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Palynziq is a brand name for Pegvaliase. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Palynziq is indicated for the treatment of patients with phenylketonuria (PKU) aged 16 years and older who have inadequate blood phenylalanine control (blood phenylalanine levels greater than 600 micromol/l) despite prior management with available treatment options. 3
Verbatim from this product's EMA label. Tap a section to expand.
Treatment with Palynziq should be directed by physicians experienced in the management of PKU. Posology Before initiating treatment, blood phenylalanine level must be obtained. Monitoring of blood phenylalanine level is recommended once a month.
Dietary phenylalanine intake should remain consistent until a maintenance dose is established. 5 mg administered once per week for 4 weeks. Titration The dose should be escalated gradually based on tolerability to the daily maintenance dose required to achieve blood phenylalanine level of 120 to 600 micromol/l according to Table 1.
e. a phenylalanine level between 120 to 600 micromol/l) taking into account patient tolerability to Palynziq and dietary protein intake (see Table 1). 4, Hypophenylalaninaemia). 2 Additional time may be required prior to each dose escalation based on patient tolerability with Palynziq.
3 The maintenance dose is individualised to achieve blood phenylalanine levels between 120 to 600 micromol/l. 4 If multiple injections are needed for a single dose, injections should be administered at the same time of day and injection sites should be at least 5 cm away from each other.
Doses should not be divided over the course of the day (see Method of administration). 4 Dose adjustments During titration and maintenance of Palynziq treatment, patients may develop blood phenylalanine levels below 30 micromol/l. To manage hypophenylalaninaemia, dietary protein intake should be increased to appropriate levels, and then, if needed, the dose of Palynziq should be reduced.
2, Exposure-effect). 4, Hypophenylalaninaemia). If hypophenylalaninaemia develops prior to reaching daily dosing, the dose may be reduced to the previous titration dose. If hypophenylalaninaemia develops once daily dosing is reached, the dose may be reduced by at least 10 mg decrements to achieve and maintain blood phenylalanine levels in the clinically acceptable range.
In patients experiencing hypophenylalaninaemia on 10 mg/day, the dose may be reduced to 5 mg/day. Special populations Paediatric population The safety and efficacy of Palynziq in paediatric patients from birth to less than 16 years have not been established.
No data are available. 1. Posology is the same in these patients as in adults. Method of administration Subcutaneous use. Each pre-filled syringe is for single use only. 8). Patients should be instructed to pre-medicate with an H1-receptor antagonist, H2-receptor antagonist, and antipyretic.
Summary of the safety profile In clinical trials, the majority of patients experienced injection site reactions (93%), arthralgia (86%), and hypersensitivity reactions (75%). 4). In clinical trials, adverse reaction rates were highest in induction and titration phases (time prior to reaching blood phenylalanine levels less than 600 micromol/l while on a stable dose) coinciding with the period when titres of IgM and anti-PEG antibodies were highest.
Rates decreased over time as the immune response matured (see Description of selected adverse reactions section). Tabulated list of adverse reactions Table 2 provides adverse reactions from clinical trials in patients treated with Palynziq.
Frequencies are defined as: 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) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
2%) General disorders and administration site conditions Injection site reaction3 Very common (90%) Very common (66%) Fatigue Very common (16%) Very common (24%) Investigations Hypophenylalaninaemia Very common (15%) Very common (65%) 10 System organ class Adverse reaction(s) Induction/Titration1 Maintenance Complement factor C3 decreased6 Very common (66%) Very common (73%) Complement factor C4 decreased6 Very common (64%) Very common (39%) High sensitivity CRP levels increased7 Very common (17%) Very common (13%) 1 Induction and titration phase reflects the time prior to reaching blood phenylalanine levels less than 600 micromol/l while on a stable dose.
Once blood phenylalanine levels less than 600 micromol/l on stable dose was reached, patients were considered to be in the maintenance phase thereafter. 2 Hypersensitivity reactions cover a group of terms, including acute systemic hypersensitivity reactions, and can manifest as a range of symptoms including angioedema, dizziness, dyspnoea, rash, serum sickness, and urticaria.
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 reactions Hypersensitivity reactions cover a group of terms that comprises acute systemic hypersensitivity reactions, other systemic hypersensitivity reactions such as angioedema and serum sickness which may have an acute or chronic presentation, and local hypersensitivity reactions such as injection site reactions or other skin reactions.
Hypersensitivity reactions including anaphylaxis have been reported in patients treated with Palynziq and can occur at any time during treatment. Palynziq may also increase hypersensitivity to other PEGylated injectable medicinal products (see Effect of Palynziq on other PEGylated injectable medicinal products).
6-fold higher in induction/titration phase compared to the maintenance phase. 8). 8). Manifestations of acute systemic hypersensitivity reactions included a combination of the following acute signs and symptoms: syncope, hypotension, hypoxia, dyspnoea, wheezing, chest discomfort/chest tightness, tachycardia, angioedema (swelling of face, lips, eyes, and tongue), flushing, rash, urticaria, pruritus, and gastrointestinal symptoms (vomiting, nausea, and diarrhoea).
Acute systemic hypersensitivity reactions were considered severe based on the presence of cyanosis or oxygen saturation (SpO2) less than or equal to 92%, hypotension (systolic blood pressure below 90 mm Hg in adults) or syncope. Four out of 16 (1%, 4/285) patients experienced a total of 5 episodes of acute systemic hypersensitivity reactions that were considered severe.
The risk of an acute systemic hypersensitivity reaction occurring is 6-fold higher in induction/titration phase compared to maintenance phase. Acute systemic hypersensitivity reactions require treatment with adrenaline and immediate medical care.
4).
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During maintenance, premedication may be reconsidered for subsequent injections based on patient tolerability to Palynziq. 8). Prior to first dose of Palynziq, the patient should be trained on the signs and symptoms of an acute systemic hypersensitivity reaction and to seek immediate medical care if a reaction occurs, and how to properly administer adrenaline injection device (auto-injector or pre-filled syringe/pen).
Patients should be instructed to carry an adrenaline injection device with them at all times during Palynziq treatment. e. when administration is not under healthcare professional supervision), an observer must be present during and for at least 60 minutes after each administration.
An observer is someone who: • would be present with the patient during and after Palynziq administration, • is able to recognise the signs and symptoms of an acute systemic hypersensitivity reaction, • can call for emergency medical support and administer adrenaline, if warranted.
After 6 months of Palynziq treatment, the need for an observer may be reconsidered. 5 Prior to independent self-injection, a healthcare professional should: • train the patient and assess patient competency on proper self-administration of this medicinal product, • train the observer to recognise signs and symptoms of an acute systemic hypersensitivity reaction and to seek immediate medical care if a reaction occurs, and how to properly administer adrenaline injection device (auto-injector or pre-filled syringe/pen).
Re-administration following mild to moderate acute systemic hypersensitivity reactions: The prescribing physician should consider the risks and […]
3 Refer to Special Warnings and Precautions. 4 The frequency of anaphylaxis in the post-marketing setting cannot be determined. 5 Abdominal pain reflects the following terms: abdominal pain, abdominal pain upper and abdominal discomfort.
6 Complement factor C3/C4 decrease is defined by changing from normal or high baseline complement value to low post-baseline complement value. 287 mg/dl) over a 6 month period. Description of selected adverse reactions Arthralgia and other joint related signs and symptoms In clinical trials, 86% of patients experienced episodes consistent with arthralgia (including back pain, musculoskeletal pain, pain in extremity, and neck pain).
Arthralgia occurred as early as the first dose and can occur at any time during treatment. 1-fold higher in induction/titration phase compared to maintenance phase. Severe arthralgia (severe pain limiting self-care activities of daily living) was experienced in 5% of patients.
g. nonsteroidal anti-inflammatory drugs, glucocorticoids, and/or antipyretic), dose reduction, treatment interruption, or treatment withdrawal, and 97% of arthralgia episodes resolved by the time of study completion. Persistent arthralgia (lasting at least 6 months) occurred in 7% of patients.
Dose was not changed for 96% of episodes and all persistent arthralgia episodes resolved without sequelae. Injection site reactions Injection site reactions were reported in 93% of patients. The most common injection site reactions (occurring in at least 10% of patients) were reaction, erythema, bruising, pruritus, pain, swelling, rash, induration, and urticaria.
2-fold higher in induction/titration phase compared to maintenance phase. Injection site reactions occurred as early as the first dose and can occur at any time during treatment. The mean duration of injection site reaction was 10 days, and 99% of injection site reactions resolved by […]
An adrenaline injection device (auto-injector or pre-filled syringe/pen) should be prescribed to patients receiving this medicinal product. Patients should be instructed to carry an adrenaline injection device with them at all times during Palynziq treatment.
Patients and the observer should be instructed to recognise the signs and symptoms of acute systemic hypersensitivity reactions, in the proper emergency use of the adrenaline injection device, and the requirement to seek immediate medical care.
The risks associated with adrenaline use should be reconsidered when prescribing Palynziq. Refer to the adrenaline product information for complete information. 3). 2, Method of administration). Patients should be instructed to pre-medicate with an H1-receptor antagonist, H2-receptor antagonist, and antipyretic.
During maintenance, premedication may be considered for subsequent injections based on patient tolerability to Palynziq. e. 2, Method of administration). g. 3). Re-administering following an acute systemic hypersensitivity reaction The prescribing physician should consider the risks and benefits of re-administering the medicinal product following resolution of the first mild to moderate acute systemic hypersensitivity reaction.
Upon re-administration, the first dose must be administered with premedication under the supervision of a healthcare professional with the ability to manage acute systemic hypersensitivity reactions. The prescribing physician should continue or consider resuming use of premedication.
Dose titration and time to achieve response Time to response (achieving blood phenylalanine levels ≤ 600 micromol/l) varies among patients. 5 to 54 months. The majority of patients (67%) reached a response by 18 months of total treatment.
An additional 8% of patients responded to Palynziq after 18 months of treatment. If a patient does not reach a clinically relevant blood phenylalanine reduction after 18 months of treatment, continuation should be reconsidered. g. ability to increase protein intake from intact food or improvement of neurocognitive symptoms).
7 Effect of Palynziq on other PEGylated injectable medicinal products PEGylated proteins have the potential to elicit an immune response. Because antibodies bind to the PEG portion of pegvaliase, there may be potential for binding with other PEGylated therapeutics and increased hypersensitivity to other […]