Pronounciation and Trade Name(s) ⬇
ANTIHEMOPHILIC FACTOR
■ VON WILLEBRAND FACTOR COMPLEX (HUMAN)
Pronounciation
- (an-tie-hee-moe-FIL-ik FAK-tor)
Trade Name(s)
Drug Category(ies) ⬆ ⬇
Usual Dose ⬆ ⬇
USUAL DOSE (International units [IU])
Pretreatment:
See Precautions.
Completely individualized. Based on degree of deficiency, desired antihemophilic factor level, body weight, severity of bleeding, and presence of factor VIII inhibitors. One international unit (IU) of factor VIII or 1 IU of von Willebrand factor:Ristocetin Cofactor (vWF:RCof) is approximately equal to the level of factor VIII activity or vWF:RCof found in 1 mL of fresh pooled human plasma.
Alphanate
Treatment of hemophilia A (adults):
Dose requirements and frequency are calculated on the basis of an expected initial response of 2% of normal FVIII:C IU/kg of body weight administered. Assess adequacy of treatment by clinical effects and monitoring of factor VIII activity. See Precautions. The following general dosages are recommended for adult patients:
| Alphanate Dose Guidelines for the Treatment of Adults With Hemophilia A |
|---|
| Hemorrhagic Event | Dosage (AHF FVIII:C IU/kg body weight) |
|---|
Minor hemorrhage:
Bruises, cuts, or scrapes or uncomplicated joint hemorrhage | FVIII:C levels should be brought to 30% of normal (15 FVIII IU/kg twice daily) until hemorrhage stops and healing has been achieved (1 to 2 days). | Moderate hemorrhage:
Nose, mouth, and gum bleeds; dental extractions; hematuria | FVIII:C levels should be brought to 50% (25 FVIII IU/kg twice daily). Continue until healing has been achieved (2 to 7 days on average). | Major hemorrhage:
Joint or muscle hemorrhage, major trauma, hematuria, intracranial and/or intraperitoneal bleeding | FVIII:C levels should be brought to 80% to 100% of normal for at least 3 to 5 days (40 to 50 FVIII IU/kg twice daily). Then maintain at 50% (25 FVIII IU/kg twice daily) until healing has been achieved. May require treatment for up to 10 days. | | Surgery | Before surgery, FVIII:C levels should be brought to 80% to 100% of normal (40 to 50 FVIII IU/kg twice daily). For the next 7 to 10 days or until healing has been achieved, patient should be maintained at 60% to 100% FVIII levels (25 to 50 FVIII IU/kg twice daily). |
|
IU, International unit.
| Alphanate Dose Guidelines for Prophylaxis During Surgery and Invasive Procedures of Adult and Pediatric Patients With von Willebrand Disease (Except Type 3 Patients Undergoing Surgery) |
|---|
| Bleeding Prophylaxis for Surgical or Invasive Procedures | Dosage (AHF vWF:RCof IU/kg body weight) |
|---|
| Adult | Preoperative dose: 60 vWF:RCof IU/kg body weight.
Subsequent infusions: 40 to 60 vWF:RCof IU/kg body weight at 8- to 12-hour intervals as clinically needed.
Dosing may be reduced after the third postoperative day.
Continue treatment until healing is complete. | | Adult | Minor procedure: vWF activity of 40% to 50% for at least 1 to 3 days postoperatively. | | Adult | Major procedure: vWF activity of 40% to 50% for at least 3 to 7 days postoperatively. | | Pediatric | Initial dose: 75 vWF:RCof IU/kg body weight.
Subsequent infusions: 50 to 75 vWF:RCof IU/kg body weight at 8- to 12-hour intervals as clinically needed.
Dosing may be reduced after the third postoperative day.
Continue treatment until healing is complete. |
|
IU, International unit.
Humate-P
Treatment of hemophilia A (adults):
As a general rule, 1 IU of factor VIII activity per kg body weight will increase the circulating factor VIII level by approximately 2 IU/dL. Assess adequacy of treatment by clinical effects and monitoring of factor VIII activity. See Precautions. The following general dosages are recommended for adult patients:
| Humate-P Dose Recommendations for the Treatment of Hemophilia Aa |
|---|
| Hemorrhage Event | Dosage (IUb FVIII:C/kg body weight) |
|---|
Minor- Early joint or muscle bleed
- Severe epistaxis
| Loading dose 15 IU FVIII:C/kg to achieve FVIII:C plasma level of approximately 30% of normal; one infusion may be sufficient.
If needed, half of the loading dose may be given once or twice daily for 1-2 days. | Moderate- Advanced joint or muscle bleed
- Neck, tongue, or pharyngeal hematoma without airway compromise
- Tooth extraction
- Severe abdominal pain
| Loading dose 25 IU FVIII:C/kg to achieve FVIII:C plasma level of approximately 50% of normal.
Followed by 15 IU FVIII:C/kg every 8-12 hours for first 1-2 days to maintain FVIII:C plasma level at 30% of normal.
Then same dose once or twice a day for up to 7 days or until adequate wound healing. | Life-threatening- Major operations
- Gastrointestinal bleeding
- Neck, tongue, or pharyngeal hematoma with potential for airway compromise
- Intracranial, intra-abdominal, or intrathoracic bleeding
- Fractures
| Initially 40-50 IU FVIII:C/kg.
Followed by 20-25 IU FVIII:C/kg every 8 hours to maintain FVIII:C plasma level at 80%-100% of normal for 7 days.
Then continue the same dose once or twice a day for another 7 days to maintain the FVIII:C level at 30%-50% of normal. |
|
Treatment of von Willebrand Disease (vWD) (adults and pediatric patients):
As a rule, 40 to 80 IU vWF:RCof (corresponding to 16 to 32 IU factor VIII in Humate-P) per kg body weight given every 8 to 12 hours. Repeat doses are administered as needed based on monitoring of appropriate clinical and laboratory measures. Expected levels of vWF:RCof are based on an expected in vivo recovery of 1.5 IU/dL rise per IU/kg vWF:RCof administered. The administration of 1 IU of factor VIII per kg body weight can be expected to lead to a rise in circulating vWF:RCof of approximately 3.5 to 4 IU/dL. The following general dosages are recommended for adult and pediatric patients:
| Humate-P Dose Recommendations for Treatment of von Willebrand Disease in Adult and Pediatric Patients |
|---|
| Classification | Hemorrhage | Dosage (IUa vWF:RCof/kg body weight) |
|---|
| TYPE 1 | Mild
(Where use of desmopressin is known or suspected to be inadequate)
Baseline vWF:RCof activity typically >30% of normal (i.e., >30 IU/dL) | Major (examples)- Severe or refractory epistaxis
- GI bleeding
- CNS trauma
- Traumatic hemorrhage
| Loading dose 40 to 60 IU/kg.
Then 40 to 50 IU/kg every 8 to 12 hours for 3 days to keep the nadir level of vWF:RCof >50% of normal (i.e., >50 IU/dL).
Then 40 to 50 IU/kg daily for a total of up to 7 days of treatment. | Moderate or Severe
Baseline vWF:RCof activity typically <30% of normal (i.e., <30 IU/dL) | Minor (examples) | 40 to 50 IU/kg (1 or 2 doses) | Major (examples)- Severe or refractory epistaxis
- GI bleeding
- CNS trauma
- Hemarthrosis
- Traumatic hemorrhage
| Loading dose of 50 to 75 IU/kg
Then 40 to 60 IU/kg every 8 to 12 hours for 3 days to keep the nadir level of vWF:RCof >50% of normal (i.e., >50 IU/dL)
Then 40 to 60 IU/kg daily for a total of up to 7 days of treatment
Factor VIII:C levels should be monitored and maintained according to the guidelines for hemophilia A therapy.b | | TYPE 2 (ALL VARIANTS) AND TYPE 3 | | Minor (clinical indications above) | 40 to 50 IU/kg (1 or 2 doses) | | Major (clinical indications above) | Loading dose of 60 to 80 IU/kg
Then 40 to 60 IU/kg every 8 to 12 hours for 3 days to keep the nadir level of vWF:RCof >50% of normal (i.e., >50 IU/dL)
Then 40 to 60 IU/kg daily for a total of up to 7 days of treatment
Factor VIII:C levels should be monitored and maintained according to the guidelines for hemophilia A therapy.b |
|
Prevention of excessive bleeding during and after surgery in vWD:
In the case of emergency surgery, administer a loading dose of 50 to 60 IU/kg Humate-P and closely monitor the patient’s trough coagulation factor levels. Measurement of incremental in vivo recovery (IVR) and assessment of baseline plasma vWF:RCof and FVIII:C levels are recommended in all patients before surgery. As shown in the following charts, calculation of the loading dose requires four values: the target peak plasma vWF:RCof level, the baseline vWF:RCof level, body weight (BW) in kilograms, and IVR. If individual recovery values are not available, a standardized loading dose can be used based on an assumed vWF:RCof IVR of 2 IU/dL per IU/kg of vWF:RCof product administered.
| vWF:RCof and FVIII:C Humate-P Loading Dose Recommendations for the Prevention of Excessive Bleeding During and After Surgery |
|---|
| Type of Surgery | vWF:RCof Target Peak Plasma Level | FVIII:C Target Peak Plasma Level | Calculation of Loading Dose (to be administered 1 to 2 hours before surgery) |
|---|
| Major | 100 IU/dL | 80 to 100 IU/dL | Δa vWF:RCof × BW (kg)/IVRb = IU vWF:RCof required.
If incremental IVR is not available, assume an IVR of 2 IU/dL per IU/kg and calculate the loading dose as follows: (100 – Baseline plasma vWF:RCof) × BW (kg)/2.
In the case of emergency surgery, administer a dose of 50 to 60 IU/kg. | | Minor/oralc | 50 to 60 IU/dL | 40 to 50 IU/dL | Δa vWF:RCof × BW (kg)/IVRb = IU vWF:RCof required. |
|
IU, International unit.
| vWF:RCof and FVIII:C Target Trough Plasma Level and Minimum Duration of Treatment Recommendations for Subsequent Maintenance Doses of Humate-P for the Prevention of Excessive Bleeding During and After Surgery |
|---|
| Type of Surgery | vWF:RCof Target Trough Plasma Levelsa | FVIII:C Target Trough Plasma Levelsa | Minimum Duration of Treatment |
|---|
| Up to 3 Days Following Surgery | After Day 3 | Up to 3 Days Following Surgery | After Day 3 |
|---|
| Major | >50 IU/dL | >30 IU/dL | >50 IU/dL | >30 IU/dL | 72 hours | | Minor | ≥30 IU/dL | — | — | >30 IU/dL | 48 hours | | Oralb | ≥30 IU/dL | — | — | >30 IU/dL | 8 to 12 hoursc |
|
IU, International unit.
Pediatric Dose ⬆ ⬇
Treatment of hemophilia A (unlabeled):
For immediate control of bleeding, follow the general recommendations for dosing and administration for adults. See Usual Dose and Maternal/Child.
Dose Adjustments ⬆ ⬇
Adjust subsequent doses based on FVIII:C plasma level achieved or as outlined in specific charts.
Dilution ⬆ ⬇
Consult individual product instructions in the package insert; each product has a specific process for dilution. Information may be updated frequently. Alphanate provides diluent, a double-ended transfer needle, and a microaggregate filter for use in administration. Humate-P provides diluent and a filter transfer set.
Alphanate and Humate-P:
Actual number of AHF units is shown on each vial. Use only the diluent provided and maintain strict aseptic technique. Use a plastic syringe to prevent binding to glass surfaces. Warm to room temperature (25° C [77° F]) before dilution and maintain throughout administration to avoid precipitation of active ingredients.
Filters:
Filters supplied by manufacturer; see Dilution.
Storage:
Alphanate:
Refrigerate before use. Avoid freezing. May be stored at CRT for up to 2 months. Label vial with date removed from refrigeration. Humate-P: Store up to 25° C (up to 77° F). Avoid freezing. Alphanate and Humate-P: Do not refrigerate after reconstitution. Confirm expiration date on vial. Administer within 3 hours of reconstitution to ensure sterility. Discard any unused solution.
Compatibality ⬆ ⬇
Compatibility information not available from manufacturer. Administration through a separate line without mixing with other IV fluids or medications is generally recommended for these products; consult a pharmacist.
Rate of Administration ⬆ ⬇
Inject solution slowly. Rapid administration may result in vasomotor reactions.
Humate-P recommends a maximum rate of 4 mL/min.
Alphanate recommends a maximum rate not to exceed 10 mL/min.
Actions ⬆ ⬇
A purified, sterile, lyophilized concentrate of antihemophilic factor (factor VIII) and von Willebrand Factor (vWF). Factor VIII is an essential cofactor in the activation of factor X, leading ultimately to the formation of thrombin and fibrin. It is the specific clotting factor deficient in patients with hemophilia A (classic hemophilia). vWF is important for correcting the coagulation defect in patients with von Willebrand disease (vWD). It promotes platelet aggregation and platelet adhesion on damaged vascular endothelium and acts as a stabilizing carrier protein for the procoagulant protein factor VIII. vWF activity is measured with an assay that uses an agglutinating cofactor called Ristocetin (RCof). The vWF:RCof assay provides a quantitative measurement of vWF function by determining how well vWF helps platelets adhere to one another. Reduced vWF:RCof activity indicates a deficiency of vWF. Following administration of FVIII/vWF, there is a rapid increase of plasma factor VIII activity, followed by a rapid decrease in activity and then a slower rate of decrease in activity. The mean initial half-life in hemophilic patients is 8.3 to 27.5 hours with Alphanate and 12.2 hours (range: 8.4 to 17.4 hours) with Humate-P. In patients with vWD, bleeding time decreases. Antihemophilic factor/von Willebrand Factor Complex is obtained from pooled human fresh frozen plasma. Multiple methods of purification are used to inactivate infectious agents, including viruses.
Indications and Uses ⬆ ⬇
Alphanate
Prevention and control of bleeding in patients with factor VIII deficiency due to hemophilia A or acquired factor VIII deficiency.
■ Prophylaxis for surgical and/or invasive procedures in adult and pediatric patients with von Willebrand disease (vWD) (type 1 or 2) in which the use of desmopressin is either ineffective or contraindicated.
■ Not indicated for patients with severe vWD (type 3).
Humate-P
Treatment and prevention of bleeding in adult patients with hemophilia A.
■ Treatment of spontaneous and trauma-induced bleeding episodes and prevention of excessive bleeding during and after surgery in adult and pediatric patients with severe vWD or with mild or moderate vWD in which the use of desmopressin is known or suspected to be inadequate.
■ Safety and efficacy of prophylactic dosing to prevent spontaneous bleeding and to prevent excessive bleeding related to surgery have not been established in patients with vWD.
Contraindications ⬆ ⬇
Alphanate:
None known when used as indicated.
Humate-P:
History of anaphylactic or severe systemic response to AHF-vWF preparations or known hypersensitivity to any of its components.
Precautions ⬆ ⬇
Alphanate and Humate-P:
For IV use only.
■ Important to establish that coagulation disorder is caused by factor VIII or vWF deficiency. Not useful in treatment of other deficiencies.
■ Healthcare professionals should use caution during administration; may have risk of exposure to viral infection.
■ Manufactured from human plasma. Risk of transmitting infectious agents (e.g., HIV, hepatitis and, theoretically, Creutzfeldt-Jakob disease) has been greatly reduced by screening, testing, and manufacturing techniques. However, risk of transmission cannot be totally eliminated.
■ Hepatitis A and B vaccines are recommended for patients receiving plasma derivatives.
■ Thrombotic events have been reported. Use caution in patients with known risk factors for thrombosis. Incidence may be higher in females.
■ Inhibitors may develop with large or frequent doses; see Monitor.
Monitor:
Complex contains blood group isoagglutinins (anti-A and anti-B). When very large or frequently repeated doses are needed, as when inhibitors are present or when presurgical and postsurgical care is involved, patients of blood groups A, B, and AB should be monitored for signs of intravascular hemolysis and decreasing hematocrit values; see Antidote.
■ Replacement therapy should be monitored by appropriate coagulation tests, especially in cases involving major surgery. Monitor factor VIII and vWF:RCof as indicated in dosing guidelines.
Patient Education:
Prophylactic hepatitis A and hepatitis B vaccines recommended.
■ Report symptoms of possibly transmitted viral infections immediately. Symptoms may include anorexia, arthralgias, fatigue, jaundice, low-grade fever, nausea, or vomiting.
■ Report rash or any other sign of hypersensitivity reaction promptly.
Maternal/Child:
Category C: use only if clearly needed.
■ Adequate and well-controlled studies with long-term evaluation of joint damage have not been done in pediatric patients. Joint damage may result from suboptimal treatment of hemarthroses.
■ Safety and effectiveness for use in neonates with vWD have not been established. Has been used safely in infants, children, and adolescents with vWD.
Elderly:
Numbers insufficient to determine differences in response compared with younger adults. Consider overall status in dosing.
Drug/Lab Interactions ⬆ ⬇
Specific information not available.
Side Effects ⬆ ⬇
Alphanate and Humate-P:
Usually well tolerated. Rare cases of hypersensitivity reactions, including anaphylaxis, have been reported (symptoms may include chest tightness, edema, fever, pruritus, rash, throat tightness). Other reported side effects include chills, headache, lethargy, nausea and vomiting, paresthesia, phlebitis, somnolence, and vasodilation. Inhibitors of factor VIII may occur.
Post-Marketing:
Alphanate:
In addition to the above, cardiac arrest, femoral venous thrombosis, flushing, itching, joint pain, pulmonary embolus, seizure, shortness of breath, swelling of the parotid gland, urticaria. Humate-P: Hypersensitivity reactions (including anaphylaxis), development of inhibitors to factor VIII, hemolysis, hypervolemia, thromboembolic complications.
Antidote ⬆
Keep physician informed of all side effects. If mild reactions occur (mild allergic reaction, chills, nausea, or stinging at the infusion site) and additional treatment is indicated, a product from a different lot should be considered. Discontinue immediately at first sign of a moderate to severe hypersensitivity reaction. Treat as necessary (antihistamines, epinephrine, corticosteroids). Development of acute hemolytic anemia, increased bleeding tendency, or hyperfibrinogenemia may require transfusion with Type O red blood cells. Discontinue administration of Alphanate/Humate-P and consider alternative therapy. Resuscitate as necessary.