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Alphanate Antihemophilic Factor/von Willebrand Factor Complex (Human) Kit

by GRIFOLS USA, LLC · 1 KIT in 1 CARTON (68516-4612-1) * 5 mL in 1 VIAL (68516-4606-1) * 5 mL in 1 VIAL, SINGLE-DOSE (68516-1001-1)

NDC 68516-4612-01

🏷️ FDA NDC (as labeled) 68516-4612-1 billing pads the package segment with a zero

Brand Discontinued Non-controlled ⚠ Discontinued by firm

🗂️ Data synced Aug 20, 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 Dr. Brian Staiger, PharmD

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

⚠️

Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. The listing was last certified through Sep 2023. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

🆔 Identity & classification

FDA NDC (as labeled) 68516-4612-1

Product NDC 68516-4612

11-digit billing NDC 68516461201

NCPDP billing unit EA — each (per item)

Application # BLA102475

SPL Set ID 5a7aea94-654c-4113-9014-c3137de0a931

DEA schedule Non-controlled

Marketing category BLA

Marketing status Discontinued

FDA listing status Discontinued by firm (certified through Sep 2023)

Marketing start 1978-08-15

Route INTRAVENOUS

Dosage form KIT

GPI-14 85100015102170

GPI class Alphanate

GCN Seq No 061158

GCN 27333

HICL code 017395

Ingredient (HICL) Antihemophilic Factor/Vwf

HIC1 code M

Therapeutic class — broad (HIC1) Blood

HIC2 code M0

Therapeutic class — intermediate (HIC2) Blood And Blood Replacement Preparations

HIC3 code M0E

Therapeutic class — specific (HIC3) Antihemophilic Factors

AHFS code 20:28.16.00

AHFS class Hemostatics

FDB label name ALPHANATE 500-200 UNIT VIAL

FDB brand name Alphanate

Legend status F — Federal legend — prescription drug or device

Biologic (Purple Book) 351(a)

Why two NDCs? The FDA registers this code as 68516-4612-1 — 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 → 68516-4612-01. 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

LabelerGRIFOLS USA, LLC

FDA applicationBLA102475 (BLA)

Labeler code68516

First marketedAug 1978

Product typePlasma Derivative

Portfolio52 products on file

🔎 All NDCs from GRIFOLS USA, LLC

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 ALPHANATE 500-200 UNIT VIAL Ingredient Antihemophilic Factor/Vwf

Patient education

📘 MedlinePlus patient leaflet ↗

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →

Where does this data come from?

Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

🧪 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.

A current SPL was checked, but it does not contain a structured or narrative inactive-ingredient list for this product. This does not mean the product has no inactive 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 system	Per each	Per package
Retail pharmacies payNADAC · weekly	Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo	No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly	No Part D plan price is available for this NDC in our data.

ℹ️

No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.

Where does this data come from?

NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

Product	Labeler	Pack	NADAC/unit	TE	Status	Price vs. this
Alphanatethis 68516-4612-01	GRIFOLS	1 kit	—	—	Discontinued	—
Alphanate 68516-4613-02	GRIFOLS	1 kit	—	—	Discontinued	—
Alphanate 68516-4616-01	GRIFOLS	1 kit	—	—	FDA listed	—
Alphanate 68516-4611-01	GRIFOLS	1 kit	—	—	Discontinued	—
Alphanate 68516-4614-02	GRIFOLS	1 kit	—	—	Discontinued	—
Alphanate 68516-4618-02	GRIFOLS	1 kit	—	—	FDA listed	—
Alphanate 68516-4619-02	GRIFOLS	1 kit	—	—	FDA listed	—
Alphanate 68516-4615-02	GRIFOLS	1 kit	—	—	Discontinued	—
Alphanate 68516-4620-02	GRIFOLS	1 kit	—	—	FDA listed	—
Alphanate 68516-4617-01	GRIFOLS	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

🏛️

1978

First FDA approval

Aug 1978

📍

2026

Currently FDA-listed

48 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.

FDA Purple Book — biosimilars & interchangeables ⓘ

Reference product

AlphanateAntihemophilic Factor/von Willebrand Factor Complex (Human) Humate-PAntihemophilic Factor/von Willebrand Factor Complex (Human)

🔒 No FDA-licensed biosimilars or interchangeable biosimilars are listed yet for this biologic. It currently has no biosimilar competition in the FDA Purple Book.

Source: FDA Purple Book (purplebooksearch.fda.gov), matched on the reference product’s active ingredient.

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.

📦 Packaging — all sizes for this product

Package NDC	Description	Marketing start	Status
68516-4612-01 You're viewing this	1 KIT in 1 CARTON (68516-4612-1) * 5 mL in 1 VIAL (68516-4606-1) * 5 mL in 1 VIAL, SINGLE-DOSE (68516-1001-1)	1978-08-15	Discontinued by firm

🧭 About this NDC listing & data coverage

Kit / multi-component package No longer marketed (per FDA listing data)

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	— Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD)	— Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.

“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.

What does the discontinued status mean for this NDC?

The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.

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 68516-4612-1, 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: 68516-4612-01, written without dashes as 68516461201. 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 68516-4612-01, the first segment (68516) is the labeler code FDA assigned to GRIFOLS USA, LLC; the middle segment (4612) 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.

Who lists this product with the FDA?

GRIFOLS USA, LLC 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.

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 ⏱️ 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 📋 Description 💬 Information for Patients

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Alphanate is an Antihemophilic Factor/von Willebrand Factor Complex (Human) indicated for: Control and prevention of bleeding in patients with hemophilia A ( 1.1 ) Surgical and/or invasive procedures in adult and pediatric patients with von Willebrand Disease in whom desmopressin (DDAVP) is either ineffective or contraindicated. It is not indicated for patients with severe VWD (Type 3) undergoing major surgery ( 1.2 ).

1.1Hemophilia A Alphanate ® , Antihemophilic Factor/von Willebrand Factor Complex (Human), is indicated for the control and prevention of bleeding in patients with Factor VIII (FVIII) deficiency due to hemophilia A. 1 1.2 von Willebrand Disease Alphanate is indicated for surgical and/or invasive procedures in adult and pediatric patients with von Willebrand Disease (VWD) in whom desmopressin (DDAVP ® ) is either ineffective or contraindicated. It is not indicated for patients with severe VWD (Type 3) undergoing major surgery.

1.2von Willebrand Disease Alphanate is indicated for surgical and/or invasive procedures in adult and pediatric patients with von Willebrand Disease (VWD) in whom desmopressin (DDAVP ® ) is either ineffective or contraindicated. It is not indicated for patients with severe VWD (Type 3) undergoing major surgery.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION For Intravenous Use Only Antihemophilic Factor (AHF) potency (FVIII:C activity) is expressed in International Units (IU) FVIII/vial on the product label. Additionally, Alphanate contains von Willebrand Factor:Ristocetin Cofactor (VWF:RCo), which is expressed in IU VWF:RCo/vial for the treatment of VWD. For Intravenous use only.

Alphanate contains the labeled amount of Factor VIII expressed in International Units (IU) FVIII/vial and Willebrand Factor:Ristocetin Cofactor activity in IU VWF:RCo/vial ( 2 ). Hemophilia A: Control and prevention of bleeding episodes ( 2.1 ) Dose (units) = body weight (kg) x desired FVIII rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL) Frequency of intravenous injection of the reconstituted product is determined by the type of bleeding episode and the recommendation of the treating physician von Willebrand Disease: Surgical and/or invasive procedure in adult and pediatric patients except Type 3 undergoing major surgery ( 2.2 ) Adults: Pre-operative dose of 60 IU VWF:RCo/kg body weight; subsequent doses of 40-60 IU VWF:RCo/kg/body weight at 8-12 hour intervals post-operative as clinically needed Pediatric: Pre-operative dose of 75 IU VWF:RCo/kg/body weight; subsequent doses of 50-75 IU VWF:RCo/kg body weight at 8-12 hour intervals post-operative as clinically needed Dosage based on protocol used in the Alphanate prospective clinical trial according to judgment of the investigator

2.1Hemophilia A Treatment with Alphanate should be initiated under the supervision of a physician experienced in the treatment of hemophilia. Dosage and duration of treatment depend on the severity of the FVIII deficiency, the location and extent of bleeding, presence of inhibitors, and the patient’s clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life-threatening bleeding episodes.

Dosing requirements and frequency of dosing is calculated on the basis of an expected initial response of 2% of normal FVIII:C increase per IU FVIII:C/kg body weight administered. 2,3 The expected in vivo peak increase in FVIII level expressed as IU/dL (or % normal) can be estimated using the following formulas: Dosage (units) = body weight (kg) x desired FVIII rise (IU/dL or % normal) x 0.5 (IU/kg per IU/dL) OR IU/dL (or % normal) = Total Dose (IU)/body weight (kg) x 2 Thus, an administered AHF dose of 50 IU/kg will be expected to increase the circulating FVIII level to 100% of normal (100 IU/dL).

Doses administered should be titrated to the patient’s clinical response, including individualized needs, severity of the deficiency, severity of the hemorrhage, presence of inhibitors, and FVIII level desired. Patients may vary in their pharmacokinetic (e.g., half-life, in vivo recovery) and clinical responses to Alphanate. Although the dose can be estimated by the calculations above, it is highly recommended that, whenever possible, appropriate laboratory tests including serial FVIII activity assays be performed.

Table 1: Dosage Guidelines for the Treatment of Hemophilia A Hemorrhagic event Dosage (IU FVIII:C/kg Body Weight) Minor hemorrhage: Large bruises Significant cuts or scrapes Uncomplicated joint hemorrhage FVIII:C levels should be brought to 30% of normal (15 IU FVIII/kg twice daily) until hemorrhage stops and healing has been achieved (1–2 days). Moderate hemorrhage: Nose, mouth and gum bleeds Dental extractions Hematuria FVIII:C levels should be brought to 50% (25 IU FVIII/kg twice daily). Treatment should continue until healing has been achieved (2–7 days, on average).

Major hemorrhage: Joint hemorrhage Muscle hemorrhage Major trauma Hematuria Intracranial and intraperitoneal bleeding FVIII:C levels should be brought to 80–100% for at least 3–5 days (40–50 IU FVIII/kg twice daily). Following this treatment period, FVIII levels should be maintained at 50% (25 IU FVIII/kg twice daily) until healing has been achieved. Major hemorrhages may require…

💊 Dosage Forms and Strengths 78 words ▾

3 DOSAGE FORMS AND STRENGTHS Alphanate is a sterile, lyophilized powder for intravenous injection after reconstitution. It is available in the following potencies: 250 IU FVIII/5 mL single dose vial 500 IU FVIII/5 mL single dose vial 1000 IU FVIII/10 mL single dose vial 1500 IU FVIII/10 mL single dose vial Alphanate is a sterile, lyophilized powder for intravenous injection after reconstitution, available as 250, 500, 1000, and 1500 IU FVIII in single dose vials ( 3 )

⛔ Contraindications 41 words ▾

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

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Anaphylaxis and severe hypersensitivity reactions are possible. Should symptoms occur, treatment with Alphanate should be discontinued, and emergency treatment should be sought ( 5.1 ) Development of activity-neutralizing antibodies has been detected in patients receiving FVIII containing products. Development of alloantibodies to VWF in Type 3 VWD patients have been occasionally reported in the literature ( 5.2 ) Thromboembolic events may be associated with AHF/VWF Complex (Human) in VWD patients, especially in the setting of known risk factors ( 5.3 ) Intravascular hemolysis may be associated with infusion of massive doses of AHF/VWF Complex (Human) ( 5.4 ) Rapid administration of a FVIII concentrate may result in vasomotor reactions ( 5.5 ) Plasma products carry a risk of transmitting infectious agents, such as viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent, despite steps designed to reduce this risk ( 5.6 )

5.1Anaphylaxis and Severe Hypersensitivity Reactions Anaphylaxis and severe hypersensitivity reactions are possible. Should symptoms occur, treatment with Alphanate should be discontinued, and emergency treatment should be administered.

5.2Neutralizing Antibodies Development of procoagulant activity-neutralizing antibodies (inhibitors) has been detected in patients receiving FVIII-containing products. Carefully monitor patients treated with AHF products for the development of FVIII inhibitors by appropriate clinical observations and laboratory tests. No studies have been conducted with Alphanate to evaluate inhibitor formation.

Therefore, it is not known whether there are greater, lesser or the same risks of developing inhibitors due to the use of this product than there are with other FVIII preparations. If expected plasma FVIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose, an assay that measures FVIII inhibitor concentration should be performed. Patients with these inhibitors may not respond to treatment with Antihemophilic Factor/von Willebrand Factor Complex (Human), or the response may be much less than would otherwise be expected; therefore, larger doses of Antihemophilic Factor/von Willebrand Factor Complex (Human) are often required.

The management of bleeding in patients with inhibitors requires careful monitoring, especially if surgical procedures are indicated. 4-6 Depending on the level of the inhibitor and/or clinical response, it may be appropriate to use an alternative ‘bypass’ therapeutic agent. Reports in the literature suggest that patients with Type 3, severe von Willebrand Disease, may develop alloantibodies to von Willebrand factor (VWF) after replacement therapy.

13 The risk of developing alloantibodies in patients with von Willebrand disease due to the use of this product is not known.

5.3Thromboembolic Events Thromboembolic events have been reported in von Willebrand Disease patients receiving AHF/VWF Complex (Human) replacement therapy, especially in the setting of known risk factors for thrombosis. 14-16 In addition, endogenous high levels of FVIII have also been associated with thrombosis but no causal relationship has been established. In all VWD patients in situations of high thrombotic risk receiving coagulation factor replacement therapy, caution should be exercised and antithrombotic measures should be considered.

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Antihemophilic Factor/von Willebrand Factor Complex (Human) contains Antihemophilic Factor (FVIII) and von Willebrand Factor (VWF), constituents of normal plasma, which are required for clotting. The administration of Alphanate temporarily increases the plasma level of FVIII, thus minimizing the hazard of hemorrhage in patients with hemophilia A. 23,24 FVIII is an essential cofactor in activation of factor X leading to formation of thrombin and fibrin.

VWF promotes platelet aggregation and platelet adhesion on damaged vascular endothelium; it also serves as a stabilizing carrier protein for the procoagulant protein FVIII. 25,26

12.3Pharmacokinetics 12.3.1 Pharmacokinetics in Hemophilia A Following the administration of Alphanate during clinical trials, the mean in vivo half-life of FVIII observed in 12 adult subjects with severe hemophilia A was 17.9 ± 9.6 hours. In this same study, the in vivo recovery was 96.7 ± 14.5% at 10 minutes postinfusion. Recovery at 10 minutes post-infusion was also determined as 2.4 ±

0.4IU FVIII rise/dL plasma per IU FVIII infused/kg body weight. 12.3.2 Pharmacokinetics in von Willebrand Disease (VWD) A pharmacokinetic crossover study was conducted in 14 non-bleeding subjects with VWD (1 type 1, 2 type 2A, and 11 type 3) comparing the pharmacokinetics of Alphanate (A-SD/HT) and an earlier formulation, Alphanate (A-SD). Subjects received, in random order at least seven days apart, a single intravenous dose of each product, 60 IU VWF:RCo/kg (75 IU VWF:RCo/kg in subjects younger than 18 years of age).

Pharmacokinetic parameters were similar for the two products and indicated that they were biochemically equivalent. Pharmacokinetic analysis of Alphanate (A-SD/HT) in the 14 subjects revealed the following results: the median plasma levels (% normal) of VWF:RCo rose from

10.00IU/dL [mean, 11.86 ±

4.97IU/dL; range: 10.00 to

27.00IU/dL] at baseline to 206.00 IU/dL [mean, 215.50 ± 101.70 IU/dL; range: 87.00 to 440.00 IU/dL] 15 minutes post-infusion; median plasma levels of FVIII:C rose from

5.00IU/dL [mean, 21.00 ±

33.83IU/dL; range: 2.00 to 114.00 IU/dL] to 206.00 IU/dL [mean, 215.29 ±

94.26IU/dL; range: 110.00 to 421.00 IU/dL]. The median bleeding time (BT) prior to infusion was 30 minutes (mean, 28.8 ± 4.41 minutes; range: 13.5 to 30 minutes), which shortened to 10.38 minutes (mean, 10.4 ± 3.20 minutes; range: 6 to 16 minutes) 1 hour post-infusion. Following infusion of Alphanate (A-SD/HT), the median half-lives for VWF:RCo, FVIII:C and VWF:Ag were 6.91 hours (mean, 7.67 ± 3.32 hours, range, 3.80 to 16.22 hours), 20.92 hours (mean, 21.58 ± 7.79 hours; range: 7.19 to 32.20 hours), and 12.80 hours (mean, 13.06 ± 2.20 hours: range: 10.34 to 17.45 hours), respectively.

The median incremental in vivo recoveries of VWF:RCo and FVIII:C were 3.12 (IU/dL)/(IU/kg) [mean, 3.29 ± 1.46 (IU/dL)/(IU/kg); range: 1.28 to 5.73 (IU/dL)/(IU/kg)] for VWF:RCo and 1.95 (IU/dL)/(IU/kg) [mean, 2.13 ± 0.58 (IU/dL)/(IU/kg); range: 1.33 to 3.32 (IU/dL)/(IU/kg)] for FVIII:C. The pharmacokinetic data in VWD are summarized in Table 6 . Table 6.

Pharmacokinetic data in VWD Parameter Plasma VWF:RCo (Mean ± SD) Plasma FVIII:C (Mean ± SD) Plasma VWF:Ag (Mean ± SD) Number of patients 14 14 14 Mean plasma levels (IU/dL) Baseline 11.86 ± 4.97 21.00 ± 33.83 - 15 minutes post infusion 215.50 ± 101.70 215.29 ± 94.26 - T½ (Half-life in hours) 7.67 ± 3.32 21.58 ± 7.79 13.06 ±

2.20Incremental in vivo recovery in (IU/dL)/(IU/kg) 3.29 ± 1.46 2.13 ± 0.58 - Following infusion of both Alphanate (A-SD) and Alphanate (A-SD/HT), an increase in the size of VWF multimers was seen and persisted for at least 24 hours. The shortening of the BT was transient, lasting less than 6 hours following treatment and did not correlate with the presence of large and intermediate size VWF multimers. 27

🧬 Mechanism of Action 93 words ▾

VWF promotes platelet aggregation and platelet adhesion on damaged vascular endothelium; it also serves as a stabilizing carrier protein for the procoagulant protein FVIII. 25,26

📦 How Supplied / Storage and Handling 190 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Alphanate is supplied in sterile, lyophilized form in a single dose vial with a vial of diluent (Sterile Water for Injection, USP) and a Mix2Vial filter transfer set. IU activity of FVIII and VWF:RCo are stated on the carton and label of each vial. Alphanate is available in the following potencies and color coded based upon assay on the carton and label as follows: Potency NDC Assay Color Code 250 IU FVIII/5 mL single dose vial 68516-4601-1 250 IU FVIII Range - grey box 500 IU FVIII/5 mL single dose vial 68516-4602-1 500 IU FVIII Range - blue box 1000 IU FVIII/10 mL single dose vial 68516-4603-2 1000 IU FVIII Range - red box 1500 IU FVIII/10 mL single dose vial 68516-4604-2 1500 IU FVIII Range - black box Storage Store under refrigeration at temperatures between 2 and 8 °C (34 to 46 °F).

Do not freeze to prevent damage to diluent vial. May be stored at room temperature not to exceed 30 ºC for up to 2 months. If stored outside the refrigerator, record the date removed on the space provided on the carton.

📋 Description ~3 min read ▾

11 DESCRIPTION Alphanate is a sterile, lyophilized concentrate of FVIII (AHF) and von Willebrand Factor (VWF). Alphanate is prepared from pooled human plasma by cryoprecipitation of FVIII, fractional solubilization, and further purification employing heparin-coupled, cross-linked agarose which has an affinity to the heparin binding domain of VWF/FVIII:C complex. 20 The product is treated with a mixture of tri-n-butyl phosphate (TNBP) and polysorbate 80 to inactivate enveloped viruses.

The product is also subjected to an 80 °C heat treatment step for 72 hours to inactivate enveloped and non-enveloped viruses. However, no procedure has been shown to be totally effective in removing viral infectivity from coagulation factor products. Alphanate is labeled with the antihemophilic factor potency (FVIII:C activity) in International Units (IU) FVIII/vial and with VWF:RCo activity expressed in IU VWF:RCo/vial.

The activities are referenced to their respective international standards established by the World Health Organization. One IU of FVIII or one IU of VWF:RCo is approximately equal to the amount of FVIII or VWF:RCo activity in 1 mL of freshly-pooled human plasma. Alphanate contains Albumin (Human) as a stabilizer, resulting in a final container concentrate with a specific activity of at least 5 FVIII:C IU/mg total protein.

Prior to the addition of the Albumin (Human) stabilizer, the specific activity is significantly higher. When reconstituted as directed, the composition of Alphanate is as follows: Component Concentration FVIII:C activity 40 – 180 IU/mL VWF:RCo activity NLT

0.4VWF:RCo IU per 1 IU of FVIII:C Albumin (Human) 0.3 – 0.9 g/100 mL Calcium NMT 5 mmol/L Glycine NMT 750 μg per FVIII:C IU Heparin NMT

1.0U/mL Histidine 10 – 40 mmol/L Imidazole NMT 0.1 mg/mL Arginine 50 – 200 mmol/L Polyethylene Glycol and Polysorbate 80 NMT 1.0 μg per FVIII:C IU Sodium NMT 10 mEq/vial Tri-n-butyl Phosphate (TNBP) NMT 0.1 μg per FVIII:C IU NMT= not more than NLT= not less than Viral Reduction Capacity The solvent detergent treatment process has been shown by Horowitz, et al., to provide a high level of viral inactivation without compromising protein structure and function. 21 The susceptibility of human pathogenic viruses such as Human Immunodeficiency viruses (HIV), hepatitis viruses, as well as marker viruses such as Sindbis virus (SIN, a model for Hepatitis C virus) and Vesicular Stomatitis virus (VSV, a model for large, enveloped RNA virus), to inactivation by organic solvent detergent treatment has been discussed in the literature.

22 In vitro inactivation studies to evaluate the solvent detergent treatment (0.3% Tri-n-butyl Phosphate and 1.0% Polysorbate 80) step in the manufacture of Alphanate demonstrated a log inactivation of ≥ 11.1 for HIV-1, ≥ 6.1 for HIV-2, ≥ 4.1 for VSV and ≥ 4.7 for SIN. No residual virus was detected after solvent detergent treatment in any of these studies. Additional steps in the manufacturing process of Alphanate were evaluated for virus elimination capability.

The dry heat cycle of 80 °C for 72 hours was shown to inactivate greater than 5.8 logs of Hepatitis A virus (HAV). Precipitation with 3.5% polyethylene glycol (PEG) and heparin-actigel-ALD chromatography are additional steps studied using Bovine Herpes virus (BHV, a model for Hepatitis B virus), Bovine Viral Diarrhea virus (BVD, a second model for Hepatitis C virus), human Poliovirus Sabin type 2 (POL, a model for Hepatitis A virus), Canine Parvovirus (CPV, a model for Parvovirus B19) and HIV-1. Table 5 summarizes the reduction factors for each virus validation study performed for the manufacturing process of Alphanate.

Table 5: Virus Log Reduction Virus (Model Virus for) 3.5% PEG Precipitation Solvent–Detergent Column Chromatography Lyophilization Dry Heat Cycle (80 °C, 72 h) Total Log Removal BHV (HBV) < 1.0 ≥ 8.0 7.6 1.3 2.1 ≥

19.0BVD (HCV) < 1.0 ≥ 4.5 < 1.0 < 1.0 ≥ 4.9 ≥

9.4POL (HAV) 3.3 – < 1.0 3.4 ≥ 2.5 ≥

9.2CPV (B19) 1.2 – < 1.0 < 1.0 4.1…

💬 Information for Patients 198 words ▾

17 PATIENT COUNSELING INFORMATION Inform patients of the early signs of hypersensitivity reaction, including hives, generalized urticaria, chest tightness, dyspnea, wheezing, faintness, hypotension, and anaphylaxis. Have epinephrine available in case of severe immediate hypersensitivity reactions. If allergic symptoms occur, discontinue treatment immediately and seek emergency treatment.

See WARNINGS AND PRECAUTIONS ( 5.1 ). Inform patients that inhibitors to FVIII and VWF have been detected in patients receiving FVIII or AHF/VWF Complex (Human). If expected levels are not obtained or if bleeding is not controlled with adequate dose, contact your physician.

See WARNINGS AND PRECAUTIONS ( 5.2 ). Inform patients that thromboembolic events may be associated with AHF/VWF Complex (Human). For patients with high thrombotic risk, antithrombotic measures should be considered.

See WARNINGS AND PRECAUTIONS ( 5.3 ). Inform patients that despite stringent procedures designed to reduce risk, the risk of transmitting infectious agents cannot be totally eliminated. Ask patients, especially pregnant women and immunocompromised individuals, to report any signs and symptoms of fever, rash, joint pain, or sore throat, to their physician immediately.

See WARNINGS AND PRECAUTIONS ( 5.6 ). Manufactured and Distributed by: Grifols Biologicals Inc. Los Angeles, CA 90032, U.S.A.

U. S. License No.

1694 3031638

Glossary — plain-language definitions of medical terms used in this label:

contraindicated: Should not be used in that situation, because the risk is considered too high.

in vitro: In a laboratory dish or test tube rather than in a living person or animal; results may not carry over to people.

in vivo: In a living person or animal rather than in a laboratory dish.

adverse event: Any unwanted medical problem that happens during treatment, whether or not the medicine actually caused it.

adverse reaction: An unwanted or harmful effect that a medicine causes in the body.

Adverse Reactions: Unwanted or harmful effects that people experienced while taking a medicine, listed on its official label.

anaphylaxis: A sudden, severe, whole-body allergic reaction that can cause trouble breathing, swelling, and a drop in blood pressure, needing emergency care.

anemia: A low level of red blood cells or the oxygen-carrying protein inside them, which can cause tiredness, weakness, and paleness.

animal reproduction studies: Tests in pregnant animals used to check whether a medicine might harm a developing baby.

asthenia: Unusual weakness or lack of physical strength and energy.

baseline: A person's starting condition, measured before treatment begins, used to see how much they change later on.

cellulitis: A spreading bacterial infection of the skin and the tissue just beneath it.

Clinical Pharmacology: The label section explaining how a medicine works in the body and how the body processes it.

Contraindications: A list of situations or health conditions in which a medicine should not be used because the chance of harm is too high.

crossover: A study design in which each person takes one treatment for a time, then switches to the other, acting as their own comparison.

diarrhea: Loose, watery bowel movements that happen more often than normal.

diluent: The liquid used to dissolve or thin a medicine before it is given.

Dosage and Administration: The label section explaining how much of a medicine to use and how to take or give it.

Drug Interactions: The label section listing other medicines, foods, or substances that can change how a medicine works or raise the chance of side effects.

dyspepsia: Discomfort, fullness, or a burning feeling in the upper belly, commonly called indigestion.

dyspnea: The medical word for shortness of breath, or the feeling that you cannot get enough air.

ecchymosis: A bruise; a flat blue or purple mark on the skin where blood has leaked underneath.

edema: Swelling caused by extra fluid trapped in the body's tissues.

efficacy: How well a treatment works under the controlled conditions of a clinical study.

Elimination: The overall removal of a medicine from the body by breaking it down and passing it out.

fetal harm: Injury or damage to a developing baby while it is growing inside the womb.

Half-life: The time it takes for the amount of medicine in the blood to drop by half.

hematocrit: A blood test showing what share of your blood is made up of red blood cells.

hematuria: Blood in the urine.

hemolysis: The breaking apart of red blood cells, which can lower the number of cells available to carry oxygen.

hemolytic anemia: A shortage of red blood cells caused by them breaking apart faster than the body can replace them.

hemorrhage: Bleeding, especially heavy or uncontrolled bleeding, either inside the body or from an outside wound.

hepatitis: Inflammation of the liver, which can be caused by infections, alcohol, or certain medicines.

How Supplied/Storage and Handling: The label section describing the forms and strengths a medicine comes in and how to store it properly.

hypersensitivity: An overreaction of the body's defense system to a substance, causing symptoms such as rash, swelling, or trouble breathing.

hypotension: Blood pressure that is lower than normal, which can cause dizziness or fainting.

immunocompromised: Having a weakened immune system, so the body is less able to fight off infections.

Indications and Usage: The label section stating which medical conditions the FDA has officially approved the medicine to treat, prevent, or manage.

infusion: Slowly delivering fluid or medicine into a vein over a period of time, usually through a drip.

inhibitor: A substance that blocks an enzyme or transporter, which can raise the levels of drugs it normally handles.

insomnia: Trouble falling asleep, staying asleep, or getting restful sleep.

intravenous: Given directly into a vein through a needle or thin tube; often written as IV.

lyophilized: Freeze-dried into a powder that is mixed with liquid before it is given.

Mechanism of Action: How a medicine produces its effect in the body, described at the level of cells or body chemistry.

NDC: A unique number that identifies a specific medicine, its maker, strength, and package size.

paresthesia: A tingling, prickling, or "pins and needles" feeling in the skin, often in the hands or feet.

Patient Counseling Information: The label section telling health professionals what to explain to patients about using a medicine safely.

Pharmacokinetics: The study of how the body takes in a medicine, spreads it around, breaks it down, and removes it over time.

potency: How much of a medicine is needed to produce a given effect; a more potent medicine works at a smaller dose.

pregnancy category: An older letter rating (A, B, C, D, or X) once used to describe a medicine's possible risk during pregnancy.

pruritus: Itching of the skin.

reconstitution: Mixing a powdered medicine with a liquid to prepare it for use, following the label's directions.

somnolence: Feeling very sleepy or drowsy, with trouble staying awake during the day.

stomatitis: Soreness, swelling, or sores on the lining inside the mouth.

thrombosis: The forming of a blood clot inside a blood vessel, which can block normal blood flow.

urticaria: Raised, itchy welts on the skin, commonly called hives.

Use in Specific Populations: The label section describing how a medicine affects particular groups, such as pregnant people, children, or older adults.

Warnings and Precautions: The label section describing serious risks to know about and safety steps to follow while using a medicine.

wheezing: A high-pitched whistling sound made while breathing, usually when the airways are narrowed.

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

← 68516-4611-01 · GRIFOLS 68516-4613-02 · GRIFOLS →

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.

Alphanate Antihemophilic Factor/von Willebrand Factor Complex (Human) Kit

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