QUADRAMET Solution for injection Ref.[10957] Active ingredients: Samarium ¹⁵³Sm lexidronam

In absence of clinical data, the injected activity should be adapted to the renal function.

Use of Quadramet in patients with evidence of compromised bone marrow reserve from previous therapy or disease involvement is not recommended unless the potential benefit of the treatment outweighs its risks.

Because of potential bone marrow suppression after administration, blood counts should be monitored weekly for at least 8 weeks, beginning 2 weeks after administration of Quadramet, or until recovery of adequate bone marrow function.

The patient should be encouraged to ingest (or receive by intravenous administration) a minimum of 500 ml of fluids prior to injection and should be encouraged to void as often as possible after injection to minimise radiation exposure to the bladder.

The clearance of Quadramet being rapid, the precautions relating to the excreted urinary radioactivity need not be taken after 6-12 hours following administration.

Special precautions, such as bladder catheterisation, should be taken during six hours following administration to incontinent patients to minimise the risk of radioactive contamination of clothing, bed linen, and the patient’s environment. For the other patients the urine should be collected for at least six (6) hours.

Bladder catheterisation should be undertaken in patients with urinary obstruction.

Radiopharmaceuticals may be received, used and administered only by authorised persons in designated clinical settings. Its receipt, storage, use, transfer and disposal are subject to the regulations and the appropriate licences of the local competent official organisations.

Radiopharmaceuticals should be prepared by the user in a manner which satisfies both radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken, complying with the requirements of Good Manufacturing Practice for pharmaceuticals.

Because of the potential for additive effects on bone marrow, the treatment should not be given concurrently with chemotherapy or external beam radiation therapy. Quadramet may be given subsequent to either of these treatments after allowing for adequate marrow recovery.

Pregnancy

Quadramet is contra-indicated (see 4.3) in pregnancy. The possibility of pregnancy must strictly be ruled out. Women of childbearing potential have to use effective contraception during the treatment and the whole period of follow-up.

Breast-feeding

There are no available clinical data relating to the excretion of Quadramet in human milk. If therefore Quadramet administration is deemed necessary, formula feeding should be substituted for breastfeeding and the expressed feeds discarded.

No studies on the effects on the ability to drive and use machines have been performed.

Decreases in white blood cell and platelet counts and anaemia were observed in patients receiving Quadramet.

In clinical trials white blood cell and platelet counts decreased to a nadir of approximately 40% to 50% of baseline 3 to 5 weeks after a dose, and generally returned to pre-treatment levels by 8 weeks post treatment.

The few patients who experienced Grade 3 or 4 hematopoietic toxicity usually either had a history of recent external beam radiation therapy or chemotherapy or had rapidly progressive disease with probable bone marrow involvement.

Postmarketing reports of thrombocytopenia have included isolated reports of intracranial haemorrhage, and cases in which the outcome was fatal.

A small number of patients have reported a transient increase in bone pain shortly after injection (flare reaction). This is usually mild and self-limiting and occurs within 72 hours of injection. Such reactions are usually responsive to analgesics.

Adverse drug reactions such as nausea, vomiting, diarrhoea and sweating were reported.

Hypersensitivity reactions including rare cases of anaphylactic reaction have been reported after Quadramet administration.

A few patients experienced cord/root compressions, disseminated intravascular coagulation and cerebrovascular accidents. The occurrence of these events may be linked to the patients' disease evolution. When there are spinal metastases at the cervico-dorsal level, an increased risk of spinal cord compression cannot be excluded.

The radiation dose resulting from therapeutic exposure may result in higher incidence of cancer and mutations. In all cases, it is necessary to ensure that the risks of the radiation are less than from the disease itself.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with the other medicinal products.