WARNINGS
Vantas, like other LH-RH agonists, causes a transient increase in serum concentrations of testosterone during the first week of treatment. Patients may experience worsening of symptoms or onset of new symptoms, including bone pain, neuropathy, hematuria, or ureteral or bladder outlet obstruction (see PRECAUTIONS). Cases of ureteral obstruction and spinal cord compression, which may contribute to paralysis with or without fatal complications, have been reported with LH-RH agonists. If spinal cord compression or renal impairment develops, standard treatment of these complications should be instituted .
PRECAUTIONS
General
Patients with metastatic vertebral lesions and/or with urinary tract obstruction should be closely observed during the first few weeks of therapy (see WARNINGS) .
Implant insertion is a surgical procedure. Careful adherence to the recommended Insertion and Removal Procedures (see DOSAGE & ADMINISTRATION) is advised to minimize the potential for complications and for implant expulsion. In addition, patients should be instructed to refrain from wetting the arm for 24 hours and from heavy lifting or strenuous exertion of the inserted arm for 7 days after implant insertion.
In all clinical trials combined, an implant was not recovered in 8 patients. For two of these (see CLINICAL PHARMACOLOGY; Clinical Studies), serum testosterone rose above castrate level and the implant was neither palpable nor visualized with ultrasound. These two implants were believed to have been extruded without appreciation by the patients. In the other six, serum testosterone remained below the castrate level, but the implant was not palpable. No further diagnostic tests were conducted. One of these patients underwent in-clinic surgical exploration that did not locate the implant. Based upon these findings, it is important to know that Vantas is not radio-opaque and therefore will not be visible through X-ray. However, in the instance where the implant is difficult to locate by palpation, ultrasound and CT scan may be used.
Information for Patients
An information leaflet for patients is included with the product and should be given to the patient.
Laboratory tests
Response to Vantas should be monitored by measuring serum concentrations of testosterone and prostate-specific antigen periodically, especially if the anticipated clinical or biochemical response to treatment has not been achieved.
Results of testosterone determinations are dependent on assay methodology. It is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions.
Drug Interactions
See PHARMACOKINETICS.
Drug/Laboratory Test Interactions
Therapy with histrelin results in suppression of the pituitary-gonadal system. Results of diagnostic tests of pituitary gonadotropic and gonadal functions conducted during and after histrelin therapy may be affected.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies were conducted in rats for 2 years at doses of 5, 25 or 150 mcg/kg/day (up to 15 times the human dose) and in mice for 18 months at doses of 20, 200, or 2000 mcg/kg/day (up to 200 times the human dose). As seen with other LH-RH agonists, histrelin acetate injection administration was associated with an increase in tumors of hormonally responsive tissues. There was a significant increase in pituitary adenomas in rats. There was an increase in pancreatic islet-cell adenomas in treated female rats and a non-dose-related increase in testicular Leydig-cell tumors (highest incidence in the low-dose group). In mice, there was significant increase in mammary-gland adenocarcinomas in all treated females. In addition, there were increases in stomach papillomas in male rats given high doses, and an increase in histiocytic sarcomas in female mice at the highest dose.
Mutagenicity studies have not been performed with histrelin acetate. Saline extracts of implants with and without histrelin were negative in a battery of genotoxicity studies. Fertility studies have been conducted in rats and monkeys given subcutaneous daily doses of histrelin acetate up to 180 mcg/kg for 6 months and full reversibility of fertility suppression was demonstrated. The development and reproductive performance of offspring from parents treated with histrelin acetate has not been investigated.
Pregnancy
Teratogenic Effects
Pregnancy Category X
(see CONTRAINDICATIONS).
Major fetal abnormalities were observed in rabbits but not in rats after administration of histrelin acetate throughout gestation. There were increased fetal mortality and decreased fetal weights in rats and rabbits. The effects on fetal mortality are expected consequences of the alterations in hormonal levels brought about by this drug. The possibility exists that spontaneous abortion may occur .
Pediatric Use
Vantas is contraindicated in pediatric patients and was not studied in children
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