"The U.S. Food and Drug Administration today approved Xofigo (radium Ra 223 dichloride) to treat men with symptomatic late-stage (metastatic) castration-resistant prostate cancer that has spread to bones but not to other organs. It is intended for"...
The safety of Viadur® (leuprolide acetate implant) was evaluated in 131 patients with prostate cancer treated for up to 24 months in two clinical trials. Viadur® (leuprolide acetate implant) , like other LHRH analogs, caused a transient increase in serum testosterone concentrations during the first 2 weeks of treatment.
Therefore, potential exacerbations of signs and symptoms of the disease during the first few weeks of treatment are of concern in patients with vertebral metastases and/or urinary obstruction or hematuria. If these conditions are aggravated, it may lead to neurological problems such as weakness and/or paresthesia of the lower limbs or worsening of urinary symptoms (see WARNINGS AND PRECAUTIONS).
In the above-described clinical trials, the transient increase in serum testosterone concentrations was associated with an exacerbation of disease symptoms, manifested by pain or bladder outlet obstructive symptoms (urinary retention or frequency) in 6 (4.6%) patients.
The majority of local reactions associated with initial insertion or removal and insertion of a new implant began and resolved within the first two weeks. Reactions persisted in 9.3% of patients. 10.3% of patients developed application-site reactions after the first two weeks following insertion.
Local reactions after initial insertion of a single implant included bruising (34.6%) and burning (5.6%). Other, less frequently reported, reactions included pulling, pressure, itching, erythema, pain, edema, and bleeding.
In these two clinical trials, four patients had local infection/inflammations that resolved after treatment with oral antibiotics.
Local reactions following insertion of a subsequent implant were comparable to those seen after initial insertion.
In the first 12 months after initial insertion of the implant(s), an implant extruded through the incision site in three of 131 patients (see Insertion And Removal Procedures for correct implant placement under DOSAGE AND ADMINISTRATION).
The following possibly or probably related systemic adverse events occurred during clinical trials within 24 months of treatment with Viadur® (leuprolide acetate implant) , and were reported in ≥ 2% of patients (Table 1).
Table 1 : Incidence (%) of Possibly or Probably Related Systemic
Adverse Events Reported by ≥ 2% of Patients Treated with Viadur® (leuprolide acetate implant) for
up to 24 Months
|Body System||Adverse Event||Number (%)|
|Body as a Whole||Asthenia||10 (7.6%)|
|Extremity pain||4 (3.1%)|
|Cardiovascular||Vasodilatation (hot flashes)*||89 (67.9%)|
|Hematology and Lymphatic||Ecchymosis||6 (4.6%)|
|Metabolic and Nutritional||Peripheral edema||4 (3.1%)|
|Weight gain||3 (2.3%)|
|Urogenital||Gynecomastia/breast enlargement*||9 (6.9%)|
|Urinary frequency||5 (3.8%)|
|Testis atrophy or pain*||5 (3.8%)|
|Breast pain*||4 (3.1%)|
|* Expected pharmacologic consequences of testosterone suppression.|
In addition, the following possibly or probably related systemic adverse events were reported by < 2% of patients using Viadur® (leuprolide acetate implant) in clinical studies.
Gastrointestinal: Constipation, nausea
Hematologic: Iron deficiency anemia
Metabolic: Edema, weight loss Musculoskeletal: Bone pain, arthritis
Changes in Bone Density
Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with an LH-RH agonist analog. In a clinical trial, 25 men with prostate cancer, 12 of whom had been treated previously with leuprolide acetate for at least 6 months, underwent bone density studies as a result of pain. The leuprolide-treated group had lower bone density scores than the nontreated control group. It can be anticipated that long periods of medical castration in men will have effects on bone density.
During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was diagnosed with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required.
Ninety-seven of the 131 patients in the two-year duration studies that supported approval of Viadur® (leuprolide acetate implant) continued in an open-label, third-year extension study. One patient prematurely withdrew due to lack of efficacy that was attributed to a defective implant. Fifty of these patients continued in an open-label, fourth-year extension study. No spontaneous implant extrusions were reported in these extension studies. Since Viadur® (leuprolide acetate implant) has been commercially available, < 1% of patients implanted have been reported to have a spontaneous implant extrusion (with or without associated infection).
Additional adverse events have been reported from US post-marketing experience with Viadur® (leuprolide acetate implant) . Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been reported infrequently and include fatigue, hypertension, migration of implant, syncope, tremor, and vomiting.
Read the Viadur (leuprolide acetate implant) Side Effects Center for a complete guide to possible side effects
Drug/Laboratory Test Interactions
Therapy with leuprolide results in suppression of the pituitary-gonadal system. Results of diagnostic tests of pituitary gonadotropic and gonadal functions conducted during and after leuprolide therapy may be affected.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 3/8/2011
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