gallium nitrate

Gallium nitrate is a medication used to reduce blood calcium levels in adults with clearly symptomatic cancer-related excessive blood calcium (hypercalcemia) that has not responded to adequate hydration. Gallium nitrate used to be administered as an intravenous infusion, but is no longer available in the U.S. because the manufacturer withdrew the product from the market in 2012, for reasons other than safety and effectiveness. Gallium nitrate has been also studied for use in the treatment of arthritis, autoimmune disorders and tumors.

Hypercalcemia is a common problem in many cancers, particularly, in non-small cell lung cancer, breast cancer, multiple myeloma, kidney cancer, and cancer of head and neck. Cancer-related hypercalcemia is believed to be caused by an imbalance in the net breakdown of bone tissue (bone resorption) and urinary excretion of calcium, which increases the concentration of calcium circulating in the blood. Extensive bone metastases in these cancers may increase the activity of osteoclasts, cells that break down bone tissue.

Gallium nitrate is a nitrate salt of gallium cation, a heavy metal. The precise mechanism of gallium nitrate in reducing blood calcium has not been established. Gallium nitrate appears to inhibit calcium resorption from bone, possibly by reducing bone turnover. Gallium gets incorporated into hydroxyapatite, an inorganic mineral in bone and teeth, promoting its crystallization, which reduces bone mineral solubility. Gallium may also reduce bone resorption by reducing acid secretion by osteoclasts.

• Do not administer gallium nitrate to patients with severe impairment of kidney function (serum creatinine above 2.5 mg/dL).
• Treatment with gallium nitrate is associated with abnormalities in kidney function including elevation of blood urea nitrogen (BUN) and serum creatinine. Cancer-related hypercalcemia itself is associated with impairment of kidney function.
  • Patients with cancer-related hypercalcemia are often dehydrated. Hydrate patients adequately with oral/intravenous fluids and establish sufficient urine output before initiating treatment with gallium nitrate.
  • Maintain adequate hydration during treatment, and avoid overhydration in patients with compromised cardiovascular status.
  • Monitor serum creatinine frequently during treatment and discontinue gallium nitrate if creatinine exceeds 2.5 mg/dL.
  • Avoid concurrent use of other drugs that are potentially toxic to the kidneys (nephrotoxic), such as aminoglycosides and amphotericin B. If other nephrotoxic drugs are required to be administered, discontinue gallium nitrate and continue hydration for several days after administration of other nephrotoxic drugs.
• A symptom complex with shortness of breath (dyspnea), associated with lung inflammation (pneumonitis) in some cases, mouth soreness and weakness (asthenia) has been observed in a few multiple myeloma patients treated with gallium nitrate, in addition to cyclophosphamide and prednisone. A causal relationship with the treatment and these events has not been established, either with gallium nitrate alone or in combination with cyclophosphamide.
• Gallium nitrate treatment can lead to mild or moderate hypocalcemia. Monitor the patient’s calcium levels and if a patient develops hypocalcemia, discontinue gallium nitrate and provide short-term calcium therapy, if required.

Common side effects of gallium nitrate include:

• Kidney damage
• Elevation in blood urea nitrogen (BUN)
• Elevate serum creatinine
• Acute kidney failure
• Hypocalcemia
• Transient drop in phosphorous level in blood (hypophosphatemia)
• Decrease in serum bicarbonate
• Respiratory alkalosis
• Low red blood cell count (anemia)
• Low count of white blood cells (leukopenia)
• Low blood pressure (hypotension)
• Rapid heart rate (tachycardia)
• Acute inflammation of the optic nerve (optic neuritis)
• Temporary or permanent loss of vision
• Ringing in the ears (tinnitus)
• Partial loss of hearing acuity
• Nausea
• Vomiting
• Diarrhea
• Constipation
• Swelling (edema) of legs
• Fever
• Low core body temperature (hypothermia)
• Shortness of breath (dyspnea)
• Abnormal breathing sounds (rales and ronchi)
• Fluid in lungs (pleural effusion)
• Pulmonary infiltrates
• Skin rash
• Abnormal skin sensations (paresthesia)
• Lethargy
• Confusion
• Abnormal dreams
• Hallucinations

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injectable Solution

• 25 mg/mL (product discontinued)

Adult:

Cancer-related Hypercalcemia

• Discontinued by the manufacturer (4/4/2012)
• Premedicate to prevent hypersensitivity reactions (e.g., dexamethasone, diphenhydramine, H2 blockers)
• 100-200 mg/m2 intravenously (IV) over 24 hours for 5 days; may shorten treatment if calcium levels return to normal in fewer days

Renal Impairment

• Moderate renal impairment: Dose adjustment not provided by manufacturer's labeling; monitor renal status
• Severe renal impairment: Contraindicated

Pediatric:

• Safety and efficacy not established

Overdose

Gallium nitrate overdose as well as rapid IV infusion of the drug can cause nausea and vomiting, and increase the risk for kidney insufficiency. In the event of overdose, gallium nitrate infusion should be immediately discontinued. Patient should be intravenously hydrated, with or without diuretics, for 2-3 days, and their serum calcium levels, kidney function and urine output should be monitored.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Gallium nitrate has no listed severe, serious, moderate, or mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• No animal reproductive studies have been conducted with gallium nitrate and it is not known if gallium nitrate can cause fetal harm if administered during pregnancy. Gallium nitrate should be used in a pregnant woman only if clearly needed.
• It is not known if gallium nitrate is present in breastmilk. Decision should be made to discontinue breastfeeding or gallium nitrate based on the importance of the drug to the nursing mother, because of the potential for serious adverse reactions in the breastfed infant.