donanemab

Therapeutic Classification: anti-Alzheimers's agents

Pharmacologic Classification: monoclonal antibodies, anti amyloid monoclonal antibodies

REMS

Alzheimer disease (with mild cognitive impairment or mild dementia).

Acts as a monoclonal antibody directed against aggregated insoluble forms of amyloid beta.

Therapeutic effects:

Reduction in clinical decline.
Reduction in amyloid beta plaques in the brain.

Absorption: IV administration results in complete bioavailability.

Distribution: Not widely distributed to extravascular tissues.

Metabolism/Excretion: Degraded into small peptides and amino acids via catabolic pathways.

Half-Life: 12.1 days.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	4 wk

Contraindicated in:

Hypersensitivity.

Use Cautiously in:

Apolipoprotein E ε4 (Apo E ε4) homozygotes (15% of patients with Alzheimer disease) (↑ risk of amyloid-related imaging abnormalities)
;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children.

Neuro: amyloid-related imaging abnormalities (ARIA) (including edema and hemosiderin deposition), headache, INTRACRANIAL HEMORRHAGE

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), infusion-related reactions

IV (Adults ): 700 mg every 4 wk for three doses; then 1400 mg every 4 wk.

Solution for injection: 17.5 mg/mL

Monitor during and for ≥30 min after infusion for signs and symptoms of hypersensitivity reaction, including anaphylaxis and angioedema. If symptoms occur, promptly stop infusion and treat as clinically indicated.
Monitor during and for ≥30 min after therapy for infusion-related reaction (chills, erythema, nausea/vomiting, dyspnea, diaphoresis, hypertension, headache, chest pain, hypotension). If infusion reaction occurs,↓ infusion rate or stop infusion and treat as clinically indicated. Consider pretreatment with antihistamine, acetaminophen, or corticosteroid prior to subsequent dose.
Monitor for intracerebral hemorrhage. If hemorrhage >1 cm in diameter occurs, hold until MRI findings stabilize and symptoms; if present, resolve. Resume dosing per clinical judgment.
Monitor for signs and symptoms of ARIA with edema (ARIA-E) or with hemosiderin deposition (ARIA-H). ARIA usually occur early in therapy and are asymptomatic or may include headache, confusion, visual changes, dizziness, nausea, and gait changes. ARIA-E can cause focal neurologic deficits that can mimic ischemic stroke.
- If mild, asymptomatic ARIA-E occur, continue scheduled dosing. If moderate or severe asymptomatic ARIA-E occur, hold until MRI indicates resolution; resume dosing per clinical judgment. If mild ARIA-E occur without symptoms disruptive to daily activities, resume dosing per clinical judgment. If moderate or severe ARIA-E occur with or without symptoms disruptive to daily activities, hold until MRI findings and symptoms resolve; resume dosing per clinical judgment and consider follow-up MRI in 2–4 mo.
- If mild asymptomatic ARIA-H occur, continue scheduled dosing. If moderate asymptomatic or mild to moderate symptomatic ARIA-H occur, hold until MRI findings stabilize and symptoms resolve; resume dosing per clinical judgment. If severe asymptomatic or symptomatic ARIA-H occur, hold until MRI findings stabilize and symptoms resolve; continue or permanently discontinue donanemab per clinical judgment. Consider a follow-up MRI in 2–4 mo for all moderate to severe findings.
Monitor PET imaging for ↓ in amyloid plaques. For amyloid levels less than predefined thresholds, consider holding therapy.

Lab Test Considerations:

Obtain Apo E ε4 status prior to initiating therapy to inform risk of developing ARIA.

Confirm presence of amyloid beta pathology prior to initiating therapy.
Obtain brain MRI at baseline and prior to 2nd, 3rd, 4th, and 7th infusions.
If infusion is missed, resume every 4 wk at same dose as soon as possible.

IV Administration:

Y-Site Incompatibility:
- Do not administer other drugs through same IV line.

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Inform patient of ↑ risk for ARIA if they are ApoE ε4 homozygote, and encourage testing for ApoE ε4 status prior to therapy initiation. Prior to testing, discuss risk of ARIA across genotypes and implications of genetic testing results.
Inform patient that symptoms of ARIA can mimic ischemic stroke and to notify a health care provider immediately of stroke symptoms (sudden weakness or numbness, difficulty speaking or understanding, visual changes, severe headache, dizziness) occur.
Advise patient to carry information that they are being treated with donanemab.
Encourage patient to enroll in registry to help further the understanding of Alzheimer disease and the impact of therapy. Call 1-800-545-5979.
Advise patient to immediately notify health care provider if signs of hypersensitivity (difficulty breathing, swelling of face) or infusion reaction occurs.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

Reduction in clinical decline.
Reduction in amyloid beta plaques in the brain.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆