Alphanate

• Hemophilia A:
  Treatment and control of bleeding episodes and for perioperative management in patients with congenital Factor VIII deficiency (Hemophilia A).
• Von Willebrand Disease (VWD):
  Treatment and control of bleeding episodes in patients with Von Willebrand Disease, particularly those with severe deficiency or those unresponsive to desmopressin (DDAVP).
• Surgical Prophylaxis:
  Prevention of bleeding during and after surgical procedures in Hemophilia A and VWD patients.
• Other Bleeding Disorders:
  Used off-label for rare bleeding disorders involving combined Factor VIII and von Willebrand factor deficiency.

• Route: Intravenous infusion only.
• Hemophilia A:
• Dose individualized based on patient’s Factor VIII activity level, severity of bleeding, and clinical response.
• Initial doses typically range from 20 to 40 IU/kg body weight, repeated every 8 to 24 hours depending on severity.
• Von Willebrand Disease:
• Dose depends on severity, bleeding type, and patient response.
• Generally, initial dose of 40 to 80 IU/kg Factor VIII activity, adjusted to achieve desired plasma levels of Factor VIII and von Willebrand factor.
• Pediatrics:
  Similar dosing guidelines as adults; careful monitoring of Factor VIII and VWF levels is essential.
• Elderly:
  Dose adjustment based on renal and cardiovascular status; monitor closely.
• Special Populations:
  No dose adjustment specifically for renal or hepatic impairment; dose guided by clinical response and factor activity levels.
• Administration Instructions:
• Reconstitute lyophilized powder with provided sterile water for injection.
• Administer via slow intravenous injection or infusion over several minutes.
• Do not mix with other drugs.
• Duration:
  Based on clinical condition and bleeding control; may require repeated doses.

Alphanate contains concentrated human plasma-derived Factor VIII and von Willebrand factor (VWF). Factor VIII acts as a cofactor for Factor IXa in the coagulation cascade, accelerating conversion of Factor X to Xa, which leads to fibrin clot formation and cessation of bleeding. VWF stabilizes circulating Factor VIII and mediates platelet adhesion to vascular subendothelium at injury sites, facilitating primary hemostasis. The combined replacement of both proteins restores effective clotting in patients deficient in either or both, controlling bleeding episodes and preventing hemorrhage during invasive procedures.

• Absorption: Administered intravenously; 100% bioavailability.
• Distribution: Factor VIII distributes mainly within the intravascular compartment; volume of distribution approximates plasma volume (~50–70 mL/kg).
• Metabolism: Catabolized by reticuloendothelial system and endothelial cells.
• Half-life:
• Factor VIII: Approximately 8 to 12 hours, variable among individuals.
• VWF: Half-life approximately 12 to 22 hours.
• Elimination: Degraded into peptides and amino acids; no renal excretion of active protein.

• Pregnancy:
  No well-controlled studies in pregnant women; use only if clearly needed. Plasma-derived products are considered relatively safe in pregnancy due to their critical therapeutic role.
• Lactation:
  Unknown if excreted in human milk; expected to be safe based on protein size and degradation. Use during breastfeeding only if clearly indicated.

• Primary Class: Hemostatic Agent
• Subclass: Plasma-derived Coagulation Factor Replacement Therapy

• Known hypersensitivity to human plasma-derived proteins or any component of the formulation
• History of anaphylactic or severe hypersensitivity reactions to Factor VIII or VWF products
• Presence of inhibitors (neutralizing antibodies) to Factor VIII may reduce efficacy; requires specialized management

• Hypersensitivity Reactions:
  Monitor for allergic reactions including anaphylaxis; discontinue if severe reaction occurs.
• Development of Inhibitors:
  Patients may develop neutralizing antibodies against Factor VIII, reducing therapeutic effect and complicating management. Regular inhibitor testing is advised.
• Thromboembolic Events:
  Risk increased in patients with predisposing conditions; monitor for signs of thrombosis.
• Transmission of Infectious Agents:
  Despite rigorous viral screening and inactivation, theoretical risk of transmission of viruses or prions exists.
• Monitoring:
  Close monitoring of coagulation parameters and clinical response required to guide dosing.

• Common:
• Injection site reactions (pain, erythema)
• Headache
• Fever
• Nausea
• Serious:
• Hypersensitivity or allergic reactions including anaphylaxis
• Development of Factor VIII inhibitors
• Thrombosis or thromboembolic events
• Timing:
  Adverse effects may occur during or shortly after infusion.

• No known direct drug interactions; however, concurrent use of anticoagulants or antiplatelet agents may alter bleeding risk.
• Immunosuppressive agents may affect inhibitor development.

• Current hemophilia management guidelines endorse plasma-derived Factor VIII/VWF concentrates like Alphanate for bleeding control and surgical prophylaxis.
• Enhanced viral inactivation techniques have improved safety profiles.
• Monitoring for inhibitors remains a cornerstone of therapy.

• Store lyophilized powder at 2°C to 25°C (36°F to 77°F).
• Protect from freezing and excessive heat.
• Keep in original packaging to protect from light.
• Reconstituted solution should be used immediately or stored at room temperature for up to 3 hours; do not refrigerate after reconstitution.