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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 mild cognitive impairment and mild dementia due to Alzheimer’s disease (AD) in adult patients that are apolipoprotein E ε4 (ApoE ε4) heterozygotes or non-carriers (see section 5.1).
Verbatim from this product's MHRA label. Tap a section to expand.
Treatment should be initiated by a physician experienced in the diagnosis and treatment of Alzheimer’s disease. 4). 1). 1). Prior to testing patients should be appropriately counselled and consented according to national or local guidelines, as applicable.
Posology The recommended dose of donanemab is 700 mg every 4 weeks for the first 3 doses, followed by 1400 mg every 4 weeks. 1). 1). 1). The benefit-risk of treatment should be re-assessed at regular intervals on an individual basis. If patient progress to moderate Alzheimer’s disease before the end of the 18 months maximum treatment, donanemab should be stopped.
Monitoring for Amyloid Related Imaging Abnormalities (ARIA) Donanemab can cause amyloid related imaging abnormalities-oedema (ARIA-E) and -haemosiderin deposition (ARIA-H), see section
). These reactions may be severe or life-threatening and typically occur during infusion or within 30 minutes post infusion. Signs and symptoms of infusion-related reactions may include erythema, chills, nausea, vomiting, sweating, headache, chest tightness, dyspnoea, and changes in blood pressure.
Appropriate resources for the management of severe reactions such as serious IRR, hypersensitivity reactions and/or anaphylactic reactions should be available. Reducing infusion rate, use of premedication or symptomatic treatment may be helpful in managing these reactions.
Administration of donanemab should be discontinued immediately and appropriate treatment should be initiated in case of serious infusion-related reactions or as clinically indicated. Higher ADA titre was associated with increased incidence of infusion-related reactions.
Amyloid-related imaging abnormalities (ARIA) ARIA has been observed very commonly in donanemab clinical studies. ARIA usually occurs early in treatment and is usually asymptomatic. 8 Undesirable Effects). ARIA includes amyloid-related imaging abnormalities-oedema/effusions (ARIA-E; also known as cerebral vasogenic oedema) and amyloid-related imaging abnormalities haemorrhage/haemosiderin deposition (ARIA-H; includes cerebral microhaemorrhage and cortical superficial siderosis).
ARIA can be detected by MRI. Most ARIA events were first observed within 24 weeks of initiation of treatment. Access to MRI should be available during the treatment period of donanemab. 2). Additional MRI is indicated if ARIA symptoms occur.
Symptoms may include headache, confusion, nausea, vomiting, unsteadiness, dizziness, tremor, visual disturbances, speech disturbances, worsening cognitive function, alteration of consciousness, and seizures. Most serious ARIA events occurred within 12 weeks of initiation of treatment and an additional MRI prior to the third dose may aid in earlier detection of ARIA, particularly for patients with ARIA risk factors such as apolipoprotein E ε4 allele (APOE ε4) carriers, baseline cerebral microhaemorrhages and superficial siderosis.
4. Access to MRI should be available during the treatment period of donanemab. Obtain a recent (within 1 year) brain magnetic resonance imaging (MRI) prior to initiating treatment. 4). For patients with radiographic findings of ARIA-E and ARIA-H, enhanced clinical vigilance for symptoms of ARIA is recommended.
4). The recommendations for dosing interruptions or treatment discontinuation for patients with amyloid-related imaging abnormalities-oedema/effusions (ARIA-E) and amyloid-related imaging abnormalities haemorrhage/haemosiderin deposition (ARIA- H) are provided in Table 1.
Table 1:
Dosing recommendations for patients with ARIA-E and ARIA-H ARIA-E and ARIA-H Severitya on MRI Clinical Symptom Mild Moderate Severe Asymptomatic Consider suspending dosing Suspend dosing Suspend dosing Symptomatic Suspend dosing aSee Table 2 for ARIA MRI radiographic severity classification Evaluation of risk factors again prior to restarting is recommended.
Supportive treatment, including corticosteroids may be considered in case of ARIA-E. ARIA-E Dosing may continue in asymptomatic, mild radiographic ARIA-E cases based on clinical judgement and with enhanced clinical monitoring and follow-up MRI scans starting two months after occurrence and every 1 or 2 months thereafter until ARIA-E has resolved.
Suspend dosing for any symptomatic or radiographically moderate or severe ARIA-E. A follow-up MRI to assess for resolution 2 to 4 months after initial identification should be performed. 4), if present, resolve, resumption of dosing should be guided by clinical judgment.
8). ARIA-H Dosing may continue in asymptomatic, mild radiographic ARIA-H cases based on clinical judgement and with enhanced clinical monitoring and follow-up MRI scans starting two months after occurrence and every 1 or 2 months thereafter until ARIA- H has stabilised.
1. Imaging findings suggestive of Cerebral Amyloid Angiopathy (CAA) that increase the risk of ARIA or intracerebral haemorrhage: - Acute or subacute cerebral haemorrhage - Superficial siderosis - More than 4 microhaemorrhages (defined as ≤ 1 cm in diameter on the T2* sequence) - Severe white matter disease - Pre-treatment MRI showing ARIA-E - Previous cerebral haemorrhage (defined as > 1 cm diameter in the T2* sequence) or previous subarachnoid haemorrhage unless it is no longer at risk of re- bleeding.
- Any finding that could prevent a satisfactory MRI evaluation for safety monitoring. 4).
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8). Donanemab is not indicated for use in patients who are ApoE ε4 homozygotes. A higher frequency of ARIA has also been observed in patients with pre-treatment cerebral microhaemorrhage and/or superficial siderosis. Caution should be exercised when initiating donanemab treatment in patients with baseline risk factors.
3). 2% (2/999) of placebo-treated patients. 3). Recommendations for Dosing Interruptions in Patients with ARIA When ARIA-H does occur, it is often in the presence of ARIA-E and managed as for ARIA-E. 2). 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 Radiographic SeverityARIA Type 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 siderosisa 1 new focal area of superficial siderosis 2 new focal areas of superficial siderosis > 2 new 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 a Includes new or increased focal areas of superficial siderosis Concomitant antithrombotic treatment The majority of exposures to antithrombotic medicines were to acetylsalicylic acid (81%) and more than 20% were treated with anticoagulants.
Patients who received donanemab and an antithrombotic medicine (acetylsalicylic acid, other antiplatelets, or anticoagulants), did not have an increased frequency of ARIA. The number of events and the limited exposure to other non-acetylsalicylic acid antithrombotic medicines limit definitive conclusions about the risk of ARIA or intracerebral haemorrhage in patients taking antithrombotic medicines.
, tissue plasminogen activator) to a patient already being treated with donanemab. • If anticoagulation needs to be commenced during therapy with donanemab (for example incident arterial thromboses, acute pulmonary embolism or other life- threatening […]
Suspend dosing for any symptomatic or radiographically moderate or severe ARIA- H. A follow-up MRI to assess for resolution 2 to 4 months after initial identification should be performed. 4), if present, resolve, resumption of dosing should be guided by clinical judgment.
8). If a second event of radiographically severe ARIA-H occurs, use clinical judgement in considering whether to restart or permanently discontinue treatment with donanemab. 4). Method of administration Kisunla 350 mg is for intravenous infusion only.
Each vial is for single use only. It should be administered over at least 30 minutes. Patients should be observed post- infusion for a minimum of 30 minutes. 6. The vial should be inspected visually for particulate matter and discolouration prior to administration.
Do not use donanemab if it is cloudy or there are visible particles. Missed dose If an infusion is missed, the missed dose should be administered at the next possible occasion. Then, resume the recommended dosing regimen every 4 weeks.
Special populations Paediatric population There is no relevant use of Kisunla in the paediatric population for the treatment of Alzheimer’s disease. 2). 2). The effect of severe hepatic and severe renal impairment on the exposure of donanemab has not been studied.
4). 1. Imaging findings suggestive of Cerebral Amyloid Angiopathy (CAA) that increase the risk of ARIA or intracerebral haemorrhage: - Acute or subacute cerebral haemorrhage - Superficial siderosis - More than 4 microhaemorrhages (defined as ≤ 1 cm in diameter on the T2* sequence) - Severe white matter disease - Pre-treatment MRI showing ARIA-E - Previous cerebral haemorrhage (defined as > 1 cm diameter in the T2* sequence) or previous subarachnoid haemorrhage unless it is no longer at risk of re- bleeding.
- Any finding that could prevent a satisfactory MRI evaluation for safety monitoring. 4). 4 Special warnings and precautions for use 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.
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. 8. Undesirable Effects). These reactions may be severe or life-threatening and typically occur during infusion or […]