GEMCITABINE HYDROCHLORIDE (Page 7 of 7)

14.4 Pancreatic Cancer

The efficacy of gemcitabine was evaluated in two trials (Studies 5 and 6), a randomized, single-blind, two-arm, active-controlled trial (Study 5) conducted in patients with locally advanced or metastatic pancreatic cancer who had received no prior chemotherapy and in a single-arm, open-label, multicenter trial (Study 6) conducted in patients with locally advanced or metastatic pancreatic cancer previously treated with fluorouracil or a fluorouracil-containing regimen. In Study 5, patients were randomized to receive either gemcitabine 1000 mg/m 2 intravenously over 30 minutes once weekly for 7 weeks followed by a one-week rest, then once weekly for 3 consecutive weeks every 28-days in subsequent cycles (n=63) or fluorouracil 600 mg/m 2 intravenously over 30 minutes once weekly (n=63). In Study 6, all patients received gemcitabine 1000 mg/m 2 intravenously over 30 minutes once weekly for 7 weeks followed by a one-week rest, then once weekly for 3 consecutive weeks every 28-days in subsequent cycles.

The major efficacy outcome measure in both trials was “clinical benefit response”. A patient was considered to have had a clinical benefit response if either of the following occurred:

  • The patient achieved a ≥50% reduction in pain intensity (Memorial Pain Assessment Card) or analgesic consumption, or a 20-point or greater improvement in performance status (Karnofsky Performance Status) for a period of at least 4 consecutive weeks, without showing any sustained worsening in any of the other parameters. Sustained worsening was defined as 4 consecutive weeks with either any increase in pain intensity or analgesic consumption or a 20-point decrease in performance status occurring during the first 12 weeks of therapy.
    OR
  • The patient was stable on all of the aforementioned parameters, and showed a marked, sustained weight gain (≥7% increase maintained for ≥4 weeks) not due to fluid accumulation.

Study 5 enrolled 126 patients. Demographics and baseline characteristics were similar between the arms (Table 22). The efficacy results are shown in Table 23 and Figure 4. Patients treated with gemcitabine had statistically significant increases in clinical benefit response, survival, and time to disease progression compared to those randomized to receive fluorouracil. No confirmed objective tumor responses were observed in either treatment arm.

Table 22: Baseline Demographics and Clinical Characteristics for Study 5

a Karnofsky Performance Status.

Gemcitabine (N=63) Fluorouracil (N=63)
Male54%54%
Median age, years62 61
Range37 to 7936 to 77
Stage IV disease71%76%
Baseline KPS a ≤70 70%68%
Table 23: Efficacy Results in Study 5

a p-value for clinical benefit response calculated using the two-sided test for difference in binomial proportions. All other p-values are calculated using log rank test.

Efficacy Parameter Gemcitabine (N= 63) Fluorouracil (N= 63)
Clinical Benefit Response 22.2% 4.8%
p-value a p=0.004
Overall Survival
Median (95% CI) in months 5.7 (4.7, 6.9) 4.2 (3.1, 5.1)
p-value a p=0.0009
Time to Disease Progression
Median (95% CI) in months 2.1 (1.9, 3.4) 0.9 (0.9, 1.1)
p-value a p=0.0013

Figure 4: Kaplan-Meier Curves for Overall Survival in Study 5

Gemcitabine for Injection Figure 4
(click image for full-size original)

15 REFERENCES

1.“OSHA Hazardous Drugs.” OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

16 HOW SUPPLIED/STORAGE AND HANDLING

Gemcitabine for Injection is a sterile white to off-white lyophilized powder available in single-dose vials individually packaged in a carton containing 200 mg, 1g or 2 g gemcitabine:

  • 200 mg vial: NDC 16729-092-03 (No. 092)
  • 1 g vial: NDC 16729-117-11 (No. 117)
  • 2 g vial: NDC 16729-118-38 (No. 118)

Gemcitabine for Injection is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1

Store at controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

Myelosuppression

Advise patients of the risks of myelosuppression Instruct patients to immediately contact their healthcare provider should any signs or symptoms of infection, including fever, or if bleeding or signs of anemia, occur [see Warnings and Precautions (5.2)].

Pulmonary Toxicity

Advise patients of the risks of pulmonary toxicity, including respiratory failure and death. Instruct patients to immediately contact their healthcare provider for development of shortness of breath, wheezing, or cough [see Warnings and Precautions (5.3)].

Hemolytic-Uremic Syndrome and Renal Failure

Advise patients of the risks of hemolytic-uremic syndrome and associated renal failure. Instruct patients to immediately contact their healthcare provider for changes in the color or volume of urine output or for increased bruising or bleeding [see Warnings and Precautions (5.4)].

Hepatic Toxicity

Advise patients of the risks of hepatic toxicity including liver failure and death. Instruct patients to immediately contact their healthcare provider for signs of jaundice or for pain/tenderness in the right upper abdominal quadrant [see Warnings and Precautions (5.5)].

Embryo-Fetal Toxicity

Advise females and males of reproductive potential that Gemcitabine for Injection can cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment with Gemcitabine for Injection and for 6 months after the final dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Gemcitabine for Injection and for 3 months after the final dose [see Warnings and Precaution (5.6), Use in Specific Populations ( 8.1, 8.3)].

Lactation

Advise women not to breastfeed during treatment with Gemcitabine for Injection and for at least one week after the last dose [see Use in Specific Populations (8.2)].

Infertility

Advise males of reproductive potential of the potential for reduced fertility with Gemcitabine for Injection [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1)].

Manufactured For:
Accord Healthcare, Inc.,
1009, Slater Road,
Suite 210-B,
Durham, NC 27703,
USA.

Manufactured By:
Intas Pharmaceuticals Limited, Ahmedabad — 380 054, INDIA.

10 0147 1 678621/Jul 2019

PRINCIPAL DISPLAY PANEL

NDC 16729- 092 -03

Gemcitabine For Injection USP

200 mg/vial

Rx Only

For intravenous use only

Sterile Single Dose Vial

Cytotoxin Agent

Lyophilized

Must be diluted

Gemcitabine For Injection 200mg Carton
(click image for full-size original)

NDC 16729- 092 -03

Gemcitabine For Injection USP

200 mg/vial Rx Only For intravenous use only

Sterile Single Dose Vial

Cytotoxin Agent

Lyophilized

Must be diluted

Gemcitabine For Injection 200 mg Label
(click image for full-size original)

NDC 16729- 092 -03

Gemcitabine For Injection USP

200 mg/vial

Rx Only

For intravenous use only

Sterile Single Dose Vial

Cytotoxin Agent

Lyophilized

Must be diluted

Gemcitabine For Injection 200mg Carton for SEZ
(click image for full-size original)

NDC 16729- 092 -03

Gemcitabine For Injection USP

200 mg/vial Rx Only For intravenous use only

Sterile Single Dose Vial

Cytotoxin Agent

Lyophilized

Must be diluted

Gemcitabine For Injection 200 mg  Label for SEZ
(click image for full-size original)

NDC 16729- 117 -11

Gemcitabine For Injection USP

1 g/vial

Rx Only

For intravenous use only

Sterile Single Dose Vial

Cytotoxin Agent

Lyophilized

Must be diluted

Gemcitabine For Injection 1g Carton
(click image for full-size original)

NDC 16729- 117 -11

Gemcitabine For Injection USP

1 g/vial Rx Only For intravenous use only

Sterile Single Dose Vial

Cytotoxin Agent

Lyophilized

Must be diluted

Gemcitabine For Injection 1 g  Label
(click image for full-size original)

NDC 16729- 117 -11

Gemcitabine For Injection USP

1 g/vial

Rx Only

For intravenous use only

Sterile Single Dose Vial

Cytotoxin Agent

Lyophilized

Must be diluted

Gemcitabine For Injection 1g Carton for SEZ
(click image for full-size original)

NDC 16729- 117 -11

Gemcitabine For Injection USP

1 g/vial Rx Only For intravenous use only

Sterile Single Dose Vial

Cytotoxin Agent

Lyophilized

Must be diluted

Gemcitabine For Injection 1 g  Label for SEZ
(click image for full-size original)

NDC 16729- 118 -38

Gemcitabine For Injection USP

2 g/vial

Rx Only

For intravenous use only

Sterile Single Dose Vial

Cytotoxin Agent

Lyophilized

Must be diluted

Gemcitabine For Injection 2g Carton
(click image for full-size original)

NDC 16729- 118 -38

Gemcitabine For Injection USP

2 g/vial Rx Only For intravenous use only

Sterile Single Dose Vial

Cytotoxin Agent

Lyophilized

Must be diluted

Gemcitabine For Injection 2 g  Label
(click image for full-size original)

NDC 16729- 118 -38

Gemcitabine For Injection USP

2 g/vial

Rx Only

For intravenous use only

Sterile Single Dose Vial

Cytotoxin Agent

Lyophilized

Must be diluted

Gemcitabine For Injection 2g Carton for SEZ
(click image for full-size original)

NDC 16729- 118 -38

Gemcitabine For Injection USP

2 g/vial

Rx Only

For intravenous use only

Sterile Single Dose Vial

Cytotoxin Agent

Lyophilized

Must be diluted

Gemcitabine For Injection 2 g  Label for SEZ
(click image for full-size original)
GEMCITABINE HYDROCHLORIDE gemcitabine hydrochloride injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:16729-092
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
GEMCITABINE HYDROCHLORIDE (GEMCITABINE) GEMCITABINE 200 mg in 5 mL
Inactive Ingredients
Ingredient Name Strength
MANNITOL 200 mg in 5 mL
SODIUM ACETATE 12.5 mg in 5 mL
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:16729-092-03 1 VIAL in 1 CARTON contains a VIAL
1 5 mL in 1 VIAL This package is contained within the CARTON (16729-092-03)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA091594 07/28/2011
GEMCITABINE HYDROCHLORIDE gemcitabine hydrochloride injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:16729-117
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
GEMCITABINE HYDROCHLORIDE (GEMCITABINE) GEMCITABINE 1 g in 25 mL
Inactive Ingredients
Ingredient Name Strength
MANNITOL 1 g in 25 mL
SODIUM ACETATE 62.5 mg in 25 mL
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:16729-117-11 1 VIAL in 1 CARTON contains a VIAL
1 25 mL in 1 VIAL This package is contained within the CARTON (16729-117-11)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA091594 08/01/2011
GEMCITABINE HYDROCHLORIDE gemcitabine hydrochloride injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:16729-118
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
GEMCITABINE HYDROCHLORIDE (GEMCITABINE) GEMCITABINE 2 g in 50 mL
Inactive Ingredients
Ingredient Name Strength
MANNITOL 2 g in 50 mL
SODIUM ACETATE 125 mg in 50 mL
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:16729-118-38 1 VIAL in 1 CARTON contains a VIAL
1 50 mL in 1 VIAL This package is contained within the CARTON (16729-118-38)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA091594 08/31/2011
Labeler — Accord Healthcare Inc. (604222237)
Establishment
Name Address ID/FEI Operations
Intas Pharmaceuticals Limited 725927649 manufacture (16729-092), manufacture (16729-117), manufacture (16729-118), analysis (16729-092), analysis (16729-117), analysis (16729-118)
Establishment
Name Address ID/FEI Operations
Intas Pharmaceuticals Limited 915837971 manufacture (16729-092), manufacture (16729-117), manufacture (16729-118), analysis (16729-092), analysis (16729-117), analysis (16729-118)

Revised: 11/2022 Accord Healthcare Inc.

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