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Alphanate Antihemophilic Factor/von Willebrand Factor Complex (Human) Kit — NDC 68516-4617-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Alphanate Antihemophilic Factor/von Willebrand Factor Complex (Human) Kit — NDC 68516-4617-1 (Billing 68516-4617-01)

by GRIFOLS USA, LLC · 1 KIT in 1 CARTON * 5 mL in 1 VIAL, GLASS * 5 mL in 1 VIAL

This is a package of Alphanate Antihemophilic Factor/von Willebrand Factor Complex (Human) Kit from GRIFOLS USA, LLC, marketed since Aug 1978 and currently FDA-listed. It is this product's only package size.

NDC 68516-4617-01
🏷️ FDA NDC (as labeled) 68516-4617-1 billing pads the package segment with a zero
Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Oct 8, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
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NDC database record

One package, one record: these facts belong to NDC 68516-4617-1 alone.

Record
FDA NDC Directory package listing · Plasma derivative
Code segments
68516 labeler · 4617 product · 1 package
Package marketed since
Aug 15, 1978
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Barcode (UPC-A, from the NDC)
3 6851646171 6
Medicaid fills, this package
11 prescriptions in the last four reported quarters
FDA record last changed
Oct 8, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 68516-4617-1
Product NDC 68516-4617
11-digit billing NDC 68516461701
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 On market
FDA listing status Listed (active directory)
Marketing start 1978-08-15
Route INTRAVENOUS
Dosage form KIT
Biologic (Purple Book) 351(a)

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

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
Quick answers
  • GSN (GCN sequence number): 061158
  • GCN: 27333
  • HICL (First Databank): 017395
  • AHFS class code: 20:28.16.00
Why two NDCs? The FDA registers this code as 68516-4617-1 — 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 → 68516-4617-01. 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.

Clinical

Label name ALPHANATE 500-200 UNIT VIAL Ingredient Antihemophilic Factor/Vwf

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.

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 $1.09 —
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J7186 $1.269 / J7186 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)68516-4617-1
11-digit billing NDC68516-4617-01
Format5-4-1 as registered → padded to 5-4-2 for billing (zero added to the package segment)
HCPCS J-codeJ7186
DescriptorInjection, antihemophilic factor viii/von willebrand factor complex (human), per factor viii i.u.
Billing units / pkg1 units
How the units are derivedThis package is 1; the HCPCS unit is PER FACTOR VIII IU, so one package = 1 billing unit.
Medicare Part B spend (2026 (Q1))$474,876 · 32 claims · $14,839.88 per claim (all NDCs under J7186)
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
68516-4617-01 You're viewing this Main listing 1 KIT in 1 CARTON * 5 mL in 1 VIAL, GLASS * 5 mL in 1 VIAL 1978-08-15 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Alphanate 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 —
Alphanatethis 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.

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.

Manufacturer & labeler

LabelerGRIFOLS USA, LLC
FDA applicationBLA102475 (BLA)
Labeler code68516
First marketedAug 1978
Product typePlasma Derivative
Portfolio52 products on file

More NDCs from GRIFOLS USA, LLC labeler code 68516

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 FDA label FDA SPL

The complete FDA label for this product, 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 📋 Description 💬 Information for Patients 🍼 Nursing Mothers 🧬 Pharmacokinetics 🔬 Clinical Studies 📚 References 📄 Package Label / Principal Display Panel
🎯 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.

1.1Hemophilia 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

1.2von 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… [Excerpted — this section continues on DailyMed.]

💊 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.

See also ADVERSE REACTIONS ( 6 ) .

5.4Intravascular Hemolysis Massive doses of AHF/VWF Complex (Human) have rarely resulted in acute hemolytic anemia, increased bleeding tendency or hyperfibrinogenemia. 17 Alphanate contains blood group specific isoagglutinins and, when large and/or frequent doses are required in patients of blood groups A, B, or AB, the patient should be monitored for signs of intravascular hemolysis and falling hematocrit. Should this condition occur, thus leading to progressive hemolytic anemia, the administration of serologically compatible Type O red blood c… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS Serious adverse reactions observed in patients receiving Alphanate are anaphylaxis/hypersensitivity reactions. Thomboembolic events have also been observed in patients receiving Alphanate for VWD. See also WARNINGS AND PRECAUTIONS ( 5.3 ) .

The most frequent adverse events reported with Alphanate in > 5% of patients are respiratory distress, pruritus, rash, urticaria, face edema, paresthesia, pain, fever, chills, joint pain and fatigue. The most frequent adverse events reported with Alphanate in > 5% of patients are respiratory distress, pruritus, rash, urticaria, face edema, paresthesia, pain, fever, chills, joint pain and fatigue ( 6 ). To report SUSPECTED ADVERSE REACTIONS , contact Grifols Biologicals Inc. at 1-888-GRIFOLS (1-888-474-3657) 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 clinical trials of another drug and may not reflect the rates observed in clinical practice. Hemophilia A In a clinical study with Alphanate, regardless of causality, 14 of 23 (60.9%) patients experienced a total of 47 adverse events. Twenty-three (48.9%) of the AEs were mild, 19 (40.4%) were moderate and 5 (10.6%) were severe.

Two of 23 (8.7%) patients experienced 10 serious AEs during the study. None of the SAEs were considered to be related to study drug. The most common AEs were pain (combined terms), with 14 episodes occurring in 7 patients, and headache, with 3 episodes occurring in 2 patients.

None of the symptoms were judged to be related to treatment (see Table 3 ). Table 3. Most Commonly Reported AEs irrespective of relationship to study drug Adverse Event Number of Episodes Number of Subjects with signs/symptoms % Body as a whole 23 11 47.8% Pain (combined terms) 14 Headache 3 Accidental injury 2 Asthenia 1 Cellulitis 1 Chest pain 1 Flu syndrome 1 Digestive system 6 4 17.4% Dyspepsia 1 GI disorder 1 Hepatitis 1 Nausea 1 Tooth disorder 1 Vomiting 1 Respiratory system 5 4 17.4% Cough increased 1 Lung disorder 1 Pharyngitis 1 Respiratory disorder 1 Rhinitis 1 Musculoskeletal system 3 3 13.0% Bone disorder 2 Bone necrosis 1 Skin and appendages 3 3 13.0% Acne 1 Dry skin 1 Sweating 1 Nervous system 2 2 8.7% Insomnia 1 Somnolence 1 Hemic and lymphatic system 2 2 8.7% Anemia 1 Ecchymosis 1 Urogenital system 2 2 8.7% Abnormal ejaculation 1 Cutaneous moniliasis 1 Special senses 1 1 4.3% Eye disorder 1 VWD In the prospective clinical study of Alphanate (A-SD/HT)** in patients with von Willebrand Disease, adverse events occurred in 18 of 36 (50.0%) subjects (irrespective of causality) and 53 of 204 (26.0%) infusions.

Most of the AEs were unrelated to study drug, however, and the proportion of subjects experiencing an AE possibly, probably, or definitely related to study drug was 5 of 36 subjects (13.9%) treated with Alphanate. The proportion of subjects with at least one serious AE, regardless of causality was 3 of 36 subjects (8.3%). There were no subjects who reported at least one serious AE possibly, probably, or definitely related to study drug.

Overall, AEs, regardless of causality, were observed in association with 53 of 204 (26.0%) infusions of Alphanate across all parts of these studies. Most AEs were unrelated to study drug, however, and the proportion of infusions associated with AEs possibly, probably, or definitely related to study drug was 14 of 204 infusions (6.9%). The proportion of infusions associated with serious AEs, regardless of causality, was only 5 of 204 (2.5%) infusions of Alphanate.

There were no observed serious AEs possibly, probably or definitely related to study drug. **Alphanate, Solvent Detergent, non heat-treated (A-SD), is the previous formulation and Alphanate, Solvent Detergent/Heat Treated (A-SD/HT), is the current formulation. Both products are biochemically equivalent and demons… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 5 words ▾

7 DRUG INTERACTIONS None known.

👥 Use in Specific Populations ~1 min read ▾

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

Use only if clearly needed ( 8.2 ). Nursing Mothers: No human or animal data. Use only if clearly needed ( 8.3 ).

Pediatric Use: Clinical trials for safety and effectiveness in pediatric hemophilia A patients have not been conducted. The hemostatic efficacy of Alphanate has been studied in 20 pediatric subjects with VWD 18 years of age and under. Based on the data from a subset of these subjects, age had no effect on the pharmacokinetics of VWF:RCo ( 8.4 ).

Geriatric Use: No human or animal data. Use only if clearly needed ( 8.5 ).

8.1Pregnancy Pregnancy Category C. Animal reproduction studies have not been conducted with Alphanate. It is also not known whether Alphanate can cause fetal harm when administered to a pregnant woman or affect reproductive capacity. Alphanate should be given to a pregnant woman only if clearly needed.

8.2Labor and Delivery No human or animal data. Use only if clearly needed.

8.3Nursing Mothers No human or animal data. Use only if clearly needed.

8.4Pediatric Use 8.4.1 Hemophilia A Indication Clinical trials for safety and effectiveness in pediatric hemophilia A patients 16 years of age and younger have not been conducted. 8.4.2 VWD Indication The hemostatic efficacy of Alphanate has been studied in 20 pediatric subjects with VWD 18 years of age and under. Based on the data from a subset of these subjects, age had no effect on the pharmacokinetics of VWF:RCo.

There were no clinically important differences between pediatric patients and adults.

8.5Geriatric Use No human or animal data. Use only if clearly needed.

🤰 Pregnancy 47 words ▾

8.1Pregnancy Pregnancy Category C. Animal reproduction studies have not been conducted with Alphanate. It is also not known whether Alphanate can cause fetal harm when administered to a pregnant woman or affect reproductive capacity. Alphanate should be given to a pregnant woman only if clearly needed.

🧒 Pediatric Use 159 words ▾

8.4Pediatric Use 8.4.1 Hemophilia A Indication Clinical trials for safety and effectiveness in pediatric hemophilia A patients 16 years of age and younger have not been conducted. 8.4.2 VWD Indication The hemostatic efficacy of Alphanate has been studied in 20 pediatric subjects with VWD 18 years of age and under. Based on the data from a subset of these subjects, age had no effect on the pharmacokinetics of VWF:RCo.

There were no clinically important differences between pediatric patients and adults.

8.4.1Hemophilia A Indication Clinical trials for safety and effectiveness in pediatric hemophilia A patients 16 years of age and younger have not been conducted.

8.4.2VWD Indication The hemostatic efficacy of Alphanate has been studied in 20 pediatric subjects with VWD 18 years of age and under. Based on the data from a subset of these subjects, age had no effect on the pharmacokinetics of VWF:RCo. There were no clinically important differences between pediatric patients and adults.

🧓 Geriatric Use 13 words ▾

8.5Geriatric Use No human or animal data. Use only if clearly needed.

🧬 Clinical Pharmacology ~3 min read ▾

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 ▾

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

📦 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… [Excerpted — this section continues on DailyMed.]

💬 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

🍼 Nursing Mothers 13 words ▾

8.3Nursing Mothers No human or animal data. Use only if clearly needed.

🧬 Pharmacokinetics ~3 min read ▾

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

12.3.1Pharmacokinetics 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.

12.3.2Pharmacokinetics 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… [Excerpted — this section continues on DailyMed.]

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES VWD: Prophylaxis for Elective Surgery – Prospective Study In a prospective, multi-center clinical study, 37 subjects with VWD (6 Type 1, 16 Type 2A, 3 Type 2B, 12 Type 3) underwent 59 surgical procedures that included 20 dental, 7 orthopedic, 8 gastrointestinal, 6 gastrointestinal (diagnostic), 9 vascular, 3 gynecologic, 2 genitourinary, 2 dermatologic and 2 head and neck procedures for which Alphanate (A-SD) or Alphanate (A-SD/HT) was administered [21 subjects were administered with Alphanate (A-SD) and 18 were administered with Alphanate (A-SD/HT), 2 received both products] for bleeding prophylaxis ( see Table 7 ).

Prior to each surgical procedure, the investigators provided an estimation of the expected blood loss during surgery for a normal person of the same sex and of similar stature and age as the subject undergoing the same type of surgical procedure. An initial preoperative infusion of 60 IU VWF:RCo/kg (75 IU VWF:RCo/kg for patients less than 18 years of age), was administered one hour preoperatively. A sample was obtained 15 minutes after the initial infusion for the determination of the plasma FVIII:C level.

The level had to equal or exceed 100% of normal for an operation to proceed. No cryoprecipitate or alternative FVIII product was administered during these surgical procedures. Platelets were required in only two subjects.

The protocol permitted intra-operative infusions of Alphanate (A-SD) and Alphanate (A-SD/HT) at 60 IU VWF:RCo/kg (75 IU VWF:RCo/kg for patients less than 18 years of age) to be administered as required according to the judgment of the investigator. Table 7. Number of and Types of Surgical Procedures Treatment with Alphanate Type of Surgical Procedure A-SD A-SD/HT Total Number of Subjects 21 18 37 Two patients received both preparations; the total number of subjects is therefore less than the sum of the columns.

Dental 14 6 20 Dermatologic 1 1 2 Gastrointestinal 4 4 8 Gastrointestinal (diagnostic) 6 0 6 Genitourinary 0 2 2 Gynecologic 2 1 3 Head and neck 1 1 2 Orthopedic 4 3 7 Vascular 3 6 9 Total number of procedures 35 24 59 Postoperative infusions at doses of 40 to 60 IU VWF:RCo/kg (50 to 75 IU VWF:RCo/kg for pediatric patients) was administered at 8- to 12-hour intervals until healing had occurred. After achieving primary hemostasis, for maintenance of secondary hemostasis the dose was reduced after the third postoperative day.

See DOSAGE AND ADMINISTRATION ( 2.2 ). Overall, in 55 surgical procedures undertaken with a prolonged BT pre-infusion, the BT at 30 minutes post-infusion was fully corrected in 18 (32.7%) cases, partially corrected in 24 (43.6%) cases, demonstrated no correction in 12 (21.8%) cases, and was not done in one case (1.8%). The mean blood loss was lower than predicted prospectively.

Bleeding exceeding the predicted value did not correlate with correction of the BT. Three patients had bleeding which exceeded by more than 50 mL the amount predicted prospectively. Among the latter subjects, the BT 30 minutes post-infusion was normal in one and only slightly lengthened in two cases.

Surgical infusion summary data are included in Table 8 . Table 8: Prophylaxis with Alphanate (A-SD) and/or Alphanate (A-SD/HT) in Surgery A-SD A-SD/HT Total Number of patients 21 18 37 Two subjects received both products Number of surgical procedures 35 24 59 Median number of infusions per surgical procedure (range) 3 (1-13) 4 (1 – 18) 4 (1-18) Median dosage IU VWF:RCo/kg Infusion #1 (range) 59.8 (19.8-75.1) 59.9 (40.6 – 75.0) 59.9 (19.8-75.1) Infusion ≥ #2 combined (range) 40.0 (4.5-75.1) 40.0 (10.0 – 63.1) 40.0 (4.5-75.1) Additionally, the surgeries were categorized as major, minor or invasive procedures according to definitions used in the study.

The outcome of each surgery was evaluated according to a clinical rating scale (excellent, good, poor or none) and was considered successful if the outcome was excellent or good. These outcomes are presented in Table 9 . Table 9.

Eff… [Excerpted — this section continues on DailyMed.]

📚 References ~3 min read ▾

15 REFERENCES Eyster, M.E. Hemophilia: A Guide for the Primary Care Physician. Postgrad Med 1978; 64:75-81.

Shanbrom, E., Thelin, M. Experimental Prophylaxis of Severe Hemophilia with a Factor VIII Concentrate. JAMA 1969; 208(9):1853-1856.

Levine, P.H. Hemophilia and Allied Conditions. In: Brain, M.C. ed.

Current Therapy in Hematology-Oncology: 1983-1984 , New York: BC Decker, 1983, pp. 147-152. Kasper, C.K.

Incidence and Course of Inhibitors Among Patients with classic Hemophilia. Thromb Diath Haemorrh 1973; 30:263-271. Rizza, C.R., Biggs, R.

The Treatment of Patients Who Have Factor VIII Antibodies Br J Haematol 1973; 24:65-82. Roberts, H.R., Knowles, M.R., Jones, T.L., McMillan, C. The Use of Factor VIII in the Management of Patients with Factor VIII Inhibitors.

In: Brinkhous, K.M., ed. Hemophilia and New Hemorrhagic States , International Symposium, New York, University of North Carolina Press, 1970, pp. 152-163.

Federici, A.B., Baudo, F., Caracciolo, C., Mancuso, G., Mazzucconi, M.G., Musso, R., Schinco, P.C., Targhetta. R., Mannucci, P.M.. Clinical efficacy of highly purified, doubly virus-inactivated factor VIII/von Willebrand factor concentrate (Fanhdi ® ) in the treatment of von Willebrand disease: a retrospective clinical study.

Haemophilia 2002; 8:761-767. Federici, A.B. Managment of von Willebrand disease with FVIII/von Willebrand factor concentrates: results from current studies and surveys.

Blood Coagul Fibrinolysis 2005;16(Suppl 1):S17-S21. Mannucci, P.M. How I treat patients with von Willebrand disease.

Blood 2001; 97:1915-1919. Mannucci, P.M. Treatment of von Willebrand’s Disease.

N Engl J Med 2004;351:683-694. Nichols, W.L. et al.; NHLBI VWD Expert Panel. The Diagnosis, Evaluation, and Management of von Willebrand Disease.

US Department of Health and Human Services, National Institutes of Health, National Heart Lung and Blood Institute 2007; NIH No. 08-5832. Mannucci, P.M., Franchini, M., Castaman, G., Federici, A.B.; Italian Association of Hemophilia Centers.

Evidence-based recommendations on the treatment of von Willebrand disease in Italy. Blood Transfus 2009; 7 (2):117-126. Mannucci, P.M., Federici, A.B.

Antibodies to von Willebrand Factor in von Willebrand Disease. In: Aledort L.M., Hoyer L.W., Reisener J.M., White II, G.C. eds. Inhibitors to coagulation factor in the 1990s, 1995, Plenum Press, pp.

87-92. Mannucci, P.M. Venous Thromboembolism in von Willebrand Disease.

Thromb Haemost 2002; 88:378-379. Markis, M., Colvin, B., Gupta, V., Shields, M.L., Smith, M.P. Venous Thrombosis Following the Use of Intermediate Purity FVIII Concentrate to Treat Patients with von Willebrand Disease.

Thromb Haemost 2002; 88: 387-388. Girolami, A., Tezza, F., Scapin, M. et al. Arterial and venous thrombosis in patients with von Willebrand’s disease: A critical review of the literature.

J Thromb Thrombolysis 21:175-178 (2006). Soni, NS, Patel AR, Vohra, RM, Shah PC. Hemophiliac with Hemolytic Anemia resulting from Factor VIII Concentrate.

Acta Haemato 1977; 58: 294-297. Biggs, R. Jaundice and Antibodies Directed Against Factors VIII and IX in Patients Treated for Haemophilia or Christmas Disease in the United Kingdom.

Br J Haematol 1974; 26:313-329. Kasper, C.K., Kipnis, S.A. Hepatitis and Clotting Factor Concentrates.

JAMA 1972; 221:510. Fujimura, Y., Titani, K., Holland, L.Z., Roberts, J.R., Kostel, P., Ruggeri, Z.M., Zimmerman, T.S. A heparin-binding domain of human von Willebrand factor: Characterization and localization to a tryptic fragment extending from amino acid residue Val-449 to Lys-728.

J Biol Chem 1987; 262(4):1734-1739. Horowitz, B. Investigations into the Application of Tri (n-Butyl) Phosphate/Detergent Mixture to Blood Derivatives.

In: Morgenthaler, J-J ed. Viral Inactivation in Plasma Products , Karger, 1989, 56:83-96. Edwards, C.A., Piet, M.P.J., Chin, S., Horowitz, B.

Tri (n-Butyl) Phosphate/Detergent Treatment of Licensed Therapeutic and Experimental Blood Derivatives. Vox Sang 1987; 52:53-59. Hershgol… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 109 words ▾

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 250 IU VIAL GRIFOLS NDC 68516-4601-1 Antihemophilic Factor/von Willebrand Factor Complex (Human) Alphanate® LOW Solvent Detergent/Heat Treated 5 mL Storage : Store between 2 and 8 °C. May be stored at room temperature not to exceed 30 °C for up to 2 months. Rx only .

Single dose container for intravenous administration only. Grifols Biologicals Inc . Los Angeles, CA 90032, USA U.S.

License No. 1694 Alphanate 250 IU VIAL

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 250 IU CARTON GRIFOLS NDC 68516-4601-1 Antihemophilic Factor/von Willebrand Factor Complex (Human) Alphanate® Solvent Detergent / Heat Treated 5 mL LOW ALPHANATE 250 IU 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
11
Units reimbursed last 4 qtrs
19K
Gross reimbursed last 4 qtrs
$20.8K
Avg / prescription
$1,894.55
Avg / unit
$1.0945
Latest quarter Q1 2026
0Rx
Fee-for-service vs managed care ⓘ
100% MCO
Fee-for-service · 0 Rx Managed care · 11 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: 19,040 units · 147 per 100k residents 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
147147
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 Pennsylvania 147 /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.

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Kit / multi-component package

Kit / multi-component package

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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.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J7186 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.
← 68516-4616-01 · GRIFOLS 68516-4618-02 · 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.