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Antihemophilic Factor (Recombinant)

Medically reviewed by Drugs.com. Last updated on Sep 28, 2020.

Pronunciation

(an tee hee moe FIL ik FAK tor ree KOM be nant)

Index Terms

  • AHF (Recombinant)
  • Antihemophilic Factor (Recombinant), Single Chain
  • Factor VIII (Recombinant)
  • Lonoctocog Alfa
  • Moroctocog Alfa
  • Octocog Alfa
  • rAHF
  • Simoctocog Alfa
  • Turoctocog Alfa

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Kit, Intravenous:

Kogenate FS: 250 units, 500 units, 1000 units

Kit, Intravenous [preservative free]:

Afstyla: 250 units, 500 units, 1000 units, 1500 units, 2000 units, 2500 units, 3000 units [contains polysorbate 80]

Helixate FS: 250 units [DSC], 500 units [DSC], 1000 units [DSC], 2000 units [DSC], 3000 units [DSC] [contains polysorbate 80]

Kogenate FS: 2000 units, 3000 units

Kogenate FS Bio-Set: 250 units [DSC], 500 units [DSC], 1000 units [DSC], 2000 units [DSC], 3000 units [DSC]

Nuwiq: 250 units, 500 units, 1000 units, 2000 units, 2500 units, 3000 units, 4000 units

Xyntha: 250 units, 500 units, 1000 units, 2000 units [albumin free; contains polysorbate 80]

Xyntha Solofuse: 250 units, 500 units, 1000 units, 2000 units, 3000 units [albumin free; contains polysorbate 80]

Solution Reconstituted, Intravenous:

Kovaltry: 250 units (1 ea); 500 units (1 ea); 1000 units (1 ea); 2000 units (1 ea); 3000 units (1 ea) [contains polysorbate 80]

Solution Reconstituted, Intravenous [preservative free]:

Advate: 250 units (1 ea); 500 units (1 ea); 1000 units (1 ea); 1500 units (1 ea); 2000 units (1 ea); 3000 units (1 ea); 4000 units (1 ea) [albumin free; contains polysorbate 80]

Novoeight: 250 units (1 ea); 500 units (1 ea); 1000 units (1 ea); 1500 units (1 ea); 2000 units (1 ea); 3000 units (1 ea) [contains polysorbate 80]

Nuwiq: 250 units (1 ea); 500 units (1 ea); 1000 units (1 ea); 2000 units (1 ea); 2500 units (1 ea); 3000 units (1 ea); 4000 units (1 ea)

Recombinate: 220-400 units (1 ea); 401-800 units (1 ea); 801-1240 units (1 ea); 1241-1800 units (1 ea); 1801-2400 units (1 ea) [contains albumin human, polyethylene glycol, polysorbate 80]

Brand Names: U.S.

  • Advate
  • Afstyla
  • Helixate FS [DSC]
  • Kogenate FS
  • Kogenate FS Bio-Set [DSC]
  • Kovaltry
  • Novoeight
  • Nuwiq
  • Recombinate
  • Xyntha
  • Xyntha Solofuse

Pharmacologic Category

  • Antihemophilic Agent

Pharmacology

Factor VIII replacement, necessary for clot formation and maintenance of hemostasis. It activates factor X in conjunction with activated factor IX; activated factor X converts prothrombin to thrombin, which converts fibrinogen to fibrin, and with factor XIII forms a stable clot.

Distribution

Vss: ~0.4 to 0.85 dL/kg

Half-Life Elimination

Advate: Children <12 years: 8.7 to 11.2 hours; Adolescents and Adults: 12 hours.

Afstyla: Children <12 years: 10.2 to 10.4 hours; Children ≥12 years and Adolescents: 14.3 hours; Adults: 14.2 hours.

Helixate FS, Kogenate FS: Children: 10.7 hours; Adults: 13.7 to 14.6 hours.

Kovaltry: Children <12 years: ~12 hours; Children ≥12 years, Adolescents, and Adults: ~14 hours.

Novoeight: Children <12 years: 7.7 to 10 hours; Adolescents and Adults: 11 to 12 hours.

Nuwiq: Children ≤12 years: 11.9 to 13.1 hours; Adolescents and Adults: 17.1 hours.

Recombinate: Adults: 14.6 ± 4.9 hours.

Xyntha, Xyntha Solofuse: Children 3.7 to 5.8 years: 8.3 ± 2.7 hours; Adolescents 14 to 15 years: 6.9 ± 2.4 hours; Adults: 11 to 17 hours.

Use: Labeled Indications

Hemophilia A:

Control and prevention of bleeding episodes: Prevention and control of bleeding episodes in adults and children with hemophilia A.

Perioperative management: Surgical prophylaxis in adults and children with hemophilia A.

Routine prophylaxis to prevent or reduce the frequency of bleeding: Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia A.

Routine prophylaxis to prevent bleeding episodes and joint damage (Helixate FS, Kogenate FS): Routine prophylactic treatment to reduce the frequency of bleeding episodes and the risk of joint damage in children without preexisting joint damage.

Limitations of use: Not indicated for the treatment of von Willebrand disease.

Contraindications

Hypersensitivity (eg, anaphylaxis) to antihemophilic factor, mouse or hamster protein (Advate, Afstyla, Helixate FS, Kogenate FS, Kovaltry, Novoeight, Recombinate, Xyntha, Zonovate [Canadian product]), bovine protein (Recombinate only), or any component of the formulation.

Dosing: Adult

Hemophilia A: IV: Individualize dosage based on clinical response and factor VIII activity evaluated at baseline and at regular intervals during treatment. In general, administration of factor VIII 1 unit/kg will increase circulating factor VIII levels by ~2% of normal. Patients with inhibitory antibodies to factor VIII may require higher doses, more frequent administration, and/or selection of alternative therapy.

Control and prevention of bleeding episodes or perioperative management:

Dosage based on desired factor VIII increase (%) (WFH [Srivastava 2013]):

To calculate dosage needed based on desired factor VIII increase (%):

[Body weight (kg) x desired factor VIII increase (%)] divided by 2 (%/units/kg) = units factor VIII required

For example:

50 kg x 30 (% increase) divided by 2 = 750 units factor VIII

Administration frequency should be determined based on product half-life, factor VIII activity, and clinical response.

World Federation of Hemophilia (WFH) treatment recommendations when no significant resource constraint exists (WFH [Srivastava 2013]):

2013 World Federation of Hemophilia Treatment Recommendations (When No Significant Resource Constraint Exists)

Site of Hemorrhage/Clinical Situation

Desired Factor VIII Peak Level

Duration

Note: Factor VIII level may either be expressed as % or as units/dL. Dosing frequency most commonly corresponds to the half-life of factor VIII but should be determined based on an assessment of factor VIII levels before the next dose.

Joint

40% to 60%

1 to 2 days, may be longer if response is inadequate

Superficial muscle/no neurovascular compromise

40% to 60%

2 to 3 days, sometimes longer if response is inadequate

Iliopsoas and deep muscle with neurovascular injury, or substantial blood loss

Initial: 80% to 100%

Initial: 1 to 2 days

Maintenance: 30% to 60%

Maintenance: 3 to 5 days, sometimes longer as secondary prophylaxis during physiotherapy

CNS/Head

Initial: 80% to 100%

Initial: 1 to 7 days

Maintenance: 50%

Maintenance: 8 to 21 days

Throat and neck

Initial: 80% to 100%

Initial: 1 to 7 days

Maintenance: 50%

Maintenance: 8 to 14 days

Gastrointestinal

Initial: 80% to 100%

Initial: 7 to 14 days

Maintenance: 50%

Maintenance: Not specified

Renal

50%

3 to 5 days

Deep laceration

50%

5 to 7 days

Surgery (major)

Preop: 80% to 100%

Postop: 60% to 80%

Postop: 1 to 3 days

Postop: 40% to 60%

Postop: 4 to 6 days

Postop: 30% to 50%

Postop: 7 to 14 days

Surgery (minor)

Preop: 50% to 80%

Postop: 30% to 80%

Postop: 1 to 5 days depending on procedure type

Continuous infusion (off-label; for patients who require prolonged periods of treatment [eg, intracranial hemorrhage or surgery] to avoid peaks and troughs associated with intermittent infusions, increase target factor VIII achievement, and reduce cost) (Batorova 2000; Batorova 2002; Batorova 2012; Martinowitz 1992; Poon 2012; Rickard 1995; WFH [Srivastava 2013]): Following initial bolus to achieve the desired factor VIII peak activity, initiate factor VIII infusion at a rate of 2 to 4 units/kg/hour. An empiric factor VIII infusion rate can be calculated using the infusion rate equation below, where factor VIII clearance is typically 3 to 4 mL/kg/hour initially (based on population pharmacokinetics). Adjust factor VIII infusion rates based on frequent evaluation of factor VIII activity, which should be used to recalculate factor VIII clearance at steady-state and the new infusion rate using the equations below. If factor VIII levels are below target, consider factor VIII bolus administration in addition to increasing the factor VIII continuous infusion rate. The decision to administer an additional bolus should be based on the severity of the bleeding event or bleeding risk of the surgery/procedure, the patient's clinical condition, and the degree below target of the factor VIII level.

Infusion rate (units/kg/hour) = (factor VIII clearance in mL/kg/hour) x (desired plasma level in units/mL)

Factor VIII clearance (mL/kg/hour) = (current infusion rate in units/kg/hour) divided by (plasma level in units/mL)

New infusion rate (units/kg/hour) = (factor VIII clearance in mL/kg/hour) x (desired plasma level in units/mL)

Manufacturer’s labeling: Refer to manufacturer's labeling for specific recommendations; varies by product.

Routine prophylaxis to prevent or reduce the frequency of bleeding episodes: Note: Maintain factor VIII trough levels between 1% and 5% as clinically indicated (Collins 2011; Rossbach 2010).

Advate: 20 to 40 units/kg every other day (3 to 4 times weekly). Alternatively, an every-third-day dosing regimen may be used to target factor VIII trough levels of ≥1%.

Afstyla: 20 to 50 units/kg 2 to 3 times weekly.

Helixate FS: 25 units/kg 3 times weekly.

Kogenate FS: 25 units/kg 3 times weekly.

Kovaltry: 20 to 40 units/kg 2 or 3 times weekly.

Novoeight: 20 to 50 units/kg 3 times weekly or 20 to 40 units/kg every other day.

Nuwiq: 30 to 40 units/kg every other day.

Xyntha, Xyntha Solofuse: 30 units/kg 3 times weekly.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hemophilia A: Individualize dosage based on clinical response and factor VIII activity evaluated at baseline and at regular intervals during treatment. In general, administration of factor VIII 1 unit/kg will increase circulating factor VIII levels by ~2% of normal. Patients with inhibitory antibodies to factor VIII may require higher doses, more frequent administration, and/or selection of alternative therapy.

General dosing for control and prevention of bleeding episodes or perioperative management: Note: Dosage is expressed in units of factor VIII activity and must be individualized based on formulation, severity of factor VIII deficiency, extent and location of bleed, individualized incremental recovery using factor VIII activity assays, and clinical situation of patient.

Infants, Children, and Adolescents: IV:

Formula for units required to raise blood level:

Number of Factor VIII Units required = body weight (in kg) x 0.5 units/kg per units/dL x desired factor VIII level increase (units/dL or %)

For example, for a desired 100% level in a 25 kg patient who has an actual level of 20%: Number of Factor VIII Units needed = 25 kg x 0.5 units/kg per units/dL x 80% = 1,000 units

Treatment recommendations (WFH [Srivastava 2020]): Note: Factor VIII level may either be expressed as % or as units/dL.

Intermittent IV: Infants, Children, and Adolescents: The following recommendations reflect WFH guidelines for higher-dose practice patterns; this dosing is typically used in areas where no significant resource constraints exist; recommendations may vary from those found within prescribing information or practitioner preference. Frequency is based on type of bleed or surgery and varies by product; see specific product labeling for details. Dosing frequency most commonly corresponds to the half-life of factor VIII but should be determined based on an assessment of factor VIII levels (if available) before the next dose.

Site of Hemorrhage/Clinical Situation

Desired Factor VIII Peak Level

FrequencyA

Duration

AFrequency is based on type of bleed or surgery and varies by product; see specific product labeling for details.

Joint

40% to 60%

Every 12 to 24 hours; some products recommend more frequent (every 8 to 24 hours) for patients <6 years

1 to 2 days, may be longer if response is inadequate

Superficial muscle/no neurovascular compromise

40% to 60%

Every 12 to 24 hours; some products recommend more frequent (every 8 to 24 hours) for patients <6 years

2 to 3 days, sometimes longer if response is inadequate

Iliopsoas and deep muscle with neurovascular injury, or substantial blood loss

Initial: 80% to 100%

Every 8 to 24 hours; some products recommend more frequent (every 6 to 12 hours) for patients <6 years

Initial: 1 to 2 days

Maintenance: 30% to 60%

Maintenance: 3 to 5 days, sometimes longer as secondary prophylaxis during physiotherapy

CNS/Head

Initial: 80% to 100%

Every 8 to 24 hours; some products recommend more frequent (every 6 to 12 hours) for patients <6 years

Initial: 1 to 7 days

Maintenance: 50%

Maintenance: 8 to 21 days

Throat and neck

Initial: 80% to 100%

Every 8 to 24 hours; some products recommend more frequent (every 6 to 12 hours) for patients <6 years

Initial: 1 to 7 days

Maintenance: 50%

Maintenance: 8 to 14 days

Gastrointestinal

Initial: 80% to 100%

Every 8 to 24 hours; some products recommend more frequent (every 6 to 12 hours) for patients <6 years

Initial: 7 to 14 days

Maintenance: 50%

Maintenance: Not specified

Renal

50%

Every 12 to 24 hours; some products recommend more frequent (every 8 to 24 hours) for patients <6 years

3 to 5 days

Deep laceration

50%

Every 12 to 24 hours; some products recommend more frequent (every 8 to 24 hours) for patients <6 years

5 to 7 days

Surgery (major)

Preop: 80% to 100%

Single dose

Postop: 60% to 80%

Every 8 to 24 hours; some products recommend more frequent (every 6 to 24 hours) dosing for patients <6 years

Postop: 1 to 3 days

Postop: 40% to 60%

Postop: 4 to 6 days

Postop: 30% to 50%

Postop: 7 to 14 days

Surgery (minor)

Preop: 50% to 80%

Single dose

Postop: 30% to 80%

Every 12 to 24 hours

Postop: 1 to 5 days depending on procedure type

Continuous IV infusion: Infants, Children, and Adolescents: Note: In general, administration of factor VIII 4 units/kg/hour will increase circulating factor VIII levels by 1 unit/mL (Prelog 2016).

Control and prevention of bleeding episodes: Limited data available: Note: For patients who require prolonged periods of treatment (eg, intracranial hemorrhage or surgery) to avoid peaks and troughs associated with intermittent infusions (Batorova 2002; Poon 2012; Prelog 2016; WFH [Srivastava 2020]):

Following initial bolus to achieve the desired factor VIII level: Initial dosing: 2 to 4 units/kg/hour; adjust dose based on frequent factor VIII assays and calculation of factor VIII clearance at steady-state using the following equations:

Factor VIII clearance (mL/kg/hour) = (current infusion rate in units/kg/hour) / (plasma Factor level in units/mL)

New infusion rate (units/kg/hour) = (factor VIII clearance in mL/kg/hour) x (desired plasma level in units/mL)

Perioperative management: Limited data available: Initial: 25 to 50 units/kg prior to surgery, followed by continuous infusion at a rate of 3 to 5 units/kg/hour; regimen based on 2 studies evaluating use in pediatric surgery patients (age range: 0.9 to 17 years); rate was adjusted and additional boluses given as needed to maintain desired factor VIII level (Batorova 2012; Dingli 2002).

Routine prophylaxis: Note: Maintain factor VIII trough levels >3% to 5% or higher as clinically indicated (WFH [Srivastava 2020]).

Product-specific dosing:

Advate: Infants, Children, and Adolescents: IV: 20 to 40 units/kg/dose every other day (3 to 4 times weekly). Alternatively, an every-third-day dosing regimen may be used to target factor VIII trough levels of ≥1%.

Afstyla:

Infants and Children <12 years: IV: 30 to 50 units/kg/dose 2 to 3 times weekly; more frequent or higher doses may be required due to higher drug clearance.

Children ≥12 years and Adolescents: IV: 20 to 50 units/kg/dose 2 to 3 times weekly.

Helixate FS, Kogenate FS:

Infants, Children, and Adolescents ≤16 years: IV: 25 units/kg/dose given every other day.

Adolescents >16 years: IV: 25 units/kg/dose 3 times a week.

Kovaltry:

Infants and Children: IV: 20 to 50 units/kg/dose every other day, twice weekly or 3 times weekly, dependent on patient response.

Adolescents: IV: 20 to 40 units/kg/dose 2 to 3 times weekly.

Novoeight:

Infants and Children <12 years: IV: 25 to 60 units/kg/dose 3 times weekly or 25 to 50 units/kg/dose every other day.

Children ≥12 years and Adolescents: IV: 20 to 50 units/kg/dose 3 times weekly or 20 to 40 units/kg/dose every other day.

Nuwiq:

Children 2 to 11 years: IV: 30 to 50 units/kg/dose every other day or 3 times weekly.

Children ≥12 years and Adolescents: IV: 30 to 40 units/kg/dose every other day.

Xyntha, Xyntha Solofuse:

Children <12 years: IV: 25 units/kg/dose every other day; more frequent or higher doses may be required due to higher drug clearance.

Children ≥12 years and Adolescents: IV: 30 units/kg/dose 3 times weekly.

Guideline dosing (WFH [Srivastava 2020]): Note: Dose should be individualized; dose intensity should take into account disease severity, patient's activity and lifestyle, and pharmacokinetic properties of product, and should be adjusted if breakthrough bleeding occurs. See guidelines for in-depth discussion of risks and benefits of each approach.

Infants, Children, and Adolescents: IV:

High dose: 25 to 40 units/kg/dose every 2 days.

Intermediate dose: 15 to 25 units/kg/dose 3 times weekly.

Low dose: 10 to 15 units/kg/dose 2 to 3 times weekly. Note: Low dose prophylaxis may be used in young patients as initial therapy to allow patients and families to gradually adjust to prophylaxis and improves adherence; close monitoring is required since patients are at a higher risk for bleeding until escalation occurs.

Dosing: Obesity

Novoeight: There are no specific dosage adjustments provided in the manufacturer's labeling. AUC is higher and clearance lower in adults with BMI ≥30 kg/m2; adjust dose as necessary in these patients.

Reconstitution

If refrigerated, the dried concentrate and diluent should be warmed to room temperature before reconstitution. Gently agitate or rotate vial after adding diluent, do not shake vigorously. Refer to product specific labeling for reconstitution instructions and for detailed information regarding compatibility with administration sets; recommendations vary by product.

Continuous infusion (off-label method of administration): Further dilution after initial reconstitution is unnecessary (Batorova 2012).

Administration

IV: Rate of administration should be determined by patient tolerability (maximum rates vary by product).

Advate: Infuse over ≤5 minutes (maximum: 10 mL/minute)

Afstyla: Infuse up to a maximum rate of 10 mL/minute

Helixate FS, Kogenate FS, Kovaltry: Infuse over 1 to 15 minutes

Novoeight: Infuse slowly over 2 to 5 minutes

Nuwiq: Infuse up to a maximum rate of 4 mL/minute

Recombinate: Infuse up to a maximum rate of 5 mL/minute

Xyntha, Xyntha Solofuse: Infuse over several minutes. Do not admix or administer in same tubing as other medications.

Continuous infusion (off-label rate): Has also been administered as a continuous infusion to avoid peaks and troughs associated with intermittent infusions in patients who require prolonged treatment periods. Refer to protocols for product selection and preparation details.

Dietary Considerations

Some products may contain sodium.

Storage

Prior to reconstitution, store refrigerated at 2°C to 8°C (36°F to 46°F); do not freeze. Do not refrigerate after reconstitution (unless otherwise noted).

Advate: May also be stored at room temperature (not to exceed 30°C [86°F]) up to 6 months; do not return to refrigerator. Use within 3 hours of reconstitution.

Afstyla: May also be stored at room temperature (not to exceed 25°C [77°F]) up to 3 months; do not return to refrigerator. Store in original package to protect from light. Use within 4 hours of reconstitution.

Helixate FS, Kogenate FS, Kovaltry: May also be stored at room temperature (not to exceed 25°C [77°F]) up to 12 months; do not return to refrigerator. Protect from extreme exposure to light during storage. Use within 3 hours of reconstitution.

Novoeight: Store in original package to protect from light. May also be stored at room temperature:

≤30°C (86°F) for up to 12 months; do not return to refrigerator; must be used within 4 hours of reconstitution if stored at this temperature

>30°C to ≤40°C (>86°F to 104°F) for up to 3 months; do not return to refrigerator; must be used within 2 hours of reconstitution if stored at this temperature

Nuwiq: May also be stored at room temperature (not to exceed 25°C [77°F]) up to 3 months; do not return to refrigerator. Store in original package to protect from light. Use within 3 hours of reconstitution.

Recombinate: May also be stored at room temperature, not to exceed 30°C (86°F). Use within 3 hours of reconstitution.

Xyntha: May also be stored at room temperature (not to exceed 25°C [77°F]) up to 3 months; after room temperature storage, product may be returned to the refrigerator until the expiration date; however, do not store at room temperature and return to refrigerator temperature more than once. Avoid prolonged exposure to light during storage. Use within 3 hours of reconstitution.

Xyntha Solofuse: May also be stored at room temperature not to exceed 25°C [77°F]) up to 3 months; do not return to refrigerator; after 3 months at room temperature, must use immediately or discard. Use within 3 hours of reconstitution.

Zonovate (Canadian product): Store in original package to protect from light. May also be stored at room temperature:

≤30°C (86°F) for up to 12 months; do not return to refrigerator; must be used within 4 hours of reconstitution if stored at this temperature.

>30°C to ≤40°C (>86°F to 104°F) for up to 3 months; do not return to refrigerator; must be used within 2 hours of reconstitution if stored at this temperature.

If intact vial stored under refrigeration, may store reconstituted vial at 2°C to 8°C (36°F to 46°F); must be used within 24 hours. Store reconstituted product in the vial, with vial adapter and syringe still attached and out of direct light; discard any unused reconstituted product.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Actual frequency may vary by product.

>10%:

Dermatologic: Pruritus (≤16%), skin rash (≤16%), urticaria (≤16%)

Hematologic & oncologic: Increased factor VIII inhibitors (≤52%)

Local: Catheter infection (18% to 19%)

Nervous system: Headache (7% to 24%)

Neuromuscular & skeletal: Arthralgia (8% to 23%)

Respiratory: Cough (12% to 13%), nasopharyngitis (12%)

Miscellaneous: Fever (≤23%)

1% to 10%:

Cardiovascular: Chest discomfort (1%), palpitations (1%), sinus tachycardia (1%)

Dermatologic: Allergic dermatitis (1%)

Gastrointestinal: Abdominal distress (2%), abdominal pain (2%), diarrhea (6% to 8%), dyspepsia (2%), vomiting (7% to 8%)

Hematologic & oncologic: Lymphadenopathy (1%)

Hypersensitivity: Hypersensitivity reaction (2%)

Local: Infusion site reaction (4% to 7%), injection site reaction (1% to 3%)

Nervous system: Chills (≤1%), dizziness (≤1%), insomnia (3%), procedural pain (5%)

Neuromuscular & skeletal: Asthenia (6%), back pain (≤3%; more common in children)

Otic:Otic infection (≤5%)

Respiratory: Nasal congestion (6%), pharyngolaryngeal pain (5%), upper respiratory tract infection (7%)

Miscellaneous: Limb injury (6%)

<1%:

Cardiovascular: Cold extremity, facial flushing, flushing, hypotension

Dermatologic: Erythema of skin, hyperhidrosis, maculopapular rash, pallor

Gastrointestinal: Dysgeusia, nausea, xerostomia

Hematologic & oncologic: Hematoma

Local: Inflammation at injection site, pain at injection site

Nervous system: Fatigue, feeling hot, vertigo

Neuromuscular & skeletal: Limb pain, paresthesia, tremor

Respiratory: Epistaxis

Frequency not defined: Endocrine & metabolic: Hot flash

Postmarketing:

Cardiovascular: Chest pain, facial edema, tachycardia

Hypersensitivity: Anaphylaxis, angioedema

Nervous system: Loss of consciousness, malaise, restlessness

Respiratory: Cyanosis, dyspnea, laryngeal edema

Warnings/Precautions

Concerns related to adverse effects:

• Antibody formation: The development of factor VIII antibodies has been reported with antihemophilic factors; monitor for signs of formation of antibodies to factor VIII; may occur at any time but more common in young children with severe hemophilia and previously untreated patients. Suspect factor VIII antibodies if the plasma factor VIII level does not increase as expected or if bleeding is not controlled after administration.

• Hypersensitivity reactions: Allergic hypersensitivity reactions (including anaphylaxis) may occur; discontinue if hypersensitivity symptoms occur and administer appropriate treatment.

Dosage form specific issues:

• Albumin: Recombinate is stabilized using human albumin.

• Bovine: Recombinate may contain bovine protein.

• Mouse/hamster protein: Some products may contain trace amounts of mouse or hamster protein.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

• Sucrose: Some products are stabilized with or may contain sucrose.

• von Willebrand factor: Some products contain naturally-occurring von Willebrand factor for stabilization; however, efficacy has not been established for the treatment of von Willebrand disease.

Other warnings/precautions:

• Dose requirements: The dosage requirement will vary in patients with factor VIII inhibitors; optimal treatment should be determined by clinical response.

Monitoring Parameters

Monitor plasma factor VIII activity (prior to and during IV administration); monitor hemoglobin/hematocrit; monitor for development of factor VIII inhibitors. Monitor heart rate and blood pressure (before and during IV administration); monitor for signs/symptoms of bleeding; hypersensitivity reactions.

Pregnancy Considerations

Pregnant hemophilia A carriers may have an increased bleeding risk following abortion, invasive procedures, miscarriage, and delivery; close surveillance is recommended. Factor VIII levels should be monitored at the first antenatal visit, once or twice during the third trimester, prior to surgical or invasive procedures, and at delivery. Although factor VIII concentrations increase in pregnant patients, factor VIII replacement is recommended if concentrations are <0.5 IU/mL and any of the following occur: need for invasive procedures (including delivery), spontaneous miscarriage, insertion and removal of epidural catheters, or active bleeding. Hemostatic factor VIII concentrations should be maintained for at least 3 to 5 days following invasive procedures or postpartum. If a replacement product is indicated, a recombinant product is preferred (NHF 2017; RCOG [Pavord 2017]; WFH [Srivastava 2013]).

Patient Education

What is this drug used for?

• It is used to treat hemophilia.

• It is used to treat or prevent bleeding.

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:

• Injection site irritation

• Headache

• Common cold symptoms

• Runny nose

• Loss of strength and energy

• Cough

• Stuffy nose

• Sore throat

• Back pain

• Dry mouth

• Joint swelling

• Joint pain

• Diarrhea

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:

• Dizziness

• Passing out

• Sensation of cold

• Shortness of breath

• Flushing

• Nausea

• Vomiting

• Agitation

• Fast heartbeat

• Chills

• Pale skin

• Mouth discoloration

• Chest pain

• Burning or numbness feeling

• 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, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Frequently Asked Questions