HomeNDC LookupIngredientsHuman C1-Esterase Inhibitor › 42227-0083-01
Cinryze HUMAN C1-ESTERASE INHIBITOR Kit — NDC 42227-0083-01 package photo

Cinryze HUMAN C1-ESTERASE INHIBITOR Kit

by Takeda Pharmaceuticals America, Inc. · 1 KIT in 1 CARTON (42227-083-01) * 5 mL in 1 VIAL, SINGLE-USE (42227-081-01) * 5 mL in 1 VIAL, GLASS (64764-515-50)
NDC 42227-0083-01
🏷️ FDA NDC (as labeled) 42227-083-01 billing pads the product segment with a zero
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 →

🆔 Identity & classification

FDA NDC (as labeled) 42227-083-01
Product NDC 42227-083
11-digit billing NDC 42227008301
NCPDP billing unit EA — each (per item)
Application # BLA125267
SPL Set ID d53a911f-070d-498a-8a61-baab72b9d0fe
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2021-01-15
Dosage form KIT
GPI-14 85802022002120
GPI class Cinryze
GCN Seq No 040429
GCN 10495
HICL code 018568
Ingredient (HICL) C1 Esterase Inhibitor
HIC1 code M
Therapeutic class — broad (HIC1) Blood
HIC2 code M0
Therapeutic class — intermediate (HIC2) Blood And Blood Replacement Preparations
HIC3 code M0N
Therapeutic class — specific (HIC3) C1 Esterase Inhibitors
AHFS code 92:32.00.00
AHFS class Complement Inhibitors (92:32)
FDB label name CINRYZE 500 UNIT VIAL-DILUENT
FDB brand name Cinryze
Legend status F — Federal legend — prescription drug or device
Biologic (Purple Book) 351(a)
Why two NDCs? The FDA registers this code as 42227-083-01 — 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 → 42227-0083-01. 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.

🏭 Manufacturer & labeler

LabelerTakeda Pharmaceuticals America, Inc.
FDA applicationBLA125267 (BLA)
Labeler code42227
First marketedJan 2021
Product typePlasma Derivative
Portfolio154 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 CINRYZE 500 UNIT VIAL-DILUENT Ingredient C1 Esterase Inhibitor
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.

🧪 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.

The FDA label contains product information, but this exact NDC could not be matched safely to one product block. We intentionally withheld sibling strengths’ ingredients.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

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

💲 Pricing

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

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $3,177.92
Medicare drug plans payPart D · Q2 2026 $3,261.98
Medicare Part B allowsASP · J0598 $66.753 / J0598 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)42227-083-01
11-digit billing NDC42227-0083-01
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ0598
DescriptorInjection, c-1 esterase inhibitor (human), cinryze, 10 units
Billing units / pkg50 units
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.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Berinert 63833-0825-02 CSL 1 kit FDA listed
HAEGARDA C1 Esterase Inhibitor Subcutaneous (Human) 63833-0828-02 CSL 1 kit FDA listed
HAEGARDA C1 Esterase Inhibitor Subcutaneous (Human) 63833-0829-02 CSL 1 kit FDA listed
Cinryzethis 42227-0083-01 Takeda 1 kit FDA listed
About this product: this is a biologic. Biologics don't have small-molecule generics — competition comes from FDA-licensed biosimilars (shown above), not generics.
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 & biosimilar status

🏛️
2008
First FDA approval
Oct 2008
📍
2026
Currently FDA-listed
18 years listed
🧬
·
Biosimilars
see Purple Book
🧬Biologic — competition comes from biosimilars

Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.

Where does this data come from?
Patents and exclusivity from the FDA Purple Book (biologics), refreshed from public FDA data. Biosimilar 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 42227-0083-01, 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
62
Units reimbursed last 4 qtrs
482
Gross reimbursed last 4 qtrs
$1.53M
Avg / prescription
$24,705.78
Avg / unit
$3,177.92
Latest quarter Q4 2025
11Rx
Fee-for-service vs managed care
61% FFS 39% MCO
Fee-for-service · 38 Rx Managed care · 24 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: 223 units · 3.8 per 100k residents WI Michigan: no data reported MI New York: 127 units · 0.6 per 100k residents 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: 132 units · 1.1 per 100k residents 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: no data reported 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
0.63.8
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 Wisconsin 3.8 /100k
2 Ohio 1.1 /100k
3 New York 0.6 /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 Cinryze — 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 Cinryze. 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
$6.67M
Claims incl. refills
65
Beneficiaries
25
Spend / beneficiary
$266,909.80
Spend / claim
$102,657.61
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.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
42227-0083-01 You're viewing this 1 KIT in 1 CARTON (42227-083-01) * 5 mL in 1 VIAL, SINGLE-USE (42227-081-01) * 5 mL in 1 VIAL, GLASS (64764-515-50) 2021-01-15 Active

🧭 About this NDC listing & data coverage

Kit / multi-component package

Kit / multi-component package

This NDC identifies a kit — a package containing more than one component. Structured data (pricing, ingredients, equivalents) is often reported per component rather than for the kit NDC itself, which can make this page look thinner than the components' own pages.

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) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is 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 — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
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 FDA registers it as 42227-083-01, 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: 42227-0083-01, written without dashes as 42227008301. 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 42227-0083-01, the first segment (42227) is the labeler code FDA assigned to Takeda Pharmaceuticals America, Inc.; the middle segment (0083) 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 Takeda Pharmaceuticals America, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Takeda Pharmaceuticals America, 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.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J0598 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.

📄 Full FDA label FDA SPL

The complete FDA label for this product, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage 48 words

1 INDICATIONS AND USAGE CINRYZE is a C1 esterase inhibitor indicated for routine prophylaxis against angioedema attacks in adolescent and adult patients with Hereditary Angioedema (HAE). CINRYZE is a C1 esterase inhibitor indicated for routine prophylaxis against angioedema attacks in adolescent and adult patients with Hereditary Angioedema (HAE).

⏱️ Dosage and Administration ~3 min read

2 DOSAGE AND ADMINISTRATION For Intravenous Use, Freeze-Dried powder for Reconstitution. Intravenous Use Only Prior to reconstitution, protect from light. Store at 2 °C - 25 °C (36 °F - 77 °F).

Do not freeze. To obtain the required dose, reconstitute 2 CINRYZE vials with 2 vials Sterile Water for Injection, USP (5 mL each) using aseptic sterile technique. Administer at room temperature within 3 hours of reconstitution.

Routine Prophylaxis Dosing Indication Dose Initial Infusion rate Maintenance infusion rate (if tolerated) Routine prophylaxis against HAE attacks 1,000 Units Intravenous every 3 or 4 days 1 mL/min (10 min) 1 mL/min (10 min)

2.1Routine prophylaxis against HAE Attacks A dose of 1,000 Units CINRYZE can be administered every 3 or 4 days for routine prophylaxis against angioedema attacks in HAE patients. CINRYZE is administered at an injection rate of 1 mL per minute. Table 1 Routine Prophylaxis Dosing Indication Dose Initial Infusion rate Maintenance infusion rate (if tolerated) Routine prophylaxis against HAE attacks 1,000 Units Intravenous every 3 or 4 days 1 mL/min (10 min) 1 mL/min (10 min)

2.2Instructions for Use The procedures below are provided as general guidelines for the reconstitution and administration of CINRYZE. Use either the Mix2Vial ® transfer device or a commercially available double-ended needle. CINRYZE IS A LYOPHILIZED POWDER THAT IS SUPPLIED IN A VACUUM-SEALED VIAL.

Always work on a clean surface and wash your hands before performing the following procedures. Reconstitution, product administration, and handling of the administration set and needles must be done with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious viruses including HIV (AIDS) and hepatitis.

Obtain immediate medical attention if injury occurs. Place needles in a sharps container after single use. Discard all equipment, including any reconstituted CINRYZE in an appropriate container.

2.3Preparation and Handling Prior to reconstitution, CINRYZE should be protected from light. CINRYZE should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The reconstituted solution should be colorless to slightly blue, and free from visible particles.

Do not use if turbid or discolored. The CINRYZE vial is for single use only. CINRYZE contains no preservative.

Any vial that has been entered should be used promptly. Partially used vials should be discarded in accordance with biohazard procedures. Do not mix CINRYZE with other materials.

Do not use if frozen. Do not use after expiration date. Reconstitution: Two vials of reconstituted CINRYZE are combined for a single dose.

Sterile Water for Injection, USP, is required and not supplied with CINRYZE. Aseptic technique should be used during the reconstitution procedure. Bring the CINRYZE (powder) and Sterile Water for Injection, USP (diluent) (not supplied) to room temperature if refrigerated.

Remove caps from the CINRYZE and diluent vials. Cleanse stoppers with an alcohol wipe or swab, and allow them to dry prior to use. Remove protective covering from the top of the Mix2Vial transfer device package.

Do not remove the device from the package. Note: Diluent vial must be accessed prior to CINRYZE vial to prevent loss of vacuum. Place diluent on a flat surface and insert the blue end of the device into the diluent vial, pushing down until the spike penetrates through the center of the diluent vial stopper and the device snaps in place ( Figure 1 ).

The Mix2Vial transfer device must be positioned completely vertical prior to penetrating the stopper closure. Remove the plastic package and discard it ( Figure 2 ). Take care not to touch the exposed end of the device.

Place vial of CINRYZE on a flat surface. Invert diluent vial containing 5 mL Sterile Water for Injection, USP, and insert the clear end into the CINRYZE vial, pushing down until the spike penetrates the rubber stopper a…

💊 Dosage Forms and Strengths 62 words

3. DOSAGE FORMS AND STRENGTHS CINRYZE is a lyophilized preparation available in a single-use vial that contains 500 Units (U) human C1 esterase inhibitor. Each vial must be reconstituted with 5 mL Sterile Water for Injection, USP (diluent) (not supplied). Two reconstituted vials must be used to make a single, 1,000 Units, dose. Approximately 500 Units (lyophilized) in an 8 mL vial.

Contraindications 35 words

4 CONTRAINDICATIONS CINRYZE is contraindicated in patients who have manifested life-threatening immediate hypersensitivity reactions, including anaphylaxis to the product. Patients who have manifested life-threatening immediate hypersensitivity reactions, including anaphylaxis, to the product ( 4 ).

⚠️ Warnings and Cautions ~2 min read

5 WARNINGS AND PRECAUTIONS Hypersensitivity reactions may occur. Epinephrine should be immediately available to treat any acute severe hypersensitivity reactions ( 5.1 ). Thrombotic events have been reported in patients receiving Cinryze for routine prophylaxis.

Thrombotic events also have been reported in patients receiving off-label high dose C1 esterase inhibitor therapy ( 5.2 ). Monitor patients with known risk factors for thrombotic events. CINRYZE is made from human plasma and may contain infectious agents e.g. viruses and, theoretically, the Creutzfeldt-Jakob disease agent.

( 5.3 )

5.1Sensitivity Severe hypersensitivity reactions may occur. The signs and symptoms of hypersensitivity reactions may include the appearance of hives, urticaria, tightness of the chest, wheezing, hypotension and/or anaphylaxis experienced during or after injection of CINRYZE. Because hypersensitivity reactions may have symptoms similar to HAE attacks, treatment methods should be carefully considered.

In case of hypersensitivity, CINRYZE infusion should be discontinued and appropriate treatment instituted. Epinephrine should be immediately available for treatment of acute severe hypersensitivity reaction. (See Patient Counseling Information [ 17 ])

5.2Thrombotic Events Thrombotic events have been reported in association with C1 esterase inhibitor products when used off-label at high doses. 2 Animal studies have supported a concern about the risk of thrombosis from intravenous administration of C1 esterase inhibitor products. 3 (see Sections 10 OVERDOSAGE and

13.2Animal Toxicology and/or Pharmacology ) In an open label trial further investigating the use of CINRYZE for prevention (n=146) of HAE attacks, 5 serious thrombotic events (including myocardial infarction, deep vein thrombosis, pulmonary embolism and 2 events of cerebrovascular accident) occurred. Subjects had underlying risk factors for thrombotic events. Patients with known risk factors for thrombotic events should be monitored closely while taking CINRYZE.

5.3Transmissible Infectious Agents Because CINRYZE is made from human blood, it may carry a risk of transmitting infectious agents, e.g. viruses, and, theoretically, the Creutzfeldt-Jakob (CJD) agent [ 11 ]. ALL infections thought by a physician possibly to have been transmitted by CINRYZE should be reported by the physician or other healthcare provider to ViroPharma Biologics, Inc. [(877) 945-1000]. The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering it to the patient.

(See Patient Counseling Information [ 17 ])

🤒 Adverse Reactions ~2 min read

6 ADVERSE REACTIONS The most serious adverse events observed in clinical studies of CINRYZE have been death due to non-catheter related foreign body embolus, pre-eclampsia resulting in emergency C-section, stroke, and exacerbation of HAE attacks, none of which have been considered drug related. The most common drug related adverse reactions observed at a rate ≥ 5% were upper respiratory tract infection, sinusitis, rash, and headache. In the clinical trial, the most common adverse reactions observed by ≥ 5% of subjects after receiving CINRYZE were upper respiratory tract infection, sinusitis, rash, and headache.

( 5.1 , 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ViroPharma Biologics, Inc. at (877) 945-1000 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience Because clinical studies 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. Routine Prophylaxis Twenty-four subjects were evaluated in study LEVP2005-1/B for routine prophylaxis. There were no treatment-emergent serious adverse reactions in study LEVP2005-1/B.

Adverse reactions in trial LEVP2005-1/B that occurred in at least two subjects during CINRYZE prophylaxis, irrespective of the causality assessment, are given in the following table: Table 2 Adverse Reactions in Routine Prophylaxis Study LEVP2005-1/B Irrespective of Causality Adverse Reaction Number of Adverse Events Number of Subjects (N = 24) Sinusitis 8 5 Rash 7 5 Headache 4 4 Upper respiratory tract infection 3 3 Viral upper respiratory tract infection 5 3 Bronchitis 2 2 Limb injury 2 2 Back pain 2 2 Pain in extremity 2 2 Pruritus 2 2 More than 9000 doses of CINRYZE have been administered to over 180 patients in all controlled and open label clinical studies.

All patients were evaluated and found negative for seroconversion to parvovirus B19, Hepatitis B, Hepatitis C and HIV. No clinically relevant antibody formation was seen in clinical trials of prophylaxis.

6.2Postmarketing Experience Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure. Postmarketing adverse reactions include local infusion site reactions (including pain, rash, erythema, inflammation or hematoma at the infusion site). Postmarketing thrombotic events have been reported, including catheter-related and deep venous thromboses, transient ischemic attack, and stroke.

Patients with known risk factors for thrombotic events should be monitored closely. (See Section

5.2 Thrombotic events in WARNINGS AND PRECAUTIONS)

🔄 Drug Interactions 17 words

7 DRUG INTERACTIONS No drug interaction studies have been conducted. No drug interaction studies have been conducted.

👥 Use in Specific Populations 202 words

8 USE IN SPECIFIC POPULATIONS Pregnancy: No human or animal data. Use only if clearly needed. ( 8.1 )

8.1Pregnancy Pregnancy Category C. No animal data are available. No adequate and well-controlled studies were conducted in pregnant women. It is not known whether CINRYZE can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. CINRYZE should be given to a pregnant woman only if clearly needed.

8.2Labor and Delivery The safety and effectiveness of CINRYZE administration prior to or during labor and delivery have not been established. Use only if clearly needed.

8.3Nursing Mothers It is not known whether CINRYZE is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when CINRYZE is administered to a nursing woman.

8.4Pediatric Use The safety and effectiveness of CINRYZE have not been established in neonates, infants, or children. Three of the 24 subjects in Study LEVP2005-1/B were under the age of 18 years (9, 14, and 16 years of age).

8.5Geriatric Use The clinical study LEVP2005-1/B did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger subjects.

🤰 Pregnancy 53 words

8.1Pregnancy Pregnancy Category C. No animal data are available. No adequate and well-controlled studies were conducted in pregnant women. It is not known whether CINRYZE can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. CINRYZE should be given to a pregnant woman only if clearly needed.

🧒 Pediatric Use 40 words

8.4Pediatric Use The safety and effectiveness of CINRYZE have not been established in neonates, infants, or children. Three of the 24 subjects in Study LEVP2005-1/B were under the age of 18 years (9, 14, and 16 years of age).

🧓 Geriatric Use 29 words

8.5Geriatric Use The clinical study LEVP2005-1/B did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger subjects.

🆘 Overdosage 130 words

10 OVERDOSAGE The maximum dose administered in clinical studies was 4000 Units given over approximately 5 hours (an average dose of 57 Units/kg) and 9000 Units given over a 7 day period. There have been no overdosages of CINRYZE reported during clinical studies. In vitro and in vivo animal thrombogenicity studies with CINRYZE showed a potential for clot formation when CINRYZE was administered at doses 14 times the recommended clinical dose (greater than 200U/kg).

Thrombotic events have been reported in association with C1 esterase inhibitor products when used off-label at high doses. 2 Animal studies have supported a concern about the risk of thrombosis from intravenous administration of C1 esterase inhibitor products. 3 (see Section

13.2 Animal Toxicology and/or Pharmacology and Section

5.2Thrombotic events in WARNINGS AND PRECAUTIONS) .

🧬 Clinical Pharmacology ~2 min read

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action C1 inhibitor is a normal constituent of human blood and is one of the serine proteinase inhibitors (serpins). The primary function of C1 inhibitor is to regulate the activation of the complement and intrinsic coagulation (contact system) pathway. C1 inhibitor also regulates the fibrinolytic system.

Regulation of these systems is performed through the formation of complexes between the proteinases and the inhibitor, resulting in inactivation of both and consumption of the C1 inhibitor. HAE patients have low levels of endogenous or functional C1 inhibitor. Although the events that induce attacks of angioedema in HAE patients are not well defined, it is thought by some that increased vascular permeability and the clinical manifestation of HAE attacks are primarily mediated through contact system activation.

Suppression of contact system activation by C1 inhibitor through the inactivation of plasma kallikrein and factor XIIa is thought to modulate this vascular permeability by preventing the generation of bradykinin 1 . Administration of CINRYZE increases plasma levels of C1 inhibitor activity.

12.2Pharmacodynamics In clinical studies, the intravenous administration of CINRYZE demonstrated an increase in plasma levels of C1 inhibitor within approximately one hour or less of administration. Biological activity of CINRYZE was shown in 35 subjects by the subsequent increase in plasma C4 levels from an average of C4 8.1 mg/mL at baseline to C4 8.6 mg/mL 12 hours after infusion of CINRYZE.

12.3Pharmacokinetics A randomized, parallel group, open label pharmacokinetics (PK) study of CINRYZE was performed in patients with non-symptomatic hereditary angioedema (HAE). The patients received either a single dose of 1,000 Units or 1,000 Units followed by a second 1,000 Units 60 minutes later. The PK results for functional C1 inhibitor are presented the following table: Table 4 Mean pharmacokinetic parameters of Functional C1 Inhibitor Numbers in parenthesis are number of subjects evaluated Single dose = 1,000 Units Double dose = 1,000 Units followed by a second 1,000 Units 60 minutes later * One Unit is equal to the mean C1 inhibitor concentration of 1 mL of normal human plasma Parameters Single Dose Double Dose C baseline (units/mL) 0.31 ± 0.20 (n = 12) 0.33 ± 0.20 (n = 12) C max (units/mL) 0.68 ± 0.08 (n = 12) 0.85 ± 0.12 (n = 13) T max (hrs) 3.9 ± 7.3 (n = 12) 2.7 ± 1.9 (n = 13) AUC (0-t) (units*hr/mL) 74.5 ± 30.3 (n = 12) 95.9 ± 19.6 (n = 13) CL (mL/min) 0.85 ± 1.07 (n = 7) 1.17 ± 0.78 (n = 9) Half-life (hours) 56 ± 36 (n = 7) 62 ± 38 (n = 9) The maximum plasma concentrations (C max ) and area under the plasma concentration-time curve (AUC) increased from the single to double dose, although the increase was not dose proportional.

The mean half-lives of CINRYZE were 56 hours (range 11 to 108 hours) for a single dose and 62 hours (range 16 to 152 hours) for the double dose. Studies have not been conducted to evaluate the PK of CINRYZE in special patient populations identified by gender, race, age (pediatric or geriatric), or the presence of renal or hepatic impairment.

🧬 Mechanism of Action 168 words

12.1Mechanism of Action C1 inhibitor is a normal constituent of human blood and is one of the serine proteinase inhibitors (serpins). The primary function of C1 inhibitor is to regulate the activation of the complement and intrinsic coagulation (contact system) pathway. C1 inhibitor also regulates the fibrinolytic system.

Regulation of these systems is performed through the formation of complexes between the proteinases and the inhibitor, resulting in inactivation of both and consumption of the C1 inhibitor. HAE patients have low levels of endogenous or functional C1 inhibitor. Although the events that induce attacks of angioedema in HAE patients are not well defined, it is thought by some that increased vascular permeability and the clinical manifestation of HAE attacks are primarily mediated through contact system activation.

Suppression of contact system activation by C1 inhibitor through the inactivation of plasma kallikrein and factor XIIa is thought to modulate this vascular permeability by preventing the generation of bradykinin 1 . Administration of CINRYZE increases plasma levels of C1 inhibitor activity.

📦 How Supplied / Storage and Handling 92 words

16 HOW SUPPLIED/STORAGE AND HANDLING CINRYZE is available in single-use vials that contain 500 Units per vial. CINRYZE is supplied as a single glass vial of CINRYZE powder to be reconstituted with 5 mL Sterile Water for Injection, USP (Not supplied). CINRYZE, packaged for sale, is stable for 24 months when stored at 2°C–25°C (36°F-77°F).

Do not freeze. Store the vial in the original carton to protect it from light. The reconstituted solution must be used within 3 hours of reconstitution.

Do not use beyond the expiration date on the CINRYZE vial.

📋 Description ~2 min read

11 DESCRIPTION CINRYZE (C1 esterase inhibitor [human]) is a sterile, stable, lyophilized preparation of C1 esterase inhibitor derived from human plasma. CINRYZE is manufactured from human plasma purified by a combination of filtration and chromatographic procedures. The specific activity of CINRYZE is 4.0 – 9.0 units/mg protein.

The purity is ≥ 90% human C1 esterase inhibitor. Following reconstitution with 5 mL of Sterile Water for Injection, USP, each vial contains approximately 500 units of functionally active C1 esterase inhibitor, pH 6.6 - 7.4, and an osmolality between 200 – 400 mosmol/kg. One Unit (U) of CINRYZE corresponds to the mean quantity of C1 esterase inhibitor present in 1 mL of normal fresh plasma.

CINRYZE, when reconstituted with 5 mL of Sterile Water for Injection, USP contains the following excipients: 4.1 mg/mL sodium chloride, 21 mg/mL sucrose, 2.6 mg/mL trisodium citrate, 2.0 mg/mL L-Valine, 1.2 mg/mL L-Alanine, and 4.5 mg/mL L-Threonine. The following manufacturing steps are designed to reduce the risk of viral transmission: Screening donors at U.S. licensed blood collection centers to rule out infection with Human Immunodeficiency Virus (HIV-1/HIV-2), Hepatitis B Virus, or Hepatitis C Virus. Testing plasma pools by in-process NAT for parvovirus B19 via minipool testing and the limit of B19 in the manufacturing pool is set not to exceed 10 4 IU of B19 DNA per mL.

Use of two independent viral reduction steps in the manufacture of CINRYZE: pasteurization (heat treatment at 60°C for 10 hours in solution with stabilizers) and nanofiltration through two sequential 15 nm filters. These viral reduction steps, along with a step in the manufacturing process, PEG precipitation, have been validated in a series of in vitro experiments for their capacity to inactivate/remove a wide range of viruses of diverse physicochemical characteristics including: Human Immunodeficiency Virus (HIV), Hepatitis A Virus (HAV), and the following model viruses: Bovine Viral Diarrhea Virus (BVDV) as a model virus for HCV, Canine Parvovirus (CPV) as a model virus for Parvovirus B19, Pseudorabies Virus (PRV) as a model virus for large enveloped DNA viruses (e.g. herpes virus).

Total mean log 10 reductions are shown in Table 3 . Table 3 Log 10 Virus Reduction Factor for Selected Viruses Process step Log 10 Virus Reduction Enveloped viruses Non-enveloped viruses HIV BVDV PRV HAV CPV PEG precipitation 5.1 ± 0.2 4.5 ± 0.3 6.0 ± 0.3 2.8 ± 0.2 4.2 ±

0.2Pasteurization > 6.1 ± 0.2 > 6.7 ± 0.3 > 6.7 ± 0.2 2.8 ± 0.3 0.1 ±

0.3Nanofiltration > 5.6 ± 0.2 > 5.5 ± 0.2 > 6.4 ± 0.3 > 4.9 ± 0.2 > 4.5 ±

0.3Total reduction > 16.8 > 16.7 > 19.1 > 10.5 > 8.7

💬 Information for Patients 210 words

17 PATIENT COUNSELING INFORMATION

17.1Allergic-type Hypersensitivity Reactions Allergic-type hypersensitivity reactions are possible [ 5.1 ]. Inform patients of the early signs of hypersensitivity reactions [including hives (itchy white elevated patches), tightness of the chest, wheezing, hypotension] and anaphylaxis. Advise patients to discontinue use of CINRYZE and contact their physicians if these symptoms occur.

17.2Pregnancy Advise female patients to notify their physician if they become pregnant or intend to become pregnant during their routine prevention with CINRYZE.

17.3Nursing Advise patients to notify their physician if they are breastfeeding or plan to breastfeed.

17.4Usage While Traveling Based on their current regimen, advise patients to bring an adequate supply of CINRYZE for routine prevention when traveling. Advise patients to consult with their healthcare professional prior to travel.

17.5Transmissible Infectious Agents Advise patient that, because CINRYZE is made from human blood, it may carry a risk of transmitting infectious agents, e.g. viruses, and, theoretically, the Creutzfeldt-Jakob (CJD) agent [ 5.3 , 11 ]. The risk of transmitting disease has been reduced, but not eliminated, by carefully selecting blood donors, testing donors for infections, and inactivating or removing most viruses during the manufacturing process. Inform patients of the risks and benefits of CINRYZE before prescribing or administering to the patient.

💬 Medication Guide ~3 min read

FDA-Approved Patient Labeling Information for the Patient CINRYZE™ (SIN- rise ) (C1 Esterase Inhibitor [Human]) This leaflet summarizes important information about CINRYZE. Please read it carefully before using CINRYZE and each time you get a refill. There may be new information.

This information does not take the place of talking with your healthcare provider, and it does not include all of the important information about CINRYZE. If you have any questions after reading this, ask your healthcare provider. Do not attempt to self-administer unless you have been taught how by your healthcare provider.

What is CINRYZE? CINRYZE is an injectable medicine that is used to help prevent swelling and/or painful attacks in teenagers and adults with Hereditary Angioedema (HAE). HAE is caused by the decreased functioning of a protein called C1 esterase inhibitor, that is present in your blood and helps control inflammation (swelling) and parts of the immune system.

CINRYZE contains C1 esterase inhibitor. Before you can inject CINRYZE into your vein (intravenous injection), you must dissolve the CINRYZE powder using Sterile Water for Injection, USP. You can get supplies, including Sterile Water for Injection, USP from your pharmacist.

Who should not use CINRYZE? You should not use CINRYZE if you have had life-threatening immediate hypersensitivity reactions, including anaphylaxis to the product. What should I tell my healthcare provider before using CINRYZE?

Tell your healthcare provider about all of your medical conditions, including if you are pregnant or planning to become pregnant. It is not known if CINRYZE can harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if CINRYZE passes into your milk and if it can harm your baby. have a history of blood clotting problems.

Very high doses of C1 esterase inhibitor could increase the risk of blood clots. Tell your healthcare provider and pharmacist about all of the medicines you take, including all prescription and non-prescription medicines such as over-the-counter medicines, supplements, or herbal remedies. What are the possible side effects of CINRYZE?

Allergic reactions may occur with CINRYZE. Call your healthcare provider or get emergency support services right away if you have any of the following symptoms: wheezing difficulty breathing chest tightness turning blue (look at lips and gums) fast heartbeat swelling of the face faintness rash hives In clinical studies, the most common side effects seen with CINRYZE were upper respiratory tract infection, sinusitis, rash, and headache. These are not all the possible side effects of CINRYZE.

Tell your healthcare provider about any side effect that bothers you or that does not go away. You can also report side effects to the FDA at 1-800-FDA-1088. You can ask your healthcare provider for information that is written for healthcare providers.

How should I store CINRYZE? Do not freeze CINRYZE. Store CINRYZE in a refrigerator or at room temperature between 36° to 77°F (2° to 25°C).

Keep CINRYZE in the original carton to protect it from light. Do not use CINRYZE after the expiration date on the vial. After preparing CINRYZE, you can store it at room temperature for up to 3 hours.

If you have not used it within 3 hours, throw it away. Only use the dissolved CINRYZE if it is colorless to slightly blue, clear and free from visible particles. What else should I know about CINRYZE?

Medicines are sometimes prescribed for purposes other than those listed here. Do not use CINRYZE for a condition for which it is not prescribed. Do not share CINRYZE with other people, even if they have the same symptoms that you have.

Because CINRYZE is made from human blood, it may carry a risk of transmitting infectious agents, e.g. viruses, and, theoretically, the Creutzfeldt-Jakob (CJD) agent. This leaflet summarizes the most important information about CINRYZE. If you would like more information, talk to your healthcare provider.

You can ask yo…

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