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Gemzar (Gemcitabine Hydrochloride) - Indications and Dosage

 
 



INDICATIONS AND USAGE

Therapeutic Indications

Ovarian Cancer

Gemzar in combination with carboplatin is indicated for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum–based therapy.

Breast Cancer

Gemzar in combination with paclitaxel is indicated for the first–line treatment of patients with metastatic breast cancer after failure of prior anthracycline–containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated.

Non–Small Cell Lung Cancer

Gemzar is indicated 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.

Pancreatic Cancer

Gemzar is indicated as first–line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. Gemzar is indicated for patients previously treated with 5–FU.

DOSAGE AND ADMINISTRATION

Gemzar is for intravenous use only.

Adults

Single–Agent Use:

Pancreatic Cancer — Gemzar should be administered by intravenous infusion at a dose of 1000 mg/m2 over 30 minutes once weekly for up to 7 weeks (or until toxicity necessitates reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles should consist of infusions once weekly for 3 consecutive weeks out of every 4 weeks.

Dose Modifications — Dosage adjustment is based upon the degree of hematologic toxicity experienced by the patient (see WARNINGS). Clearance in women and the elderly is reduced and women were somewhat less able to progress to subsequent cycles (see Human Pharmacokinetics under CLINICAL PHARMACOLOGY and PRECAUTIONS).

Patients receiving Gemzar should be monitored prior to each dose with a complete blood count (CBC), including differential and platelet count. If marrow suppression is detected, therapy should be modified or suspended according to the guidelines in Table 13.

Table 13: Dosage Reduction Guidelines

Absolute granulocyte count
(x 106/L)

Platelet count
(x 106/L)

% of full dose

≥1000

and

≥100,000

100

500–999

or

50,000–99,999

75

<500

or

<50,000

Hold

Laboratory evaluation of renal and hepatic function, including transaminases and serum creatinine, should be performed prior to initiation of therapy and periodically thereafter. Gemzar should be administered with caution in patients with evidence of significant renal or hepatic impairment as there is insufficient information from clinical studies to allow clear dose recommendation for these patient populations.

Patients treated with Gemzar who complete an entire cycle of therapy may have the dose for subsequent cycles increased by 25%, provided that the absolute granulocyte count (AGC) and platelet nadirs exceed 1500 x 106/L and 100,000 x 106/L, respectively, and if non–hematologic toxicity has not been greater than WHO Grade 1. If patients tolerate the subsequent course of Gemzar at the increased dose, the dose for the next cycle can be further increased by 20%, provided again that the AGC and platelet nadirs exceed 1500 x 106/L and 100,000 x 106/L, respectively, and that non–hematologic toxicity has not been greater than WHO Grade 1.

Combination Use:

Non–Small Cell Lung Cancer — Two schedules have been investigated and the optimum schedule has not been determined (see CLINICAL STUDIES). With the 4–week schedule, Gemzar should be administered intravenously at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15 of each 28–day cycle. Cisplatin should be administered intravenously at 100 mg/m2 on Day 1 after the infusion of Gemzar. With the 3–week schedule, Gemzar should be administered intravenously at 1250 mg/m2 over 30 minutes on Days 1 and 8 of each 21–day cycle. Cisplatin at a dose of 100 mg/m2 should be administered intravenously after the infusion of Gemzar on Day 1. See prescribing information for cisplatin administration and hydration guidelines.

Dose Modifications — Dosage adjustments for hematologic toxicity may be required for Gemzar and for cisplatin. Gemzar dosage adjustment for hematological toxicity is based on the granulocyte and platelet counts taken on the day of therapy. Patients receiving Gemzar should be monitored prior to each dose with a complete blood count (CBC), including differential and platelet counts. If marrow suppression is detected, therapy should be modified or suspended according to the guidelines in Table 13. For cisplatin dosage adjustment, see manufacturer’s prescribing information.

In general, for severe (Grade 3 or 4) non–hematological toxicity, except alopecia and nausea/vomiting, therapy with Gemzar plus cisplatin should be held or decreased by 50% depending on the judgment of the treating physician. During combination therapy with cisplatin, serum creatinine, serum potassium, serum calcium, and serum magnesium should be carefully monitored (Grade 3/4 serum creatinine toxicity for Gemzar plus cisplatin was 5% versus 2% for cisplatin alone).

Breast Cancer — Gemzar should be administered intravenously at a dose of 1250 mg/m2 over 30 minutes on Days 1 and 8 of each 21–day cycle. Paclitaxel should be administered at 175 mg/m2 on Day 1 as a 3–hour intravenous infusion before Gemzar administration. Patients should be monitored prior to each dose with a complete blood count, including differential counts. Patients should have an absolute granulocyte count ≥1500 x 106/L and a platelet count ≥100,000 x 106/L prior to each cycle.

Dose Modifications — Gemzar dosage adjustments for hematological toxicity is based on the granulocyte and platelet counts taken on Day 8 of therapy. If marrow suppression is detected, Gemzar dosage should be modified according to the guidelines in Table 14.

Table 14: Day 8 Dosage Reduction Guidelines for Gemzar in Combination with Paclitaxel

Absolute granulocyte count
(x 106/L)

Platelet count
(x 106/L)

% of full dose

≥1200

and

>75,000

100

1000–1199

or

50,000–75,000

75

700–999

and

≥50,000

50

<700

or

<50,000

Hold

In general, for severe (Grade 3 or 4) non–hematological toxicity, except alopecia and nausea/vomiting, therapy with Gemzar should be held or decreased by 50% depending on the judgment of the treating physician. For paclitaxel dosage adjustment, see manufacturer’s prescribing information.

Ovarian Cancer — Gemzar should be administered intravenously at a dose of 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21–day cycle. Carboplatin AUC 4 should be administered intravenously on Day 1 after Gemzar administration. Patients should be monitored prior to each dose with a complete blood count, including differential counts. Patients should have an absolute granulocyte count ≥1500 x 106/L and a platelet count ≥100,000 x 106/L prior to each cycle.

Dose Modifications — Gemzar dosage adjustments for hematological toxicity within a cycle of treatment is based on the granulocyte and platelet counts taken on Day 8 of therapy. If marrow suppression is detected, Gemzar dosage should be modified according to guidelines in Table 15.

Table 15: Day 8 Dosage Reduction Guidelines for Gemzar in Combination with Carboplatin

Absolute granulocyte count
(x 106/L)

Platelet count
(x 106/L)

% of full dose

≥1500

and

≥100,000

100

1000–1499

and/or

75,000–99,999

50

<1000

and/or

<75,000

Hold

In general, for severe (Grade 3 or 4) non–hematological toxicity, except nausea/vomiting, therapy with Gemzar should be held or decreased by 50% depending on the judgment of the treating physician. For carboplatin dosage adjustment, see manufacturer’s prescribing information.

Dose adjustment for Gemzar in combination with carboplatin for subsequent cycles is based upon observed toxicity. The dose of Gemzar in subsequent cycles should be reduced to 800 mg/m2 on Days 1 and 8 in case of any of the following hematologic toxicities:

  • Absolute granulocyte count <500 x 106/L for more than 5 days

  • Absolute granulocyte count <100 x 106/L for more than 3 days

  • Febrile neutropenia

  • Platelets <25,000 x 106/L

  • Cycle delay of more than one week due to toxicity

If any of the above toxicities recur after the initial dose reduction, for the subsequent cycle, Gemzar should be given on Day 1 only at 800 mg/m2.

Gemzar may be administered on an outpatient basis.

Instructions for Use/Handling

The recommended diluent for reconstitution of Gemzar is 0.9% Sodium Chloride Injection without preservatives. Due to solubility considerations, the maximum concentration for Gemzar upon reconstitution is 40 mg/mL. Reconstitution at concentrations greater than 40 mg/mL may result in incomplete dissolution, and should be avoided.

To reconstitute, add 5 mL of 0.9% Sodium Chloride Injection to the 200–mg vial or 25 mL of 0.9% Sodium Chloride Injection to the 1–g vial. Shake to dissolve. These dilutions each yield a gemcitabine concentration of 38 mg/mL which includes accounting for the displacement volume of the lyophilized powder (0.26 mL for the 200–mg vial or 1.3 mL for the 1–g vial). The total volume upon reconstitution will be 5.26 mL or 26.3 mL, respectively. Complete withdrawal of the vial contents will provide 200 mg or 1 g of gemcitabine, respectively. The appropriate amount of drug may be administered as prepared or further diluted with 0.9% Sodium Chloride Injection to concentrations as low as 0.1 mg/mL.

Reconstituted Gemzar is a clear, colorless to light straw–colored solution. After reconstitution with 0.9% Sodium Chloride Injection, the pH of the resulting solution lies in the range of 2.7 to 3.3. The solution should be inspected visually for particulate matter and discoloration, prior to administration, whenever solution or container permit. If particulate matter or discoloration is found, do not administer.

When prepared as directed, Gemzar solutions are stable for 24 hours at controlled room temperature 20° to 25°C (68° to 77°F) [ See USP]. Discard unused portion. Solutions of reconstituted Gemzar should not be refrigerated, as crystallization may occur.

The compatibility of Gemzar with other drugs has not been studied. No incompatibilities have been observed with infusion bottles or polyvinyl chloride bags and administration sets.

Unopened vials of Gemzar are stable until the expiration date indicated on the package when stored at controlled room temperature 20° to 25°C (68° to 77°F) [ See USP].

Caution should be exercised in handling and preparing Gemzar solutions. The use of gloves is recommended. If Gemzar solution contacts the skin or mucosa, immediately wash the skin thoroughly with soap and water or rinse the mucosa with copious amounts of water. Although acute dermal irritation has not been observed in animal studies, 2 of 3 rabbits exhibited drug–related systemic toxicities (death, hypoactivity, nasal discharge, shallow breathing) due to dermal absorption.

Procedures for proper handling and disposal of anti–cancer drugs should be considered. Several guidelines on this subject have been published.1–5 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

HOW SUPPLIED

Vials:

200 mg white, lyophilized powder in a 10–mL size sterile single use vial (No. 7501)
         NDC 0002–7501–01

1 g white, lyophilized powder in a 50–mL size sterile single use vial (No. 7502)
         NDC 0002–7502–01

Store at controlled room temperature 20° to 25°C (68° to 77°F). The USP has defined controlled room temperature as “A temperature maintained thermostatically that encompasses the usual and customary working environment of 20° to 25°C (68° to 77°F); that results in a mean kinetic temperature calculated to be not more than 25°C; and that allows for excursions between 15° and 30°C (59° and 86°F) that are experienced in pharmacies, hospitals, and warehouses.”

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