Nafarelin

Nafarelin is delivered as an intranasal spray, typically twice daily for endometriosis; central precocious puberty can require more frequent daily administration.

Nafarelin acetate, developed as RS-94991 and marketed as Synarel, is a synthetic ten-amino-acid GnRH/LHRH analog. It is absorbed through nasal lining rather than injected. Nasal congestion and decongestant sprays can reduce absorption. US approval began in 1990.

Repeated GnRH-receptor exposure first stimulates, then desensitizes and downregulates the pituitary. LH and FSH secretion falls. In women this creates a reversible menopause-like low-estrogen state, reducing estrogen-dependent endometriosis lesions and pain during treatment. Higher divided daily dosing suppresses premature hormonal activation in central precocious puberty.

A multicenter double-blind trial found that nasal nafarelin reduced laparoscopic endometriosis scores about as effectively as oral danazol, with most patients improving and without danazol’s adverse lipid effects. Because low estrogen causes bone loss, an endometriosis course is generally limited to about six months.

FDA approved nafarelin for endometriosis in 1990, with central precocious puberty added afterward. The metered Synarel nasal spray delivers 200 micrograms per spray.

Uses include endometriosis pain management and lesion reduction, and treatment of central precocious puberty in children. Pregnancy is a contraindication. Nasal decongestants are generally avoided around administration because they can lower drug absorption.

Common effects include hot flashes, sweating, vaginal dryness, reduced libido, headache, nasal irritation or rhinitis, acne and emotional lability. Important risks include bone-density loss, fetal exposure in pregnancy, irritability, crying or depression, and convulsions. Pediatric labeling also warns about pseudotumor cerebri, or raised pressure around the brain.