Quadramet
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Questions & Answers
Side Effects & Adverse Reactions
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.
|
|
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 ≥4.0 x 10 3µL, and Platelets ≥150,000/µL.
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 myelotoxic 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.
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 child-bearing 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 child-bearing 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®.
Legal Issues
There is currently no legal information available for this drug.
FDA Safety Alerts
There are currently no FDA safety alerts available for this drug.
Manufacturer Warnings
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Uses
QUADRAMET® is indicated for relief of pain in patients with confirmed osteoblastic metastatic bone lesions that enhance on radionuclide bone scan.
History
There is currently no drug history available for this drug.
Other Information
QUADRAMET® is a therapeutic agent consisting of radioactive samarium and a tetraphosphonate chelator, ethylenediaminetetramethylenephosphonic acid (EDTMP). QUADRAMET® is formulated as a sterile, non-pyrogenic, clear, colorless to light amber isotonic solution of samarium-153 lexidronam for intravenous administration. QUADRAMET® does not contain a preservative.
Each milliliter contains 35 mg EDTMP•H2O, 5.3 mg Ca [as Ca(OH)2], 14.1 mg Na [as NaOH], equivalent to 44 mg Ca/Na EDTMP (anhydrous calc.), 5-46 µg samarium (specific activity of approximately 1.0-11.0 mCi/µg Sm), and 1850 ± 185 MBq (50 ± 5 mCi) of samarium-153 at calibration.
The structural formula of samarium lexidronam pentasodium is:
The ionic formula is 153Sm+3 [CH2N(CH2PO3-2)2]2 and the ionic formula weight is 581.1 daltons (pentasodium form, 696).
The pH of the solution is 7.0 to 8.5.
QUADRAMET® is supplied frozen in single-dose glass vials containing 3 mL with 5550 MBq (150 mCi) of samarium-153 at calibration.
Samarium-153 is produced in high yield and purity by neutron irradiation of isotopically enriched samarium Sm 152 oxide (152Sm2O3). It emits both medium-energy beta particles and a gamma photon, and has a physical half-life of 46.3 hours (1.93 days). Samarium-153 has average and maximum beta particle ranges in water of 0.5 mm and 3.0 mm, respectively. The primary radiation emissions of samarium-153 are shown in Table 1.
|
|
Radiation |
Abundance |
| Beta |
640 |
30% |
| Beta |
710 |
50% |
| Beta |
810 |
20% |
| Gamma |
103 |
29% |
The specific gamma-ray constant for samarium-153 is 0.46 R/mCi-hr at 1 cm (1.24x10-5 mSv/MBq- hr at 1 Meter). The half-value thickness of lead (Pb) for samarium-153 is approximately 0.10 mm. The use of 1 mm of lead will decrease the external radiation exposure by a factor of approximately 1,000. QUADRAMET® should be stored in a lead-shielded container and frozen until use.
Radioactive decay factors to be applied to the stated value for radioactive concentration at calibration are given in Table 2. All radioactivity is calibrated to the reference date and time on the vial.
| Time |
Factor |
Time |
Factor |
| -56.0 |
2.31 |
+1.0 |
0.99 |
| -48.0 |
2.05 |
+2.0 |
0.97 |
| -36.0 |
1.71 |
+3.0 |
0.96 |
| -24.0 |
1.43 |
+4.0 |
0.94 |
| -20.0 |
1.35 |
+6.0 |
0.91 |
| -16.0 |
1.27 |
+8.0 |
0.89 |
| -12.0 |
1.20 |
+12.0 |
0.84 |
| -8.0 |
1.13 |
+16.0 |
0.80 |
| -6.0 |
1.09 |
+20.0 |
0.74 |
| -4.0 |
1.06 |
+24.0 |
0.70 |
| -3.0 |
1.05 |
+36.0 |
0.58 |
| -2.0 |
1.03 |
+48.0 |
0.49 |
| -1.0 |
1.02 |
+56.0 |
0.43 |
Sources
Quadramet Manufacturers
-
Jazz Pharmaceuticals, Inc.
![Quadramet (Samarium Sm 153 Lexidronam) Injection, Solution [Jazz Pharmaceuticals, Inc.]](/wp-content/themes/bootstrap/assets/img/loading2.gif)
Quadramet | Jazz Pharmaceuticals, Inc.
The recommended dose of QUADRAMET® is 1.0 mCi/kg, administered intravenously over a period of one minute through a secure in-dwelling catheter and followed with a saline flush. Dose adjustment in patients at the extremes of weight have not been studied. Caution should be exercised when determining the dose in very thin or very obese patients.
The dose should be measured by a suitable radioactivity calibration system, such as a radioisotope dose calibrator, immediately before administration.
The dose of radioactivity to be administered and the patient should be verified before administering QUADRAMET®. Patients should not be released until their radioactivity levels and exposure rates comply with federal and local regulations.
The patient should ingest (or receive by i.v. administration) a minimum of 500 mL (2 cups) of fluids prior to injection and should void as often as possible after injection to minimize radiation exposure to the bladder.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The solution should not be used if it is cloudy or if it contains particulate matter.
QUADRAMET® contains calcium and may be incompatible with solutions that contain molecules that can complex with and form calcium precipitates.
QUADRAMET® should not be diluted or mixed with other solutions.
Thaw at room temperature before administration and use within 8 hours of thawing.
Radiation DosimetryThe estimated absorbed radiation doses to an average 70 kg adult patient from an i.v. injection of QUADRAMET® are shown in Table 7. The dosimetry estimates were based on clinical biodistribution studies using methods developed for radiation dose calculations by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine.
Radiation exposure is based on a urinary voiding interval of 4.8 hours. Radiation dose estimates for bone and marrow assume that radioactivity is deposited on bone surfaces, as noted in autoradiograms of biopsy bone samples in 7 patients who received QUADRAMET®. Although electron emissions from 153Sm are abundant, with energies up to 810 keV, rapid blood clearance of QUADRAMET® and low energy and abundant photon emissions generally result in low radiation doses to those parts of the body where the complex does not localize.
When blastic osseous lesions are present, significantly enhanced localization of the radiopharmaceutical will occur, with correspondingly higher doses to the lesions compared with normal bones and other organs. (See Clinical Pharmacology, Skeletal Uptake and Pharmacodynamics Sections).
TABLE 7 RADIATION ABSORBED DOSES70 kg ADULT
Target Organ
Rad/mCi
mGy/MBq
Bone Surfaces
25.0
6.76
Red Marrow
5.70
1.54
Urinary Bladder Wall
3.60
0.097
Kidneys
0.065
0.018
Whole Body
0.040
0.011
Lower large intestine
0.037
0.010
Ovaries
0.032
0.0086
Muscle
0.028
0.0076
Small Intestine
0.023
0.0062
Upper Large Intestine
0.020
0.0054
Testes
0.020
0.0054
Liver
0.019
0.0051
Spleen
0.018
0.0049
Stomach
0.015
0.0041
-
Lantheus Medical Imaging, Inc.
Quadramet | Lantheus Medical Imaging, Inc.
The recommended dose of QUADRAMET® is 1.0 mCi/kg, administered intravenously over a period of one minute through a secure in-dwelling catheter and followed with a saline flush. Dose adjustment in patients at the extremes of weight have not been studied. Caution should be exercised when determining the dose in very thin or very obese patients.
The dose should be measured by a suitable radioactivity calibration system, such as a radioisotope dose calibrator, immediately before administration.
The dose of radioactivity to be administered and the patient should be verified before administering QUADRAMET®. Patients should not be released until their radioactivity levels and exposure rates comply with federal and local regulations.
The patient should ingest (or receive by i.v. administration) a minimum of 500 mL (2 cups) of fluids prior to injection and should void as often as possible after injection to minimize radiation exposure to the bladder.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The solution should not be used if it is cloudy or if it contains particulate matter.
QUADRAMET® contains calcium and may be incompatible with solutions that contain molecules that can complex with and form calcium precipitates.
QUADRAMET® should not be diluted or mixed with other solutions.
Thaw at room temperature before administration and use within 8 hours of thawing.
Radiation DosimetryThe estimated absorbed radiation doses to an average 70 kg adult patient from an i.v. injection of QUADRAMET® are shown in Table 7. The dosimetry estimates were based on clinical biodistribution studies using methods developed for radiation dose calculations by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine.
Radiation exposure is based on a urinary voiding interval of 4.8 hours. Radiation dose estimates for bone and marrow assume that radioactivity is deposited on bone surfaces, as noted in autoradiograms of biopsy bone samples in 7 patients who received QUADRAMET®. Although electron emissions from 153Sm are abundant, with energies up to 810 keV, rapid blood clearance of QUADRAMET® and low energy and abundant photon emissions generally result in low radiation doses to those parts of the body where the complex does not localize.
When blastic osseous lesions are present, significantly enhanced localization of the radiopharmaceutical will occur, with correspondingly higher doses to the lesions compared with normal bones and other organs. (See Clinical Pharmacology, Skeletal Uptake and Pharmacodynamics Sections).
TABLE 7 RADIATION ABSORBED DOSES70 kg ADULT
Target Organ
Rad/mCi
mGy/MBq
Bone Surfaces
25.0
6.76
Red Marrow
5.70
1.54
Urinary Bladder Wall
3.60
0.097
Kidneys
0.065
0.018
Whole Body
0.040
0.011
Lower large intestine
0.037
0.010
Ovaries
0.032
0.0086
Muscle
0.028
0.0076
Small Intestine
0.023
0.0062
Upper Large Intestine
0.020
0.0054
Testes
0.020
0.0054
Liver
0.019
0.0051
Spleen
0.018
0.0049
Stomach
0.015
0.0041
![Quadramet (Samarium Sm 153 Lexidronam) Injection, Solution [Lantheus Medical Imaging, Inc.]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=61e84808-0999-4923-910c-2a480d5f971a&name=quadramet-02.jpg)
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