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Jivi is a brand name for Damoctocog Alfa Pegol. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Treatment and prophylaxis of bleeding in previously treated patients ≥ 7 years of age with haemophilia A (congenital factor VIII deficiency).
Verbatim from this product's EMA label. Tap a section to expand.
Treatment should be under the supervision of a physician experienced in the treatment of haemophilia. Treatment monitoring During the course of treatment, appropriate determination of factor VIII levels is advised to confirm that adequate FVIII levels have been achieved.
Individual patients may vary in their response to factor VIII, demonstrating different half-lives and recoveries. Dose based on bodyweight may require adjustment in overweight patients. In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor VIII activity) is indispensable.
When using an in vitro activated partial thromboplastin time (aPTT)-based one stage clotting assay for determining factor VIII activity in patients’ blood samples, plasma factor VIII activity results can be significantly affected by both the type of aPTT reagent and the reference standard used in the assay, which can result in over- or under-estimation of factor VIII activity.
It should be noted that there can be significant discrepancies between assay results obtained by specific reagents used in the aPTT- based one stage clotting assay and the chromogenic assay. This is of importance when monitoring the factor VIII activity of Jivi, and when changing laboratory and/or reagents used in the assay.
This applies also for modified long-acting factor VIII products. Laboratories intending to measure Jivi activity should check their procedures for accuracy. A field study has indicated that the factor VIII activity of Jivi can be accurately measured in plasma using either a validated chromogenic substrate (CS) assay or a one-stage (OS) clotting assay using specific reagents.
g. with kaolin-based activators, have the potential for overestimation. The clinical effect of factor VIII is the most important element in evaluating the effectiveness of treatment. It may be necessary to adjust the individual dosing at patient level in order to attain satisfactory clinical results.
4). 4 Posology The dose and duration of substitution therapy depends on the severity of the factor VIII deficiency, the location and extent of the bleeding and on the patient's clinical condition. The number of units of factor VIII administered is expressed in International Units (IU), which are related to the current WHO concentrate standard for factor VIII products.
Summary of the safety profile Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the injection site, chills, flushing, generalized urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed and may in some cases progress to severe anaphylaxis (including shock).
1). If such inhibitors occur, the condition will manifest itself as an insufficient clinical response. In such cases, it is recommended that a specialized haemophilia centre be contacted. The most frequently reported adverse reactions in clinical studies in PTPs were headache, cough and pyrexia.
Tabulated list of adverse reactions A total of 256 patients constituted the safety population from 4 pivotal Phase I and III studies (one phase I study and 3 phase III studies), 148 adolescents/adults and 108 paediatric patients < 12 years.
9 The median number of exposure days to Jivi per patient was 195 (min-max: 1-698) for all patients in the clinical studies. Overall, in all studies 75 patients, 39 of them below 12 years of age, were observed for a treatment duration of more than 5 years.
1 for additional details on the clinical studies. The table presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level). Frequencies have been evaluated according to the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥1/10 000 to <1/1 000); very rare (<1/10 000).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 2:
Frequency of adverse drug reactions in clinical studies MedDRA Standard System Organ Class Adverse reactions Frequency Blood and lymphatic system disorders FVIII inhibition Uncommon (PTPs)a Immune system disorders Hypersensitivity common Psychiatric disorders Insomnia common Nervous system disorders Headache very common Dizziness common Dysgeusia uncommon Vascular disorders Flushing uncommon Respiratory, thoracic and mediastinal disorders Cough common Gastrointestinal disorders Abdominal pain, Nausea, Vomiting common Skin and subcutaneous tissue disorders Erythemac, Rashd common Pruritus uncommon General disorders and administration site conditions Injection site reactions b, Pyrexia common PTPs: previously treated patients a Frequency is based on studies with all factor VIII products which included patients with severe haemophilia A b Includes injection site pruritus, injection site rash, infusion site pain and vessel puncture site pruritus c Includes erythema and erythema multiforme d Includes rash and rash papular There was no change in the safety profile during the PROTECT VIII and the PROTECT Kids extension studies.
Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Hypersensitivity Allergic type hypersensitivity reactions are possible with Jivi.
The medicinal product may contain traces of mouse and hamster proteins. Hypersensitivity reactions could also be related to antibodies against PEG (see paragraph Immune response to polyethylene glycol (PEG)). If symptoms of hypersensitivity occur, patients should be advised to discontinue the use of the medicinal product immediately and contact their physician.
Patients should be informed of the early signs of hypersensitivity reactions including hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis. Symptomatic treatment for hypersensitivity should be instituted as appropriate.
In case of anaphylaxis or shock, the current medical standards for treatment should be implemented. Inhibitors The formation of neutralising antibodies (inhibitors) to factor VIII is a known complication in the management of individuals with haemophilia A.
These inhibitors are usually IgG immunoglobulins directed against the factor VIII procoagulant activity, which are quantified in Bethesda Units (BU) per mL of plasma using the modified Bethesda assay. The risk of developing inhibitors is correlated to the severity of the disease as well as the exposure to factor VIII, this risk being highest within the first 50 exposure days (ED) but continues throughout life although the risk is uncommon.
Rarely, inhibitors may develop after the first 50 exposure days. The clinical relevance of inhibitor development will depend on the titre of the inhibitor, with low titre posing less of a risk of insufficient clinical response than high titre inhibitors.
In general, all patients treated with coagulation factor VIII products should be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests. 7 If the expected factor VIII activity plasma levels are not attained, or if bleeding is not controlled with an appropriate dose, testing for factor VIII inhibitor presence should be performed.
1. Known allergic reactions to mouse or hamster proteins.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Factor VIII activity in plasma is expressed either as a percentage (relative to normal human plasma) or preferably in IU (relative to an International Standard for factor VIII in plasma). One IU of factor VIII activity is equivalent to that quantity of factor VIII in one mL of normal human plasma.
5 % of normal activity. e. 0%). The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness required in the individual case. In the case of the following haemorrhagic events, the factor VIII activity should not fall below the given plasma activity level (in % of normal) in the corresponding period.
The following table can be used to guide dosing in bleeding episodes and surgery: 5 Table 1: Guide for dosing in bleeding episodes and surgery Degree of haemorrhage/Type of surgical procedure Factor VIII level required (%) (IU/dL) Frequency of doses (hours) / Duration of therapy (days) Haemorrhage Early haemarthrosis, muscle bleeding or oral bleeding 20-40 Repeat injection every 24-48 hours.
At least 1 day, until bleeding episode as indicated by pain is resolved or healing is achieved More extensive haemarthrosis, muscle bleeding or haematoma 30-60 Repeat injection every 24-48 hours for 3 to 4 days or more until pain and acute disability are resolved.
Life-threatening Haemorrhages 60-100 Repeat injection every 8 to 24 hours until threat is resolved. Surgery Minor surgery including tooth extraction 30-60 Every 24 hours, at least 1 day, until healing is achieved. Major surgery 80-100 (pre- and post-operative) Repeat dose every 12-24 hours until adequate wound healing, then therapy for at least another 7 days to maintain factor VIII activity of 30-60% (IU/dL).
Prophylaxis All treatment decisions for identifying appropriate prophylactic treatment regimens should be guided by clinical judgement based on individual patient characteristics and treatment response. Adjustments of doses and administration intervals may be considered based on achieved factor VIII levels and individual bleeding tendency.
1. Adults and adolescents 12 years of age and older The dose is 45-60 IU/kg every 5 days. 2). 2). The recommended starting dose is 60 IU/kg two times per week. For overweight patients, the maximum dose per injection for prophylaxis should not be higher than approximately 6 000 IU.
Special populations Paediatric population Jivi is not indicated in previously untreated patients and in patients less than 7 […]
Description of selected adverse reactions Immunogenicity Immunogenicity was evaluated during clinical studies with Jivi in 159 (including surgery patients) previously treated adolescents (≥ 12 to < 18 years of age, n=14) and adults (n=145) diagnosed with severe haemophilia A (FVIII:C < 1%), and ≥ 150 previous exposure days and 108 paediatric PTPs < 12 years of age (n=60 aged 7-<12 years) and ≥ 50 previous exposure days.
10 FVIII inhibitors No de novo or confirmed cases of inhibitor against factor VIII occurred. 7 BU/mL) was reported in one adult patient undergoing surgery. Anti-PEG antibodies Immunogenicity against PEG with development of specific IgM anti-PEG antibodies was observed in 2 patients.
In one patient > 12 years of age, the immune response was accompanied by a clinical hypersensitivity reaction after 4 injections of Jivi. Antibodies to PEG disappeared after discontinuation of Jivi. One child ˃ 7 years, developed high titre neutralising anti-PEG IgM antibodies within the first 4 exposure days associated with loss of drug effect.
Antibodies disappeared after discontinuation and patient safely re-started treatment with Jivi 2 months later. Transient low titre anti-PEG antibodies of the IgM isotype were observed in some patients within the first 4 ED resulting in minor reduction of recovery.
No clinical immune response to PEG resulting in loss of drug efficacy or hypersensitivity was observed from the 5th ED through the end of the extension studies. Paediatric population in the PROTECT Kids study In the completed clinical study with 73 paediatric PTPs < 12 years (44 PTPs < 6 years, 29 PTPs 6- < 12 years), adverse reactions due to immune response to PEG were observed in children less than 6 years of age.
In 10 of 44 patients (23%) in the age group of younger than 6 years of age loss of drug effect due to neutralising anti-PEG antibodies during the first 4 exposure days was observed. 4). No triggers or predictors of the immune response to PEG could be identified.
Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In patients with high levels of inhibitor, factor VIII therapy may not be effective and other therapeutic options should be considered. Management of such patients should be directed by physicians with experience in the care of haemophilia and factor VIII inhibitors.
Immune response to polyethylene glycol (PEG) A clinical immune response associated with anti-PEG antibodies, manifested as symptoms of acute hypersensitivity and/or loss of drug effect has been observed primarily within the first 4 exposure days.
Low post-injection factor VIII levels in the absence of detectable factor VIII inhibitors indicate that loss of drug effect is likely due to anti-PEG antibodies; in such cases Jivi should be discontinued and patients switched to a previously effective factor VIII product.
In case of clinical suspicion of loss of therapeutic effect, testing for Factor VIII inhibitors and Factor VIII recovery is recommended. A significant decrease in the risk of an immune response to PEG was observed with an increase in age.
This effect may be related to a developmental change in immunity, and although it is difficult to define a clear cut-off age for the change in risk, this phenomenon predominantly occurs in young children with haemophilia. The implications of any potential risk to affected patients with a hypersensitivity reaction to pegylated proteins are unknown.
Data show that in the affected patients, following discontinuation of Jivi, the anti-PEG IgM antibodies decreased in titre and became undetectable over time. No cross-reactivity of anti-PEG IgM antibodies with other unmodified factor VIII products was observed.
All patients could be successfully treated with their previous factor VIII products. 2). Patients should be monitored for recovery upon restart of treatment. Decreased factor VIII incremental recovery A minor reduction of recovery (recovery around 1 IU/dL per IU/kg) after start of treatment was observed and may be due to transient low titer anti PEG IgM antibodies mainly in children.
Low incremental recovery could potentially be associated with reduced efficacy during this time period. Monitoring of paediatric patients, including monitoring of post dose factor VIII activity, is recommended. If a bleeding is not controlled with the recommended dose and/or the expected Factor VIII activity levels are not attained in the absence of FVIII inhibitors, consider adjusting the dose, dosing frequency or discontinuing the product.
Cardiovascular events In patients with existing cardiovascular risk factors, substitution therapy with factor VIII may increase the cardiovascular risk. Catheter-related complications If a central venous access device (CVAD) is required, risk of CVAD-related complications including local infections, bacteraemia and catheter site thrombosis should be considered.
Paediatric population The listed warnings and precautions apply to adults, adolescents and children aged 7 to < 12 years. Jivi is not indicated in patients < 7 years of age and in previously untreated patients. 8 Information about excipients Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.
08 mg/mL solution for injection. Polysorbates may cause allergic reactions.