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FIX-US-1198 06/17

ALPROLIX

®

[Coagulation Factor IX (Recombinant), Fc Fusion Protein],

Lyophilized Powder for Solution For Intravenous Injection.

Brief Summary of Full Prescribing Information.

The risk information provided here is not comprehensive. The FDA-approved product labeling can be

found at

www.alprolix.com

or 1-855-692-5776. You are encouraged to report negative side effects of

prescription drugs to the FDA. Visit

www.fda.gov/medwatch

, or call 1-800-FDA-1088.

INDICATIONS AND USAGE

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 de ciency) 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 indicated for induction of immune tolerance in patients with hemophilia B

[

see Warnings and Precautions

].

CONTRAINDICATIONS

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).

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

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.

Neutralizing Antibodies

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), of full

Prescribing Information and/or Monitoring Laboratory Tests

]

.

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.

Thromboembolic Complications

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), of full Prescribing Information

]

.

The safety of ALPROLIX administration by continuous infusion has not

been studied.

Monitoring Laboratory Tests

• To con rm adequate Factor IX levels have been achieved and maintained, monitor plasma

Factor IX activity by performing the one-stage clotting assay [

see Dosage and Administration

(2.1), of full Prescribing Information

]. Factor IX results can be affected by the type of aPTT

reagent used. Measurement with a one-stage clotting assay using a kaolin-based aPTT reagent will

likely result in an underestimation of activity level.

• Monitor for the development of Factor IX inhibitors if the expected Factor IX activity levels in plasma

are not attained, or if bleeding is not controlled with the recommended dose of ALPROLIX. Perform a

Bethesda assay to determine if Factor IX inhibitors are present.

ADVERSE REACTIONS

Common adverse reactions (incidence ≥1%) reported in clinical trials were headache and oral paresthesia.

Clinical Trials 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 re ect 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.

Table 3: Summary of Adverse Reactions

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)

*119 previously treated patients (PTPs) on routine prophylaxis or episodic (on-demand) therapy

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 speci city of the assay, sample handling, timing of sample collection, concomitant

medications and underlying disease.

Postmarketing Experience

The following adverse reaction has been identi ed 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

USE IN SPECIFIC POPULATIONS

Pregnancy

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.

Labor and Delivery

There is no information available on the effect of Factor IX replacement therapy on labor and delivery.

Use only if the potential bene t justi es the potential risk.

Nursing Mothers

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.

Pediatric Use

Safety, ef cacy, 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.

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 pro le in subjects under

12 years of age is acceptable. Ef cacy can be extrapolated from pharmacokinetic data to subjects

<2 years of age [

see Clinical Pharmacology (12.3), of full Prescribing information

]

.

Geriatric Use

Clinical studies of ALPROLIX did not include a suf cient number of subjects age 65 and over to

determine whether or not they respond differently than younger subjects.

PATIENT COUNSELING INFORMATION

Advise patient to read the FDA-approved patient labeling (Patient Information and Instructions

for Use).

• Advise patients to report any adverse reactions or problems following ALPROLIX administration

to their physician or healthcare provider.

• Advise patients to contact their healthcare provider or treatment facility for further treatment

and/or assessment if they experience a lack of a clinical response to Factor IX therapy, as this

may indicate the development of an inhibitor.

• Inform patients of the early signs of hypersensitivity reactions (including hives, chest tightness,

wheezing, dif culty breathing and swelling of the face) and anaphylaxis. Instruct patients to

discontinue use of the product and contact their healthcare provider if these symptoms occur.

• Advise patients to contact their healthcare provider or go to the emergency department right away

if a thromboembolic event occurs.

Manufactured by:

Biogen Inc.

Cambridge, MA 02142 USA

U.S. License #1697

©2014-2017 Bioverativ. All rights reserved.