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Nafarelin (Monograph)

Brand name: Synarel
Drug class: Gonadotropins
ATC class: H01CA02
VA class: HS900
Chemical name: 6-[3-(2-naphthalenyl)-d-alanine]-hydrate acetate (salt) luteinizing hormone-releasing factor (pig)
Molecular formula: C66H83N17O13•xC2H4O2•yH2O
CAS number: 86220-42-0

Medically reviewed by on Oct 6, 2023. Written by ASHP.


Gonadotropin-releasing hormone (GnRH) agonist; synthetic decapeptide analog of GnRH (luteinizing hormone-releasing hormone, gonadorelin); structurally related to goserelin, leuprolide, and triptorelin.

Uses for Nafarelin


Palliative treatment of endometriosis (e.g., pain relief, reduction in endometrial lesions). Experience limited to women ≥18 years of age treated for 6 consecutive months.

Precocious Puberty

Treatment of central (via activation of the hypothalamic-pituitary-gonadal axis) precocious puberty (true precocious puberty, GnRH-dependent precocious precocity, complete isosexual precocity) in children of both sexes (designated as an orphan drug by FDA for this use).

Nafarelin Dosage and Administration



Intranasal Inhalation

Administer by nasal inhalation using a metered spray pump.

Avoid sneezing during or immediately after administration.

Prior to initial use, prime the nasal inhaler. To prime, hold bottle upright and quickly depress the side arms of pump toward the bottle 7–10 times, until a fine spray occurs.

Clear nasal passages prior to administration.

Tilt the head slightly backward, insert the spray tip into one nostril, and point the tip toward the back of the nose. Rapidly and firmly press and actuate into the nostril while holding the other nostril closed and concurrently inspire through the nose. After removing the spray tip from the nostril, remain with head tilted backward for a few seconds. If additional sprays are indicated for the same nostril, wait 30 seconds before repeating the procedure.

Following administration, rinse spray tip with warm water while wiping tip with finger or soft cloth for 15 seconds; dry spray tip with a soft cloth or tissue.


Available as nafarelin acetate; dosage is expressed in terms of nafarelin.

After priming, the commercially available nasal pump delivers 200 mcg of nafarelin per spray and approximately 60 sprays per 8-mL container.

Missed doses may cause breakthrough bleeding or ovulation, or restart pubertal development. Full efficacy is dependent on dosage compliance for full duration of treatment.

Pediatric Patients

Precocious Puberty

Children: 2 sprays in each nostril (800 mcg total) in the morning and 2 sprays in each nostril in the evening (total daily dosage: 1600 mcg).

If lack of suppression of the pituitary-gonadal axis, may increase dosage to 3 sprays (600 mcg) into alternating nostrils 3 times daily (total daily dosage: 1800 mcg).

Continue therapy until resumption of puberty is desired.



Women ≥18 years of age: 1 spray (200 mcg) in one nostril every morning and 1 spray (200 mcg) in the other nostril every evening (total daily dosage: 400 mcg) for 6 consecutive months.

If regular menstruation persists after 2 months of therapy, may increase dosage to 1 spray in each nostril (400 mcg total) in the morning and 1 spray in each nostril in the evening (total daily dosage: 800 mcg).

Retreatment with additional courses of therapy not recommended currently by manufacturer. (See Retreatment in Endometriosis under Cautions.)

Special Populations

No special population dosage recommendations at this time.

Cautions for Nafarelin




Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; embryotoxicity and fetotoxicity demonstrated in animals. (See Contraindications under Cautions.)

Exclude pregnancy immediately prior to initiation of therapy. Use nonhormonal method of contraception during therapy. If used during pregnancy or if patient becomes pregnant during therapy, discontinue drug and apprise of potential fetal hazard.

Although nafarelin usually inhibits ovulation and stops menstruation, contraception is not ensured, especially if patient misses successive doses.

Patient Monitoring in Central Precocious Puberty

Carefully exclude other causes of sexual precocity (e.g., congenital adrenal hyperplasia, testotoxicosis, testicular tumors, other autonomous feminizing or masculinizing disorder) and establish diagnosis of central precocious puberty before initiating treatment.

Regularly monitor patients, especially during the initial 6–8 weeks of therapy, to ensure compliance and adequate patient response (i.e., rapid suppression of pituitary-gonadal function). (See General under Dosage and Administration and also see Dosage: Precocious Puberty under Dosage and Administration.)

Assess bone age and growth velocity within 3–6 months of initiation of therapy and periodically thereafter.

Sensitivity Reactions

Possible sensitivity reactions (e.g., shortness of breath, chest pain, urticaria, rash, pruritus) reported.

Major Toxicities

Pituitary Apoplexy

Pituitary apoplexy, a clinical syndrome secondary to pituitary gland infarction (e.g., headache, vomiting, visual changes, ophthalmoplegia, altered mental status, possible cardiovascular collapse) reported rarely following GnRH agonist administration. Most cases occurred within 2 weeks of first dose, although they have occurred within the first hour in some patients. Immediate medical attention required.

General Precautions

Endocrine Effects in Endometriosis

Ovarian cysts reported during the first 2 months of therapy in adult women; most cases occurred in patients with polycystic ovarian disease. May resolve spontaneously (usually within 4–6 weeks of therapy); may require discontinuance of the drug and/or surgical intervention. Relevance to females <18 years of age unknown.

Decreases in vertebral trabecular bone mineral density and total vertebral bone mass reported in women; some loss may not be reversible. Concurrent use of hormone replacement therapy or bisphosphonates (e.g., alendronate) may minimize bone mineral loss associated with therapy without compromising efficacy of endometriosis management.

If major risk factors for decreased bone mineral content (e.g., chronic alcohol and/or tobacco use, strong family history of osteoporosis, chronic use of drugs that can reduce bone mass [e.g., anticonvulsants, corticosteroids]), weigh risks and benefits carefully before initiating therapy. (See Retreatment in Endometriosis under Cautions.)

Possible increased risk of diabetes in patients receiving GnRH agonists for treatment of prostate cancer. Studies evaluating risk of diabetes in women and children receiving GnRH agonists not performed to date.

Retreatment in Endometriosis

Safety established only for initial 6-month treatment course; therefore, manufacturer cannot recommend retreatment. (See Endocrine Effects in Endometriosis under Cautions.)

If considering retreatment after initial 6-month course, assess bone density to ensure values are within normal limits before beginning retreatment. Repeated courses not advised in patients with major risk factors for loss of bone mineral content.

Laboratory Abnormalities

May alter serum lipoprotein concentrations; risk of increased triglycerides and total cholesterol.

Hyperphosphatemia and eosinophilia may occur.

Hypocalcemia and leukopenia may occur.

Cardiovascular Effects

Thromboembolic events (e.g., DVT, PE, MI, stroke, TIA) reported. Possible increased risk of cardiovascular disease (e.g., MI, sudden cardiac death, stroke) in patients receiving GnRH agonists for treatment of prostate cancer. Studies evaluating risk of cardiovascular disease in women and children receiving GnRH agonists not performed to date.

Specific Populations


Category X. (See Contraindications and also Fetal/Neonatal Morbidity and Mortality under Cautions.)


Not known whether nafarelin is distributed into milk. Do not use in nursing women. (See Contraindications under Cautions.)

Pediatric Use

Safety and efficacy not established in children <18 years of age for uses other than treatment of central precocious puberty.

Common Adverse Effects

Women with endometriosis: Hot flushes (flashes), decreased libido, vaginal dryness, headache, emotional lability, acne, myalgia, reduction in breast size, nasal irritation.

Children with central precocious puberty: Acne, transient breast enlargement, emotional lability, transient increases in pubic hair, body odor, seborrhea, hot flushes (flashes), rhinitis, vaginal bleeding, white or brown vaginal discharge.

Drug Interactions

No formal drug interaction studies to date.

The manufacturer states drug interactions not expected to occur because nafarelin is a peptide mainly degraded by peptidases and not by CYP microsomal enzymes and because of the drug’s limited protein binding.

Specific Drugs and Laboratory Tests

Drug or Test



Decongestants (topical nasal)

Possible interaction

Delay administration of a topical nasal decongestant ≥2 hours after administration of nafarelin

Tests, diagnostic tests of pituitary gonadotropic and gonadal function

Possible erroneous results when diagnostic tests of pituitary gonadotropic and gonadal function obtained during treatment and up to 4–8 weeks after discontinuance of nafarelin

Normal function usually restored 4–8 weeks after discontinuance of nafarelin

Nafarelin Pharmacokinetics



Rapidly absorbed into systemic circulation following nasal administration.

Bioavailability averages 2.8% (range 1.2–5.6%) in adult women.

Nasal congestion or rhinitis does not appear to affect bioavailability.

Following intranasal administration in children and adult women, maximum serum concentrations occur at 10–45 minutes and 10–40 minutes, respectively.



Not known whether nafarelin is distributed into milk.

Plasma Protein Binding

About 80% at 4°C.


Elimination Route

Excreted in urine (44–55%) and feces (19–44%) mainly as metabolites.


Children: 2.5 hours.

Women: 3 hours.




Nasal Solution

Upright at 25°C (may be exposed to 15–30°C). Protect from light; do not freeze.


Advice to Patients


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Nafarelin Acetate


Dosage Forms


Brand Names




200 mcg (of nafarelin) per metered spray



AHFS DI Essentials™. © Copyright 2024, Selected Revisions October 16, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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