ADVERSE REACTIONS
The safety of Vantas was evaluated in 171 patients with prostate cancer treated for up to 36 months in two clinical trials . The pivotal study (study 301) consisted of 138 patients, while a separate supportive study (study 302) consisted of 33 patients.
Vantas, like other LH-RH analogs, caused a transient increase in serum testosterone concentrations during the first week 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 first 12 months after initial insertion of the implant(s), an implant extruded through the incision site in eight of 171 patients in the clinical trials (see Insertion and Removal Procedures for correct implant placement) .
In the pivotal study (Study 301) a detailed evaluation for implant site reactions was conducted. Out of the 138 patients in the study, 19 patients (13.8%) experienced local or insertion site reactions . All these local site reactions were reported as mild in severity. The majority were associated with initial insertion or removal and insertion of a new implant, and began and resolved within the first two weeks following implant insertion. Reactions persisted in 4 (2.8%) patients. An additional 4 (2.8%) patients developed application-site reactions after the first two weeks following insertion .
Local reactions after implant insertion included bruising (7.2% of patients) and pain/soreness/tenderness (3.6% of patients). Other, less frequently reported, reactions included erythema (2.8% of patients) and swelling (0.7% of patients). In this study, two patients had events described as local infections/inflammations, one that resolved after treatment with oral antibiotics and the other without treatment.
Local reactions following insertion of a subsequent implant were comparable to those seen after initial insertion .
The following possibly or probably related systemic adverse events occurred during clinical trials of up to 24 months of treatment with Vantas, 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 Vantas for up to 24 Months | Body System | Adverse Event | Number (%) |
|---|
| Vascular Disorders | Hot flashesExpected pharmacological consequences of testosterone suppression. | 112 (65.5%) |
| | | |
| General Disorders | Fatigue
Weight increased | 17 (9.9%)
4 (2.3%) |
| Skin and Appendage Disorders | Implant site reaction | 10 (5.8%) |
| Reproductive System and Breast Disorders | Erectile dysfunction
Gynecomastia
Testicular atrophy | 6 (3.5%)
7 (4.1%)
9 (5.3%) |
| Psychiatric Disorders | Insomnia
Libido decreased | 5 (2.9%)
4 (2.3%) |
| Renal and Urinary Disorders | Renal impairment5 of the 8 patients had a single occurrence of mild renal impairment (defined as creatinine clearance ≥ 30 < 60 mL/min), which returned to a normal range by the next visit. | 8 (4.7%) |
| Gastrointestinal Disorders | Constipation | 6 (3.5%) |
| Nervous System Disorders | Headache | 5 (2.9%) |
Hot flashes were the most common adverse event reported (65.5 % of patients). In terms of severity, 2.3% of patients reported severe hot flashes, 25.4 % of patients reported moderate hot flashes and 37.7% reported mild hot flashes. In addition, the following possibly or probably related systemic adverse events were reported by <2% of patients using Vantas in clinical studies.
Blood and Lymphatic System Disorders: Anemia
Cardiac Disorders: Palpitations, ventricular extrasystoles
Gastrointestinal Disorders: Abdominal discomfort, nausea
General Disorders: Feeling cold, lethargy, malaise, edema peripheral, pain, pain exacerbated, weakness, weight decreased
Hepatobiliary Disorders: Hepatic disorder
Injury, Poisoning and Procedural Complications: Stent occlusion
Laboratory Investigations: Aspartate aminotransferase increased, blood glucose increased, blood lactate dehydrogenase increased, blood testosterone increased, creatinine clearance decreased, prostatic acid phosphatase increased
Metabolism and Nutrition Disorders: Appetite increased, fluid retention, food craving, hypercalcemia, hypercholesterolemia
Musculoskeletal and Connective Tissue Disorders: Arthralgia, back pain, back pain aggravated, bone pain, muscle twitching, myalgia, neck pain, pain in limb
Nervous System Disorders: Dizziness, tremor
Psychiatric Disorders: Depression, irritability
Renal and Urinary Disorders: Calculus renal, dysuria, hematuria aggravated, renal failure aggravated, urinary frequency, urinary frequency aggravated, urinary retention
Reproductive System and Breast Disorders: Breast pain, breast tenderness, genital pruritus male, gynecomastia aggravated, sexual dysfunction
Respiratory, Thoracic and Mediastinal Disorders: Dyspnea exertional
Skin and Subcutaneous Tissue Disorders: Contusion, hypotrichosis, night sweats, pruritus, sweating increased
Vascular Disorders: Flushing, hematoma
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. It can be anticipated that long periods of medical castration in men will have effects on bone density.
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