Profilnine by is a Other medication manufactured, distributed, or labeled by GRIFOLS USA, LLC, Grifols Biologicals LLC, LABORATORIOS GRIFOLS SA, GRIFOLS BIOLOGICALS LLC. Drug facts, warnings, and ingredients follow.
Profilnine®, Factor IX Complex, is a solvent/detergent treated, nanofiltered, sterile, lyophilized concentrate of coagulation factors IX, II, X, and low levels of factor VII. The factor II content is not more than (NMT) 150 units* per 100 factor IX units, the factor X content is NMT 100 units per 100 factor IX units, and the factor VII content is NMT 35 units per 100 factor IX units. Profilnine does not contain heparin and contains no preservatives. Profilnine contains few, if any, activated factors based on results from the non-activated partial thromboplastin time (NAPTT) test1,2.
Profilnine is intended for intravenous administration only. Each vial is a single-dose container and is labeled with the factor IX potency expressed in International Units.
Profilnine is prepared from pooled human plasma and purified by diethylaminoethyl (DEAE) cellulose adsorption. The risk of transmission of infective agents by Profilnine has been substantially reduced by donor selection procedures and virus screening of individual donations and plasma pools by serological and nucleic acid testing. In addition, virus elimination steps such as nanofiltration3 and solvent/detergent (tri-n-butyl phosphate) treatment4 have been incorporated into the Profilnine manufacturing process. Additional removal of some viruses occurs during the DEAE cellulose product purification step.
The ability of the manufacturing process to eliminate virus from Profilnine was evaluated in the laboratory by intentionally adding virus to product just prior to the elimination step and monitoring virus removal. Table 1 shows the amounts of virus that can be removed by solvent/detergent treatment, nanofiltration, and purification by DEAE chromatography when vesicular stomatitis virus (VSV), human immunodeficiency virus-1 and 2 (HIV-1, HIV-2), parvovirus, West Nile virus (WNV), bovine viral diarrhea virus (BVDV), hepatitis A virus (HAV), and pseudorabies virus (PRV) were evaluated in these virus spiking studies. The results indicate that the solvent/detergent treatment step inactivates enveloped viruses and the nanofiltration step removes both enveloped and non-enveloped viruses.
___________________________________
* Unit refers to International Unit in the labeling of Profilnine.
* Porcine, NT=Not tested, Env=Enveloped |
|||||
Virus |
Virus Type |
Model For: | Virus Reduction (log10) | ||
Process Step | |||||
1st DEAE Chromatography | Solvent-Detergent | Nanofiltration | |||
Sindbis | Env | Hepatitis C | 1.4 | ≥ 5.3 | NT |
VSV | Env | Robust enveloped viruses | NT | ≥ 4.9 | NT |
HIV-1 | Env | HIV-1 | NT | ≥ 12.2 | ≥ 6.2 |
HIV-2 | Env | HIV-2 | NT | ≥ 6.0 | NT |
WNV | Env | WNV | NT | NT | ≥ 6.6 |
BVDV | Env | Hepatitis C | NT | NT | ≥ 4.9 |
Parvo* | Non-Env | Parvovirus B19 | NT | NT | ≥ 6.1 |
HAV | Non-Env | HAV | NT | NT | ≥ 5.8 |
PRV | Env | Hepatitis B | NT | NT | ≥ 5.3 |
Profilnine is a mixture of the vitamin K-dependent clotting factors IX, II, X, and low levels of VII. The administration of Profilnine temporarily increases the plasma levels of factor IX, thus enabling a temporary correction of the factor deficiency.
A clinical study that evaluated twelve subjects with hemophilia B indicated that, following administration of Profilnine, the factor IX in vivo half-life was 24.68 ± 8.29 hours and recovery was 1.15 ± 0.16 units/dL per unit infused per kg body weight.
Administration of Factor IX Complex can result in higher than normal levels of factor II due to the significantly longer half-life of factor II5.
Because Profilnine is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
Patients can develop neutralizing antibodies (inhibitors) after treatment with Profilnine. Monitor patients for inhibitors, which should be quantified in Bethesda Units (BU) using appropriate laboratory testing.
Hypersensitivity, including anaphylaxis, has been reported. Inform patients of the early symptoms and signs of hypersensitivity reaction, including hives, generalized urticaria, angioedema, chest tightness, dyspnea, wheezing, faintness, hypotension, tachycardia, and anaphylaxis.
The use of factor IX complex concentrates has been associated with the development of thromboembolic complications. Patients at increased risk for thrombosis include those undergoing surgery, post surgery, with known liver disease, and with signs of fibrinolysis, thrombosis, or disseminated intravascular coagulation (DIC)5. When administering Profilnine to these high-risk patients, monitor for early signs of consumptive coagulopathy with appropriate laboratory testing. Only administer Profilnine to patients when the benefits outweigh the risks.
Vasomotor reactions may result from overly rapid administration. Do not exceed the recommended infusion rate of 10 mL/min.
Advise patients to report to their physician any decrease in effectiveness of Factor IX treatment, as this can indicate development of inhibitors.
Hypersensitivity, including anaphylaxis, has been reported for factor IX complex concentrate products. Inform patients of the early symptoms and signs of hypersensitivity reaction, including hives, rash, swelling, chest tightness, shortness of breath, wheezing, faintness, decrease in blood pressure, and rapid heartbeat. Advise patients to discontinue use of the product and contact their physician and/or seek immediate emergency care if these symptoms occur.
Adverse reactions with Profilnine may include headache, fever, chills, flushing, nausea, vomiting, tingling, lethargy, urticaria, and manifestations of allergic reactions.
The following adverse reactions have been identified during post-approval use of Profilnine: hypersensitivity reactions including shortness of breath, diaphoresis, and hypotension, as well as thrombosis including pulmonary embolism and deep vein thrombosis, disseminated intravascular coagulation, and inhibitor development. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
To report SUSPECTED ADVERSE REACTIONS, contact Grifols at 1-888-GRIFOLS (1-888-474-3657) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Each vial of Profilnine is labeled with total units expressed as International Units (IU). According to the WHO International Standard, one unit approximates the activity in one mL of normal plasma.
A 1% increase in factor IX (0.01 units) per unit administered per kg body weight can be expected1. The amount of Profilnine required to establish hemostasis will vary with each patient and circumstance. Use the following formula and example as guides in determining the number of units to be administered:
Body weight (in kg) | X | Desired increase in Plasma Factor IX (Percent) | X | 1 Units/kg | = | Number of Factor IX Units Required |
Example: | ||||||
50 kg | X | 25 (% increase) | X | 1 Units/kg | = | 1,250 Units of factor IX |
Due to variability among patients and their clinical condition, monitor the factor IX level of each patient frequently during replacement therapy.
Table 2 below provides treatment guidelines for hemorrhagic events and surgery in patients with factor IX deficiency.
Type of Bleeding or Surgical Procedure | Factor IX Level Required, % of Normal (Dose) | Frequency of Doses | Duration of Therapy (Days) |
Minor to Moderate Hemorrhages | 20-30% (20-30 IU FIX/kg) until hemorrhage stops and healing has been achieved. | Every 16-24 hrs | Minor: 1-2 days Moderate: 2-7 days |
Major Hemorrhages | 30-50% (30-50 IU FIX/kg). Following this treatment period, maintain FIX levels at 20% (20 IU FIX/kg) until healing has been achieved. | Every 16-24 hrs | 3-10 days |
Surgery | Prior to surgery, 30-50% (30-50 IU FIX/kg). For dental extractions, bring FIX levels to 50% immediately prior to the procedure. Maintain FIX levels at 30-50% (30-50 IU FIX/kg) until healing has been achieved. | Every 16-24 hrs | 7-10 days |
Dosing requirements and frequency of dosing are calculated on the basis of an initial response of 1% FIX increase achieved per IU of FIX infused per kg body weight and an average half-life for FIX of 24 hours. If dosing studies reveal that a particular patient exhibits a lower response, monitor blood levels and adjust the dose accordingly.
Use Aseptic Technique
For intravenous administration only,
Profilnine is supplied in sterile lyophilized form in single-dose vials accompanied by a suitable volume of diluent (Sterile Water for Injection, USP), according to factor IX potency. Each vial is labeled with the factor IX potency expressed in International Units which is referenced to the WHO International Standard. Profilnine is packaged with a Mix2Vial filter transfer set for use in administration.
The product is available in several potencies, with carton and vial label color coded based upon assay as follows:
Potency | Carton NDC | Assay Color Code |
500 units FIX/5 mL | 68516-3201-1 or 68516-3207-1 | 500 units FIX Range - blue |
1000 units FIX/10 mL | 68516-3202-2 or 68516-3208-2 | 1000 units FIX Range - red |
1500 units FIX/10 mL | 68516-3203-2 or 68516-3209-2 | 1500 units FIX Range - black |
The diluent vial stopper contains natural rubber latex. All other components of the kit are not made with natural rubber latex.
Manufactured by:
Grifols Biologicals LLC
5555 Valley Boulevard
Los Angeles, CA 90032, U.S.A.
U.S. License No. 1694
DATE OF REVISION: June 2018
3051561
GRIFOLS
NDC: 68516-3204-1
Factor IX Complex
Profilnine®
500 IU FIX Range
5 mL
Storage: Store at temperatures not exceeding 25 °C (77 °F)
Rx Only. Single dose container for intravenous
administration only.
Grifols Biologicals LLC
5555 Valley Boulevard, Los Angeles, CA 90032, U.S.A.
U.S. License No. 1694
Instructions: Reconstitute with 5 mL Sterile Water for Injection, USP.
Administer intravenously at room temperature within three hours of reconstitution.
Discard unused contents.
Contains Factors II, IX, X, and low levels of Factor VII.
Contains no preservatives.
For information on dosage and directions for administration, see accompanying pamphlet.
The patient and physician should discuss the risks and benefits of this product.
3051562
Lot
EXP
IU FIX/Vial
Lot
IU FIX/Vial
Profilnine® 5 mL NDC: 68516-3204-1
GRIFOLS
NDC: 68516-3205-2
Factor IX Complex
Profilnine®
1000 IU FIX Range
10 mL
Storage: Store at temperatures not exceeding 25 °C (77 °F).
Rx Only. Single dose container for intravenous
administration only.
Grifols Biologicals LLC
5555 Valley Boulevard, Los Angeles, CA 90032, U.S.A.
U.S. License No. 1694
Instructions: Reconstitute with 10 mL Sterile Water for Injection, USP.
Administer intravenously at room temperature within three hours of reconstitution.
Discard unused contents.
Contains Factors II, IX, X, and low levels of Factor VII.
Contains no preservatives.
For information on dosage and directions for administration, see accompanying pamphlet.
The patient and physician should discuss the risks and benefits of this product.
3051565
Lot
EXP
IU FIX/Vial
Lot
IU FIX/Vial
Profilnine® 10 mL NDC: 68516-3205-2
GRIFOLS
NDC: 68516-3206-2
Factor IX Complex
Profilnine®
1500 IU FIX Range
10 mL
Storage: Store at temperatures not exceeding 25 °C (77 °F).
Rx Only. Single dose container for intravenous
administration only.
Grifols Biologicals LLC
5555 Valley Boulevard, Los Angeles, CA 90032, U.S.A.
U.S. License No. 1694
Instructions: Reconstitute with 10 mL Sterile Water for Injection, USP.
Administer intravenously at room temperature within three hours of reconstitution.
Discard unused contents.
Contains Factors II, IX, X, and low levels of Factor VII.
Contains no preservatives.
For information on dosage and directions for administration, see accompanying pamphlet.
The patient and physician should discuss the risks and benefits of this product.
3051568
Lot
EXP
IU FIX/Vial
Lot
IU FIX/Vial
Profilnine® 10 mL NDC: 68516-3206-2
NDC: 63323-185-05 18505
STERILE
WATER
FOR INJECTION, USP
FOR DRUG DILUENT USE ONLY
Rx only
5 mL Single Dose Vial
Sterile, Nonpyrogenic
Preservative Free
Discard unused portion.
Warning: Do not administer intravenously unless rendered nearly isotonic.
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
APP Pharmaceuticals, LLC
Schaumburg, IL 60173
401745D
LOT/EXP
NDC: 63323-185-10 918510
STERILE WATER
FOR INJECTION, USP
FOR DRUG DILUENT USE ONLY
Rx only
10 mL Single Dose Vial
Sterile, Nonpyrogenic
Preservative Free
Discard unused portion.
Do no administer intravenously unless rendered nearly isotonic.
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
APP Pharmaceuticals, LLC
Schaumburg, IL 60173
401753E
LOT/EXP
GRIFOLS
NDC: 68516-3207-1
Factor IX Complex
Profilnine®
5 mL
500 IU FIX Range
For Intravenous Administration
Contents: One vial Factor IX Complex, Profilnine®, one vial 5 mL Sterile Water for Injection, USP, one Mix2Vial® filter transfer set, and directions for use. Contains Factors II, IX, X and low levels of Factor VII.
The reconstituted product contains not more than 2.5 µg polysorbate 80 and 0.40 µg tri (n-butyl) phosphate per IU of Factor IX.
Contains no preservatives.
Administer within three hours of reconstitution.
Warning: This product is prepared from large pools of human plasma. Human blood and its components may transmit infectious agents. See package insert, WARNINGS AND PRECAUTIONS.
Instructions: The patient and physician should discuss the risks and benefits of this product. For information on dosage and directions for administration, see enclosed package insert.
Storage: Store at temperatures not exceeding 25 °C (77 °F). Do not freeze.
Rx only
Grifols Biologicals LLC
5555 Valley Boulevard
Los Angeles, CA 90032, U.S.A.
U.S. License No. 1694
GTIN 00368516320716
LOT XXXXXXXXXX
EXP DDMMMYYYY
SN XXXXXXXX XXXXXXXX
IU FIX/Vial XXXX
3051564
NDC: 68516-1001-1
Sterile Water for Injection, USP
5 mL
Rx Only
For reconstitution of accompanying product
Single-Dose Container, Nonpyrogenic
Do not use unless clear.
No antimicrobial agent or other substance has been added.
Do not use for intravascular injection without making approximately isotonic by addition of suitable solute.
Discard unused portion.
Mfd by: Laboratorios Grifols, S. A. Parets del Vallès, Barcelona 08150 Spain
Mfd for: Grifols Biologicals LLC Los Angeles, CA 90032, USA
Lot
EXP
3051532
GRIFOLS
NDC: 68516-3208-2
Factor IX Complex
Profilnine®
10 mL
1000 IU FIX Range
For Intravenous Administration
Contents: One vial Factor IX Complex, Profilnine®, one vial 10 mL Sterile Water for Injection, USP, one Mix2Vial® filter transfer set, and directions for use. Contains Factors II, IX, X and low levels of Factor VII.
The reconstituted product contains not more than 2.5 µg polysorbate 80 and 0.40 µg tri (n-butyl) phosphate per IU of Factor IX.
Contains no preservatives.
Administer within three hours of reconstitution.
Warning: This product is prepared from large pools of human plasma. Human blood and its components may transmit infectious agents. See package insert, WARNINGS AND PRECAUTIONS.
Instructions: The patient and physician should discuss the risks and benefits of this product. For information on dosage and directions for administration, see enclosed package insert.
Storage: Store at temperatures not exceeding 25 °C (77 °F). Do not freeze.
Rx only
Grifols Biologicals LLC
5555 Valley Boulevard
Los Angeles, CA 90032, U.S.A.
U.S. License No. 1694
GTIN 00368516320822
LOT XXXXXXXXXX
EXP DDMMMYYYY
SN XXXXXXXX XXXXXXXX
IU FIX/Vial XXXX
3051567
NDC: 68516-1002-2
Sterile Water for Injection, USP
10 mL
Rx Only
For reconstitution of accompanying product
Single-Dose Container, Nonpyrogenic
Do not use unless clear.
No antimicrobial agent or other substance has been added.
Do not use for intravascular injection without making approximately isotonic by addition of suitable solute.
Discard unused portion.
Mfd by: Laboratorios Grifols, S. A. Parets del Vallès, Barcelona 08150 Spain
Mfd for: Grifols Biologicals LLC Los Angeles, CA 90032, USA
Lot
EXP
3051533
GRIFOLS
NDC: 68516-3209-2
Factor IX Complex
Profilnine®
10 mL
1500 IU FIX Range
For Intravenous Administration
Contents: One vial Factor IX Complex, Profilnine®, one vial 10 mL Sterile Water for Injection, USP, one Mix2Vial® filter transfer set, and directions for use. Contains Factors II, IX, X and low levels of Factor VII.
The reconstituted product contains not more than 2.5 µg polysorbate 80 and 0.40 µg tri (n-butyl) phosphate per IU of Factor IX.
Contains no preservatives.
Administer within three hours of reconstitution.
Warning: This product is prepared from large pools of human plasma. Human blood and its components may transmit infectious agents. See package insert, WARNINGS AND PRECAUTIONS.
Instructions: The patient and physician should discuss the risks and benefits of this product. For information on dosage and directions for administration, see enclosed package insert.
Storage: Store at temperatures not exceeding 25 °C (77 °F). Do not freeze.
Rx only
Grifols Biologicals LLC
5555 Valley Boulevard
Los Angeles, CA 90032, U.S.A.
U.S. License No. 1694
GTIN 00368516320921
LOT XXXXXXXXXX
EXP DDMMMYYYY
SN XXXXXXXX XXXXXXXX
IU FIX/Vial XXXX
3051570
PROFILNINE
factor ix complex kit |
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factor ix complex kit |
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PROFILNINE
factor ix complex kit |
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factor ix complex kit |
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PROFILNINE
factor ix complex kit |
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Labeler - GRIFOLS USA, LLC (048987452) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
Grifols Biologicals LLC | 092694538 | manufacture(68516-3201, 68516-3202, 68516-3203, 68516-3204, 68516-3205, 68516-3206, 68516-3207, 68516-3208, 68516-3209) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
Grifols Biologicals LLC | 121076871 | manufacture(68516-3201, 68516-3202, 68516-3203, 68516-3204, 68516-3205, 68516-3206, 68516-3207, 68516-3208, 68516-3209) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
LABORATORIOS GRIFOLS SA | 463719725 | manufacture(68516-1001, 68516-1002) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
Fresenius Kabi USA LLC | 840771732 | manufacture(63323-185) |
Mark Image Registration | Serial | Company Trademark Application Date |
---|---|
PROFILNINE 73410690 1270548 Live/Registered |
Alpha Therapeutic Corporation 1983-01-24 |