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Kisunla is a brand name for Donanemab. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Donanemab is indicated for the treatment of adult patients with a clinical diagnosis of mild cognitive impairment and mild dementia due to Alzheimer’s disease (Early symptomatic Alzheimer’s disease) who are apolipoprotein E ε4 (ApoE ε4) heterozygotes or non-carriers with confirmed amyloid pathology (see section 4.4).
Verbatim from this product's EMA label. Tap a section to expand.
Treatment should be initiated by a physician experienced in the diagnosis and treatment of Alzheimer’s disease (AD) with timely access to Magnetic Resonance Imaging (MRI). Donanemab should be administered under the supervision of a multidisciplinary team trained in detection, monitoring and management of amyloid-related imaging abnormalities (ARIA) and experienced in detecting and managing infusion related reactions (IRR).
Patients treated with donanemab must be given the patient card and be informed about the risks of donanemab (see also package leaflet). ApoE ε4 Testing ApoE ε4 genotype should be assessed by a CE-marked in vitro diagnostic (IVD) with the corresponding intended purpose.
1). 4). Prior to testing patients should be appropriately counselled and consented according to national or local guidelines, as applicable. g. positron emission tomography [PET] scan, cerebrospinal fluid [CSF] or another appropriate test).
Donanemab should be administered every 4 weeks. The recommended dose of donanemab is 350 mg for the first dose, 700 mg for the second dose, 1 050 mg for the third dose, followed by 1 400 mg every 4 weeks. g. 1) as confirmed using a validated method.
The maximum treatment duration is 18 months which should not be exceeded even if plaque clearance is not confirmed. The benefit-risk of treatment should be reassessed at regular intervals on an individual basis and considering the rate of disease progression.
Consideration should be given to discontinuing treatment before the end of the 18 months maximum treatment if patients progress to moderate AD. Missed dose If an infusion is missed, administration should be resumed every 4 weeks at the same dose as soon as possible.
Monitoring, dosing interruption, and treatment discontinuation for amyloid related imaging abnormalities Donanemab can cause ARIA, characterized as ARIA with oedema (ARIA-E), which can be observed on MRI as brain oedema or sulcal effusions, and ARIA with haemosiderin deposition (ARIA-H), which includes microhaemorrhage and superficial siderosis.
In addition to ARIA, intracerebral haemorrhages greater than 1 cm in diameter have occurred in patients treated with donanemab. A recent (within 6 months) brain MRI should be available prior to initiating treatment with donanemab to evaluate for pre-existing ARIA.
1), a total of 853 adult subjects received at least one dose of donanemab. Of these, 710 participants concerned the indicated population (ApoE ε4 heterozygotes and non-carriers). 8 % (143/853) were homozygotes. With the exception of events of ARIA, the safety profile was similar across genotypes.
6 %). 4 %). 4). Tabulated list of adverse reactions Adverse reactions from clinical studies with donanemab (Table 3) are listed by MedDRA system organ class. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first.
In addition, the corresponding frequency category for each reaction is based on 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).
Table 3. Adverse reactions System organ class Very common Common Uncommon Nervous system disorders ARIA-Ea,b ARIA-Ha,b Microhaemorrhage Superficial siderosis Headache Intracranial haemorrhagec Gastrointestinal disorders Nausea Vomiting Injury, poisoning and procedural complications Infusion-related reactiond Hypersensitivity Anaphylactic reaction a As assessed by MRI.
b Symptoms may include headache, confusion, nausea, vomiting, unsteadiness, dizziness, tremor, visual disturbances, speech disturbances, worsening cognitive function, alteration of consciousness, and seizures. c Includes subdural haematoma, subarachnoid haemorrhage, cerebral haemorrhage, haemorrhagic stroke and cerebrovascular accident.
d Signs and symptoms of infusion-related reactions and hypersensitivity may include erythema, chills, nausea, vomiting, sweating, headache, chest tightness, dyspnoea, and changes in blood pressure. 5 % (98/728) of heterozygotes and non-carrier patients on placebo.
4 % (10/710) of patients treated with donanemab. 4 %, three patients). Clinical symptoms associated with ARIA-E resolved in approximately 80 % of patients. ARIA-E symptoms may include headache, confusion, nausea, vomiting, unsteadiness, dizziness, tremor, visual disturbances, speech disturbances, worsening cognitive function, alteration of consciousness, and seizures.
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. Controlled access programme In order to promote the safe and effective use of donanemab, initiation of treatment in all patients should be through a central registration system implemented as part of a controlled access programme.
Educational materials Prescribers should be familiar with the educational material prepared for the detection and management of ARIA, and discuss the benefits and risks of donanemab therapy with the patient/caregiver. MRI scans and signs or symptoms of adverse reactions, and when to seek attention from a healthcare professional must also be discussed with the patient.
The patient will be provided with the patient card and instructed to carry the card at all times. Amyloid beta pathology The presence of amyloid beta pathology must be confirmed via an appropriate test prior to initiating treatment.
Amyloid-related imaging abnormalities (ARIA) ARIA-H generally occurs in association with an occurrence of ARIA-E. ARIA has been observed very commonly in donanemab clinical studies. ARIA usually occurs early in treatment and is usually asymptomatic.
When present, reported symptoms associated with ARIA may include headache, confusion, nausea, vomiting, unsteadiness, dizziness, tremor, visual disturbances, speech disturbances, worsening cognitive function, alteration of consciousness, and seizures.
8). 8). 8). ARIA can be detected by MRI and while ARIA-E typically resolves on imaging, ARIA-H may persist and stabilise. Most ARIA events were first observed within 24 weeks of initiation of treatment. Most serious ARIA events occurred within 12 weeks of initiation of treatment.
Access to MRI should be available during the treatment period of donanemab. Given preexisting risk factors, patients who are eligible for amyloid treatment therapies are also at risk for spontaneous ARIA. ARIA should be considered as a possible aetiology for neurological symptoms.
1. 4). - Patients with bleeding disorders that are not under adequate control. 4). 4). - Patients with poorly controlled hypertension. - Conditions that do not allow MRI assessment, including claustrophobia or the presence of metal (ferromagnetic) implants/cardiac pacemaker.
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An MRI should be performed prior to the second dose (at 1 month), prior to the third dose (at 2 months), prior to the fourth dose (at 3 months), and prior to the seventh dose (at 6 months). An additional MRI at one year of treatment (prior to the twelfth dose) in patients with ARIA risk factors such as ApoE ε4 heterozygotes, and/or patients with previous ARIA events earlier in treatment, should be performed.
4). The recommendations for dosing interruptions or treatment discontinuation for patients with ARIA-E and ARIA-H are provided in Table 1.
Table 1:
Dosing recommendations for patients with ARIA-E and ARIA-H Clinical symptom ARIA-E and ARIA-H severitya on MRI Mild Moderate Severe Asymptomatic Consider suspending dosing Suspend dosing Discontinue dosing Symptomatic Suspend dosing Suspend dosing Discontinue dosing aSee Table 2 for ARIA MRI radiographic severity classification criteria 4 In case of asymptomatic mild ARIA, consider dose suspension based on radiological features of ARIA, number of ARIA episodes and clinical condition.
In case of asymptomatic moderate ARIA and symptomatic mild/moderate ARIA, suspend dose until MRI demonstrates radiographic resolution (ARIA-E) or stabilisation (ARIA-H) and symptoms, if present, resolve. A follow-up MRI to assess for resolution (ARIA-E) or stabilization (ARIA-H) should be performed 2 to 4 months after initial identification.
4). 8). In the event of radiographically or symptomatic severe ARIA-E or ARIA-H, treatment with donanemab should be permanently discontinued. Donanemab should also be permanently discontinued after clinically serious ARIA-E, serious ARIA- H, or intracerebral haemorrhage greater than 1 cm.
Clinical judgment should be used in considering whether to continue dosing in patients with recurrent ARIA. Treatment with donanemab should be discontinued following recurrent symptomatic or radiographically moderate or severe ARIA events.
2). Paediatric population There is no relevant use of donanemab in the paediatric population for the treatment of Alzheimer’s disease. Method of administration Donanemab is for intravenous use only. Each vial is for single use only. Diluted solution should be administered over a period of at least 30 minutes.
Patients should be observed post-infusion for a minimum of 30 minutes. 6.
8 % (13/728) of patients on placebo. 4 % (10/710) of patients. 6 % (40/710) of patients treated with donanemab in the pivotal study. 3 weeks. 3 % (35/144) experienced multiple episodes of ARIA-E. 2 % (89/728) of patients on placebo. 6 % (54/710) of patients.
3 % (2/728) of patients on placebo. 5 % (84/728) on placebo. 9 % (70/195) of participants experienced multiple episodes of ARIA-H. The majority of first ARIA radiographic events in the placebo-controlled studies occurred early in treatment (within 24 weeks of initiation of treatment), although ARIA can occur at any time and patients can have more than one episode.
Standard supportive treatment, including corticosteroids may be considered in case of ARIA-E, however the effectiveness of treatment has not been established. 8 % (6/728) of patients on placebo. 3 % (2/728) in placebo treated patients.
Additionally, in a participant with baseline superficial siderosis treated with donanemab in the pivotal study, fatal ARIA-H was reported with concurrent intracerebral haemorrhage. 7 % donanemab vs. 6 % donanemab vs. 1 […]
8). 2). Enhanced clinical vigilance for ARIA is recommended during the first 24 weeks of treatment with donanemab. 4 “Amyloid-related imaging abnormalities - ARIA”). 6 Recommendations for dosing interruptions and treatment discontinuations in patients with ARIA If symptoms of ARIA-H occur, it is often in the presence of ARIA-E and managed as for ARIA-E.
2). Donanemab should be permanently discontinued if serious ARIA-E, serious ARIA-H, intracerebral haemorrhage greater than 1 cm, or recurrent symptomatic or radiographically moderate or severe ARIA events occur. Radiographic severity The radiographic severity of ARIA associated with donanemab was classified by the criteria shown in Table 2.
Table 2:
ARIA MRI Classification criteria ARIA Type Radiographic Severity Mild Moderate Severe ARIA-E FLAIR hyperintensity confined to sulcus and/or cortex/subcortex white matter in one location < 5 cm. FLAIR hyperintensity 5 to 10 cm in single greatest dimension, or more than 1 site of involvement, each measuring < 10 cm.
FLAIR hyperintensity > 10 cm with associated gyral swelling and sulcal effacement. One or more separate/independent sites of involvement may be noted. ARIA-H microhaemorrhage ≤ 4 new incident microhaemorrhages 5 - 9 new incident microhaemorrhages ≥ 10 new incident microhaemorrhages ARIA-H superficial siderosis 1 new or increased focal area of superficial siderosis 2 new or increased focal areas of superficial siderosis > 2 new or increased focal areas of superficial siderosis Abbreviations: FLAIR = fluid-attenuated inversion recovery; ARIA-E = amyloid-related imaging abnormalities- oedema/effusions; ARIA-H = amyloid-related imaging abnormalities haemorrhage/hemosiderin deposition ApoE ε4 carrier status and risk of ARIA ApoE ε4 carriers have a higher frequency (homozygotes greater than heterozygotes) of ARIA-E and ARIA-H, including serious and symptomatic ARIA, compared to non-carriers.
1). 2). Prior to testing, prescribers should discuss with patients the risk of ARIA across genotypes. Increased intracerebral haemorrhage risk Caution should be exercised when considering the use of donanemab in patients with factors that indicate an increased risk for intracerebral haemorrhage.
8). Concomitant antithrombotic treatment Baseline use of antithrombotic medicinal products (aspirin, other antiplatelets, or anticoagulants) was allowed in clinical trials with donanemab. The majority of exposures to antithrombotic medicines were to acetylsalicylic acid.
Patients who received donanemab and an antithrombotic medicine (acetylsalicylic acid, other […]