Rixubis

>10% (BeneFIX)

Headache (10.8%)

1-10% (BeneFIX)

Dizziness (7.7%)

Injection site reaction (7.7%)

Injection site pain (6.2%)

Nausea (6.2%)

Rash (6.2%)

Taste perversion (4.6%)

Hives (3.1%)

Flushing (3.1%)

Fever (3.1%)

Factor IX inhibition (1.5%)

Blurred vision (1.5%)

Vomiting (1.5%)

Cellulitis at IV site (1.5%)

Phlebitis at IV site (1.5%)

Shaking (1.5%)

Drowsiness (1.5%)

Renal infarct (1.5%)

Dry cough (1.5%)

Hypoxia (1.5%)

Chest tightness (1.5%)

1-10% (Rixubis)

Factor IX or furin antibodies (7.7%)

Dysgeusia (1.1%)

Pain in extremity (1.1%)

Positive furin antibody test (1.1%)

1-10% (Alprolix)

Headache (1.7%)

Oral paresthesia (1.7%)

<1% (Alprolix)

Dizziness

Dysgeusia

Breath odor

Fatigue

Infusion site pain

Palpitations

Obstructive uropathy

Hypotension

RIXUBIS [Coagulation Factor IX (Recombinant)] is a purified protein produced by recombinant DNA technology. Its amino acid sequence is identical to that of the Ala-148 allelic form of plasma derived factor IX, and its structural and functional characteristics are similar to those of plasma derived factor IX. RIXUBIS is produced by a genetically engineered CHO cell line. No human or animal proteins are added during any stage of manufacturing or formulation of RIXUBIS. The CHO cell line secretes recombinant factor IX into a defined cell culture medium that does not contain hormones, and the recombinant factor IX is purified by a chromatography purification process that does not require a monoclonal antibody step. The process includes validated virus inactivation/removal steps, namely solvent/detergent treatment and 15 nm nanofiltration. RIXUBIS is predominantly a single component by sodium dodecyl sulfate-polyacrylamide gel electrophoresis evaluation. The specific activity of RIXUBIS is ≥ 200 international units per milligram of protein. Factor IX preactivation, the percent of Factor IXa/Factor IX as measured by activity assays, is ≤ 0.03%. The potency in international units is determined using an in vitro thromboplastin time (aPTT)-based one-stage clotting assay calibrated against the World Health Organization (WHO) International Standard for Factor IX concentrate. Factor IX potency results can be affected by the type of aPTT reagent and reference standard used in the assay; differences of up to 40% have been observed.

RIXUBIS is formulated as a sterile, nonpyrogenic lyophilized powder to be reconstituted with Sterile Water for Injection for intravenous administration. It does not contain any preservatives and is available in single-use vials containing the labeled amount of factor IX activity, expressed in international units. Each vial contains nominally 250, 500, 1000, 2000 or 3000 international units of recombinant coagulation factor IX. After reconstitution of the lyophilized powder, all dosage strengths yield a clear, colorless solution. The concentrations of excipients are:

No information provided.

Common adverse reactions observed in > 1% of subjects in clinical studies were dysgeusia, pain in extremity, and positive furin antibody test.

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 the clinical trials of another drug and may not reflect the rates observed in clinical practice.

During clinical development, in a combined trial, 99 male previously treated patients (PTPs; exposed to a factor IX-containing product for ≥ 150 days) received at least one infusion of RIXUBIS as part of either on-demand treatment of bleeding episodes, perioperative management of major and minor surgical, dental, or other invasive procedures, routine prophylaxis, or pharmacokinetic evaluation of RIXUBIS. Eleven subjects (11.1%) were < 6 years of age, 12 (12.1%) were 6 to < 12 years of age, 3 (3%) were adolescents (12 to < 16 years of age), and 73 (73.7%) were adults (16 years of age and older). The subjects received a total of 14,018 infusions with a median of 163 infusions of RIXUBIS (range 8 to 327 infusions), for a median of 156 exposure days (range 8 to 316 days).

A total of 337 adverse events were reported in 80 (80.8%) of the 99 subjects. Adverse reactions that occurred in > 1% of subjects are shown in Table 3.

Table 3 : Summary of Adverse Reactions

All 99 subjects were monitored for inhibitory and binding antibodies to factor IX, and binding antibodies to CHO protein and furin, at the following time points: at screening, at 72 hours following the first infusion of RIXUBIS and the commercial recombinant factor IX product in the crossover portion of the pharmacokinetic trial, after 5 and 13 weeks following first exposure to RIXUBIS, and thereafter every 3 months. Antibodies against furin were tested by an in-house enzyme-linked immunosorbent assay (ELISA). A titer of 1:20 or 1:40 was considered to be indeterminate for the above validated assay, as these titers were too low to be verified by the confirmatory assay.

No subjects developed neutralizing antibodies to factor IX. Low-titer, non-neutralizing antibodies against factor IX were observed in 21 (21.2%) subjects at one or more time points. Three of these 21 subjects were found to have these antibodies at screening, prior to receiving RIXUBIS. Six of the 21 subjects were pediatric (2 subjects in < 6 years of age cohort, 4 subjects in 6 to < 12 years age cohort). No clinical adverse findings were observed in any of these 21 subjects.

Nineteen subjects (19.2%) had signals for antibodies against furin (indeterminate specificity). Five of these 19 subjects expressed signals for antibodies at screening, prior to RIXUBIS treatment. One subject had an antibody signal after treatment with the comparator product and prior to RIXUBIS treatment. Two additional subjects had a positive titer of 1:80 that was not present when checked at a later time point and therefore considered transient. Two of the 19 subjects were pediatric (6 to < 12 years age cohort). All post-treatment antibody titer increases in these two pediatric subjects were < 2 dilution steps and therefore considered unrelated to treatment. No clinical adverse findings were observed in any of these 19 subjects.

In a trial of 500 normal volunteers, using the same assay as in the clinical trial, 7% had titers of 1:20 or 1:40 and 1.2% had higher titers ranging from 1:80 to 1:320. These antibodies are thought to be part of a natural immune system response. To date, these antibodies have not been associated with any clinical adverse findings.

The detection of antibody formation is dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.

There was no clinical evidence of thromboembolic complications in any of the subjects. Out-of-range values for thrombogenicity markers (thrombin-antithrombin III, prothrombin fragment 1.2, and D-dimer), determined during the pharmacokinetic portion of the combined trial, did not reveal any pattern indicative of clinically relevant thrombogenicity with either RIXUBIS or a comparator factor IX-containing product.

Post-marketing Experience

Because the following 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.

Hypersensitivity (including symptoms such as dyspnea, pruritus)

Urticaria, rash

The following class adverse reactions have been seen with another recombinant factor IX: inadequate factor IX recovery, inhibitor development, anaphylaxis, angioedema, hypotension, and thrombosis.

Read the entire FDA prescribing information for Rixubis (Coagulation Factor IX (Recombinant) for Intramuscular Injection)

• Baxter Healthcare Corporation

Take Rixubis exactly as prescribed.

Rixubis is given directly into the bloodstream. Rixubis should be administered as ordered by your healthcare provider. You should be trained on how to do infusions by your healthcare provider or hemophilia treatment center. Many people with hemophilia B learn to infuse their Rixubis by themselves or with the help of a family member.

You may have to have blood tests done after getting Rixubis to be sure that your blood level of factor IX is high enough to clot your blood. Call your healthcare provider right away if your bleeding does not stop after taking Rixubis.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take 2doses of Rixubis at the same time.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

• If you have an allergy to Factor IX or any other part of this medicine (Rixubis).
• If you are allergic to hamsters, talk with the doctor.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Irritation where the shot is given.
• Pain where the shot was given.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.