Ganite

Bone resorption inhibitor.1

Nephrotoxic Drugs

Potential increased risk of nephrotoxicity.1 Discontinue gallium if use of a potentially nephrotoxic drug is indicated; continue hydration for several days after administration of the nephrotoxic drug.1 Closely monitor Scr and urine output during and after this period.1 If Scr >2.5 mg/dL, discontinue gallium therapy.1

Specific Drugs

• Risk of renal function abnormalities, hypocalcemia, and transient hypophosphatemia.1 Importance of laboratory monitoring.1

• Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

General Asymptomatic or mild to moderate hypocalcemia (6.5 - 8.0 mg/dL, corrected for serum albumin) occurred in approximately 38% of patients treated with Ganite in the controlled clinical trial. One patient exhibited a positive Chvostek’s sign. If hypocalcemia occurs, Ganite therapy should be stopped and short-term calcium therapy may be necessary.

Laboratory Tests Renal function (serum creatinine and BUN) and serum calcium must be closely monitored during Ganite therapy. In addition to baseline assessment, the suggested frequency of calcium and phosphorus determinations is daily and twice weekly, respectively. Ganite should be discontinued if the serum creatinine exceeds 2.5 mg/dL.

Drug Interactions The concomitant use of highly nephrotoxic drugs in combination with Ganite may increase the risk for development of renal insufficiency (see WARNINGS). Available information does not indicate any adverse interaction with diuretics such as furosemide. A symptom complex of dyspnea (associated with interstitial pneumonitis in some instances), mouth soreness, and asthenia has been reported in a small number of multiple myeloma patients receiving low dose (40 mg) gallium nitrate subcutaneously in addition to oral cyclophosphamide and prednisone. The serious nature of the underlying condition of these patients precludes a precise understanding of the relationship of these events to either gallium nitrate treatment alone or with cyclophosphamide.

Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been performed to evaluate the carcinogenic potential of gallium nitrate. Gallium nitrate is not mutagenic in standard tests (i.e., Ames test and chromosomal aberration studies on human lymphocytes).

Usage in Pregnancy Pregnancy Category C. Animal reproduction studies have not been conducted with gallium nitrate. It is also not known whether gallium nitrate can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Ganite should be administered to a pregnant woman only if clearly needed.

Nursing Mothers It is not known whether gallium nitrate is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from gallium nitrate, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use The safety and effectiveness of Ganite in children have not been established.

Kidney Adverse renal effects, as demonstrated by rising BUN and creatinine, have been reported in about 12.5% of patients treated with Ganite. In a controlled clinical trial of patients with cancer-related hypercalcemia, two patients receiving Ganite and one patient receiving calcitonin developed acute renal failure. Due to the serious nature of the patients’ underlying conditions, the relationship of these events to the drug was unclear. Ganite should not be administered to patients with serum creatinine >2.5 mg/dL (see CONTRAINDICATIONS and WARNINGS).

Metabolic Hypocalcemia may occur after Ganite treatment (see PRECAUTIONS).

Transient hypophosphatemia of mild-to-moderate degree may occur in up to 79% of hypercalcemic patients following treatment with Ganite. In a controlled clinical trial, 33% of patients had at least 1 serum phosphorus measurement between 1.5-2.4 mg/dL, while 46% of patients had at least 1 serum phosphorus value <1.5 mg/dL. Patients who develop hypophosphatemia may require oral phosphorus therapy.

Decreased serum bicarbonate, possibly secondary to mild respiratory alkalosis was reported in 40-50% of cancer patients treated with Ganite. The cause for this effect is not clear. This effect has been asymptomatic and has not required specific treatment.

Hematologic The use of very high doses of gallium nitrate (up to 1400 mg/m2) in treating patients for advanced cancer has been associated with anemia, and several patients have received red blood cell transfusions. Due to the serious nature of the underlying illness, it is uncertain that the anemia was caused by gallium nitrate.

Blood Pressure A decrease in mean systolic and diastolic blood pressure was observed several days after treatment with gallium nitrate in a controlled clinical trial. The decrease in blood pressure was asymptomatic and did not require specific treatment.

Visual and Auditory In cancer chemotherapy trials, a small proportion (<1%) of patients treated with multiple high doses of gallium nitrate combined with other investigational anticancer drugs, have developed acute optic neuritis. While these patients were critically ill and had received multiple drugs, a reaction to high-dose gallium nitrate is possible. Most patients had full recovery; however, at least one case of permanent blindness has been reported. One patient with cancer-related hypercalcemia was reported to develop decreased hearing following gallium nitrate administration. Due to the patient’s underlying condition and concurrent therapies, the relationship of this event to gallium nitrate administration is unclear. Tinnitus and partial loss of auditory acuity have been reported rarely (<1%) in patients who received high-dose gallium nitrate as anticancer treatment.

Miscellaneous Other clinical events reported in association with gallium nitrate treatment for cancer as well as cancer-related hypercalcemia include: nausea and/or vomiting, tachycardia, lethargy, confusion, dreams and hallucinations, diarrhea, constipation, lower extremity edema, hypothermia, fever, dyspnea, rales and rhonchi, anemia, leukopenia, paresthesia, skin rash, pleural effusion, and pulmonary infiltrates. Due to the serious nature of the underlying condition of these patients, the relationship of these events to therapy with gallium nitrate is unknown. A single case of encephalopathy followed rapidly by coma and death has been reported after treatment in a cancer chemotherapy trial with gallium nitrate 300 mg/m2/day for 7 days. Treatment with gallium nitrate other than as described in this labeling may be complicated by adverse events not listed.

The usual recommended dose of Ganite is 200 mg per square meter of body surface area (200 mg/m2) daily for 5 consecutive days. In patients with mild hypercalcemia and few symptoms, a lower dosage of 100 mg/m2/day for 5 days may be considered. If serum calcium levels are lowered into the normal range in less than 5 days, treatment may be discontinued early. The daily dose must be administered as an intravenous infusion over 24 hours. The daily dose should be diluted, preferably in 1,000 mL of 0.9% Sodium Chloride Injection USP, or 5% Dextrose Injection USP, for administration as an intravenous infusion over 24 hours. Adequate hydration must be maintained throughout the treatment period, with careful attention to avoid overhydration in patients with compromised cardiovascular status. Controlled studies have not been undertaken to evaluate the safety and effectiveness of retreatment with gallium nitrate.

When Ganite is added to either 0.9% Sodium Chloride Injection USP or 5% Dextrose Injection USP, it is stable for 48 hours at room temperature (15°C to 30°C) or for 7 days if stored under refrigeration (2°C to 8°C). Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Ganite® (gallium nitrate injection) is supplied as a 5-unit carton, NDC 66657-301-05.

Each carton contains 5 single-dose, flip-top vials (NDC 66657-301-01) each containing 500 mg of gallium nitrate (25 mg/mL) in 20 mL.

Store at controlled room temperature 20°-25°C (68°-77°F).

Contains no preservative. Discard unused portion.

Rx only

Ganite® is a trademark of Genta Incorporated.

Manufactured for:
Genta Incorporated
Berkeley Heights, NJ 07922
1-888-TO-GENTA

Revised: October 2006

30105902

Vial Label

Rx only NDC 66657-301-01

Ganite®

(gallium nitrate injection)

500mg

25mg/mL

Sterile Solution • For Intravenous Use

20mL Single-Use Vial

Sterile, aqueous, preservative-free, buffered
solution. For parenteral administration via infusion.
Discard unused portion.

Dilute in an isotonic saline or dextrose solution.

Each mL contains: Gallium nitrate 25mg (on an
anhydrous basis) and Sodium citrate dihydrate
(28.75mg).

Store at controlled room temperature
20°-25°C (68°-77°F).

Manufactured for:
Genta Incorporated
Berkeley Heights, NJ 07922
1-888-TO-GENTA