openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 2 matching rows.
warnings
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 MARROW TOXICITY IN CLINICAL TRIALS OF QUADRAMET ® 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 3 µL, 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. 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 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 ® .
ADVERSE EVENTS Adverse events were evaluated in a total of 580 patients who received QUADRAMET ® in clinical trials. Of the 580 patients, there were 472 men and 108 women with a mean age of 66 (range 20 to 87). Of these patients, 472 (81%) had at least one adverse event. In a subgroup of 399 patients who received QUADRAMET ® 1.0 mCi/kg, there were 23 deaths and 46 serious adverse events. The deaths occurred an average of 67 days (9 to 130) after QUADRAMET ® . Serious events occurred an average of 46 days (1 - 118) after QUADRAMET ® . Although most of the patient deaths and serious adverse events appear to be related to the underlying disease, the relationship of end stage disease, marrow invasion by cancer cells, previous myelotoxic treatment and QUADRAMET ® toxicity can not be easily distinguished. In clinical studies, two patients with rapidly progressive prostate cancer developed thrombocytopenia and died 4 weeks after receiving QUADRAMET ® . One of the patients showed evidence of disseminated intravascular coagulation (DIC); the other patient experienced a fatal cerebrovascular accident, with a suspicion of DIC. The relationship of the DIC to the bone marrow suppressive effect of Samarium is not known. Marrow toxicity occurred in 277 (48%) patients (See Warnings section). In controlled studies, 7% of patients receiving 1.0 mCi/kg QUADRAMET ® (as compared to 6% of patients receiving placebo) reported a transient increase in bone pain shortly after injection (flare reaction). This was usually mild, self-limiting, and responded to analgesics. The most common adverse events observed in controlled clinical studies of QUADRAMET ® , are given in Table 6. TABLE 6 SELECTED ADVERSE EVENTS REPORTED IN ≥ 1.0 % OF PEOPLE WHO RECEIVED QUADRAMET ® OR PLACEBO IN CONTROLLED CLINICAL TRIALS ADVERSE EVENT Placebo N = 90 QUADRAMET ® 1.0 mCi/kg N = 199 # Patients with Any Adverse Event 72 (80%) 169 (85%) Body As A Whole 56 (62%) 100 (50%) Pain Flare Reaction 5 (5.6%) 14 (7.0%) Cardiovascular 19 (21%) 32 (16%) Arrhythmias 2 (2.2%) 10 (5.0%) Chest Pain 4 (4.4%) 8 (4.0%) Hypertension 0 6 (3.0%) Hypotension 2 (2.2%) 4 (2.0%) Digestive 44 (49%) 82 (41%) Abdominal Pain 7 (7.8%) 12 (6.0%) Diarrhea 3 (3.3%) 12 (6.0%) Nausea &/or Vomiting 37 (41.1%) 65 (32.7%) Hematologic & Lymphatic 12 (13%) 54 (27%) Coagulation Disorder 0 3 (1.5%) Hemoglobin Decreased 21 (23.3%) 81 (40.7%) Leukopenia 6 (6.7%) 118(59.3%) Lymphadenopathy 0 4 (2.0%) Thrombocytopenia 8 (8.9%) 138(69.3%) Any Bleeding Manifestations* 8 (8.9%) 32 (16.1%) Ecchymosis 1 (1.1%) 3 (3.0%) Epistaxis 1 (1.1%) 4 (2.0%) Hematuria 3 (3.3%) 10 (5%) Infection 10 (11.1%) 34 (17.1%) Fever and/or Chills 10 (11.1%) 17 (8.5%) Infection, Not Specified 4 (4.4%) 14 (7.0%) Oral Moniliasis 1 (1.1%) 4 (2.0%) Pneumonia 1 (1.1%) 3 (1.5%) Musculoskeletal 28 (31%) 55 (27%) Myasthenia 8 (8.9%) 13 (6.5%) Pathologic Fracture 2 (2.2%) 5 (2.5%) Nervous 39 (43%) 59 (30%) Dizziness 1 (1.1%) 8 (4.0%) Paresthesia 7 (7.8%) 4 (2.0%) Spinal Cord Compression 5 (5.5%) 13 (6.5%) Cerebrovascular Accident/Stroke 0 2 (1.0%) Respiratory 24 (27%) 35 (18%) Bronchitis/Cough Increased 2 (2.2%) 8 (4.0%) Special Senses 11 (12%) 11 (6%) Skin & Appendages 17 (19%) 13 (7%) Purpura 0 2 (1%) Rash 2 (2.2%) 2 (1%) • *Includes hemorrhage (gastrointestinal, ocular) reported in <1%. In an additional 200 patients who received QUADRAMET ® in uncontrolled clinical trials, adverse events that were reported at a rate of ≥ 1.0% were similar except for 9 (4.5%) patients who had agranulocytosis. Other selected adverse events that were reported in <1% of the patients who received QUADRAMET ® 1.0 mCi/kg in any clinical trial include: alopecia, angina, congestive heart failure, sinus bradycardia, and vasodilation.