Included as part of the PRECAUTIONS section.
Capillary Leak Syndrome (CLS)
Capillary leak syndrome (CLS), including life-threatening
cases, has been reported among patients treated with LUMOXITI and is
characterized by hypoalbuminemia, hypotension, symptoms of fluid overload, and
hemoconcentration. In the combined safety database of HCL patients treated with
LUMOXITI, CLS occurred in 34% (44/129) of patients, including Grade 2 in 23%
(30/129), Grade 3 in 1.6% (2/129), and Grade 4 in 2% (3/129).
Most cases of CLS occurred in the first 8 days (range: 1
to 19) of a treatment cycle, however, cases have also been reported on other
days throughout the cycle. The median time to resolution of CLS was 12 days
(range: 1 to 53).
Monitor patient weight and blood pressure prior to each
LUMOXITI infusion and as clinically indicated during treatment. Assess patients
for signs and symptoms of CLS, including weight gain (increase in 5.5 pounds
(2.5 kg) or ≥ 5% from Day 1 of current cycle), hypotension, peripheral
edema, shortness of breath or cough, and pulmonary edema and/or serosal
effusions. In addition, the following changes in laboratory parameters may help
identify CLS: hypoalbuminemia, elevated hematocrit, leukocytosis, and
thrombocytosis [see DOSAGE AND ADMINISTRATION].
CLS may be life-threatening or fatal if treatment is
delayed. Counsel patients to seek immediate medical attention should signs or
symptoms of CLS occur at any time. Patients who develop CLS should receive
appropriate supportive measures, including concomitant oral or intravenous
corticosteroids, and hospitalization as clinically indicated. Withhold LUMOXITI
for Grade 2 CLS until resolution, and permanently discontinue for Grade ≥
3 CLS [see DOSAGE AND ADMINISTRATION].
Hemolytic Uremic Syndrome (HUS)
Hemolytic Uremic Syndrome (HUS), including life
threatening cases, has been reported in patients treated with LUMOXITI and is
characterized by the triad of microangiopathic hemolytic anemia,
thrombocytopenia, and progressive renal failure. In the combined safety
database of HCL patients treated with LUMOXITI, HUS occurred in 7% (9/129) of
patients, including Grade 3 in 3% (4/129) and Grade 4 in 0.8% (1/129).
Most cases of HUS occurred in the first 9 days (range: 1
to 16) of a treatment cycle, however, cases have also been reported on other
days throughout the cycle. The median time to resolution of HUS was 11.5 days
(range: 2 to 44). All cases resolved, including those who discontinued
Avoid LUMOXITI in patients with prior history of severe
thrombotic microangiopathy (TMA) or HUS. Administer prophylactic intravenous
fluids before and after LUMOXITI infusions [see DOSAGE AND ADMINISTRATION].
In Study 1053, patients with a platelet count ≥ 100,000/mm³ received
low-dose aspirin on Days 1 through 8 of each 28-day cycle for prophylaxis of
Monitor blood chemistry and complete blood counts prior
to each dose and on Day 8 of each treatment cycle. Monitoring mid-cycle is also
recommended. Consider the diagnosis of HUS in patients who develop hemolytic
anemia, worsening or sudden onset of thrombocytopenia, increase in creatinine
levels, elevation of bilirubin and/or LDH, and have evidence of hemolysis based
on peripheral blood smear schistocytes [see DOSAGE AND ADMINISTRATION].
The events of HUS may be life-threatening if treatment is
delayed with increased risk of progressive renal failure requiring dialysis. If
HUS is suspected initiate appropriate supportive measures, including fluid
repletion, hemodynamic monitoring, and consider hospitalization as clinically
indicated. Discontinue LUMOXITI in patients with HUS [see DOSAGE AND
Renal toxicity has been reported in patients treated with
LUMOXITI therapy. In the combined safety database of HCL patients treated with
LUMOXITI, 26% (34/129) reported adverse events of renal toxicity, including
acute kidney injury (2.3%), renal failure (2.3%), renal impairment (1.6%),
serum creatinine increased (17%), and proteinuria (8%). Grade 3 acute kidney
injury occurred in 1.6% (2/129) of patients. All other events were mild to
moderate in severity.
Based on laboratory findings, during treatment, serum
creatinine increased by two or more grades from baseline in 22% (29/129) of
patients, including increases of Grade 3 in 1.6% (2/129) of patients. At the
end of treatment, serum creatinine levels remained elevated at 1.5-to 3-times
the upper limit of normal in 5% of patients. Patients who experience HUS, those
≥ 65 years of age, or those with baseline renal impairment may be at
increased risk for worsening of renal function following treatment with
LUMOXITI [see Use In Specific Populations].
Monitor renal function prior to each infusion of
LUMOXITI, and as clinically indicated throughout treatment. Delay LUMOXITI
dosing in patients with Grade ≥ 3 elevations in creatinine, or upon
worsening from baseline by ≥ 2 grades [see DOSAGE AND ADMINISTRATION].
Infusion Related Reactions
Infusion related reactions occurred in patients treated
with LUMOXITI, and were defined as the occurrence of any one of the following
events on the day of study drug infusion: chills, cough, dizziness, dyspnea,
feeling hot, flushing, headache, hypertension, hypotension, infusion related
reaction, myalgia nausea, pyrexia, sinus tachycardia, tachycardia, vomiting, or
wheezing. In Study 1053, infusion related reactions occurred in 50% (40/80) of
patients. Grade 3 infusion related events as defined, occurred in 11% (9/80) of
LUMOXITI-treated patients. The most frequently reported infusion related events
were nausea (15%), pyrexia (14%), chills (14%), vomiting (11%), headache (9%),
and infusion related reaction (9%).
Infusion related reactions may occur during any cycle of
treatment with LUMOXITI. Prior to each dose of LUMOXITI, premedicate with
antihistamines and antipyretics. If a severe infusion related reaction occurs,
interrupt the LUMOXITI infusion and institute appropriate medical management.
Administer an oral or intravenous corticosteroid approximately 30 minutes
before resuming, or before the next LUMOXITI infusion [see DOSAGE AND
In the combined safety database of HCL patients treated
with LUMOXITI, electrolyte abnormalities occurred in 57% (73/129) of patients
with the most common electrolyte abnormality being hypocalcemia occurring in
25% of patients. Grade 3 electrolyte abnormalities occurred in 14% (18/129) of
patients and Grade 4 electrolyte abnormalities occurred in 0.8% (1/129) of
patients. Electrolyte abnormalities co-occurred in the same treatment cycle
with CLS, HUS, fluid retention, or renal toxicity in 37% (48/129) of patients.
Monitor serum electrolytes prior to each dose and on Day
8 of each treatment cycle. Monitoring mid-cycle is also recommended.
Patient Counseling Information
Advise the patient to read the FDA-approved patient
labeling (Medication Guide).
Capillary Leak Syndrome
Advise patients on the risk of developing capillary leak
syndrome. Advise patients to immediately report any symptoms suggestive of
capillary leak syndrome, such as difficulty breathing, rapid weight gain,
hypotension, or swelling of their arms, legs, and/or face to their healthcare
provider for further evaluation [see WARNINGS AND PRECAUTIONS].
Hemolytic Uremic Syndrome
Advise patients on the risk of developing hemolytic
uremic syndrome. Advise patients on the importance of maintaining high fluid
intake, and the need for frequent monitoring of blood chemistry values [see WARNINGS
Inform patients that taking LUMOXITI may cause decreased
renal function. Advise patients to report any changes to urine output to their
healthcare provider for further evaluation [see WARNINGS AND PRECAUTIONS
and ADVERSE REACTIONS].
Infusion Related Reactions
Advise patients to contact their healthcare provider
immediately for signs or symptoms of infusion related reactions [see WARNINGS
Advise patients to report symptoms of electrolyte
abnormalities (e.g., muscle cramping, paresthesias, irregular or fast
heartbeat, nausea, seizures) to their healthcare provider immediately [see WARNINGS
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No studies have been conducted to assess the carcinogenic
or genotoxic potential of moxetumomab pasudotox-tdfk. Animal fertility studies
have not been conducted with moxetumomab pasudotox-tdfk.
Use In Specific Populations
Based on its mechanism of action and findings in non-pregnant
female animals, LUMOXITI is expected to cause maternal and embryo-fetal
toxicity when administered to a pregnant woman [see CLINICAL PHARMACOLOGY
and Nonclinical Toxicology]. There are no available data on LUMOXITI use
in pregnant women to inform a drug-associated risk of major birth defects and
miscarriage. Animal reproduction or developmental toxicity studies have not
been conducted with LUMOXITI. Advise pregnant women of the potential risk to a
The estimated background risk of major birth defects and
miscarriage for the indicated population is unknown. All pregnancies have a
background risk of birth defect, loss, or other adverse outcomes. In the U.S.
general population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2-4% and 15-20%,
No data are available regarding the presence of
moxetumomab pasudotox-tdfk in human milk, the effects on the breastfed child,
or the effects on milk production. The developmental and health benefits of
breastfeeding should be considered along with the mother's clinical need for
LUMOXITI and any potential adverse effects on the breastfed child from LUMOXITI
or from the underlying maternal condition.
Females And Males Of Reproductive Potential
To avoid potential exposure to the fetus, women of
reproductive potential should use effective contraception during treatment with
LUMOXITI and for at least 30 days after the last dose is received. Verify the
pregnancy status of females of reproductive potential prior to initiating
Safety and effectiveness have not been established in
In the combined safety database of HCL patients treated
with LUMOXITI, 31% (40/129) of patients treated with LUMOXITI were 65 years of
age or older and 8% (10/129) were 75 years of age or older. Exploratory
analyses across this population suggest a higher incidence of adverse reactions
leading to drug discontinuation (23% versus 7%) and renal toxicity (40% versus
20%) for patients 65 years of age or older as compared to those younger than 65
years. Clinical studies of LUMOXITI did not include sufficient numbers of
subjects aged 65 and over to determine whether there were differences in
efficacy between younger and older patients.