Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/750
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
VUMON (Injection, Solution)
|
| dailymed-instance:dosage |
NOTE: Contact of undiluted VUMON (teniposide injection)
with plastic equipment or devices used to prepare solutions for infusion may
result in softening or cracking and possible drug product leakage. This effect
has not been reported with diluted solutions of
VUMON. In order to prevent extraction of the plasticizer DEHP [di(2-ethylhexyl)
phthalate], solutions of VUMON (teniposide injection) should be prepared in
non-DEHP containing LVP containers such as glass or polyolefin plastic bags
or containers. VUMON solutions should be administered with non-DEHP containing
IV administration sets. In one study, childhood ALL patients failing induction therapy
with a cytarabine-containing regimen were treated with the combination of
VUMON 165 mg/mand cytarabine 300 mg/mintravenously,
twice weekly for 8 to 9 doses. In another study, patients with childhood ALL
refractory to vincristine/prednisone-containing regimens were treated with
the combination of VUMON 250 mg/mand vincristine
1.5 mg/mintravenously, weekly for 4 to 8 weeks
and prednisone 40 mg/morally for 28 days. Adequate data in patients with hepatic insufficiency and/or renal
insufficiency are lacking, but dose adjustments may be necessary for patients
with significant renal or hepatic impairment.<br/>Preparation and Administration Precautions: VUMON is a cytotoxic anticancer drug and, as with other potentially
toxic compounds, caution should be exercised in handling and preparing the
solution of VUMON. Skin reactions associated with accidental exposure to VUMON
may occur. The use of gloves is recommended. If VUMON solution contacts the
skin, immediately wash the skin thoroughly with soap and water. If VUMON contacts
mucous membranes, the membranes should be flushed thoroughly with water.<br/>Preparation for Intravenous Administration: VUMON must be diluted with either 5% Dextrose Injection, USP or
0.9% Sodium Chloride Injection, USP, to give final teniposide concentrations
of 0.1 mg/mL, 0.2 mg/mL, 0.4 mg/mL, or 1.0 mg/mL. Solutions prepared in 5%
Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP at teniposide
concentrations of 0.1 mg/mL, 0.2 mg/mL, or 0.4 mg/mL are stable at room temperature
for up to 24 hours after preparation. VUMON solutions prepared at a final
teniposide concentration of 1.0 mg/mL should be administered within 4 hours
of preparation to reduce the potential for precipitation. Refrigeration
of VUMON solutions is not recommended. Stability and use times are
identical in glass and plastic parenteral solution containers. Although solutions are chemically stable under the conditions indicated,
precipitation of teniposide may occur at the recommended concentrations, especially
if the diluted solution is subjected to more agitation than is recommended
to prepare the drug solution for parenteral administration. In addition, storage
time prior to administration should be minimized and care should be taken
to avoid contact of the diluted solution with other drugs or fluids. Parenteral
drug products should be inspected visually for particulate matter and discoloration
prior to administration whenever solution and container permit. Precipitation
has been reported during 24-hour infusions of VUMON diluted to teniposide
concentrations of 0.1 to 0.2 mg/mL, resulting in occlusion
of central venous access catheters in several patients. Heparin solution can
cause precipitation of teniposide, therefore, the administration apparatus
should be flushed thoroughly with 5% Dextrose Injection, USP or 0.9% Sodium
Chloride Injection, USP before and after administration of VUMON. Hypotension has been reported following rapid intravenous administration;
it is recommended that the VUMON solution be administered over at least a
30- to 60-minute period. VUMON should not be given by rapid intravenous
injection. In a 24-hour study under simulated conditions of actual use of
the product relative to dilution strength, diluent and administration rates,
dilutions at 0.1 to 1.0 mg/mL were chemically stable for at least 24 hours.
Data collected for the presence of the extractable DEHP [di(2-ethylhexyl)
phthalate] from PVC containers show that levels increased with time and concentration
of the solutions. The data appeared similar for 0.9% Sodium Chloride Injection,
USP, and 5% Dextrose Injection, USP. Consequently, the use of PVC containers
is not recommended. Similarly, the use of non-DEHP IV administration sets is recommended.
Lipid administration sets or low DEHP-containing nitroglycerin sets will keep
patient's exposure to DEHP at low levels and are suitable for use. The diluted
solutions are chemically and physically compatible with the recommended IV
administration sets and LVP containers for up to 24 hours at ambient room
temperatureand lighting conditions. Because of the potential for precipitation,
compatibility with other drugs, infusion materials, or IV pumps cannot be
assured.<br/>Stability: Unopened ampules of VUMON (teniposide injection) are stable until
the date indicated on the package when stored under refrigeration (2��-8��C) in the original package. Freezing does not adversely affect the product.
|
| dailymed-instance:descripti... |
VUMON (teniposide injection) (also
commonly known as VM-26), is supplied as a sterile nonpyrogenic solution in
a nonaqueous medium intended for dilution with a suitable parenteral vehicle
prior to intravenous infusion. VUMON is available in 50 mg (5 mL) ampules.
Each mL contains 10 mg teniposide, 30 mg benzyl alcohol, 60 mg N,N-dimethylacetamide,
500 mg purified Cremophor EL (polyoxyethylated
castor oil)* and 42.7% (V/V) dehydrated alcohol. The pH of the clear solution
is adjusted to approximately 5 with maleic acid. Teniposide is a semisynthetic derivative of podophyllotoxin. The
chemical name for teniposide is 4'-demethylepipodophyllotoxin 9-[4,6-0-(R)-2-thenylidene-��-D-glucopyranoside].
Teniposide differs from etoposide, another podophyllotoxin derivative, by
the substitution of a thenylidene group on the glucopyranoside ring. Teniposide has the following structural formula: Teniposide is a white to off-white crystalline powder with the
empirical formula CHOS
and a molecular weight of 656.66. It is a lipophilic compound with a partition
coefficient value (octanol/water) of approximately 100. Teniposide is insoluble
in water and ether. It is slightly soluble in methanol and very soluble in
acetone and dimethylformamide.
|
| dailymed-instance:clinicalP... |
Teniposide is a phase-specific cytotoxic drug, acting in the late
S or early Gphase of the cell cycle, thus preventing
cells from entering mitosis. Teniposide causes dose-dependent single- and double-stranded breaks
in DNA and DNA-protein cross-links. The mechanism of action appears to be
related to the inhibition of type II topoisomerase activity since teniposide
does not intercalate into DNA or bind strongly to DNA. The cytotoxic effects
of teniposide are related to the relative numberof double-stranded DNA breaks
produced in cells, which are a reflection of the stabilization of a topoisomerase
II-DNA intermediate. Teniposide has a broad spectrum of in vivo antitumoractivity against murine tumors, including hematologic malignancies and various
solid tumors. Notably, teniposide is active against sublines of certain murine
leukemias with acquired resistance to cisplatin, doxorubicin, amsacrine, daunorubicin,
mitoxantrone, or vincristine. Plasma drug levels declined biexponentially following intravenous
infusion (155 mg/mover 1 to 2.5 hours) of VUMON
given to eight children (4-11 years old) with newly diagnosed acute lymphoblastic
leukemia (ALL). The observed average pharmacokinetic parameters and associated
coefficients of variation (CV%) based on a two-compartmental model analysis
of the data are as follows: There appears to be some association between an increase in serum
alkaline phosphatase or gamma glutamyl-transpeptidase and a decrease in plasma
clearance of teniposide. Therefore, caution should be exercised if VUMON is
to be administered to patients with hepatic dysfunction. In adults, at doses of 100 to 333 mg/m/day,
plasma levels increased linearly with dose. Drug accumulation in adult patients
did not occur after daily administration of VUMON for 3 days. In pediatric
patients, maximum plasma concentrations (C) after
infusions of 137 to 203 mg/mover
a period of one to two hours exceeded 40��g/mL; by 20 to 24 hours after infusion
plasma levels were generally<2��g/mL. Renal clearance of parent teniposide accounts for about 10% of
total body clearance. In adults, after intravenous administration of 10 mg/kg
or 67 mg/mof tritium-labeled teniposide, 44%
of the radiolabel was recovered in urine (parent drug and metabolites) within
120 hours after dosing. From 4% to 12% of a dose is excreted in urine as parent
drug. Fecal excretion of radioactivity within 72 hours after dosing accounted
for 0% to 10% of the dose. Mean steady-state volumes of distribution range from 8 to 44 L/mfor
adults and 3 to 11 L/mfor children. The blood-brain
barrier appears to limit diffusion of teniposide into the brain, although
in a study in patients with brain tumors, CSF levels of teniposide were higher
than CSF levels reported in other studies of patients who did not have brain
tumors. Teniposide is highly protein bound. In vitro plasma
protein binding of teniposide is>99%. The high affinity of teniposide for
plasma proteins may be an important factor in limiting distribution of drug
within the body. Steady-state volume of distribution of the drug increases
with a decrease in plasma albumin levels. Therefore, careful monitoring of
children with hypoalbuminemia is indicated during therapy. Levels of teniposide
in saliva, CSF and malignant ascites fluid are low relative to simultaneously
measured plasma levels. The pharmacokinetic characteristics of teniposide differ from those
of etoposide, another podophyllotoxin. Teniposide is more extensively bound
to plasma proteins and its cellular uptake is greater. Teniposide also has
a lower systemic clearance, a longer elimination half-life, and is excreted
in the urine as parent drug to a lesser extent than etoposide. In a study at St. Jude Children's Research Hospital (SJCRH), 9
children with acute lymphocytic leukemia (ALL) failing induction therapy with
a cytarabine-containing regimen, were treated with VUMON plus cytarabine.
Three of these patients were induced into complete remission with durations
of remission of 30 weeks, 59 weeks, and 13 years. In another study at SJCRH,
16 children with ALL refractory to vincristine/prednisone-containing regimens
were treated with VUMON plus vincristine and prednisone. Three of these patients
were induced into complete remission with durations of remission of 5.5, 37,
and 73 weeks. In these two studies, patients served as their own control based
on the premise that long-term complete remissions could not be achieved by
re-treatment with drugs to which they had previously failed to respond.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
VUMON is generally contraindicated in patients who have demonstrated
a previous hypersensitivity to teniposide and/or Cremophor EL
(polyoxyethylated castor oil).
|
| dailymed-instance:supply |
VUMON (teniposide injection)<br/>Storage: Store the unopened ampules under refrigeration (2��-8��C). Retain in original package to protect from light.<br/>Handling and Disposal: Procedures for proper handling and disposal of anticancer drugs
should be considered. Several guidelines on this subject have been published.There
is no general agreement that all of the procedures recommended in the guidelines
are necessary or appropriate. To minimize the risk of dermal exposure, always wear impervious
gloves when handling ampules containing VUMON (teniposide injection). This
includes all handling activities in clinical settings, pharmacies, storerooms,
and home healthcare settings, including during unpacking and inspection, transport
within a facility, and dose preparation and administration.
|
| dailymed-instance:genericDr... | |
| dailymed-instance:boxedWarn... |
WARNING: VUMON (teniposide injection) is a cytotoxic drug, which should
be administered under the supervision of a qualified physician experienced
in the use of cancer chemotherapeutic agents. Appropriate management of therapy
and complications is possible only when adequate treatment facilities are
readily available. Severe myelosuppression with resulting infection or bleeding may
occur. Hypersensitivity reactions, including anaphylaxis-like symptoms, may
occur with initial dosing or at repeated exposure to VUMON. Epinephrine, with
or without corticosteroids and antihistamines, has been employed to alleviate
hypersensitivity reaction symptoms.
|
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... | |
| dailymed-instance:possibleD... | |
| dailymed-instance:precautio... |
General: In all instances where the use of VUMON is considered for chemotherapy,
the physician must evaluate the need and usefulness of the drug against the
risk of adverse reactions. Most such adverse reactions are reversible if detected
early. If severe reactions occur, the drug should be reduced in dosage or
discontinued and appropriate corrective measures should be taken according
to the clinical judgment of the physician. Reinstitution of VUMON therapy
should be carried out with caution, and with adequate consideration of the
further need for the drug and alertness as to possible recurrence of toxicity. VUMON must be administered as an intravenous infusion. Care should
be taken to ensure that the intravenous catheter or needle is in the proper
position and functional prior to infusion. Improper administration of VUMON
may result in extravasation causing local tissue necrosis and/or thrombophlebitis.
In some instances, occlusion of central venous access devices has occurred
during 24-hour infusion of VUMON at a concentration of 0.1 to 0.2 mg/mL. Frequent
observation during these infusions is necessary to minimize this risk.<br/>Laboratory Tests: Periodic complete blood counts and assessments of renal and hepatic
function should be done during the course of VUMON treatment. They should
be performed prior to therapy and at clinically appropriate intervals during
and after therapy. There should be at least one determination of hematologic
status prior to therapy with VUMON.<br/>Drug Interactions: In a study in which 34 different drugs were tested, therapeutically
relevant concentrations of tolbutamide, sodium salicylate, and sulfamethizole
displaced protein-bound teniposide in fresh human serum to a small but significant
extent. Because of the extremely high binding of teniposide to plasma proteins,
these small decreases in binding could cause substantial increases in free
drug levels in plasma which could result in potentiation of drug toxicity.
Therefore, caution should be used in administering VUMON to patients receiving
these other agents. There was no change in the plasma kinetics of teniposide
when coadministered with methotrexate. However, the plasma clearance of methotrexate
was slightly increased. An increase in intracellular levels of methotrexate
was observed in vitro in the presence of teniposide.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: Children at SJCRH with ALL in remission who received maintenance
therapy with VUMON at weekly or twice weekly doses (plus other chemotherapeutic
agents), had a relative risk of developing secondary acute nonlymphocytic
leukemia (ANLL) approximately 12 times that of patients treated according
to other less intensive schedules. A short course of VUMON for remission-induction and/or consolidation
therapy was not associated with an increased risk of secondary ANLL, but the
number of patients assessed was small. The potential benefit from VUMON must
be weighed on a case by case basis against the potential risk of the induction
of a secondary leukemia. The carcinogenicity of teniposide has not been studied
in laboratory animals. Compounds with similar mechanisms of action and mutagenicity
profiles have been reported to be carcinogenic and teniposide should be considered
a potential carcinogen in humans. Teniposide has been shown to be mutagenic
in various bacterial and mammalian genetic toxicity tests. These include positive
mutagenic effects in the Ames/Salmonella and B. subtilis bacterial
mutagenicity assays. Teniposide caused gene mutations in both Chinese hamster
ovary cells and mouse lymphoma cells and DNA damage as measured by alkaline
elution in human lung carcinoma derived cell lines. In addition, teniposide
induced aberrations in chromosome structure in primary cultures of human lymphocytes in
vitro and in L5178y/TK +/- mouselymphoma cells in vitro.
Chromosome aberrations were observed in vivo in the embryonic
tissue of pregnant Swiss albino mice treated with teniposide. Teniposide also
caused a dose-related increase in sister chromatid exchanges in Chinese hamster
ovary cells, and it has been shown to be embryotoxic and teratogenic in rats
receiving teniposide during organogenesis. Treatment of pregnant rats IV with
doses between 1.0 and 3.0 mg/kg/day on alternate days from day 6 to 16 post
coitum caused retardation of embryonic development, prenatal mortality and
fetal abnormalities.<br/>Pregnancy:<br/>Pregnancy Category D: See WARNINGS.<br/>Nursing Mothers: It is not known whether this drug is excreted in human milk. Because
many drugs are excreted in human milk and because of the potential for serious
adverse reactions in nursing infants, a decision should be made whether to
discontinue nursing or to discontinue the drug, taking into account the importance
of VUMON therapy to the mother.<br/>Pediatric Use: Adverse events were evaluated in 7 studies involving 303 patients
(age range 0.5 months to 20 years) who received VUMON as a single agent . No association between any particular
age group and adverse effects was reported in any of these investigations.<br/>Patients with Down Syndrome: Patients with both Down Syndrome and leukemia may be especially
sensitive to myelosuppressive chemotherapy, therefore, initial dosing with
VUMON should be reduced in these patients. It is suggested that the first
course of VUMON should be given at half the usual dose. Subsequent courses
may be administered at higher dosages depending on the degree of myelosuppression
and mucositis encountered in earlier courses in an individual patient.
|
| dailymed-instance:overdosag... |
There is no known antidote for VUMON overdosage. The anticipated
complications of overdosage are secondary to bone marrow suppression. Treatment
should consist of supportive care, including blood products and antibiotics
as indicated.
|
| dailymed-instance:genericMe... |
TENIPOSIDE
|
| dailymed-instance:fullName |
VUMON (Injection, Solution)
|
| dailymed-instance:adverseRe... |
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 atstart of therapy with VUMON
and were expected to develop significant myelosuppression as an endpoint of
treatment.<br/>Hematologic Toxicity: VUMON, when used with other chemotherapeutic agents for the treatment
of ALL, results in 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.)<br/>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.<br/>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.<br/>Allergic Reactions: Hypersensitivity reactions characterized by chills, fever, tachycardia,
flushing, bronchospasm, dyspnea, 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.<br/>Central Nervous System: 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 of the VUMON formulation may place patients
receiving higher than recommended doses of VUMON at risk for central nervous
system depression.<br/>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.
|
| dailymed-instance:warning |
VUMON is a potent drug and should be used only by physicians experienced
in the administration of cancer chemotherapeutic drugs. Blood counts, as well
as renal and hepatic function tests, should be carefully monitored prior to
and during therapy. Patients being treated with VUMON (teniposide injection) should
be observed frequently for myelosuppression both during and after therapy.
Dose-limiting bone marrow suppression is the most significant toxicity associated
with VUMON therapy. Therefore, the following studies should be obtained at
the start of therapy and prior to each subsequent dose of VUMON: hemoglobin,
white blood cell count anddifferential, and platelet count. If necessary,
repeat bone marrow examination should be performed prior to the decision to
continue therapy in the setting of severe myelosuppression. Physicians should be aware of the possible occurrence of
a hypersensitivity reaction variably manifested by chills, fever, urticaria,
tachycardia, bronchospasm, dyspnea, hypertension or hypotension, and facial
flushing. This reaction may occur with the first dose of VUMON and may be
life threatening if not treated promptly with antihistamines, corticosteroids,
epinephrine, intravenous fluids, and other supportive measures as clinically
indicated. The exact cause of these reactions is unknown. They may be due
to the Cremophor EL (polyoxyethylated castor
oil)component of the vehicle or to teniposide itself. Patients who have experienced
prior hypersensitivity reactions to VUMON are at risk for recurrence of symptoms
and should only be re-treated with VUMON if the antileukemic benefit already
demonstrated clearly outweighs the risk of a probable hypersensitivity reaction
for that patient. When a decision is made to re-treat a patient with VUMON
in spite of an earlier hypersensitivity reaction, the patient should be pretreated
with corticosteroids and antihistamines and receive careful clinical observation
during and after VUMON infusion. In the clinical experience with VUMON at
SJCRH and the National Cancer Institute (NCI), re-treatment of patients with
prior hypersensitivity reactions has been accomplished using measures described
above. To date, there is no evidence to suggest cross-sensitization between
VUMON and VePesid. 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. (See ADVERSE
REACTIONS.) Patients receiving VUMON treatment should be under continuous
observation for at least the first 60 minutes following the start of the infusion
and at frequent intervals thereafter. If symptoms or signs of anaphylaxis
occur, the infusion should be stopped immediately, followed by the administration
of epinephrine, corticosteroids, antihistamines, pressor agents, or volume
expanders at the discretion of the physician. An aqueous solution of epinephrine
1:1000 and a source of oxygen should be available at the bedside. For parenteral administration, VUMON should be given only by slow
intravenous infusion (lasting at least 30 to 60 minutes) since hypotension
has been reported as a possible side effect of rapid intravenous injection,
perhaps due to a direct effect of Cremophor EL.
If clinically significant hypotension develops, the VUMON infusion should
be discontinued. The blood pressure usually normalizes within hours in response
to cessation of the infusion and administration of fluids or other supportive
therapy as appropriate. If the infusion is restarted, a slower administration
rate should be used and the patient should be carefully monitored. 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.<br/>Pregnancy:<br/>Pregnancy Category D: VUMON may cause fetal harm when administered to a pregnant woman.
VUMON has been shown to be teratogenic and embryotoxic in laboratory animals.
In pregnant rats, intravenous administration of VUMON, 0.1-3 mg/kg (0.6-18
mg/m), every second day from day 6 to day 16 post
coitum caused dose-related embryotoxicity and teratogenicity. Major anomalies
included spinal and rib defects, deformed extremities, anophthalmia, and celosomia. There are no adequate and well-controlled studies in pregnant women.
If VUMON is used during pregnancy, or if the patient becomes pregnant while
receiving this drug, the patient should be apprised of the potential hazard
to the fetus. Women of childbearing potential should be advised to avoid becoming
pregnant during therapy with VUMON.
|
| dailymed-instance:indicatio... |
VUMON, in combination with other approved anticancer agents, is
indicated for induction therapy in patients with refractory childhood acute
lymphoblastic leukemia.
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
VUMON
|