Radiopharmaceuticals should only be used by physicians who are qualified by training and experience in the safe use and handling of radionuclides and whose experience and training have been approved by the appropriate government agency authorized to license the use of radionuclides.

Metastron, like other radioactive drugs, must be handled with care and appropriate safety measures taken to minimize radiation to clinical personnel.

In view of the delayed onset of pain relief, typically 7 to 20 days post injection, administration of Metastron to patients with very short life expectancy is not recommended.

A calcium-like flushing sensation has been observed in patients following a rapid (less than 30 second injection) administration.

Special precautions, such as urinary catheterization, should be taken following administration to patients who are incontinent to minimize the risk of radioactive contamination of clothing, bed linen and the patient's environment.

Metastron is excreted primarily by the kidneys. In patients with renal dysfunction, the possible risks of administering Metastron should be weighed against the possible benefits.

Carcinogenesis, Mutagenesis, Impairment of Fertility
Data from a repetitive dose animal study suggests that Strontium-89 Chloride is a potential carcinogen. Thirty-three of 40 rats injected with Strontium-89 Chloride in ten consecutive monthly doses of either 250 or 350 µCi/kg developed malignant bone tumors after a latency period of approximately 9 months. No neoplasia was observed in the control animals. Treatment with Strontium-89 Chloride should be restricted to patients with well documented metastatic bone disease.

Adequate studies with Strontium-89 Chloride have not been performed to eva luate mutagenic potential or effects on fertility.

Pregnancy
Teratogenic effects
Pregnancy Category D. See Warnings section.

Nursing Mothers
Because Strontium acts as a calcium analog, secretion of Strontium-89 Chloride into human milk is likely. It is recommended that nursing be discontinued by mothers about to receive intravenous Strontium-89 Chloride. It is not known whether this drug is excreted in human milk.

Pediatric Use
Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

ADVERSE REACTIONS
A single case of fatal septicemia following leukopenia was reported during clinical trials. Most severe reactions of marrow toxicity can be managed by conventional means.

A small number of patients have reported a transient increase in bone pain at 36 to 72 hours after injection. This is usually mild and self-limiting, and controllable with analgesics. A single patient reported chills and fever 12 hours after injection without long-term sequelae.

DOSAGE AND ADMINISTRATION
The recommended dose of Metastron is 148 MBq, 4 mCi, administered by slow intravenous injection (1-2 minutes).

Alternatively, a dose of 1.5 - 2.2 MBq/kg, 40-60 µCi/kg body weight may be used.

Repeated administrations of Metastron should be based on an individual patient's response to therapy, current symptoms, and hematologic status, and are generally not recommended at intervals of less than 90 days.

The patient dose should be measured by a suitable radioactivity calibratio