Warning
Melphalan should
be administered under the supervision of a qualified physician experienced in
the use of cancer chemotherapeutic agents. Severe bone marrow suppression with
resulting infection or bleeding may occur. Controlled trials comparing
intravenous (IV) to oral melphalan have shown more myelosuppression with the IV
formulation. Hypersensitivity reactions, including anaphylaxis, have occurred
in approximately 2% of patients who received the IV formulation. Melphalan is
leukemogenic in humans. Melphalan produces chromosomal aberrations in vitro and
in vivo and, therefore, should be considered potentially mutagenic in humans.
Alkeran
Description
Melphalan, also
known as L-phenylalanine mustard, phenylalanine mustard, L-PAM, or
L-sarcolysin, is a phenylalanine derivative of nitrogen mustard. Melphalan is a
bifunctional alkylating agent that is active against selected human neoplastic
diseases. It is known chemically as 4-[bis(2-chloroethyl)amino]-L-phenylalanine.
The molecular formula is C13H18Cl2N2O2 and the
molecular weight is 305.20. The structural formula is:
Melphalan is the
active L-isomer of the compound and was first synthesized in 1953 by Bergel and
Stock; the D-isomer, known as medphalan, is less active against certain animal
tumors, and the dose needed to produce effects on chromosomes is larger than
that required with the L-isomer. The racemic (DL-) form is known as merphalan
or sarcolysin.
Melphalan is
practically insoluble in water and has a pKa1 of ∼2.5.
Alkeran for
Injection is supplied as a sterile, nonpyrogenic, freeze-dried powder. Each
single-use vial contains melphalan hydrochloride equivalent to 50 mg
melphalan and 20 mg povidone. Alkeran for Injection is reconstituted using
the sterile diluent provided. Each vial of sterile diluent contains sodium
citrate 0.2 g, propylene glycol 6.0 mL, ethanol (96%) 0.52 mL,
and Water for Injection to a total of 10 mL. Alkeran for Injection is
administered intravenously.
Alkeran -
Clinical Pharmacology
Melphalan is an
alkylating agent of the bischloroethylamine type. As a result, its cytotoxicity
appears to be related to the extent of its interstrand cross-linking with DNA,
probably by binding at the N7 position of guanine. Like other
bifunctional alkylating agents, it is active against both resting and rapidly
dividing tumor cells.
Pharmacokinetics
Following
injection, drug plasma concentrations declined rapidly in a biexponential
manner with distribution phase and terminal elimination phase half-lives of
approximately 10 and 75 minutes, respectively. Estimates of average total
body clearance varied among studies, but typical values of approximately 7 to
9 mL/min/kg (250 to 325 mL/min/m2) were observed.
One study has reported that on repeat dosing of 0.5 mg/kg every
6 weeks, the clearance of melphalan decreased from 8.1 mL/min/kg
after the first course, to 5.5 mL/min/kg after the third course, but did
not decrease appreciably after the third course. Mean (±SD) peak melphalan
plasma concentrations in myeloma patients given IV melphalan at doses of 10 or
20 mg/m2 were 1.2 ± 0.4 and
2.8 ± 1.9 mcg/mL, respectively.
The steady-state
volume of distribution of melphalan is 0.5 L/kg. Penetration into
cerebrospinal fluid (CSF) is low. The average melphalan binding to plasma
proteins is highly variable (range: 53% to 92%). Serum albumin is the major
binding protein, accounting for approximately 40% to 60% of the plasma protein
binding, while α1-acid glycoprotein accounts for about 20% of the plasma
protein binding. Approximately 30% of melphalan is (covalently) irreversibly
bound to plasma proteins. Interactions with immunoglobulins have been found to
be negligible.
Melphalan is
eliminated from plasma primarily by chemical hydrolysis to monohydroxymelphalan
and dihydroxymelphalan. Aside from these hydrolysis products, no other
melphalan metabolites have been observed in humans. Although the contribution
of renal elimination to melphalan clearance appears to be low, one study noted
an increase in the occurrence of severe leukopenia in patients with elevated
BUN after 10 weeks of therapy.
Clinical Trial
A randomized
trial compared prednisone plus IV melphalan to prednisone plus oral melphalan
in the treatment of myeloma. As discussed below, overall response rates at
week 22 were comparable; however, because of changes in trial design,
conclusions as to the relative activity of the 2 formulations after
week 22 are impossible to make.
Both arms
received oral prednisone starting at 0.8 mg/kg/day with doses tapered over
6 weeks. Melphalan doses in each arm were:
Arm 1: Oral
melphalan 0.15 mg/kg/day x 7 followed by 0.05 mg/kg/day when WBC
began to rise.
Arm 2: IV
melphalan 16 mg/m2 q 2 weeks x 4 (over
6 weeks) followed by the same dose every 4 weeks.
Doses of
melphalan were adjusted according to the following criteria:
Table 1. Criteria for Dosage Adjustment in a Randomized
Clinical Trial
|
|
WBC/mm3
|
Platelets
|
Percent of Full Dose
|
|
≥4,000
|
≥100,000
|
100
|
|
≥3,000
|
≥75,000
|
75
|
|
≥2,000
|
≥50,000
|
50
|
|
<2,000
|
<50,000
|
0
|
One hundred
seven patients were randomized to the oral melphalan arm and 203 patients
to the IV melphalan arm. More patients had a poor-risk classification (58%
versus 44%) and high tumor load (51% versus 34%) on the oral compared to the IV
arm (P<0.04). Response rates at week 22 are shown in
the following table:
Table 2. Response Rates at Week 22
|
|
Initial Arm
|
Evaluable
Patients
|
Responders
n (%)
|
P
|
|
Oral melphalan
|
100
|
44 (44%)
|
P>0.2
|
|
IV melphalan
|
195
|
74 (38%)
|
Because of
changes in protocol design after week 22, other efficacy parameters such
as response duration and survival cannot be compared.
Severe
myelotoxicity (WBC ≤1,000 and/or platelets ≤25,000) was more common in the IV
melphalan arm (28%) than in the oral melphalan arm (11%).
An association
was noted between poor renal function and myelosuppression; consequently, an
amendment to the protocol required a 50% reduction in IV melphalan dose if the
BUN was ≥30 mg/dL. The rate of severe leukopenia in the IV arm in the
patients with BUN over 30 mg/dL decreased from 50% (8/16) before protocol
amendment to 11% (3/28) (P = 0.01) after the amendment.
Before the
dosing amendment, there was a 10% (8/77) incidence of drug-related death in the
IV arm. After the dosing amendment, this incidence was 3% (3/108). This
compares to an overall 1% (1/100) incidence of drug-related death in the oral
arm.
Indications and
Usage for Alkeran
Alkeran for
Injection is indicated for the palliative treatment of patients with multiple
myeloma for whom oral therapy is not appropriate.
Contraindications
Melphalan should
not be used in patients whose disease has demonstrated prior resistance to this
agent. Patients who have demonstrated hypersensitivity to melphalan should not
be given the drug.
Warnings
Alkeran for
Injection may cause local tissue damage should extravasation occur, and
consequently it should not be administered by direct injection into a
peripheral vein. It is recommended that Alkeran for Injection be administered
by injecting slowly into a fast-running IV infusion via an injection port, or
via a central venous line (see DOSAGE AND ADMINISTRATION: Administration
Precautions).
Melphalan should
be administered in carefully adjusted dosage by or under the supervision of
experienced physicians who are familiar with the drug's actions and the
possible complications of its use.
As with other
nitrogen mustard drugs, excessive dosage will produce marked bone marrow
suppression. Bone marrow suppression is the most significant toxicity
associated with Alkeran for Injection in most patients. Therefore, the
following tests should be performed at the start of therapy and prior to each
subsequent dose of Alkeran: platelet count, hemoglobin, white blood cell count,
and differential. Thrombocytopenia and/or leukopenia are indications to
withhold further therapy until the blood counts have sufficiently recovered.
Frequent blood counts are essential to determine optimal dosage and to avoid
toxicity. Dose adjustment on the basis of blood counts at the nadir and day of
treatment should be considered.
Hypersensitivity
reactions including anaphylaxis have occurred in approximately 2% of patients
who received the IV formulation (see ADVERSE REACTIONS). These reactions
usually occur after multiple courses of treatment. Treatment is symptomatic.
The infusion should be terminated immediately, followed by the administration
of volume expanders, pressor agents, corticosteroids, or antihistamines at the
discretion of the physician. If a hypersensitivity reaction occurs, IV or oral
melphalan should not be readministered since hypersensitivity reactions have
also been reported with oral melphalan.
Carcinogenesis
Secondary
malignancies, including acute nonlymphocytic leukemia, myeloproliferative
syndrome, and carcinoma, have been reported in patients with cancer treated
with alkylating agents (including melphalan). Some patients also received other
chemotherapeutic agents or radiation therapy. Precise quantitation of the risk
of acute leukemia, myeloproliferative syndrome, or carcinoma is not possible.
Published reports of leukemia in patients who have received melphalan (and
other alkylating agents) suggest that the risk of leukemogenesis increases with
chronicity of treatment and with cumulative dose. In one study, the 10-year
cumulative risk of developing acute leukemia or myeloproliferative syndrome
after oral melphalan therapy was 19.5% for cumulative doses ranging from 730 to
9,652 mg. In this same study, as well as in an additional study, the
10-year cumulative risk of developing acute leukemia or myeloproliferative
syndrome after oral melphalan therapy was less than 2% for cumulative doses
under 600 mg. This does not mean that there is a cumulative dose below
which there is no risk of the induction of secondary malignancy. The potential
benefits from melphalan therapy must be weighed on an individual basis against
the possible risk of the induction of a second malignancy.
Adequate and
well-controlled carcinogenicity studies have not been conducted in animals.
However, intraperitoneal (IP) administration of melphalan in rats (5.4 to
10.8 mg/m2) and in mice (2.25 to 4.5 mg/m2) 3 times
per week for 6 months followed by 12 months post-dose observation
produced peritoneal sarcoma and lung tumors, respectively.
Mutagenesis
Melphalan has been
shown to cause chromatid or chromosome damage in humans. Intramuscular
administration of melphalan at 6 and 60 mg/m2 produced
structural aberrations of the chromatid and chromosomes in bone marrow cells of
Wistar rats.
Impairment of
Fertility
Melphalan causes
suppression of ovarian function in premenopausal women, resulting in amenorrhea
in a significant number of patients. Reversible and irreversible testicular
suppression have also been reported.
Pregnancy
Pregnancy
Category D. Melphalan may cause fetal harm when administered to
a pregnant woman. While adequate animal studies have not been conducted with IV
melphalan, oral (6 to 18 mg/m2/day for 10 days) and IP
(18 mg/m2) administration in rats was embryolethal and
teratogenic. Malformations resulting from melphalan included alterations of the
brain (underdevelopment, deformation, meningocele, and encephalocele) and eye
(anophthalmia and microphthalmos), reduction of the mandible and tail, as well
as hepatocele (exomphaly). There are no adequate and well-controlled studies in
pregnant women. If this drug is used during pregnancy, or if the patient
becomes pregnant while taking 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.
Precautions
General
In all instances
where the use of Alkeran for Injection is considered for chemotherapy, the
physician must evaluate the need and usefulness of the drug against the risk of
adverse events. Melphalan should be used with extreme caution in patients whose
bone marrow reserve may have been compromised by prior irradiation or
chemotherapy or whose marrow function is recovering from previous cytotoxic
therapy.
Dose reduction
should be considered in patients with renal insufficiency receiving IV
melphalan. In one trial, increased bone marrow suppression was observed in
patients with BUN levels ≥30 mg/dL. A 50% reduction in the IV melphalan
dose decreased the incidence of severe bone marrow suppression in the latter
portion of this study.
Administration
of live vaccines to immunocompromised patients should be avoided.
Information for
Patients
Patients should
be informed that the major acute toxicities of melphalan are related to bone
marrow suppression, hypersensitivity reactions, gastrointestinal toxicity, and
pulmonary toxicity. The major long-term toxicities are related to infertility
and secondary malignancies. Patients should never be allowed to take the drug
without close medical supervision and should be advised to consult their
physicians if they experience skin rash, signs or symptoms of vasculitis,
bleeding, fever, persistent cough, nausea, vomiting, amenorrhea, weight loss,
or unusual lumps/masses. Women of childbearing potential should be advised to
avoid becoming pregnant.
Laboratory Tests
Periodic
complete blood counts with differentials should be performed during the course
of treatment with melphalan. At least 1 determination should be obtained prior
to each dose. Patients should be observed closely for consequences of bone
marrow suppression, which include severe infections, bleeding, and symptomatic
anemia (see WARNINGS).
Drug
Interactions
The development
of severe renal failure has been reported in patients treated with a single
dose of IV melphalan followed by standard oral doses of cyclosporine. Cisplatin
may affect melphalan kinetics by inducing renal dysfunction and subsequently
altering melphalan clearance. IV melphalan may also reduce the threshold for
BCNU lung toxicity. When nalidixic acid and IV melphalan are given
simultaneously, the incidence of severe hemorrhagic necrotic enterocolitis has
been reported to increase in pediatric patients.
Carcinogenesis,
Mutagenesis, Impairment of Fertility
See WARNINGS
section.
Pregnancy
Teratogenic
Effects
Pregnancy
Category D: See WARNINGS section.
Nursing Mothers
It is not known
whether this drug is excreted in human milk. IV melphalan should not be given
to nursing mothers.
Pediatric Use
The safety and
effectiveness in pediatric patients have not been established.
Geriatric Use
Clinical studies
of Alkeran for Injection did not include sufficient numbers of subjects aged 65
and over to determine whether they respond differently from younger subjects.
Other reported clinical experience has not identified differences in responses
between the elderly and younger patients. In general, dose selection for an
elderly patient should be cautious, usually starting at the low end of the
dosing range, reflecting the greater frequency of decreased hepatic, renal, or
cardiac function, and of concomitant disease or other drug therapy.
ADVERSE
REACTIONS (SEE OVERDOSAGE)
The following
information on adverse reactions is based on data from both oral and IV
administration of melphalan as a single agent, using several different dose
schedules for treatment of a wide variety of malignancies.
Hematologic
The most common
side effect is bone marrow suppression leading to leukopenia, thrombocytopenia,
and anemia. White blood cell count and platelet count nadirs usually occur 2 to
3 weeks after treatment, with recovery in 4 to 5 weeks after
treatment. Irreversible bone marrow failure has been reported.
Gastrointestinal
Gastrointestinal
disturbances such as nausea and vomiting, diarrhea, and oral ulceration occur
infrequently. Hepatic disorders ranging from abnormal liver function tests to
clinical manifestations such as hepatitis and jaundice have been reported.
Hepatic veno-occlusive disease has been reported.
Hypersensitivity
Acute
hypersensitivity reactions including anaphylaxis were reported in 2.4% of
425 patients receiving Alkeran for Injection for myeloma (see WARNINGS).
These reactions were characterized by urticaria, pruritus, edema, skin rashes,
and in some patients, tachycardia, bronchospasm, dyspnea, and hypotension.
These patients appeared to respond to antihistamine and corticosteroid therapy.
If a hypersensitivity reaction occurs, IV or oral melphalan should not be
readministered since hypersensitivity reactions have also been reported with
oral melphalan. Cardiac arrest has also been reported rarely in association
with such reports.
Miscellaneous
Other reported
adverse reactions include skin hypersensitivity, skin ulceration at injection
site, skin necrosis rarely requiring skin grafting, maculopapular rashes,
vasculitis, alopecia, hemolytic anemia, allergic reaction, pulmonary fibrosis
(including fatal outcomes), and interstitial pneumonitis. Temporary significant
elevation of the blood urea has been seen in the early stages of therapy in
patients with renal damage. Subjective and transient sensation of warmth and/or
tingling.
Overdosage
Overdoses
resulting in death have been reported. Overdoses, including doses up to
290 mg/m2, have produced the following symptoms: severe nausea and
vomiting, decreased consciousness, convulsions, muscular paralysis, and
cholinomimetic effects. Severe mucositis, stomatitis, colitis, diarrhea, and
hemorrhage of the gastrointestinal tract occur at high doses (>100 mg/m2). Elevations in
liver enzymes and veno-occlusive disease occur infrequently. Significant
hyponatremia caused by an associated inappropriate secretion of ADH syndrome
has been observed. Nephrotoxicity and adult respiratory distress syndrome have
been reported rarely. The principal toxic effect is bone marrow suppression.
Hematologic parameters should be closely followed for 3 to 6 weeks. An
uncontrolled study suggests that administration of autologous bone marrow or
hematopoietic growth factors (i.e., sargramostim, filgrastim) may shorten the
period of pancytopenia. General supportive measures together with appropriate
blood transfusions and antibiotics should be instituted as deemed necessary by
the physician. This drug is not removed from plasma to any significant degree
by hemodialysis or hemoperfusion. A pediatric patient survived a 254-mg/m2 overdose
treated with standard supportive care.
Alkeran Dosage
and Administration
The usual IV
dose is 16 mg/m2. Dosage reduction of up to 50% should be considered in
patients with renal insufficiency (BUN ≥30 mg/dL) (see PRECAUTIONS:
General). The drug is administered as a single infusion over 15 to
20 minutes. Melphalan is administered at 2-week intervals for
4 doses, then, after adequate recovery from toxicity, at 4-week intervals.
Available evidence suggests about one third to one half of the patients with
multiple myeloma show a favorable response to the drug. Experience with oral
melphalan suggests that repeated courses should be given since improvement may
continue slowly over many months, and the maximum benefit may be missed if
treatment is abandoned prematurely. Dose adjustment on the basis of blood cell
counts at the nadir and day of treatment should be considered.
Administration
Precautions
As with other
toxic compounds, caution should be exercised in handling and preparing the
solution of Alkeran. Skin reactions associated with accidental exposure may
occur. The use of gloves is recommended. If the solution of Alkeran contacts
the skin or mucosa, immediately wash the skin or mucosa thoroughly with soap
and water.
Procedures for
proper handling and disposal of anticancer drugs should be considered. Several
guidelines on this subject have been published.1-4 There is no
general agreement that all of the procedures recommended in the guidelines are
necessary or appropriate.
Parenteral drug
products should be visually inspected for particulate matter and discoloration
prior to administration whenever solution and container permit. If either
occurs, do not use this product.
Care should be
taken to avoid possible extravasation of melphalan and in cases of poor
peripheral venous access, consideration should be given to use of a central
venous line (see WARNINGS).
Preparation for
Administration/Stability
1.
Alkeran for
Injection must be reconstituted by rapidly injecting 10 mL of the supplied
diluent directly into the vial of lyophilized powder using a sterile needle
(20-gauge or larger needle diameter) and syringe. Immediately shake vial
vigorously until a clear solution is obtained. This provides a 5-mg/mL solution
of melphalan. Rapid addition of the diluent followed by immediate vigorous
shaking is important for proper dissolution.
2.
Immediately dilute the dose to be administered in 0.9% Sodium
Chloride Injection, USP, to a concentration not greater than 0.45 mg/mL.
3.
Administer the
diluted product over a minimum of 15 minutes.
4.
Complete
administration within 60 minutes of reconstitution.
The time between reconstitution/dilution and
administration of Alkeran should be kept to a minimum because reconstituted and
diluted solutions of Alkeran are unstable. Over as short a time as
30 minutes, a citrate derivative of melphalan has been detected in
reconstituted material from the reaction of Alkeran with Sterile Diluent for
Alkeran. Upon further dilution with saline, nearly 1% label strength of melphalan
hydrolyzes every 10 minutes.
A precipitate
forms if the reconstituted solution is stored at 5°C. DO NOT REFRIGERATE THE
RECONSTITUTED PRODUCT.
How is Alkeran Supplied
Alkeran for
Injection is supplied in a carton containing one single-use clear glass vial of
freeze-dried melphalan hydrochloride equivalent to 50 mg melphalan and one
10-mL clear glass vial of sterile diluent (NDC 52609-3001-0).
Store at controlled room temperature 15° to 30°C (59° to
86°F) and protect from light.
REFERENCES
1.
NIOSH Alert:
Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs
in Healthcare Settings. U.S. Department of Health and Human Services, Public
Health Service. Centers for Disease Control and Prevention, National Institute
for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.
2.
OSHA Technical
Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure
to Hazardous Drugs. OSHA, 1999.
http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html
3.
American Society
of Health-System Pharmacists. (2006) ASHP Guidelines on Handling Hazardous
Drugs. Am J Health-Syst Pharm. 2006;63:1172-1193.
4.
Polovich M,
White JM, Kelleher LO (eds.) 2005. Chemotherapy and Biotherapy Guidelines and
Recommendations for Practice. (2nd ed.) Pittsburgh, PA: Oncology
Nursing Society.
Alkeran is a
registered trademark of GlaxoSmithKline.
Alkeran and
Diluent manufactured by:
GlaxoSmithKline
Research
Triangle Park, NC 27709
Distributed by:
ApoPharma USA
Inc
Rockville, MD
20850
©2011,
GlaxoSmithKline. All rights reserved.
June 2011
ALJ-AP:2PI
PRINICIPAL DISPLAY PANEL
NDC 52609-3001-0
Alkeran®
(melphalan hydrochloride)
for Injection
SINGLE-USE
Rx only
One vial of
Alkeran for injection containing sterile, nonpyrogenic, freeze-dried melphalan
hydrochloride equivalent to 50 mg melphalan and 20 mg povidone.
One vial of
sterile, nonpyrogenic diluent containing 0.2 g sodium citrate, 6.0 mL propylene
glycol, 0.52 mL ethanol (96%), and Water for Injection to a total of 10 mL.
For Intravenous Infusion.
Reconstitute
with enclosed diluent. See enclosed package insert for additional
reconstitution and administration instructions.
See prescribing
information for Dosage and Administration.
Store at
controlled room temperature, 15o to 30oC (59o to 86oF) and protect
from light.
Add diluent rapidly.
Immediately shake vial vigorously.
Alkeran and
Diluent
Manufactured by:
GlaxoSmithKline
Research
Triangle Park, NC 27709
Distributed by:
ApoPharma USA Inc
Rockville, MD
20850
10000000101311
Rev. 11/11
|
Alkeran melphalan
hydrochloride kit
|
|
Product Information
|
|
Product Type
|
HUMAN PRESCRIPTION DRUG LABEL
|
Item Code (Source)
|
NDC:52609-3001
|
|
|
Packaging
|
|
#
|
Item Code
|
Package Description
|
|
|
1
|
NDC:52609-3001-0
|
1 KIT in 1 CARTON
|
|
|
|
Quantity of Parts
|
|
Part #
|
Package Quantity
|
Total Product Quantity
|
|
|
|
Part 1
|
1 VIAL, SINGLE-DOSE
|
10 mL
|
|
|
|
Part 2
|
1 VIAL, SINGLE-USE
|
10 mL
|
|
|
|
|
Part 1 of 2
|
|
Alkeran melphalan
hydrochloride injection, powder, for solution
|
|
|
Product Information
|
|
Item Code (Source)
|
NDC:52609-3002
|
|
|
|
Route of Administration
|
INTRAVENOUS
|
DEA Schedule
|
|
|
|
Active Ingredient/Active Moiety
|
|
Ingredient Name
|
Basis of Strength
|
Strength
|
|
MELPHALAN HYDROCHLORIDE (MELPHALAN)
|
MELPHALAN
|
50 mg in 10 mL
|
|
|
Inactive Ingredients
|
|
Ingredient Name
|
Strength
|
|
POVIDONES
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package Description
|
|
|
1
|
NDC:52609-3002-0
|
10 mL in 1 VIAL, SINGLE-DOSE
|
|
|
|
|
|
Marketing Information
|
|
Marketing Category
|
Application Number or Monograph Citation
|
Marketing Start Date
|
Marketing End Date
|
|
NDA
|
NDA020207
|
01/01/2011
|
|
|
|
Part 2 of 2
|
|
DILUENT water
injection
|
|
|
Product Information
|
|
Item Code (Source)
|
NDC:52609-3003
|
|
|
|
Route of Administration
|
INTRAVENOUS
|
DEA Schedule
|
|
|
|
Inactive Ingredients
|
|
Ingredient Name
|
Strength
|
|
WATER
|
|
|
SODIUM CITRATE
|
|
|
PROPYLENE GLYCOL
|
|
|
ALCOHOL
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package Description
|
|
|
1
|
NDC:52609-3003-0
|
10 mL in 1 VIAL, SINGLE-USE
|
|
|
|
|
|
Marketing Information
|
|
Marketing Category
|
Application Number or Monograph Citation
|
Marketing Start Date
|
Marketing End Date
|
|
NDA
|
NDA020207
|
01/01/2011
|
|
|
|
|
|
Marketing Information
|
|
Marketing Category
|
Application Number or Monograph Citation
|
Marketing Start Date
|
Marketing End Date
|
|
NDA
|
NDA020207
|
01/01/2011
|
|
|
|
Labeler - Apo-Pharma USA, Inc (962810821)
|
Revised: 02/2012
Apo-Pharma USA, Inc
