ALPROLIX, Coagulation Factor IX (Recombinant), Fc Fusion Protein, is a recombinant DNA derived, coagulation Factor IX concentrate indicated in adults and children with hemophilia B (congenital Factor IX deficiency) for: On demand treatment and control of bleeding episodes, Perioperative management of bleeding, Routine prophylaxis to reduce the frequency of bleeding episodes. Limitation of Use ALPROLIX is not indic...
For intravenous use after reconstitution only Initiate treatment with ALPROLIX under the supervision of a qualified healthcare professional experienced in the treatment of hemophilia B. Dose and duration of treatment depend on the severity of the Factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition. Patients may vary in their pharmacokinetic (e.g., half-life, in vivo reco...
How Supplied ALPROLIX is supplied as a kit comprising: one single-use rFIXFc vial, one pre-filled syringe containing 5 mL diluent and sealed with a plunger stopper and tip-cap, and one sterile vial adapter (reconstitution device). ALPROLIX vials are available in 250, 500, 1000, 2000, 3000, or 4000 IU nominal dosage strengths. The actual Factor IX potency, expressed in IU is stated on every rFIXFc vial and kit cart...
www.fda.gov/medwatch
www.ALPROLIX.comALPROLIX, Coagulation Factor IX (Recombinant), Fc Fusion Protein, is a recombinant DNA derived, coagulation Factor IX concentrate indicated in adults and children with hemophilia B (congenital Factor IX deficiency) for:
Limitation of Use
ALPROLIX is not indicated for induction of immune tolerance in patients with hemophilia B [see Warnings and Precautions (5.3)].
For intravenous use after reconstitution only
| IU/dL (or % of normal) = |
| [Total Dose (IU)/Body Weight (kg)] x Recovery (IU/dL per IU/kg) |
| OR |
| Dose (IU) = |
| Body Weight (kg) x Desired Factor IX Rise (IU/dL or, |
| % of normal) x Reciprocal of Recovery (IU/kg per IU/dL) |
On Demand Treatment and Control of Bleeding Episodes
ALPROLIX dosing for the on demand treatment and control of bleeding episodes is provided in Table 1.
| Type of Bleeding | Circulating Factor IX Level Required (IU/dL or % of normal) | Dosing Interval (hours) |
|---|---|---|
| Minor and Moderate For example: Uncomplicated hemarthroses, superficial muscle (except iliopsoas) without neurovascular compromise, superficial soft tissue, mucous membranes | 30-60 | Repeat every 48 hours if there is further evidence of bleeding |
| Major For example: Iliopsoas and deep muscle with neurovascular injury, or substantial blood loss; Pharyngeal, retropharyngeal, retroperitoneal, CNS | 80-100 | Consider a repeat dose after 6-10 hours and then every 24 hours for the first 3 days. Due to the long half-life of ALPROLIX, the dose may be reduced and frequency of dosing may be extended after day 3 to every 48 hours or longer until bleeding stops and healing is achieved. |
Perioperative Management
ALPROLIX dosing for perioperative management is provided in Table 2.
| Type of Surgery | Circulating Factor IX Level Required (IU/dL or % of normal) | Dosing Interval (hours) |
|---|---|---|
| Minor (including uncomplicated dental extraction) | 50 to 80 | A single infusion may be sufficient. Repeat as needed after 24-48 hours until bleeding stops and healing is achieved. |
| Major | 60 to 100 (initial level) | Consider a repeat dose after 6-10 hours and then every 24 hours for the first 3 days. Due to the long half-life of ALPROLIX, the dose may be reduced and frequency of dosing in the post-surgical setting may be extended after day 3 to every 48 hours or longer until bleeding stops and healing is achieved. |
Routine Prophylaxis
Completely remove the backing from the vial adapter package by peeling back the lid. Do not remove the vial adapter from the package or touch the inside of the package of the adapter.
Place the vial on a flat surface and use one hand to hold the vial steady. Use the other hand to place the vial adapter over the vial. Place the adapter spike directly above the center of the rubber stopper and push the adapter straight down until the spike punctures the center of the vial stopper and is fully inserted.
Lift the package cover away from the vial adapter and discard the cover.
Hold the plunger rod at the circular disk. Place the tip of the plunger rod into the end of the syringe. Turn clockwise until it is securely attached. Only use the diluent syringe provided in the ALPROLIX package.
To combine two or more vials of ALPROLIX, after step 12 above, follow these pooling steps:
For intravenous injection only
Administration Steps:
After infusing ALPROLIX, remove and properly discard the infusion set.
ALPROLIX is available as a lyophilized powder in single use vials containing nominally 250, 500, 1000, 2000, 3000, or 4000 international units (IU) per vial. The actual Factor IX potency is stated on each ALPROLIX vial.
ALPROLIX is contraindicated in individuals who have a known history of hypersensitivity reactions, including anaphylaxis, to the product or its excipients (sucrose, mannitol, sodium chloride, L-histidine and polysorbate 20) .
.
Hypersensitivity reactions have been reported with ALPROLIX. Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with Factor IX replacement products.
The presence of inhibitors has been associated with allergic reactions with Factor IX replacement therapies, including with ALPROLIX. Evaluate patients experiencing allergic reactions for the presence of an inhibitor. Early signs of allergic reactions, which can progress to anaphylaxis, may include angioedema, chest tightness, hypotension, rash, nausea, vomiting, paresthesia, restlessness, wheezing and dyspnea. Discontinue use of ALPROLIX if hypersensitivity symptoms occur, and initiate appropriate treatment.
Formation of neutralizing antibodies (inhibitors) to Factor IX has been reported following administration of ALPROLIX, including in previously untreated patients. Monitor all patients regularly for the development of inhibitors by appropriate clinical observations and laboratory tests [see Warnings and Precautions (5.4)].
Evaluate patients experiencing allergic reactions for the presence of an inhibitor. Closely observe patients for signs and symptoms of acute hypersensitivity reactions, particularly during the early phases of exposure to the product.
Individuals with Factor IX inhibitors may be at an increased risk of anaphylaxis upon subsequent challenge with ALPROLIX.
The use of Factor IX products has been associated with the development of thromboembolic complications, especially in individuals receiving continuous infusion through a central venous catheter. ALPROLIX should be administered as bolus infusion over several minutes [see Dosage and Administration (2.3)]. The safety of ALPROLIX administration by continuous infusion has not been studied.
Common adverse reactions (incidence ≥1%) reported in clinical trials were headache and oral paresthesia.
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.
In the multi-center, prospective, open-label clinical trial with ALPROLIX, 123 previously treated patients (PTPs, exposed to a Factor IX containing product for ≥100 exposure days) were evaluated, with 115 subjects treated for at least 26 weeks and 56 subjects treated for at least 52 weeks.
Adverse reactions (ARs) were reported in 10 of 119 (8.4%) subjects treated with routine prophylaxis or episodic (on-demand) therapy. They are summarized in Table 3.
No subject was withdrawn from the trial due to an adverse reaction. In the trial, no inhibitors were detected and no events of anaphylaxis were reported.
| ||
| System Organ Class | Adverse Reactions (AR) | Number of Subjects (%) N=119* |
| Nervous system disorders | Headache Dizziness Dysgeusia | 2 (1.7) 1 (0.8) 1 (0.8) |
| Gastrointestinal disorders | Paresthesia oral Breath odor | 2 (1.7) 1 (0.8) |
| General disorders and administration site conditions | Fatigue Infusion site pain | 1 (0.8) 1 (0.8) |
| Cardiac disorders | Palpitations | 1 (0.8) |
| Renal and urinary disorders | Obstructive uropathy | 1 (0.8) |
| Vascular disorders | Hypotension | 1 (0.8) |
Obstructive uropathy was reported in one subject with hematuria who developed an obstructing clot in the urinary collecting system. The event resolved with hydration and the subject continued prophylactic treatment with ALPROLIX. A causal relationship of clot formation to ALPROLIX was not established.
Immunogenicity
Previously-treated patients participating in clinical trials were monitored for neutralizing antibodies to Factor IX. No subjects developed neutralizing antibodies to Factor IX.
The detection of antibodies that are reactive to Factor IX is highly dependent on many factors, including the sensitivity and specificity of the assay, sample handling, timing of sample collection, concomitant medications and underlying disease.
The following adverse reaction has been identified during the post-approval use of ALPROLIX. 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.
Blood and lymphatic system disorders: Factor IX inhibitor development
Immune system disorders: hypersensitivity
Pregnancy Category C
Animal reproductive studies have not been conducted with ALPROLIX. It is also not known whether ALPROLIX can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. ALPROLIX should be given to a pregnant woman only if clearly needed.
There is no information available on the effect of Factor IX replacement therapy on labor and delivery. Use only if the potential benefit justifies the potential risk.
It is not known if ALPROLIX is excreted into human milk. Because many drugs are excreted in human milk, caution should be exercised if ALPROLIX is administered to nursing women.
Safety, efficacy, and pharmacokinetics of ALPROLIX have been evaluated in previously treated pediatric patients 12 years of age and older. No dose adjustment is required for adolescents.
Children under 12 years of age may have higher Factor IX body weight-adjusted clearance, shorter half-life, and lower recovery. Higher dose per kilogram body weight or more frequent dosing may be needed in these patients [see Clinical Pharmacology (12.3)].
The use of ALPROLIX in children younger than 12 years of age is supported by the clinical trial of ALPROLIX in subjects 12 years of age and older and interim pharmacokinetic and safety data from a trial of pediatric subjects including 8 subjects 2 to 5 years of age and 15 subjects 6 to 11 years of age who were exposed for a median of 21.3 weeks (1.1 to 45.7 weeks). The safety profile in subjects under 12 years of age is acceptable. Efficacy can be extrapolated from pharmacokinetic data to subjects < 2 years of age. [see Clinical Pharmacology (12.3)]
Clinical studies of ALPROLIX did not include a sufficient number of subjects age 65 and over to determine whether or not they respond differently than younger subjects.
Coagulation Factor IX (Recombinant), Fc Fusion Protein [rFIXFc], the active ingredient in ALPROLIX, is a recombinant coagulation Factor IX protein consisting of the human coagulation Factor IX sequence covalently linked to the Fc domain of human immunoglobulin G1 (IgG1). The Factor IX portion of rFIXFc has a primary amino acid sequence that is identical to the Thr148 allelic form of plasma derived Factor IX and has structural and functional properties similar to endogenous Factor IX. The Fc domain of rFIXFc contains the hinge, CH2, and CH3 regions of IgG1. rFIXFc contains 867 amino acids with a molecular weight of approximately 98 kilodaltons.
ALPROLIX is not derived from human blood and contains no preservatives. The recombinant Factor IX Fc fusion protein is expressed in a human embryonic kidney (HEK) cell line, which produces rFIXFc into a defined cell culture medium that does not contain proteins derived from animal or human sources. The purification process for rFIXFc does not include use of a monoclonal antibody reagent. To enhance viral safety, the production process also incorporates two dedicated viral clearance steps – a detergent treatment step for inactivation and a 15 nm filtration step for removal of viruses. The content of activated Factor IX Fc fusion protein (FIXaFc) is limited to ≤0.035 mole percent FIXaFc/FIXFc.
ALPROLIX is a sterile, non-pyrogenic, preservative-free, white to off-white, lyophilized powder to cake for reconstitution with the provided diluent, for intravenous injection. After reconstitution, the solution has a clear to slightly opalescent appearance and contains the excipients: sucrose, mannitol, sodium chloride, L-histidine and polysorbate 20. ALPROLIX is available in single-use vials containing the labeled amount of Factor IX activity, expressed in international units. Each vial contains nominally 250 IU, 500 IU, 1000 IU, 2000 IU 3000, or 4000 IU.
ALPROLIX is a recombinant, fusion protein that temporarily replaces the missing coagulation Factor IX needed for effective hemostasis. ALPROLIX contains the Fc region of human IgG1, which binds to the neonatal Fc receptor (FcRn). FcRn is part of a naturally occurring pathway that delays lysosomal degradation of immunoglobulins by cycling them back into circulation, and prolonging their plasma half-life.
Hemophilia B is a bleeding disorder characterized by a deficiency of functional coagulation Factor IX (FIX), which leads to a prolonged clotting time in the activated partial thromboplastin time (aPTT) assay, an established in vitro test for the biological activity of Factor IX. Treatment with ALPROLIX shortens the aPTT over the effective dosing period.
The pharmacokinetics (PK) of ALPROLIX (rFIXFc) were evaluated in 22 subjects following a 10 minute intravenous infusion of a single dose of 50 IU/kg. The PK parameters (Table 4) were based on plasma FIX activity measured by the one-stage clotting assay. Blood samples for PK analysis were collected prior to dosing and at 11 time points up to 240 hours (10 days) after dosing. The PK data demonstrate that ALPROLIX has a prolonged circulating half-life.
| |
| PK Parameters | rFIXFc (50 IU/kg) (N = 22) |
| Cmax (IU/dL) | 46.04 (68.3%) |
| AUCinf (h*IU/dL) | 1619.1 (26.1%) |
| CL (mL/kg/h) | 3.304 (28.4%) |
| Vss (mL/kg) | 327.0 (28.2%) |
| Terminal T1/2 (h) | 86.52 (37.2%) |
| MRT (h) | 101.96 (29.7%) |
| IR (IU/dL per IU/kg) | 1.0154 (58.7%) |
| Time to 1% FIX activity (d) | 11.489 (23.8%) |
The ALPROLIX PK profile was stable over repeated dosing as shown by comparable PK parameters at Week 26.
The PK parameters following a 100 IU/kg dose of ALPROLIX were evaluated in a subset of 27 subjects. For this subset, the mean drug clearance (CL) was 2.65 (21.7%) mL/kg/h, the maximum activity (Cmax) was 99.89 IU/dL (20.1%) and the time to 1% FIX activity was 15.8 days (21.3%).
Pediatric and Adolescent Pharmacokinetics
Pharmacokinetic (PK) parameters of ALPROLIX (rFIXFc) were determined for adolescents (12 to 17 years of age) and children (2 to 11 years of age) in open-label, multi-center studies of previously treated patients [see Use in Specific Populations (8.4)].
Pharmacokinetic parameters were evaluated following a 10 minute intravenous infusion in 11 evaluable adolescents who received a single dose of ALPROLIX. PK samples were collected prior to dosing and at multiple time points up to 336 hours (14 days) after dosing. In a separate study, PK parameters were evaluated following a 10 minute intravenous infusion in 18 evaluable children (2 to 11 years of age) who received a single dose of ALPROLIX. PK samples were collected prior to dosing and at multiple time points up to 168 hours (7 days) after dosing. PK parameters for ALPROLIX were estimated based on the plasma FIX activity over time profile.
Table 5 presents the PK parameters calculated from the pediatric data of 29 subjects 2 to 17 years of age. Compared to adults, incremental recovery appeared to be lower and body weight- adjusted clearance appeared to be higher in children under 12 years of age. This may result in a need for per kg body weight dose and interval adjustments in children under 12 years of age. [see Use in Specific Populations (8.4)]
| |||
| |||
| PK parameters1 | 2 to 5 years (N = 5) | 6 to 11 years (N = 13) | 12 to 17 years (N = 11) |
| IR (IU/dL per IU/kg) | 0.5980 (15.7%) | 0.7422 (29.2%) | 0.8929 (36.4%) |
| AUC/Dose (IU·h/dL per IU/kg) | 23.18 (15.9%) | 29.38 (26.6%) | 30.23 (22.2%) |
| T1/2 (h) | 66.40 (32.1%) | 72.23 (23.1%) | 83.59 (19.1%) |
| MRT (h) | 80.52 (22.3%) | 84.06 (18.6%) | 95.13 (19.4%) |
| CL (mL/h/kg) | 4.406 (16.8%) | 3.613 (25.1%) | 3.483 (25.6%) |
| Vss (mL/kg) | 349.0 (19.2%) | 303.0 (28.5%) | 326.0 (24.9%) |
Long-term studies in animals to evaluate the carcinogenic potential of ALPROLIX, or studies to determine the effects of ALPROLIX on genotoxicity or fertility have not been performed. An assessment of the carcinogenic potential of ALPROLIX was completed and no carcinogenic risk from product use has been identified.
The safety and efficacy of ALPROLIX was evaluated in a multi-center, prospective, open-label clinical trial that compared each of two prophylactic treatment regimens (fixed weekly and individualized interval) to episodic (on-demand) treatment; determined hemostatic efficacy in the treatment of bleeding episodes; and determined hemostatic efficacy during perioperative management of subjects undergoing major surgical procedures. A total of 123 previously treated patients (PTPs) with severe hemophilia B (≤ 2% endogenous FIX activity), ages 12-71, were followed for up to 77 weeks.
Sixty three subjects in the fixed weekly interval arm received ALPROLIX for routine prophylaxis starting at an initial dose of 50 IU/kg. The dose was adjusted to maintain FIX trough level between 1% and 3% above baseline or higher, as clinically indicated to prevent bleeding. Fifty subjects required at least one dose adjustment and the median number of dose adjustments was one. The overall median dose on study was 45.2 IU/kg (interquartile range: 38.1, 53.7). The median weekly dose during the last 6 months on study in 58 subjects who were on study for at least 9 months was 40.7 IU/kg (interquartile range: 32.3, 54.1).
Twenty nine subjects in the individualized interval arm received ALPROLIX for routine prophylaxis at a dose of 100 IU/kg every 10 days, with the interval adjusted to maintain FIX trough level between 1% and 3% above baseline or higher, as clinically indicated to prevent bleeding. The overall median interval on study was 12.5 days (interquartile range: 10.4, 13.4). The median interval during the last 6 months in 26 subjects who were on study for at least 9 months was 13.8 days (interquartile range: 10.5, 14.0).
Twenty seven subjects received ALPROLIX as needed for the treatment of bleeding episodes in the episodic (on-demand) treatment arm.
Twelve subjects received ALPROLIX for perioperative management in 14 major surgical procedures. Major surgery was defined as any surgical procedure with or without general anesthesia in which a major body cavity was penetrated and exposed, or a substantial impairment of physical or physiological functions was produced. Four subjects in this arm did not participate in the other arms.
On Demand Treatment and Control of Bleeding Episodes
A total of 636 bleeding events were observed by 114 subjects in the fixed weekly interval prophylaxis, individualized interval prophylaxis, and the episodic (on-demand) arms. The median total dose to treat a bleeding episode was 46.99 IU/kg (interquartile range: 33.33, 62.50). Assessment of response to each injection was recorded by subjects at 8-12 hours after treatment. Efficacy in control of bleeding episodes is summarized in Table 6.
| New Bleeding Episodes | (n=636) |
|---|---|
| |
| Number of injections to treat bleeding episodes | |
| 1 injection | 575 (90.4%) |
| 2 injections | 44 (6.9%) |
| 3 injections | 17 (2.7%) |
| Response* to first injection | (n=613) |
| Excellent or good | 513 (83.7%) |
| Moderate | 90 (14.7%) |
| No response | 10 (1.6%) |
Routine Prophylaxis
Using a negative binomial model, a reduction in annualized bleeding rate (ABR) of 83% (76-89%) for subjects in the fixed weekly interval arm and a reduction of 87% (80-92%) for subjects in the individualized interval arm compared to the episodic (on-demand) treatment arm was observed.
The median duration of treatment on study was 51.4 weeks (range <1-77). A comparison of the ABRs in subjects evaluable for efficacy is summarized in
| |||
| |||
| Bleeding Episode Etiology | Prophylaxis Fixed Weekly Interval (N=61) | Prophylaxis Individualized Interval (N=26) | Episodic (On Demand) (N=27) |
| Overall ABR (IQR)* | 2.95 (1.01, 4.35) | 1.38 (0.00, 3.43) | 17.69 (10.77, 23.24) |
| Spontaneous ABR (IQR)* | 1.04 (0.00, 2.19) | 0.88 (0.00, 2.30) | 11.78 (2.62, 19.78) |
Perioperative Management
Fourteen major surgical procedures were performed in 12 subjects, including 5 knee replacements, abdominal surgery and a complex dental procedure. Perioperative Factor IX replacement with ALPROLIX was by bolus infusion only. The safety of continuous infusion was not evaluated. Hemostasis was assessed by the investigator at 24 hours after surgery using a 4-point scale of excellent, good, fair, and none. The hemostatic response was rated as excellent (n=13) or good (n=1) in 100% of major surgeries. There were an additional 15 minor surgical procedures in 13 subjects. There was no clinical evidence of thrombotic complications in any of the subjects.
How Supplied
ALPROLIX is supplied as a kit comprising:
ALPROLIX vials are available in 250, 500, 1000, 2000, 3000, or 4000 IU nominal dosage strengths. The actual Factor IX potency, expressed in IU is stated on every rFIXFc vial and kit carton label. Components used in the packaging of ALPROLIX do not contain natural rubber latex.
| Strength | Kit NDC Number |
|---|---|
| 250 IU | 64406-966-01 |
| 500 IU | 64406-911-01 |
| 1000 IU | 64406-922-01 |
| 2000 IU | 64406-933-01 |
| 3000 IU | 64406-944-01 |
| 4000 IU | 64406-977-01 |
Storage and Handling
Manufactured by
Biogen Inc.
Cambridge, MA 02142 USA
U.S. License #1697
© Bioverativ 2014-2017. All rights reserved.
Patient Information
ALPROLIX® /all' prō liks /
[Coagulation Factor IX (Recombinant), Fc Fusion Protein]
Please read this Patient Information carefully before using ALPROLIX and each time you get a refill, as there may be new information. This Patient Information does not take the place of talking with your healthcare provider about your medical condition or your treatment.
What is ALPROLIX?
ALPROLIX is an injectable medicine that is used to help control and prevent bleeding in people with hemophilia B. Hemophilia B is also called congenital Factor IX deficiency.
Your healthcare provider may give you ALPROLIX when you have surgery.
Who should not use ALPROLIX?
You should not use ALPROLIX if you are allergic to ALPROLIX or any of the other ingredients in ALPROLIX. Tell your healthcare provider if you have had an allergic reaction to any Factor IX product prior to using ALPROLIX.
What should I tell my healthcare provider before using ALPROLIX?
Tell your healthcare provider about all of the medicines you take, including all prescription and non-prescription medicines, such as over-the-counter medicines, supplements, or herbal medicines.
Tell your doctor about all of your medical conditions, including if you:
How should I use ALPROLIX?
ALPROLIX should be administered as ordered by your healthcare provider. You should be trained on how to do infusions by your healthcare provider. Many people with hemophilia B learn to infuse their ALPROLIX by themselves or with the help of a family member.
See the Instructions for Use for directions on infusing ALPROLIX. The steps in the Instructions for Use are general guidelines for using ALPROLIX. Always follow any specific instructions from your healthcare provider. If you are unsure of the procedure, please ask your healthcare provider. Do not use ALPROLIX as a continuous intravenous infusion.
Contact your healthcare provider immediately if bleeding is not controlled after using ALPROLIX.
What are the possible side effects of ALPROLIX?
Common side effects of ALPROLIX include headache and abnormal sensation in the mouth.
Allergic reactions may occur. Call your healthcare provider or get emergency treatment right away if you have any of the following symptoms: hives, chest tightness, wheezing, difficulty breathing, or swelling of the face.
ALPROLIX may increase the risk of forming abnormal blood clots in your body, especially if you have risk factors for developing blood clots. Call your healthcare provider or seek emergency care if you have symptoms of a possible abnormal blood clot, which may include: chest pain, difficulty breathing, unexpected swelling of an arm or leg with or without pain or tenderness.
Your body can also make antibodies called, “inhibitors,” against ALPROLIX, which may stop ALPROLIX from working properly. Your healthcare provider may need to test your blood for inhibitors from time to time.
These are not all the possible side effects of ALPROLIX.
Talk to your healthcare provider about any side effect that bothers you or that does not go away.
How should I store ALPROLIX?
Store ALPROLIX vials at 2°C to 8°C (36°F to 46°F). Do not freeze.
ALPROLIX vials may also be stored at room temperature up to 30°C (86°F) for a single 6 month period.
If you choose to store ALPROLIX at room temperature:
Do not use product or diluent after the expiration date printed on the carton, vial or syringe.
After Reconstitution:
What else should I know about ALPROLIX?
Medicines are sometimes prescribed for purposes other than those listed here. Do not use ALPROLIX for a condition for which it was not prescribed. Do not share ALPROLIX with other people, even if they have the same symptoms that you have.
Manufactured by
Biogen Inc.
Cambridge, MA 02142 USA
U.S. License #1697
© Bioverativ 2014-2017. All rights reserved.
ALPROLIX™
Coagulation Factor IX (Recombinant), Fc Fusion Protein
INSTRUCTIONS FOR USE
Read the Instructions for Use before you start using ALPROLIX™ and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
Your healthcare provider should show you or your caregiver how to reconstitute and administer ALPROLIX™ the first time ALPROLIX™ is used.
Check the expiration date on the ALPROLIX™ kit.
Do notuse the product if past the expiration date.
Allow the ALPROLIX™ vial and the diluent to come to room temperature.
Do notuse external heat sources such as putting the vial and/or diluent in hot water.
Find a clean, flat work surface and collect all the supplies you will need to reconstitute and administer ALPROLIX™.
Wash your hands with soap and water. Aseptic technique (clean and germ free) should be used.
YOUR KIT CONTAINS:
RECONSTITUTION
| Step 1 Remove the plastic cap from the ALPROLIX™ vial. Wipe the rubber stopper of the vial with an alcohol wipe and allow it to dry. After cleaning, do not touch the rubber stopper with your hand or allow it to touch any surface. |  |
| Step 2 Completely remove the backing from the vial adapter package by peeling back the lid. Do notremove the vial adapter from the package or touch the inside of the vial adapter. |  |
| Step 3 Keep the vial on a flat surface. Hold the vial adapter package with one hand and using the other hand, place the vial adapter over the vial. The spike should be placed directly above the center of the rubber stopper. Push the vial adapter straight down until the adapter spike punctures the center of the vial stopper and is fully inserted. |  |
| Step 4 Lift the package cover away from the vial adapter and discard the cover. |  |
| Step 5 Only usethe diluent syringe provided to reconstitute the drug product. Hold the plunger rod at the circular disk. Place the tip of the plunger rod into the end of the syringe. Turn in a clockwise motion until it is securely attached. |  |
| Step 6 With one hand, hold the diluent syringe right under the cap, and with the cap pointing up. Make sure you are holding the diluent syringe by the ridged part directly under the cap. Do notuse if the cap has been removed or is not securely attached. |  |
| Step 7 With your other hand, grasp the cap and bend it at a 90° angle until it snaps off. After the cap snaps off, you will see the glass tip of the syringe. Do not touch the glass tip of the syringe or inside of the cap. |  |
| Step 8 Be sure the vial is sitting on a flat surface. Insert the tip of the syringe into the adapter opening. Turn the syringe in a clockwise motion until it is securely attached to the adapter. |  |
| Step 9 Slowly depress the plunger rod to inject all of the diluent into the vial. The plunger rod may rise slightly after this process. This is normal. |  |
| Step 10 With the syringe still connected to the adapter, gently swirl the vial until the product is completely dissolved. The appearance of the solution should be clear to slightly opalescent and colorless. Do notshake. Do notuse the reconstituted ALPROLIX™ if it contains visible particles or is cloudy.
|  |
| Step 11 Make sure the plunger rod is completely depressed. Turn the vial upside-down. Slowly pull on the plunger rod to draw the solution into the syringe. Be careful not topull the plunger rod completely out of the syringe. |  |
| Step 12 Gently unscrew the syringe from the vial adapter and dispose of the vial with the adapter still attached. Do nottouch the syringe tip or the inside of the cap. Reconstituted ALPROLIX™ should be administered as soon as possible. |  |
POOLING
POOLING is the process of combining two or more reconstituted vials into a larger syringe (not into the diluent syringe) prior to intravenous administration.
If you are using two or more vials, follow these pooling steps.
Be sure to leave the vial adapter attached to the vial as you will need it for attaching a large luer lock syringe.
Do notdetach the diluent syringe or the large luer syringe until you are ready to attach the large luer lock syringe to the next vial (with vial adapter attached).
| Step 1 Remove the diluents syringe from the vial adapter by turning it counterclockwise until it is completely detached. |  |
| Step 2 Attach a separate large luer lock syringe by turning clockwise until it is securely attached. |  |
| Step 3 Slowly pull on the plunger rod to draw the solution into the syringe. Repeat this pooling procedure with each vial you will be using. Once you have pooled the required dose, proceed to administration using the large luer lock syringe. |  |
ADMINISTRATION (Intravenous Injection)
ALPROLIX™ is administered by intravenous infusion after reconstitution of the drug powder with the diluent.
Your healthcare provider should teach you how to infuse ALPROLIX™. Once you have been taught to self-infuse, you can follow these instructions.
Do notadminister reconstituted ALPROLIX™ if it contains particulate matter, is discolored, or is cloudy.
| Step 1 Attach the syringe to the connector end of the infusion set tubing by turning clockwise until it is securely attached. Do notadminister reconstituted ALPROLIX™ in the same tubing or container with other medicinal products. |  |
| Step 2 Apply a tourniquet and clean the skin area where you will perform the infusion using an alcohol wipe. |  |
| Step 3 Depress the plunger until all air is removed from the syringe and ALPROLIX™ has reached the end of the infusion set tubing. Do not push ALPROLIX™ through the needle. |  |
| Step 4 Remove the protective needle cover from the infusion set tubing. Insert the needle on the infusion set tubing into the vein. Remove the tourniquet. Alwaysverify proper needle placement when performing intravenous administration. |  |
| Step 5 Slowly depress the plunger on the syringe to administer ALPROLIX™. ALPROLIX™ should be injected intravenously over several minutes. The rate of administration should be determined by your comfort level. The small amount of drug product left in the infusion set will not affect treatment. |  |
| Step 6 After infusing ALPROLIX™, remove the infusion set and use a sterile gauze to put pressure on the infusion site for several minutes. Apply an adhesive bandage if necessary. Dispose of all unused solution, empty vial(s), and other used medical supplies in an appropriate medical waste container. |  |
STORAGE CONDITIONS - PRODUCT KIT
Keep refrigerated until use.
Keep away from direct sunlight.
STORAGE CONDITIONS - RECONSTITUTED
ALPROLIX™ should be administered within 3 hours after reconstitution.
Do not refrigerate after reconstitution.
Keep away from direct sunlight
Revised March 2014
Manufactured by:
Biogen Idec, Inc.
14 Cambridge Center, Cambridge, MA 02142 USA
U.S. License #1697
©2014 Biogen Idec Inc. All rights reserved.
For more information go to www.ALPROLIX.com or call 1-855-692-5776
Principal Display Panel - 250 IU Nominal Carton Label
NDC 64406-966-01
One single-use vial
with 5 mL prefilled
diluent syringe
ALPROLIX™
Coagulation Factor IX
(Recombinant), Fc Fusion Protein
For Intravenous Administration
Rx Only
Manufactured by:
Biogen Inc.
Cambridge, MA 02142
US License Number 1697
Principal Display Panel - 250 IU Vial Label
ALPROLIX™ NDC 64406-952-01
Coagulation Factor IX (Recombinant), Fc Fusion Protein
For Intravenous Administration Rx Only
Store in a refrigerator
at 2°C to 8°/36°F to 46°F.
RECONSTITUTE ONLY
WITH DILUENT PROVIDED
Dosage & Administration:
See Package Insert
No preservatives
Manufactured by:
Biogen Inc.
Cambridge, MA 02142
US License Number 1697
Principal Display Panel - 500 IU Nominal Carton Label
NDC 64406-911-01
One single-use vial
with 5 mL prefilled
diluent syringe
ALPROLIX™
Coagulation Factor IX
(Recombinant), Fc Fusion Protein
For Intravenous Administration
Rx Only
Manufactured by:
Biogen Inc.
Cambridge, MA 02142
US License Number 1697
Principal Display Panel - 500 IU Vial Label
ALPROLIX™ NDC 64406-953-09
Coagulation Factor IX (Recombinant), Fc Fusion Protein
For Intravenous Administration Rx Only
Store in a refrigerator
at 2°C to 8°/36°F to 46°F.
RECONSTITUTE ONLY
WITH DILUENT PROVIDED
Dosage & Administration:
See Package Insert
No preservatives
Manufactured by:
Biogen Inc.
Cambridge, MA 02142
US License Number 1697
Principal Display Panel - 1000 IU Nominal Carton Label
NDC 64406-922-01
One single-use vial
with 5 mL prefilled
diluent syringe
ALPROLIX™
Coagulation Factor IX
(Recombinant), Fc Fusion Protein
For Intravenous Administration
Rx Only
Manufactured by:
Biogen Inc.
Cambridge, MA 02142
US License Number 1697
Principal Display Panel - 1000 IU Vial Label
ALPROLIX™ NDC 64406-954-09
Coagulation Factor IX (Recombinant), Fc Fusion Protein
For Intravenous Administration Rx Only
Store in a refrigerator
at 2°C to 8°/36°F to 46°F.
RECONSTITUTE ONLY
WITH DILUENT PROVIDED
Dosage & Administration:
See Package Insert
No preservatives
Manufactured by:
Biogen Inc.
Cambridge, MA 02142
US License Number 1697
Principal Display Panel - 2000 IU Nominal Carton Label
NDC 64406-933-01
One single-use vial
with 5 mL prefilled
diluent syringe
ALPROLIX™
Coagulation Factor IX
(Recombinant), Fc Fusion Protein
For Intravenous Administration
Rx Only
Manufactured by:
Biogen Inc.
Cambridge, MA 02142
US License Number 1697
Principal Display Panel - 2000 IU Vial Label
ALPROLIX™ NDC 64406-955-09
Coagulation Factor IX (Recombinant), Fc Fusion Protein
For Intravenous Administration Rx Only
Store in a refrigerator
at 2°C to 8°/36°F to 46°F.
RECONSTITUTE ONLY
WITH DILUENT PROVIDED
Dosage & Administration:
See Package Insert
No preservatives
Manufactured by:
Biogen Inc.
Cambridge, MA 02142
US License Number 1697
Principal Display Panel - 3000 IU Nominal Carton Label
NDC 64406-944-01
One single-use vial
with 5 mL prefilled
diluent syringe
ALPROLIX™
Coagulation Factor IX
(Recombinant), Fc Fusion Protein
For Intravenous Administration
Rx Only
Manufactured by:
Biogen Inc.
Cambridge, MA 02142
US License Number 1697
Principal Display Panel - 3000 IU Vial Label
ALPROLIX™ NDC 64406-956-09
Coagulation Factor IX (Recombinant), Fc Fusion Protein
For Intravenous Administration Rx Only
Store in a refrigerator
at 2°C to 8°/36°F to 46°F.
RECONSTITUTE ONLY
WITH DILUENT PROVIDED
Dosage & Administration:
See Package Insert
No preservatives
Manufactured by:
Biogen Inc.
Cambridge, MA 02142
US License Number 1697
Principal Display Panel - 4000 IU Nominal Carton Label
NDC 64406-977-01
One single-use vial
with 5 mL prefilled
diluent syringe
ALPROLIX™
Coagulation Factor IX
(Recombinant), Fc Fusion Protein
For Intravenous Administration
Rx Only
Manufactured by:
Biogen Inc.
Cambridge, MA 02142
US License Number 1697
Principal Display Panel - 4000 IU Vial Label
ALPROLIX™ NDC 64406-951-09
Coagulation Factor IX (Recombinant), Fc Fusion Protein
For Intravenous Administration Rx Only
Store in a refrigerator
at 2°C to 8°/36°F to 46°F.
RECONSTITUTE ONLY
WITH DILUENT PROVIDED
Dosage & Administration:
See Package Insert
No preservatives
Manufactured by:
Biogen Inc.
Cambridge, MA 02142
US License Number 1697
Principal Display Panel - Diluent Vial Label
Sterile Sodium Chloride
Solution 0.325% 5 mL
Diluent for accompanying product.
For intravenous use.
Single-use. Rx only
Contains no preservatives.
Manufactured for:
Biogen Inc., Cambridge, MA 02142
US License # 1697
Manufactured by:
Vetter Pharma-Fertigung GmbH & Co. KG
88212 Ravensburg, Germany
| Package NDC | Billing unit | Product NDC | DailyMed indexing SPL | SPL version | Effective |
|---|---|---|---|---|---|
| 64406-911-01 | EA - Each | 64406-911 | 9aa70b09-18f1-4c27-8d0d-26961d197381 | 1 | 2014-05-02 |
| 64406-922-01 | EA - Each | 64406-922 | 8065fc00-43ff-4861-8aec-6562043841a4 | 1 | 2014-05-02 |
| 64406-933-01 | EA - Each | 64406-933 | 34590d82-367a-447d-a797-958dab853add | 1 | 2014-05-02 |
| 64406-944-01 | EA - Each | 64406-944 | aa846eb7-64a2-41f0-9020-f8c455dcc765 | 1 | 2014-05-02 |
| 64406-966-01 | EA - Each | 64406-966 | 2ef0835a-f50e-4f59-bc0c-fe8fdb199717 | 1 | 2016-04-04 |
| 64406-977-01 | EA - Each | 64406-977 | 8d79f641-7ce3-4a34-b810-47c48a8a2e23 | 1 | 2016-11-08 |
| Ingredient | Type | UNII | SPL version | Uploaded |
|---|---|---|---|---|
| Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein | ACTIVE INGREDIENT | 02E00T2QDE | 4 | |
| eftrenonacog alfa | ACTIVE MOIETY | 02E00T2QDE | 4 | |
| histidine | INACTIVE INGREDIENT | 4QD397987E | 4 | |
| mannitol | INACTIVE INGREDIENT | 3OWL53L36A | 4 | |
| polysorbate 20 | INACTIVE INGREDIENT | 7T1F30V5YH | 4 | |
| sucrose | INACTIVE INGREDIENT | C151H8M554 | 4 |
Every source-derived product name is available through these pages.
| BLA | Proprietary name | Proper name | License type | Status | Latest source |
|---|---|---|---|---|---|
| 125444 | Alprolix | Coagulation Factor IX (Recombinant), Fc Fusion Protein | 351(a) | Rx | 2026-09-01 |
Every source-derived ingredient row is available through these pages.
Inactive Ingredient Database values describe FDA-listed use contexts. The match method and ambiguity count are shown because ingredient names, routes, and dosage forms are not always unique. Browse recovered IID releases and source provenance.
| DailyMed ingredient | IID ingredient | UNII | Dosage form / route | Potency | Maximum daily exposure | Match |
|---|---|---|---|---|---|---|
| sucrose | SUCROSE | C151H8M554 | POWDER, FOR SOLUTION / ORAL | 38666 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | SOLUTION, CONCENTRATE / INTRAVENOUS | 220 mg | ||
| polysorbate 20 | POLYSORBATE 20 | 7T1F30V5YH | POWDER, FOR SUSPENSION / ORAL | 1.3 mg/5ml | ||
| sucrose | SUCROSE | C151H8M554 | TROCHE / ORAL | NA | ||
| mannitol | MANNITOL | 3OWL53L36A | POWDER / RESPIRATORY (INHALATION) | 6 mg | ||
| polysorbate 20 | POLYSORBATE 20 | 7T1F30V5YH | SUPPOSITORY / VAGINAL | NA | ||
| sucrose | SUCROSE | C151H8M554 | WAFER / ORAL | 155.2 mg | ||
| sucrose | SUCROSE | C151H8M554 | INJECTION, SOLUTION / INTRAVENOUS | NA | ||
| mannitol | MANNITOL | 3OWL53L36A | CAPSULE, EXTENDED RELEASE / ORAL | 160 mg | ||
| histidine | HISTIDINE | 4QD397987E | INJECTABLE, LIPOSOMAL / INTRAVENOUS | 63 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | INJECTION, POWDER, FOR SOLUTION / SUBCUTANEOUS | 35 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | POWDER, FOR SUSPENSION / ORAL | 7093 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | SUSPENSION, EXTENDED RELEASE / ORAL | 2464.6 mg | ||
| histidine | HISTIDINE | 4QD397987E | CAPSULE / ORAL | 0.76 mg | ||
| polysorbate 20 | POLYSORBATE 20 | 7T1F30V5YH | INJECTION / INTRAMUSCULAR | 1.62 %w/v | ||
| mannitol | MANNITOL | 3OWL53L36A | CAPSULE / ORAL | 1562 mg | ||
| sucrose | SUCROSE | C151H8M554 | GRANULE / ORAL | NA | ||
| polysorbate 20 | POLYSORBATE 20 | 7T1F30V5YH | INJECTION, SOLUTION / SUBCUTANEOUS | NA | ||
| sucrose | SUCROSE | C151H8M554 | CAPSULE, COATED PELLETS / ORAL | 59.8 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | INJECTION, SOLUTION / INTRAVENOUS | 15400 mg | ||
| polysorbate 20 | POLYSORBATE 20 | 7T1F30V5YH | SHAMPOO / TOPICAL | 8 %w/w | ||
| mannitol | MANNITOL | 3OWL53L36A | INJECTION, SUSPENSION / INTRAVENOUS | 2.5 %w/v | ||
| mannitol | MANNITOL | 3OWL53L36A | GEL / OPHTHALMIC | 25 mg | ||
| polysorbate 20 | POLYSORBATE 20 | 7T1F30V5YH | SUSPENSION / ORAL | 80 mg | ||
| sucrose | SUCROSE | C151H8M554 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 2000 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | INJECTION, POWDER, FOR SOLUTION / PARENTERAL | 200 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAMUSCULAR | 113 mg | ||
| polysorbate 20 | POLYSORBATE 20 | 7T1F30V5YH | GEL / TOPICAL | 5 %w/w | ||
| mannitol | MANNITOL | 3OWL53L36A | TABLET, DELAYED RELEASE / ORAL | 639 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | INJECTION, POWDER, FOR SUSPENSION / SUBCUTANEOUS | 180 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | INJECTION, POWDER, FOR SUSPENSION / INTRAVENOUS | 181 mg | ||
| sucrose | SUCROSE | C151H8M554 | CAPSULE / ORAL | 3568 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 15400 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | INJECTION, POWDER, FOR SOLUTION / INTRAMUSCULAR | 300 mg | ||
| polysorbate 20 | POLYSORBATE 20 | 7T1F30V5YH | SPRAY, METERED / NASAL | 40 mg | ||
| polysorbate 20 | POLYSORBATE 20 | 7T1F30V5YH | EMULSION / TOPICAL | 2 %w/w | ||
| sucrose | SUCROSE | C151H8M554 | TABLET, FILM COATED / ORAL | 145 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | SOLUTION / SUBCUTANEOUS | 4.54 %w/v | ||
| sucrose | SUCROSE | C151H8M554 | INJECTABLE, LIPOSOMAL / INTRAVENOUS | 7560 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | TABLET, CHEWABLE, EXTENDED RELEASE / ORAL | 616 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | INJECTION, SUSPENSION / INTRAMUSCULAR | 71 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | TABLET / SUBLINGUAL | 495 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | TABLET, CHEWABLE / ORAL | 3726 mg | ||
| sucrose | SUCROSE | C151H8M554 | TABLET, FILM COATED, EXTENDED RELEASE / ORAL | 119.12 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | INJECTION, SOLUTION / SUBMUCOSAL | 2.94 %w/v | ||
| sucrose | SUCROSE | C151H8M554 | LIQUID / ORAL | 37500 mg | ||
| sucrose | SUCROSE | C151H8M554 | SUPPOSITORY / RECTAL | NA | ||
| sucrose | SUCROSE | C151H8M554 | INJECTION / SUBCUTANEOUS | 47.75 mg | ||
| histidine | HISTIDINE | 4QD397987E | INJECTION, SOLUTION / INTRAVENOUS | 0.09 %w/v | ||
| sucrose | SUCROSE | C151H8M554 | TROCHE / BUCCAL | NA | ||
| sucrose | SUCROSE | C151H8M554 | INJECTION, SUSPENSION, LIPOSOMAL / INTRAVENOUS | 9.4 %w/v | ||
| sucrose | SUCROSE | C151H8M554 | ELIXIR / ORAL | 18000 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | SOLUTION, GEL FORMING / DROPS / OPHTHALMIC | 4 mg | ||
| polysorbate 20 | POLYSORBATE 20 | 7T1F30V5YH | INJECTION, SOLUTION / INTRAVENOUS | 30 mg | ||
| sucrose | SUCROSE | C151H8M554 | TABLET / SUBLINGUAL | 109 mg | ||
| histidine | HISTIDINE | 4QD397987E | SUSPENSION / ORAL | 5 mg/1ml | ||
| sucrose | SUCROSE | C151H8M554 | SUSPENSION / ORAL | 48209 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | INJECTION, POWDER, FOR SOLUTION / INTRAVENOUS | 980.4 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | SOLUTION / INTRAVENOUS | 15400 mg | ||
| mannitol | MANNITOL | 3OWL53L36A | INJECTION, SOLUTION / SUBCUTANEOUS | 99 mg |
Adverse event summaries are temporarily unavailable. Other product information remains available.
