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GIVLAARI givosiran sodium 189 mg/mL Injection, Solution, 1 vial — NDC 71336-1001-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

GIVLAARI givosiran sodium 189 mg/mL Injection, Solution, 1 vial — NDC 71336-1001-1 (Billing 71336-1001-01)

by Alnylam Pharmaceuticals, Inc. · 1 VIAL, SINGLE-USE in 1 CARTON / 1 mL in 1 VIAL, SINGLE-USE

This is a package of 1 vial of GIVLAARI givosiran sodium 189 mg/mL Injection, Solution from Alnylam Pharmaceuticals, Inc., marketed since Dec 2019 and currently FDA-listed. It is this product's only package size.

NDC 71336-1001-01
🏷️ FDA NDC (as labeled) 71336-1001-1 billing pads the package segment with a zero
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

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

NDC database record

One package, one record: these facts belong to NDC 71336-1001-1 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
71336 labeler · 1001 product · 1 package
Package marketed since
Dec 12, 2019
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC-A, from the NDC)
3 7133610011 6
Medicaid fills, this package
242 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 71336-1001-1
Product NDC 71336-1001
11-digit billing NDC 71336100101
NCPDP billing unit ML — per mL (volume)
RxCUI 2265716, 2265721
UNII 5XE21E41RT
Application # NDA212194
SPL Set ID 167e663c-11e1-497b-a3fc-951d65d58eaa
Established class (EPC) Aminolevulinate Synthase 1-directed RNA Interaction; RNA; Small Interfering RNA
Physiologic effect Decreased RNA Integrity
Chemical class Small Interfering
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2019-12-12
Route SUBCUTANEOUS
Dosage form INJECTION, SOLUTION
Substance GIVOSIRAN SODIUM

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

GPI-14 85080025202020
GPI class Givlaari
GCN Seq No 080500
GCN 47364
HICL code 046222
Ingredient (HICL) Givosiran Sodium
HIC1 code D
Therapeutic class — broad (HIC1) Biliary System/Gastro-Intestinal System
HIC2 code D7
Therapeutic class — intermediate (HIC2) Act Primarily On Liver/Biliary Tract
HIC3 code D7K
Therapeutic class — specific (HIC3) Drugs To Treat Acute Hepatic Porphyria (Ahp)
AHFS code 92:92.00.00
AHFS class Other Miscellaneous Therapeutic Agents
FDB label name GIVLAARI 189 MG/ML VIAL
FDB brand name Givlaari
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 080500
  • GCN: 47364
  • GPI-14 (Medi-Span): 85080025202020
  • HICL (First Databank): 046222
  • AHFS class code: 92:92.00.00
  • RxCUI (RxNorm): 2265716
Why two NDCs? The FDA registers this code as 71336-1001-1 — a 5-4-1 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the package segment → 71336-1001-01. 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 Small Interfering RNA class.

Pharmacologic class Small Interfering RNA, Aminolevulinate Synthase 1-directed RNA Interaction
Drug family (ATC) Various alimentary tract and metabolism 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.

Clinical

Label name GIVLAARI 189 MG/ML VIAL Ingredient Givosiran Sodium
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

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

Price systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $41,574.89 $41,574.89 / 1 ml
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J0223 $120.915 / J0223 unit —
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.

Billing & reimbursement

FDA NDC (as labeled)71336-1001-1
11-digit billing NDC71336-1001-01
Format5-4-1 as registered → padded to 5-4-2 for billing (zero added to the package segment)
HCPCS J-codeJ0223
DescriptorInjection, givosiran, 0.5 mg
Billing units / pkg378 units
How the units are derivedThis package is 1; the HCPCS unit is 0.5 MG, so one package = 378 billing units.
Medicare Part B spend (2026 (Q1))$4,727,788 · 105 claims · $45,026.55 per claim (all NDCs under J0223)
Crosswalk sourceCMS ASP NDC-HCPCS Crosswalk
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
71336-1001-01 You're viewing this Main listing 1 VIAL, SINGLE-USE in 1 CARTON / 1 mL in 1 VIAL, SINGLE-USE 2019-12-12 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Givlaari 189 mg/mLthis 71336-1001-01 Alnylam 1 vial — — 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

🏛️
2019
First FDA approval
Nov 2019
📍
2026
Currently FDA-listed
7 years listed
🛡️
2034
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 Oct 2034. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Nov 20, 2019 RLD RS ⏳ ~8 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 9631193 — method of use (U-2672)
US 10131907 — drug substance (U-2672)
US 10125364 — drug substance (U-2672)
US 8106022 — drug substance (U-2672)
US 10119143 — drug substance (U-2672)
US 9133461 — drug substance (U-2672)
US 8828956 — drug substance (U-2672)
US 11028392 — drug substance (U-2672)
Exclusivity ODE-273
2019 2021 2023 2025 2027 2029 2031 2033
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 (8)
PatentTypeUse codeExpires
US 9631193 ↗ Method of use U-2672 Mar 15, 2033
US 10131907 ↗ Drug substance U-2672 Aug 24, 2028
US 10125364 ↗ Drug substance U-2672 Mar 15, 2033
US 8106022 ↗ Drug substance U-2672 Dec 12, 2029
US 10119143 ↗ Drug substance U-2672 Oct 3, 2034
US 9133461 ↗ Drug substance U-2672 Nov 30, 2033
US 8828956 ↗ Drug substance U-2672 Dec 4, 2028
US 11028392 ↗ Drug substance U-2672 Oct 3, 2034
FDA exclusivity
CodeWhat it grantsExpires
ODE-273Orphan Drug Exclusivity (7-year)Nov 20, 2026
Common questions
Is there a generic version of GIVLAARI 189 MG/ML VIAL?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for GIVLAARI 189 MG/ML VIAL. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Oct 2034 — 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.

What it looks like

Color Yellow
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 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

1 inactive ingredient listed in the exact product block matched to this NDC.

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

Inactive ingredient FAQ

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

Manufacturer & labeler

LabelerAlnylam Pharmaceuticals, Inc.
Application holderALNYLAM PHARMACEUTICALS INC
FDA applicationNDA212194 (NDA)
Labeler code71336
First marketedDec 2019
Product typeHuman Prescription Drug
Portfolio4 products on file

More NDCs from Alnylam Pharmaceuticals, Inc. labeler code 71336

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

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 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 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 40 words ▾

1 INDICATIONS AND USAGE GIVLAARI is indicated for the treatment of adults with acute hepatic porphyria (AHP). GIVLAARI is an aminolevulinate synthase 1-directed small interfering RNA indicated for the treatment of adults with acute hepatic porphyria (AHP). ( 1 )

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION The recommended dose of GIVLAARI is 2.5 mg/kg once monthly by subcutaneous injection. ( 2.1 )

2.1Recommended Dosage The recommended dose of GIVLAARI is 2.5 mg/kg administered via subcutaneous injection once monthly. Dosing is based on actual body weight. Missed Dose Administer GIVLAARI as soon as possible after a missed dose.

Resume dosing at monthly intervals following administration of the missed dose. Dose Modification for Adverse Reactions In patients with severe or clinically significant transaminase elevations, who have dose interruption and subsequent improvement, reduce the dose to 1.25 mg/kg once monthly [see Warnings and Precautions (5.2) ] . In patients who resume dosing at 1.25 mg/kg once monthly without recurrence of severe or clinically significant transaminase elevations, the dose may be increased to the recommended dose of 2.5 mg/kg once monthly.

2.2Administration Instructions Ensure that medical support is available to appropriately manage anaphylactic reactions when administering GIVLAARI [see Warnings and Precautions (5.1) ]. GIVLAARI is intended for subcutaneous use by a healthcare professional only. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

GIVLAARI is a sterile, preservative-free, clear, colorless-to-yellow solution. It is supplied in a single-dose vial, as a ready-to-use solution that does not require additional reconstitution or dilution prior to administration. Use aseptic technique.

Calculate the required volume of GIVLAARI based on the recommended weight-based dosage [see Dosage and Administration (2.1) ] . Withdraw the indicated injection volume of GIVLAARI using a 21-gauge or larger needle. Divide doses requiring volumes greater than 1.5 mL equally into multiple syringes.

Replace the 21-gauge or larger needle with either a 25-gauge or 27-gauge needle with 1/2" or 5/8" needle length. Avoid having GIVLAARI on the needle tip until the needle is in the subcutaneous space. Administer injection into the abdomen, the back or side of the upper arms, or the thighs.

Rotate injection sites. An injection should never be given into scar tissue or areas that are reddened, inflamed, or swollen. If injecting into the abdomen, avoid a 5 cm diameter circle around the navel.

If more than one injection is needed for a single dose of GIVLAARI, the injection sites should be at least 2 cm apart from previous injection locations. Discard unused portion of the drug.

💊 Dosage Forms and Strengths 25 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: 189 mg/mL clear, colorless-to-yellow solution in a single-dose vial Injection: 189 mg/mL in a single-dose vial. ( 3 )

⛔ Contraindications 30 words ▾

4 CONTRAINDICATIONS GIVLAARI is contraindicated in patients with known severe hypersensitivity to givosiran. Reactions have included anaphylaxis [see Warnings and Precautions (5.1) ]. Severe hypersensitivity to givosiran. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Anaphylactic Reaction: Ensure that medical support is available to appropriately manage anaphylactic reactions when administering GIVLAARI. Monitor for signs and symptoms. If anaphylaxis occurs, discontinue GIVLAARI and administer appropriate medical treatment.

( 5.1 ) Hepatic Toxicity: Measure liver function at baseline and periodically during treatment with GIVLAARI. Interrupt or discontinue treatment with GIVLAARI for severe or clinically significant transaminase elevations. ( 2.1 , 5.2 ) Renal Toxicity: Monitor renal function during treatment with GIVLAARI as clinically indicated.

( 5.3 ) Injection Site Reactions: May occur, including recall reactions. Monitor for reactions and manage clinically as needed. ( 5.4 ) Blood Homocysteine Increased: Measure blood homocysteine at baseline and monitor for changes during treatment with GIVLAARI.

In patients with elevated blood homocysteine, consider supplementation with vitamin B6 (as monotherapy or multivitamin). ( 5.5 ) Pancreatitis: Consider acute pancreatitis as a potential diagnosis in GIVLAARI-treated patients with acute upper abdominal pain, clinically significant elevation of pancreatic enzymes and/or imaging findings of acute pancreatitis, to ensure appropriate management. ( 5.6 )

5.1Anaphylactic Reaction Anaphylaxis has occurred with GIVLAARI treatment (<1% of patients in clinical trials) [see Adverse Reactions (6.1) ] . Ensure that medical support is available to appropriately manage anaphylactic reactions when administering GIVLAARI. Monitor for signs and symptoms of anaphylaxis. If anaphylaxis occurs, immediately discontinue administration of GIVLAARI and institute appropriate medical treatment.

5.2Hepatic Toxicity Transaminase elevations (ALT) of at least 3 times the upper limit of normal (ULN) were observed in 15% of patients treated with GIVLAARI in the placebo-controlled trial [see Adverse Reactions (6.1) ] . Transaminase elevations primarily occurred between 3 to 5 months following initiation of treatment. Measure liver function tests prior to initiating treatment with GIVLAARI, repeat every month during the first 6 months of treatment, and as clinically indicated thereafter.

Interrupt or discontinue treatment with GIVLAARI for severe or clinically significant transaminase elevations. For resumption of dosing after interruption, see Dosage and Administration (2.1) .

5.3Renal Toxicity Increases in serum creatinine levels and decreases in estimated glomerular filtration rate (eGFR) have been reported during treatment with GIVLAARI [see Adverse Reactions (6.1) ] . In the placebo-controlled study, 15% of the patients in the GIVLAARI arm experienced a renally-related adverse reaction. The median increase in creatinine at Month 3 was 0.07 mg/dL. Monitor renal function during treatment with GIVLAARI as clinically indicated.

5.4Injection Site Reactions Injection site reactions have been reported in 25% of patients receiving GIVLAARI in the placebo-controlled trial. Symptoms included erythema, pain, pruritus, rash, discoloration, or swelling around the injection site. Among 12 patients with reactions, the highest severity of the reaction was mild among 11 (92%) patients and moderate in one (8%) patient.

One (2%) patient experienced a single, transient, recall reaction of erythema at a prior injection site with a subsequent dose administration [see Adverse Reactions (6.1) ] .

5.5Blood Homocysteine Increased Increases in blood homocysteine levels have occurred in patients receiving GIVLAARI [see Adverse Reactions (6.1) ] . In the ENVISION study, during the open label extension, adverse reactions of blood homocysteine increased were reported in 15 of 93 (16%) patients treated with GIVLAARI. The clinical relevance of the elevations in blood homocysteine during treatment with GIVLAARI is unknown.

Measure blood homocysteine levels prior to initiating treatment and monitor for changes during treatment with GIVLAARI. In patients with elevated blood… [Excerpted — this section continues on DailyMed.]

🤒 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: Anaphylactic Reaction [see Warnings and Precautions (5.1) ] Transaminase Elevations [see Warnings and Precautions (5.2) ] Serum Creatinine Increase [see Warnings and Precautions (5.3) ] Injection Site Reactions [see Warnings and Precautions (5.4) ] Blood Homocysteine Increased [see Warnings and Precautions (5.5) ] Pancreatitis [see Warnings and Precautions (5.6) ] The most common adverse reactions (≥20% of patients) included nausea and injection site reactions.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alnylam Pharmaceuticals at 1-877-256-9526 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trial 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. In the pivotal placebo-controlled, double-blind study (ENVISION), 48 patients received 2.5 mg/kg GIVLAARI and 46 patients received placebo, administered once monthly via subcutaneous injection for up to 6 months. Patients received GIVLAARI for a median of 5.5 months (range 2.7-6.4 months).

Of these, 47 patients received ≥5 months of treatment. The most frequently occurring (≥20% incidence) adverse reactions reported in patients treated with GIVLAARI were nausea (27%) and injection site reactions (25%). Permanent discontinuation occurred in one patient due to elevated transaminases.

Table 1: Adverse Reactions that Occurred at Least 5% More Frequently in Patients Treated with GIVLAARI Compared to Patients Treated with Placebo Adverse Reaction GIVLAARI N=48 N (%) Placebo N=46 N (%) Nausea 13 (27) 5 (11) Injection site reactions 12 (25) 0 Rash Grouped term includes pruritus, eczema, erythema, rash, rash pruritic, urticaria 8 (17) 2 (4) Serum creatinine increase Grouped term includes blood creatinine increased, glomerular filtration rate decreased, chronic kidney disease (decreased eGFR) 7 (15) 2 (4) Transaminase elevations 6 (13) 1 (2) Fatigue 5 (10) 2 (4) Adverse reactions observed at a lower frequency occurring in placebo-controlled and open-label clinical studies included anaphylactic reaction (one patient, 0.9%) and hypersensitivity (one patient, 0.9%).

In the ENVISION study, during the open label extension, adverse reactions of blood homocysteine increased were reported in 15 of 93 (16%) patients treated with GIVLAARI [see Warnings and Precautions (5.5) ].

6.2Immunogenicity As with all oligonucleotides, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.

For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other products may be misleading. In placebo-controlled and open-label clinical studies, 1 of 111 patients with AHP (0.9%) developed treatment-emergent anti-drug antibodies (ADA) during treatment with GIVLAARI. No clinically significant differences in the clinical efficacy, safety, pharmacokinetic, or pharmacodynamic profiles of GIVLAARI were observed in the patient who tested positive for anti-givosiran antibodies.

6.3Postmarketing Experience The following additional adverse reactions have been reported during post-approval use. Because these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 109 words ▾

7 DRUG INTERACTIONS Sensitive CYP1A2 and CYP2D6 Substrates: Avoid concomitant use with CYP1A2 and CYP2D6 substrates for which minimal concentration changes may lead to serious or life-threatening toxicities. ( 7.1 )

7.1Effect of GIVLAARI on Other Drugs Sensitive CYP1A2 and CYP2D6 Substrates Concomitant use of GIVLAARI increases the concentration of CYP1A2 or CYP2D6 substrates [see Clinical Pharmacology (12.3) ] , which may increase adverse reactions of these substrates. Avoid concomitant use of GIVLAARI with CYP1A2 or CYP2D6 substrates, for which minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP1A2 or CYP2D6 substrate dosage in accordance with approved product labeling.

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary In animal reproduction studies, subcutaneous administration of givosiran to pregnant rabbits during the period of organogenesis resulted in adverse developmental outcomes at doses that produced maternal toxicity (see Data ). There are no available data with GIVLAARI use in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Consider the benefits and risks of GIVLAARI for the mother and potential adverse effects to the fetus when prescribing GIVLAARI to a pregnant woman.

The estimated background risk of major birth defects and miscarriage in 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.

Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Porphyria attacks during pregnancy, often triggered by hormonal changes, occur in 24% to 95% of AHP patients, with maternal mortality ranging from 2% to 42%. Pregnancy in AHP patients is associated with higher rates of spontaneous abortion, hypertension and low birth weight infants. Data Animal Data In an embryo-fetal development study in pregnant rabbits, givosiran was administered subcutaneously at doses of 0.5, 1.5, and 5 mg/kg/day during organogenesis (gestational days 7-19) or 20 mg/kg as a single administration on gestation day 7.

Administration of givosiran was maternally toxic based on decreased body weight gain at all dose levels tested and resulted in increased postimplantation loss starting at 1.5 mg/kg/day. An increased incidence of skeletal variations of the sternebrae was observed at 20 mg/kg. The 1.5 mg/kg/day dose in rabbits is 5 times the maximum recommended human dose (MRHD) of 2.5 mg/kg/month normalized to 0.089 mg/kg/day, based on body surface area.

In a combined fertility and embryo-fetal development study in female rats, givosiran was administered subcutaneously at doses of 0.5 to 5 mg/kg/day during organogenesis (gestational days 6-17). The 5 mg/kg/day dose (9 times the normalized MRHD based on body surface area) was associated with a skeletal variation (incomplete ossification of pubes) and produced maternal toxicity. In a pre- and postnatal development study, givosiran administered subcutaneously to pregnant rats on gestation days 7, 13, and 19 and postnatal days 6, 12, and 18 at doses up to 30 mg/kg did not produce maternal toxicity or developmental effects in the offspring.

8.2Lactation Risk Summary There are no data on the presence of GIVLAARI in human milk, the effects on the breastfed child, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for GIVLAARI and any potential adverse effects on the breastfed child from GIVLAARI or from the underlying maternal condition.

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

8.5Geriatric Use Clinical studies of GIVLAARI did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary In animal reproduction studies, subcutaneous administration of givosiran to pregnant rabbits during the period of organogenesis resulted in adverse developmental outcomes at doses that produced maternal toxicity (see Data ). There are no available data with GIVLAARI use in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Consider the benefits and risks of GIVLAARI for the mother and potential adverse effects to the fetus when prescribing GIVLAARI to a pregnant woman.

The estimated background risk of major birth defects and miscarriage in 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.

Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Porphyria attacks during pregnancy, often triggered by hormonal changes, occur in 24% to 95% of AHP patients, with maternal mortality ranging from 2% to 42%. Pregnancy in AHP patients is associated with higher rates of spontaneous abortion, hypertension and low birth weight infants. Data Animal Data In an embryo-fetal development study in pregnant rabbits, givosiran was administered subcutaneously at doses of 0.5, 1.5, and 5 mg/kg/day during organogenesis (gestational days 7-19) or 20 mg/kg as a single administration on gestation day 7.

Administration of givosiran was maternally toxic based on decreased body weight gain at all dose levels tested and resulted in increased postimplantation loss starting at 1.5 mg/kg/day. An increased incidence of skeletal variations of the sternebrae was observed at 20 mg/kg. The 1.5 mg/kg/day dose in rabbits is 5 times the maximum recommended human dose (MRHD) of 2.5 mg/kg/month normalized to 0.089 mg/kg/day, based on body surface area.

In a combined fertility and embryo-fetal development study in female rats, givosiran was administered subcutaneously at doses of 0.5 to 5 mg/kg/day during organogenesis (gestational days 6-17). The 5 mg/kg/day dose (9 times the normalized MRHD based on body surface area) was associated with a skeletal variation (incomplete ossification of pubes) and produced maternal toxicity. In a pre- and postnatal development study, givosiran administered subcutaneously to pregnant rats on gestation days 7, 13, and 19 and postnatal days 6, 12, and 18 at doses up to 30 mg/kg did not produce maternal toxicity or developmental effects in the offspring.

🧒 Pediatric Use 13 words ▾

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

🧓 Geriatric Use 27 words ▾

8.5Geriatric Use Clinical studies of GIVLAARI did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Givosiran is a double-stranded small interfering RNA that causes degradation of aminolevulinate synthase 1 ( ALAS1 ) mRNA in hepatocytes through RNA interference, reducing the elevated levels of liver ALAS1 mRNA. This leads to reduced circulating levels of neurotoxic intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG), factors associated with attacks and other disease manifestations of AHP.

12.2Pharmacodynamics The pharmacodynamic effects of GIVLAARI were evaluated in chronic high excreters treated with 0.035 to 2.5 mg/kg single dose and AHP patients treated with 2.5 to 5 mg/kg once monthly and 2.5 to 5 mg/kg once quarterly dose via subcutaneous injection. Dose-dependent reduction in urinary ALAS1 mRNA, ALA and PBG levels was observed over the 0.035 to 5 mg/kg dose range (0.14 to 2-fold the approved recommended dosage). Median reductions from baseline in urinary ALA and PBG of 83.7% and 75.1%, respectively, were observed 14 days after the first dose of GIVLAARI 2.5 mg/kg once monthly in AHP patients.

Maximal reductions in ALA and PBG levels were achieved around Month 3, with median reductions from baseline of 93.8% for ALA and 94.5% for PBG, and were sustained thereafter with repeated once monthly dosing. Cardiac Electrophysiology The effect of GIVLAARI on the QTc interval was evaluated in a double-blind, placebo-controlled study and the open-label extension in 94 patients. No large mean increase in QTc (i.e. >20 ms) was detected at the 2.5 mg/kg once monthly dose level.

A dedicated thorough QT study has not been conducted with GIVLAARI.

12.3Pharmacokinetics The pharmacokinetics of givosiran and its active metabolite [AS(N-1)3′ givosiran] were evaluated following single and multiple dosing in chronic high excreter subjects and AHP patients as summarized in Table 2. Table 2. Pharmacokinetic Parameters of Givosiran and Its Active Metabolite Givosiran AS(N-1)3′ Givosiran General Information Steady-State Exposure C max [Mean (CV%)] 321 ng/mL (51%) 123 ng/mL (64%) AUC 24 [Mean (CV%)] 4130 ng∙h/mL (43%) 1930 ng∙h/mL (63%) Dose Proportionality Steady-state maximum plasma concentration (C max ) and area under the curve (AUC) for givosiran and AS(N-1)3′ givosiran increase proportionally over the 0.35 mg/kg to 2.5 mg/kg once monthly dose range (0.14 to 1-fold the approved recommended dosage).

C max and AUC for givosiran and AS(N-1)3′ givosiran increase slightly greater than proportionally at doses greater than 2.5 mg/kg once monthly. Accumulation No accumulation of givosiran or AS(N-1)3′ givosiran was observed following multiple dosing. Absorption T max [Median (range)] 3 (0.5-8) hours 7 (1.5-12) hours Distribution Apparent Central Volume of Distribution (Vz/F) [Mean (RSE%)] Based on population PK model estimation.

10.4L (2.3%) Protein Binding 90% Givosiran plasma protein binding was concentration-dependent and decreased with increasing givosiran concentrations (from 92% at 1 µg/mL to 21% at 50 µg/mL). Not evaluated Organ Distribution Givosiran and AS(N-1)3′ givosiran distribute primarily to the liver after subcutaneous dosing. Elimination Half-Life [Mean (CV%)] 6 hours (46%) 6 hours (41%) Apparent Clearance [Mean (CV%)]

35.1 L/hr (18%)

64.7L/hr (33%) Metabolism Primary Pathway Givosiran is metabolized by nucleases to oligonucleotides of shorter lengths. Givosiran is not a substrate of CYP enzymes Based on in vitro study result. . Active Metabolite The active metabolite, AS(N-1)3′ givosiran, is equipotent to givosiran in plasma and the AUC 0-24 represents 45% of givosiran AUC, at the approved recommended givosiran dosage.

Excretion Primary Pathway The dose recovered in urine was 5%-14% as givosiran and 4%-13% as AS(N-1)3′ givosiran After single and multiple subcutaneous doses of givosiran 2.5 mg/kg and 5 mg/kg. . Specific Populations No clinically meaningful differences in givosiran pharmacokinetics or pharmacodynamics (percent reduction in urinary ALA and PBG) were obs… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 60 words ▾

12.1Mechanism of Action Givosiran is a double-stranded small interfering RNA that causes degradation of aminolevulinate synthase 1 ( ALAS1 ) mRNA in hepatocytes through RNA interference, reducing the elevated levels of liver ALAS1 mRNA. This leads to reduced circulating levels of neurotoxic intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG), factors associated with attacks and other disease manifestations of AHP.

📦 How Supplied / Storage and Handling 52 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied GIVLAARI (givosiran) is a clear, colorless-to-yellow ready-to-use solution available in single-dose vials of 189 mg/mL in cartons containing one vial (NDC 71336-1001-1).

16.2Storage and Handling Store at 2°C to 25°C (36°F to 77°F). Store GIVLAARI in its original container until ready for use.

📦 Storage and Handling 22 words ▾

16.2Storage and Handling Store at 2°C to 25°C (36°F to 77°F). Store GIVLAARI in its original container until ready for use.

📋 Description ~1 min read ▾

11 DESCRIPTION GIVLAARI is an aminolevulinate synthase 1-directed small interfering RNA (siRNA), covalently linked to a ligand containing three N-acetylgalactosamine (GalNAc) residues to enable delivery of the siRNA to hepatocytes. The structural formulas of the givosiran drug substance in its sodium form, and the ligand (L96), are presented below. Abbreviations: Af = adenine 2'-F ribonucleoside; Cf = cytosine 2'-F ribonucleoside; Uf = uracil 2'-F ribonucleoside; Am = adenine 2'-OMe ribonucleoside; Cm = cytosine 2'-OMe ribonucleoside; Gf = guanine 2'-F ribonucleoside; Gm = guanine 2'-OMe ribonucleoside; Um = uracil 2'-OMe ribonucleoside; L96 = triantennary GalNAc (N-acetylgalactosamine) GIVLAARI is supplied as a sterile, preservative-free, 1-mL colorless-to-yellow solution for subcutaneous injection containing 189 mg givosiran in a single-dose, 2-mL Type 1 glass vial with a fluoropolymer-coated rubber stopper and a flip-off aluminum seal.

GIVLAARI is available in cartons containing one single-dose vial each . GIVLAARI is formulated in Water for Injection. Sodium hydroxide and/or phosphoric acid may have been added for pH adjustment during product manufacturing.

The molecular formula of givosiran sodium is C 524 H 651 F 16 N 173 Na 43 O 316 P 43 S 6 with a molecular weight of 17,245.56 Da. The molecular formula of givosiran (free acid) is C 524 H 694 F 16 N 173 O 316 P 43 S 6 with a molecular weight of 16,300.34 Da. Chemical Structure

💬 Information for Patients 183 words ▾

17 PATIENT COUNSELING INFORMATION Advise patients of the potential risks of GIVLAARI treatment: Anaphylactic Reaction: Inform patients about the risk and possible symptoms of severe hypersensitivity reactions that could occur [see Warnings and Precautions (5.1) ] . Hepatic Toxicity: Inform patients that transaminase elevations may occur, and that laboratory testing will be conducted in the first 6 months of treatment and as clinically indicated thereafter [see Warnings and Precautions (5.2) ] . Renal Toxicity: Inform patients that increases in serum creatinine and decreases in eGFR have been reported and that laboratory testing will be conducted as clinically indicated [see Warnings and Precautions (5.3) ] .

Injection Site Reactions: Inform patients of the signs and symptoms of injection site reactions (examples include redness, pain, itching, rash, discoloration, or localized swelling) [see Warnings and Precautions (5.4) ]. Blood Homocysteine Increased : Inform patients that increases in blood homocysteine levels have been reported when using GIVLAARI, and that laboratory testing will be conducted prior to and during treatment with GIVLAARI. Vitamin supplementation may be considered for elevated blood homocysteine levels [see Warnings and Precautions (5.5) ].

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics The pharmacokinetics of givosiran and its active metabolite [AS(N-1)3′ givosiran] were evaluated following single and multiple dosing in chronic high excreter subjects and AHP patients as summarized in Table 2. Table 2. Pharmacokinetic Parameters of Givosiran and Its Active Metabolite Givosiran AS(N-1)3′ Givosiran General Information Steady-State Exposure C max [Mean (CV%)] 321 ng/mL (51%) 123 ng/mL (64%) AUC 24 [Mean (CV%)] 4130 ng∙h/mL (43%) 1930 ng∙h/mL (63%) Dose Proportionality Steady-state maximum plasma concentration (C max ) and area under the curve (AUC) for givosiran and AS(N-1)3′ givosiran increase proportionally over the 0.35 mg/kg to 2.5 mg/kg once monthly dose range (0.14 to 1-fold the approved recommended dosage).

C max and AUC for givosiran and AS(N-1)3′ givosiran increase slightly greater than proportionally at doses greater than 2.5 mg/kg once monthly. Accumulation No accumulation of givosiran or AS(N-1)3′ givosiran was observed following multiple dosing. Absorption T max [Median (range)] 3 (0.5-8) hours 7 (1.5-12) hours Distribution Apparent Central Volume of Distribution (Vz/F) [Mean (RSE%)] Based on population PK model estimation.

10.4L (2.3%) Protein Binding 90% Givosiran plasma protein binding was concentration-dependent and decreased with increasing givosiran concentrations (from 92% at 1 µg/mL to 21% at 50 µg/mL). Not evaluated Organ Distribution Givosiran and AS(N-1)3′ givosiran distribute primarily to the liver after subcutaneous dosing. Elimination Half-Life [Mean (CV%)] 6 hours (46%) 6 hours (41%) Apparent Clearance [Mean (CV%)]

35.1 L/hr (18%)

64.7L/hr (33%) Metabolism Primary Pathway Givosiran is metabolized by nucleases to oligonucleotides of shorter lengths. Givosiran is not a substrate of CYP enzymes Based on in vitro study result. . Active Metabolite The active metabolite, AS(N-1)3′ givosiran, is equipotent to givosiran in plasma and the AUC 0-24 represents 45% of givosiran AUC, at the approved recommended givosiran dosage.

Excretion Primary Pathway The dose recovered in urine was 5%-14% as givosiran and 4%-13% as AS(N-1)3′ givosiran After single and multiple subcutaneous doses of givosiran 2.5 mg/kg and 5 mg/kg. . Specific Populations No clinically meaningful differences in givosiran pharmacokinetics or pharmacodynamics (percent reduction in urinary ALA and PBG) were observed based on age (19 to 65 years), sex, race/ethnicity, mild, moderate or severe renal impairment (eGFR ≥15 to <89 mL/min/1.73m 2 estimated by the Modification of Diet in Renal Disease [MDRD] formula), and mild hepatic impairment (bilirubin ≤1×ULN and AST >1×ULN, or bilirubin >1×ULN to 1.5×ULN).The effect of end-stage renal disease (eGFR <15 mL/min/1.73m 2 ), and moderate to severe hepatic impairment on givosiran pharmacokinetics is unknown.

Drug Interaction Studies Clinical Studies Effect of givosiran on CYP1A2 Substrates: Concomitant use of a single subcutaneous dose of givosiran 2.5 mg/kg increased caffeine (sensitive CYP1A2 substrate) AUC by 3.1-fold and C max by 1.3-fold [see Drug Interactions (7.1) ] . Effect of givosiran on CYP2D6 Substrates: Concomitant use of a single subcutaneous dose of givosiran 2.5 mg/kg increased dextromethorphan (sensitive CYP2D6 substrate) AUC by 2.4-fold and C max by 2.0-fold [see Drug Interactions (7.1) ] . Effect of givosiran on other CYP450 Substrates: Concomitant use of a single subcutaneous dose of givosiran 2.5 mg/kg increased losartan (CYP2C9 substrate) AUC by 1.1-fold with no change in C max ; increased omeprazole (sensitive CYP2C19 substrate) AUC by 1.6-fold and C max by 1.1-fold; increased midazolam (sensitive CYP3A4 substrate) AUC by 1.5-fold and C max by 1.2-fold.

These changes in exposure were not considered clinically relevant. In Vitro Studies Effect of givosiran on CYP450 Enzymes: In vitro studies indicate that givosiran does not directly inhibit or induce CYP enzymes; however, because of its pharmacological effects on the hepatic heme biosynthesis pa… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 189 words ▾

12.2Pharmacodynamics The pharmacodynamic effects of GIVLAARI were evaluated in chronic high excreters treated with 0.035 to 2.5 mg/kg single dose and AHP patients treated with 2.5 to 5 mg/kg once monthly and 2.5 to 5 mg/kg once quarterly dose via subcutaneous injection. Dose-dependent reduction in urinary ALAS1 mRNA, ALA and PBG levels was observed over the 0.035 to 5 mg/kg dose range (0.14 to 2-fold the approved recommended dosage). Median reductions from baseline in urinary ALA and PBG of 83.7% and 75.1%, respectively, were observed 14 days after the first dose of GIVLAARI 2.5 mg/kg once monthly in AHP patients.

Maximal reductions in ALA and PBG levels were achieved around Month 3, with median reductions from baseline of 93.8% for ALA and 94.5% for PBG, and were sustained thereafter with repeated once monthly dosing. Cardiac Electrophysiology The effect of GIVLAARI on the QTc interval was evaluated in a double-blind, placebo-controlled study and the open-label extension in 94 patients. No large mean increase in QTc (i.e. >20 ms) was detected at the 2.5 mg/kg once monthly dose level.

A dedicated thorough QT study has not been conducted with GIVLAARI.

🔬 Clinical Studies ~2 min read ▾

14 CLINICAL STUDIES The efficacy of GIVLAARI in patients with acute hepatic porphyria was evaluated in the ENVISION trial (NCT03338816), a randomized, double-blind, placebo-controlled, multinational study. ENVISION enrolled 94 patients with acute hepatic porphyria (AHP) (89 patients with AIP, 2 patients with variegate porphyria [VP], 1 patient with hereditary coproporphyria [HCP], and 2 patients with no identified mutation). Eligible patients were randomized 1:1 to receive once monthly subcutaneous injections of GIVLAARI 2.5 mg/kg or placebo during the 6-month double-blind period.

In this study, inclusion criteria specified a minimum of 2 porphyria attacks requiring hospitalization, urgent healthcare visit, or intravenous hemin administration at home in the 6 months prior to study entry. After the 6 month treatment period patients were enrolled in an open label extension period for up to 30 months. Ninety-three patients were enrolled in the open label extension period.

Hemin use during the study was permitted for the treatment of acute porphyria attacks. The median age of patients studied was 37.5 years (range 19 to 65 years), 89% of patients were female, and 78% were white. GIVLAARI and placebo arms were balanced with respect to historical porphyria attack rate, hemin prophylaxis prior to study entry, use of opioid medications, and patient-reported measures of pain symptoms between attacks.

Efficacy in the 6-month double-blind period was measured by the rate of porphyria attacks that required hospitalizations, urgent healthcare visit, or intravenous hemin administration at home. Efficacy results for GIVLAARI are provided in Table 3. On average, AHP patients on GIVLAARI experienced 70% (95% CI: 60%, 80%) fewer porphyria attacks compared to placebo.

Table 3. Rate of Porphyria Attacks Attacks that require hospitalization, urgent healthcare visits, or intravenous hemin administration at home. and Days of Hemin Use in Patients with AHP Over the 6-Month Double-blind Period of ENVISION Patients with AHP GIVLAARI (N=48) Placebo (N=46) Mean Rate (95% CI) of Porphyria Attacks 1.9 (1.3, 2.8) 6.5 (4.5, 9.3) Rate Ratio Adjusted for prior hemin prophylaxis status and historical attack rates. A ratio <1 represents a favorable outcome for GIVLAARI.

(95% CI) (GIVLAARI/placebo) 0.3 p < 0.0001 (0.2, 0.4) Mean Days (95% CI) of Hemin Use 4.7 (2.8, 7.9) 12.8 (7.6, 21.4) Ratio (95% CI) (GIVLAARI/placebo) 0.3 p = 0.0002 (0.1, 0.5) GIVLAARI also resulted in a reduction in hemin use, urinary ALA, and urinary PBG.

🧪 Nonclinical Toxicology 189 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility In a carcinogenicity study in Sprague Dawley rats administered 25, 50, or 100 mg/kg givosiran by subcutaneous injection every 28 days for up to 89 weeks (males) or 85 weeks (females), givosiran doses in rats were 2, 3, and 6 times, respectively, the MRHD based on body surface area. A statistically significant increase in hepatocellular adenomas occurred in males at 100 mg/kg/month, the clinical significance of which is uncertain. In a carcinogenicity study in male and female Tg.rasH2 mice administered givosiran by subcutaneous injection every 28 days for 26 weeks, up to 1500 mg/kg, givosiran was not carcinogenic.

Givosiran was not genotoxic in the in vitro bacterial reverse mutation (Ames) assays, an in vitro chromosomal aberration assay in cultured human peripheral blood lymphocytes or the in vivo micronucleus assay in rats. In fertility and early embryonic development studies, givosiran administered subcutaneously once weekly at doses up to 30 mg/kg in male and female rats prior to and during mating, and continuing in females throughout organogenesis, resulted in no adverse effects on fertility or reproductive function in male or female animals.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 186 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility In a carcinogenicity study in Sprague Dawley rats administered 25, 50, or 100 mg/kg givosiran by subcutaneous injection every 28 days for up to 89 weeks (males) or 85 weeks (females), givosiran doses in rats were 2, 3, and 6 times, respectively, the MRHD based on body surface area. A statistically significant increase in hepatocellular adenomas occurred in males at 100 mg/kg/month, the clinical significance of which is uncertain. In a carcinogenicity study in male and female Tg.rasH2 mice administered givosiran by subcutaneous injection every 28 days for 26 weeks, up to 1500 mg/kg, givosiran was not carcinogenic.

Givosiran was not genotoxic in the in vitro bacterial reverse mutation (Ames) assays, an in vitro chromosomal aberration assay in cultured human peripheral blood lymphocytes or the in vivo micronucleus assay in rats. In fertility and early embryonic development studies, givosiran administered subcutaneously once weekly at doses up to 30 mg/kg in male and female rats prior to and during mating, and continuing in females throughout organogenesis, resulted in no adverse effects on fertility or reproductive function in male or female animals.

📄 Package Label / Principal Display Panel 39 words ▾

PRINCIPAL DISPLAY PANEL - 189 mg/mL Vial Carton NDC 71336-1001-1 Rx Only GIVLAARI ® (givosiran) injection 189 mg/mL For Subcutaneous Injection By Healthcare Professional Only 1 Single-Dose Vial Discard Unused Portion PRINCIPAL DISPLAY PANEL - 189 mg/mL Vial Carton

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

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
242
Units reimbursed last 4 qtrs
262
Gross reimbursed last 4 qtrs
$10.89M
Avg / prescription
$45,010.83
Avg / unit
$41,517.68
Latest quarter Q1 2026
66Rx
Fee-for-service vs managed care ⓘ
50% FFS 50% MCO
Fee-for-service · 120 Rx Managed care · 122 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: 113 units · 0.3 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: 32 units · 0.5 per 100k residents MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: 61 units · 0.7 per 100k residents VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: 44 units · 0.6 per 100k residents AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 13 units · 0.1 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
0.10.7
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 Virginia 0.7 /100k
2 Arizona 0.6 /100k
3 Missouri 0.5 /100k
4 California 0.3 /100k
5 North Carolina 0.1 /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 Givlaari — 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 Givlaari. 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
$5.21M
Claims incl. refills
93
Beneficiaries
41
Spend / beneficiary
$127,134.67
Spend / claim
$56,048.62
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 GIVLAARI (this brand).

Top reported reactions

Porphyria Acute469
Hospitalisation171
Nausea105
Intentional Dose Omission103
Therapy Interrupted100
Fatigue97
Pain85

Age at onset

Adult3
Elderly1

Reporter sex

1,462 reports
Male · 12%
Female · 85%
Unknown · 2%

Serious outcomes

Hospitalization713
Death47
Disabling20
Life-threatening16
Reports over time (by year) — tap or hover for the count & year
2020 2022 2024 2026 310 75
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.

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 ✓ Available
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 form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
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 Alnylam Pharmaceuticals, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Alnylam Pharmaceuticals, Inc. 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.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J0223 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
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.
← 71336-1000-01 · Alnylam 71336-1002-01 · Alnylam →
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.