Alprolix

Drug overview for ALPROLIX (factor ix recombinant, fc fusion protein):

Generic name: factor IX recombinant, Fc fusion protein (FACK-ter nine)
Drug class: Factor IX
Therapeutic class: Hematological Agents

Factor IX (recombinant), Fc fusion protein is a biosynthetic (recombinant DNA origin) preparation of blood coagulation factor IX covalently linked to the Fc domain of human immunoglobulin G1 (IgG1).

No enhanced Uses information available for this drug.

DRUG IMAGES

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The following indications for ALPROLIX (factor ix recombinant, fc fusion protein) have been approved by the FDA:

Indications:
Hemophilia B

Professional Synonyms:
Christmas disease
Factor IX deficiency
Factor IX dysfunction
Plasma thromboplastin component deficiency
PTC deficiency

The following drug interaction information is available for ALPROLIX (factor ix recombinant, fc fusion protein):

Contraindicated
Severe
Moderate

There are 1 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Antifibrinolytics/Factor IX; Anti-Inhibitor Coagulant Conc SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Concurrent use may result in additive or synergistic effects on the coagulation pathways.(1-3) CLINICAL EFFECTS: Concurrent use may result in thrombosis.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of aminocaproic acid states that aminocaproic acid should not be administered concomitantly with Factor IX Complex concentrates or with Anti-inhibitor Coagulant concentrates.(1) The manufacturer of tranexamic acid states that tranexamic acid should not be administered concomitantly with Factor IX Complex concentrates or with Anti-inhibitor Coagulant concentrates.(2,3) Concurrent use may be warranted in select patients with hemophilia A or hemophilia B. Monitor patients closely for signs of thrombosis, disseminated intravascular coagulation, and hypercoagulability if concurrent use is deemed necessary.(4-6) DISCUSSION: Because of the increased risk of thrombosis, the manufacturer of aminocaproic acid states that aminocaproic acid should not be administered concomitantly with Factor IX Complex concentrates or with Anti-inhibitor Coagulant concentrates.(1) Because of the increased risk of thrombosis, the manufacturer of tranexamic acid states that tranexamic acid should not be administered concomitantly with Factor IX Complex concentrates or with Anti-inhibitor Coagulant concentrates.(2,3) In a study, eight hemophilia B patients undergoing dental extraction procedures received combination therapy with aminocaproic acid or tranexamic acid and monoclonal antibody purified factor IX for bleeding prophylaxis. All patients achieved hemostasis without clinical evidence of thrombosis as well as no changes were seen in hemoglobin, hematocrit, or in markers of hemostatic system activation.(4) In a study, seven hemophilia A patients with inhibitors and one with acquired hemophilia patient received activated prothrombin complex concentrate (APCC) and tranexamic acid for management of bleeding episodes and prevention of hemorrhage during surgery. Hemostatic outcomes were rated excellent or good in 10 out of 11 (91%) treatment episodes. No episodes of thrombosis or disseminated intravascular coagulation occurred during treatment.(5) A study in six hemophilia A patients and five healthy volunteers evaluated the use of tranexamic acid as an adjunct to APCC to control bleeding. Patients who received tranexamic acid had a significant increase in maximum clot firmness compared to healthy controls. No clinical or laboratory signs of thromboembolic events, disseminated intravascular coagulation, or hypercoagulability were observed.(6)	AMICAR, AMINOCAPROIC ACID, CYKLOKAPRON, TRANEXAMIC ACID, TRANEXAMIC ACID-NACL

Drug Interaction

Drug Names

Antifibrinolytics/Factor IX; Anti-Inhibitor Coagulant Conc

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Concurrent use may result in additive or synergistic effects on the coagulation pathways.(1-3)

CLINICAL EFFECTS: Concurrent use may result in thrombosis.(1-3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of aminocaproic acid states that aminocaproic acid should not be administered concomitantly with Factor IX Complex concentrates or with Anti-inhibitor Coagulant concentrates.(1) The manufacturer of tranexamic acid states that tranexamic acid should not be administered concomitantly with Factor IX Complex concentrates or with Anti-inhibitor Coagulant concentrates.(2,3) Concurrent use may be warranted in select patients with hemophilia A or hemophilia B. Monitor patients closely for signs of thrombosis, disseminated intravascular coagulation, and hypercoagulability if concurrent use is deemed necessary.(4-6)

DISCUSSION: Because of the increased risk of thrombosis, the manufacturer of aminocaproic acid states that aminocaproic acid should not be administered concomitantly with Factor IX Complex concentrates or with Anti-inhibitor Coagulant concentrates.(1) Because of the increased risk of thrombosis, the manufacturer of tranexamic acid states that tranexamic acid should not be administered concomitantly with Factor IX Complex concentrates or with Anti-inhibitor Coagulant concentrates.(2,3) In a study, eight hemophilia B patients undergoing dental extraction procedures received combination therapy with aminocaproic acid or tranexamic acid and monoclonal antibody purified factor IX for bleeding prophylaxis.

All patients achieved hemostasis without clinical evidence of thrombosis as well as no changes were seen in hemoglobin, hematocrit, or in markers of hemostatic system activation.(4) In a study, seven hemophilia A patients with inhibitors and one with acquired hemophilia patient received activated prothrombin complex concentrate (APCC) and tranexamic acid for management of bleeding episodes and prevention of hemorrhage during surgery. Hemostatic outcomes were rated excellent or good in 10 out of 11 (91%) treatment episodes.

No episodes of thrombosis or disseminated intravascular coagulation occurred during treatment.(5) A study in six hemophilia A patients and five healthy volunteers evaluated the use of tranexamic acid as an adjunct to APCC to control bleeding. Patients who received tranexamic acid had a significant increase in maximum clot firmness compared to healthy controls. No clinical or laboratory signs of thromboembolic events, disseminated intravascular coagulation, or hypercoagulability were observed.(6)

AMICAR, AMINOCAPROIC ACID, CYKLOKAPRON, TRANEXAMIC ACID, TRANEXAMIC ACID-NACL

There are 2 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
IgG Antibodies and Derivatives/Efgartigimod-alfa SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3) DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3)	VYVGART, VYVGART HYTRULO
IgG Antibodies and Derivatives/Nipocalimab-aahu SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3) DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3)	IMAAVY

Drug Interaction

Drug Names

IgG Antibodies and Derivatives/Efgartigimod-alfa

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3)

VYVGART, VYVGART HYTRULO

IgG Antibodies and Derivatives/Nipocalimab-aahu

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3)

IMAAVY

There are 1 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
IgG Antibodies and Derivatives/Rozanolixizumab-noli SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3) DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)	RYSTIGGO

Drug Interaction

Drug Names

IgG Antibodies and Derivatives/Rozanolixizumab-noli

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3)

DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)

RYSTIGGO

Severe List
Disseminated intravascular coagulation
Thromboembolic disorder

The following adverse reaction information is available for ALPROLIX (factor ix recombinant, fc fusion protein):

Overview
Severe
Less Severe

Adverse reaction overview.

The most common adverse effects observed in at least 1% of previously treated patients receiving factor IX (recombinant), Fc fusion protein in clinical trials were headache and oral paresthesia.

There are 10 severe adverse reactions.

More Frequent	Less Frequent
Acute myocardial infarction Disseminated intravascular coagulation Pulmonary thromboembolism Thromboembolic disorder Thrombotic disorder	Anaphylaxis Urinary tract obstructive uropathy

Rare/Very Rare
Hypersensitivity drug reaction Hypotension Renal colic

There are 16 less severe adverse reactions.

More Frequent	Less Frequent
None.	Chills Injection site sequelae Nausea Oral paresthesia

Rare/Very Rare
Anorexia Dizziness Dysgeusia Fatigue Fever Halitosis Headache disorder Hematuria Lethargy Palpitations Paresthesia Urticaria

The following precautions are available for ALPROLIX (factor ix recombinant, fc fusion protein):

Pediatric
Pregnant
Lactation
Geriatric

The safety, efficacy, and pharmacokinetics of factor IX (recombinant), Fc fusion protein have been evaluated in previously treated patients 12-18 years of age in the principal efficacy study. The manufacturer states that findings from this study may be extrapolated and applied to patients younger than 12 years of age. In addition, the pharmacokinetics and safety of factor IX (recombinant), Fc fusion protein have been evaluated in a limited number of patients 2-11 years of age.

Efficacy of the drug in patients younger than 2 years of age can be extrapolated from pharmacokinetic data. No specific safety issues have been identified in patients younger than 12 years of age. Compared with adults and adolescents, patients younger than 12 years of age may have higher body weight-adjusted clearance, shorter half-life, and lower factor IX recovery; higher doses or more frequent dosing may be required. (See Dosage and Administration: Dosage.)

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Category C. (See Users Guide.)

It is not known whether factor IX (recombinant), Fc fusion protein is distributed into human milk. Because many drugs are distributed into milk, the drug should be used with caution in nursing women.

Clinical studies of factor IX (recombinant), Fc fusion protein did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients.