Nafarelin is not available for use by any other routes than intranasal administration. Side effects
Side effects of nafarelin are related to sex hormone deficiency and include hot flashes, vaginal dryness, headaches, mood changes, and sexual dysfunction. Nafarelin causes erectile dysfunction in more than half of men with benign prostatic hyperplasia treated with it. Some people may experience acne, muscle pain, reduced breast size, and nasal irritation. These side effects are reversible and should resolve after stopping the medication. There is a case report of severe hyperkalemia during nafarelin therapy in a woman with uterine fibroids. The mechanism is unknown. Pharmacology
Pharmacodynamics
Nafarelin is a GnRH agonist, or an agonist of the GnRH receptor, the biological target of GnRH. It works by continuously activating the GnRH receptor, which results in profound desensitization of the receptor such that it becomes non-functional. As a result, nafarelin suppresses the GnRH-induced secretion of the gonadotropins, luteinizing hormone and follicle-stimulating hormone, from the pituitary gland. This, in turn, results in profound suppression of gonadal sex hormone production, as well as reversible suppression of fertility. Pharmacokinetics
The bioavailability of nafarelin with intranasal administration is 2.8% on average, with a range of 1.2 to 5.6%. The plasma protein binding of nafarelin is 80%. It is metabolized primarily by peptidases and not by cytochrome P450 enzymes. The elimination half-life of nafarelin is 2.5 to 3.0 hours by intranasal administration, whereas the half-life of nafarelin and its metabolites by subcutaneous injection is 85.5 hours. Nafarelin is eliminated 44 to 55% in urine and 18.5 to 44.2% in feces.
Craniomandibular osteopathy, also known as lions jaw, is a developmental disease in dogs causing extensive bony changes in the mandible and skull. In this disease, a cyclical resorption of normal bone and replacement by immature bone occurs along the inner and outer surfaces of the affected bones. It usually occurs between the ages of 3 and 8 months. Breeds most commonly affected include the West Highland White Terrier, Scottish Terrier, Cairn Terrier, and Boston Terrier. It is rare in large-breed dogs, but it has been reported. Symptoms include firm swelling of the jaw, drooling, pain, and difficulty eating. It is an inherited disease, especially in Westies, in which it has been recognized as an autosomal recessive trait. Canine distemper has also been indicated as a possible cause, as has E. coli infection, which could be why it is seen occasionally in large-breed dogs. Growth of lesions will usually stop around the age of one year, and possibly regress. This timing coincides with the normal completion of endochondral bone growth and ossification. If the disease is extensive, especially around the tympanic bulla (middle ear), then the prognosis is guarded. A similar disease seen in young Bullmastiffs is known as calvarial hyperostotic syndrome. It is also similar to human infantile cortical hyperostosis. It is characterized by irregular, progressive bony proliferation and thickening of the cortical bone of the calvaria, which is part of the skull. Asymmetry of the lesions may occur, which makes it different from craniomandibular osteopathy.