HomeNDC LookupIngredientsNafarelin Acetate › 00025-0166-08
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Synarel nafarelin acetate 2 mg/mL Spray, Metered

by Pfizer Laboratories Div Pfizer Inc · 1 BOTTLE, SPRAY in 1 CARTON (0025-0166-08) / 8 mL in 1 BOTTLE, SPRAY
NDC 00025-0166-08
🏷️ FDA NDC (as labeled) 0025-0166-08 billing pads the labeler segment with a zero
Rx only Brand On market Non-controlled
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

🆔 Identity & classification

FDA NDC (as labeled) 0025-0166-08
Product NDC 0025-0166
11-digit billing NDC 00025016608
NCPDP billing unit ML — per mL (volume)
RxCUI 1797878, 1797880
UNII 8ENZ0QJW4H
Application # NDA019886
SPL Set ID d0aa57cb-d2f4-46d7-af43-7c8b06aa81a6
Established class (EPC) Gonadotropin Releasing Hormone Receptor Agonist
Mechanism of action Gonadotropin Releasing Hormone Receptor Agonists
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 1990-02-13
Route NASAL
Dosage form SPRAY, METERED
Substance NAFARELIN ACETATE
GPI-14 30080055102020
GPI class Synarel
GCN Seq No 044984
GCN 84354
HICL code 021103
Ingredient (HICL) Nafarelin Acetate
HIC1 code P
Therapeutic class — broad (HIC1) Endocrine System
HIC2 code P1
Therapeutic class — intermediate (HIC2) Anteriorpituitary Hormones
HIC3 code P1M
Therapeutic class — specific (HIC3) Lhrh (Gnrh) Agonist Analog Pituitary Suppressants
AHFS code 68:18.08.00
AHFS class Gonadotropins
FDB label name SYNAREL 2 MG/ML NASAL SPRAY
FDB brand name Synarel
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 0025-0166-08 — a 4-4-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the labeler segment → 00025-0166-08. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Gonadotropin Releasing Hormone Receptor Agonist class.

Pharmacologic class Gonadotropin Releasing Hormone Receptor Agonist
Drug family (ATC) Gonadotropin-releasing hormones
How it works Gonadotropin Releasing Hormone Receptor Agonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerPfizer Laboratories Div Pfizer Inc
Application holderPFIZER INC
FDA applicationNDA019886 (NDA)
Labeler code00025
First marketedFeb 1990
Product typeHuman Prescription Drug
Portfolio242 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name SYNAREL 2 MG/ML NASAL SPRAY Ingredient Nafarelin Acetate
📗 Our plain-language guide HelloPharmacist
  • Synarel works by interrupting the hormone signals that drive endometriosis or early puberty. It mimics a natural brain hormone so closely that, with daily use, it actually shuts do...
  • What exactly does Synarel do, and why do I need a nasal spray for a hormonal condition?
  • Because Synarel lowers estrogen, hot flashes, mood changes, and changes in your menstrual cycle are very common and expected. In children, you might see a short burst of puberty-li...
  • What side effects should I expect, and which ones mean I need to call my doctor?
📖 Read our full Nafarelin Nasal Spray guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

🧪 Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $406.13 $3,249.01 / 8 ml
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Synarel 2 mg/mLthis 00025-0166-08 Pfizer 1 bottle FDA listed
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
1990
On the market since
Feb 1990
📍
2026
Currently FDA-listed
36 years listed
🔒
·
No generic listed yet
brand only
ℹ️No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

📊 Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)

Medicare Part D (outpatient prescription) spending for Synarel — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Synarel. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Total Part D spend
$96.4K
Claims incl. refills
29
Beneficiaries
Spend / beneficiary
Spend / claim
$3,323.95
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
00025-0166-08 You're viewing this 1 BOTTLE, SPRAY in 1 CARTON (0025-0166-08) / 8 mL in 1 BOTTLE, SPRAY 1990-02-13 Active

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos — Not published for this NDC No photo available yet for this listing.
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 0025-0166-08, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 00025-0166-08, written without dashes as 00025016608. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 00025-0166-08, the first segment (00025) is the labeler code FDA assigned to Pfizer Laboratories Div Pfizer Inc; the middle segment (0166) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (08) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Pfizer Laboratories Div Pfizer Inc. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Pfizer Laboratories Div Pfizer Inc is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ~1 min read

INDICATIONS AND USAGE FOR CENTRAL PRECOCIOUS PUBERTY (For Endometriosis, See Reverse Side ) SYNAREL is indicated for treatment of central precocious puberty (CPP) (gonadotropin-dependent precocious puberty) in children of both sexes. The diagnosis of central precocious puberty (CPP) is suspected when premature development of secondary sexual characteristics occurs at or before the age of 8 years in girls and 9 years in boys, and is accompanied by significant advancement of bone age and/or a poor adult height prediction.

The diagnosis should be confirmed by pubertal gonadal sex steroid levels and a pubertal LH response to stimulation by native GnRH. Pelvic ultrasound assessment in girls usually reveals enlarged uterus and ovaries, the latter often with multiple cystic formations. Magnetic resonance imaging or CT-scanning of the brain is recommended to detect hypothalamic or pituitary tumors, or anatomical changes associated with increased intracranial pressure.

Other causes of sexual precocity, such as congenital adrenal hyperplasia, testotoxicosis, testicular tumors and/or other autonomous feminizing or masculinizing disorders must be excluded by proper clinical hormonal and diagnostic imaging examinations.

INDICATIONS AND USAGE FOR ENDOMETRIOSIS (For Central Precocious Puberty, See Reverse Side ) SYNAREL is indicated for management of endometriosis, including pain relief and reduction of endometriotic lesions. Experience with SYNAREL for the management of endometriosis has been limited to women 18 years of age and older treated for 6 months.

⏱️ Dosage and Administration ~2 min read

DOSAGE AND ADMINISTRATION For the treatment of central precocious puberty (CPP), the recommended daily dose of SYNAREL is 1600 µg. The dose can be increased to 1800 µg daily if adequate suppression cannot be achieved at 1600 µg/day. The 1600 µg dose is achieved by two sprays (400 µg) into each nostril in the morning (4 sprays) and two sprays into each nostril in the evening (4 sprays), a total of 8 sprays per day.

The 1800 µg dose is achieved by 3 sprays (600 µg) into alternating nostrils three times a day, a total of 9 sprays per day. The patient's head should be tilted back slightly, and 30 seconds should elapse between sprays. If the prescribed therapy has been well tolerated by the patient, treatment of CPP with SYNAREL should continue until resumption of puberty is desired.

There appeared to be no significant effect of rhinitis, i.e., nasal congestion, on the systemic bioavailability of SYNAREL; however, if the use of a nasal decongestant for rhinitis is necessary during treatment with SYNAREL, the decongestant should not be used until at least 2 hours following dosing with SYNAREL. Sneezing during or immediately after dosing with SYNAREL should be avoided, if possible, since this may impair drug absorption. At 1600 µg/day, a bottle of SYNAREL provides about a 7-day supply (about 56 sprays).

If the daily dose is increased, increase the supply to the patient to ensure uninterrupted treatment for the duration of therapy.

DOSAGE AND ADMINISTRATION For the management of endometriosis, the recommended daily dose of SYNAREL is 400 µg. This is achieved by one spray (200 µg) into one nostril in the morning and one spray into the other nostril in the evening. Treatment should be started between days 2 and 4 of the menstrual cycle.

In an occasional patient, the 400 µg daily dose may not produce amenorrhea. For these patients with persistent regular menstruation after 2 months of treatment, the dose of SYNAREL may be increased to 800 µg daily. The 800 µg dose is administered as one spray into each nostril in the morning (a total of two sprays) and again in the evening.

The recommended duration of administration is six months. Retreatment cannot be recommended since safety data for retreatment are not available. If the symptoms of endometriosis recur after a course of therapy, and further treatment with SYNAREL is contemplated, it is recommended that bone density be assessed before retreatment begins to ensure that values are within normal limits.

There appeared to be no significant effect of rhinitis, i.e., nasal congestion, on the systemic bioavailability of SYNAREL; however, if the use of a nasal decongestant for rhinitis is necessary during treatment with SYNAREL, the decongestant should not be used until at least 2 hours following dosing with SYNAREL. Sneezing during or immediately after dosing with SYNAREL should be avoided, if possible, since this may impair drug absorption. At 400 µg/day, a bottle of SYNAREL provides a 30-day (about 60 sprays) supply.

If the daily dose is increased, increase the supply to the patient to ensure uninterrupted treatment for the recommended duration of therapy.

Contraindications ~1 min read

CONTRAINDICATIONS 1. Hypersensitivity to GnRH, GnRH agonist analogs or any of the excipients in SYNAREL; 2. Undiagnosed abnormal vaginal bleeding; 3.

Use in pregnancy or in women who may become pregnant while receiving the drug. SYNAREL may cause fetal harm when administered to a pregnant woman. Major fetal abnormalities were observed in rats, but not in mice or rabbits after administration of SYNAREL during the period of organogenesis.

There was a dose-related increase in fetal mortality and a decrease in fetal weight in rats [see Pregnancy ] . The effects on rat fetal mortality are expected consequences of the alterations in hormonal levels brought about by the drug. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus; 4.

Use in women who are breast-feeding [see Nursing Mothers ] .

CONTRAINDICATIONS 1. Hypersensitivity to GnRH, GnRH agonist analogs or any of the excipients in SYNAREL; 2. Undiagnosed abnormal vaginal bleeding; 3.

Use in pregnancy or in women who may become pregnant while receiving the drug. SYNAREL may cause fetal harm when administered to a pregnant woman. Major fetal abnormalities were observed in rats, but not in mice or rabbits after administration of SYNAREL during the period of organogenesis.

There was a dose-related increase in fetal mortality and a decrease in fetal weight in rats [see Pregnancy ] . The effects on rat fetal mortality are expected consequences of the alterations in hormonal levels brought about by the drug. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus; 4.

Use in women who are breast-feeding [see Nursing Mothers ] .

⚠️ Warnings ~3 min read

WARNINGS The diagnosis of central precocious puberty (CPP) must be established before treatment is initiated. Regular monitoring of CPP patients is needed to assess both patient response as well as compliance. This is particularly important during the first 6 to 8 weeks of treatment to assure that suppression of pituitary-gonadal function is rapid.

Testing may include LH response to GnRH stimulation and circulating gonadal sex steroid levels. Assessment of growth velocity and bone age velocity should begin within 3 to 6 months of treatment initiation. Some patients may not show suppression of the pituitary-gonadal axis by clinical and/or biochemical parameters.

This may be due to lack of compliance with the recommended treatment regimen and may be rectified by recommending that the dosing be done by caregivers. If compliance problems are excluded, the possibility of gonadotropin independent sexual precocity should be reconsidered and appropriate examinations should be conducted. If compliance problems are excluded and if gonadotropin independent sexual precocity is not present, the dose of SYNAREL may be increased to 1800 µg/day administered as 600 µg tid.

Psychiatric events have been reported in patients taking GnRH agonists. Postmarketing reports with this class of drugs includes symptoms of emotional lability, such as crying, irritability, impatience, anger, and aggression. Monitor for development or worsening of psychiatric symptoms during treatment with SYNAREL.

Post-marketing reports of convulsions have been observed in patients receiving GnRH agonists. These have included patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs. Convulsions have also been reported in patients in the absence of any of the conditions mentioned above.

Severe cutaneous adverse reactions (SCARs) have been reported in patients receiving other GnRH agonists. These reactions include Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), including cases with visceral involvement and/or requiring skin grafts. If a SCAR is suspected, discontinue SYNAREL.

Consult with a healthcare provider with expertise in the diagnosis and management of SCARs. If a diagnosis of SCAR is confirmed, permanently discontinue SYNAREL. Pseudotumor cerebri (idiopathic intracranial hypertension) has been reported in pediatric patients receiving GnRH agonists.

Monitor patients for signs and symptoms of pseudotumor cerebri, including headache, papilledema, blurred vision, diplopia, loss of vision, pain behind the eye or pain with eye movement, tinnitus, dizziness, and nausea.

WARNINGS Safe use of nafarelin acetate in pregnancy has not been established clinically. Before starting treatment with SYNAREL, pregnancy must be excluded. When used regularly at the recommended dose, SYNAREL usually inhibits ovulation and stops menstruation.

Contraception is not insured, however, by taking SYNAREL, particularly if patients miss successive doses. Therefore, patients should use nonhormonal methods of contraception. Patients should be advised to see their physician if they believe they may be pregnant.

If a patient becomes pregnant during treatment, the drug must be discontinued and the patient must be apprised of the potential risk to the fetus. Clinical Depression Depression may occur or worsen during treatment with GnRH agonists including SYNAREL 2 mg/mL. Carefully observe women for depression, especially those with a history of depression and consider whether the risks of continuing SYNAREL 2 mg/mL outweigh the benefits.

Women with new or worsening depression should be referred to a mental health professional, as appropriate [see Precautions ] . Severe cutaneous adverse reactions (SCARs) h…

🤒 Adverse Reactions ~3 min read

ADVERSE REACTIONS In clinical trials of 155 pediatric patients, 2.6% reported symptoms suggestive of drug sensitivity, such as shortness of breath, chest pain, urticaria, rash, and pruritus. In these 155 patients treated for an average of 41 months and as long as 80 months (6.7 years), adverse events most frequently reported (>3% of patients) consisted largely of episodes occurring during the first 6 weeks of treatment as a result of the transient stimulatory action of nafarelin upon the pituitary-gonadal axis: acne (10%) transient breast enlargement (8%) vaginal bleeding (8%) emotional lability (6%) [see Warnings ] transient increase in pubic hair (5%) body odor (4%) seborrhea (3%) Hot flashes, common in adult women treated for endometriosis, occurred in only 3% of treated children and were transient.

Other adverse events thought to be drug-related, and occurring in >3% of patients were rhinitis (5%) and white or brownish vaginal discharge (3%). Approximately 3% of patients withdrew from clinical trials due to adverse events. In one male patient with concomitant congenital adrenal hyperplasia, and who had discontinued treatment 8 months previously to resume puberty, adrenal rest tumors were found in the left testis.

Relationship to SYNAREL is unlikely. Regular examinations of the pituitary gland by magnetic resonance imaging (MRI) or computer assisted tomography (CT) of children during long-term nafarelin therapy as well as during the post-treatment period has occasionally revealed changes in the shape and size of the pituitary gland. These changes include asymmetry and enlargement of the pituitary gland, and a pituitary microadenoma has been suspected in a few children.

The relationship of these findings to SYNAREL is not known. Post-Marketing Pituitary apoplexy: During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was diagnosed, with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour.

In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required. Psychiatric adverse events: Emotional lability, such as crying, irritability, impatience, anger, and aggression has been observed with GnRH agonists [see Warnings ] ; Depression, including rare reports of suicidal ideation and attempt, has been reported for GnRH agonists in children treated for central precocious puberty.

Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression. Central/peripheral nervous adverse events: Convulsion, pseudotumor cerebri (idiopathic intracranial hypertension).

ADVERSE REACTIONS Clinical Studies In formal clinical trials of 1509 healthy adult patients, symptoms suggestive of drug sensitivity, such as shortness of breath, chest pain, urticaria, rash and pruritus occurred in 3 patients (approximately 0.2%). As would be expected with a drug which lowers serum estradiol levels, the most frequently reported adverse reactions were those related to hypoestrogenism. In controlled studies comparing SYNAREL (400 µg/day) and danazol (600 or 800 mg/day), adverse reactions most frequently reported and thought to be drug-related are shown in the figure below: In addition, less than 1% of patients experienced paresthesia, palpitations, chloasma, maculopapular rash, eye pain, asthenia, lactation, breast engorgement, and arthralgia.

Figure Changes in Bone Density After six months of treatment with SYNAREL, vertebral trabecular bone density and total vertebral bone mass, measured by quantitative computed tomography (QCT), decreased by an average of 8.7% and…

🔄 Drug Interactions 104 words

Drug Interactions No pharmacokinetic-based drug-drug interaction studies have been conducted with SYNAREL. However, because nafarelin acetate is a peptide that is primarily degraded by peptidase and not by cytochrome P-450 enzymes, and the drug is only about 80% bound to plasma proteins at 4°C, drug interactions would not be expected to occur.

Drug Interactions No pharmacokinetic-based drug-drug interaction studies have been conducted with SYNAREL. However, because nafarelin acetate is a peptide that is primarily degraded by peptidase and not by cytochrome P-450 enzymes, and the drug is only about 80% bound to plasma proteins at 4°C, drug interactions would not be expected to occur.

🔄 Drug / Laboratory Test Interactions 58 words

Drug/Laboratory Test Interactions Administration of SYNAREL in therapeutic doses results in suppression of the pituitary-gonadal system. Normal function is usually restored within 4 to 8 weeks after treatment is discontinued. Therefore, diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment and up to 4 to 8 weeks after discontinuation of therapy with SYNAREL may be misleading.

🤰 Pregnancy ~1 min read

Pregnancy Teratogenic Effects See Contraindications . Intramuscular SYNAREL was administered to rats during the period of organogenesis at 0.4, 1.6, and 6.4 µg/kg/day (about 0.5, 2, and 7 times the maximum recommended human intranasal dose based on the relative bioavailability by the two routes of administration). An increase in major fetal abnormalities was observed in 4/80 fetuses at the highest dose.

A similar, repeat study at the same doses in rats and studies in mice and rabbits at doses up to 600 µg/kg/day and 0.18 µg/kg/day, respectively, failed to demonstrate an increase in fetal abnormalities after administration during the period of organogenesis. In rats and rabbits, there was a dose-related increase in fetal mortality and a decrease in fetal weight with the highest dose.

Pregnancy Teratogenic Effects See Contraindications . Intramuscular SYNAREL was administered to rats during the period of organogenesis at 0.4, 1.6, and 6.4 µg/kg/day (about 0.5, 2, and 7 times the maximum recommended human intranasal dose based on the relative bioavailability by the two routes of administration). An increase in major fetal abnormalities was observed in 4/80 fetuses at the highest dose.

A similar, repeat study at the same doses in rats and studies in mice and rabbits at doses up to 600 µg/kg/day and 0.18 µg/kg/day, respectively, failed to demonstrate an increase in fetal abnormalities after administration during the period of organogenesis. In rats and rabbits, there was a dose-related increase in fetal mortality and a decrease in fetal weight with the highest dose.

🧒 Pediatric Use 19 words

Pediatric Use Safety and effectiveness of SYNAREL for endometriosis in patients younger than 18 years have not been established.

🆘 Overdosage 112 words

OVERDOSAGE In experimental animals, a single subcutaneous administration of up to 60 times the recommended human dose (on a µg/kg basis, not adjusted for bioavailability) had no adverse effects. At present, there is no clinical evidence of adverse effects following overdosage of GnRH analogs. Based on studies in monkeys, SYNAREL is not absorbed after oral administration.

OVERDOSAGE In experimental animals, a single subcutaneous administration of up to 60 times the recommended human dose (on a µg/kg basis, not adjusted for bioavailability) had no adverse effects. At present, there is no clinical evidence of adverse effects following overdosage of GnRH analogs. Based on studies in monkeys, SYNAREL is not absorbed after oral administration.

🧬 Clinical Pharmacology ~3 min read

CLINICAL PHARMACOLOGY Nafarelin acetate is a potent agonistic analog of gonadotropin-releasing hormone (GnRH). At the onset of administration, nafarelin stimulates the release of the pituitary gonadotropins, LH and FSH, resulting in a temporary increase of gonadal steroidogenesis. Repeated dosing abolishes the stimulatory effect on the pituitary gland.

Twice daily administration leads to decreased secretion of gonadal steroids by about 4 weeks; consequently, tissues and functions that depend on gonadal steroids for their maintenance become quiescent. In children, nafarelin acetate was rapidly absorbed into the systemic circulation after intranasal administration. Maximum serum concentrations (measured by RIA) were achieved between 10 and 45 minutes.

Following a single dose of 400 µg base, the observed peak concentration was 2.2 ng/mL, whereas following a single dose of 600 µg base, the observed peak concentration was 6.6 ng/mL. The average serum half-life of nafarelin following intranasal administration of a 400 µg dose was approximately 2.5 hours. It is not known and cannot be predicted what the pharmacokinetics of nafarelin will be in children given a dose above 600 µg.

In adult women, nafarelin acetate was rapidly absorbed into the systemic circulation after intranasal administration. Maximum serum concentrations (measured by RIA) were achieved between 10 and 40 minutes. Following a single dose of 200 µg base, the observed average peak concentration was 0.6 ng/mL (range 0.2 to 1.4 ng/mL), whereas following a single dose of 400 µg base, the observed average peak concentration was 1.8 ng/mL (range 0.5 to 5.3 ng/mL).

Bioavailability from a 400 µg dose averaged 2.8% (range 1.2 to 5.6%). The average serum half-life of nafarelin following intranasal administration was approximately 3 hours. About 80% of nafarelin acetate was bound to plasma proteins at 4°C.

Twice daily intranasal administration of 200 or 400 µg of SYNAREL in 18 healthy women for 22 days did not lead to significant accumulation of the drug. Based on the mean C min levels on Days 15 and 22, there appeared to be dose proportionality across the two dose levels. After subcutaneous administration of 14 C-nafarelin acetate to men, 44–55% of the dose was recovered in urine and 18.5–44.2% was recovered in feces.

Approximately 3% of the administered dose appeared as unchanged nafarelin in urine. The 14 C serum half-life of the metabolites was about 85.5 hours. Six metabolites of nafarelin have been identified of which the major metabolite is Tyr-D(2)-Nal-Leu-Arg-Pro-Gly-NH 2 (5–10).

The activity of the metabolites, the metabolism of nafarelin by nasal mucosa, and the pharmacokinetics of the drug in hepatically- and renally-impaired patients have not been determined. There appeared to be no significant effect of rhinitis, i.e., nasal congestion, on the systemic bioavailability of SYNAREL; however, if the use of a nasal decongestant for rhinitis is necessary during treatment with SYNAREL, the decongestant should not be used until at least 2 hours following dosing with SYNAREL. When used regularly in girls and boys with central precocious puberty (CPP) at the recommended dose, SYNAREL suppresses LH and sex steroid hormone levels to prepubertal levels, affects a corresponding arrest of secondary sexual development, and slows linear growth and skeletal maturation.

In some cases, initial estrogen withdrawal bleeding may occur, generally within 6 weeks after initiation of therapy. Thereafter, menstruation should cease. In clinical studies the peak response of LH to GnRH stimulation was reduced from a pubertal response to a prepubertal response (<15 mlU/mL) within one month of treatment.

Linear growth velocity, which is commonly pubertal in children with CPP, is reduced in most children within the first year of treatment to values of 5 to 6 cm/year or less. Children with CPP are frequently taller than their chronological age peers; height for chronological age approaches normal in…

📦 How Supplied / Storage and Handling 134 words

HOW SUPPLIED Each 0.5 ounce bottle (NDC 0025-0166-08) contains 8 mL SYNAREL (nafarelin acetate) Nasal Solution 2 mg/mL (as nafarelin base), and is supplied with a metered spray pump that delivers 200 µg of nafarelin per spray. A dust cover and a leaflet of patient instructions are also included. Store upright at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Protect from light.

HOW SUPPLIED Each 0.5 ounce bottle (NDC 0025-0166-08) contains 8 mL SYNAREL (nafarelin acetate) Nasal Solution 2 mg/mL (as nafarelin base), and is supplied with a metered spray pump that delivers 200 µg of nafarelin per spray. A dust cover and a leaflet of patient instructions are also included. Store upright at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Protect from light.

📦 Storage and Handling 36 words

Store upright at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Protect from light.

Store upright at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Protect from light.

📋 Description ~2 min read

DESCRIPTION SYNAREL (nafarelin acetate) Nasal Solution is intended for administration as a spray to the nasal mucosa. Nafarelin acetate, the active component of SYNAREL Nasal Solution, is a decapeptide with the chemical name: 5-oxo- L -prolyl- L -histidyl- L -tryptophyl- L -seryl- L -tyrosyl-3-(2-naphthyl)- D -alanyl- L -leucyl- L -arginyl- L -prolyl-glycinamide acetate. Nafarelin acetate is a synthetic analog of the naturally occurring gonadotropin-releasing hormone (GnRH).

Nafarelin acetate has the following chemical structure: ∙ x CH 3 COOH ∙ y H 2 O (1 ⩽ x ⩽ 2; 2 ⩽ y ⩽ 8) SYNAREL Nasal Solution contains nafarelin acetate (2 mg/mL, content expressed as nafarelin base) in a solution of benzalkonium chloride, glacial acetic acid, sodium hydroxide or hydrochloric acid (to adjust pH), sorbitol, and purified water. After priming the pump unit for SYNAREL, each actuation of the unit delivers approximately 100 µL of the spray containing approximately 200 µg nafarelin base. The contents of one spray bottle are intended to deliver at least 60 sprays.

Chemical Structure

DESCRIPTION SYNAREL (nafarelin acetate) Nasal Solution is intended for administration as a spray to the nasal mucosa. Nafarelin acetate, the active component of SYNAREL Nasal Solution, is a decapeptide with the chemical name: 5-oxo- L -prolyl- L -histidyl- L -tryptophyl- L -seryl- L -tyrosyl-3-(2-naphthyl)- D -alanyl- L -leucyl- L -arginyl- L -prolyl-glycinamide acetate. Nafarelin acetate is a synthetic analog of the naturally occurring gonadotropin-releasing hormone (GnRH).

Nafarelin acetate has the following chemical structure: ∙ x CH3COOH ∙ y H2O (1 ⩽ x ⩽ 2; 2 ⩽ y ⩽ 8) SYNAREL Nasal Solution contains nafarelin acetate (2 mg/mL, content expressed as nafarelin base) in a solution of benzalkonium chloride, glacial acetic acid, sodium hydroxide or hydrochloric acid (to adjust pH), sorbitol, and purified water. After priming the pump unit for SYNAREL, each actuation of the unit delivers approximately 100 µL of the spray containing approximately 200 µg nafarelin base. The contents of one spray bottle are intended to deliver at least 60 sprays.

Chemical Structure

💬 Information for Patients ~3 min read

Information for Patients, Patients' Parents or Guardians An information pamphlet for patients is included with the product. Patients and their caregivers should be aware of the following information: 1. Reversibility of the suppressive effects of nafarelin has been demonstrated by the appearance or return of menses, by the return of pubertal gonadotropin and gonadal sex steroid levels, and/or by advancement of secondary sexual development.

Semen analysis was normal in the two ejaculated specimens obtained thus far from boys who have been taken off therapy to resume puberty. Fertility has not been documented by pregnancies and the effect of long-term use of the drug on fertility is not known. 2.

Patients and their caregivers should be adequately counseled to assure full compliance; irregular or incomplete daily doses may result in stimulation of the pituitary-gonadal axis. 3. Inform parents and caregivers that reports of convulsions have been observed in patients receiving GnRH agonists.

Patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with convulsions may be at increased risk [see Warnings ]. 4. Inform patients and caregivers that reports of pseudotumor cerebri (idiopathic intracranial hypertension) have been observed in pediatric patients receiving GnRH agonists.

Advise patients and caregivers to monitor for headache, and vision issues such as blurred vision, double vision, loss of vision, pain behind the eye or pain with eye movement, ringing in the ears, dizziness, and nausea. Advise patients and caregivers to contact their healthcare provider if the patient develops any of these symptoms [see Warnings ] . 5.

During the first month of treatment with SYNAREL, some signs of puberty, e.g., vaginal bleeding or breast enlargement, may occur. This is the expected initial effect of the drug. Such changes should resolve soon after the first month.

If such resolution does not occur within the first two months of treatment, this may be due to lack of compliance or the presence of gonadotropin independent sexual precocity. If both possibilities are definitively excluded, the dose of SYNAREL may be increased to 1800 µg/day administered as 600 µg tid. 6.

Patients with intercurrent rhinitis should consult their physician for the use of a topical nasal decongestant. If the use of a topical nasal decongestant is required during treatment with SYNAREL, the decongestant should not be used until at least 2 hours following dosing with SYNAREL. Sneezing during or immediately after dosing with SYNAREL should be avoided, if possible, since this may impair drug absorption.

Information for Patients An information pamphlet for patients is included with the product. Patients should be aware of the following information: 1. Since menstruation should stop with effective doses of SYNAREL, the patient should notify her physician if regular menstruation persists.

The cause of vaginal spotting, bleeding or menstruation could be noncompliance with the treatment regimen, or it could be that a higher dose of the drug is required to achieve amenorrhea. The patient should be questioned regarding her compliance. If she is careful and compliant, and menstruation persists to the second month, consideration should be given to doubling the dose of SYNAREL.

If the patient has missed several doses, she should be counseled on the importance of taking SYNAREL regularly as prescribed. 2. Patients should not use SYNAREL if they are pregnant, breastfeeding, have undiagnosed abnormal vaginal bleeding, or are allergic to any of the ingredients in SYNAREL.

3. Safe use of the drug in pregnancy has not been established clinically. Therefore, a nonhormonal method of contraception should be used during treatment.

Patients should be advised that if they miss successive doses of SYNAREL, breakthrough bleeding or ovulation may occur with the potenti…

💬 Medication Guide ~3 min read

MEDICATION GUIDE SYNAREL ( sin-na-rell ) (nafarelin acetate) nasal solution What is the most important information I should know about SYNAREL? • Some people taking GnRH agonists like SYNAREL have had new or worsened mental (psychiatric) problems. Mental (psychiatric) problems may include emotional symptoms such as: • crying • irritability • restlessness (impatience) • anger • acting aggressive Call your child's doctor right away if your child has any new or worsening mental symptoms or problems while taking SYNAREL • Some people taking GnRH agonists like SYNAREL have had seizures.

The risk of seizures may be higher in people who: • have a history of seizures. • have a history of epilepsy. • have a history of brain or brain vessel (cerebrovascular) problems or tumors. • are taking a medicine that has been connected to seizures such as taking bupropion or selective serotonin reuptake inhibitors (SSRIs). Seizures have also happened in people who have not had any of these problems. Call your child's doctor right away if your child has a seizure while taking SYNAREL .

Severe cutaneous (skin) adverse reactions may happen during treatment with GnRH agonists like SYNAREL. Stop using SYNAREL and call your child’s doctor right away if your child has any of the following signs or symptoms during treatment with SYNAREL: • skin rash or acne • dry skin • itching • blisters on your skin • redness or swelling of your face, hands, or soles of your feet • blisters or sores in your mouth • peeling of your skin • fever • muscle or joint aches • swollen glands What is SYNAREL? SYNAREL is a gonadotropin releasing hormone (GnRH) medicine used for the treatment of children with central precocious puberty (CPP).

Do not give SYNAREL if your child: • is allergic to gonadotropin releasing hormone (GnRH), GnRH agonist medicines, or any of the ingredients in SYNAREL. See the end of this Medication Guide for a complete list of ingredients in SYNAREL. • has unusual vaginal bleeding that has not been checked by her doctor. • is pregnant or may become pregnant. SYNAREL can cause birth defects or loss of the baby.

If your child becomes pregnant call your doctor. • is breastfeeding or plans to breastfeed. It is not known if SYNAREL passes into breast milk. You and your child's doctor should decide if your child will take SYNAREL or breastfeed.

Do not breastfeed while taking SYNAREL. Before your child takes SYNAREL, tell your doctor about all of your child's medical conditions, including if they: • have a history of mental (psychiatric) problems. • have or have had a history of seizures. • have a history of epilepsy. • have a history of brain or brain vessel (cerebrovascular) problems or tumors • are taking a medicine that has been connected to seizures such as bupropion or selective serotonin reuptake inhibitors (SSRIs). Tell your doctor about all the medicines your child takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should your child take SYNAREL? • Your child's doctor should do tests to make sure your child has CPP before treating your child with SYNAREL. • Keep all scheduled visits to the doctor. If scheduled doses are missed, your child may start having signs of puberty again. The doctor will do regular exams and blood tests to check for signs of puberty. • Take SYNAREL exactly as your doctor tells you to take it.

See detailed " Instructions for Use " at the end of this Medication Guide for information about the right way to use SYNAREL. • Your child's doctor will tell you how much SYNAREL your child is to take and when to take it. If your doctor increases your child's daily dose of SYNAREL, 1 bottle will not last the standard 7 days. Talk with your child's doctor to make sure your child has enough SYNAREL to take their prescribed dose every day.

What should your child avoid while taking SYNAREL? • Your child should avoid sneezing while taking SYNAREL or right after using it, if possible. This could redu…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.