KISUNLATM (donanemab-azbt) injection
Drug UPDATES: [Drug information (pdf)]
PACKAGE INSERT -Dosing: Click (+) next to Dosage and Administration section (drug info link)
See below. Also Dosage and Administration.
Dilution Instructions
- Prior to administration, KISUNLA must be diluted with 0.9% sodium chloride injection (see Table 4).
- Use aseptic technique when preparing the diluted KISUNLA solution for intravenous infusion.
- Allow KISUNLA to equilibrate to room temperature before preparation.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. KISUNLA solution is clear to opalescent, colorless to slightly yellow to slightly brown. Do not use if particulate matter or discolorations are present.
- Withdraw required volume of KISUNLA and mix with 0.9% sodium chloride injection, to the recommended total volume for a final concentration of 4 mg/mL to 10 mg/mL (see Table 4). Use only 0.9% sodium chloride injection for dilution.
| KISUNLA Dose (mg) | KISUNLA Volume (mL) | Volume of 0.9% Sodium Chloride Injection Diluent (mL) | Final Volume of Diluted Solution to be Infused (mL) | Final Concentration of Diluted Solution (mg/mL)a |
| 700 mg | 40 mLb | 30 mL to 135 mL | 70 mL to 175 mL | 700 mg/175 mL (4 mg/mL) to 700 mg/70 mL (10 mg/mL) |
| 1400 mg | 80 mLc | 60 mL to 270 mL | 140 mL to 350 mL | 1400 mg/350 mL (4 mg/mL) to 1400 mg/140 mL (10 mg/mL) |
|
a. final concentration of 4 mg/mL to 10 mg/mL |
|
b. 2 vials of KISUNLA |
|
c. 4 vials of KISUNLA |
Administration Instructions
- Visually inspect the diluted KISUNLA solution for particles or discoloration prior to administration. Do not use if it is discolored, or opaque or foreign particles are seen.
- Prior to infusion, if the diluted solution has been stored under refrigeration, allow the diluted KISUNLA solution to warm to room temperature.
- Administer the entire diluted solution intravenously over approximately 30 minutes.
- Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity-type reaction [see Warnings and Precautions (5.2)].
- Flush the line only with 0.9% sodium chloride injection at the end of the infusion per access specific line maintenance protocol.
- Observe the patient post-infusion for a minimum of 30 minutes to evaluate for infusion reactions and hypersensitivity reactions
Storage and stability:
Unopened Vial
- Store refrigerated at 2°C to 8°C (36°F to 46°F).
- Keep the vial in the outer carton to protect from light.
- Do not freeze or shake.
- If refrigeration is not available, may be stored at room temperature (20°C to 25°C [68°F to 77°F]) for up to 3 days.
Diluted Solution
- Each vial is for one-time use only. Discard any unused portion left in the vial.
- Gently invert the diluted KISUNLA solution to mix completely. Do not shake.
- After dilution, immediate use is recommended [see Description (11)]. If the diluted KISUNLA solution is not administered immediately, store refrigerated at 2°C to 8°C (36°F to 46°F) for up to 72 hours or at room temperature (20°C to 25°C [68°F to 77°F]) for up to 12 hours.
- Do not freeze the diluted KISUNLA solution.
- Storage times include the duration of infusion.
| WARNING: WARNING: AMYLOID RELATED IMAGING ABNORMALITIES See full prescribing information for complete boxed warning. Monoclonal antibodies directed against aggregated forms of beta amyloid, including KISUNLA, can cause amyloid related imaging abnormalities (ARIA), as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). ARIA is usually asymptomatic, although serious and life-threatening events can rarely occur. Serious intracerebral hemorrhages >1 cm have occurred in patients treated with this class of medications. ARIA-E can cause focal neurologic deficits that can mimic ischemic stroke. (5.1, 6.1) ApoE ε4 Homozygotes Consider the benefit for the treatment of Alzheimer's disease and risk of ARIA when deciding to treat with KISUNLA. (5.1, 14) Drug information (pdf) |
KISUNLA (donanemab-azbt) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow to slightly brown solution for intravenous infusion after dilution. KISUNLA is supplied in single-dose vials available in a concentration of 350 mg/20 mL (17.5 mg/mL).
Each mL of solution contains 17.5 mg donanemab-azbt, anhydrous citric acid (0.32 mg), polysorbate 80 (0.20 mg), sodium citrate (2.15 mg), sucrose (80 mg), and Water for Injection, USP, at a pH of 5.5 to 6.5.
Donanemab-azbt is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against insoluble N-truncated pyroglutamate amyloid beta. The accumulation of amyloid beta plaques in the brain is a defining pathophysiological feature of Alzheimer's disease. Donanemab-azbt reduces amyloid beta plaques, as evaluated in Study
KISUNLATM is indicated for the treatment of Alzheimer's disease. Treatment with KISUNLA should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in the clinical trials.
KISUNLA is contraindicated in patients with known serious hypersensitivity to donanemab-azbt or to any of the excipients.
- Amyloid Related Imaging Abnormalities (ARIA): Enhanced clinical vigilance for ARIA is recommended during the first 24 weeks of treatment with KISUNLA. Risk of ARIA, including symptomatic ARIA, was increased in apolipoprotein E ε4 (ApoE ε4) homozygotes compared to heterozygotes and noncarriers. The risk of ARIA-E and ARIA-H is increased in KISUNLA-treated patients with pretreatment microhemorrhages and/or superficial siderosis. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI scanning if indicated. (2.3, 5.1)
- Infusion-Related Reactions: The infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Consider pre-treatment with antihistamines, acetaminophen, or corticosteroids prior to subsequent dosing. (5.3)Drug information (pdf)
Most common adverse reactions (at least 10% and higher incidence compared to placebo): ARIA-E, ARIA-H microhemorrhage, ARIA-H superficial siderosis, and headache. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Drug information (pdf)
Revised: 7/2024
2.1 Patient Selection
Confirm the presence of amyloid beta pathology prior to initiating treatment [see Clinical Pharmacology Drug information (pdf)]
2.2 Dosing Instructions
The recommended dosage of KISUNLA is 700 mg every four weeks for three doses, then 1400 mg every four weeks (see Table 1). KISUNLA is administered every four weeks as an intravenous infusion over approximately 30 minutes. KISUNLA must be diluted prior to administration (see Table 4).
| Intravenous Infusion (every 4 weeks) |
KISUNLA Dosage (administered over approximately 30 minutes) |
| Infusions 1, 2, and 3 | 700 mg |
| Infusion 4 and beyond | 1400 mg |
Consider stopping dosing with KISUNLA based on reduction of amyloid plaques to minimal levels on amyloid PET imaging. In Study 1, dosing was stopped based on a reduction of amyloid levels below predefined thresholds on PET imaging [see Clinical Studies (14) Drug information (pdf)].
If an infusion is missed, resume administration every 4 weeks at the same dose as soon as possible.
2.3 Monitoring and Dosing Interruption for Amyloid Related Imaging Abnormalities
KISUNLA can cause amyloid related imaging abnormalities -edema (ARIA-E) and -hemosiderin deposition (ARIA-H) [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].
Monitoring for ARIA
Obtain a recent baseline brain magnetic resonance imaging (MRI) prior to initiating treatment with KISUNLA. Obtain an MRI prior to the 2nd, 3rd, 4th, and 7th infusions. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including an MRI if indicated.
Recommendations for Dosing Interruptions in Patients with ARIA
ARIA-E
The recommendations for dosing interruptions for patients with ARIA-E are provided in Table 2.
| Clinical Symptom Severitya | ARIA-E Severity on MRI | ||
| Mild | Moderate | Severe | |
| Asymptomatic | May continue dosing at current dose and schedule | Suspend dosingb | Suspend dosingb |
| Mild | May continue dosing based on clinical judgment | Suspend dosingb | |
| Moderate or Severe | Suspend dosingb | ||
|
a. Mild: discomfort noticed, but no disruption of normal daily activity. |
|
b. Suspend until MRI demonstrates radiographic resolution and symptoms, if present, resolve; consider a follow-up MRI to assess for resolution 2 to 4 months after initial identification. Resumption of dosing should be guided by clinical judgment. |
ARIA-H
The recommendations for dosing interruptions for patients with ARIA-H are provided in Table 3.
Table 3: Dosing Recommendations for Patients With ARIA-H
| Clinical Symptom Severity | ARIA-H Severity on MRI | ||
| Mild | Moderate | Severe | |
| Asymptomatic | May continue dosing at current dose and schedule | Suspend dosinga | Suspend dosingb |
| Symptomatic | Suspend dosinga | Suspend dosinga | |
a. Suspend until MRI demonstrates radiographic stabilization and symptoms, if present, resolve; resumption of dosing should be guided by clinical judgment; consider a follow-up MRI to assess for stabilization 2 to 4 months after initial identification.
b. Suspend until MRI demonstrates radiographic stabilization and symptoms, if present, resolve. Use clinical judgment when considering whether to continue treatment or permanently discontinue KISUNLA.
In patients who develop intracerebral hemorrhage greater than 1 cm in diameter during treatment with KISUNLA, suspend dosing until MRI demonstrates radiographic stabilization and symptoms, if present, resolve. Resumption of dosing should be guided by clinical judgment.
2.4 Dilution Instructions
- Prior to administration, KISUNLA must be diluted with 0.9% sodium chloride injection (see Table 4).
- Use aseptic technique when preparing the diluted KISUNLA solution for intravenous infusion.
- Allow KISUNLA to equilibrate to room temperature before preparation.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. KISUNLA solution is clear to opalescent, colorless to slightly yellow to slightly brown. Do not use if particulate matter or discolorations are present.
- Withdraw required volume of KISUNLA and mix with 0.9% sodium chloride injection, to the recommended total volume for a final concentration of 4 mg/mL to 10 mg/mL (see Table 4). Use only 0.9% sodium chloride injection for dilution.
| KISUNLA Dose (mg) | KISUNLA Volume (mL) | Volume of 0.9% Sodium Chloride Injection Diluent (mL) | Final Volume of Diluted Solution to be Infused (mL) | Final Concentration of Diluted Solution (mg/mL)a |
| 700 mg | 40 mLb | 30 mL to 135 mL | 70 mL to 175 mL | 700 mg/175 mL (4 mg/mL) to 700 mg/70 mL (10 mg/mL) |
| 1400 mg | 80 mLc | 60 mL to 270 mL | 140 mL to 350 mL | 1400 mg/350 mL (4 mg/mL) to 1400 mg/140 mL (10 mg/mL) |
|
a. final concentration of 4 mg/mL to 10 mg/mL |
|
b. 2 vials of KISUNLA |
|
c. 4 vials of KISUNLA |
- Each vial is for one-time use only. Discard any unused portion left in the vial.
- Gently invert the diluted KISUNLA solution to mix completely. Do not shake.
- After dilution, immediate use is recommended [see Description (11)]. If the diluted KISUNLA solution is not administered immediately, store refrigerated at 2°C to 8°C (36°F to 46°F) for up to 72 hours or at room temperature (20°C to 25°C [68°F to 77°F]) for up to 12 hours.
- Do not freeze the diluted KISUNLA solution.
- Storage times include the duration of infusion.
2.5 Administration Instructions
- Visually inspect the diluted KISUNLA solution for particles or discoloration prior to administration. Do not use if it is discolored, or opaque or foreign particles are seen.
- Prior to infusion, if the diluted solution has been stored under refrigeration, allow the diluted KISUNLA solution to warm to room temperature.
- Administer the entire diluted solution intravenously over approximately 30 minutes.
- Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity-type reaction [see Warnings and Precautions (5.2)].
- Flush the line only with 0.9% sodium chloride injection at the end of the infusion per access specific line maintenance protocol.
- Observe the patient post-infusion for a minimum of 30 minutes to evaluate for infusion reactions and hypersensitivity reactions [see Warnings and Precautions (5.2)].
KISUNLA (donanemab-azbt) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow to slightly brown solution. KISUNLA is supplied in one vial per carton as follows:
350 mg/20 mL (17.5 mg/mL) single-dose vial: NDC 0002-9401-01.
Unopened Vial
- Store refrigerated at 2°C to 8°C (36°F to 46°F).
- Keep the vial in the outer carton to protect from light.
- Do not freeze or shake.
- If refrigeration is not available, may be stored at room temperature (20°C to 25°C [68°F to 77°F]) for up to 3 days.
Diluted Solution
- Each vial is for one-time use only. Discard any unused portion left in the vial.
- Gently invert the diluted KISUNLA solution to mix completely. Do not shake.
- After dilution, immediate use is recommended [see Description (11)]. If the diluted KISUNLA solution is not administered immediately, store refrigerated at 2°C to 8°C (36°F to 46°F) for up to 72 hours or at room temperature (20°C to 25°C [68°F to 77°F]) for up to 12 hours.
- Do not freeze the diluted KISUNLA solution.
- Storage times include the duration of infusion.
