Coagulation Factor IX (recombinant), Glycopegylated (Monograph)

Brand name: Rebinyn
Drug class: Hemostatics

Introduction

Coagulation factor IX (recombinant), glycopegylated is a recombinant DNA-derived preparation of human Factor IX conjugated with polyethylene glycol (PEG).

Uses for Coagulation Factor IX (recombinant), Glycopegylated

Coagulation factor IX (recombinant), glycopegylated has the following uses:

Coagulation factor IX (recombinant), glycopegylated is used in adults and children with hemophilia B (congenital Factor IX deficiency) for on-demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes.

Coagulation factor IX (recombinant), glycopegylated is not indicated for immune tolerance induction in patients with hemophilia B.

Coagulation Factor IX (recombinant), Glycopegylated Dosage and Administration

General

Coagulation factor IX (recombinant), glycopegylated is available in the following dosage form(s) and strength(s):

Single-dose vials containing lyophilized powder (500, 1000, 2000, and 3000 IU) for reconstitution prior to IV administration.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Pediatric Patients

Dosage and Administration

• Each carton and vial label for coagulation factor IX (recombinant), glycopegylated states the actual Factor IX potency in international units (IU).

• For IV infusion after reconstitution only.

• Dose and duration of treatment depend on the location and extent of bleeding, and the patient’s clinical condition.

• Recommended dose for on-demand treatment and control of bleeding episodes: 40 IU/kg body weight for minor and moderate bleeds, and 80 IU/kg body weight for major bleeds. Additional doses of 40 IU/kg can be given.

• Recommended dose for perioperative management: A single pre-operative dose of 40 IU/kg body weight for minor surgery, and 80 IU/kg body weight for major surgery. As clinically needed for the perioperative management of bleeding, repeated doses of 40 IU/kg (in 1-3 day intervals) within the first week after major surgery may be administered. Frequency of dosing in the post-surgical setting may be extended to once weekly after the first week until bleeding stops and healing is achieved.

• Recommended dosage for routine prophylaxis: 40 IU/kg body weight once weekly. Adjust dosing regimen based on individual patient’s bleeding pattern and physical activity.

Adults

Dosage and Administration

• Each carton and vial label for coagulation factor IX (recombinant), glycopegylated states the actual Factor IX potency in international units (IU).

• For IV infusion after reconstitution only.

• Dose and duration of treatment depend on the location and extent of bleeding, and the patient’s clinical condition.

• Recommended dose for on-demand treatment and control of bleeding episodes: 40 IU/kg body weight for minor and moderate bleeds, and 80 IU/kg body weight for major bleeds. Additional doses of 40 IU/kg can be given.

• Recommended dose for perioperative management: A single pre-operative dose of 40 IU/kg body weight for minor surgery, and 80 IU/kg body weight for major surgery. As clinically needed for the perioperative management of bleeding, repeated doses of 40 IU/kg (in 1-3 day intervals) within the first week after major surgery may be administered. Frequency of dosing in the post-surgical setting may be extended to once weekly after the first week until bleeding stops and healing is achieved.

• Recommended dosage for routine prophylaxis: 40 IU/kg body weight once weekly. Adjust dosing regimen based on individual patient’s bleeding pattern and physical activity.

Related/similar drugs

tranexamic acid, Hemgenix, Cyklokapron, BeneFix, Idelvion, coagulation factor ix, Alprolix

Cautions for Coagulation Factor IX (recombinant), Glycopegylated

Contraindications

• Patients who have known hypersensitivity to coagulation factor IX (recombinant), glycopegylated or its components, including hamster proteins.

Warnings/Precautions

Hypersensitivity Reactions

Allergic-type hypersensitivity reactions, including anaphylaxis, have occurred with coagulation factor IX (recombinant), glycopegylated. The product may contain traces of hamster proteins which in some patients may cause allergic reactions. Signs of allergic reactions, which can progress to anaphylaxis, may include angioedema, chest tightness, difficulty breathing, wheezing, urticaria, and itching. Observe patients for signs and symptoms of acute hypersensitivity reactions, particularly during the early phases of exposure to the product. Discontinue use of the drug if allergic- or anaphylactic-type reactions occur, and initiate appropriate treatment.

Inhibitors

The formation of inhibitors (neutralizing antibodies) to Factor IX has occurred following treatment with coagulation factor IX (recombinant), glycopegylated. If expected plasma factor IX activity levels are not attained, or if bleeding is not controlled as expected with the administered dose, perform an assay that measures Factor IX inhibitor concentration. Monitor all patients using clinical observations and laboratory tests for the development of inhibitors.

An association between the development of Factor IX inhibitors and allergic reactions has been reported. Evaluate patients experiencing allergic reactions for the presence of an inhibitor. Patients with Factor IX inhibitors may be at an increased risk of severe allergic reactions with subsequent exposure to Factor IX.

Thrombotic Events

The use of Factor IX-containing products has been associated with thromboembolic complications. Due to the potential risk of thromboembolic complications, monitor patients for early signs of thrombotic and consumptive coagulopathy when administering this product to patients with liver disease, post-operatively, to newborn infants, or to patients at risk of thrombosis or disseminated intravascular coagulation (DIC). In each of these situations, the benefit of treatment with coagulation factor IX (recombinant), glycopegylated should be weighed against the risk of these complications.

Nephrotic Syndrome

Nephrotic syndrome has been reported following immune tolerance induction therapy with Factor IX products in hemophilia B patients with Factor IX inhibitors, often with a history of allergic reactions to Factor IX. The safety and efficacy of using coagulation factor IX (recombinant), glycopegylated for immune tolerance induction have not been established.

Monitoring Laboratory Tests

If monitoring of Factor IX activity is performed, use a chromogenic assay or selected one-stage clotting assay validated for use with coagulation factor IX (recombinant), glycopegylated.

The one-stage clotting assay results can be significantly affected by the type of activated partial thromboplastin time (aPTT) reagent used, which can result in over- or under-estimation of Factor IX activity. Avoid the use of silica-based reagents, as some may overestimate the activity of coagulation factor IX (recombinant), glycopegylated. If a validated one-stage clotting or chromogenic assay is not available locally, then use of a reference laboratory is recommended.

If bleeding is not controlled with the recommended dose of coagulation factor IX (recombinant), glycopegylated, or if the expected Factor IX activity levels in plasma are not attained, then perform a Bethesda assay to determine if Factor IX inhibitors are present.

Specific Populations

Pregnancy

There are no data with coagulation factor IX (recombinant), glycopegylated use in pregnant women to determine whether there is a drug-associated risk. Animal reproduction studies have not been conducted with the drug. It is unknown whether coagulation factor IX (recombinant), glycopegylated can cause fetal harm when administered to a pregnant woman or can affect fertility. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Lactation

There is no information regarding the presence of coagulation factor IX (recombinant), glycopegylated in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for coagulation factor IX (recombinant), glycopegylated and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

Pediatric Use

Safety and efficacy of coagulation factor IX (recombinant), glycopegylated were evaluated in four clinical trials that included 43 pediatric previously treated patients (PTPs) and in one clinical trial that included 50 pediatric previously untreated patients (PUPs). Twelve of these subjects were ≤ 6 years of age; 13 subjects were 7 to 12 years of age; and 18 subjects were 13 to 17 years of age. Pharmacokinetic parameters were evaluated for 28 of the pediatric PTPs who were treated with coagulation factor IX (recombinant), glycopegylated 40 IU/kg.

Body weight-adjusted clearance was observed to be higher for pediatric subjects than for adult subjects. However, in clinical trials, no dose adjustment was needed in pediatric subjects who received a fixed dose of 40 IU/kg every week for routine prophylaxis.

Geriatric Use

Clinical studies of coagulation factor IX (recombinant), glycopegylated did not include sufficient numbers of subjects 65 years of age and older to determine whether or not they respond differently than younger subjects.

Animals administered repeat doses of coagulation factor IX (recombinant), glycopegylated showed accumulation of PEG in the choroid plexus, pituitary, circumventricular organs, and cranial motor neurons. The potential clinical implications of these animal findings are unknown. No adverse neurologic effects of PEG have been reported in adults exposed to coagulation factor IX (recombinant), glycopegylated during clinical trials, however, use in older adults with baseline cognitive dysfunction has not been fully evaluated.

Common Adverse Effects

The most frequently reported adverse reactions (≥ 1%) in previously treated patients (PTPs) and previously untreated patients (PUPs) were itching and injection site reactions.

Additional frequently reported adverse reactions (≥ 1%) in PUPs included rash, Factor IX inhibition, hypersensitivity, and anaphylactic reaction.

In animals administered repeat doses of coagulation factor IX (recombinant), glycopegylated, accumulation of polyethylene-glycol (PEG) was observed in the choroid plexus, pituitary, circumventricular organs, and cranial motor neurons. The potential clinical implications of these animal findings are unknown.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Patients with hemophilia B are deficient in coagulation Factor IX, which is required for effective hemostasis. Treatment with coagulation factor IX (recombinant), glycopegylated temporarily replaces the missing coagulation Factor IX.

The Factor IX in coagulation factor IX (recombinant), glycopegylated is conjugated to a 40-kDa polyethylene glycol molecule, which slows down its removal from the blood circulation.

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

• Inform patients of the early signs of hypersensitivity reactions including rash, hives, itching, facial swelling, tightness of the chest, and wheezing. Advise patients to discontinue use of the product and contact their healthcare provider if these symptoms occur.

• Advise patients to contact their healthcare provider for further treatment and/or assessment if they experience a lack of a clinical response to Factor IX therapy, as in some cases this may be a manifestation of an inhibitor.

• Advise patients to contact their healthcare provider if they experience any thrombotic complications.

• Advise patients to follow the recommendations regarding proper sharps disposal provided in the FDA-approved Instructions for Use.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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