Alphanate Dosage

Generic name: antihemophilic factor, von willebrand factor complex (human)
Dosage form: injection

The information at Drugs.com is not a substitute for medical advice. ALWAYS consult your doctor or pharmacist.

For Intravenous Use Only

Antihemophilic Factor (AHF) potency (FVIII:C activity) is expressed in International Units (IU) FVIII/vial on the product label.  Additionally, Alphanate contains von Willebrand Factor:Ristocetin Cofactor (VWF:RCo), which is expressed in IU VWF:RCo/vial for the treatment of VWD.

Hemophilia A

  • Treatment with Alphanate should be initiated under the supervision of a physician experienced in the treatment of hemophilia.
  • Dosage and duration of treatment depend on the severity of the FVIII deficiency, the location and extent of bleeding, presence of inhibitors, and the patient’s clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life-threatening bleeding episodes.
  • Dosing requirements and frequency of dosing is calculated on the basis of an expected initial response of 2% of normal FVIII:C increase per IU FVIII:C/kg body weight administered. 2,3

The expected in vivo peak increase in FVIII level expressed as IU/dL (or % normal) can be estimated using the following formulas:

Dosage (units) = body weight (kg) x desired FVIII rise (IU/dL or % normal) x 0.5 (IU/kg per IU/dL)

OR

 IU/dL (or % normal) = Total Dose (IU)/body weight (kg) x 2

 

Thus, an administered AHF dose of 50 IU/kg will be expected to increase the circulating FVIII level to 100% of normal (100 IU/dL).

 

Doses administered should be titrated to the patient’s clinical response, including individualized needs, severity of the deficiency, severity of the hemorrhage, presence of inhibitors, and FVIII level desired. Patients may vary in their pharmacokinetic (e.g., half-life, in vivo recovery) and clinical responses to Alphanate. Although the dose can be estimated by the calculations above, it is highly recommended that, whenever possible, appropriate laboratory tests including serial FVIII activity assays be performed. 

Table 1: Dosage Guidelines for the Treatment of Hemophilia A
Hemorrhagic event Dosage (IU FVIII:C/kg Body Weight)
 Minor hemorrhage:
  • Large bruises
  • Significant cuts or scrapes
  • Uncomplicated joint hemorrhage
FVIII:C levels should be brought to 30% of normal
(15 IU FVIII/kg twice daily) until hemorrhage stops and healing has been achieved (1–2 days).
 Moderate hemorrhage:
  • Nose, mouth and gum bleeds
  • Dental extractions
  • Hematuria
FVIII:C levels should be brought to 50% (25 IU FVIII/kg twice daily). Treatment should continue until healing has been achieved (2–7 days, on average).
 Major hemorrhage:
  • Joint hemorrhage
  • Muscle hemorrhage
  • Major trauma
  • Hematuria
  • Intracranial and intraperitoneal bleeding   
FVIII:C levels should be brought to 80–100% for at least
3–5 days (40–50 IU FVIII/kg twice daily). Following this treatment period, FVIII levels should be maintained at 50% (25 IU FVIII/kg twice daily) until healing has been achieved. Major hemorrhages may require treatment for up to 10 days. Intracranial hemorrhages may require prophylaxis therapy for up to 6 months.
Surgery Prior to surgery, the levels of FVIII:C should be brought to 80–100% of normal (40–50 IU FVIII/kg). For the next 7–10 days, or until healing has been achieved, the patient should be maintained at 60–100% FVIII levels
(30–50 IU FVIII/kg twice daily).

Dosing requirements and frequency of dosing is calculated on the basis of an expected initial response of 2% FVIII:C increase per IU FVIII:C/kg body weight (i.e., 2% per IU/kg) and an average half-life for FVIII:C of 12 hours. If dosing studies have determined that a particular patient exhibits a lower than expected response and shorter half-life, the dose and the frequency of dosing should be adjusted accordingly. Failure to achieve the expected plasma FVIII:C level or to control bleeding after an appropriately calculated dosage may be indicative of the development of an inhibitor (an antibody to FVIII:C). Its presence should be documented and the inhibitor level quantitated by appropriate laboratory procedures. Treatment with AHF in such cases must be individualized .4-6

Plasma FVIII levels should be monitored periodically to evaluate individual patient response to the dosage regime. Depending on the level of the inhibitor and/or clinical response, it may be appropriate to use an alternative ‘bypass’ therapeutic agent.

von Willebrand Disease

  • Treatment with Alphanate should be initiated under the supervision of a physician experienced in the treatment of VWD.
  • The ratio of VWF:RCo to FVIII in Alphanate varies by lot, so dosage should be re-evaluated whenever lot selection is changed.
  • Dosage and duration of treatment depend on the severity of the VWF deficiency, the location and extent of bleeding, and the patient’s clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life-threatening bleeding episodes. Overdosage resulting in FVIII levels above 150% should be avoided.

The median incremental in vivo recoveries of VWF:RCo and FVIII:C were 3.12 (IU/dL)/(IU/kg) [mean, 3.29 ± 1.46 (IU/dL)/(IU/kg); range: 1.28 to 5.73 (IU/dL)/(IU/kg)] for VWF:RCo and 1.95 (IU/dL)/(IU/kg) [mean, 2.13 ± 0.58 (IU/dL)/(IU/kg); range: 1.33 to 3.32 (IU/dL)/(IU/kg)] for FVIII:C.

The following table provides dosing guidelines for pediatric and adult patients with von Willebrand Disease.7-10

Table 2: Dosage Guidelines for Prophylaxis During Surgery and Invasive Procedure of von Willebrand Disease (Except Type 3 Subjects Undergoing Major Surgery)
Minor Surgery/Bleeding
   VWF:RCo

Target

FVIII:C Activity Levels
 Pre-operative/pre- procedure dose:  

Adults: 60 IU VWF:RCo/kg body weight.

 

Pediatrics: 75 IU VWF:RCo/kg body weight.
 40-50 IU/dL
 Maintenance dose:  

Adults: 40 to 60 IU VWF:RCo/kg body weight at 8 to 12 hour intervals as clinically needed  for 1-3 days.   

 

Pediatrics: 50 to 75 IU VWF:RCo/kg body weight at 8 to 12 hour intervals as clinically needed for 1-3 days.
 40-50 IU/dL
 Safety Monitoring: Peak and trough at least once daily   Peak and trough at least once daily
 Therapeutic Goal  (Trough)* : >50 IU/dL  >50 IU/dL
 Safety Parameter†: Should not exceed 150 IU/dL  

     Should not exceed 150 IU/dL

*
 The therapeutic goal is referenced in the NHLBI Guidelines.11 
 The safety paramenter is extracted from Mannucci 2009.12 
Major Surgery/Bleeding
   VWF:RCo

Target

FVIII:C Activity Levels
 Pre-operative/pre- procedure dose:  

Adults: 60 IU VWF:RCo/kg body weight.



Pediatrics: 75 IU VWF:RCo/kg body weight.
 100 IU/dL
 Maintenance dose:  

Adults: 40 to 60 IU VWF:RCo/kg body weight at 8 to 12 hour intervals as clinically needed  for atleast 3-7 days.   



Pediatrics: 50 to 75 IU VWF:RCo/kg body weight at 8 to 12 hour intervals as clinically needed for atleast 3-7 days.
 100 IU/dL
 Safety Monitoring: Peak and trough at least daily  Peak and trough at least daily
 Therapeutic Goal  (Trough)* : >50 IU/dL >50 IU/dL
 Safety Parameter : Should not exceed 150 IU/dL  

Should not exceed 150 IU/dL

Reconstitution

Always Use Aseptic Technique

  1. Warm diluent (Sterile Water for Injection, USP) and concentrate (Alphanate) to at least room temperature (but not above 37 °C).
  2. Remove the plastic flip off cap from the diluent vial.
  3. Gently swab the exposed stopper surface with a cleansing agent such as alcohol trying to avoid leaving any excess cleansing agent on the stopper.
  4. Open the Mix2Vial® package by peeling away the lid (Figure 1). Leave the Mix2Vial in the clear outer packaging.
  5. Place the diluent vial upright on an even surface and hold the vial tight and pick up the Mix2Vial in its clear outer packaging. Holding the diluent vial securely, push the blue end of the Mix2Vial vertically down through the diluent vial stopper (Figure 2).
  6. While holding onto the diluent vial, carefully remove the clear outer packaging from the Mix2Vial set, ensuring the Mix2Vial remains attached to the diluent vial (Figure 3).
  7. Place the product vial upright on an even surface, invert the diluent vial with the Mix2Vial attached.
  8. While holding the product vial securely on a flat surface, push the clear end of the Mix2Vial set vertically down through the product vial stopper (Figure 4). The diluent will automatically transfer out of its vial into the product vial. (NOTE: If the Mix2Vial is connected at an angle, the vacuum may be released from the product vial and the diluent will not transfer into the product vial.) 
  9. With the diluent and product vials still attached to the Mix2Vial, gently swirl the product vial to ensure the product is fully dissolved (Figure 5). Reconstitution requires less than 5 minutes. Do not shake the vial.
  10. Disconnect the Mix2Vial into two separate pieces (Figure 6) by holding each vial adapter and twisting counterclockwise.  After separating, discard the diluent vial with the blue end of the Mix2Vial.
  11. Draw air into an empty, sterile syringe. Keeping the product vial upright with the clear end of the Mix2Vial attached, screw the disposable syringe onto the luer lock portion of the Mix2Vial device by pressing and twisting clockwise. Inject air into the product vial. 
  12. While keeping the syringe plunger depressed, invert the system upside down and draw the reconstituted product into the syringe by pulling the plunger back slowly (Figure 7).
  13. When the reconstituted product has been transferred into the syringe, firmly hold the barrel of the syringe and the clear vial adapter (keeping the syringe plunger facing down) and unscrew the syringe from the Mix2Vial (Figure 8). Hold the syringe upright and push the plunger until no air is left in the syringe. Attach the syringe to a venipuncture set.
  14. NOTE: If the same patient is to receive more than one vial of concentrate, the contents of two vials may be drawn into the same syringe through a separate unused Mix2Vial set before attaching to the venipuncture set. 
  15. Use the prepared drug as soon as possible within 3 hours after reconstitution.
  16. After reconstitution, parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. When reconstitution procedure is strictly followed, a few small particles may occasionally remain. The Mix2Vial set will remove particles and the labeled potency will not be reduced.
  17. Discard all administration equipment after use into the appropriate safety container. Do not reuse.
Reconstitution Figure

Administration

Instruction for Use:
Alphanate is for intravenous use only after reconstitution. Use plastic disposable syringes. Do not refrigerate after reconstitution. Reconstituted Alphanate may be stored at room temperature (not to exceed 30 °C) prior to administration, but administer intravenously within three hours.

 

Discard any unused contents into the appropriate safety container.
Do not administer Alphanate at a rate exceeding 10 mL/minute.

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