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Roctavian is a brand name for Valoctocogene Roxaparvovec. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: ROCTAVIAN is indicated for the treatment of severe haemophilia A (congenital factor VIII deficiency) in adult patients without a history of factor VIII inhibitors and without detectable antibodies to adeno-associated virus serotype 5 (AAV5).
Verbatim from this product's EMA label. Tap a section to expand.
Treatment should be initiated under the supervision of a physician experienced in the treatment of haemophilia and/or bleeding disorders. 8). 3 ROCTAVIAN should only be administered to patients who have demonstrated absence of anti-AAV5 antibodies by a validated assay.
Posology The recommended dose of ROCTAVIAN is 6 × 1013 vector genomes per kilogram (vg/kg) body weight, administered as a single intravenous infusion. Calculating the patient’s dose in millilitres (mL) and number of vials required • Calculation of patient’s dose volume in mL: Body weight in kg multiplied by 3 = dose in mL The multiplication factor 3 represents the per kilogram dose (6 × 1013 vg/kg) divided by the amount of vector genomes per mL of the ROCTAVIAN solution (2 × 1013 vg/mL).
• Calculation of number of vials to be thawed: Patient’s dose volume (mL) divided by 8 = number of vials to be thawed (round up to next whole number of vials). The division factor 8 represents the minimum volume of ROCTAVIAN extractable from a vial (8 mL).
25) Discontinuation of factor VIII concentrates/haemostatic agents When discontinuing factor VIII concentrates/haemostatic agents, physicians should consider the following: • Patient’s factor VIII activity levels are sufficient to prevent spontaneous bleeding episodes.
• The duration of effect of factor VIII concentrates/haemostatic agents. Special populations Hepatic impairment The safety and efficacy of valoctocogene roxaparvovec in patients with hepatic disorders have not been established. 3). 4).
Renal impairment No dose adjustments are recommended in patients with renal impairment. Elderly No dose adjustments are recommended in elderly patients. Limited data are available in patients aged 65 years and older. 4 Paediatric population The safety and efficacy of ROCTAVIAN in children and adolescents less than 18 years of age have not yet been established.
No data are available. Method of administration ROCTAVIAN must be administered via intravenous infusion. Do not infuse as an intravenous push or bolus. 8). ROCTAVIAN administration can begin at an infusion rate of 1 mL/min, which can be increased every 30 minutes by 1 mL/min to up to a maximum rate of 4 mL/min.
4). 6.
Summary of the safety profile The most common adverse reactions to ROCTAVIAN were increases in ALT (83%), AST (70%), LDH (57%), and CPK (48%), nausea (37%), and headache (35%). 1). Adverse reactions are listed by MedDRA body system organ class and by frequency.
Frequencies are categorised as follows: 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), not known (cannot be estimated from the available data).
14 Table 4: Tabulated list of adverse reactions to valoctocogene roxaparvovec MedDRA system organ class Adverse reaction Frequency Infections and infestations Flu-like symptoms Common Blood and lymphatic system disorders Factor VIII activity levels above ULNa Very common Immune system disorders Hypersensitivity reactionb Common Nervous system disorders Headache Very common Dizzinessb Common Presyncopeb Uncommon Cardiac disorders Increased blood pressureb Common Respiratory, thoracic and mediastinal disorders Dyspnoeab Uncommon Gastrointestinal disorders Nausea, vomiting, abdominal pain, diarrhoea Very common Dyspepsia Common Hepatobiliary disordersc ALT increased, AST increased, GGT increased, bilirubin increased, and LDH increased Very common Skin and subcutaneous tissue disorders Rashd, pruritusb Common Musculoskeletal and connective tissue disorders CPK increased Very common Myalgia Common General disorders and administration site conditions Fatiguee Very common Infusion-related reactionf Common a One or more instances of factor VIII activity levels > 170 IU/dL (ULN of the CSA used) or > 150 IU/dL (ULN of the OSA used).
See Description of selected adverse reactions. b Considered an adverse reaction only during first 48 hours after infusion. c Reflects laboratory abnormalities above the ULN. d Rash includes maculopapular rash and urticaria. e Fatigue includes lethargy and malaise.
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. Patients with pre-existing antibodies to the AAV5 vector capsid Experience in patients with pre-existing antibodies to the AAV5 vector capsid is limited.
1). Anti-AAV5 antibody formation can take place after natural exposure. As it is not yet known whether or under what conditions valoctocogene roxaparvovec can be safely and effectively administered in the presence of anti-AAV5 antibodies, this medicinal product is not indicated for use in patients with detectable anti-AAV5 antibodies.
1). Safety and efficacy of ROCTAVIAN in these circumstances have not been established. The efficacy of valoctocogene roxaparvovec relies on hepatocellular expression of hFVIII-SQ. , due to active hepatitis or exposure to hepatotoxic agents) may affect the therapeutic effect of valoctocogene roxaparvovec.
3). 4 or above) or in patients with a history of hepatic malignancy (see Hepatic function and factor VIII monitoring). Patients should be screened for hepatic malignancy prior to prescribing valoctocogene roxaparvovec. 8). The effect of alcohol consumption on the magnitude and duration of the therapeutic effect is not known.
In clinical studies, some ALT elevations have been attributed to alcohol consumption. It is recommended that patients abstain from consuming alcohol for at least one year after administration of this medicinal product and, thereafter limit alcohol use.
8); some of these reactions were temporally associated with decreased expression of the factor VIII transgene protein. The mechanism of these reactions has not yet been established. ALT and factor VIII activity levels should be monitored after valoctocogene roxaparvovec administration (see Hepatic function and factor VIII monitoring), and corticosteroid treatment should be instituted in response to ALT elevations as needed, to control hepatic reactions and prevent or mitigate a potential reduction in transgene expression.
1. 4).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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f Infusion-related reactions includes manifestations such as skin, mucosal, and respiratory tract (including urticaria, pruritus, maculopapular rash, sneezing, coughing, dyspnoea, rhinorrhoea, watery eyes, and tingling throat), gastrointestinal (including nausea and diarrhoea), cardiovascular (including increased blood pressure, hypotension, tachycardia, and presyncope) and musculoskeletal (including myalgia and lower back pain), as well as pyrexia, rigours, and chills.
15 Description of selected adverse reactions Infusion-related reactions Eleven patients (8%; 11/141) experienced infusion-related reactions with symptoms during or within 6 hours after the end of infusion that included one or more of the following: skin, mucosal, and respiratory tract manifestations (including urticaria, pruritus, maculopapular rash, sneezing, coughing, dyspnoea, rhinorrhoea, watery eyes, and tingling throat), gastrointestinal manifestations (including nausea and diarrhoea), cardiovascular manifestations (including increased blood pressure, hypotension, tachycardia, and presyncope) and musculoskeletal manifestations (including myalgia and lower back pain), as well as pyrexia, rigours, and chills.
87) from the start of the infusion, and median duration was 1 hour. Four patients had reactions during the infusion. Three of these patients experienced CTCAE Grade 3 hypersensitivity reaction, and temporary interruption of the infusion was required, followed by re-initiation at a slower rate.
All patients who experienced infusion-related reactions completed their infusions. Seven of the 11 patients received one or more of the following medications: systemic antihistamines, corticosteroids, and/or antiemetics. In addition, 1 patient received intravenous fluids and epinephrine.
All events of infusion-related reactions resolved without sequelae. Hepatic laboratory abnormalities Table 5 describes hepatic laboratory abnormalities following administration of ROCTAVIAN. 4). 0 × ULN ALT increases Forty-four percent of ALT increases above ULN occurred within the first 26 weeks; 29% of ALT increases occurred within week 27 to 52, and 27% of ALT increases occurred beyond 52 weeks after administration.
The median duration of ALT increases above ULN was 3 weeks. Ninety-seven of the 141 patients (69%) had two or more episodes of ALT increases above ULN. 16 Twelve (9%) patients experienced Grade 3 ALT elevations (15 episodes total). The range of Grade 3 ALT elevations were 216 IU/dL to 623 IU/dL.
The majority of Grade 3 ALT elevations (73%) occurred within the first 26 weeks, 3 (20%) occurred within week 27 to 52, and 1 (7%) occurred beyond 52 weeks after administration. All Grade 3 ALT elevations resolved with corticosteroids, including 2 patients that received IV methylprednisolone.
In the patients who had ALT increases above ULN, the median (range) time to initial reduction […]
When establishing indication and timing of valoctocogene roxaparvovec administration for an individual patient, physicians should ensure the availability of the patient for close monitoring of hepatic laboratory parameters and factor VIII activity after administration and verify that the risks associated with the corticosteroid regimen are acceptable for the individual patient.
8). Factor VIII assays Factor VIII activity produced by ROCTAVIAN in human plasma is higher if measured with one-stage clotting assays (OSA) compared to chromogenic substrate assays (CSA). In clinical studies, there was a high correlation between OSA and CSA factor VIII activity levels across the entire range of each assay's results.
For routine clinical monitoring of factor VIII activity levels, either assay may be used. 5 × CSA. For example, a factor VIII activity level of 50 IU/dL using CSA calculates to a level of 75 IU/dL using OSA. The following central laboratory tests were used in clinical studies: ellagic acid for OSA (similar results were obtained for silica and kaolin) and bovine factor IX for CSA (similar results were obtained for human factor IX).
, emicizumab) prior to valoctocogene roxaparvovec therapy, physicians should refer to the relevant product information to avoid the potential for factor VIII activity assay interference during the transition period. 8). Following the first year of administration, hepatic and factor VIII monitoring is intended to routinely assess liver health and bleeding risk, respectively.
A baseline assessment of liver health (including liver function tests within 3 months and recent fibrosis assessment using either imaging modalities, such as ultrasound elastography, or […]