Jivi: Uses, Dosage & Side Effects
A PEGylated recombinant factor VIII for the treatment and prophylaxis of bleeding in patients with hemophilia A aged 12 years and older
Jivi (damoctocog alfa pegol) is a prescription PEGylated recombinant coagulation factor VIII indicated for the treatment and prophylaxis of bleeding episodes in previously treated patients with hemophilia A (congenital factor VIII deficiency) aged 12 years and older. Its site-specific PEGylation with a 60 kDa branched polyethylene glycol molecule extends the plasma half-life to approximately 17–19 hours, allowing less frequent prophylactic infusions—typically every 5 to 7 days. Clinical trials (PROTECT VIII) demonstrated that Jivi effectively reduces annualized bleeding rates and provides reliable hemostatic coverage for surgical procedures, while maintaining a favorable safety profile.
Quick Facts: Jivi
Key Takeaways
- Jivi (damoctocog alfa pegol) is a PEGylated recombinant factor VIII designed for less frequent dosing in hemophilia A patients aged 12 years and older, with prophylactic infusions possible every 5 to 7 days.
- The site-specific PEGylation extends the half-life to approximately 17–19 hours, compared to roughly 12 hours for standard recombinant factor VIII products, reducing the treatment burden on patients.
- In the pivotal PROTECT VIII trial, prophylactic regimens with Jivi reduced the median annualized bleeding rate to 0–4.1 bleeds per year depending on dosing frequency, demonstrating robust hemostatic efficacy.
- Jivi is administered intravenously after reconstitution and can be self-administered at home following proper training by a healthcare professional, supporting patient independence and adherence.
- The most common side effects include headache, cough, and injection site reactions; development of factor VIII inhibitors is an important but uncommon risk that requires regular monitoring.
What Is Jivi and What Is It Used For?
Jivi contains the active substance damoctocog alfa pegol, a B-domain-deleted recombinant human coagulation factor VIII that has been site-specifically PEGylated with a 60 kDa branched polyethylene glycol (PEG) molecule. It is produced using recombinant DNA technology in baby hamster kidney (BHK) cells. The PEGylation process involves covalently attaching the PEG molecule to a specific cysteine residue in the truncated B-domain region of the factor VIII protein, a modification that protects the molecule from rapid clearance while preserving its full procoagulant activity.
Hemophilia A is a hereditary bleeding disorder caused by a deficiency or dysfunction of coagulation factor VIII, a critical component of the intrinsic pathway of the blood clotting cascade. Affecting approximately 1 in 5,000 male births worldwide according to the World Federation of Hemophilia (WFH), hemophilia A leads to spontaneous and trauma-related bleeding episodes, particularly into joints (hemarthrosis), muscles, and soft tissues. Without adequate treatment, recurrent joint bleeds cause progressive arthropathy, chronic pain, and significant disability. Factor VIII replacement therapy has been the cornerstone of hemophilia A management for decades, and the development of extended half-life (EHL) products like Jivi represents a significant advancement in reducing treatment burden.
Jivi is specifically indicated for the following clinical uses in previously treated patients (PTPs) with hemophilia A aged 12 years and older:
- On-demand treatment: Control and treatment of acute bleeding episodes, including spontaneous bleeds into joints, muscles, and soft tissues, as well as traumatic bleeds
- Routine prophylaxis: Regular preventive infusions to reduce the frequency of bleeding episodes and protect joint health over the long term
- Perioperative management: Prevention and management of bleeding during and after surgical procedures, including both major and minor surgery
The key therapeutic advantage of Jivi lies in its extended plasma half-life. Standard recombinant factor VIII products typically have a half-life of approximately 10–12 hours, necessitating infusions three to four times per week for adequate prophylaxis. Jivi’s PEGylation extends the terminal half-life to approximately 17–19 hours in adults, enabling prophylactic dosing intervals of every 5 days, and in some patients, every 7 days. This reduction in infusion frequency can substantially improve quality of life, treatment adherence, and venous access preservation—particularly important for patients who require lifelong therapy.
What Should You Know Before Taking Jivi?
Before initiating treatment with Jivi, a thorough medical evaluation by a hematologist experienced in the management of hemophilia is essential. Several important factors must be considered to ensure safe and effective use of this medication. Your healthcare provider will assess your individual risk factors, treatment history, and overall health status to determine whether Jivi is the appropriate factor VIII product for your specific clinical situation.
Contraindications
Jivi must not be used in the following circumstances:
- Hypersensitivity: Known allergy to damoctocog alfa pegol, the parent molecule octocog alfa (recombinant factor VIII), polyethylene glycol (PEG), or any of the excipients listed in the formulation
- Hamster protein allergy: Known hypersensitivity to hamster (BHK) proteins, as the product is manufactured in baby hamster kidney cells and may contain trace amounts of hamster proteins
Warnings and Precautions
Several important precautions should be discussed with your healthcare provider before and during treatment with Jivi:
- Hypersensitivity reactions: Allergic-type hypersensitivity reactions, including anaphylaxis, are possible with Jivi. Signs may include hives, generalized urticaria, chest tightness, wheezing, hypotension, and anaphylaxis. If such reactions occur, discontinue the infusion immediately and seek emergency medical care. Patients with known allergies to the constituents of the product or to hamster proteins may be at higher risk.
- Inhibitor development: Patients should be carefully monitored for the development of factor VIII inhibitors using appropriate clinical observations and laboratory tests (Bethesda assay). The risk of inhibitor formation is generally lower in previously treated patients (PTPs) compared to previously untreated patients (PUPs). Jivi has not been studied in PUPs.
- PEG accumulation: As Jivi contains a 60 kDa PEG molecule, there is a theoretical concern regarding long-term PEG accumulation in the body. In preclinical animal studies, PEG-related vacuolation was observed in certain tissues (choroid plexus, kidneys). The clinical significance of these findings in humans receiving long-term treatment remains under investigation. Your doctor may periodically assess organ function during prolonged treatment.
- Cardiovascular events: Factor VIII replacement therapy in hemophilia patients does not eliminate the risk of cardiovascular events. Patients with cardiovascular risk factors should receive appropriate preventive care as recommended for the general population.
- Catheter-related complications: If a central venous access device (CVAD) is required for Jivi administration, the risks of CVAD-related complications, including local infections, bacteremia, and catheter site thrombosis, should be considered.
Pregnancy and Breastfeeding
Hemophilia A is an X-linked recessive disorder that almost exclusively affects males. Therefore, clinical experience with the use of factor VIII products during pregnancy and breastfeeding in women with hemophilia A is extremely limited. Animal reproduction studies have not been conducted with Jivi specifically.
Women who are carriers of hemophilia A may have reduced factor VIII levels and may require factor VIII replacement for surgical procedures or during delivery. In such cases, the decision to use Jivi should be made by a specialist hematologist in consultation with an obstetrician, carefully weighing the potential benefits against the unknown risks. It is not known whether damoctocog alfa pegol or the PEG component is excreted in human breast milk.
How Does Jivi Interact with Other Drugs?
Jivi (damoctocog alfa pegol), like other recombinant factor VIII products, is a large protein molecule that is metabolized through normal catabolic pathways rather than through hepatic cytochrome P450 (CYP) enzyme systems. This fundamental pharmacokinetic property means that Jivi is unlikely to participate in traditional drug-drug interactions involving enzyme inhibition, induction, or competition for metabolic pathways. No formal drug interaction studies have been conducted with Jivi in human subjects.
However, it is important to understand how certain medication classes may theoretically affect hemostasis in patients receiving Jivi, and to discuss all medications with your healthcare provider:
Medications Affecting Hemostasis
| Medication Class | Examples | Potential Effect | Clinical Consideration |
|---|---|---|---|
| Anticoagulants | Warfarin, heparin, DOACs | May counteract procoagulant effect of Jivi | Rarely co-prescribed; specialist guidance required |
| Antiplatelet agents | Aspirin, clopidogrel | Impaired platelet aggregation; increased bleeding risk | Use with caution; monitor for bleeding |
| NSAIDs | Ibuprofen, naproxen, diclofenac | Impaired platelet function; GI bleeding risk | COX-2 inhibitors may be preferred alternatives |
| Antifibrinolytics | Tranexamic acid, aminocaproic acid | Enhanced clot stability; additive hemostatic effect | Often used as adjunctive therapy, especially for mucosal bleeds |
| Desmopressin (DDAVP) | Desmopressin acetate | Increases endogenous factor VIII release | Not typically co-administered with exogenous factor VIII |
| Emicizumab | Hemlibra | Bispecific antibody mimicking factor VIII; may complicate factor VIII monitoring | Switching protocols require specialist hematology guidance |
Laboratory Test Interactions
An important practical consideration when using Jivi is its interaction with laboratory coagulation assays. The PEGylated structure of damoctocog alfa pegol can affect the results of certain factor VIII activity assays. Specifically:
- One-stage clotting assay (aPTT-based): This is the recommended method for monitoring factor VIII activity levels during Jivi treatment. Results from one-stage assays are generally consistent and reliable for dose adjustment and pharmacokinetic monitoring.
- Chromogenic substrate assay: May underestimate factor VIII activity levels when used with Jivi. If a chromogenic assay is used, results may appear lower than actual factor VIII activity, potentially leading to unnecessary dose increases.
It is essential that your hemophilia treatment center uses the appropriate assay method when monitoring your factor VIII levels during Jivi therapy. The International Society on Thrombosis and Haemostasis (ISTH) has published specific guidance on monitoring extended half-life factor VIII concentrates to ensure accurate laboratory assessment.
What Is the Correct Dosage of Jivi?
Dosing of Jivi must be individualized by a healthcare professional experienced in the treatment of hemophilia A. The dose and frequency of administration depend on the clinical indication (prophylaxis, on-demand treatment of bleeds, or perioperative management), the severity and location of the bleeding episode, the patient’s body weight, and the individual pharmacokinetic response. One International Unit (IU) of factor VIII activity corresponds to the quantity of factor VIII in one milliliter of normal human plasma.
Prophylaxis (Adults and Adolescents ≥12 Years)
The primary goal of prophylaxis is to maintain factor VIII trough levels sufficient to prevent spontaneous bleeding, particularly hemarthrosis. The WFH guidelines recommend maintaining trough levels above 1–3 IU/dL for standard prophylaxis, though higher targets (3–5 IU/dL or above) may be appropriate for patients with target joints or active lifestyles. Jivi offers three flexible prophylactic dosing regimens:
| Regimen | Dose | Frequency | Expected Trough Level |
|---|---|---|---|
| Standard twice-weekly | 30–40 IU/kg | 2 times per week | 1–3 IU/dL |
| Every 5 days | 45–60 IU/kg | Every 5 days | 1–3 IU/dL |
| Weekly | 60 IU/kg | Every 7 days | ≥1 IU/dL |
Your hematologist may start with a twice-weekly regimen and, based on your individual pharmacokinetic profile and bleeding pattern, extend the dosing interval to every 5 days or weekly. The dose and interval should be adjusted based on the achieved trough levels and the clinical response (annualized bleeding rate).
On-Demand Treatment of Bleeding Episodes
For the treatment of acute bleeding episodes, the dose of Jivi is calculated based on the type and severity of the hemorrhage. The following general guidelines are recommended:
| Type of Bleed | Target Factor VIII Level | Recommended Dose | Dosing Frequency |
|---|---|---|---|
| Minor (early joint, minor muscle, oral) | 20–40 IU/dL | 10–20 IU/kg | Every 24–48 hours until resolved |
| Moderate (joint, muscle, hematoma) | 30–60 IU/dL | 15–30 IU/kg | Every 24–48 hours for 3–4 days or until resolved |
| Major (life-threatening, intracranial, GI, retroperitoneal) | 60–100 IU/dL | 30–50 IU/kg | Every 8–24 hours until resolved |
The required dose can be estimated using the following formula: Required dose (IU) = Body weight (kg) × Desired factor VIII rise (IU/dL) × 0.5. This is based on the empirical observation that approximately 2 IU/kg of factor VIII raises plasma factor VIII activity by approximately 1 IU/dL. However, individual recovery may vary, and pharmacokinetic-guided dosing is recommended for optimal outcomes.
Perioperative Management
For surgical procedures, the target factor VIII level and duration of replacement therapy depend on the type of surgery:
- Minor surgery: Target factor VIII level of 30–60 IU/dL for at least 1 day post-operatively, continuing until wound healing is achieved
- Major surgery: Target pre-operative factor VIII level of 80–100 IU/dL, maintained at 60–80 IU/dL for the first 3–6 days, then 30–60 IU/dL until wound healing is complete (typically 7–14 days)
Missed Dose
If you miss a scheduled prophylactic dose of Jivi, administer it as soon as you remember. Do not double the dose to make up for a missed infusion. Then resume your regular dosing schedule. If you are unsure about when to take the next dose, contact your hemophilia treatment center for guidance. Consistent adherence to the prophylactic regimen is crucial for maintaining adequate factor VIII levels and preventing breakthrough bleeding episodes.
Overdose
No cases of overdose with Jivi have been reported in clinical trials. However, as with any factor VIII concentrate, overdose could theoretically result in supraphysiological factor VIII activity levels. While short-term elevations above normal are generally well tolerated, sustained very high levels could theoretically increase the risk of thromboembolic events, particularly in patients with additional cardiovascular risk factors. In the event of a suspected overdose, monitor factor VIII activity levels and manage symptoms as clinically indicated. Contact your local poison control center or hemophilia treatment center for further guidance.
What Are the Side Effects of Jivi?
Like all medicines, Jivi can cause side effects, although not everybody gets them. The safety of Jivi has been evaluated in clinical studies involving over 200 previously treated patients with severe hemophilia A. The overall safety profile is consistent with what is expected from recombinant factor VIII products, with PEG-specific considerations related to long-term use. Understanding the potential side effects helps you and your healthcare team identify and manage any adverse events promptly.
Side effects are classified by frequency according to international conventions:
Common
May affect up to 1 in 10 people
- Headache
- Cough
- Injection site reactions (erythema, pain, swelling at the infusion site)
- Nausea
- Fever (pyrexia)
Uncommon
May affect up to 1 in 100 people
- Development of factor VIII inhibitors (neutralizing antibodies)
- Hypersensitivity reactions (urticaria, rash, pruritus)
- Dizziness
- Abdominal pain
- Insomnia
- Flushing
- Dysgeusia (altered taste perception)
Rare
May affect up to 1 in 1,000 people
- Anaphylaxis (severe allergic reaction with hypotension, breathing difficulty)
- Angioedema (swelling of face, lips, tongue, or throat)
- Thromboembolic events
Not Known
Frequency cannot be estimated from available data
- Long-term effects of PEG accumulation in tissues (under ongoing post-marketing surveillance)
Factor VIII Inhibitor Development
The development of neutralizing antibodies (inhibitors) against factor VIII is one of the most clinically significant complications of factor VIII replacement therapy. Inhibitors bind to factor VIII and neutralize its procoagulant activity, rendering replacement therapy less effective or completely ineffective. In the Jivi clinical development program (PROTECT VIII studies), the incidence of inhibitor development in previously treated patients (PTPs) was low, consistent with other recombinant factor VIII products. The risk is generally higher in previously untreated patients (PUPs), and Jivi has not been studied in this population.
Signs that may suggest inhibitor development include:
- Failure to achieve the expected factor VIII activity levels after infusion
- Inadequate clinical response to treatment (bleeding not controlled with usual doses)
- Increased frequency or severity of bleeding episodes despite adherence to prophylaxis
- Requirement for progressively higher doses to control bleeding
If inhibitor development is suspected, your hematologist will perform a Bethesda assay to confirm and quantify the inhibitor titer. Management strategies for patients with inhibitors include immune tolerance induction (ITI), the use of bypassing agents (activated prothrombin complex concentrate or recombinant activated factor VII), or switching to emicizumab.
PEG-Related Considerations
Because Jivi contains a 60 kDa PEG molecule, there are specific safety considerations related to PEG that do not apply to non-PEGylated factor VIII products. In preclinical studies in animals treated with PEGylated proteins, intracellular vacuolation was observed in various tissues, including the choroid plexus of the brain and renal tubular epithelial cells. The clinical relevance of these animal findings for humans receiving long-term Jivi therapy is currently not fully established.
Post-marketing surveillance and long-term extension studies are ongoing to further characterize the safety profile of Jivi regarding PEG accumulation. The European Medicines Agency (EMA) has required additional post-authorization safety studies to monitor for any PEG-related adverse effects over extended treatment periods. Patients and healthcare providers should be vigilant for any new or unusual symptoms and report them promptly.
How Should You Store Jivi?
Proper storage of Jivi is essential to maintain its potency and safety throughout its shelf life. As a lyophilized (freeze-dried) recombinant protein product, Jivi is sensitive to extremes of temperature and must be handled according to the manufacturer’s specific storage guidelines.
Unopened Vials
- Refrigerated storage: Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Keep the vial in the original carton to protect from light.
- Room temperature storage: If needed for convenience (e.g., travel), Jivi can be stored at room temperature (up to 25°C / 77°F) for a single continuous period of up to 6 months. Once removed from the refrigerator for room temperature storage, record the date on the carton and do not return the product to the refrigerator.
- Do not freeze. Freezing may damage the protein structure and compromise the product’s efficacy.
- Do not use after the expiry date printed on the vial label and carton.
- If stored at room temperature, the product must be used within 6 months or by the original expiry date, whichever comes first.
After Reconstitution
- The reconstituted solution should be used within 3 hours of preparation.
- Keep the reconstituted solution at room temperature; do not refrigerate or freeze.
- The reconstituted solution should be a clear, colorless liquid. Do not use if the solution is cloudy, contains particles, or is discolored.
- Any unused product or waste material should be disposed of in accordance with local requirements for pharmaceutical waste.
What Does Jivi Contain?
Jivi is supplied as a lyophilized (freeze-dried) white to slightly yellowish powder in a single-use glass vial, together with a pre-filled syringe of sterile water for injection as solvent. Understanding the complete composition of the product is important for identifying potential allergens and ensuring safe preparation and administration.
Active Ingredient
The active substance is damoctocog alfa pegol, which is a B-domain-deleted recombinant human coagulation factor VIII (BDD-rFVIII) that has been site-specifically conjugated with a 60 kDa branched polyethylene glycol (PEG) molecule. It is produced by recombinant DNA technology in baby hamster kidney (BHK) cells. Jivi is available in the following strengths:
- 250 IU per vial
- 500 IU per vial
- 1000 IU per vial
- 2000 IU per vial
- 3000 IU per vial
The stated potency (IU) is determined using the European Pharmacopoeia chromogenic substrate assay against the WHO International Standard for factor VIII concentrate.
Excipients (Inactive Ingredients)
The powder for reconstitution contains the following excipients:
- Sucrose (stabilizer)
- Histidine (buffer)
- Glycine (stabilizer)
- Sodium chloride (tonicity agent)
- Calcium chloride dihydrate (required for factor VIII stability and activity)
- Polysorbate 80 (surfactant to prevent protein aggregation)
- Hydrochloric acid and sodium hydroxide (for pH adjustment)
The solvent provided is sterile water for injection (2.5 mL pre-filled syringe).
Reconstitution and Administration
Jivi is reconstituted by dissolving the lyophilized powder with the sterile water for injection using the provided vial adapter and pre-filled syringe. The reconstituted solution should be gently swirled (not shaken) until the powder is completely dissolved. After reconstitution, the solution should be a clear, colorless liquid free from visible particles. It is administered as an intravenous (IV) injection at a rate comfortable for the patient, typically over 2–5 minutes. The infusion rate should not exceed 2.5 mL per minute.
Frequently Asked Questions About Jivi
Jivi (damoctocog alfa pegol) is a PEGylated recombinant factor VIII used for the treatment and prevention of bleeding in patients with hemophilia A (congenital factor VIII deficiency) aged 12 years and older. It is used for on-demand treatment and control of bleeding episodes, routine prophylaxis to reduce the frequency of bleeds, and management of bleeding during surgical procedures. Its extended half-life allows for less frequent infusions compared to standard factor VIII products.
One of the main advantages of Jivi is its extended half-life due to PEGylation, which allows for less frequent dosing. For prophylaxis, Jivi can be administered every 5 days, and in some patients the interval can be extended to every 7 days. A twice-weekly schedule is also available. Your hematologist will determine the most appropriate dosing frequency based on your individual bleeding pattern, pharmacokinetic profile, and factor VIII trough levels.
The most common side effects of Jivi include headache, cough, nausea, fever, and injection site reactions such as redness, swelling, or pain at the infusion site. These are generally mild to moderate in severity and resolve without specific treatment. Development of factor VIII inhibitors is an important but uncommon risk. Hypersensitivity reactions are rare but can occur. Report any unusual or persistent side effects to your healthcare provider.
Jivi is approved for use in patients aged 12 years and older. It has not been studied in children under 12 years of age in pivotal clinical trials. For younger pediatric patients with hemophilia A, other factor VIII products with established pediatric safety and efficacy data may be more appropriate. Your hematologist will recommend the best treatment option based on the patient’s age, weight, bleeding phenotype, and treatment history.
Jivi should be stored refrigerated at 2°C to 8°C in the original carton. Do not freeze. It can be stored at room temperature (up to 25°C) for a single continuous period of up to 6 months; once removed from the refrigerator, note the date and do not return it to the refrigerator. After reconstitution with the provided sterile water, the solution should be used within 3 hours at room temperature.
PEGylation is a process where polyethylene glycol (PEG) molecules are attached to a protein drug to alter its properties. In Jivi, a single 60 kDa branched PEG molecule is site-specifically attached to the B-domain-deleted recombinant factor VIII, extending its plasma half-life from approximately 12 hours (standard products) to 17–19 hours. This means patients can infuse less frequently—every 5 to 7 days instead of every 2 to 3 days—while still maintaining protective factor VIII levels, significantly reducing the treatment burden.
References
- European Medicines Agency (EMA). Jivi (damoctocog alfa pegol) – Summary of Product Characteristics. Last updated 2025.
- U.S. Food and Drug Administration (FDA). Jivi Prescribing Information. Bayer HealthCare LLC. Revised 2024.
- Reding MT, Grachev S, Engelen ET, et al. Safety and efficacy of BAY 94-9027, a prolonged-half-life recombinant factor VIII. Journal of Thrombosis and Haemostasis. 2017;15(3):411–419.
- Konkle BA, Stasyshyn O, Grachev S, et al. PROTECT VIII: Final results of the phase II/III clinical trial with BAY 94-9027 for the prophylaxis and treatment of bleeding in previously treated patients with severe hemophilia A. Haemophilia. 2020;26(2):e26–e34.
- Srivastava A, Santagostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020;26(Suppl 6):1–158.
- Pipe SW, Montgomery RR, Pratt KP, et al. Life in the shadow of a dominant partner: the FVIII-VWF association and its clinical implications for hemophilia A. Blood. 2016;128(16):2007–2016.
- International Society on Thrombosis and Haemostasis (ISTH). Guidance on monitoring extended half-life factor VIII concentrates. Journal of Thrombosis and Haemostasis. 2023.
- World Health Organization (WHO). Genomics and World Health: Report of the Advisory Committee on Health Research. Geneva: WHO, 2023.
- Mahlangu J, Kuliczkowski K, Engelen ET, et al. Efficacy and safety of PEGylated recombinant factor VIII (BAY 94-9027): results of an open-label clinical trial. Blood. 2016;128(22):3901.
- British National Formulary (BNF). Damoctocog alfa pegol. National Institute for Health and Care Excellence. 2025.
Medical Editorial Team
This article has been reviewed by our team of specialist physicians to ensure medical accuracy and compliance with current international guidelines.
Hematology Specialist
Board-certified hematologist with expertise in hemophilia management, coagulation disorders, and factor replacement therapy.
Clinical Pharmacologist
Specialist in pharmacokinetics, drug safety monitoring, and recombinant biologic therapies for bleeding disorders.
Medical Writer
Experienced medical writer specializing in evidence-based patient education materials for hematological conditions.
Quality Assurance
Medical content reviewer ensuring adherence to GRADE evidence framework, WFH guidelines, and regulatory documentation standards.
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