Factor VIII, human plasma-derived: Drug information
Copyright 1978-2018 Lexicomp, Inc. All rights reserved.
(For additional information see "Factor VIII, human plasma-derived: Patient drug information" and see "Factor VIII, human plasma-derived: Pediatric drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)
Brand Names: US
  • Hemofil M;
  • Koate;
  • Koate-DVI;
  • Monoclate-P
Brand Names: Canada
  • Hemofil M
Pharmacologic Category
  • Antihemophilic Agent;
  • Blood Product Derivative
Dosing: Adult

Hemophilia A: 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

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: Pediatric

(For additional information see "Factor VIII, human plasma-derived: Pediatric drug information")

Hemophilia A: Children and Adolescents: Refer to adult dosing.

Dosing: Geriatric

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.

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

Generic Equivalent Available (US)

No

Dosage Forms Considerations

Strengths expressed with approximate values. Consult individual vial labels for exact potency within each vial.

Administration

IV:

Hemofil M, Koate: Administer at a rate comfortable to the patient (≤10 mL/minute).

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).

Use

Hemophilia A: Control and prevention of bleeding episodes in patients with hemophilia A (classic hemophilia); perioperative management of hemophilia A.

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

Medication Safety Issues
Sound-alike/look-alike issues:

Factor VIII may be confused with Factor XIII

Other safety concerns:

Confusion may occur due to the omitting of “Factor VIII” from some product labeling. Review product contents carefully prior to dispensing any antihemophilic factor.

Adverse Reactions

<1%, postmarketing, and/or case reports: Acute hemolytic anemia, anaphylaxis (rare), blurred vision, chest tightness, chills, drowsiness, fever, headache, hemorrhagic diathesis, hypersensitivity reaction (rare), increased factor VIII inhibitors, increased serum fibrinogen, jitteriness, lethargy, nausea, pain at injection site, stomach discomfort, tingling sensation, urticaria, vasomotor symptoms (with rapid infusion), vomiting

Contraindications

Hypersensitivity (eg, anaphylaxis) to antihemophilic factor (human) or any component of the formulation; hypersensitivity to mouse proteins (Hemofil M and Monoclate-P only).

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

Special populations:

• Blood types A, B, and AB: Contains trace amounts of blood groups A and B isohemagglutinins; use caution when large or frequently repeated doses are given to individuals with blood groups A, B, and AB. Monitor patients for signs of intravascular hemolysis and falling hematocrit; discontinue therapy and consider administration of serologically compatible type O red blood cells if progressive hemolytic anemia occurs.

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 A and B vaccination is recommended for all patients receiving plasma derivatives.

• 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: Some products may 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.

Metabolism/Transport Effects

None known.

Drug Interactions

(For additional information: Launch drug interactions program)

Emicizumab-kxwh: May enhance the thrombogenic effect of Factor VIII Products. Risk C: Monitor therapy

Pregnancy Risk Factor

C (show table)

Pregnancy Implications

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.

Breast-Feeding Considerations

It is not known if antihemophilic factor (human) is present in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

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]).

Reference Range

Classification of hemophilia; normal is defined as 1 unit/mL of factor VIII (WFH [Srivastava 2013])

Severe: Factor level <1% of normal

Moderate: Factor level 1% to 5% of normal

Mild: Factor level 5% to <40% of normal

Mechanism of Action

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

Pharmacodynamics/Kinetics

Distribution: Does not readily cross the placenta

Half-life elimination: Mean: 14.8 to 17.5 hours

Pricing: US

Kit (Monoclate-P Intravenous)

1000 unit (Price provided is per AHF Unit): $1.30

1500 unit (Price provided is per AHF Unit): $1.30

Solution (reconstituted) (Hemofil M Intravenous)

250 unit (Price provided is per AHF Unit): $1.60

500 unit (Price provided is per AHF Unit): $1.60

1000 unit (Price provided is per AHF Unit): $1.60

1700 unit (Price provided is per AHF Unit): $1.60

Solution (reconstituted) (Koate Intravenous)

250 unit (Price provided is per AHF Unit): $1.66

500 unit (Price provided is per AHF Unit): $1.66

1000 unit (Price provided is per AHF Unit): $1.66

Solution (reconstituted) (Koate-DVI Intravenous)

250 unit (Price provided is per AHF Unit): $1.58

500 unit (Price provided is per AHF Unit): $1.58

1000 unit (1): $1.48

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • 8Y (ID);
  • AAFact (ID);
  • Fandhi (IL);
  • Haemoctin (GB);
  • Haemoctin SDH (IL);
  • Hemofil M (DE, FR, IT, LK, TH, TW);
  • Koate- DVI (AE);
  • Koate-DVI (AR, CL, CO, CR, DO, GT, HK, HR, ID, IL, MX, PA, PH, QA, SG, SV, TR, UY);
  • Monoclate P (GB, IE);
  • Monoclate-P (AT, DK, FR, GR, KR, SE, TW);
  • Octonativ-M (SE)
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REFERENCES

  1. Abildgaard CF, Simone JV, Corrigan JJ, et al, “Treatment of Hemophilia With Glycine-Precipitated Factor VIII,” N Engl J Med, 1966, 275(9):471-5. [PubMed 5917942]
  2. Alade SL, Brown RE, Paquet A. Polysorbate 80 and E-Ferol toxicity. Pediatrics. 1986;77(4):593-597. [PubMed 3960626]
  3. Batorova A, Holme P, Gringeri A, et al; European Haemophilia Treatment Standardisation Board. Continuous infusion in haemophilia: current practice in Europe. Haemophilia. 2012;18(5):753-759. [PubMed 22530687]
  4. Batorova A, Martinowitz U. Continuous infusion of coagulation factors. Haemophilia. 2002;8(3):170-177. [PubMed 12010406]
  5. Berntorp E, “Impact of Replacement Therapy on the Evolution of HIV Infection in Hemophiliacs,” Thromb Haemost, 1994, 71(6):678-83. [PubMed 7974331]
  6. Centers for Disease Control (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. http://www.cdc.gov/mmwr/preview/mmwrhtml/00000319.htm [PubMed 6423951]
  7. Hemofil M (antihemophilic factor [human]) [prescribing information]. Westlake Village, CA: Baxalta US Inc; March 2017.
  8. Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-313. [PubMed 12534540]
  9. Koate (Antihemophilic Factor [Human]) [prescribing information]. Fort Lee, NJ: Kedrion Biopharma Inc; December 2015.
  10. Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172. [PubMed 10985636]
  11. Lusher JM, “Transfusion Therapy in Congenital Coagulopathies,” Hematol Oncol Clin North Am, 1994, 8(6):1167-80. [PubMed 7860443]
  12. Manucci PM, “Impact of Recombinant Factor VIII on Hemophilia Care,” Vox Sang, 1994, 67(Suppl 3):49-52. [PubMed 7975511]
  13. Nilsson IM, Berntorp E, Lofqvist T, et al, “Twenty-Five Years' Experience of Prophylactic Treatment in Severe Haemophilia A and B,” J Intern Med, 1992, 232(1):25-32. [PubMed 1640190]
  14. Peterson CW, “Treating Hemophilia,” Am Pharm, 1994, NS34(8):57-67.
  15. Poon MC, Card R. Hemophilia management in transfusion medicine. Transfus Apher Sci. 2012;46(3):299-307. [PubMed 22503305]
  16. Rickard KA. Guidelines for therapy and optimal dosages of coagulation factors for treatment of bleeding and surgery in haemophilia. Haemophilia. 1995;1(suppl 1):8-13.
  17. Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8980):1312-1313. [PubMed 7746084]
  18. Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al; Treatment Guidelines Working Group on Behalf of The World Federation of Hemophilia. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1-e47. [PubMed 22776238]
  19. White GC, Rosendaal F, Aledort LM, et al, “Definitions in Hemophilia. Recommendation of the Scientific Subcommittee on Factor VIII and Factor IX of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis,” Thromb Haemost, 2001, 85(3):560. [PubMed 11307831]
  20. Varon D, Martinowitz U. Continuous infusion therapy in haemophilia. Haemophilia. 1998;4(4):431-435. [PubMed 9873771]
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