Ganite

Generic Name: Gallium Nitrate
Class: Bone Resorption Inhibitors
ATC Class: V09HX01
VA Class: HS900
Chemical Name: Nitric acid gallium salt nonahydrate
Molecular Formula: GaN3O9•9H2O
CAS Number: 135886-70-3

Warning(s)

  • Concomitant Use with Nephrotoxic Drugs
  • Risk of severe renal insufficiency in patients with cancer-related hypercalcemia when administered concomitantly with other potentially nephrotoxic drugs (e.g., aminoglycosides, amphotericin B).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 exceeds 2.5 mg/dL, discontinue gallium therapy.1

Introduction

Bone resorption inhibitor.1

Uses for Ganite

Hypercalcemia

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 designated an orphan drug by FDA for this use.5

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More conservative measures than gallium therapy (e.g., hydration alone or combined with diuretics) generally are used for mild or asymptomatic hypercalcemia.1

Bladder Cancer

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; however, other agents are preferred.6 9 18

Ganite Dosage and Administration

General

  • Hypercalcemia
  • Prior to initiating therapy, establish adequate hydration and urinary output in order to increase renal excretion of calcium.1 2

  • Maintain adequate hydration throughout therapy.1

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by slow IV infusion.1

Dilution

Dilute calculated daily dose, preferably in 1 L of 0.9% sodium chloride injection or 5% dextrose injection.1 Discard unused portion of vial.1

Rate of Administration

Administer by slow IV infusion over 24 hours.1

Dosage

Adults

Hypercalcemia
IV

200 mg/m2 daily for 5 consecutive days.1 4

If used for mild hypercalcemia and few associated symptoms, 100 mg/m2 daily for 5 days may be used.1

If optimum serum calcium concentrations are achieved in <5 days, therapy may be discontinued early.1

Prescribing Limits

Adults

Hypercalcemia
IV

Safety and efficacy of repeated courses not established.1

Special Populations

Renal Impairment

Hypercalcemia
IV

Contraindicated in patients with severe renal impairment (Scr >2.5 mg/dL).1

Caution if used in patients with mild to moderate renal impairment (Scr 2–2.5 mg/dL); manufacturer makes no specific recommendations regarding dosage in these patients.1 (See Renal Impairment under Cautions.)

Cautions for Ganite

Contraindications

  • Severe renal impairment (Scr >2.5 mg/dL).1

Warnings/Precautions

Warnings

Renal Effects

Renal function abnormalities reported in clinical trials with gallium; hypercalcemia in cancer patients is commonly associated with impaired renal function.1

Establish adequate hydration and satisfactory urine output (e.g., 2 L daily) before initiating therapy.1 Maintain adequate hydration throughout treatment period.1 Avoid overhydration in patients with compromised cardiovascular status.1

Monitoring of Scr during gallium therapy is strongly recommended.1 Discontinue gallium if Scr >2.5 mg/dL.1

Concomitant use of gallium with other nephrotoxic drugs may increase the risk of renal insufficiency in patients with cancer-related hypercalcemia.1 (See Boxed Warning.)

General Precautions

Hypocalcemia

Asymptomatic or mild to moderate hypocalcemia (6.5–8 mg/dL, corrected for albumin) may occur.1 Manufacturer recommends daily monitoring of serum calcium concentrations.1 If hypocalcemia occurs, discontinue gallium; short-term calcium replacement may be necessary.1

Hypophosphatemia

Transient hypophosphatemia may occur.1 Manufacturer recommends twice-weekly monitoring of serum phosphorus concentrations.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether gallium is distributed into milk.1 Discontinue nursing or the drug. 1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 2

Renal Impairment

Contraindicated in patients with Scr >2.5 mg/dL.1 Safety and efficacy in these patients have not been examined systematically.1

If used in patients with Scr of 2–2.5 mg/dL, monitor renal function frequently.1 Discontinue if Scr increases beyond 2.5 mg/dL.1

Common Adverse Effects

Increased BUN and Scr, hypocalcemia, transient hypophosphatemia, decreased serum bicarbonate, decreased BP. 1

Interactions for Ganite

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

Drug

Interaction

Cyclophosphamide

Dyspnea (occasionally associated with interstitial pneumonitis), mouth soreness, and asthenia reported in small number of multiple myeloma patients receiving low-dose gallium concomitantly with cyclophosphamide and prednisone1

Diuretics (e.g., furosemide)

No apparent adverse interaction1

Ganite Pharmacokinetics

Absorption

Serum Concentrations

Steady state reached in 24–48 hours.1

Elimination

Metabolism

Not metabolized by liver or kidneys. 1

Elimination Route

Substantially excreted by kidneys.1 Average plasma clearance: 0.15 L/hour per kg. 1

Stability

Storage

Parenteral

Injection

20–25°C.1

Stable for 48 hours at 15–30°C or for 7 days at 2–8°C when diluted as recommended. 1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility1

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Y-Site CompatibilityHID

Compatible

Acyclovir sodium

Allopurinol sodium

Amifostine

Aminophylline

Ampicillin sodium-sulbactam sodium

Aztreonam

Cefazolin sodium

Ceftazidime

Ceftriaxone sodium

Cimetidine HCl

Ciprofloxacin

Cladribine

Co-trimoxazole

Cyclophosphamide

Dexamethasone sodium phosphate

Diphenhydramine HCl

Filgrastim

Fluconazole

Furosemide

Granisetron HCl

Heparin sodium

Hydrocortisone sodium succinate

Ifosfamide

Magnesium sulfate

Mannitol

Melphalan HCl

Meperidine HCl

Mesna

Methotrexate sodium

Metoclopramide HCl

Ondansetron HCl

Piperacillin sodium-tazobactam sodium

Potassium chloride

Ranitidine HCl

Sodium bicarbonate

Teniposide

Thiotepa

Ticarcillin disodium-clavulanate potassium

Vancomycin HCl

Vinorelbine tartrate

Incompatible

Cefepime HCl

Cisplatin

Cytarabine

Doxorubicin HCl

Etoposide

Fluorouracil

Haloperidol lactate

Hydromorphone HCl

Imipenem-cilastatin sodium

Lorazepam

Morphine sulfate

Prochlorperazine edisylate

Actions

  • Exerts hypocalcemic effect by inhibiting calcium resorption from bone, possibly by reducing increased bone turnover. 1

  • No cytotoxic effects were seen on bone cells of animals treated with gallium.1

Advice to Patients

  • 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.)

Preparations

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

Gallium Nitrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

25 mg/mL (500 mg)

Ganite

Genta

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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. [IDIS 242855] [PubMed 3282463]

4. Bilezikian JP. Management of acute hypercalcemia. N Engl J Med. 1992; 326:1196-203. [IDIS 295128] [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. [IDIS 388904] [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. [IDIS 396655] [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. [IDIS 378327] [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. [IDIS 338059] [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. [IDIS 291282] [PubMed 1933802]

18. Reviewers’ comments (personal observations) on bladder cancer.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:770-2.

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