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Antihemophilic Factor (Recombinant [Pegylated])

Pronunciation

(an tee hee moe FIL ik FAK tor ree KOM be nant PEG i late ed)

Index Terms

  • AHF (Recombinant [Pegylated])
  • Factor VIII (Recombinant [Pegylated])

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Adynovate: 250 units (1 ea); 500 units (1 ea); 1000 units (1 ea); 2000 units (1 ea) [contains mouse (murine) and/or hamster protein, polysorbate 80]

Brand Names: U.S.

  • Adynovate

Pharmacologic Category

  • Antihemophilic Agent

Pharmacology

Factor VIII replacement, necessary for clot formation and maintenance of hemostasis, 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: Children and Adolescents 12 to <18 years: 0.56 ± 0.18 dL/kg; Adults ≥18 years: 0.43 ± 0.11 dL/kg

Time to Peak

Children and Adolescents 12 to <18 years: 0.26 ± 0.1 hours; Adults ≥18 years: 0.46 ± 0.29 hours

Half-Life Elimination

Children and Adolescents 12 to <18 years: 13.43 ± 4.05 hours; Adults ≥18 years: 14.69 ± 3.79 hours

Use: Labeled Indications

Hemophilia A:

Treatment and control of bleeding episodes: For the on-demand treatment and control of bleeding episodes in adults and children 12 years and older with hemophilia A.

Routine prophylaxis to reduce the frequency of bleeding: For routine prophylaxis to reduce the frequency of bleeding episodes in adults and children 12 years and older with hemophilia A.

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

Contraindications

Anaphylactic reaction to antihemophilic factor (recombinant/pegylated), antihemophilic factor (recombinant), mouse or hamster protein, or any component of the formulation (eg, Tris, mannitol, trehalose, glutathione, and/or polysorbate 80)

Dosing: Adult

Hemophilia A: IV: Dose, dosing frequency, and duration based on location and severity of bleeding, target factor VIII levels, and clinical condition of the patient. Individualize dosage based on coagulation studies performed prior to treatment and at regular intervals during treatment. In general, administration of factor VIII 1 unit/kg will increase circulating factor VIII levels by ~2 units/dL.

Treatment and control of bleeding episodes:

Dosage based on desired factor VIII increase (%):

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

Dosage based on expected factor VIII increase (%):

It is also possible to calculate the expected % factor VIII increase:

[# units administered x 2(%/units/kg)] divided by body weight (kg) = expected % factor VIII increase

For example:

[1,400 units x 2] divided by 70 kg = 40%

General Antihemophilic Factor Dosing for On-demand Treatment and Control of Bleeding Episodes

Type of Bleeding

Target Factor VIII Level (Units/dL or % of normal)

Dose (Units/kg)

Frequency of Dosing (hours)

Duration of therapy

Note: Factor VIII level may either be expressed as units/dL or as %. 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.

Minor early hemarthrosis, mild muscle bleeding, or mild oral bleeding episode

20 to 40

10 to 20

12 to 24

Until bleeding is resolved

Moderate muscle bleeding, moderate bleeding into the oral cavity, definite hemarthroses, and known trauma.

30 to 60

15 to 30

12 to 24

Until bleeding is resolved

Major Significant gastrointestinal bleeding, intracranial, intra-abdominal or intrathoracic bleeding, central nervous system bleeding, bleeding in the retropharyngeal or retroperitoneal spaces or iliopsoas sheath, fractures, head trauma.

60 to 100

30 to 50

8 to 24

Until bleeding is resolved

Table has been converted to the following text.

General Antihemophilic Factor Dosing for On-demand Treatment and Control of Bleeding Episodes:

Minor Early hemarthrosis, mild muscle bleeding, or mild oral bleeding episode: 20 to 40 units/dL (or % or normal) as the target factor VIII level with a dose of 10 to 20 units/kg/dose every 12 to 24 hours until bleeding is resolved.

Moderate Muscle bleeding, moderate bleeding into the oral cavity, definite hemarthroses, and known trauma: 30 to 60 units/dL (or % or normal) as the target factor VIII level with a dose of 15 to 30 units/kg/dose every 12 to 24 hours until bleeding is resolved.

Major Significant gastrointestinal bleeding, intracranial, intra-abdominal or intrathoracic bleeding, central nervous system bleeding, bleeding in the retropharyngeal or retroperitoneal spaces or iliopsoas sheath, fractures, head trauma: 60 to 100 units/dL (or % or normal) as the target factor VIII level with a dose of 30 to 50 units/kg/dose every 8 to 24 hours until bleeding is resolved.

Note: Factor VIII level may either be expressed as units/dL or as %. 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.

Routine prophylaxis to prevent or reduce the frequency of bleeding episodes: 40 to 50 units/kg/dose twice weekly; adjust dose based on clinical response.

Dosing: Geriatric

Although clinical trials did not include patients ≥65 years of age, response in the elderly is not expected to differ from that of younger patients; dosage should be individualized. Refer to adult dosing.

Dosing: Pediatric

Hemophilia A:

Treatment and control of bleeding episodes: Children ≥12 years and Adolescents: IV: Refer to adult dosing.

Routine prophylaxis to prevent bleeding episodes: Children ≥12 years and Adolescents: IV: Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Reconstitution

Allow vial and diluent to warm to room temperature before reconstitution. Gently swirl vial in a circular motion after adding diluent until dissolved. See product information for additional details.

Administration

IV: Over 5 minutes or less (maximum infusion rate of 10 mL/minute)

Dietary Considerations

Some products may contain sodium.

Storage

Prior to reconstitution, store at 2°C to 8°C (36°F to 46°F). Do not freeze. May be stored at room temperature up to 30°C (86°F) for a period of up to 1 month. After storage at room temperature, do not return the product to the refrigerator. Store intact vials in original package to protect from extreme exposure to light. After reconstitution, do not refrigerate solution; use immediately or within 3 hours after reconstitution.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Frequency not always defined.

Central nervous system: Headache (3%)

Gastrointestinal: Nausea (1%)

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

<1% (Limited to important or life-threatening): Acute pancreatitis, diarrhea, flushing

Warnings/Precautions

Concerns related to adverse effects:

• Antibody formation: Formation of antibodies (inhibitors) to factor VIII antibodies may occur; monitor patients for the development of antibodies by clinical observation and laboratory tests. Suspect factor VIII antibodies if the plasma factor VIII level does not increase as expected or if bleeding is not controlled after administration. If inhibitory antibodies are suspected and there is a lack of clinical response, consider other therapy.

• Hypersensitivity reactions: May occur; discontinue immediately if allergic or anaphylactic-type reactions occur.

Dosage form specific issues:

• Hamster protein: May contain trace amounts of hamster proteins.

• Polysorbate 80: 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.

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

Hypersensitivity reactions, heart rate and blood pressure (before and during IV administration); plasma factor VIII activity prior to and during treatment using a one-stage clotting assay to confirm adequate factor VIII levels have been achieved and maintained); development of factor VIII inhibitors using the Bethesda inhibitor assay; signs of bleeding; hemoglobin, hematocrit.

Pregnancy Considerations

Animal reproduction studies have not been conducted. Factor VIII concentrations may increase in pregnant women with coagulation disorders. Pregnant women should have clotting factors monitored, particularly at 28 and 34 weeks gestation and prior to invasive procedures. Prophylaxis may be needed if concentrations are <50 units/mL at term and treatment should continue for 3 to 5 days postpartum depending on route of delivery. The neonate may also be at an increased risk of bleeding following delivery and should be tested for the coagulation disorder (Kadir 2009; Lee 2006). Although recombinant products are generally preferred when therapy in pregnancy is needed, initial studies conducted with the pegylated product were done only in males (Konkle 2015).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache. Have patient report immediately to prescriber shortness of breath, wheezing, angina, dizziness, passing out, severe nausea, or severe vomiting (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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