VANTAS SIDE EFFECTS

SIDE EFFECTS

Adverse Reactions In Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

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 1) consisted of 138 patients, while a separate supportive study (Study 2) consisted of 33 patients.

VANTAS, like other GnRH 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.

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.

In the pivotal study (Study 1) 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

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, hypercalcaemia, 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 a GnRH agonist analog. It can be anticipated that long periods of medical castration in men will have effects on bone density.

Post-Marketing

The following adverse reactions have been identified during post approval use of VANTAS. Because these reactions 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.

Pituitary Apoplexy

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 final dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, opthalmoplegia, altered mental status, and sometimes cardiovascular collapse.

Immediate medical attention has been required.

Drug-Induced Liver Injury

Severe liver injury has been reported in association with VANTAS. The toxicity was reversible with the removal of the VANTAS implant.

Nervous System Disorders

Convulsions

SRC: NLM .