DOXORUBICIN HYDROCHLORIDE Dailymed

7 Drug Interactions

No formal drug interaction studies have been conducted with doxorubicin hydrochloride liposomal infusion.

8 Use In Specific Populations

• Lactation: Discontinue breastfeeding (8.2).

8.1 Pregnancy

Risk Summary

Based on findings in animals and its mechanism of action, doxorubicin hydrochloride liposomal infusion can cause fetal harm when administered to a pregnant woman; avoid the use of doxorubicin hydrochloride liposomal infusion during the 1^st trimester. In animal reproduction studies, doxorubicin hydrochloride liposomal infusion was embryotoxic in rats and abortifacient in rabbits following intravenous administration during organogenesis at doses approximately 0.12 times the recommended clinical dose (see Data). Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2^nd and 3^rd trimesters. Advise pregnant women of the potential risk to a fetus.

The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.

Data

Animal Data

Doxorubicin hydrochloride liposomal infusion was embryotoxic at doses of 1 mg/kg/day in rats and was embryotoxic and abortifacient at 0.5 mg/kg/day in rabbits (both doses are about 0.12 times the recommended dose of 50 mg/m² human dose on a mg/m² basis). Embryotoxicity was characterized by increased embryo-fetal deaths and reduced live litter sizes.

8.2 Lactation

Risk Summary

It is not known whether doxorubicin hydrochloride liposomal infusion is present in human milk. Because many drugs, including anthracyclines, are excreted in human milk and because of the potential for serious adverse reactions in breastfed infants from doxorubicin hydrochloride liposomal infusion, discontinue breastfeeding during treatment with doxorubicin hydrochloride liposomal infusion.

8.3 Females and Males of Reproductive Potential

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential prior to initiating doxorubicin hydrochloride liposomal infusion.

Contraception

Females

Doxorubicin hydrochloride liposomal infusion can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during and for 6 months after treatment with doxorubicin hydrochloride liposomal infusion.

Males

Doxorubicin hydrochloride liposomal infusion may damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities. Males with female sexual partners of reproductive potential should use effective contraception during and for 6 months after treatment with doxorubicin hydrochloride liposomal infusion [see Non-clinical Toxicology (13.1)].

Infertility

Females

In females of reproductive potential, doxorubicin hydrochloride liposomal infusion may cause infertility and result in amenorrhea. Premature menopause can occur with doxorubicin hydrochloride. Recovery of menses and ovulation is related to age at treatment.

Males

Doxorubicin hydrochloride liposomal infusion may result in oligospermia, azoospermia, and permanent loss of fertility. Sperm counts have been reported to return to normal levels in some men. This may occur several years after the end of therapy [see Non-clinical Toxicology (13.1)].

8.4 Pediatric Use

The safety and effectiveness of doxorubicin hydrochloride liposomal infusion in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of doxorubicin hydrochloride liposomal infusion conducted in patients with either epithelial ovarian cancer (Trial 4) or with AIDS-related Kaposi's sarcoma (Trial 5) did not contain sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects.

In Trial 6, of 318 patients treated with doxorubicin hydrochloride liposomal infusion in combination with bortezomib for multiple myeloma, 37% were 65 years of age or older and 8% were 75 years of age or older. No overall differences in safety or efficacy were observed between these patients and younger patients.

8.6 Hepatic Impairment

The pharmacokinetics of doxorubicin hydrochloride liposomal infusion has not been adequately evaluated in patients with hepatic impairment. Doxorubicin is eliminated in large part by the liver. Reduce doxorubicin hydrochloride liposomal infusion for serum bilirubin of 1.2 mg/dL or higher.

10 Overdosage

Acute overdosage with doxorubicin hydrochloride causes increased risk of severe mucositis, leukopenia, and thrombocytopenia.

11 Description

Doxorubicin hydrochloride liposomal infusion is doxorubicin hydrochloride, an anthracycline topoisomerase inhibitor, that is encapsulated in pegylated liposomes for intravenous use.

The chemical name of doxorubicin hydrochloride is (8S,10S)-10-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-8-glycolyl-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12-naphthacenedione hydrochloride. The molecular formula is C₂₇H₂₉NO₁₁∙HCl and the molecular weight is 579.99.

The structural formula is:
Doxorubicin hydrochloride liposomal infusion is a sterile, translucent, red liposomal dispersion. Each single-dose vial contains 20 mg or 50 mg doxorubicin hydrochloride at a concentration of 2 mg/mL (equivalent to 1.87 mg/mL of doxorubicin). The pegylated liposome carriers are composed of cholesterol, 3.19 mg/mL; fully hydrogenated soy phosphatidylcholine (HSPC), 9.58 mg/mL; and N-(carbonyl-methoxypolyethylene glycol 2,000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine sodium salt (MPEG-DSPE), 3.19 mg/mL. Each mL also contains ammonium sulfate, approximately 0.6 mg; histidine as a buffer; hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment (6.0 to 7.0); and sucrose, 94 mg to maintain isotonicity. Greater than 90% of the drug is encapsulated in the pegylated liposomes.

MPEG-DSPE has the following structural formula:
HSPC has the following structural formula:
Representation of a pegylated liposome:

12 Clinical Pharmacology

12.1 Mechanism of Action

The active ingredient of doxorubicin hydrochloride liposomal infusion is doxorubicin hydrochloride. The mechanism of action of doxorubicin hydrochloride is thought to be related to its ability to bind DNA and inhibit nucleic acid synthesis. Cell structure studies have demonstrated rapid cell penetration and perinuclear chromatin binding, rapid inhibition of mitotic activity and nucleic acid synthesis, and induction of mutagenesis and chromosomal aberrations.

12.3 Pharmacokinetics

The pharmacokinetic parameters for total doxorubicin following a single dose of doxorubicin hydrochloride liposome injection infused over 30 minutes are presented in Table 8.

Table 8: Pharmacokinetic Parameters of Total Doxorubicin from Doxorubicin Hydrochloride Liposomal Infusion in Patients With AIDS-Related Kaposi's Sarcoma

N=23
Mean ± Standard Error
	Dose
Parameter (units)	10 mg/m2	20 mg/m2
Peak Plasma Concentration (µg/mL)	4.12 ± 0.215	8.34 ± 0.49
Plasma Clearance (L/h/m2)	0.056 ± 0.01	0.041 ± 0.004
Steady State Volume of Distribution (L/m2)	2.83 ± 0.145	2.72 ± 0.120
AUC (µg/mL∙h)	277 ± 32.9	590 ± 58.7
First Phase (λ1) Half-Life (h)	4.7 ± 1.1	5.2 ± 1.4
Second Phase (λ1) Half-Life (h)	52.3 ± 5.6	55.0 ± 4.8

Doxorubicin hydrochloride liposomal infusion displayed linear pharmacokinetics over the range of 10 to 20 mg/m². Relative to doxorubicin hydrochloride liposomal infusion doses at or below 20 mg/m², the pharmacokinetics of total doxorubicin following a 50 mg/m² doxorubicin hydrochloride liposomal infusion dose are nonlinear. At this dose, the elimination half-life of doxorubicin hydrochloride liposomal infusion is longer and the clearance lower compared to a 20 mg/m² dose.

Distribution

Direct measurement of liposomal doxorubicin shows that at least 90% of the drug (the assay used cannot quantify less than 5-10% free doxorubicin) remains liposome-encapsulated during circulation.

In contrast to doxorubicin, which displays a large volume of distribution (range 700 to 1,100 L/m²), the small steady state volume of distribution of liposomal doxorubicin suggests that doxorubicin hydrochloride liposomal infusion is largely confined to vascular fluid. Doxorubicin becomes available after the liposomes are extravasated. Plasma protein binding of doxorubicin hydrochloride liposome injection has not been determined; the plasma protein binding of doxorubicin is approximately 70%.

Metabolism

Doxorubicinol, the major metabolite of doxorubicin, was detected at concentrations of 0.8 to 26.2 ng/mL in the plasma of patients who received 10 or 20 mg/m² doxorubicin hydrochloride liposomal infusion.

Elimination

The plasma clearance of total doxorubicin from doxorubicin hydrochloride liposomal infusion was 0.041 L/h/m² at a dose of 20 mg/m². Following administration of doxorubicin hydrochloride, the plasma clearance of doxorubicin is 24 to 35 L/h/m².

13 Nonclinical Toxicology

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

Mutagenicity or carcinogenicity studies have not been conducted with doxorubicin hydrochloride liposomal infusion, however doxorubicin was shown to be mutagenic in the in vitro Ames assay, and clastogenic in multiple in vitro assays (CHO cell, V79 hamster cell, human lymphoblast, and SCE assays) and the in vivo mouse micronucleus assay. The possible adverse effects on fertility in animals have not been adequately evaluated. Doxorubicin hydrochloride liposomal infusion resulted in mild to moderate ovarian and testicular atrophy in mice after administration of a single dose of 36 mg/kg (about 2 times the 50 mg/m² human dose on a mg/m² basis). Decreased testicular weights and hypospermia were observed in rats after repeat doses ≥ 0.25 mg/kg/day (about 0.03 times the 50 mg/m² human dose on a mg/m² basis), and diffuse degeneration of the seminiferous tubules and a marked decrease in spermatogenesis were observed in dogs after repeat doses of 1 mg/kg/day (about 0.4 times the 50 mg/m² human dose on a mg/m² basis).

14 Clinical Studies

14.1 Ovarian Cancer

Doxorubicin hydrochloride liposomal infusion was studied in three open-label, single-arm, clinical studies of 176 patients with metastatic ovarian cancer (Trials 1, 2, and 3). One hundred forty-five of these patients were refractory to both paclitaxel- and platinum-based chemotherapy regimens, defined as disease progression while on treatment or relapse within 6 months of completing treatment. Patients received doxorubicin hydrochloride liposomal infusion at 50 mg/m² every 3 or 4 weeks for 3-6+ cycles in the absence of dose-limiting toxicity or disease progression.

The median age at diagnosis ranged from 52 to 64 years in the 3 studies, and the range was 22 to 85. Most patients had International Federation of Obstetricians and Gynecologists (FIGO) stage III or IV disease (ranging from 83% to 93%). Approximately one third of the patients had three or more prior lines of therapy (ranging from 22% to 33%).

The primary outcome measure was confirmed response rate based on Southwestern Oncology Group (SWOG) criteria for patients refractory to both paclitaxel- and a platinum-containing regimen. Secondary efficacy parameters were time to response, duration of response, and time to progression.

The response rates for the individual single arm trials are given in Table 9 below.

Table 9: Response Rates in Patients With Refractory Ovarian Cancer From Single Arm Ovarian Cancer Trials

	Trial 1 (U.S.) N=27	Trial 2 (U.S.) N=82	Trial 3 (non-U.S.) N=36
Response Rate	22.2%	17.1%	0%
95% Confidence Interval	8.6% - 42.3%	9.7% - 27.0%	0.0% - 9.7%

In a pooled analysis of Trials 1-3, the response rate for all patients refractory to paclitaxel and platinum agents was 13.8% (95% CI 8.1% to 19.3%). The median time to progression was 15.9 weeks, the median time to response was 17.6 weeks, and the duration of response was 39.4 weeks.

In Trial 4, a randomized, multicenter, open-label, trial in 474 patients with epithelial ovarian cancer after platinum-based chemotherapy, patients were randomized to receive either doxorubicin hydrochloride liposomal infusion 50 mg/m² every 4 weeks (n=239) or topotecan 1.5 mg/m² daily for 5 consecutive days every 3 weeks (n=235). Patients were stratified according to platinum sensitivity (response to initial platinum-based therapy and a progression-free interval of greater than 6 months off treatment) and the presence of bulky disease (tumor mass greater than 5 cm in size). The primary outcome measure was time to progression (TTP). Other endpoints included overall survival and objective response rate.

Of the 474 patients, the median age at diagnosis was 60 years (range 25 to 87), 90% were FIGO stage III and IV; 46% were platinum sensitive; and 45% had bulky disease.

There was no statistically significant difference in TTP between the two arms. Results are provided in Table 10.

Table 10: Results of Efficacy Analyses¹

1Analysis based on investigators' strata for protocol defined ITT population.
2Kaplan-Meier estimates.
3p-value is based on the stratified log-rank test.
4Hazard ratio is based on Cox proportional-hazard model with the treatment as single independent variable. A hazard ratio less than 1 indicates an advantage for doxorubicin hydrochloride liposomal infusion.
5p-value not adjusted for multiple comparisons.
	Protocol Defined ITT Population
	Doxorubicin Hydrochloride Liposomal Infusion (n=239)	Topotecan (n=235)
TTP (Protocol Specified Primary Endpoint)
Median (Months)2	4.1	4.2
p-value3	0.62
Hazard Ratio4	0.96
95% CI for Hazard Ratio	(0.76, 1.20)
Overall Survival
Median (Months)2	14.4	13.7
p-value5	0.05
Hazard Ratio4	0.82
95% CI for Hazard Ratio	(0.68, 1.00)
Response Rate
Overall Response n (%)	47 (19.7)	40 (17.0)
Complete Response n (%)	9 (3.8)	11 (4.7)
Partial Response n (%)	38 (15.9)	29 (12.3)
Median Duration of Response (Months)2	6.9	5.9

14.2 AIDS-Related Kaposi's Sarcoma

Doxorubicin hydrochloride liposomal infusion was studied in an open-label, single-arm, multicenter study at a dose of 20 mg/m² every 3 weeks, until disease progression or unacceptable toxicity (Trial 5).

Data is described for a cohort of 77 patients retrospectively identified as having disease progression on prior systemic combination chemotherapy (at least two cycles of a regimen containing at least two of three treatments: bleomycin, vincristine or vinblastine, or doxorubicin) or as being intolerant to such therapy. Forty-nine of the 77 (64%) patients had received prior doxorubicin hydrochloride.

The median time on study was 5.1 months (range 1 day to 15 months). The median cumulative dose of doxorubicin hydrochloride liposomal infusion was 154 mg/m² (range 20 to 620 mg/m²). Among the 77 patients, mean age was 38 years (range 24 to 54); 87% were Caucasian, 5% Hispanic, 4% Black, and 4% Asian/Other/Unknown; median CD4 count was 10 cells/mm³; ACTG staging criteria were 78% poor risk for tumor burden, 96% poor risk for immune system, and 58% poor risk for systemic illness at baseline; and mean Karnofsky status score was 74%. All patients had cutaneous or subcutaneous lesions, 40% also had oral lesions, 26% pulmonary lesions, and 14% had lesions of the stomach/intestine.

Two analyses of tumor response were used: one based on investigator assessment of changes in lesions based on modified ACTG criteria (partial response defined as no new lesions, sites of disease, or worsening edema; flattening of ≥50% of previously raised lesions or area of indicator lesions decreasing by ≥50%; and response lasting at least 21 days with no prior progression), and one based on changes in up to five prospectively indentified representative indicator lesions (partial response defined as flattening of ≥50% of previously raised indicator lesions, or >50% decrease in the area of indicator lesions and lasting at least 21 days with no prior progression).

Of the 77 patients, 34 were evaluable for investigator assessment and 42 were evaluable for indicator lesion assessment; analyses of tumor responses are shown in Table 11.

Table 11: Response in Patients with Refractory¹ AIDS-Related Kaposi's Sarcoma

1 Patients with disease that progressed on prior combination chemotherapy or who were intolerant to such therapy.
2 There were no complete responses in this population.
Investigator Assessment	All Evaluable Patients (n=34)	Evaluable Patients Who Received Prior Doxorubicin (n=20)
Response2
Partial (PR)	27%	30%
Stable	29%	40%
Progression	44%	30%
Duration of PR (Days)
Median	73	89
Range	42+ to 210+	42+ to 210+
Time to PR (Days)
Median	43	53
Range	15 to 133	15 to 109
Indicator Lesion Assessment	All Evaluable Patients (n=42)	Evaluable Patients Who Received Prior Doxorubicin (n=23)
Response2
Partial (PR)	48%	52%
Stable	26%	30%
Progression	26%	17%
Duration of PR (Days)
Median	71	79
Range	22+ to 210+	35 to 210+
Time to PR (Days)
Median	22	48
Range	15 to 109	15 to 109

Retrospective efficacy analyses were performed in two trials that had subsets of patients who received single-agent doxorubicin hydrochloride liposomal infusion and who were on stable antiretroviral therapy for at least 60 days prior to enrollment and until a response was demonstrated. In one trial, 7 of 17 (40%) patients had a durable response (median duration not reached but was longer than 11.6 months). In the second trial, 4 of 11 patients (40%) on a stable antiretroviral therapy demonstrated durable responses.

14.3 Multiple Myeloma

The efficacy of doxorubicin hydrochloride liposomal infusion in combination with bortezomib was evaluated in Trial 6, a randomized, open-label, international, multicenter study in 646 patients who had not previously received bortezomib and whose disease progressed during or after at least one prior therapy. Patients were randomized (1:1) to receive either doxorubicin hydrochloride liposomal infusion (30 mg/m²) administered intravenous on day 4 following bortezomib (1.3 mg/m² intravenous on days 1, 4, 8 and 11) or bortezomib alone every 3 weeks for up to 8 cycles or until disease progression or unacceptable toxicity. Patients who maintained a response were allowed to receive further treatment. The median number of cycles in each treatment arm was 5 (range 1-18).

The baseline demographics and clinical characteristics of the patients with multiple myeloma were similar between treatment arms (Table 12).

Table 12: Summary of Baseline Patient and Disease Characteristics

Patient Characteristics	Doxorubicin Hydrochloride Liposomal Infusion + bortezomib n=324	bortezomib n=322
Median age in years (range)	61 (28, 85)	62 (34, 88)
% Male/female	58 / 42	54 / 46
% Caucasian/Black/other	90 / 6 / 4	94 / 4 / 2
Disease Characteristics
% with IgG/IgA/Light chain	57 / 27 / 12	62 / 24 / 11
% β2-microglobulin group
≤2.5 mg/L	14	14
>2.5 mg/L and ≤5.5 mg/L	56	55
>5.5 mg/L	30	31
Serum M-protein (g/dL): Median (Range)	2.5 (0-10.0)	2.7 (0-10.0)
Urine M-protein (mg/24 hours): Median (Range)	107 (0-24883)	66 (0-39657)
Median Months Since Diagnosis	35.2	37.5
% Prior Therapy
One	34	34
More than one	66	66
Prior Systemic Therapies for Multiple Myeloma
Corticosteroid (%)	99	>99
Anthracyclines	68	67
Alkylating agent (%)	92	90
Thalidomide/lenalidomide (%)	40	43
Stem cell transplantation (%)	57	54

The primary outcome measure was time to progression (TTP). TTP was defined as the time from randomization to the first occurrence of progressive disease or death due to progressive disease. The combination arm demonstrated significant improvement in TTP. As the prespecified primary objective was achieved at the interim analysis, patients in the bortezomib monotherapy group were then allowed to receive the doxorubicin hydrochloride liposomal infusion + bortezomib combination. Efficacy results are as shown in Table 13 and Figure 1.

Table 13: Efficacy of Doxorubicin Hydrochloride Liposomal Infusion in Combination With Bortezomib in the Treatment of Patients With Multiple Myeloma

1 Kaplan Meier estimate.
2 Hazard ratio based on stratified Cox proportional hazards regression. A hazard ratio <1 indicates an advantage for doxorubicin hydrochloride liposomal infusion + bortezomib.
3 Stratified log-rank test.
4 RR as per EBMT criteria.
5 Cochran-Mantel-Haenszel test adjusted for the stratification factors.
Endpoint	Doxorubicin Hydrochloride Liposomal Infusion + bortezomib n=324	Bortezomib n=322
Time to Progression 1
Progression or death due to progression (n)	99	150
Censored (n)	225	172
Median in days (months)	282 (9.3)	197 (6.5)
95% CI	250; 338	170; 217
Hazard ratio2	0.55
(95% CI)	(0.43, 0.71)
p-value3	<0.001
Response (n) 4	303	310
% Complete Response (CR)	5	3
% Partial Response (PR)	43	40
% CR + PR	48	43
p-value5	0.25
Median Duration of Response (months)	10.2	7.0
(95% CI)	(10.2; 12.9)	(5.9; 8.3)

Figure 1- Time to Progression Kaplan-Meier Curve

At the final analysis of survival, 78% of subjects in the doxorubicin hydrochloride liposomal infusion and bortezomib combination therapy group and 80% of subjects in the bortezomib monotherapy group had died after a median follow up of 8.6 years. The median survival was 33 months in the doxorubicin hydrochloride liposomal infusion and bortezomib combination therapy group and 31 months in the bortezomib monotherapy group. There was no difference observed in overall survival at the final analysis [HR for doxorubicin hydrochloride liposomal infusion + bortezomib vs. bortezomib = 0.96 (95% CI 0.80, 1.14)].

Seventy-eight percent of subjects in the doxorubicin hydrochloride liposomal infusion and bortezomib combination therapy group and 80% of subjects in the bortezomib monotherapy group had received subsequent therapy.

15 References

• "Hazardous Drugs", OSHA, http://www.osha.gov/SLTC/hazardousdrugs/index.html

16 How Supplied/storage And Handling

Doxorubicin hydrochloride liposome injection is a sterile, translucent, red liposomal dispersion in 10 mL or 30 mL glass, single dose vials.

The following individually cartoned vials are available:

Table 14

Vial Concentration	Vial Size	NDC number
20 mg/10 mL (2 mg/ mL)	10 mL	70710-1530-1
50 mg/25 mL (2 mg/mL)	30 mL	70710-1531-1

Refrigerate unopened vials of doxorubicin hydrochloride liposomal infusion at 2° to 8°C (36° to 46°F). Do not freeze. Discard unused portion.

Doxorubicin hydrochloride liposomal infusion is a cytotoxic drug. Follow applicable special handling and disposal procedures.¹

17 Patient Counseling Information

Cardiomyopathy

Advise patients to contact their healthcare provider if they develop symptoms of heart failure [see Warnings and Precautions (5.1)].

Infusion-Related Reactions

Advise patients about the symptoms of infusion related reactions and to seek immediate medical attention if they develop any of these symptoms [see Warnings and Precautions (5.2)].

Myelosuppression

Advise patients to contact their healthcare provider for a new onset fever or symptoms of infection.

Hand-Foot Syndrome

Advise patients to notify their healthcare provider if they experience tingling or burning, redness, flaking, bothersome swelling, small bulers, or small sores on the palms of their hands or soles of their feet (symptoms of Hand-Foot Syndrome) [see Warnings and Precautions (5.3)].

Stomatitis

Advise patients to notify their healthcare provider if they develop painful redness, swelling, or sores in the mouth (symptoms of stomatitis).

Embry-Fetal Toxicity

Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider with a known or suspected pregnancy [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1)].

Advise females and males of reproductive potential to use effective contraception during and for 6 months following treatment with doxorubicin hydrochloride liposomal infusion [see Use in Specific Populations (8.3)].

Lactation

Advise females not to breastfeed during treatment with doxorubicin hydrochloride liposomal infusion [see Use in Specific Populations (8.2)].

Infertility

Advise females and males of reproductive potential that doxorubicin hydrochloride liposomal infusion may cause temporary or permanent infertility [see Use in Specific Populations (8.3)].

Discoloration of Urine and Body Fluids

Inform patients that following doxorubicin hydrochloride liposomal infusion administration, a reddish-orange color to the urine and other body fluids may be observed. This nontoxic reaction is due to the color of the product and will dissipate as the drug is eliminated from the body.

Manufactured by:

Zydus Lifesciences Ltd.

Ahmedabad, India

Distributed by:

Zydus Pharmaceuticals (USA) Inc.

Pennington, NJ 08534

Revision: 10/2022

Package Label.principal Display Panel

Principal Display Panel – 20 mg/10 mL Container Label

NDC 70710-1530-1

DOXOrubicin Hydrochloride Liposome Injection

20 mg/10 mL

(2 mg/mL)

Cytotoxic Agent                           Must be diluted

LIPOSOMAL FORMULATION – DO NOT SUBSTITUTE FOR DOXORUBICIN HCL

FOR INTRAVENOUS INFUSION ONLY

10 mL Single-Dose Vial

Rx only
Principal Display Panel – 20 mg/10 mL Carton Label

NDC 70710-1530-1

DOXOrubicin Hydrochloride Liposome Injection

20 mg/10 mL

(2 mg/mL)

Cytotoxic Agent                           Must be diluted

LIPOSOMAL FORMULATION – DO NOT SUBSTITUTE FOR DOXORUBICIN HCL

FOR INTRAVENOUS INFUSION ONLY

Sterile

Refrigerate at 2⁰ to 8℃ (36⁰ to 46℉)

Do not freeze

10 mL Single-Dose Vial

Rx only
Principal Display Panel – 50 mg/25 mL Container Label

NDC 70710-1531-1

DOXOrubicin Hydrochloride Liposome Injection

50 mg/25 mL

(2 mg/mL)

Cytotoxic Agent                           Must be diluted

LIPOSOMAL FORMULATION – DO NOT SUBSTITUTE FOR DOXORUBICIN HCL

FOR INTRAVENOUS INFUSION ONLY

25 mL Single-Dose Vial

Rx only
Principal Display Panel – 50 mg/25 mL Carton Label

NDC 70710-1531-1

DOXOrubicin Hydrochloride Liposome Injection

50 mg/25 mL

(2 mg/mL)

Cytotoxic Agent                           Must be diluted

LIPOSOMAL FORMULATION – DO NOT SUBSTITUTE FOR DOXORUBICIN HCL

FOR INTRAVENOUS INFUSION ONLY

Sterile

Refrigerate at 2⁰ to 8℃ (36⁰ to 46℉)

Do not freeze

25 mL Single-Dose Vial

Rx only