Active Ingredient: Donanemab
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.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Intravenous, 350 milligrams donanemab, one dose, over the duration of 4 weeks. Afterwards, intravenous, 700 milligrams donanemab, one dose, over the duration of 4 weeks. Afterwards, intravenous, 1,050 milligrams donanemab, one dose, over the duration of 4 weeks. Afterwards, intravenous, 1,400 milligrams donanemab, once every 4 weeks.
Beta amyloid evidence consistent with AD should be confirmed using a validated test (e.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. Treatment should be maintained until amyloid plaques are cleared (e.g. at 6 or 12 months) 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.
If an infusion is missed, administration should be resumed every 4 weeks at the same dose as soon as possible.
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. 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. If a patient experiences symptoms suggestive of ARIA at any time during treatment, clinical evaluation should be performed including an MRI.
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 |
a See Table 2 for ARIA MRI radiographic severity classification criteria
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. Resumption of dosing or permanent discontinuation after ARIA-E resolution and ARIA-H stabilization should be guided by clinical judgment including re-evaluation of risk factors. Standard supportive treatment, including corticosteroids may be considered in case of ARIA-E.
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.
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
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.
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