Sexual & reproductive GnRH agonist
Nafarelin
Regulatory status
Status at a glance
503A compounding status
Not nominated
We found no pending nomination for the 503A bulks list. Unless the substance has another legal pathway (for example, a USP monograph or use in an FDA-approved drug), 503A pharmacies generally may not compound with it.
- Also known as
- Synarel
- FDA approval
- An FDA-approved product contains this peptide
- 503B outsourcing
- Not determined
- Anti-doping (WADA)
- Not on the WADA Prohibited List
- DEA schedule
- Not a controlled substance
About peptide status
Most peptides discussed here are not FDA-approved for any use, and products labeled “research use only” are not for human use. Removal from Category 2 does not authorize compounding. PCAC votes are non-binding recommendations; FDA and HHS make the final decisions.
This is not medical or legal advice, and we do not publish dosing, sourcing or reconstitution information. Talk with a licensed clinician before using any peptide.
If you think you are having a medical emergency, call 911.
Key takeaway
Nafarelin (nafarelin acetate, sold as Synarel) is a synthetic decapeptide agonist of gonadotropin-releasing hormone given as a nasal spray that suppresses the pituitary and the sex hormones it controls. It is used for endometriosis and central precocious puberty, and in a multicenter trial it reduced endometriosis lesions about as well as the older drug danazol with a different side-effect profile. It has been FDA-approved in the U.S. since 1990 and is unusual in its class for being delivered intranasally.
At a glance
- What it is
- A GnRH (LHRH) receptor agonist peptide given as a nasal spray
- Approved for
- Endometriosis and central precocious puberty
- Key fact
- In a multicenter trial, intranasal nafarelin reduced laparoscopic disease scores comparably to danazol, without danazol's adverse lipid changes
- Route
- Intranasal spray, used twice daily (more often for precocious puberty)
- Evidence strength
- FDA approved
Summary
Nafarelin is an FDA-approved GnRH agonist nasal spray for endometriosis and central precocious puberty. See how it works and what trials show.
What is nafarelin?
Nafarelin, known generically as nafarelin acetate and sold under the brand Synarel, is a synthetic ten-amino-acid analog of gonadotropin-releasing hormone (GnRH, also called LHRH). It is distinctive in its class for being absorbed through the lining of the nose rather than injected, which makes it convenient but means absorption can be reduced by nasal congestion or decongestant sprays. It was developed under the code RS-94991 and approved in the United States in 1990.
How does nafarelin work?
Nafarelin binds the GnRH receptor on the pituitary. Repeated dosing first stimulates the gland, then, through continuous rather than pulsatile exposure, downregulates and desensitizes the receptors so that luteinizing hormone and follicle-stimulating hormone output falls. In women this lowers ovarian estrogen to produce a reversible, menopause-like low-estrogen state.
That hypoestrogenic state is what treats endometriosis: estrogen-dependent lesions regress and the associated pain eases while treatment continues. In central precocious puberty, higher divided daily dosing suppresses the premature hormone signal and halts early sexual development. In a multicenter double-blind trial, intranasal nafarelin reduced laparoscopic endometriosis scores about as effectively as oral danazol, with most patients improving, while avoiding danazol's unfavorable effects on blood lipids. Because the low-estrogen state causes bone loss, treatment for endometriosis is generally limited to about six months.
Is it FDA-approved?
Editor’s note
Status: Yes. Nafarelin was approved by the FDA in 1990 for endometriosis, with central precocious puberty added shortly afterward. It is marketed as a metered nasal spray delivering 200 micrograms per spray.
Category: FDA-approved · Primary body area: Sexual & reproductive
Yes. Nafarelin was approved by the FDA in 1990 for endometriosis, with central precocious puberty added shortly afterward. It is marketed as a metered nasal spray delivering 200 micrograms per spray.
What is nafarelin prescribed for?
Nafarelin is prescribed for the management of endometriosis, including pain relief and reduction of lesions, and for central precocious puberty in children. It is contraindicated in pregnancy, and patients are usually advised to avoid nasal decongestants around dosing because they can lower absorption.
What are the side effects?
According to the prescribing information, common side effects reflect low estrogen and the nasal route:
- Hot flashes and sweating
- Vaginal dryness and decreased libido
- Headache
- Nasal irritation or rhinitis
- Acne and emotional lability
More serious considerations include:
- Bone-density loss, which limits the duration of endometriosis treatment
- Fetal exposure risk, so it must not be used in pregnancy
- Mood and behavior changes such as irritability, crying, and depression
- Convulsions
- Raised pressure around the brain (pseudotumor cerebri) in children
Sources: FDA prescribing information for Synarel; the nafarelin-versus-danazol endometriosis trial (Henzl et al., New England Journal of Medicine, 1988, DOI: 10.1056/NEJM198802253180805), indexed on PubMed. This document is educational and does not constitute medical advice.
Registered human trials
0 registered human trials on ClinicalTrials.gov that we reviewed
Sources
- [1]
- [2]
- [3]
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