Alphanate

Alphanate

factor viii

Manufacturer:

Grifols

Distributor:

The Glory Medicina
/
DKSH
Full Prescribing Info
Contents
Antihemophilic factor (human), solvent detergent treated.
Description
Alphanate is supplied in sterile, lyophilized form in a single dose vials accompanied by a suitable volume of diluent (Sterile Water for Injection, USP), according to AHF potency. Each vial is labeled with the Factor VIII:C potency expressed in AHF international units. Alphanate is packaged with a double-ended transfer needle and microaggregate filter for use in administration.
Alphanate is a single dose, sterile, lyophilized concentrate of Factor VIII (AHF) intended for IV administration in the treatment of hemophilia A or acquired factor VIII deficiency.
Alphanate is prepared from pooled human plasma by cryoprecipitation of the Factor VIII, fractional solubilization and further purification employing heparin-coupled, cross-linked agarose, which has an affinity to the heparin-binding domain of vWf/FVIII:C complex. Alphanate is treated with a mixture of tri (n-butyl) phosphate (TNBP) and polysorbate 80 to reduce the risks of transmission of viral infection. In order to provide an additional safeguard against potential nonlipid enveloped viral contaminants, Alphanate is also subjected to an 80°C heat treatment step for 72 hrs. However, no procedure has been shown to be totally effective in removing viral infectivity from coagulation factor products.
Alphanate is labeled with the antihemophilic factor potency (Factor VIII:C activity) expressed in international units (iu)/vial, which is referenced to the WHO international standard.
Alphanate contains albumin (human) as a stabilizer, resulting in a final container with a specific activity of at least 5 iu FVIII:C/mg total proteins. Prior to the addition of the albumin (human) stabilizer, the specific activity is significantly higher.
When reconstituted with the appropriate volume of Sterile Water for Injection, USP, Alphanate contains 0.3-0.9 g albumin (human)/100 mL; not more than 5 mmol calcium/L; not more than 750 mcg glycine/iu FVIII:C; not more than 1 unit heparin/mL; 10-40 mmol histidine/L; not more than 0.1 mg imidazole/mL; 50-200 mmol arginine/L; not more than 1 mcg polyethylene glycol and polysorbate 80/iu FVIII:C; not more than 10 mEq sodium/vial; and not more than 0.1 mcg TNBP/iu FVIII:C.
Action
Pharmacology: Antihemophilic factor (human) is a constituent of normal plasma and is required for clotting. The administration of Alphanate temporarily increases the plasma level of this clotting factor, thus minimizing the hazard of hemorrhage. Following the administration of Alphanate during clinical trials, the mean in vivo half-life of Factor VIII observed in 12 adult subjects with severe hemophilia A was 17.9±9.6 hrs. In this same study, the in vivo recovery was 96.7±14.5% at 10 min post-infusion. Recovery at 10 min post-infusion was also determined as 2.4±0.4 iu FVIII rise/dL plasma per iu FVIII infused per kg body weight.
The solvent detergent treatment process has been shown by Horowitz, et al, to provide a high level of virus kill without compromising protein structure and function. The susceptibility of human pathogenic viruses eg, the human immunodeficiency viruses, hepatitis viruses, as well as marker viruses eg, sindbis virus and vesicular stomatitis virus (VSV), to inactivation by organic solvent detergent treatment has been discussed in the literature.
In vitro inactivation studies to evaluate the solvent detergent treatment step used in the manufacture of Alphanate employed an assay with a sensitivity of 2 logs of virus for the marker virus, VSV and sindbis virus. The studies demonstrated a log kill of ≥4.1 for VSV and ≥4.7 for sindbis virus, ≥11.1 logs of HIV-1 and ≥6.1 logs of HIV-2 were inactivated by the solvent detergent treatment step. The number of viral particles inactivated by the process represents the maximum amount of virus added initially to the sample, thus the results of the study indicate that all the added HIV virus was killed.
In another study, the dry heat cycle of 80°C for 72 hrs of the Alphanate manufacturing process was shown to inactivate ≥5.8 logs of hepatitis A virus (HAV).
In a different study, the following steps in the manufacturing process of Alphanate were evaluated for virus reduction/removal capability: Precipitation with 3.5% polyethylene glycol (PEG), solvent detergent treatment with 0.3% tri-n-butyl phosphate and 1% polysorbate 80, heparin actigel ALD chromatography, lyophilization of factor VIII and heat treatment at 80°C for 72 hrs. The following viruses were used in these studies: Bovine herpes (BHV), bovine viral diarrhea virus (BVD), human poliovirus Sabin type 2 (POL), canine parvovirus (CPV) and human immunodeficiency virus, type 1 (HIV-1).
The table summarizes the reduction factors for each virus evaluated for each viral inactivation/removal step validated in the manufacturing process of Alphanate.
However, no treatment method has yet been shown capable of totally eliminating all potential infective viruses in preparations of coagulation factor concentrates.

Click on icon to see table/diagram/image
Indications/Uses
Prevention and control of bleeding in patients with Factor VIII deficiency due to hemophilia A or acquired Factor VIII deficiency. No clinical trials have as yet been conducted using Alphanate for treatment of von Willebrand's disease therefore Alphanate is not approved for this use.
Dosage/Direction for Use
Adult: Following reconstitution with the supplied diluent, Alphanate should be administered IV within 3 hrs after reconstitution to avoid the potential ill effect of any inadvertent bacterial contamination occurring during reconstitution. Alphanate may be administered by injection (plastic disposable syringes are recommended). Administer at room temperature, do not refrigerate after reconstitution and discard any unused contents into the appropriate safety container.
Antihemophilic factor potency (Factor VIII:C activity) is expressed in international units (iu) on the product label. One unit approximates the activity in 1 mL of normal human plasma. Replacement therapy studies have shown a linear dose-response relationship with a 2-2.5% increase in Factor VIII activity for each factor of 0.5 iu/kg can be calculated.
The following formula provides a guide for dosage calculation the plasma Factor VIII may vary depending upon the age, weight, severity of hemorrhage or surgical procedure of the patient:

Click on icon to see table/diagram/image

Mild to moderate hemorrhages can usually be treated with a single administration of Alphanate sufficient to raise the plasma Factor VIII level to 20-30%. In the event of more serious hemorrhage, the patient's plasma Factor VIII level should be raised to 30-50%. Infusions are generally required at twice daily intervals over several days.
Surgery in patients with Factor VIII requires that postoperatively the Factor VIII level be raised to 50-80% and maintained at or above 30% for approximately 2 weeks. For dental extractions, the Factor VIII level should be raised to 50% immediately prior to the procedure; additional Alphanate may be given if bleeding recurs.
In patients with severe Factor VIII deficiency who experience frequent hemorrhages. Alphanate may be administered prophylactically on a daily or every other day schedule to raise the Factor VIII level to approximately 15%.
Factor VIII levels should be monitored periodically to evaluate individual patient response dose to regime.
Administration: Use aseptic technique.
Reconstitution: Warm diluent (Sterile Water for Injection, USP) and concentrate (Alphanate) to at least room temperature (but not above 37°C).
Remove plastic caps from the diluent and concentrate vials.
Swab the exposed stopper surfaces with a cleansing agent eg, alcohol. Do not leave excess cleansing agent on the stoppers.
Remove cover from one end of the double-ended transfer needle. Insert the exposed end of the needle through the center of the stopper in the diluent vial.
Remove plastic cap from the other end of the double-ended transfer needle now seated in the stopper of the diluent vial. To reduce any foaming, invert the vial of diluent and insert the exposed end of the needle through the center of the stopper in the concentrate vial at an angle, making certain that the diluent vial is always above the concentrate vial. The angle of insertion directs the flow of diluent against the side of the concentrate vial. There should be enough vacuums in the vial to transfer all of the diluent.
Disconnect the 2 vials by removing the transfer needle from the diluent vial stopper. Remove the double-ended transfer needle from the concentrate vial and discard the needle into the appropriate safety container.
Let the vial stand contents are in solution, then gently swirl until all concentrate is dissolved. Reconstitution requires <5 min.
Do not shake the contents of the vial. Do not invert the concentrate vial until ready to withdraw contents.
Use as soon as possible after reconstitution.
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 microaggregate filter will remove particles and the labeled potency will not be reduced.
Administration by Syringe: Peel cover from microaggregate filter package and securely install the syringe into the exposed Luer inlet of the filter, using a slight clockwise twisting motion.
Remove filter from packaging. Remove protective cover from the spike end of the filter.
Pull back plunger drawing sufficient air into the syringe to allow reconstituted product to be withdrawn.
Insert the spike end of the filter into the reconstituted concentrate vial. Inject air and withdraw the reconstituted product from the vial into the syringe.
Remove the filter from the syringe; discard the filter and the empty concentrate vial into the appropriate safety container. Attach syringe to an infusion set; expel air from the syringe and infusion set. Perform venipuncture and administer slowly at a rate not exceeding 10 mL/min.
If the patient is to receive >1 vial of concentrate, the infusion set will allow administration of multiple vials to be performed with a single venipuncture.
Discard all administration equipment after use into the appropriate safety container. Do not re-use.
Contraindications
None known.
Warnings
Because Alphanate is made from pooled human plasma, it may carry a risk of transmitting infectious agents eg, viruses and theoretically, the Creutzieldt-Jakob disease (CJD) agent. Stringent procedures designed to reduce the risk of adventitious agent transmission have been employed in the manufacture of Alphanate, from the screening of plasma donors and the collection and testing of plasma, through the application of viral elimination/reduction steps eg, solvent detergent and heat treatment in the manufacturing process. Despite these measures, such products can still potentially transmit disease; therefore, the risk of infectious agents cannot be totally eliminated. The physician should weigh the risk and benefits of the use of Alphanate and should discuss these with the patient.
Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections particularly hepatitis C. Incubation in a solvent detergent mixture during the manufacturing process is designed to reduce the risk of transmitting viral infection. However, scientific opinion encourages hepatitis A and hepatitis B vaccinations for patients with hemophilia at birth or at the time of prognosis.
Special Precautions
General: Alphanate should not be administered at a rate exceeding 10 mL/min. Rapid administration of a Factor VIII concentrate may result in vasomotor reactions.
Some patients develop inhibitors to Factor VIII. Factor VIII inhibitors are circulating antibodies (ie, globulins) that neutralize the procoagulant activity of Factor VIII. No studies have been conducted with Alphanate to evaluate inhibitor formation. Therefore, it is not known whether there are greater, lesser or the same risks of developing inhibitors due to the use of Alphanate than there are with other antihemophilic factor preparations. Patients with these inhibitors may not respond to treatment with antihemophilic factor (human) or the response may be much less than would otherwise be expected; therefore, larger doses of antihemophilic factor (human) are often required. The management of bleeding in patients with inhibitors requires careful monitoring, especially if surgical procedures are indicated.
Nursing personnel and others who administer Alphanate should exercise appropriate caution when handling due to the risk of exposure to viral infection. Discard any unused contents into the appropriate safety container. Discard administration equipment after single use into the appropriate safety container. Do not re-sterilize components.
Patients should be informed of the early symptoms and signs of hypersensitivity reactions, including hives, generalized urticaria, chest tightness, dyspnea, wheezing, faintness, hypotension and anaphylaxis. Patients should be advised to discontinue use of Alphanate and contact their physician and/or seek immediate emergency care, depending on the severity of the reaction, if these symptoms occur.
Some viruses eg, parvovirus B19 or hepatitis A are particularly difficult to remove or inactivate at this time. Parvovirus B19 may most seriously affect sero-negative pregnant women or immunocompromised individuals. The majority of parvovirus B19 and hepatitis A infections are acquired by environmental (natural) sources.
Use in pregnancy: Animal reproduction studies have not been conducted with Alphanate. Therefore, it is not known whether it can cause fetal harm when administered to a pregnant woman or affect the reproductive capacity of a woman. Alphanate should be given to a pregnant woman only if clearly needed.
Use in children: Clinical trials for safety and effectiveness in pediatric patients ≤16 years have been conducted. Across well controlled half-life and recovery clinical trial in patients previously treated with factor VIII concentrates for hemophilia A, the one pediatric patient receiving Alphanate (solvent detergent) responded similarly when compared with 12 adult patients. No adverse events were reported in either pediatric or adult patients with Alphanate.
Use In Pregnancy & Lactation
Use in pregnancy: Animal reproduction studies have not been conducted with Alphanate. Therefore, it is not known whether it can cause fetal harm when administered to a pregnant woman or affect the reproductive capacity of a woman. Alphanate should be given to a pregnant woman only if clearly needed.
Adverse Reactions
Adverse reactions may include urticaria, fever, chills, nausea, vomiting, headache, somnolence or lethargy.
Occasionally, mild reactions occur following the administration of antihemophilic factor (human) eg, allergic reactions, chills, nausea or stinging at the infusion site. If a reaction is experienced and the patient requires additional antihemophilic factor (human), product from a different lot should be administered.
Massive doses of antihemophilic factor (human) have rarely resulted in acute hemolytic anemia, increased bleeding tendency or hyperfibrinogenemia. Alphanate contains blood group specific isoagglutins and when large and/or frequent doses are required in patients of blood groups A, B or AB, the patient should be monitored for signs of intravascular hemolysis and falling hematocrit. Should this condition occur, thus leading to progressive hemolytic anemia, the administration of serologically compatible type O red blood cells should be considered or the administration of antihemophilia factor (human) produced from group specific plasma should be considered.
Storage
Store at temperatures between 2 °C and 8°C. Do not freeze to prevent damage to diluent vial. May be stored from refrigeration, record the data removed on the space provided on the carton.
MIMS Class
ATC Classification
B02BD02 - coagulation factor VIII ; Belongs to the class of blood coagulation factors. Used in the treatment of hemorrhage.
Presentation/Packing
Vial 250 iu x 1's. 500 iu x 1's. 1000 iu x 1's. 1500 iu x 1's.
Exclusive offer for doctors
Register for a MIMS account and receive free medical publications worth $768 a year.
Sign up for free
Already a member? Sign in