A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Quadramet Warnings, Precautions, Pregnancy, Nursing, Abuse - Samarium SM 153 Lexidronam
Quadramet Warnings, Precautions, Pregnancy, Nursing, Abuse - Samarium SM 153 Lexidronam
WARNINGS
Quadramet causes bone marrow suppression. In clinical trials,
white blood cell counts and platelet counts decreased to a nadir of approximately
40% to 50% of baseline in 123 (95%) of patients within 3 to 5 weeks after Quadramet,
and tended to return to pretreatment levels by 8 weeks. The grade of marrow
toxicity is shown in Table 5 below.
|
TABLE 5:NUMBER AND PERCENT OF PATIENTS WHO EXPERIENCED
MAR ROW TOXICITY IN CLINICAL TRIALS OF QUAD RAMET
|
| |
Hemoglobin
|
Leucocytes
|
Platelets
|
|
Toxicity Grade*
|
Placebo N=85
|
1.0 mCi/kg N=185
|
Placebo N=85
|
1.0 mCi/kg N=184
|
Placebo N=85
|
1.0 mCi/kg N=185
|
|
0 -2
|
78 (92%)
|
162 (88%)
|
85 (100%)
|
169 (92%)
|
85 (100%)
|
173 (94%)
|
|
3
|
6 (7%)
|
20 (11%)
|
0 (0%)
|
15 (8%)
|
0 (0%)
|
10 (5%)
|
|
4
|
1 (1%)
|
3 (2%)
|
0 (0%)
|
0 (0%)
|
0 (0%)
|
2 (1%)
|
* Toxicity Grade based upon National Cancer Institute Criteria;
normal levels are Hemoglobin >10g/dL, Leucocyte ³
4.0 x 103 mL, and Platelets ³
150,000/mL.
Before Quadramet is administered, consideration should be given
to the patient’s current clinical and hematologic status and bone marrow response
history to treatment with myelo-toxic agents. Metastatic prostate and other
cancers can be associated with disseminated intravascular coagulation (DIC);
caution should be exercised in treating cancer patients whose platelet counts
are falling or who have other clinical or laboratory findings suggesting DIC.
Because of the unknown potential for additive effects on bone marrow, Quadramet
should not be given concurrently with chemotherapy or external beam radiation
therapy unless the clinical benefits outweigh the risks. Use of Quadramet in
patients with evidence of compromised bone marrow reserve from previous therapy
or disease involvement is not recommended unless the potential benefits of the
treatment outweigh the risks. Blood counts should be monitored weekly for at
least 8 weeks, or until recovery of adequate bone marrow function.
Pregnancy: As with other radiopharmaceutical drugs, Quadramet
can cause fetal harm when administered to a pregnant woman. Adequate and well
controlled studies have not been conducted in animals or pregnant women. Women
of childbearing age should have a negative pregnancy test before administration
of Quadramet. If this drug is used during pregnancy, or if a patient becomes
pregnant after taking this drug, the patient should be apprised of the potential
hazard to the fetus. Women of childbearing potential should be advised to avoid
becoming pregnant soon after receiving Quadramet. Men and women patients should
be advised to use an effective method of contraception after the administration
of Quadramet.
PRECAUTIONS
EDTMP is a chelating agent. Although the chelating effects
have not been evaluated thoroughly in humans, dogs that received non-radioactive
samarium EDTMP (6 times the human dose based on body weight, 3 times based on
surface area) developed a variety of electrocardiographic (ECG) changes (with
or without the presence of hypocalcemia). The causal relationship between the
hypocal-cemia and ECG changes has not been studied. Whether Quadramet causes
electrocardiographic changes or arrhythmias in humans has not been studied.
Caution and appropriate monitoring should be given when administering Quadramet
to patients.
Because concomitant hydration is recommended to promote the
urinary excretion of Quadramet, appropriate monitoring and consideration of
additional supportive treatment should be used in patients with a history of
congestive heart failure or renal insufficiency.
This drug should be used with caution in patients with compromised
bone marrow reserves. See Warnings.
Skeletal: Spinal cord compression frequently occurs in patients
with known metastases to the cervical, thoracic or lumbar spine. In clinical
studies of Quadramet, spinal cord compression was reported in 7% of patients
who received placebo and in 8.3% of patients who received 1.0 mCi/kg Quadramet.
Quadramet is not indicated for treatment of spinal cord compression. Quadramet
administration for pain relief of metastatic bone cancer does not prevent the
development of spinal cord compression. When there is a clinical suspicion of
spinal cord compression, appropriate diagnostic and therapeutic measures must
be taken immediately to avoid permanent disability.
Radiopharmaceutical agents should be used only 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.
Quadramet, like other radioactive drugs, must be handled with
care, and appropriate safety measures must be taken to minimize radiation exposure
of clinical personnel and others in the patient environment.
Special precautions, such as bladder catheterization, should
be taken with incontinent patients to minimize the risk of radioactive contamination
of clothing, bed linen, and the patient’s environment. Urinary excretion of
radioactivity occurs over about 12 hours (with 35% occurring during the first
6 hours). Studies have not been done on the use of Quadramet in patients with
renal impairment.
Information for Patients
Patients who receive Quadramet should be advised that for several
hours following administration, radioactivity will be present in excreted urine.
To help protect themselves and others in their environment, precautions need
to be taken for 12 hours following administration. Whenever possible, a toilet
should be used, rather than a urinal, and the toilet should be flushed several
times after each use. Spilled urine should be cleaned up completely and patients
should wash their hands thoroughly. If blood or urine gets onto clothing, the
clothing should be washed separately, or stored for 1-2 weeks to allow for decay
of the Sm-153.
Some 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.
Patients who respond to Quadramet might begin to notice the
onset of pain relief one week after Quadramet. Maximal pain relief generally
occurs at 3-4 weeks after injection of Quadramet. Patients who experience a
reduction in pain may be encouraged to decrease their use of opioid analgesics.
Laboratory Tests: Because of the potential for bone
marrow suppression, beginning 2 weeks after Quadramet administration, blood
counts should be monitored weekly for at least 8 weeks, or until recovery of
adequate bone marrow function.
In a subset of 31 patients who had serum calcium monitored
during the first 2 hours after Quadramet infusion, a clear pattern of calcium
change was not identified. However, 10 (32%) patients had at least one serum
calcium level that was below normal (7.16 to 8.28). The extent to which samarium-153-EDTMP
is related to this hypocalcemia is not known. Caution should be exercised when
administering Quadramet to patients at risk for developing hypocalcemia.
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