Introduction
Jivi (damoctocog alfa pegol) is a recombinant antihemophilic factor indicated for the control and prevention of bleeding episodes, perioperative management, and routine prophylaxis in adults and adolescents with hemophilia A. It is an extended half-life factor VIII product created through PEGylation technology, offering prolonged protection and reduced infusion frequency compared to standard factor VIII concentrates.
Mechanism of Action
Jivi is a B-domain deleted recombinant factor VIII molecule covalently bonded to polyethylene glycol (PEG). It replaces the missing or deficient endogenous factor VIII in hemophilia A patients. Factor VIII serves as a cofactor for factor IX in the activation of factor X, which is essential for the conversion of prothrombin to thrombin in the coagulation cascade. Thrombin then converts fibrinogen to fibrin, forming a stable clot. The PEGylation extends the circulating half-life of the molecule by reducing renal clearance and protecting it from proteolytic degradation.
Indications
- Control and prevention of bleeding episodes in hemophilia A
- Perioperative management of bleeding in hemophilia A
- Routine prophylaxis to prevent or reduce the frequency of bleeding episodes in hemophilia A
- Approved for use in adults and adolescents (12 years and older)
Dosage and Administration
Dosing: Individualized based on the severity of factor VIII deficiency, bleeding location and severity, and patient's clinical condition Prophylaxis:- 30-40 IU/kg every other day OR
- 45-60 IU/kg twice weekly
- Minor bleeding: 15-30 IU/kg (may require repeat doses every 24-48 hours)
- Moderate bleeding: 20-40 IU/kg (may require repeat doses every 24-48 hours)
- Severe bleeding: 40-50 IU/kg (may require repeat doses every 12-24 hours)
- Minor surgery: 30-60 IU/kg (repeat may be needed after 24-48 hours)
- Major surgery: 50-80 IU/kg preoperatively (then monitor levels and administer every 12-24 hours)
Pharmacokinetics
Absorption: Administered intravenously, resulting in complete bioavailability Distribution: Volume of distribution approximately 41-44 mL/kg Metabolism: Primarily metabolized via proteolytic pathways; PEG portion metabolized by hepatic microsomal enzymes Elimination: Terminal half-life approximately 19 hours (1.6-1.8 times longer than standard rFVIII) Excretion: Metabolic products excreted in urine and fecesContraindications
- Known hypersensitivity to damoctocog alfa pegol or any component of the formulation
- History of anaphylactic reaction to the product
- Patients with known hypersensitivity to hamster proteins
Warnings and Precautions
Inhibitor development: Monitor patients for development of factor VIII inhibitors (neutralizing antibodies) Hypersensitivity reactions: Anaphylactic reactions possible; observe patients during and after administration Cardiovascular events: Use with caution in patients with cardiovascular disease due to potential thrombotic risk PEG-related concerns: Theoretical concerns about PEG accumulation with long-term use; monitor for unusual symptoms Viral safety: Although produced from recombinant technology, theoretical risk of transmitting infectious agentsDrug Interactions
- No formal drug interaction studies conducted
- Theoretical interactions with anticoagulants and antiplatelet agents may increase bleeding risk
- Use caution with other PEGylated products due to potential for PEG accumulation
Adverse Effects
Most common (>10%):- Headache
- Diarrhea
- Nausea
- Pyrexia
- Dizziness
- Injection site reactions
- Fatigue
- Arthralgia
- Rash
- Factor VIII inhibition
- Anaphylaxis
- Inhibitor development
- Thrombotic events (rare)
Monitoring Parameters
- Factor VIII activity levels (especially during initial treatment and surgery)
- Signs and symptoms of bleeding
- Development of inhibitors (Bethesda assay if clinical response decreases)
- Vital signs during infusion
- Signs of hypersensitivity reactions
- Liver function tests (periodically)
- PEG accumulation markers (in long-term therapy)
Patient Education
- Recognize signs of bleeding and when to seek treatment
- Proper storage and reconstitution techniques
- Importance of regular prophylaxis dosing
- Recognition of hypersensitivity reactions (hives, wheezing, chest tightness)
- Importance of regular follow-up with hematologist
- Carry identification indicating hemophilia diagnosis and treatment
- Report any decreased response to treatment
- Do not share medication or administration equipment
- Keep a treatment log including bleeding episodes and doses administered
References
1. US Food and Drug Administration. Jivi prescribing information. 2018. 2. Lissitchkov T, et al. Haemophilia. 2019;25(1):73-80. 3. Tiede A, et al. Haemophilia. 2020;26(1):47-55. 4. Mahlangu J, et al. Blood. 2018;132(Supplement 1):116. 5. European Medicines Agency. Jivi assessment report. 2018. 6. ClinicalTrials.gov: NCT02234323, NCT03061188 7. Pipe SW, et al. J Thromb Haemost. 2021;19(1):98-108. 8. National Hemophilia Foundation. MASAC recommendations concerning products licensed for the treatment of hemophilia. 2022.