Usual Adult Dose for Ovarian Cancer

1000 mg/m2 IV over 30 minutes on Day 1 and 8 of each 21-day cycle in combination with carboplatin AUC 4 administered IV on Day 1 of each 21-day cycle after gemcitabine administration

Comments:

• Monitor complete blood count, including differential counts, prior to each dose.

Use: In combination with carboplatin for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy

Usual Adult Dose for Breast Cancer

1250 mg/m2 IV over 30 minutes on Day 1 and 8 of each 21-day cycle in combination with paclitaxel 175 mg/m2 IV over 3 hours on Day 1 before gemcitabine administration

Comments:

• Monitor complete blood count, including differential counts, prior to each dose.

Use: In combination with paclitaxel for first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were contraindicated

Usual Adult Dose for Non-Small Cell Lung Cancer

28-Day Schedule:
1000 mg/m2 IV over 30 minutes on Day 1, 8, and 15 in combination with cisplatin 100 mg/m2 IV on Day 1 after gemcitabine administration

21-Day Schedule:
1250 mg/m2 IV over 30 minutes on Day 1 and 8 in combination with cisplatin 100 mg/m2 IV on Day 1 after gemcitabine administration

Comments:

• Monitor complete blood count, including differential counts, prior to each dose.

Use: In combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB) or metastatic (Stage IV) non-small cell lung cancer

Usual Adult Dose for Pancreatic Cancer

1000 mg/m2 IV over 30 minutes

• Weeks 1 through 8: Weekly dosing for the first 7 weeks, followed by one week of rest
• After week 8: Weekly dosing on Days 1, 8, and 15 of each 28-Day cycle

Comments:

• Monitor complete blood count, including differential counts, prior to each dose.

Use: As first-line treatment for locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas in patients previously treated with fluorouracil (5-FU)

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Mild to moderate hepatic dysfunction: Dose adjustment(s) may be required; however, no specific guidelines have been suggested. Caution recommended.
Severe hepatic impairment: Permanently discontinue therapy.

Dose Adjustments

HEMATOLOGIC TOXICITY:
***Recommended dose modifications for Myelosuppression on Day of Treatment in Ovarian Cancer:
TREATMENT DAY 1:

• Absolute neutrophil count 1500 x 10(6)/L or greater AND platelet count 100,000 x 10(6)/L or greater: No adjustment recommended.
• Absolute neutrophil count less than 1500 x 10(6)/L OR platelet count less than 100,000 x 10(6)/L: Delay treatment cycle.

TREATMENT DAY 8:

• Absolute neutrophil count 1500 x 10(6)/L or greater AND platelet count 100,000 x 10(6)/L or greater: No adjustment recommended.
• Absolute neutrophil count 1000 to 1499 x 10(6)/L OR platelet count 75,000 to 99,999 x 10(6)/L: Administer 50% of the full dose.
• Absolute neutrophil count less than 1000 x 10(6)/L OR platelet count less than 75,000 x 10(6)/L: Withhold therapy.

***Recommended Dose Modifications for Myelosuppression in Previous Cycle in Ovarian Cancer:
INITIAL OCCURRENCE:

• Absolute neutrophil count less than 500 x 10(6)/L for more than 5 days OR absolute neutrophil count less than 100 x 10(6)/L for more than 3 days OR febrile neutropenia OR platelets less than 25,000 x 10(6)/L OR cycle delay for more than one week due to toxicity: Permanently reduce the dose to 800 mg/m2 on Days 1 and 8.

SUBSEQUENT OCCURRENCE:

• If any toxicities occur after the initial dose reduction: Permanently reduce the dose to 800 mg/m2 on Day 1 only.

***Recommended Dosage Modifications for Myelosuppression on Day of Treatment in Breast Cancer:
TREATMENT DAY 1:

• Absolute neutrophil count 1500 x 10(6)/L or greater AND platelet count 100,000 x 10(6)/L or greater: No adjustment recommended.
• Absolute neutrophil count less than 1500 x 10(6)/L OR platelet count less than 100,000 x 10(6)/L: Withhold therapy.

TREATMENT DAY 8:

• Absolute neutrophil count 1200 x 10(6)/L or greater AND platelet count 75,000 x 10(6)/L or greater: No adjustment recommended.
• Absolute neutrophil count 1000 to 1199 x 10(6)/L OR platelet count 50,000 to 75,000 x 10(6)/L: Administer 75% of the full dose.
• Absolute neutrophil count 700 to 999 x 10(6)/L AND platelet count 50,000 x 10(6)/L or greater: Administer 50% of the full dose.
• Absolute neutrophil count less than 700 x 10(6)/L OR platelet count less than 50,000 x 10(6)/L: Withhold therapy.

***Recommended Dosage Modifications for Myelosuppression in Pancreatic Cancer and Non-Small Cell Lung Cancer:

• Absolute neutrophil count 1000 x 10(6)/L or greater AND platelet count 100,000 x 10(6) or greater: No adjustment recommended.
• Absolute neutrophil count 500 to 999 x 10(6)/L OR platelet count 50,000 to 99,999 x 10(6)/L: Administer 75% of the full dose.
• Absolute neutrophil count less than 500 x 10(6) OR platelet count less than 50,000 x 10(6)/L: Withhold therapy.

NONHEMATOLOGIC TOXICITY:
Permanently discontinue therapy for any of the following:

• Unexplained dyspnea or severe pulmonary toxicity
• Hemolytic uremic syndrome (HUS) or severe renal impairment
• Severe hepatic toxicity
• Capillary leak syndrome (CLS)
• Posterior reversible encephalopathy syndrome (PRES)

• Withhold therapy or reduce dose by 50% for other Grade 3 or 4 nonhematologic adverse reactions until resolved.
• No dose modifications are recommended for alopecia, nausea, or vomiting.

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Storage requirements:

• Store solutions (reconstituted and diluted) at controlled room temperature of 20C to 25C (68F to 77F).
• Do not refrigerate as crystallization can occur.
• Discard gemcitabine solutions if not used within 24 hours after reconstitution.

Reconstitution/preparation techniques:

• Vials of this drug contain no antimicrobial preservatives and are intended for single use only.
• This drug is cytotoxic. Follow applicable special handling and disposal procedures.
• Exercise caution and wear gloves when preparing this drug solution.
• Immediately wash the skin thoroughly or rinse the mucosa with copious amounts of water if this drug contacts the skin or mucus membranes. Death has occurred in animal studies due to dermal absorption.
• The manufacturer product information should be consulted for complete reconstitution instructions.

IV compatibility:

• Reconstitute with 0.9% sodium chloride injection

Monitoring:

• Laboratory evaluation of renal and hepatic function, including transaminases and serum creatinine should be performed prior to initiation of therapy and periodically during therapy.