VA Class:HS900
AHFS Class:
- Bone Resorption Inhibitors 92:24
Generic Name(s):
Chemical Name:
- Nitric acid gallium salt nonahydrate
Molecular Formula:
Gallium nitrate is a synthetic bone resorption inhibitor.1
Hypercalcemia 
Gallium nitrate is used in conjunction with adequate hydration for the management of symptomatic hypercalcemia associated with malignant neoplasms in patients whose hypercalcemia is not adequately managed with conventional methods of treatment (e.g., hydration alone).1,3,4 The drug is designated an orphan drug by the US Food and Drug Administration (FDA) for use in this condition.5 The hypocalcemic effect of gallium nitrate appears to result principally from inhibition of bone resorption1,3,4 and does not depend on cytotoxic activity.3 Prior to initiating gallium nitrate therapy in the management of malignancy-associated hypercalcemia, it is important to establish adequate hydration and urinary output in order to increase renal excretion of calcium;1,2 adequate hydration should be maintained throughout therapy with the drug.1 For the treatment of mild or asymptomatic hypercalcemia, measures more conservative (e.g., hydration alone or combined with diuretics) than therapy with agents such as gallium nitrate generally are used.1
Bladder Cancer
Although gallium nitrate has been used alone8,14,15,17 and in combination with other antineoplastic agents11,12,16 for the treatment of advanced or metastatic bladder carcinoma†, other agents are preferred for the treatment of this neoplasm.6,9,18
In a randomized phase II trial, combination therapy with gallium nitrate and fluorouracil was inferior to combination therapy with cisplatin, methotrexate, vinblastine, and doxorubicin (abbreviated as M-VAC), a currently preferred regimen for the treatment of advanced or metastatic bladder carcinoma.7 Combination therapy with gallium nitrate, ifosfamide, and vinblastine (abbreviated as VIG) produces response rates that appear to be comparable to those observed with M-VAC in patients with advanced or metastatic bladder carcinoma;11,12 however, because of the excessive toxicity (particularly hematologic and cardiac toxicity), sometimes fatal, associated with this regimen, no further clinical trials are planned for VIG in patients with transitional cell bladder carcinoma.10,11,12,13
Substantial nephrotoxicity was observed in patients receiving gallium nitrate by rapid IV infusion for the treatment of advanced bladder cancer,14 and renal toxicity was less pronounced when the drug was administered by continuous IV infusion.15,17 Concomitant administration of calcitriol was used in patients with advanced bladder carcinoma to reduce the severity of hypocalcemia associated with gallium nitrate therapy.11,12
Reconstitution and Administration
Gallium nitrate is administered by slow IV infusion.1
The manufacturer recommends that the calculated daily dose of gallium nitrate injection be diluted preferably in 1 L of 0.9% sodium chloride injection or 5% dextrose injection and states that this dose must be infused over a 24-hour period.1
Dosage
The manufacturer states that safety and efficacy of gallium nitrate in children younger than 18 years of age have not been established.1,2
For the management of malignancy-associated hypercalcemia in adults, the usual dosage of gallium nitrate is 200 mg/m2 daily for 5 consecutive days.1,4 If the drug is used for the management of mild hypercalcemia with few associated symptoms, a lower dosage of 100 mg/m2 daily for 5 days may be used.1 If optimum serum calcium concentrations are achieved in less than 5 days, gallium nitrate therapy may be discontinued.1 If hypocalcemia develops, gallium nitrate therapy should be discontinued, and short-term calcium replacement may be necessary. Adequate hydration must be maintained throughout the treatment period, while avoiding overhydration in patients with compromised cardiovascular status.1 The safety and efficacy of repeated courses of gallium nitrate therapy currently are being investigated but remain to be established.1
Dosage in Renal Impairment
Safety and efficacy of gallium nitrate therapy in hypercalcemic patients with marked renal insufficiency (serum creatinine concentration exceeding 2.5 mg/dL) have not been examined systematically, and use in such patients currently is stated by the manufacturer as contraindicated. The manufacturer makes no specific recommendations concerning dosage adjustment in patients with renal impairment.1 If the drug is used in patients with less pronounced impairment (serum creatinine concentration of 2-2.5 mg/dL), frequent monitoring of renal function is recommended; the manufacturer recommends that gallium nitrate be discontinued if serum creatinine concentration increases beyond 2.5 mg/dL during therapy with the drug.1
Description
Gallium nitrate is a synthetic inhibitor of bone resorption.1
Additional Information
SumMon® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the labeling be consulted for detailed information on the usual cautions, precautions, and contraindications.
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.
Gallium Nitrate
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|
Parenteral | Injection | 25 mg/mL (500 mg) | Ganite® | Genta |
AHFS® Drug Information. © Copyright, 1959-2022, Selected Revisions January 1, 2008. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
1. Genta Incorporated. Ganite® (gallium nitrate) injection prescribing information. Berkeley Heights, NJ; 2003 Sep.
2. Fujisawa Pharmaceutical Company: Personal communication.
3. Warrell RP Jr, Israel R, Frisone M et al. Gallium nitrate for acute treatment of cancer-related hypercalcemia: a randomized, double-blind comparison to calcitonin. Ann Intern Med . 1988; 108:669-74. [PubMed 3282463]
4. Bilezikian JP. Management of acute hypercalcemia. N Engl J Med . 1992; 326:1196-203. [PubMed 1532633]
5. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to June 28, 1996. Rockville, MD; 1996 Jul.
6. Scher HI, Shipley WU, Herr HW. Cancer of the bladder. In: DeVita VT Jr, Hellman S, Rosenberg SA eds. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven Publishers; 1997:1300-22.
7. McCaffrey JA, Hilton S, Mazumdar M et al. Phase II randomized trial of gallium nitrate plus fluorouracil versus methotrexate, vinblastine, doxorubicin, and cisplatin in patients with advanced transitional-cell carcinoma. J Clin Oncol . 1997; 15:2449-55. [PubMed 9196161]
8. Anon. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther . 2000; 42:83-92. [PubMed 10994034]
9. Roth BJ. Chemotherapy for advanced bladder cancer. Semin Oncol . 1996; 23:633-44. [PubMed 8893874]
10. Stadler WM, Kuzel T, Roth B et al. Phase II study of single-agent gemcitabine in previously untreated patients with metastatic urothelial cancer. J Clin Oncol . 1997; 15:3394-8. [PubMed 9363871]
11. Dreicer R, Propert KJ, Roth BJ et al. Vinblastine, ifosfamide, and gallium nitrate—an active new regimen in patients with advanced carcinoma of the urothelium: a phase II trial of the Eastern Cooperative Oncology Group (E5892). Cancer . 1997; 79:110-4. [PubMed 8988734]
12. Einhorn LH, Roth BJ, Ansari R et al. Phase II trial of vinblastine, ifosfamide, and gallium combination chemotherapy in metastatic urothelial carcinoma. J Clin Oncol . 1994; 12:2271-6. [PubMed 7525884]
13. Roth BJ. Ifosfamide in the treatment of bladder cancer. Semin Oncol . 1996; 23(Suppl 6):50-5. [PubMed 8677450]
14. Crawford ED, Saiers JH, Baker LH et al. Gallium nitrate in advanced bladder cancer: Southwest Oncology Group study. Urology . 1991; 38:355-7. [PubMed 1755146]
15. Seligman PA, Crawford ED. Treatment of advanced transitional cell carcinoma of the bladder with continuous-infusion gallium nitrate. J Natl Cancer Inst . 1991; 83:1582-4. [PubMed 1960756]
16. Schultz P, Bajorin D, Kelly WK et al. Combination gallium nitrate and 5-fluorouracil for platinum-resistant metastatic transitional cell carcinoma of the bladder. Proc Annu Meet Am Soc Clin Oncol . 1993; 34:203.
17. Seidman AD, Scher HI, Heinemann MH et al. Continuous infusion gallium nitrate for patients with advanced refractory urothelial tract tumors. Cancer . 1991; 68:2561-5. [PubMed 1933802]
18. Reviewers' comments (personal observations) on bladder cancer.