2, 2029
US 9150552 ↗ Method of use U-2375 Dec 4, 2028
US 9670163 ↗ Method of use U-2376 Dec 28, 2026
US 8716338 ↗ Method of use U-2396 Sep 20, 2030
US 9931334 ↗ Method of use U-2376 Dec 28, 2026
US 8741933 ↗ Method of use U-2374 Nov 8, 2026
US 9192606 ↗ Method of use U-2397 Sep 29, 2029
US 9192606 ↗ Method of use U-2397 Sep 29, 2029
US 12458635 ↗ Method of use U-4335 Aug 13, 2029
US 12458635 ↗ Method of use U-4335 Aug 13, 2029
US 12458635 ↗ Method of use U-4335 Aug 13, 2029
US 8324242 ↗ Method of use U-3424 Aug 5, 2027
US 7973038 ↗ Method of use U-3424 Nov 8, 2026
US 8716338 ↗ Method of use U-3426 Sep 20, 2030
US 8741933 ↗ Method of use U-3424 Nov 8, 2026
US 8846718 ↗ Method of use U-3427 Jul 2, 2029
US 9150552 ↗ Method of use U-3427 Dec 4, 2028
US 11564916 ↗ Method of use U-3526 Aug 13, 2029
US 11564916 ↗ Method of use U-3526 Aug 13, 2029
US 11564916 ↗ Method of use U-3526 Aug 13, 2029
US 10597384 ↗ Drug substance U-2778 Dec 4, 2028
US 10597384 ↗ Drug substance U-2778 Dec 4, 2028
US 7973038 ↗ Method of use U-2374 Nov 8, 2026
US 9150552 ↗ Method of use U-2375 Dec 4, 2028
US 8324242 ↗ Method of use U-2374 Aug 5, 2027
US 8846718 ↗ Method of use U-2375 Jul 2, 2029
US 12065432 ↗ Method of use U-3983 Dec 4, 2028
US 12065432 ↗ Method of use U-3983 Dec 4, 2028
US 12065432 ↗ Method of use U-3983 Dec 4, 2028
US 9670163 ↗ Method of use U-2376 Dec 28, 2026
US 9192606 ↗ Method of use U-3428 Sep 29, 2029
US 9670163 ↗ Method of use U-3429 Dec 28, 2026
US 9931334 ↗ Method of use U-3429 Dec 28, 2026
US 10597384 ↗ Drug substance U-3430 Dec 4, 2028
US 9216969 ↗ Drug product — Nov 8, 2026
US 8653103 ↗ Drug product — Dec 4, 2028
US 7495103 ↗ Drug substance — May 20, 2027
US 8653103 ↗ Drug product — Dec 4, 2028
US 8754224 ↗ Drug substance — Dec 28, 2026
US 7495103 ↗ Drug substance — May 20, 2027
US 10646481 ↗ Drug product — Aug 13, 2029
US 8410274 ↗ Drug product — Dec 28, 2026
US 7495103 ↗ Drug substance — May 20, 2027
US 8507534 ↗ Drug substance — Sep 20, 2030
US 8507534 ↗ Drug substance — Sep 20, 2030
US 8754224 ↗ Drug substance — Dec 28, 2026
US 8993600 ↗ Drug product — Dec 11, 2030
US 9216969 ↗ Drug product — Nov 8, 2026
US 9216969 ↗ Drug product — Nov 8, 2026
US 8507534 ↗ Drug substance — Sep 20, 2030
US 10646481 ↗ Drug product — Aug 13, 2029
US 8410274 ↗ Drug product — Dec 28, 2026
US 8653103 ↗ Drug product — Dec 4, 2028
US 8410274 ↗ Drug product — Dec 28, 2026
US 8754224 ↗ Drug substance — Dec 28, 2026
US 10646481 ↗ Drug product — Aug 13, 2029
US 8993600 ↗ Drug product — Dec 11, 2030
US 8993600 ↗ Drug product — Dec 11, 2030
US 8716338*PED ↗ Drug product — Mar 20, 2031
US 8716338*PED ↗ Drug product — Mar 20, 2031
US 7973038*PED ↗ Drug product — May 8, 2027
US 8410274*PED ↗ Drug product — Jun 28, 2027
US 8324242*PED ↗ Drug product — Feb 5, 2028
US 7495103*PED ↗ Drug product — Nov 20, 2027
US 7495103*PED ↗ Drug product — Nov 20, 2027
US 8324242*PED ↗ Drug product — Feb 5, 2028
US 7973038*PED ↗ Drug product — May 8, 2027
US 8410274*PED ↗ Drug product — Jun 28, 2027
US 8507534*PED ↗ Drug product — Mar 20, 2031
US 8653103*PED ↗ Drug product — Jun 4, 2029
US 8741933*PED ↗ Drug product — May 8, 2027
US 8653103*PED ↗ Drug product — Jun 4, 2029
US 8507534*PED ↗ Drug product — Mar 20, 2031
US 8741933*PED ↗ Drug product — May 8, 2027
US 9150552*PED ↗ Drug product — Jun 4, 2029
US 8754224*PED ↗ Drug product — Jun 28, 2027
US 8993600*PED ↗ Drug product — Jun 11, 2031
US 8846718*PED ↗ Drug product — Jan 2, 2030
US 8993600*PED ↗ Drug product — Jun 11, 2031
US 8754224*PED ↗ Drug product — Jun 28, 2027
US 8846718*PED ↗ Drug product — Jan 2, 2030
US 9150552*PED ↗ Drug product — Jun 4, 2029
US 9931334*PED ↗ Drug product — Jun 28, 2027
US 9670163*PED ↗ Drug product — Jun 28, 2027
US 9216969*PED ↗ Drug product — May 8, 2027
US 9670163*PED ↗ Drug product — Jun 28, 2027
US 9216969*PED ↗ Drug product — May 8, 2027
US 9931334*PED ↗ Drug product — Jun 28, 2027
US 9192606*PED ↗ Drug product — Mar 29, 2030
US 9192606*PED ↗ Drug product — Mar 29, 2030
US 10597384*PED ↗ Drug product — Jun 4, 2029
US 9192606*PED ↗ Drug product — Mar 29, 2030
US 9216969*PED ↗ Drug product — May 8, 2027
US 9670163*PED ↗ Drug product — Jun 28, 2027
US 9931334*PED ↗ Drug product — Jun 28, 2027
US 10646481*PED ↗ Drug product — Feb 13, 2030
US 12065432*PED ↗ Drug product — Jun 4, 2029
US 12065432*PED ↗ Drug product — Jun 4, 2029
US 12065432*PED ↗ Drug product — Jun 4, 2029
US 10597384*PED ↗ Drug product — Jun 4, 2029
US 10597384*PED ↗ Drug product — Jun 4, 2029
US 10646481*PED ↗ Drug product — Feb 13, 2030
US 10646481*PED ↗ Drug product — Feb 13, 2030
US 12458635*PED ↗ Drug product — Feb 13, 2030
US 12458635*PED ↗ Drug product — Feb 13, 2030
US 12458635*PED ↗ Drug product — Feb 13, 2030
US 7495103*PED ↗ Drug product — Nov 20, 2027
US 8324242*PED ↗ Drug product — Feb 5, 2028
US 7973038*PED ↗ Drug product — May 8, 2027
US 8410274*PED ↗ Drug product — Jun 28, 2027
US 8507534*PED ↗ Drug product — Mar 20, 2031
US 8653103*PED ↗ Drug product — Jun 4, 2029
US 8716338*PED ↗ Drug product — Mar 20, 2031
US 8741933*PED ↗ Drug product — May 8, 2027
US 8754224*PED ↗ Drug product — Jun 28, 2027
US 8846718*PED ↗ Drug product — Jan 2, 2030
US 8993600*PED ↗ Drug product — Jun 11, 2031
US 9150552*PED ↗ Drug product — Jun 4, 2029
US 11564916*PED ↗ Drug product — Feb 13, 2030
US 11564916*PED ↗ Drug product — Feb 13, 2030
US 11564916*PED ↗ Drug product — Feb 13, 2030
FDA exclusivity
CodeWhat it grantsExpires
M-14New indication / labeling change (3-year)Dec 13, 2027
ODE-408Orphan Drug Exclusivity (7-year)Sep 2, 2029
M-14New indication / labeling change (3-year)Dec 13, 2027
ODE-408Orphan Drug Exclusivity (7-year)Sep 2, 2029
M-14New indication / labeling change (3-year)Dec 13, 2027
ODE-408Orphan Drug Exclusivity (7-year)Sep 2, 2029
PEDPediatric Exclusivity (+6 months)Mar 2, 2030
PEDPediatric Exclusivity (+6 months)Mar 2, 2030
PEDPediatric Exclusivity (+6 months)Mar 2, 2030
PEDPediatric Exclusivity (+6 months)Jun 13, 2028
PEDPediatric Exclusivity (+6 months)Jun 13, 2028
PEDPediatric Exclusivity (+6 months)Jun 13, 2028
Common questions
Is there a generic version of ORKAMBI 75-94 MG GRANULE PKT?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for ORKAMBI 75-94 MG GRANULE PKT. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Jun 2031 — 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 51167-0122-01, 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
50
Units reimbursed last 4 qtrs
2.8K
Gross reimbursed last 4 qtrs
$1.16M
Avg / prescription
$23,249.22
Avg / unit
$415.16
Latest quarter Q4 2025
11Rx
Fee-for-service vs managed care ⓘ
100% MCO
Fee-for-service · 0 Rx Managed care · 50 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: no data reported NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: no data reported CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 2,800 units · 25.8 per 100k residents NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
25.825.8
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 North Carolina 25.8 /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 · 2025 (Q1-Q4)

Medicare Part D (outpatient prescription) spending for Orkambi — 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 Orkambi. 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.
Total Part D spend
$640.9K
Claims incl. refills
32
Beneficiaries
—
Spend / beneficiary
—
Spend / claim
$20,027.47
💵 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.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
51167-0122-01 You're viewing this 56 PACKET in 1 CARTON (51167-122-01) / 1 GRANULE in 1 PACKET 2022-09-02 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 51167-122-01, 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: 51167-0122-01, written without dashes as 51167012201. 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 51167-0122-01, the first segment (51167) is the labeler code FDA assigned to Vertex Pharmaceuticals Incorporated; the middle segment (0122) 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.
🎯 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
🎯 Indications and Usage 189 words ▾

1 INDICATIONS AND USAGE ORKAMBI is indicated for the treatment of cystic fibrosis (CF) in patients aged 1 year and older who are homozygous for the F508del mutation in the CFTR gene. If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene. ORKAMBI is a combination of ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, and lumacaftor, indicated for the treatment of cystic fibrosis (CF) in patients aged 1 year and older who are homozygous for the F508del mutation in the CFTR gene.

If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene. ( 1 ) Limitations of Use: The efficacy and safety of ORKAMBI have not been established in patients with CF other than those homozygous for the F508del mutation. ( 1 ) Limitations of Use The efficacy and safety of ORKAMBI have not been established in patients with CF other than those homozygous for the F508del mutation .

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Age Group Weight Dose Administration 1 through 2 years 7 kg to <9 kg 1 packet of lumacaftor 75 mg/ivacaftor 94 mg granules Mixed with one teaspoon (5 mL) of soft food or liquid and administered orally every 12 hours with fat-containing food 9 kg to <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg granules 2 through 5 years <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg granules 6 through 11 years - 2 tablets of lumacaftor 100 mg/ivacaftor 125 mg (lumacaftor 200 mg/ivacaftor 250 mg per dose) Taken orally every 12 hours with fat-containing food 12 years and older - 2 tablets of lumacaftor 200 mg/ivacaftor 125 mg (lumacaftor 400 mg/ivacaftor 250 mg per dose) Reduce dosage in patients with moderate or severe hepatic impairment.

( 2.2 , 8.6 , 12.3 ) When initiating ORKAMBI in patients taking strong CYP3A inhibitors, reduce ORKAMBI dosage for the first week of treatment. ( 2.3 , 7.1 , 12.3 )

2.1Recommended Dosage in Adults and Pediatric Patients Aged 1 Year and Older The recommended dosage of ORKAMBI in adults and pediatric patients aged one year and older is based on patient's age and weight as described in Table 1. Table 1: Recommended Oral Dosage of ORKAMBI in Patients Aged 1 Year and Older Age Group Weight ORKAMBI Daily Dose (every 12 hours) Morning Dose Evening Dose 1 through 2 years 7 kg to <9 kg 1 packet of lumacaftor 75 mg/ivacaftor 94 mg oral granules 1 packet of lumacaftor 75 mg/ivacaftor 94 mg oral granules 9 kg to <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 2 through 5 years <14 kg 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules 1 packet of lumacaftor 100 mg/ivacaftor 125 mg oral granules ≥14 kg 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 1 packet of lumacaftor 150 mg/ivacaftor 188 mg oral granules 6 through 11 years - 2 tablets of lumacaftor 100 mg/ivacaftor 125 mg (lumacaftor 200 mg/ivacaftor 250 mg per dose) 2 tablets of lumacaftor 100 mg/ivacaftor 125 mg (lumacaftor 200 mg/ivacaftor 250 mg per dose) 12 years and older - 2 tablets of lumacaftor 200 mg/ivacaftor 125 mg (lumacaftor 400 mg/ivacaftor 250 mg per dose) 2 tablets of lumacaftor 200 mg/ivacaftor 125 mg (lumacaftor 400 mg/ivacaftor 250 mg per dose) Administration Instructions for ORKAMBI Oral Granules The entire content of each packet of oral granules should be mixed with one teaspoon (5 mL) of age-appropriate soft food or liquid and the mixture completely consumed.

Some examples of soft foods or liquids include puréed fruits or vegetables, flavored yogurt or pudding, applesauce, water, milk, breast milk, infant formula or juice. Food should be at room temperature or below. Each packet is for single use only.

Once mixed, the product has been shown to be stable for one hour, and therefore should be ingested during this period. Administration with Fat-Containing Food for ORKAMBI Tablets and Oral Granules A fat-containing meal or snack should be consumed just before or just after dosing for all formulations. Examples of appropriate fat-containing foods include eggs, avocados, nuts, butter, peanut butter, cheese pizza, breast milk, infant formula, whole-milk dairy products (such as whole milk, cheese, and yogurt), etc.

Missed Dose If a patient misses a dose and remembers the missed dose within 6 hours, the patient should take the dose with fat-containing food. If more than 6 hours elapsed after the recommended dosing time, the patient should skip that dose and resume the normal schedule for the following dose. A double dose should not be taken to make up for the forgotten dose [see Clinical Pharmacology (12.3) and Patient Counseling Information (17) ] .

2.2 Dosa…

💊 Dosage Forms and Strengths 176 words ▾

3 DOSAGE FORMS AND STRENGTHS Tablets: 100 mg lumacaftor and 125 mg ivacaftor; supplied as pink, oval-shaped, film-coated, fixed-dose combination tablets containing 100 mg of lumacaftor and 125 mg of ivacaftor. Each tablet is printed with the characters "1V125" in black ink on one side and plain on the other. Tablets: 200 mg lumacaftor and 125 mg ivacaftor; supplied as pink, oval-shaped, film-coated, fixed-dose combination tablets containing 200 mg of lumacaftor and 125 mg of ivacaftor.

Each tablet is printed with the characters "2V125" in black ink on one side and plain on the other. Oral granules: Unit-dose packets containing lumacaftor 75 mg/ivacaftor 94 mg or lumacaftor 100 mg/ivacaftor 125 mg or lumacaftor 150 mg/ivacaftor 188 mg per packet; supplied as small, white to off-white granules in unit-dose packets. Tablets: lumacaftor 100 mg and ivacaftor 125 mg; lumacaftor 200 mg and ivacaftor 125 mg.

( 3 ) Oral granules: Unit-dose packets of lumacaftor 75 mg and ivacaftor 94 mg; lumacaftor 100 mg and ivacaftor 125 mg; lumacaftor 150 mg and ivacaftor 188 mg. ( 3 )

⛔ Contraindications 7 words ▾

4 CONTRAINDICATIONS None. None. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Use in patients with advanced liver disease: ORKAMBI should be used with caution in these patients and only if the benefits are expected to outweigh the risks. If ORKAMBI is used in these patients, they should be closely monitored after the initiation of treatment and the dosage should be reduced. Liver function decompensation, including liver failure leading to death, has been reported in CF patients with pre-existing cirrhosis with portal hypertension.

( 2.2 , 5.1 , 6.1 ) Liver-related events: Elevated transaminases (ALT/AST) have been observed in some cases associated with elevated bilirubin. Measure serum transaminases and bilirubin before initiating ORKAMBI, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of ALT, AST, or bilirubin elevations, more frequent monitoring should be considered.

Interrupt dosing in patients with ALT or AST >5 × upper limit of normal (ULN), or ALT or AST >3 × ULN with bilirubin >2 × ULN. Following resolution, consider the benefits and risks of resuming dosing. ( 5.2 , 6.1 ) Hypersensitivity reactions: Angioedema and anaphylaxis have been reported with ORKAMBI in the postmarketing setting.

Initiate appropriate therapy in the event of a hypersensitivity reaction. ( 5.3 ) Intracranial hypertension: Intracranial hypertension (IH) has been reported in the postmarketing setting with the use of ORKAMBI. If an unusual headache or visual disturbances occur during treatment, and IH is suspected, interrupt ORKAMBI 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 ORKAMBI 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 ORKAMBI should be interrupted at the occurrence of neuropsychiatric symptoms.

( 5.5 ) Respiratory events: Chest discomfort, dyspnea, and respiration abnormal were observed more commonly during initiation of ORKAMBI. Clinical experience in patients with percent predicted FEV 1 (ppFEV 1 ) <40 is limited, and additional monitoring of these patients is recommended during initiation of therapy. ( 5.6 , 6.1 ) Blood pressure: Increased blood pressure has been observed in some patients.

Periodically monitor blood pressure in all patients. ( 5.7 , 6.1 ) Drug interactions: Use with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index may decrease systemic exposure of the medicinal products and co-administration is not recommended. Hormonal contraceptives should not be relied upon as an effective method of contraception and their use is associated with increased menstruation-related adverse reactions.

Use with strong CYP3A inducers may diminish exposure of ivacaftor, which may diminish its effectiveness; therefore, co-administration is not recommended. ( 5.8 , 6.1 , 7 , 12.3 ) Cataracts: Non-congenital lens opacities/cataracts have been reported in pediatric patients treated with ORKAMBI and ivacaftor, a component of ORKAMBI. Baseline and follow-up examinations are recommended in pediatric patients initiating ORKAMBI.

( 5.9 )

5.1Use in Patients with Advanced Liver Disease Worsening of liver function, including hepatic encephalopathy, in patients with advanced liver disease has been reported. Liver function decompensation, including liver failure leading to death, has been reported in CF patients with pre-existing cirrhosis with portal hypertension while receiving ORKAMBI. Use ORKAMBI with caution in patients with advanced liver disease and only if the benefits are expected to outweigh the risks.

If ORKAMBI is used in these patients, they should be closely monitored after the initiation of treatme…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Use in Patients with Advanced Liver Disease [see Warnings and Precautions (5.1) ] Liver-related Events [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions, Including Anaphylaxis [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) ] Respiratory Events [see Warnings and Precautions (5.6) ] Effect on Blood Pressure [see Warnings and Precautions (5.7) ] Cataracts [see Warnings and Precautions (5.9) ] The most common adverse reactions to ORKAMBI (occurring in ≥5% of patients with CF homozygous for the F508del mutation in the CFTR gene) were dyspnea, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, fatigue, respiration abnormal, blood creatine phosphokinase increased, rash, flatulence, rhinorrhea, influenza.

( 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 practice. The overall safety profile of ORKAMBI is based on the pooled data from 1108 patients with CF aged 12 years and older who are homozygous for the F508del mutation in the CFTR gene and who received at least one dose of study drug in two double-blind, placebo-controlled, Phase 3 clinical trials, each with 24 weeks of treatment (Trials 1 and 2).

In addition, the following clinical trials have been conducted: A 24-week, open-label trial (Trial 3) in 58 patients with CF aged 6 through 11 years homozygous for the F508del-CFTR mutation. A 24-week, placebo-controlled trial (Trial 4) in 204 patients aged 6 through 11 years homozygous for the F508del-CFTR mutation. A 24-week, open-label trial (Trial 5) in 46 patients aged 12 years and older homozygous for the F508del-CFTR mutation and with advanced lung disease (ppFEV 1 <40).

A 24-week, open-label trial (Trial 6) in 60 patients aged 2 through 5 years homozygous for the F508del-CFTR mutation. A 24-week, open-label trial (Trial 7) in 46 patients aged 1 through 2 years homozygous for the F508del - CFTR mutation. Of the 1108 patients, in the pooled analyses of Trial 1 and Trial 2, 49% were female and 99% were Caucasian; 369 patients received ORKAMBI every 12 hours and 370 patients received placebo.

The proportion of patients who prematurely discontinued study drug due to adverse events was 5% for patients treated with ORKAMBI and 2% for patients who received placebo. Serious adverse reactions, whether considered drug-related or not by the investigators, that occurred more frequently in patients treated with ORKAMBI included pneumonia, hemoptysis, cough, increased blood creatine phosphokinase, and transaminase elevations. These occurred in 1% or less of patients.

Table 3 shows adverse reactions occurring in ≥5% of patients with CF aged 12 years and older treated with ORKAMBI who are homozygous for the F508del mutation in the CFTR gene that also occurred at a higher rate than in patients who received placebo in the two double-blind, placebo-controlled trials. Table 3: Incidence of Adverse Drug Reactions in ≥5% of ORKAMBI-Treated Patients Aged 12 Years and Older Who are Homozygous for the F508del Mutation in the CFTR Gene in 2 Placebo-Controlled Phase 3 Clinical Trials of 24 Weeks Duration Adverse Reaction (Preferred Term) ORKAMBI N=369 (%) Placebo N=370 (%) Dyspnea 48 (13) 29 (8) Nasopharyngitis 48 (13) 40 (11) Nausea 46 (13) 28 (8) Diarrhea 45 (12) 31 (8) Upper respiratory tract infection 37 (10) 20 (5) Fatigue 34 (9) 29 (8) Respiration abnormal 32 (9)…

🔄 Drug Interactions ~3 min read ▾

5.8Drug Interactions Substrates of CYP3A Lumacaftor is a strong inducer of CYP3A. Administration of ORKAMBI may decrease systemic exposure of medicinal products that are substrates of CYP3A, which may decrease therapeutic effect. Co-administration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index is not recommended.

ORKAMBI may substantially decrease hormonal contraceptive exposure, reducing their effectiveness and increasing the incidence of menstruation-associated adverse reactions, e.g., amenorrhea, dysmenorrhea, menorrhagia, menstrual irregular (27% in women using hormonal contraceptives compared with 3% in women not using hormonal contraceptives). Hormonal contraceptives, including oral, injectable, transdermal, and implantable, should not be relied upon as an effective method of contraception when co-administered with ORKAMBI [see Adverse Reactions (6.1) , Drug Interactions (7.3 , 7.11) , and Clinical Pharmacology (12.3) ] .

Strong CYP3A Inducers Ivacaftor is a substrate of CYP3A4 and CYP3A5 isoenzymes. Use of ORKAMBI with strong CYP3A inducers, such as rifampin, significantly reduces ivacaftor exposure, which may reduce the therapeutic effectiveness of ORKAMBI. Therefore, co-administration with strong CYP3A inducers (e.g., rifampin, St.

John's wort [ Hypericum perforatum ]) is not recommended [see Drug Interactions (7.2) and Clinical Pharmacology (12.3) ] .

7 DRUG INTERACTIONS See Full Prescribing Information for a complete list. ( 2.3 , 7 , 12.3 ) Potential for Other Drugs to Affect Lumacaftor/Ivacaftor

7.1Inhibitors of CYP3A Co-administration of lumacaftor/ivacaftor with itraconazole, a strong CYP3A inhibitor, did not impact the exposure of lumacaftor, but increased ivacaftor exposure by 4.3-fold. Due to the induction effect of lumacaftor on CYP3A, at steady-state, the net exposure of ivacaftor is not expected to exceed that when given in the absence of lumacaftor at a dose of 150 mg every 12 hours (the approved dose of ivacaftor monotherapy). Therefore, no dosage adjustment is necessary when CYP3A inhibitors are initiated in patients currently taking ORKAMBI.

However, when initiating ORKAMBI in patients taking strong CYP3A inhibitors, reduce the ORKAMBI dosage as recommended for the first week of treatment to allow for the steady-state induction effect of lumacaftor. Following this period, continue with the recommended daily dose [see Dosage and Administration (2.3) ] . Examples of strong CYP3A inhibitors include: ketoconazole, itraconazole, posaconazole, and voriconazole. telithromycin, clarithromycin.

No dosage adjustment is recommended when used with moderate or weak CYP3A inhibitors.

7.2Inducers of CYP3A Co-administration of lumacaftor/ivacaftor with rifampin, a strong CYP3A inducer, had minimal effect on the exposure of lumacaftor, but decreased ivacaftor exposure (AUC) by 57%. This may reduce the effectiveness of ORKAMBI. Therefore, co-administration with strong CYP3A inducers, such as rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, and St.

John's wort ( Hypericum perforatum ), is not recommended [see Warnings and Precautions (5.8) and Clinical Pharmacology (12.3) ] . No dosage adjustment is recommended when used with moderate or weak CYP3A inducers. Potential for Lumacaftor/Ivacaftor to Affect Other Drugs

7.3CYP3A Substrates Lumacaftor is a strong inducer of CYP3A. Co-administration of lumacaftor with ivacaftor, a sensitive CYP3A substrate, decreased ivacaftor exposure by approximately 80%. Administration of ORKAMBI may decrease systemic exposure of medicinal products which are substrates of CYP3A, thereby decreasing the therapeutic effect of the medicinal product.

Co-administration of ORKAMBI is not recommended with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index [see Warnings and Precautions (5.8) and Clinical Pharmacology (12.3) ] such as: Benzodiazepines : midazolam, triazolam (consider an alternative to these benzodiazepin…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary There are limited and incomplete human data from clinical trials and postmarketing reports on use of ORKAMBI or its individual components, lumacaftor or ivacaftor, in pregnant women to inform a drug-associated risk. In animal reproduction studies, oral administration of lumacaftor to pregnant rats and rabbits during organogenesis demonstrated no adverse effects on fetal development at doses that produced maternal exposures up to approximately 8 (rats) and 5 (rabbits) times the exposure at the maximum recommended human dose (MRHD).

Oral administration of ivacaftor to pregnant rats and rabbits during organogenesis demonstrated no adverse effects on fetal development at doses that produced maternal exposures up to approximately 7 (rats) and 45 (rabbits) times the exposure at the MRHD. No adverse developmental effects were observed after oral administration of either lumacaftor or ivacaftor to pregnant rats from organogenesis through lactation at doses that produced maternal exposures approximately 8 and 5 times the exposures at the MRHD, respectively (see Data ) .

There are no animal reproduction studies with concomitant administration of lumacaftor and ivacaftor. The background risk of major birth defects and miscarriage for the indicated population is unknown. 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 Lumacaftor In an embryo-fetal development (EFD) study, pregnant rats were administered lumacaftor at oral doses of 500, 1000, or 2000 mg/kg/day during the period of organogenesis from gestation days 7-17. Lumacaftor did not affect fetal development or survival at exposures up to 8 times the MRHD (on an AUC basis at maternal oral doses up to 2000 mg/kg/day). In an EFD study, pregnant rabbits were administered lumacaftor at oral doses of 50, 100, or 200 mg/kg/day during the period of organogenesis from gestation days 7-19.

Lumacaftor did not affect fetal development or survival at exposures up to 5 times the MRHD (on an AUC basis at maternal oral doses up to 200 mg/kg/day). Maternal toxicity as evidenced by decreased body weight, decreased food consumption, and clinical signs was observed at 100 and 200 mg/kg/day without any adverse fetal effects. In a pre- and post-natal development study in pregnant female rats administered lumacaftor at 250, 500, or 1000 mg/kg/day from gestation day 6 through lactation day 20, lumacaftor had no effects on delivery or growth and development of offspring at exposures up to 8 times the MRHD (on an AUC basis at maternal oral doses up to 1000 mg/kg/day).

Placental transfer of lumacaftor was observed in pregnant rats and rabbits. Ivacaftor In an EFD study, pregnant rats were administered ivacaftor at oral doses of 50, 100, or 200 mg/kg/day during the period of organogenesis from gestation days 7-17. Ivacaftor did not affect fetal survival at exposures up to 7 times the MRHD (based on summed AUCs for ivacaftor and its metabolites at maternal oral doses up to 200 mg/kg/day).

Maternal toxicity (i.e., decreased mean body weight and body weight gain) was observed at 100 and 200 mg/kg/day (5 and 7 times the exposure at the MRHD, respectively) and was associated with a decrease in fetal body weights at a maternal dose of 200 mg/kg/day (7 times the MRHD). In an EFD study, pregnant rabbits were administered ivacaftor at oral doses of 25, 50, or 100 mg/kg/day during the period of organogenesis from gestation days 7-19. Ivacaftor did not affect fetal development or survival at exposures up to 45 times the MRHD (on an ivacaftor AUC basis at maternal oral doses up to 100 mg/kg/day).

Maternal toxicity (i.e., death, decreased food consumption, decreased mean body weight and body weight gain, decreased clinical condition, abortions) was observed at doses greater than or equal to 50 mg/kg/day (approximately 15…

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary There are limited and incomplete human data from clinical trials and postmarketing reports on use of ORKAMBI or its individual components, lumacaftor or ivacaftor, in pregnant women to inform a drug-associated risk. In animal reproduction studies, oral administration of lumacaftor to pregnant rats and rabbits during organogenesis demonstrated no adverse effects on fetal development at doses that produced maternal exposures up to approximately 8 (rats) and 5 (rabbits) times the exposure at the maximum recommended human dose (MRHD).

Oral administration of ivacaftor to pregnant rats and rabbits during organogenesis demonstrated no adverse effects on fetal development at doses that produced maternal exposures up to approximately 7 (rats) and 45 (rabbits) times the exposure at the MRHD. No adverse developmental effects were observed after oral administration of either lumacaftor or ivacaftor to pregnant rats from organogenesis through lactation at doses that produced maternal exposures approximately 8 and 5 times the exposures at the MRHD, respectively (see Data ) .

There are no animal reproduction studies with concomitant administration of lumacaftor and ivacaftor. The background risk of major birth defects and miscarriage for the indicated population is unknown. 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 Lumacaftor In an embryo-fetal development (EFD) study, pregnant rats were administered lumacaftor at oral doses of 500, 1000, or 2000 mg/kg/day during the period of organogenesis from gestation days 7-17. Lumacaftor did not affect fetal development or survival at exposures up to 8 times the MRHD (on an AUC basis at maternal oral doses up to 2000 mg/kg/day). In an EFD study, pregnant rabbits were administered lumacaftor at oral doses of 50, 100, or 200 mg/kg/day during the period of organogenesis from gestation days 7-19.

Lumacaftor did not affect fetal development or survival at exposures up to 5 times the MRHD (on an AUC basis at maternal oral doses up to 200 mg/kg/day). Maternal toxicity as evidenced by decreased body weight, decreased food consumption, and clinical signs was observed at 100 and 200 mg/kg/day without any adverse fetal effects. In a pre- and post-natal development study in pregnant female rats administered lumacaftor at 250, 500, or 1000 mg/kg/day from gestation day 6 through lactation day 20, lumacaftor had no effects on delivery or growth and development of offspring at exposures up to 8 times the MRHD (on an AUC basis at maternal oral doses up to 1000 mg/kg/day).

Placental transfer of lumacaftor was observed in pregnant rats and rabbits. Ivacaftor In an EFD study, pregnant rats were administered ivacaftor at oral doses of 50, 100, or 200 mg/kg/day during the period of organogenesis from gestation days 7-17. Ivacaftor did not affect fetal survival at exposures up to 7 times the MRHD (based on summed AUCs for ivacaftor and its metabolites at maternal oral doses up to 200 mg/kg/day).

Maternal toxicity (i.e., decreased mean body weight and body weight gain) was observed at 100 and 200 mg/kg/day (5 and 7 times the exposure at the MRHD, respectively) and was associated with a decrease in fetal body weights at a maternal dose of 200 mg/kg/day (7 times the MRHD). In an EFD study, pregnant rabbits were administered ivacaftor at oral doses of 25, 50, or 100 mg/kg/day during the period of organogenesis from gestation days 7-19. Ivacaftor did not affect fetal development or survival at exposures up to 45 times the MRHD (on an ivacaftor AUC basis at maternal oral doses up to 100 mg/kg/day).

Maternal toxicity (i.e., death, decreased food consumption, decreased mean body weight and body weight gain, decreased clinical condition, abortions) was observed at doses greater than or equal to 50 mg/kg/day (approximately 15 times the MRHD). In a pre- and…

🧒 Pediatric Use ~3 min read ▾

8.4Pediatric Use The safety and effectiveness of ORKAMBI in pediatric patients aged one year and older have been established. Use of ORKAMBI in these age groups is supported by evidence from adequate and well-controlled studies of ORKAMBI in patients aged 12 years and older [see Clinical Studies (14) and Adverse Reactions (6.1) ] with additional data as follows: Extrapolation of efficacy in patients aged 12 years and older homozygous for the F508del mutation in the CFTR gene to pediatric patients aged 1 through 11 years with support from population pharmacokinetic analyses showing similar drug exposure levels in patients aged 12 years and older and in patients aged 1 through 11 years [see Clinical Pharmacology (12.3) ] .

Safety data were obtained from a 24-week, open-label, clinical trial in 58 patients aged 6 through 11 years, mean age 9 years (Trial 3) and a 24-week, placebo-controlled, clinical trial in 204 patients aged 6 through 11 years (Trial 4). Trial 3 evaluated subjects with a screening ppFEV 1 ≥40 [mean ppFEV 1 91.4 at baseline (range: 55 to 122.7)]. Trial 4 evaluated subjects with a screening ppFEV 1 ≥70 [mean ppFEV 1 89.8 at baseline (range: 48.6 to 119.6)].

The safety profile of ORKAMBI in pediatric patients 6 through 11 years of age was similar to that in patients aged 12 years and older [see Adverse Reactions (6.1) ] . In Trial 3, spirometry (ppFEV 1 ) was assessed as a planned safety endpoint. The within-group LS mean absolute change from baseline in ppFEV 1 at Week 24 was 2.5 percentage points.

At the Week 26 safety follow-up visit (following a planned discontinuation) ppFEV 1 was also assessed. The within-group LS mean absolute change in ppFEV 1 from Week 24 at Week 26 was -3.2 percentage points. Additional safety data were obtained from Trial 6, a 24-week, open-label, clinical trial in 60 patients aged 2 through 5 years at screening (mean age at baseline 3.7 years).

The safety profile in Trial 6 was similar to that in patients aged 6 years and older [see Adverse Reactions (6.1) ] . Additional safety data were obtained from Trial 7, a 24-week, open-label, clinical trial in 46 patients aged 1 to 2 years at screening (mean age at baseline 18.1 months). The safety profile in Trial 7 was similar to that in patients aged 2 years and older [see Adverse Reactions (6.1) ] .

Safety was evaluated in a 96-week open-label clinical trial (Trial 8) in 52 patients (39 rolled over from Trial 7 and 13 ORKAMBI naïve) aged 1 to 2 years. Adverse reactions from trial 8 were generally similar to those reported in Trial 7. The safety and effectiveness of ORKAMBI in patients with CF younger than 1 year of age have not been established.

Cases of non-congenital lens opacities have been reported in pediatric patients treated with ORKAMBI and ivacaftor, a component of ORKAMBI. Although other risk factors were present in some cases (such as corticosteroid use and exposure to radiation), a possible risk attributable to ivacaftor cannot be excluded [see Warnings and Precautions (5.9) ] . Juvenile Animal Toxicity Data In a juvenile toxicology study in which ivacaftor was administered to rats from post-natal days 7 to 35, cataracts were observed at all dose levels, ranging from 0.3 to 2 times the MRHD (based on summed AUCs for ivacaftor and its metabolites at oral doses of 10-50 mg/kg/day).

This finding has not been observed in older animals.

🧓 Geriatric Use 39 words ▾

8.5Geriatric Use CF is largely a disease of children and young adults. Clinical trials of ORKAMBI did not include sufficient numbers of patients 65 years of age and over to determine whether they respond differently from younger patients.

🆘 Overdosage 105 words ▾

10 OVERDOSAGE There have been no reports of overdose with ORKAMBI. The highest repeated dose was lumacaftor 1000 mg once daily/ivacaftor 450 mg q12h administered to 49 healthy subjects for 7 days in a trial evaluating the effect of ORKAMBI on electrocardiograms (ECGs). Adverse events reported at an increased incidence of ≥5% compared to the lumacaftor 600 mg/ivacaftor 250 mg dosing period and placebo included: headache (29%), transaminase increased (18%), and generalized rash (10%).

No specific antidote is available for overdose with ORKAMBI. Treatment of overdose consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The CFTR protein is a chloride channel present at the surface of epithelial cells in multiple organs. The F508del mutation results in protein misfolding, causing a defect in cellular processing and trafficking that targets the protein for degradation and therefore reduces the quantity of CFTR at the cell surface. The small amount of F508del-CFTR that reaches the cell surface is less stable and has low channel-open probability (defective gating activity) compared to wild-type CFTR protein.

Lumacaftor improves the conformational stability of F508del-CFTR, resulting in increased processing and trafficking of mature protein to the cell surface. Ivacaftor is a CFTR potentiator that facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein at the cell surface. In vitro studies have demonstrated that both lumacaftor and ivacaftor act directly on the CFTR protein in primary human bronchial epithelial cultures and other cell lines harboring the F508del-CFTR mutation to increase the quantity, stability, and function of F508del-CFTR at the cell surface, resulting in increased chloride ion transport.

In vitro responses do not necessarily correspond to in vivo pharmacodynamic response or clinical benefit.

12.2Pharmacodynamics Sweat Chloride Evaluation Changes in sweat chloride in response to relevant doses of lumacaftor alone or in combination with ivacaftor were evaluated in a double-blind, placebo-controlled, Phase 2 clinical trial in patients with CF aged 18 years and older either homozygous or heterozygous for the F508del mutation. In that trial, 10 patients (homozygous for F508del ) completed dosing with lumacaftor alone 400 mg q12h for 28 days followed by the addition of ivacaftor 250 mg q12h for an additional 28 days and 25 patients (homozygous or heterozygous for F508del ) completed dosing with placebo.

The treatment difference between lumacaftor 400 mg q12h alone and placebo evaluated as mean change in sweat chloride from baseline to Day 28 compared to placebo was -8.2 mmol/L (95% CI: -14, -2). The treatment difference between the combination of lumacaftor 400 mg/ivacaftor 250 mg q12h and placebo evaluated as mean change in sweat chloride from baseline to Day 56 compared to placebo was -11 mmol/L (95% CI: -18, -4). Changes in sweat chloride in response to lumacaftor/ivacaftor were also evaluated in a 24-week, open-label, clinical trial (Trial 3) in 58 patients with CF, aged 6 through 11 years (homozygous for F508del ) who received lumacaftor 200 mg/ivacaftor 250 mg q12h for 24 weeks.

Patients treated with lumacaftor/ivacaftor had a reduction in sweat chloride at Day 15 that was sustained through Week 24. The within-group LS mean absolute change from baseline in sweat chloride was -20.4 mmol/L at Day 15 and -24.8 mmol/L at Week 24. In addition, sweat chloride was also assessed after a 2-week washout period to evaluate the off-drug response.

The within-group LS mean absolute change in sweat chloride from Week 24 at Week 26 following the 2-week washout period was 21.3 mmol/L. Changes in sweat chloride in response to lumacaftor/ivacaftor were also evaluated in a 24-week, open-label, clinical trial (Trial 6) in 60 patients with CF, aged 2 through 5 years (homozygous for F508del ) who received either lumacaftor 100 mg/ivacaftor 125 mg every 12 hours or lumacaftor 150 mg/ivacaftor 188 mg every 12 hours for 24 weeks. Treatment with lumacaftor/ivacaftor demonstrated a reduction in sweat chloride at Week 4 that was sustained through Week 24.

The mean absolute change from baseline in sweat chloride was –31.7 mmol/L (95% CI: -35.7, -27.6) at Week 24. In addition, sweat chloride was also assessed after a 2-week washout period to evaluate the off-drug response. The mean absolute change in sweat chloride from Week 24 at Week 26 following the 2-week washout period was an increase of 33.0 mmol/L (95% CI: 28.9, 37.1; P <0.0001).

Changes in…

🧬 Mechanism of Action 188 words ▾

12.1Mechanism of Action The CFTR protein is a chloride channel present at the surface of epithelial cells in multiple organs. The F508del mutation results in protein misfolding, causing a defect in cellular processing and trafficking that targets the protein for degradation and therefore reduces the quantity of CFTR at the cell surface. The small amount of F508del-CFTR that reaches the cell surface is less stable and has low channel-open probability (defective gating activity) compared to wild-type CFTR protein.

Lumacaftor improves the conformational stability of F508del-CFTR, resulting in increased processing and trafficking of mature protein to the cell surface. Ivacaftor is a CFTR potentiator that facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein at the cell surface. In vitro studies have demonstrated that both lumacaftor and ivacaftor act directly on the CFTR protein in primary human bronchial epithelial cultures and other cell lines harboring the F508del-CFTR mutation to increase the quantity, stability, and function of F508del-CFTR at the cell surface, resulting in increased chloride ion transport.

In vitro responses do not necessarily correspond to in vivo pharmacodynamic response or clinical benefit.

📦 How Supplied / Storage and Handling ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING ORKAMBI (lumacaftor 200 mg/ivacaftor 125 mg) is supplied as pink, oval-shaped tablets; each tablet contains 200 mg of lumacaftor and 125 mg of ivacaftor, printed with "2V125" in black ink on one side and plain on the other, and is packaged as follows: 112–count tablet box containing a 4-week supply (4 weekly cartons of 7 daily blister strips with 4 tablets per strip). NDC 51167-809-01 ORKAMBI (lumacaftor 100 mg/ivacaftor 125 mg) is supplied as pink, oval-shaped tablets; each tablet contains 100 mg of lumacaftor and 125 mg of ivacaftor, printed with "1V125" in black ink on one side and plain on the other, and is packaged as follows: 112–count tablet box containing a 4-week supply (4 weekly cartons of 7 daily blister strips with 4 tablets per strip).

NDC 51167-700-02 ORKAMBI (lumacaftor/ivacaftor) oral granules are supplied as small white to off-white granules and enclosed in unit-dose packets as follows: 56-count carton (contains 56 unit-dose packets of lumacaftor 75 mg/ivacaftor 94 mg per packet) NDC 51167-122-01 56-count carton (contains 56 unit-dose packets of lumacaftor 100 mg/ivacaftor 125 mg per packet) NDC 51167-900-01 56-count carton (contains 56 unit-dose packets of lumacaftor 150 mg/ivacaftor 188 mg per packet) NDC 51167-500-02 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 ~2 min read ▾

11 DESCRIPTION The active ingredients in ORKAMBI tablets are lumacaftor, which has the following chemical name: 3-[6-({[1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl}amino)-3-methylpyridin-2-yl]benzoic acid, and ivacaftor, a CFTR potentiator, which has the following chemical name: N -(2,4-di-tert-butyl-5-hydroxyphenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide. The molecular formula for lumacaftor is C 24 H 18 F 2 N 2 O 5 and for ivacaftor is C 24 H 28 N 2 O 3 . The molecular weights for lumacaftor and ivacaftor are 452.41 and 392.49, respectively.

The structural formulas are: lumacaftor ivacaftor Lumacaftor is a white to off-white powder that is practically insoluble in water (0.02 mg/mL). Ivacaftor is a white to off-white powder that is practically insoluble in water (<0.05 µg/mL). ORKAMBI is available as a pink, oval-shaped, film-coated tablet for oral administration containing 200 mg of lumacaftor and 125 mg of ivacaftor.

Each ORKAMBI tablet contains 200 mg of lumacaftor and 125 mg of ivacaftor, and the following inactive ingredients: cellulose, microcrystalline; croscarmellose sodium; hypromellose acetate succinate; magnesium stearate; povidone; and sodium lauryl sulfate. The tablet film coat contains carmine, FD&C Blue #1, FD&C Blue #2, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. The printing ink contains ammonium hydroxide, iron oxide black, propylene glycol, and shellac.

ORKAMBI is also available as a pink, oval-shaped, film-coated tablet for oral administration containing 100 mg of lumacaftor and 125 mg of ivacaftor. Each ORKAMBI tablet contains 100 mg of lumacaftor and 125 mg of ivacaftor, and the following inactive ingredients: cellulose, microcrystalline; croscarmellose sodium; hypromellose acetate succinate; magnesium stearate; povidone; and sodium lauryl sulfate. The tablet film coat contains carmine, FD&C Blue #1, FD&C Blue #2, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.

The printing ink contains ammonium hydroxide, iron oxide black, propylene glycol, and shellac. ORKAMBI is also available as white to off-white granules for oral administration and enclosed in a unit-dose packet containing lumacaftor 75 mg/ivacaftor 94 mg, lumacaftor 100 mg/ivacaftor 125 mg or lumacaftor 150 mg/ivacaftor 188 mg per packet. Each unit-dose packet of ORKAMBI oral granules contains lumacaftor 75 mg/ivacaftor 94 mg, lumacaftor 100 mg/ivacaftor 125 mg or lumacaftor 150 mg/ivacaftor 188 mg per packet and the following inactive ingredients: cellulose, microcrystalline; croscarmellose sodium; hypromellose acetate succinate; povidone; and sodium lauryl sulfate.

Chemical Structure Chemical Structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Advanced Liver Disease Inform patients that worsening of liver function, including hepatic encephalopathy, in patients with advanced liver disease occurred in some patients treated with ORKAMBI. Liver function decompensation, including liver failure leading to death, has been reported in CF patients with pre-existing cirrhosis with portal hypertension while receiving ORKAMBI [see Warnings and Precautions (5.1) ] .

Abnormalities in Liver Function and Testing Inform patients that abnormalities in liver function have occurred in patients treated with ORKAMBI. Blood tests to measure transaminases (ALT and AST) and bilirubin will be performed prior to initiating ORKAMBI, every 3 months during the first year of therapy, and annually thereafter. Advise patients to contact their healthcare provider if they develop symptoms consistent with hepatotoxicity [see Warnings and Precautions (5.2) ] .

Hypersensitivity Reactions, Including Anaphylaxis Hypersensitivity reactions including angioedema and anaphylaxis are possible with use of ORKAMBI. Inform patients of the early signs of hypersensitivity reactions including rash, hives, itching, facial swelling, tightness of the chest and wheezing. Advise patients to discontinue use of ORKAMBI immediately and contact their physician or go to the emergency department if these symptoms occur.

Intracranial Hypertension Inform patients that intracranial hypertension has occurred with the use of ORKAMBI. 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 ORKAMBI or drugs containing the same or similar active ingredients as ORKAMBI.

The symptoms have been observed in patients with and without a history of similar symptoms and may occur within three months of ORKAMBI 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) ] . Respiratory Events Inform patients that chest discomfort, dyspnea, and respiration abnormal were more common during initiation of ORKAMBI therapy, especially in patients with advanced lung disease and to contact their healthcare provider if they develop any of these symptoms [see Warnings and Precautions (5.6) ] .

Effect on Blood Pressure Inform patients that increased blood pressure has been observed in some patients treated with ORKAMBI and that periodic monitoring of their blood pressure during treatment is recommended and to contact their healthcare provider if they develop elevated blood pressure or notice elevations in pre-existing high blood pressure [see Warnings and Precautions (5.7) ] . Drug Interactions with CYP3A Inhibitors and Inducers Advise patients to inform their healthcare providers of all concomitant medications, herbal and dietary supplements.

Advise patients to avoid grapefruit products during the first week after treatment initiation with ORKAMBI [see Dosage and Administration (2.3) , Warnings and Precautions (5.8) , and Drug Interactions (7) ] . Instruct post-menarchal patients including females of reproductive potential on alternative methods of birth control because hormonal contraceptives should not be relied upon as an effective method of contraception. ORKAMBI may decrease the effectiveness of hormonal contraceptives and there is an increased incidence of menstruation-related adverse reactions when co-administered wit…

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