Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Pfizer Limited, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK
ATC code: H01CA02
Nafarelin is a potent agonistic analogue of gonadotrophin releasing hormone (GnRH). Given as a single dose, nafarelin stimulates release of the pituitary gonadotrophins, LH and FSH, with consequent increase of ovarian and testicular steroidogenesis. During repeated dosing this response to stimulation gradually diminishes. Within three to four weeks, daily administration leads to decreased pituitary gonadotrophin secretion and/or the secretion of gonadotrophin secretion and/or the secretion of gonadotrophins with lowered biological activity. There is a consequent suppression of gonadal steroidogenesis and inhibition of functions in tissues that depend on gonadal steroids for their maintenance.
Nafarelin is rapidly absorbed into the circulation after intranasal administration. Maximum plasma concentration is achieved 20 minutes after dosing and the plasma half-life is approximately 4 hours. Bioavailability of the intranasal dose averages 2.8% (range 1.2-5.6%).
As seen with other GnRH agonists, nafarelin given parenterally in high doses to laboratory rodents for prolonged periods induced hyperplasia and neoplasia of endocrine organs, including the anterior pituitary (adenoma/carcinoma) of both mice and rats; tumours of the pancreatic islets, adrenal medulla, testes and ovaries occurred only in long-term studies in rats. No metastases of these tumours were observed. Monkeys treated with high doses of nafarelin for one year did not develop any tumours or proliferative changes. Experience in humans is limited but there is no evidence for tumorigenesis of GnRH analogues in human beings.
In vitro studies conducted in bacterial and mammalian systems provided no indication of a mutagenic potential for nafarelin.
Reproduction studies in rats of both sexes have shown full reversibility of fertility suppression when drug treatment was discontinued after continuous administration for up to six months.
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