Dosage & Administration
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Kisunla Prescribing Information
Monoclonal antibodies directed against aggregated forms of beta amyloid, including KISUNLA, can cause amyloid related imaging abnormalities (ARIA), characterized as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). Incidence and timing of ARIA vary among treatments. ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events rarely can occur. Serious intracerebral hemorrhages >1 cm, some of which have been fatal, have been observed in patients treated with this class of medications. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, treating clinicians should consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy in a patient being treated with KISUNLA[see Warnings and Precautions , Adverse Reactions ].
ApoE ε4 Homozygotes
Patients who are apolipoprotein E ε4 (ApoE ε4) homozygotes (approximately 15% of Alzheimer's disease patients) treated with this class of medications, including KISUNLA, have a higher incidence of ARIA, including symptomatic, serious, and severe radiographic ARIA, compared to heterozygotes and noncarriers[see Warnings and Precautions ]. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to testing, prescribers should discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results. Prescribers should inform patients that if genotype testing is not performed,they can still be treated with KISUNLA; however, it cannot be determined if they are ApoE ε4 homozygotes and at higher risk for ARIA[see Warnings and Precautions ].
Consider the benefit of KISUNLA for the treatment of Alzheimer's disease and potential risk of serious adverse events associated with ARIA when deciding to initiate treatment with KISUNLA[see Warnings and Precautions and Clinical Studies ].
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.
Patient Selection
Confirm the presence of amyloid beta pathology prior to initiating treatment [see Clinical Pharmacology ].
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 ].
If an infusion is missed, resume administration every 4 weeks at the same dose as soon as possible.
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 and Adverse Reactions ].
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.
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. | |||
| 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 | ||
ARIA-H
The recommendations for dosing interruptions for patients with ARIA-H are provided in Table 3.
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. | |||
| 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 | |
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.
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.
a final concentration of 4 mg/mL to 10 mg/mL | ||||
b 2 vials of KISUNLA | ||||
c 4 vials of KISUNLA | ||||
| 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) |
- 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 ]. 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.
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 ].
- 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 ].
Injection: 350 mg/20 mL (17.5 mg/mL) clear to opalescent, colorless to slightly yellow to slightly brown solution in a single-dose vial.
Pregnancy
Risk Summary
There are no adequate data on KISUNLA use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. No animal studies have been conducted to assess the potential reproductive or developmental toxicity of KISUNLA.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.
Lactation
Risk Summary
There are no data on the presence of donanemab-azbt in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Published data from other monoclonal antibodies generally indicate low passage of monoclonal antibodies into human milk and limited systemic exposure in the breastfed infant. The effects of this limited exposure are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for KISUNLA and any potential adverse effects on the breastfed infant from KISUNLA or from the underlying maternal condition.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
In Study 1, the age of patients exposed to KISUNLA ranged from 59 to 86 years, with a mean age of 73 years; 90% were 65 years and older, and 41% were 75 years and older. No overall differences in safety or effectiveness of KISUNLA have been observed between patients 65 years of age and older and younger adult patients.
KISUNLA is contraindicated in patients with known serious hypersensitivity to donanemab-azbt or to any of the excipients. Reactions have included anaphylaxis [see Warnings and Precautions ].