ADVERSE REACTIONS
The table below presents the incidences
of adverse reactions derived from an analysis of data contained within literature
reports of 7 studies involving 303 pediatric patients in which VUMON was administered
by injection as a single agent in a variety of doses and schedules for a variety
of hematologic malignancies and solid tumors. The total number of patients
evaluable for a given event was not 303 since the individual studies did not
address the occurrence of each event listed. Five of these 7 studies assessed
VUMON activity in hematologic malignancies, such as leukemia. Thus, many of
these patients had abnormal hematologic status at start of therapy with VUMON
and were expected to develop significant myelosuppression as an endpoint of
treatment.
Single-Agent VUMON Summary of Toxicity for All Evaluable Pediatric
Patients
Toxicity
|
Incidence in Evaluable
Patients (%)
|
Hematologic Toxicity |
|
Myelosuppression, nonspecified |
75 |
Leukopenia (<3,000 WBC/mcL) |
89 |
Neutropenia (<2,000 ANC/mcL) |
95 |
Thrombocytopenia (<100,000 plt/mcL) |
85 |
Anemia |
88 |
Non-Hematologic Toxicity |
|
Mucositis |
76 |
Diarrhea |
33 |
Nausea/vomiting |
29 |
Infection |
12 |
Alopecia |
9 |
Bleeding |
5 |
Hypersensitivity reactions |
5 |
Rash |
3 |
Fever |
3 |
Hypotension/Cardiovascular |
2 |
Neurotoxicity |
<1 |
Hepatic dysfunction |
<1 |
Renal dysfunction |
<1 |
Metabolic abnormalities |
<1 |
Hematologic Toxicity
VUMON, when used with other chemotherapeutic agents for the treatment
of ALL, results in severe myelosuppression. Sepsis, sometimes fatal, may be a consequence of severe myelosuppression. Early onset of profound myelosuppression
with delayed recovery can be expected when using the doses and schedules of
VUMON necessary for treatment of refractory ALL, since bone marrow hypoplasia
is a desired endpoint of therapy. The occurrence of acute non-lymphocytic
leukemia (ANLL), with or without a preleukemic phase, has been reported in
patients treated with VUMON in combination with other antineoplastic agents.
(See
PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment
of Fertility.)
Gastrointestinal Toxicity
Nausea and vomiting are the most common gastrointestinal toxicities,
having occurred in 29% of evaluable pediatric patients. The severity of this
nausea and vomiting is generally mild to moderate.
Hypotension
Transient hypotension following rapid intravenous administration
has been reported in 2% of evaluable pediatric patients. One episode of sudden
death, attributed to probable arrhythmia and intractable hypotension, has
been reported in an elderly patient receiving VUMON combination therapy for
a non-leukemic malignancy.
No other cardiac toxicity or electrocardiographic changes have
been documented. No delayed hypotension has been noted.
Allergic Reactions
Hypersensitivity reactions characterized by chills, fever, tachycardia,
flushing, bronchospasm, dyspnea, rash, and blood pressure changes (hypertension
or hypotension) have been reported to occur in approximately 5% of evaluable
pediatric patients receiving intravenous VUMON. The incidence of hypersensitivity
reactions to VUMON appears to be increased in patients with brain tumors and
in patients with neuroblastoma.
Central Nervous System
Neurotoxicity has been reported, including severe cases of neuropathy, in patients receiving vincristine sulfate and VUMON concomitantly.
Acute central nervous system depression
and hypotension have been observed in patients receiving investigational infusions
of high-dose VUMON who were pretreated with antiemetic drugs. The depressant
effects of the antiemetic agents and the alcohol content of the VUMON formulation
may place patients receiving higher than recommended doses of VUMON at risk
for central nervous system depression.
Alopecia
Alopecia, sometimes progressing to total baldness, was observed
in 9% of evaluable pediatric patients who received VUMON as single-agent therapy.
It was usually reversible.
Other Adverse Reactions
The following adverse reactions have been reported: headache, confusion, and asthenia. Headache and confusion were associated with hypersensitivity reactions.
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