Version May 2024
Endometriosis: Intranasal: One spray (200 mcg) into 1 nostril each morning and 1 spray (200 mcg) into the other nostril each evening starting between days 2 and 4 of menstrual cycle (total: 2 sprays [400 mcg] daily). If regular menstruation persists after 2 months of therapy, may increase dose to 2 sprays (400 mcg; 1 spray in each nostril) in the morning and evening (total: 4 sprays [800 mcg] daily). Total duration of therapy should not exceed 6 months due to decreases in bone mineral density; retreatment is not recommended by the manufacturer.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
Central precocious puberty: Intranasal: Males/Females: (US labeling): Two sprays (400 mcg) into each nostril in the morning and 2 sprays (400 mcg) into each nostril in the evening (total: 8 sprays [1,600 mcg] daily). If inadequate suppression, may increase dose to 3 sprays (600 mcg) into alternating nostrils 3 times daily (total: 9 sprays [1,800 mcg] daily). Continue therapy until resumption of puberty is desired.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Central precocious puberty:
Reported adverse reactions are for children and adolescents.
1% to 10%:
Dermatologic: Acne vulgaris (10%), body odor (4%), hypertrichosis (transient, pubic region: 5%), seborrhea (3%)
Endocrine & metabolic: Hot flashes (3%; transient)
Genitourinary: Breast hypertrophy (8%; transient), vaginal discharge (3%), vaginal hemorrhage (8%)
Hypersensitivity: Hypersensitivity reaction (3%)
Nervous system: Emotional lability (6%)
Respiratory: Rhinitis (5%)
Endometriosis:
Reported adverse reactions are for adults.
>10%:
Dermatologic: Acne vulgaris (14%)
Endocrine & metabolic: Decreased libido (23%), decreased serum calcium (10% to 15%), hot flash (90%), increased serum phosphate (10% to 15%), increased serum triglycerides (12%)
Genitourinary: Vaginal dryness (19%)
Hematologic & oncologic: Decreased white blood cell count (10% to 15%), eosinophilia (10% to 15%)
Nervous system: Emotional lability (16%), headache (18%)
1% to 10%:
Cardiovascular: Edema (8%)
Dermatologic: Seborrhea (8%)
Endocrine & metabolic: Hirsutism (3%), increased libido (2%), increased serum cholesterol (6%), weight gain (8%), weight loss (2%)
Genitourinary: Breast atrophy (10%)
Nervous system: Depression (3%), insomnia (9%)
Neuromuscular & skeletal: Myalgia (10%)
Respiratory: Nasal mucosa irritation (10%)
<1%:
Cardiovascular: Palpitations
Dermatologic: Chloasma, maculopapular rash
Genitourinary: Breast engorgement, lactation
Hepatic: Increased serum alanine aminotransferase, increased serum aspartate aminotransferase
Hypersensitivity: Hypersensitivity reaction
Nervous system: Asthenia, paresthesia
Neuromuscular & skeletal: Arthralgia
Ophthalmic: Eye pain
Frequency not defined: Neuromuscular & skeletal: Decreased bone mineral density
Postmarketing (any indication):
Cardiovascular: Acute myocardial infarction, arterial thromboembolism, venous thromboembolism (including deep vein thrombosis and pulmonary embolism)
Genitourinary: Ovarian cyst
Hepatic: Hepatic injury
Nervous system: Cerebrovascular accident, intracranial hypertension (idiopathic), seizure, suicidal ideation, suicidal tendencies, transient ischemic attacks
Hypersensitivity to gonadotropin-releasing hormone (GnRH), GnRH-agonist analogs, or any component of the formulation; undiagnosed abnormal vaginal bleeding; pregnant patients or those who may become pregnant; breastfeeding.
Concerns related to adverse effects:
• Decreased bone density: Has been reported and may be irreversible. Use with caution in patients with risk factors for bone loss (eg, chronic alcohol use, antiseizure or corticosteroid therapy, family history of osteoporosis). Repeat courses are not recommended in patients with major risk factors for bone loss.
• Ovarian cysts: May occur within the first 2 months of therapy and may occur more commonly in patients with polycystic ovarian disease. These cysts may resolve spontaneously, generally by about 4 to 6 weeks of therapy, but sometimes require discontinuation of therapy and/or surgical intervention.
• Pituitary apoplexy: Rare cases of pituitary apoplexy (frequently secondary to pituitary adenoma) have been observed with GnRH agonist administration (onset from 1 hour to usually <2 weeks); may present as sudden headache, vomiting, visual or mental status changes, and infrequently cardiovascular collapse; immediate medical attention may be required.
• Pseudotumor cerebri: Pseudotumor cerebri (idiopathic intracranial hypertension) has been reported in pediatric patients receiving GnRH agonists, including nafarelin.
• Psychiatric events: Emotional lability, such as crying, irritability, impatience, anger, and aggression, has been reported in patients taking GnRH agonists. Depression, including rare reports of suicidal ideation and attempt, has been reported for GnRH agonists in children treated for CPP; many of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression. Depression may also occur or worsen in patients being treated for endometriosis. Monitor for development or worsening of psychiatric symptoms, including depression, during treatment; consider referral to a mental health professional in patients with new or worsening depression.
• Seizures: Have been observed in patients receiving GnRH agonists; patients with a history of seizures, cerebrovascular disorders, CNS anomalies/tumors, and patients on concomitant medications that have been associated with seizures are at increased risk; has also been reported in patients without risk factors.
Disease-related concerns:
• CPP use: When used for the treatment of CPP, some signs of puberty (eg vaginal bleeding, breast enlargement) may occur but should resolve within the first 2 months of therapy.
Synarel 8 mL bottles contain at least 60 sprays.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Nasal:
Synarel: 2 mg/mL (8 mL)
No
Solution (Synarel Nasal)
2 mg/mL (per mL): $453.65
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Nasal:
Synarel: 2 mg/mL (8 mL) [contains benzalkonium chloride]
Intranasal: Nasal spray: Prior to initial use, prime pump by releasing 7 to 10 sprays until a fine spray is released. After priming, hold the bottle horizontal and run spray tip under warm water for 15 seconds while wiping with finger or soft cloth; dry tip with tissue or soft cloth. Repeat this cleaning procedure before and after each use to prevent tip from clogging; do not clean spray tip using a pointed object. Blow nose gently to clear nostrils before use. Allow ~30 seconds to elapse between sprays. Sneezing during or immediately after dosing should be avoided (may decrease drug absorption). Do not use a topical nasal decongestant for at least 2 hours (US labeling) or at least 30 minutes (Canadian labeling) after nafarelin use.
Intranasal: Nasal spray: Prior to initial use, prime pump by releasing 7 to 10 sprays until a fine spray is released; after priming, hold the bottle horizontal and run spray tip under warm water for 15 seconds while wiping with finger or soft cloth; dry tip with tissue or soft cloth. Repeat this cleaning procedure before and after each use to prevent tip from clogging; do not clean spray tip using a pointed object. Blow nose gently to clear nostrils before use. Insert tip into nostril, aim tip toward the back and outer side of nose and close off the other nostril. Administer nasal spray while inhaling; allow ~30 seconds to elapse between sprays. Sneezing during or immediately after dosing should be avoided (may decrease drug absorption). Do not use a topical nasal decongestant for at least 2 hours following nafarelin use.
Hazardous agent (NIOSH 2016 [group 3]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.
NIOSH recommends double gloving, a protective gown, and (if liquid that could splash) eye/face protection for administration of a topical product; if there is potential for inhalation, respiratory protection is recommended (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Synarel: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/019886s039lbl.pdf#page=28
Central precocious puberty: Treatment of central precocious puberty (CPP) (gonadotropin-dependent precocious puberty) in children of both sexes.
Endometriosis: Management of endometriosis, including pain relief and reduction of endometriotic lesions.
Limitations of use: Treatment for endometriosis is limited to patients ≥18 years of age treated for 6 months.
Nafarelin may be confused with Anafranil, enalapril
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Choline C 11: Luteinizing Hormone-Releasing Hormone Analogs may diminish the therapeutic effect of Choline C 11. Risk C: Monitor therapy
Corifollitropin Alfa: Luteinizing Hormone-Releasing Hormone Analogs may enhance the therapeutic effect of Corifollitropin Alfa. Risk X: Avoid combination
Flotufolastat F18: Androgen Deprivation Therapy Agents may diminish the diagnostic effect of Flotufolastat F18. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of flotufolastat F18 in prostate cancer. The impact of ADT on the performance of flotufolastat F18 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification
Gallium Ga 68 PSMA-11: Androgen Deprivation Therapy Agents may diminish the therapeutic effect of Gallium Ga 68 PSMA-11. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of gallium Ga 68 PSMA-11 (gozetotide) in prostate cancer. The impact of ADT on the performance of gallium Ga 68 PSMA-11 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification
Indium 111 Capromab Pendetide: Luteinizing Hormone-Releasing Hormone Analogs may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination
Piflufolastat F18: Androgen Deprivation Therapy Agents may diminish the diagnostic effect of Piflufolastat F18. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of piflufolastat F18 in prostate cancer. The impact of ADT on the performance of piflufolastat F18 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification
Exclude pregnancy prior to use. Use is contraindicated in patients who may become pregnant during therapy.
Ovulation is inhibited and menstruation is stopped when used appropriately for the treatment of endometriosis; however, contraception is not assured. Nonhormonal contraception is recommended. Breakthrough bleeding or ovulation may occur if successive doses are missed. There is no evidence that pregnancy rates are enhanced or adversely affected by use.
Use is contraindicated in during pregnancy.
It is not known if nafarelin is present in breast milk.
Use in patients who are breastfeeding is contraindicated.
CPP: Bone mineral density (BMD), GnRH testing (blood LH and FSH levels), measurement of bone age, Tanner staging; monitor for development or worsening of psychiatric symptoms, including depression; signs/symptoms of pseudotumor cerebri.
Endometriosis: Menstruation, vaginal bleeding or spotting which persists after 2 months of treatment. BMD if retreatment is considered following a 6-month course of therapy. Signs and symptoms of depression.
Potent synthetic decapeptide analogue of gonadotropin-releasing hormone (GnRH; LHRH) which is approximately 200 times more potent than GnRH in terms of pituitary release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Effects on the pituitary gland and sex hormones are dependent upon its length of administration. After acute administration, an initial stimulation of the release of LH and FSH from the pituitary is observed; an increase in androgens and estrogens subsequently follows. Continued administration of nafarelin, however, suppresses gonadotrope responsiveness to endogenous GnRH resulting in reduced secretion of LH and FSH and, secondarily, decreased ovarian and testicular steroid production.
Protein binding, plasma: ~80%
Metabolism: Degraded by peptidase; forms metabolites
Bioavailability: ~1% to 6%
Half-life elimination: ~3 hours; Metabolites: ~86 hours
Time to peak, serum: 10 to 45 minutes
Excretion: Urine (44% to 55%, ~3% as unchanged drug); feces (19% to 44%)
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