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Antihemophilic Factor (Human)

Pronunciation

(an tee hee moe FIL ik FAK tor HYU man)

Index Terms

  • AHF (Human)
  • Factor VIII (Human)
  • Kaote DVI

Dosage Forms

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

Kit, Intravenous:

Monoclate-P: ~250 units [DSC], ~500 units [DSC], ~1000 units, ~1500 units [contains mouse (murine) and/or hamster protein]

Solution Reconstituted, Intravenous:

Koate-DVI: ~500 units (1 ea) [contains albumin human, polyethylene glycol, polysorbate 80]

Solution Reconstituted, Intravenous [preservative free]:

Hemofil M: ~250 units (1 ea) [contains albumin human, mouse (murine) and/or hamster protein, polyethylene glycol]

Hemofil M: ~250 units (1 ea [DSC]) [contains mouse (murine) and/or hamster protein, polyethylene glycol]

Hemofil M: ~500 units (1 ea) [contains albumin human, mouse (murine) and/or hamster protein, polyethylene glycol]

Hemofil M: ~500 units (1 ea [DSC]) [contains mouse (murine) and/or hamster protein, polyethylene glycol]

Hemofil M: ~1000 units (1 ea); ~1700 units (1 ea) [contains albumin human, mouse (murine) and/or hamster protein, polyethylene glycol]

Koate-DVI: ~250 units (1 ea); ~500 units (1 ea [DSC]); ~1000 units (1 ea) [contains albumin human, polyethylene glycol, polysorbate 80]

Brand Names: U.S.

  • Hemofil M
  • Koate-DVI
  • Monoclate-P

Pharmacologic Category

  • Antihemophilic Agent
  • Blood Product Derivative

Pharmacology

Protein (factor VIII) in normal plasma which is 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

Does not readily cross the placenta

Half-Life Elimination

Mean: 14.8 to 17.5 hours

Use: Labeled Indications

Hemophilia A: Prevention and treatment of hemorrhagic episodes in patients with hemophilia A (classic hemophilia); perioperative management of hemophilia A.

Note: Can be of significant therapeutic value in patients with acquired factor VIII inhibitors not exceeding 10 Bethesda units/mL

Limitations of use: Not effective in controlling bleeding in patients with von Willebrand disease and therefore is not indicated for this use.

Contraindications

Hemofil M and Monoclate-P: Hypersensitivity to any component of the formulation or mouse proteins

Koate-DVI: There are no contraindications listed in the manufacturer’s labeling.

Dosing: Adult

Hemophilia: IV: 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. Refer to product information for specific manufacturer recommended dosing. Alternatively, the World Federation of Hemophilia (WFH) has recommended general dosing for factor VIII products.

Dosage based on desired factor VIII increase (%):

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

Body weight (kg) x 0.5 units/kg x desired factor VIII increase (%) = units factor VIII required

For example:

50 kg x 0.5 units/kg x 30 (% increase) = 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:

(1400 units x 2%/units/kg) divided by 70 kg = 40%

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 Level to Maintain

Duration

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.

Joint

40 to 60 units/dL

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

Superficial muscle/no neurovascular compromise

40 to 60 units/dL

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 units/dL

Initial: 1 to 2 days

Maintenance: 30 to 60 units/dL

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

CNS/Head

Initial: 80 to 100 units/dL

Initial: 1 to 7 days

Maintenance: 50 units/dL

Maintenance: 8 to 21 days

Throat and neck

Initial: 80 to 100 units/dL

Initial: 1 to 7 days

Maintenance: 50 units/dL

Maintenance: 8 to 14 days

Gastrointestinal

Initial: 80 to 100 units/dL

Initial: 7 to 14 days

Maintenance: 50 units/dL

Maintenance: Not specified

Renal

50 units/dL

3 to 5 days

Deep laceration

50 units/dL

5 to 7 days

Surgery (major)

Preop: 80 to 100 units/dL

Postop: 60 to 80 units/dL

Postop: 1 to 3 days

Postop: 40 to 60 units/dL

Postop: 4 to 6 days

Postop: 30 to 50 units/dL

Postop: 7 to 14 days

Surgery (minor)

Preop: 50 to 80 units/dL

Postop: 30 to 80 units/dL

Postop: 1 to 5 days depending on procedure type

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

Desired Factor VIII Level to Maintain and Duration Based on Site of Hemorrhage/Clinical Situation:

Joint: 40 to 60 units/dL for 1 to 2 days, may be longer if response is inadequate

Superficial muscle (no neurovascular compromise): 40 to 60 units/dL for 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 units/dL for 1 to 2 days; Maintenance: 30 to 60 units/dL for 3 to 5 days, sometimes longer as secondary prophylaxis during physiotherapy

CNS/head: Initial: 80 to 100 units/dL for 1 to 7 days; Maintenance: 50 units/dL for 8 to 21 days

Throat and neck: Initial: 80 to 100 units/dL for 1 to 7 days; Maintenance: 50 units/dL for 8 to 14 days

Gastrointestinal: Initial: 80 to 100 units/dL for 7 to 14 days; Maintenance: 50 units/dL (duration not specified)

Renal: 50 units/dL for 3 to 5 days

Deep laceration: 50 units/dL for 5 to 7 days

Surgery (major): Preop: 80 to 100 units/dL; Postop: 60 to 80 units/dL for 1 to 3 days; then 40 to 60 units/dL for 4 to 6 days; then 30 to 50 units/dL for 7 to 14 days

Surgery (minor): Preop: 50 to 80 units/dL; Postop: 30 to 80 units/dL for 1 to 5 days depending on procedure type

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.

Continuous infusion (for patients who require prolonged periods of treatment [eg, intracranial hemorrhage or surgery] to avoid peaks and troughs associated with intermittent infusions) (Batorova 2002; Batorova 2012; Poon 2012; Rickard 1995; WFH [Srivastava 2013]): Following initial bolus to achieve the desired factor VIII level, initiate 2 to 4 units/kg/hour; adjust dose based on frequent factor 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) 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)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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

If refrigerated, the dried concentrate and diluent should be warmed to room temperature before reconstitution. Gently swirl or rotate vial after adding diluent; do not shake vigorously.

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

Administration

IV:

Hemofil M: May administer at a rate up to 10 mL/minute.

Koate-DVI: May administer over 5 to 10 minutes.

Monoclate-P: Administer at a rate comfortable to the patient (~2 mL/minute).

According to the World Federation of Hemophilia (WFH), infuse by slow IV injection at a rate not to exceed 3 mL/minute (adults) or 100 units/minute (young children); may also administer as a continuous infusion in select patients (WFH [Srivastava 2013]). When administering as a continuous infusion, may use a portable mini-pump or syringe pump (Batorova 2012).

Storage

Store under refrigeration, 2°C to 8°C (36°F to 46°F); avoid freezing. Use within 3 hours of reconstitution. Do not refrigerate after reconstitution, precipitation may occur.

Hemofil M: May also be stored at room temperature not to exceed 30°C (86°F).

Koate-DVI; Monoclate-P: May also be stored at room temperature of 25°C (77°F) for ≤6 months.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

<1% (Limited to important or life-threatening): Acute hemolytic anemia, anaphylaxis (rare), blurred vision, chest tightness, chills, drowsiness, fever, fibrinogenemia, headache, hemorrhagic diathesis, hypersensitivity reaction (rare), increased factor VIII inhibitors, jitteriness, lethargy, nausea, pain at injection site, stomach discomfort, tingling sensation, urticaria, vasomotor symptoms (with rapid infusion), vomiting

Warnings/Precautions

Special populations:

• Blood types A, B, and AB: Contains trace amounts of blood groups A and B isohemagglutinins and when large or frequently repeated doses are given to individuals with blood groups A, B, and AB, the patient should be monitored for signs of progressive anemia and the possibility of intravascular hemolysis should be considered.

Dosage form specific issues:

• Albumin: Products vary by preparation method; final formulations contain human albumin.

• Human plasma: Product of human plasma; may potentially contain infectious agents which could transmit disease. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer. Hepatitis B vaccination is recommended for all patients. Hepatitis A vaccination is also recommended for seronegative patients.

• Latex: Natural rubber latex is a component of Koate-DVI and Hemofil M packaging.

• Mouse protein: Hemofil M and Monoclate-P contain trace amounts of mouse protein; use is contraindicated in patients with hypersensitivity to mouse 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.

• von Willebrand factor: 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:

• Appropriate use: Dosage requirements will vary in patients with factor VIII inhibitors; optimal treatment should be determined by clinical response. Frequency of use is determined by the severity of the disorder or bleeding pattern.

Monitoring Parameters

Heart rate and blood pressure (before and during IV administration); AHF levels prior to and during treatment; in patients with circulating inhibitors, the inhibitor level should be monitored; hematocrit; monitor for signs and symptoms of intravascular hemolysis; bleeding

When administering as a continuous infusion, monitor frequently for pump failure (WFH [Srivastava 2013]).

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. Parvovirus B19 or hepatitis A, which may be present in plasma-derived products, may affect a pregnant woman more seriously than nonpregnant women.

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?)

• Have patient report immediately to prescriber signs of parvovirus B19 or hepatitis A infection (chills, severe fatigue, rhinorrhea, rash, joint pain, lack of appetite, nausea, vomiting, abdominal pain, or jaundice), shortness of breath, severe dizziness, passing out, severe nausea, vomiting, flushing, severe loss of strength and energy, tachycardia, or angina (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 healthcare 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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