Adult Dosing

Hemophilia A, bleeding prophylaxis

• Dosage and duration depend on severity of factor VIII (antihemophilic factor) deficiency, location and extent of bleeding, and the patient's clinical condition
• Dosage should be calculated as follows: Dose required (IU) = body weight (kg) × desired increase in factor VIII level (% of normal or IU/dL) × 0.5

Management of hemorrhage

Minor hemorrhage (early hemarthroses, minor muscle or oral bleeds)

• Advate
• 10-20 IU/kg IV (or dose necessary to increase plasma levels of AHF by 20-40%) q12-24 hrs x 1-3 days until healing is complete or bleeding episode resolves

• Helixate FS, Kogenate FS
• 10-20 IU/kg IV (or dose necessary to increase plasma levels of AHF by 20-40%); repeat this dose if there is evidence of further bleeding

• Recombinate
• Administer doses necessary to increase plasma levels of AHF by 20-40% of normal q12-24 hrs x 1-3 days until bleeding resolves

• ReFacto and Xyntha
• Administer doses necessary to increase plasma levels of AHF by 20-40% of normal q12-24 hrs x 1-3 days until bleeding resolves

• Novoeight
• Administer doses necessary to increase plasma levels of AHF by 20-40% of normal q12-24 hrs x minimum 1 day until bleeding resolves

Minor to moderate hemorrhage (Joint, superficial muscle, deep lacerations and superficial soft tissue, mucous membranes bleeds)

• Eloctate
• 20-30 IU/kg IV (or dose necessary to increase plasma levels of AHF by 40-60%) repeat q24-48 hours until bleeding episode resolves

Moderate hemorrhage (bleeding into muscles, bleeding into the oral cavity, mild head trauma)

• Novoeight
• Administer doses necessary to increase plasma levels of AHF by 30-60% of normal q12-24 hrs x 3-4 days until pain and disability resolve

Moderate to major hemorrhage (definite hemarthroses/bleeding into muscles, bleeding into the oral cavity, known trauma)

• Advate
• 15-30 IU/kg IV (or dose necessary to increase plasma levels of AHF by 30-60%) q12-24 hrs x 3-4 days until bleeding resolves

• Helixate FS, Kogenate FS
• 15-30 IU/kg IV (or dose necessary to increase plasma levels of AHF by 30-60%) q12-24 hrs x 3-4 days until bleeding resolves

• Recombinate
• Administer doses necessary to increase plasma levels of AHF by 30-60% of normal q12-24 hrs x 3-4 days until pain and disability resolve

• ReFacto and Xyntha
• Administer doses necessary to increase plasma levels of AHF by 30-60% of normal q12-24 hrs x 3-4 days until adequate local hemostasis is achieved

Major to life-threatening hemorrhage (GI bleeding, intracranial/intra-abdominal/ intrathoracic bleeding, CNS bleeding, bleeding in retropharyngeal/retroperitoneal spaces, fractures, head trauma)

• Advate
• 30-50 IU/kg IV (or dose necessary to increase plasma levels of AHF by 60-100%)
• Repeat this dose q8-24 hrs until bleeding is resolved

• Helixate FS, Kogenate FS
• 40-50 IU/kg IV (or dose necessary to increase plasma levels of AHF by 80-100% of normal)
• Repeat doses of 20-25 IU/kg q8-12 hrs until bleeding is resolved

• Recombinate
• Administer doses necessary to increase plasma levels of AHF by 60-100% of normal, q8-24 hrs until bleeding is resolved

• ReFacto and Xyntha
• Administer doses necessary to increase plasma levels of AHF by 60-100% of normal, q8-24 hrs until bleeding is resolved

• Novoeight
• Administer doses necessary to increase plasma levels of AHF by 60-100% of normal, q8-24 hrs x 7-10 days until bleeding is resolved

• Eloctate
• 40-50 IU/kg IV (or dose necessary to increase plasma levels of AHF by 80-100%) q12-24 hours x 7-10 days until bleeding resolves

Surgical prophylaxis

Minor surgery (tooth extraction)

• Advate
• Administer 30-50 IU/kg IV (or dose necessary to increase plasma levels of AHF by 60-100% of normal) within 1 hr of the procedure and optional additional doses may be given q12-24 hrs as needed to control bleeding

• Helixate FS, Kogenate FS
• Administer single dose of 15-30 IU/kg IV (or dose necessary to increase plasma levels of AHF by 30-60% of normal); repeat this dose q12-24 hrs until bleeding is resolved

• Recombinate
• Administer single dose necessary to increase plasma levels of AHF by 60-80% of normal within 1 hr of the procedure; if given in conjunction with oral antifibrinolytics, a single dose may be sufficient

• ReFacto and Xyntha
• Administer single dose necessary to increase plasma levels of AHF by 30-60% of normal within 1 hr of the procedure; if given in conjunction with oral antifibrinolytics, a single dose may be sufficient

• Novoeight
• Administer IV doses necessary to increase plasma levels of AHF by 30-60% of normal q24 hrs, x minimum 1 day until healing is achieved

• Eloctate
• Administer 25-40 IU/kg IV (or dose necessary to increase plasma levels of AHF 50-80 % of normal) repeat q 12-24 hours until wound healing is achieved (Generally 1day)

Major surgery (intracranial/intra-abdominal/intrathoracic or joint replacement surgery)

• Advate
• 40-60 IU/kg IV (or dose necessary to increase plasma levels of AHF by 80-120% of normal) prior to surgery
• Repeat q8-24 hrs, until hemostasis and wound healing are achieved (generally 10-14 days)

• Helixate FS, Kogenate FS
• Administer 50 IU/kg IV (or dose necessary to increase plasma levels of AHF by 100% of normal) prior to surgery
• Repeat doses q6-12 hrs, until hemostasis and wound healing are achieved (generally 10-14 days)

• Recombinate
• Administer IV doses necessary to increase plasma levels of AHF by 80-100% of normal
• Repeat doses q8-24 hrs, until hemostasis and wound healing are achieved

• ReFacto and Xyntha
• Administer doses necessary to increase plasma levels of AHF by 60-100% of normal
• Repeat doses q8-24 hrs, until adequate local hemostasis and wound healing are achieved

• Novoeight
• Administer IV doses necessary to increase plasma levels of AHF by 80-100% of normal (pre-and post-operative)
• Repeat doses q8-24 hrs, until hemostasis and wound healing are achieved and continue for minimum 7 days to maintain AHF activity of 30-60%

• Eloctate
• 40-60 IU/kg IV (or dose necessary to increase plasma levels of AHF by 80-120% of normal) prior to surgery
• Repeat 40-50 IU/kg q8-24 hours, until wound healing is achieved (generally 7 days)

Routine Prophylaxis

• 20-50 IU/kg IV 3 times a week
• Eloctate
• 50 IU/kg IV q4 days
• Range: 25-65 IU/kg at 3-5 days interval, based on patient response

Note:

• Dosing is highly variable, the above mentioned dosages serve as general guidelines. Dosage should be individualized based on desired percentage increase of AHF factor, baseline factor VIII levels, and clinical condition of the patient
• For short-term routine prophylaxis to prevent or reduce the frequency of spontaneous musculoskeletal hemorrhage in hemophilia A patients, ReFacto should be given at least twice weekly
• An AHF dose of 25-40 IU/kg 3 times a week or every other day is usually recommended for routine prophylaxis in patients with hemophilia A; prophylactic therapy should be started at a young age prior to onset of frequent bleeding
• Re-evaluate patients periodically to determine the need for continued therapy, as some patients may require life-long prophylaxis

Pediatric Dosing

Hemophilia A, bleeding prophylaxis

• Dosage and duration depend on severity of factor VIII (antihemophilic factor) deficiency, location and extent of bleeding, and the patient's clinical condition
• Dosage should be calculated as follows: Dose required (IU) = body weight (kg) × desired increase in factor VIII level (% of normal or IU/dL) × 0.5

Management of hemorrhage

Minor hemorrhage (early hemarthroses, minor muscle or oral bleeds)

• Advate
• 10-20 IU/kg IV (or dose necessary to increase plasma levels of AHF by 20-40%) q12-24 hrs (8-24 hrs for children <6 yrs of age) x 1-3 days until healing is complete or bleeding episode resolves

• Helixate FS, Kogenate FS
• 10-20 IU/kg IV (or dose necessary to increase plasma levels of AHF by 20-40%); repeat this dose if there is evidence of further bleeding

• Recombinate
• Administer doses necessary to increase plasma levels of AHF by 20-40% of normal q12-24 hrs x 1-3 days until bleeding resolves

• ReFacto and Xyntha
• Administer doses necessary to increase plasma levels of AHF by 20-40% of normal q12-24 hrs x 1-3 days until bleeding resolves

• Novoeight
• Administer doses necessary to increase plasma levels of AHF by 20-40% of normal q12-24 hrs x minimum 1 day until bleeding resolves

Minor to moderate hemorrhage (Joint, superficial muscle, deep lacerations and superficial soft tissue, mucous membranes bleeds)

• Eloctate
• 20-30 IU/kg IV (or dose necessary to increase plasma levels of AHF by 40-60%) repeat q12-24hours until bleeding episode resolves

Moderate hemorrhage (bleeding into muscles, bleeding into the oral cavity, mild head trauma)

• Novoeight
• Administer doses necessary to increase plasma levels of AHF by 30-60% of normal q12-24 hrs x 3-4 days until pain and disability resolve

Moderate to major hemorrhage (definite hemarthroses/bleeding into muscles, bleeding into the oral cavity, known trauma

• Advate
• 15-30 IU/kg IV (or dose necessary to increase plasma levels of AHF by 30-60%) q12-24 (8-24 hrs for children <6 yrs) hrs x 3-4 days until bleeding resolves

• Helixate FS, Kogenate FS
• 15-30 IU/kg IV (or dose necessary to increase plasma levels of AHF by 30-60%) q12-24 hrs x 3-4 days until bleeding resolves

• Recombinate
• Administer doses necessary to increase plasma levels of AHF by 30-60% of normal q12-24 hrs x 3-4 days until pain and disability resolve

• ReFacto and Xyntha
• Administer doses necessary to increase plasma levels of AHF by 30-60% of normal q12-24 hrs x 3-4 days until adequate local hemostasis is achieved

Major to life-threatening hemorrhage (GI bleeding, intracranial/intra-abdominal/ intrathoracic bleeding, CNS bleeding, bleeding in retropharyngeal/retroperitoneal spaces, fractures, head trauma)

• Advate
• 30-50 IU/kg IV (or dose necessary to increase plasma levels of AHF by 60-100%)
• Repeat this dose q8-24 (6-12 hrs for children <6 yrs) hrs until bleeding is resolved

• Helixate FS, Kogenate FS
• 40-50 IU/kg IV (or dose necessary to increase plasma levels of AHF by 80-100% of normal)
• Repeat doses of 20-25 IU/kg q8-12 hrs until bleeding is resolved

• Recombinate
• Administer doses necessary to increase plasma levels of AHF by 60-100% of normal, q8-24 hrs until bleeding is resolved

• ReFacto and Xyntha
• Administer doses necessary to increase plasma levels of AHF by 60-100% of normal, q8-24 hrs until bleeding is resolved

• Novoeight
• Administer doses necessary to increase plasma levels of AHF by 60-100% of normal, q8-24 hrs x 7-10 days until bleeding is resolved

• Eloctate
• 40-50 IU/kg IV (or dose necessary to increase plasma levels of AHF by 80-100%) q8-24 hours x 7-10 days until bleeding resolves

Surgical prophylaxis

Minor surgery (tooth extraction)

• Advate
• Administer 30-50 IU/kg IV (or dose necessary to increase plasma levels of AHF by 60-100% of normal) within 1 hr of the procedure and optional additional doses may be given q12-24 hrs as needed to control bleeding

• Helixate FS, Kogenate FS
• Administer single dose of 15-30 IU/kg IV (or dose necessary to increase plasma levels of AHF by 30-60% of normal); repeat this dose q12-24 hrs until bleeding is resolved

• Recombinate
• Administer single dose necessary to increase plasma levels of AHF by 60-80% of normal within 1 hr of the procedure; if given in conjunction with oral antifibrinolytics, a single dose may be sufficient

• ReFacto and Xyntha
• Administer single dose necessary to increase plasma levels of AHF by 30-60% of normal within 1 hr of the procedure; if given in conjunction with oral antifibrinolytics, a single dose may be sufficient

• Novoeight
• Administer IV doses necessary to increase plasma levels of AHF by 30-60% of normal q24 hrs, x minimum 1 day until healing is achieved

• Eloctate
• Administer 25-40 IU/kg IV (or dose necessary to increase plasma levels of AHF 50-80 % of normal) repeat q 12-24 hours until wound healing is achieved (Generally 1day)

Major surgery (intracranial, intra-abdominal, intrathoracic, joint replacement)

• Advate
• 40-60 IU/kg IV (or dose necessary to increase plasma levels of AHF by 80-120% of normal) prior to surgery
• Repeat q8-24 (6-24 hrs for children <6 yrs) hrs, until hemostasis and wound healing are achieved (generally 10-14 days)

• Helixate FS, Kogenate FS
• Administer 50 IU/kg IV (or dose necessary to increase plasma levels of AHF by 100% of normal) prior to surgery
• Repeat doses q6-12 hrs, until hemostasis and wound healing are achieved (generally 10-14 days)

• Recombinate
• Administer IV doses necessary to increase plasma levels of AHF by 80-100% of normal
• Repeat doses q8-24 hrs, until hemostasis and wound healing are achieved

• ReFacto and Xyntha
• Administer doses necessary to increase plasma levels of AHF by 60-100% of normal
• Repeat doses q8-24 hrs, until adequate local hemostasis and wound healing are achieved

• Novoeight
• Administer IV doses necessary to increase plasma levels of AHF by 80-100% of normal (pre-and post-operative)
• Repeat doses q8-24 hrs, until hemostasis and wound healing are achieved and continue for minimum 7 days to maintain AHF activity of 30-60%

• Eloctate
• 40-60 IU/kg IV (or dose necessary to increase plasma levels of AHF by 80-120% of normal) prior to surgery
• Repeat 40-50 IU/kg q6-24hrs then every 24 hours until wound healing is achieved (generally 7 days)

Routine Prophylaxis

• 20-50 IU/kg IV 3 times a week
• Eloctate
• 50 IU/kg IV q4 days
• Range: 25-65 IU/kg at 3-5 days interval, based on patient response
• Children < 6 yrs: More frequent and higher dose upto 80 IU/kg may be required

Note:

• Dosing is highly variable, the above mentioned dosages serve as general guidelines. Dosage should be individualized based on desired percentage increase of AHF factor, baseline factor VIII levels, and clinical condition of the patient
• For short-term routine prophylaxis to prevent or reduce the frequency of spontaneous musculoskeletal hemorrhage in hemophilia A patients, ReFacto should be given at least twice weekly
• An AHF dose of 25-40 IU/kg 3 times a week or every other day is usually recommended for routine prophylaxis in patients with hemophilia A; prophylactic therapy should be started at a young age prior to onset of frequent bleeding
• Re-evaluate patients periodically to determine the need for continued therapy, as some patients may require life-long prophylaxis

[Outline]

• Adult Dosing
• Pediatric Dosing

• Control and prevention of bleeding episodes in children and adults with hemophilia A
• Indicated for surgical prophylaxis in patients with hemophilia A
• Routine prophylactic treatment to reduce the frequency of bleeding episodes and the risk of joint damage in children with no preexisting joint damage [Helixate FS, Kogenate FS]

• Hypersensitivity to any of the ingredients of the product
• Hypersensitivity to murine proteins
• Hypersensitivity to hamster proteins
• Hypersensitivity to bovine proteins (Recombinate)

• N/A

Renal Dose Adjustment

• Renal impairment: Dose adjustments not defined

Hepatic Dose Adjustment

• Hepatic impairment: Dose adjustments not defined

See Supplemental Patient Information

• Carefully monitor patients treated with AHF products for development of factor VIII inhibitors by appropriate clinical observations and lab tests. If bleeding is not controlled or plasma factor VIII activity level fails to increase with an expected dose, suspect the presence of an inhibitor (neutralizing antibodies) and perform an assay that measures factor VIII inhibitor concentration
• Clinical response to therapy may vary. If bleeding is not controlled with the recommended dose, determine the plasma level of factor VIII and administer a sufficient dose to achieve a satisfactory clinical response
• Antihemophilic factor [recombinant factor VIII] can cause allergic-type hypersensitivity reactions including anaphylaxis; discontinue therapy if hypersensitivity symptoms occur and initiate appropriate treatment
• Patients treated with this drug may develop hypersensitivity to non-human mammalian proteins

Caution: Use cautiously in

• Hypersensitivity to latex (Recombinate)

Supplemental Patient Information

• Advise patients to contact their physician for further assessment and/or treatment if they experience a lack of clinical response to factor VIII replacement therapy, as this may be a manifestation of an inhibitor
• Instruct patients to consult with their clinicians prior to travel. Advise patients to bring an adequate supply of therapy based on their current regimen of treatment
• Advise patients to discontinue use if they experience hypersensitivity reactions and initiate appropriate emergency treatment

Pregnancy Category:C

Breastfeeding: Safety unknown. Manufacturer advises caution. Therapy should be administered to nursing mothers only if clinically needed.

• CNS: Headache, dizziness
• NEURO: Paresthesia
• GI: Nausea, constipation, diarrhea, vomiting, taste changes
• RESP: Influenza, nasopharyngitis, URTI, cough, nasal congestion
• EENT: Otitis media, sinusitis, rhinorrhoea, ear pain
• DERM: Rash, pruritus, urticaria, flushing
• HEMA: Factor VIII inhibitor formation
• Local: Injection site reaction
• MUSC: Arthralgia, joint swelling, pain in extremity, limb injury
• HYPERSENSITIVITY: Anaphylaxis/anaphylactoid reactions, allergic reactions
• MISC: Fever, fatigue, chills, central venous access device line infection, viral transmission risk

• Antihemophilic agent; increases plasma levels of factor VIII, temporarily correcting the coagulation defect caused by factor VIII deficiency in patients with hemophilia A
• Metabolism: Unknown; CYP450: Unknown
• Excretion: Unknown
• Mean Half-Life
• Advate: 12.03 +/- 4.15 hrs
• Helixate FS, Kogenate FS: 14.07 +/- 2.62 hrs
• Novoeight: 10.8 hrs (clotting assay method) and 12.0 hrs (chromogenic assay method)
• ReFacto: 14.8 +/- 5.6 hrs
• Recombinate: 14.6 +/- 4.9 hrs
• Xyntha: 8.03 +/- 2.44 hrs
• Novoeight: 10.8 (clotting assay method) and 12.0 (chromogenic asay method)

US Trade Name(s)

• Advate
• Helixate FS
• Kogenate FS
• Novoeight
• Recombinate
• ReFacto
• Xyntha
• Eloctate

US Availability

Advate

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial
• PWDR for INJ: 1500 IU/vial
• PWDR for INJ: 2000 IU/vial
• PWDR for INJ: 3000 IU/vial

Kogenate FS, Helixate FS

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial
• PWDR for INJ: 2000 IU/vial
• PWDR for INJ: 3000 IU/vial

Novoeight

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial
• PWDR for INJ: 1500 IU/vial
• PWDR for INJ: 2000 IU/vial
• PWDR for INJ: 3000 IU/vial

Recombinate

• PWDR for INJ: 220 - 400 IU/vial
• PWDR for INJ: 401-800 IU/vial
• PWDR for INJ: 801-1240 IU/vial
• PWDR for INJ: 1241-1800 IU/vial
• PWDR for INJ: 1801-2400 IU/vial

ReFacto

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial

Xyntha

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial
• PWDR for INJ: 2000 IU/vial

Eloctate

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 750 IU/vial
• PWDR for INJ: 1000 IU/vial
• PWDR for INJ: 1500 IU/vial
• PWDR for INJ: 2000 IU/vial
• PWDR for INJ: 3000 IU/vial

Canadian Trade Name(s)

• Advate
• Helixate FS
• Kogenate FS

Canadian Availability

Advate

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial
• PWDR for INJ: 1500 IU/vial
• PWDR for INJ: 2000 IU/vial
• PWDR for INJ: 3000 IU/vial

Helixate FS

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial
• PWDR for INJ: 2000 IU/vial

Kogenate FS

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial
• PWDR for INJ: 2000 IU/vial
• PWDR for INJ: 3000 IU/vial

UK Trade Name(s)

• Helixate NexGen
• Kogenate
• ReFacto AF

UK Availability

Helixate NexGen, Kogenate

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial
• PWDR for INJ: 2000 IU/vial
• PWDR for INJ: 3000 IU/vial

ReFacto AF

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial
• PWDR for INJ: 2000 IU/vial

Australian Trade Name(s)

• Advate
• Kogenate FS
• Recombinate
• ReFacto
• Xyntha

Australian Availability

Advate

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial
• PWDR for INJ: 1500 IU/vial

Kogenate FS

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial
• PWDR for INJ: 2000 IU/vial
• PWDR for INJ: 3000 IU/vial

Recombinate

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial

ReFacto

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial
• PWDR for INJ: 2000 IU/vial

Xyntha

• PWDR for INJ: 250 IU/vial
• PWDR for INJ: 500 IU/vial
• PWDR for INJ: 1000 IU/vial
• PWDR for INJ: 2000 IU/vial

[Outline]

Hematology/Oncology

Clotting Factors