DAUNORUBICIN HCL
DESCRIPTION:
WARNINGS
1. Cardiac function should be monitored
regularly in patients receiving DAUNOCIN
because of the potential risk for cardiac
toxicity and congestive heart failure.
Cardiac monitoring is advised especially in
those patients who have received prior
anthracyclines or who have pre-existing
cardiac disease.
2. Severe myelosuppression may occur.
3. DAUNOCIN should be administered only
under the supervision of a physician who is
experienced in the use of cancer
chemotherapeutic agents.
4. Dosage should be reduced in patients
with impaired hepatic function. (SEE DOSAGE
AND ADMINISTRATION)
5. A triad of back pain, flushing, and
chest tightness has been reported in 13.8%
of the patients (16/116) treated with
DAUNOCIN in the Phase III clinical trial,
and in 2.7% of treatment cycles (27/994).
This triad generally occurs during the
first five minutes of the infusion,
subsides with interruption of the infusion,
and generally does not recur if the
infusion is then resumed at a slower rate.
DAUNOCIN is a sterile, pyrogen-free, preservative-free product in a single use
vial for intravenous infusion.
DAUNOCIN contains an aqueous solution of the citrate salt of daunorubicin
encapsulated within lipid vesicles (liposomes) composed of a lipid bilayer of
distearoylphosphatidylcholine and cholesterol (2:1 molar ratio), with a mean
diameter of about 45 nm. The lipid to drug weight ratio is 18.7:1 (total
lipid:daunorubicin base), equivalent to a 10:5:1 molar ratio of
distearoylphosphatidylcholine:cholesterol:daunoru bicin. Daunorubicin is an
anthracycline antibiotic with antineoplastic activity, originally obtained from
Streptomyces Peucetius. Daunorubicin has a 4-ring anthracycline moiety linked by
a glycosidic bond to daunosamine, an amino sugar. Daunorubicin may also be
isolated from Streptomyces Coeruleorubidus and has the following chemical name:
(8S-cis)-8-acetyl- 10-((3-amino-2,3,6-trideoxy-alpha-L-lyxo- hexopyranosyl)oxy)-
7,8,9,10-tetrahydro- 6,8,11-trihydroxy-1-methoxy-5,12-naphthacenedione
hydrochloride.
ACTIONS/CLINICAL PHARMACOLOGY:
MECHANISM OF ACTION
DAUNOCIN is a liposomal preparation of daunorubicin formulated to maximize the
selectivity of daunorubicin for solid tumors In Situ. While in the circulation,
the DAUNOCIN formulation helps to protect the entrapped daunorubicin from
chemical and enzymatic degradation, minimizes protein binding, and generally
decreases uptake by normal (non- reticuloendothelial system) tissues. The
specific mechanism by which DAUNOCIN is able to deliver daunorubicin to solid
tumors In Situ is not known. However, it is believed to be a function of
increased permeability of the tumor neovasculature to some particles in the size
range of DAUNOCIN. In animal studies, daunorubicin has been shown to accumulate
in tumors to a greater extent when administered as DAUNOCIN than when
administered as daunorubicin. Once within the tumor environment, daunorubicin is
released over time enabling it to exert its antineoplastic activity.
PHARMACOKINETICS
Following intravenous injection of DAUNOCIN, plasma clearance of daunorubicin
shows monoexponential decline. The pharmacokinetic parameter values for total
daunorubicin following a single 40 mg/M(squared) dose of DAUNOCIN administered
over a 30-60 minute period to patients with AIDS-related Kaposi's sarcoma and
following a single rapid intravenous, 80 mg/M(squared) dose of conventional
daunorubicin to patients with disseminated solid malignancies are shown in Table
I.
TABLE I
PHARMACOKINETIC PARAMETERS OF
DAUNOCIN IN AIDS PATIENTS WITH
KAPOSI'S SARCOMA AND REPORTED
PARAMETERS FOR CONVENTIONAL
DAUNORUBICIN
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(b)CONVENTIONAL
PARAMETER (UNITS) (a)DAUNOCIN DAUNORUBICIN
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Plasma Clearance (mL/min) 17.3 +/- 6.1 (c)236 +/- 181
-----------------------------------------------------------------------------------------------------------------------------------------------------
Volume of Distribution (L) 6.4 +/- 1.5 1006 +/- 622
-----------------------------------------------------------------------------------------------------------------------------------------------------
Distribution Half-Life (h) 4.41 +/- 2.33 0.77 +/- 0.3
-----------------------------------------------------------------------------------------------------------------------------------------------------
Elimination Half-Life (h) ------------ 55.4 +/- 13.7
-----------------------------------------------------------------------------------------------------------------------------------------------------
(a)N=30, (b)N=4, (c)Calculated
The plasma pharmacokinetics of DAUNOCIN differ significantly from the results
reported for conventional daunorubicin hydrochloride. DAUNOCIN has a small
steady-state volume of distribution 6.4 L, (probably because it is confined to
vascular fluid volume), and clearance of 17 mL/min. These differences in the
volume of distribution and clearance result in a higher daunorubicin exposure
(in terms of plasma AUC) from DAUNOCIN than with conventional daunorubicin
hydrochloride. The apparent elimination half-life of DAUNOCIN is 4.4 hours, far
shorter than that of daunorubicin, and probably represents a distribution half-
life. Although preclinical biodistribution data in animals suggest that
DAUNOCIN crosses the normal blood-brain barrier, it is unknown whether
DAUNOCIN crosses the blood-brain barrier in humans.
METABOLISM: Daunorubicinol, the major active metabolite of daunorubicin, was
detected at low levels in the plasma following intravenous administration of
DAUNOCIN.
No formal assessments of pharmacokinetic drug- drug interactions between
DAUNOCIN and other agents have been conducted.
SPECIAL POPULATIONS: The pharmacokinetics of DAUNOCIN have not been evaluated
in women, in different ethnic groups, or in subjects with renal and hepatic
insufficiency.
CLINICAL STUDIES:
CLINICAL STUDY
In an open-label, randomized, controlled clinical study conducted at 13 centers
in the U.S.A. and Canada in advanced (25 or more mucocutaneous lesions; the
development of 10 or more lesions in a one month period of time; symptomatic
visceral involvement; or tumor-associated edema) HIV- related Kaposi's sarcoma,
two treatment regimens were compared as first line cytotoxic therapy: DAUNOCIN
40 mg/M(squared) and ABV (doxorubicin (Adriamycin(R)*) 10 mg/M(squared),
bleomycin 15 U, and vincristine 1.0 mg). All drugs were administered
intravenously every 2 weeks. Responses were assessed using the AIDS Clinical
Trials Group Oncology Committee of the National Institute of Allergy and
Infectious Diseases (ACTG) criteria (a response required at least one of any of
the following for at least 28 days; a. >/=50% reduction in the number; b. >/=50%
reduction in the sums of the products of the largest perpendicular diameters of
bidimensionally measurable marker lesions; or c. complete flattening of >/=50%
of all previously raised lesions). Table II summarizes the efficacy results.
*Andriamycin is a registered trademark of Adria Laboratories, Columbus, OH.
TABLE II
EFFICACY DATA
FIRST LINE CYTOTOXIC THERAPY FOR
ADVANCED KAPOSI'S SARCOMA
---------------------------------------------------------------------------------------------------------------
DAUNOCIN ABV
n=116 n=111
Response Rate 23%* 30%
---------------------------------------------------------------------------------------------------------------
Duration of Response,
Median 110 days** 113 days
---------------------------------------------------------------------------------------------------------------
Time to Progression,
Median 92 days**/* 105 days
---------------------------------------------------------------------------------------------------------------
Survival 342 days# 291 days
---------------------------------------------------------------------------------------------------------------
* The 95% confidence interval for difference in the response rates
(ABV - DAUNOCIN) was (-5%, 18%)
** The hazard ratio (ABV/DAUNOCIN) for duration of response was 0.80,
and the 95% confidence intervals were (0.44, 1.46)
**/*The hazard ratio (ABV/DAUNOCIN) for time to progression was 0.78,
and the 95% confidence intervals were (0.57, 1.07)
# The hazard ratio for mortality (ABV/DAUNOCIN) was 1.29, and 95%
confidence intervals were (0.92, 1.79)
Twenty of the 33 ABV responders responded to therapy by criteria more stringent
than flattening of lesions (i.e., shrinkage of lesions and/or reduction in the
number of lesions). Eleven of the 27 DAUNOCIN responders responded to therapy
by criteria other than flattening of lesions. Photographic evidence of tumor
response to DAUNOCIN and ABV was comparable across all anatomic sites (e.g.,
face, oral cavity, trunk, legs, and feet).
INDICATIONS AND USAGE:
DAUNOCIN is indicated as a first line cytotoxic therapy for advanced HIV-
associated Kaposi's sarcoma. DAUNOCIN is not recommended in patients with less
than advanced HIV-related Kaposi's sarcoma.
CONTRAINDICATIONS:
Therapy with DAUNOCIN is contraindicated in patients who have experienced a
serious hypersensitivity reaction to previous doses of DAUNOCIN or to any of
its constituents.
WARNINGS:
1. Cardiac function should be monitored
regularly in patients receiving DAUNOCIN
because of the potential risk for cardiac
toxicity and congestive heart failure.
Cardiac monitoring is advised especially in
those patients who have received prior
anthracyclines or who have pre-existing
cardiac disease.
2. Severe myelosuppression may occur.
3. DAUNOCIN should be administered only
under the supervision of a physician who is
experienced in the use of cancer
chemotherapeutic agents.
4. Dosage should be reduced in patients
with impaired hepatic function. (SEE DOSAGE
AND ADMINISTRATION)
5. A triad of back pain, flushing, and
chest tightness has been reported in 13.8%
of the patients (16/116) treated with
DAUNOCIN in the Phase III clinical trial,
and in 2.7% of treatment cycles (27/994).
This triad generally occurs during the
first five minutes of the infusion,
subsides with interruption of the infusion,
and generally does not recur if the
infusion is then resumed at a slower rate.
DAUNOCIN is intended for administration under the supervision of a physician
who is experienced in the use of cancer chemotherapeutic agents.
The primary toxicity of DAUNOCIN is myelosuppression, especially of the
granulocytic series, which may be severe, with much less marked effects on the
platelets and erythroid series. Careful hematologic monitoring is required and
since patients with HIV infection are immunocompromised, patients must be
observed carefully for evidence of intercurrent or opportunistic infections.
Special attention must be given to the potential cardiac toxicity of DAUNOCIN,
particularly in patients who have received prior anthracyclines or who have pre-
existing cardiac disease. Although there is no reliable means of predicting
congestive heart failure, cardiomyopathy induced by anthracyclines is usually
associated with a decrease of the left ventricular ejection fraction (LVEF).
Cardiac function should be evaluated in each patient by means of a history and
physical examination before each course of DAUNOCIN and determination of LVEF
should be performed at total cumulative doses of DAUNOCIN of 320 mg/M(squared),
480 mg/M(squared) and every 240 mg/M(squared) thereafter.
A triad of back pain, flushing, and chest tightness has been reported in 13.8%
of the patients (16/116) treated with DAUNOCIN in the randomized clinical trial
and in 2.7% of treatment cycles (27/994). This triad generally occurs during the
first five minutes of the infusion, subsides with interruption of the infusion,
and generally does not recur if the infusion is then resumed at a slower rate.
This combination of symptoms appears to be related to the lipid component of
DAUNOCIN, as a similar set of signs and symptoms has been observed with other
liposomal products not containing daunorubicin.
Daunorubicin has been associated with local tissue necrosis at the site of drug
extravasation. Although no such local tissue necrosis has been observed with
DAUNOCIN, care should be taken to ensure that there is no extravasation of drug
when DAUNOCIN is administered.
Dosage should be reduced in patients with impaired hepatic function. (SEE DOSAGE
AND ADMINISTRATION)
PREGNANCY CATEGORY D
DAUNOCIN can cause fetal harm when administered to a pregnant woman. DAUNOCIN
was administered to rats on gestation days 6 through 15 at 0.3, 1.0 or 2.0
mg/kg/day, (about 1/20th, 1/6th, or 1/3rd the recommended human dose on a
mg/M(squared) basis. DAUNOCIN produced severe maternal toxicity and
embryolethality at 2.0 mg/kg/day and was embryotoxic and caused fetal
malformations (anophthalmia, microphthalmia, incomplete ossification) at 0.3
mg/kg/day. Embryotoxicity was characterized by increased embryo-fetal deaths,
reduced number of litters, and reduced litter sizes.
There are no studies of DAUNOCIN in pregnant women. If DAUNOCIN is used during
pregnancy, or if the patient becomes pregnant while taking DAUNOCIN, the
patient must be warned of the potential hazard to the fetus. Patients should be
advised to avoid becoming pregnant while taking DAUNOCIN.
PRECAUTIONS:
DRUG INTERACTIONS
In the patient population studied, DAUNOCIN has been administered to patients
receiving a variety of concomitant medications (e.g., antiretroviral agents,
antiviral agents, anti-infective agents). Although interactions of DAUNOCIN
with other drugs have not been observed, no systematic studies of interactions
have been conducted.
CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY
No carcinogenesis, mutagenesis, or impairment of fertility studies were
conducted with DAUNOCIN.
Carcinogenesis: Carcinogenicity and mutagenicity studies have been conducted
with daunorubicin, the active component of DAUNOCIN. A high incidence of
mammary tumors was observed about 120 days after a single intravenous dose of
12.5 mg/kg daunorubicin in rats (about 2 times the human dose on a mg/M(squared)
basis). Mutagenesis: Daunorubicin was mutagenic in In Vitro tests (Ames assay,
V79 hamster cell assay), and clastogenic in In Vitro (CCRFCEM human
lymphoblasts) and in In Vivo (SCE assay in mouse bone marrow) tests. Impairment
of Fertility: Daunorubicin intravenous doses of 0.25 mg/kg/day (about 8 times
the human dose on a mg/M(squared) basis) in male dogs caused testicular atrophy
and total aplasia of spermatocytes in the seminiferous tubules.
PREGNANCY
Pregnancy "Category D". See WARNINGS Section.
PEDIATRIC USE
Safety and effectiveness in pediatric patients have not been established.
USE IN THE ELDERLY
Safety and effectiveness in the elderly have not been established.
SPECIAL POPULATIONS
Safety has not been established in patients with pre-existing hepatic or renal
dysfunction.
DRUG INTERACTIONS:
In the patient population studied, DAUNOCIN has been administered to patients
receiving a variety of concomitant medications (e.g., antiretroviral agents,
antiviral agents, anti-infective agents). Although interactions of DAUNOCIN
with other drugs have not been observed, no systematic studies of interactions
have been conducted.
(See Also PRECAUTIONS.)
ADVERSE REACTIONS:
DAUNOCIN contains daunorubicin, encapsulated within a liposome. Conventional
daunorubicin has acute myelosuppression as its dose limiting side effect, with
the greatest effect on the granulocytic series. In addition, daunorubicin causes
alopecia, and nausea and vomiting in a significant number of patients treated.
Extravasation of conventional daunorubicin can cause severe local tissue
necrosis. Chronic therapy at total doses above 300 mg/M(squared) causes a
cumulative-dose-related cardiomyopathy with congestive heart failure.
Administered as DAUNOCIN, daunorubicin has substantially altered
pharmacokinetics and some differences in toxicity. The most important acute
toxicity of DAUNOCIN remains myelosuppression, principally of the granulocytic
series, with much less marked effects on the platelets and erythroid series.
In an open-label, randomized, controlled clinical trial conducted in 13 centers
in the U.S.A. and Canada in advanced HIV-related Kaposi's sarcoma, two treatment
regimens were compared as first line cytotoxic therapy: DAUNOCIN and ABV
(doxorubicin (Adriamycin(R)*), bleomycin, and vincristine). All drugs were
administered intravenously every 2 weeks. The safety data presented below
include all reported or observed adverse experiences, including those not
considered to be drug related. Patients with advanced HIV-associated Kaposi's
sarcoma are seriously ill due to their underlying infection and are receiving
several concomitant medications including potentially toxic antiviral and
antiretroviral agents. The contribution of the study drugs to the adverse
experience profile is therefore difficult to establish.
Table III summarizes the important safety data.
TABLE III
SUMMARY OF IMPORTANT SAFETY DATA
-------------------------------------------------------------------------------------------------------------------------
DAUNOCIN ABV
(N=116) (N=111)
% of patients % of patients
--------------------------------------------------------------------------------------------------------------------------
Neutropenia
(<1000 cells/mm(cubed)) 36% 35%
Neutropenia
(<500 cells/mm(cubed)) 15% 5%
-------------------------------------------------------------------------------------------------------------------------
Opportunistic Infections/ 40% 27%
Illnesses, % of patients
------------------------------------------------------------------------------------------------------------------------
Median time to first 214 days 412 days**
Opportunistic Infections/
Illnesses
------------------------------------------------------------------------------------------------------------------------
Number of cases with 3 1
absolute reduction in
ejection fraction of
20-25%*
------------------------------------------------------------------------------------------------------------------------
Number of cases removed 2 0
from therapy due to
cardiac causes*
------------------------------------------------------------------------------------------------------------------------
Alopecia 8% 36%#
All grades % of patients
------------------------------------------------------------------------------------------------------------------------
Neuropathy 13% 41%#
All grades % of patients
------------------------------------------------------------------------------------------------------------------------
* The denominator is uncertain since there were several instances of
missing repeat cardiac evaluations
** p=0.21
# p<0.001
A triad of back pain, flushing and chest tightness was reported in 13.8% of the
patients (16/116) treated with DAUNOCIN in the Phase III clinical trial and in
2.7% of treatment cycles (27/994). Most of the episodes were mild to moderate in
severity (12% of patients and 2.5% of treatment cycles).
Mild alopecia was reported in 6% of patients treated with DAUNOCIN and moderate
alopecia in 2% of patients. Mild nausea was reported in 35% of DAUNOCIN
patients, moderate nausea in 16% of patients and severe nausea in 3% of
patients. For patients treated with DAUNOCIN, mild vomiting was reported in
10%, moderate in 10%, and severe in 3% of patients. Although grade 3-4 injection
site inflammation was reported in 2 patients treated with DAUNOCIN, no
instances of local tissue necrosis were observed with extravasation.
Table IV is a listing of all the mild-moderate and severe adverse events
reported on both treatment arms in Protocol 103-09 in >/=5% of DAUNOCIN
patients.
TABLE IV
ADVERSE EXPERIENCES:
PROTOCOL 103-09
-------------------------------------------------------------------------------------------------------------------------------------
DAUNOCIN ABV
(N=116) (N=111)
-----------------------------------------------------------------------------------------------------
Mild Mild
Moderate Severe Moderate Severe
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Nausea 51% 3% 45% 5%
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Fatigue 43% 6% 44% 7%
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Fever 42% 5% 49% 5%
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Diarrhea 34% 4% 29% 6%
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Cough 26% 2% 19% 0%
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Dyspnea 23% 3% 17% 3%
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Headache 22% 3% 23% 2%
------------------------------------------------------------------------------------------------------------------------------------
Allergic Reactions 21% 3% 19% 2%
------------------------------------------------------------------------------------------------------------------------------------
Abdominal Pain 20% 3% 23% 4%
------------------------------------------------------------------------------------------------------------------------------------
Anorexia 21% 2% 26% 2%
------------------------------------------------------------------------------------------------------------------------------------
Vomiting 20% 3% 26% 2%
------------------------------------------------------------------------------------------------------------------------------------
Rigors 19% 0% 23% 0%
------------------------------------------------------------------------------------------------------------------------------------
Back Pain 16% 0% 8% 0%
------------------------------------------------------------------------------------------------------------------------------------
Increased Sweating 12% 2% 12% 0%
------------------------------------------------------------------------------------------------------------------------------------
Neuropathy 12% 1% 38% 3%
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Rhinitis 12% 0% 6% 0%
------------------------------------------------------------------------------------------------------------------------------------
Edema 9% 2% 8% 1%
-----------------------------------------------------------------------------------------------------------------------------------
Chest Pain 9% 1% 7% 0%
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Depression 7% 3% 6% 0%
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Malaise 9% 1% 11% 1%
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Stomatitis 9% 1% 8% 0%
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Alopecia 8% 0% 36% 0%
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Dizziness 8% 0% 9% 0%
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Sinusitis 8% 0% 5% 1%
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Arthralgia 7% 0% 6% 0%
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Constipation 7% 0% 18% 0%
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Myalgia 7% 0% 12% 0%
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Pruritus 7% 0% 14% 0%
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Insomnia 6% 0% 14% 0%
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Influenza-like 5% 0% 5% 0%
symptoms
------------------------------------------------------------------------------------------------------------------------------------
Tenesmus 4% 1% 1% 0%
-------------------------------------------------------------------------------------------------------------------------------------
Abnormal vision 3% 2% 3% 0%
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The following adverse events were reported in =5% of patients treated with
DAUNOCIN, tabulated by body system.
BODY AS A WHOLE: Infection site inflammation
CARDIOVASCULAR: Hot flushes, hypertension, palpitation, syncope, tachycardia
DIGESTIVE: Increased appetite, dysphagia, GI hemorrhage, gastritis, gingival
bleeding, hemorrhoids, hepatomegaly, melena, dry mouth, tooth caries
HEMIC AND LYMPHATIC: Lymphadenopathy, splenomegaly
METABOLIC AND NUTRITIONAL: Dehydration, thirst
NERVOUS: Amnesia, anxiety, ataxia, confusion, convulsions, emotional
liability, abnormal gait, hallucination, hyperkinesia, hypertonia, meningitis,
somnolence, abnormal thinking, tremor
RESPIRATORY: Hemoptysis, hiccups, pulmonary infiltration, increased sputum
SKIN: Folliculitis, seborrhea, dry skin
SPECIAL SENSES: Conjunctivitis, deafness, earache, eye pain, taste perversion,
tinnitus
UROGENITAL: Dysuria, nocturia, polyuria
OVERDOSAGE:
The symptoms of acute overdosage are increased severities of the observed dose-
limiting toxicities of therapeutic doses of DAUNOCIN, myelosuppression
(especially granulocytopenia), fatigue, and nausea and vomiting.
DOSAGE AND ADMINISTRATION:
DAUNOCIN should be administered intravenously over a 60 minute period at a dose
of 40 mg/M(squared), with doses repeated every two weeks. Blood counts should be
repeated prior to each dose, and therapy withheld if the absolute granulocyte
count is less than 750 cells/mm(cubed). Treatment should be continued until
there is evidence of progressive disease (e.g., based on best response achieved:
new visceral sites of involvement, or progression of visceral disease;
development of 10 or more new, cutaneous lesions or a 25% increase in the number
of lesions compared to baseline; a change in the character of 25% or more of all
previously counted flat lesions to raised; increase in surface area of the
indicator lesions), or until other intercurrent complications of HIV disease
preclude continuation of therapy.
PATIENTS WITH IMPAIRED HEPATIC AND RENAL FUNCTION
Limited clinical experience exists in treating hepatically and renally impaired
patients with DAUNOCIN.
Therefore, based on experience with daunorubicin HCl, it is recommended that the
dosage of DAUNOCIN Be Reduced if the bilirubin or creatinine is elevated as
follows: Serum bilirubin 1.2 to 3 mg/dL, give 3/4 the normal dose; serum
bilirubin or creatinine >3 mg/dL, give 1/2 the normal dose.
Do not mix DAUNOCIN with other drugs.
PREPARATION OF SOLUTION
DAUNOCIN should be diluted 1:1 with 5% Dextrose Injection (D5W) before
administration. Each vial of DAUNOCIN contains daunorubicin citrate equivalent
to 50 mg daunorubicin base, at a concentration of 2 mg/mL. The recommended
concentration after dilution is 1 mg daunorubicin/mL of solution.
USE ASEPTIC TECHNIQUE.
Aseptic technique must be strictly observed in all handling, since no
preservative or bacteriostatic agent is present in DAUNOCIN or in the materials
recommended for dilution.
Withdraw the calculated volume of DAUNOCIN from the vial into a sterile
syringe, and transfer it into a sterile infusion bag containing an equivalent
amount of D5W. Administer diluted DAUNOCIN immediately. If not used
immediately, diluted DAUNOCIN should be stored refrigerated at 2 deg-8 deg C
(36 deg-46 deg F) for a maximum of 6 hours
CAUTION: THE ONLY fluid which may be mixed with DAUNOCIN is D5W; DAUNOCIN must
not be mixed with saline, bacteriostatic agents such as benzyl alcohol, or any
other solution.
Do not use an in-line filter for the intravenous infusion of DAUNOCIN.
ALL PARENTERAL DRUG PRODUCTS SHOULD BE INSPECTED VISUALLY FOR PARTICULATE MATTER
AND DISCOLORATION PRIOR TO ADMINISTRATION, WHENEVER SOLUTION AND CONTAINER
PERMIT. DAUNOCIN IS A TRANSLUCENT DISPERSION OF LIPOSOMES THAT SCATTERS LIGHT
TO SOME DEGREE. DO NOT USE DAUNOCIN IF IT APPEARS OPAQUE, OR HAS PRECIPITATE OR
FOREIGN MATTER PRESENT.
Procedures for proper handling and disposal of anticancer drugs should be
followed. (REF. 1-7)
REFERENCES:
1. Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs. NIH
Publication No. 83-2621. For sale by the Superintendent of Documents, US
Government Printing Office, Washington, DC 20402.
2. AMA Council Report, Guidelines for Handling Parenteral Antineoplastics. JAMA
1985; 253(11): 1590-1592.
3. National Study Commission on Cytotoxic Exposure-Recommendations for Handling
Cytotoxic Agents. Available from Louis P. Jeffrey, Sc.D., Chairman, National
Study Commission on Cytotoxic Exposure Massachusetts College of Pharmacy and
Allied Health Sciences, 179 Longwood Avenue, Boston, Massachusetts 02115.
4. Clinical Oncological Society of Australia. Guidelines and Recommendations for
Safe Handling of Antineoplastic Agents. Med. J. Australia 1983; 1: 426-428.
5. Jones RB, et al; Safe Handling of Chemotherapeutic Agents: A report from the
Mount Sinai Medical Center. CA-A Cancer Journal for Clinicians 1983; (Sept/Oct)
258-263.
6. American Society of Hospital Pharmacists Technical Assistance Bulletin on
Handling Cytotoxic and Hazardous Drugs. Am. J. Hosp. Pharm. 1990; 47: 1033-1049.
7. OSHA Work-Practice Guidelines for Personnel Dealing with Cytotoxic
(Antineoplastic) Drugs. Am. J. Hosp. Pharm. 1986; 43: 1193-1204.
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