Alprolix

Name: Alprolix

Indications

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:

  • Control and prevention of bleeding episodes,
  • Perioperative management,
  • Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

ALPROLIX™ is not indicated for induction of immune tolerance in patients with hemophilia B [see WARNINGS AND PRECAUTIONS].

Overdose

No information provided.

Manufacturer

  • Biogen Idec Inc.

Inform MD

Before taking Alprolix, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

  • have or have had any medical problems
  • have any allergies, including allergies to hamsters
  • are breastfeeding. It is not known if Alprolix passes into your milk and if it can harm your baby.
  • are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Uses for Alprolix

Hemophilia B

On-demand treatment and control of hemorrhagic episodes in patients with hemophilia B (congenital factor IX deficiency, or Christmas disease).1 4 6 156 Designated an orphan drug by FDA for such use.3

Maintenance of hemostasis in patients with hemophilia B undergoing surgery (i.e., perioperative management of bleeding).1 4 6

Routine prophylaxis (i.e., administration at regular intervals on an ongoing basis) to reduce frequency of hemorrhagic events.1 4 Such prophylactic therapy with factor IX concentrates considered the current standard of care for patients with hemophilia B.17 171 176 Decreases frequency of spontaneous musculoskeletal hemorrhage, preserves joint function, and improves quality of life.171 185 186

Half-life of factor IX (recombinant), Fc fusion protein longer than that of conventional preparations of recombinant factor IX; may allow for less frequent dosing and possibly improve patient compliance with prophylactic regimens.4 5 7 8 9 11 12 16 17

Several factor IX concentrates are currently available in the US, including a variety of recombinant and plasma-derived preparations;1 15 156 the Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation recommends preferential use of recombinant factor IX preparations because of their potentially superior safety profile with respect to pathogen transmission.155 156 176 Other experts (e.g., World Federation of Hemophilia) state that choice of preparation should be determined by local criteria.171 When selecting an appropriate factor IX preparation, consider characteristics of each clotting factor concentrate, individual patient variables, patient/provider preference, and emerging data.155 156 171 187

Not indicated for induction of immune tolerance in patients with hemophilia B.1

Alprolix Dosage and Administration

General

  • Initiate therapy under supervision of a clinician experienced in the treatment of hemophilia B.1

  • Monitor factor IX activity (with one-stage clotting assay) to individualize dosage and assess response to therapy.1 Ensure that adequate levels are attained and maintained.1 (See Laboratory Monitoring under Cautions.)

Administration

IV Administration

Administer by slow IV injection.1 (See Rate of Administration under Dosage and Administration.)

Safety and efficacy of continuous IV infusions of the drug not established.1 Thromboembolic complications reported with use of other factor IX preparations administered as a continuous IV infusion.1 15 (See Thromboembolic Complications under Cautions.)

Reconstitution

Reconstitute with manufacturer-supplied prefilled diluent syringe.1 2 May require reconstitution of more than one vial depending on dose.1

Allow drug vial and diluent syringe to warm to room temperature prior to reconstitution.1 After addition of diluent, gently swirl vial until powder is completely dissolved; do not shake.1 Resultant solution should be clear to slightly opalescent and colorless; do not use if cloudy, discolored, or particulate matter observed.1

Administer immediately or within 3 hours after reconstitution; do not refrigerate reconstituted solution.1

Do not administer in the same tubing or container with other drugs.1

Consult manufacturer's labeling for specific instructions on reconstitution and administration of factor IX (recombinant), Fc fusion protein.1 2

Rate of Administration

Inject over a period of several minutes; determine administration rate by patient's comfort level (not to exceed 10 mL/minute).1

Dosage

Dose (potency) expressed in terms of international units (IU, units) of factor IX activity.1 Potency determined by an aPTT-based one-stage clotting assay calibrated against a WHO standard.1 14 Administration of 1 unit/kg of factor IX (recombinant), Fc fusion protein increases factor IX levels by approximately 1%.1 5

Individualize dosage and duration of therapy based on severity of factor IX deficiency, location and extent of bleeding, and patient's clinical and pharmacokinetic (e.g., in-vivo recovery, half-life) response.1 171

Estimate dose required to achieve a particular percentage increase in plasma factor IX level using the following formula:

Dose (units) = body weight (in kg) × desired factor IX increase (in units/dL or % of normal) x reciprocal of recovery (in units/kg per units/dL)1

Determine desired factor IX level by the clinical situation and severity of hemorrhage.1 For recommendations on target factor IX levels for a given clinical situation, see the specific dosage sections below. These calculations and suggested dosage regimens are only approximations and should not preclude appropriate clinical monitoring and individualization of dosage based on the hemostatic requirements of patients.1 Measure factor IX activity after a dose is given to verify calculated dose.1 171

If calculated dose is ineffective in achieving appropriate factor IX levels, consider possibility of inhibitor development.1 171 (See Development of Inhibitors to Factor IX under Cautions.)

Pediatric Patients

Hemophilia B

Higher doses or more frequent dosing may be required in patients <12 years of age because of increased clearance, shorter half-life, and lower recovery of factor IX.1

On-Demand Treatment and Control of Bleeding IV

Minor or moderate hemorrhage (e.g., uncomplicated hemarthroses, superficial muscle [except iliopsoas] without neurovascular compromise, superficial soft tissue, mucous membranes): Administer appropriate dose to achieve factor IX levels of 30–60% of normal; repeat dose every 48 hours until bleeding resolves.1

Major hemorrhage (e.g., iliopsoas and deep muscle with neurovascular injury or substantial blood loss, pharyngeal, retropharyngeal, retroperitoneal, CNS): Administer appropriate dose to achieve factor IX levels of 80–100% of normal; consider repeat dose after 6–10 hours, and then every 24 hours for the first 3 days.1 After third day, may reduce dose and extend dosing frequency to every 48 hours or longer until bleeding resolves and healing is achieved.1

Perioperative Hemostasis IV

Minor surgery (e.g., uncomplicated dental extraction): Administer appropriate dose to achieve a factor IX level of 50–80% of normal.1 Repeat every 24–48 hours as needed until bleeding resolves or healing is achieved; a single injection usually is sufficient.1

Major surgery: Administer appropriate dose to achieve an initial factor IX level of 60–100% of normal.1 Consider repeat dose after 6–10 hours, and then every 24 hours for the first 3 days.1 After third day, may reduce dose and extend dosing frequency to every 48 hours or longer until bleeding resolves and healing is achieved.1

Routine Prophylaxis IV

Initially, 50 units/kg once a week or 100 units/kg once every 10 days.1 Adjust dosage based on patient response.1 5 9 12 17 171

MASAC states that prophylactic therapy should be instituted at an early age (e.g., 1–2 years), prior to the onset of frequent bleeding; however, optimum duration of prophylaxis not known.176

Individualize prophylactic dosage regimens; evaluate patients periodically to determine continued need for prophylaxis.1 171 176

Adults

Hemophilia B On-Demand Treatment and Control of Bleeding IV

Minor or moderate hemorrhage (e.g., uncomplicated hemarthroses, superficial muscle [except iliopsoas] without neurovascular compromise, superficial soft tissue, mucous membranes): Administer appropriate dose to achieve factor IX levels of 30–60% of normal; repeat every 48 hours until bleeding resolves.1

Major hemorrhage (e.g., iliopsoas and deep muscle with neurovascular injury or substantial blood loss, pharyngeal, retropharyngeal, retroperitoneal, CNS): Administer appropriate dose to achieve factor IX levels of 80–100% of normal; consider repeat dose after 6–10 hours, and then every 24 hours for the first 3 days.1 After third day, may reduce dose and extend dosing frequency to every 48 hours or longer until bleeding resolves and healing is achieved.1

Perioperative Hemostasis IV

Minor surgery (e.g., uncomplicated dental extraction): Administer appropriate dose to achieve a factor IX level of 50–80% of normal.1 Repeat every 24–48 hours as needed until bleeding resolves or healing is achieved; a single injection usually is sufficient.1

Major surgery: Administer appropriate dose to achieve an initial factor IX level of 60–100% of normal.1 Consider repeat dose after 6–10 hours, and then every 24 hours for the first 3 days.1 After third day, may reduce dose and extend dosing frequency to every 48 hours or longer until bleeding resolves and healing is achieved.1

Routine Prophylaxis IV

Initially, 50 units/kg once a week or 100 units/kg once every 10 days.1 Adjust dosage based on patient response.1 5 9

Individualize prophylactic dosage regimens; evaluate patients periodically to determine continued need for prophylaxis.1 171 176

Actions

  • Biosynthetic (recombinant DNA-origin) preparation of blood coagulation factor IX covalently linked to the Fc domain of IgG1.1 7 10 13 16 Fc portion prolongs half-life of factor IX through interaction with the Fc neonatal receptor.1 5 7 8 9 13 Factor IX portion is similar in structure and function to endogenous factor IX.1

  • Patients with hemophilia B have decreased levels of endogenous factor IX, resulting in a hemorrhagic tendency and clinical manifestations such as bleeding into soft tissues, muscles, joints, and internal organs.1 8 171 Clinical severity and frequency of bleeding generally correlate with degree of deficiency of factor IX activity.171 Patients with mild hemophilia B generally have >5% of normal activity, those with moderate disease generally have 1–5% of normal activity, and those with severe disease have <1% of normal activity.171

  • Administration of factor IX (recombinant), Fc fusion protein to patients with hemophilia B increases plasma levels of factor IX and temporarily corrects coagulation defect.1 Also may shorten aPTT, which is typically prolonged in patients with hemophilia B.1

  • Produced by recombinant DNA technology in a human embryonic kidney (HEK) cell line; undergoes several purification processes (e.g., nanofiltration, column chromatography) and is manufactured without human and animal proteins.1 8 13 155 156

What do I need to tell my doctor BEFORE I take Alprolix?

  • If you have an allergy to Alprolix (factor IX (recombinant [fc fusion protein])) or any part of this medicine.
  • 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 Alprolix with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • A burning, numbness, or tingling feeling that is not normal.
  • Upset stomach or throwing up.
  • Shortness of breath.
  • Dizziness or passing out.
  • Restlessness.
  • Call your doctor right away if you have signs of a blood clot like chest pain or pressure; coughing up blood; shortness of breath; swelling, warmth, numbness, change of color, or pain in a leg or arm; or trouble speaking or swallowing.

How do I store and/or throw out Alprolix?

  • Store in a refrigerator. Do not freeze.
  • Store in original container.
  • If needed, you may store at room temperature.
  • If stored at room temperature, make a note of the date it was placed at room temperature.
  • If stored at room temperature, throw away any unused vials after 6 months or after the expiration date, whichever comes first.
  • Do not put this medicine back in the refrigerator after it has been stored at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Usual Adult Dose for Hemophilia B

Dosage and duration of treatment for all factor IX products depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition, age and recovery of factor IX.

In general, one IU of coagulation factor IX per kilogram of body weight increased the circulating activity of factor IX as follows: 0.8 + or - 0.2 IU/dL [range 0.4 to 1.2 IU/dL].

One international unit of Rixubis per kg of body weight increased the circulating activity of factor IX by 0.9 international units/dL.

The following formula may be used as a guide in determining the dose for treatment of bleeding episodes:
Initial dose (number of factor IX IU required) = body weight (kg) x desired factor IX increase (% or IU/dL) x reciprocal of observed recovery (IU/dL per IU/kg)

Control and Prevention of Bleeding Episodes and Perioperative Management:
Minor
Uncomplicated hemarthroses, superficial muscle, or soft tissue:
Circulating Factor IX Activity Required: 20-30 [% or (IU/dL)]
Dosing Interval: 12 to 24 hours
Duration of Therapy: 1 to 2 days

Moderate
Intramuscular or soft tissue with dissection, mucous membranes, dental extractions, or hematuria:
Circulating Factor IX Activity Required: 25 to 50 [% or (IU/dL)]
Dosing Interval: 12 to 24 hours
Duration of Therapy: Treat until bleeding stops and healing begins, about 2 to 7 days

Major
Pharynx, retropharynx, retroperitoneum, CNS, surgery:
Circulating Factor IX Activity Required: 50 to 100 [% or (IU/dL)]
Dosing Interval: 12 to 24 hours
Duration of Therapy: 7 to 10 days

Rixubis dosing for Perioperative Management:
Minor
Tooth extraction:
Circulating Factor IX Activity Required: 30 to 60 [% or (IU/dL)]
Dosing Interval: 24 hours
Duration of Therapy: At least 1 day, until healing is achieved

Major
Intracranial, intraabdominal, intrathoracic, joint replacement:
Circulating Factor IX Activity Required: 80 to 100 [% or (IU/dL)]
Dosing Interval: 8 to 24 hours
Duration of Therapy: 7 to 10 days

Rixubis Routine Prophylaxis dose: 40 to 60 international units per kg IV twice weekly

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