Synarela (Nafarelin)
GnRH agonist nasal spray for endometriosis and IVF pre-treatment
Synarela is a prescription nasal spray containing nafarelin, a synthetic gonadotropin-releasing hormone (GnRH) agonist. It is primarily used to treat endometriosis by suppressing estrogen production, and as a pre-treatment in assisted reproduction (IVF) to prevent premature ovulation. This guide covers uses, dosage, side effects, warnings, and practical administration instructions based on international clinical guidelines.
Quick Facts
Key Takeaways
- Synarela (nafarelin) is a GnRH agonist nasal spray that suppresses estrogen production by desensitizing the pituitary gland within 2–3 weeks of continuous use.
- It is approved for two main indications: treatment of endometriosis (up to 6 months) and pre-treatment before IVF to prevent spontaneous ovulation.
- Non-hormonal contraception (condoms or diaphragm) must be used during treatment, as Synarela is contraindicated in pregnancy.
- Most side effects are caused by low estrogen levels and include hot flashes, mood changes, headache, and vaginal dryness — these typically resolve after treatment ends.
- The nasal spray tip must be cleaned before and after every use to prevent clogging and ensure accurate dosing.
What Is Synarela and What Is It Used For?
Quick Answer: Synarela is a nasal spray containing nafarelin, a synthetic version of gonadotropin-releasing hormone (GnRH). It works by initially stimulating, then suppressing the production of female sex hormones (estrogen and progesterone), making it effective for treating endometriosis and preparing for IVF procedures.
Nafarelin, the active substance in Synarela, is structurally similar to the naturally occurring gonadotropin-releasing hormone (GnRH) produced in the hypothalamus region of the brain. Under normal physiological conditions, GnRH is released in a pulsatile manner and stimulates the pituitary gland to produce two key hormones: luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These gonadotropins in turn stimulate the ovaries to produce the female sex hormones estrogen and progesterone, which are essential for the menstrual cycle and reproductive function.
When Synarela is administered as a continuous (non-pulsatile) nasal spray, it initially stimulates the pituitary gland, causing a temporary increase in estrogen and progesterone production. However, within approximately 2 to 3 weeks of regular use, the pituitary gland becomes desensitized to the continuous GnRH stimulation. This desensitization leads to a marked suppression of LH and FSH secretion, which in turn causes the ovaries to significantly reduce or cease production of estrogen and progesterone. This therapeutic effect is sometimes referred to as creating a "medical menopause" or a hypoestrogenic state.
Treatment of Endometriosis
Endometriosis is a chronic condition in which tissue similar to the uterine lining (endometrium) grows outside the uterus, commonly on the ovaries, fallopian tubes, and the pelvic peritoneum. These endometriotic implants are estrogen-dependent, meaning they grow and bleed in response to the hormonal fluctuations of the menstrual cycle. This process causes significant pain, inflammation, and can lead to scar tissue formation (adhesions) and impaired fertility.
By suppressing estrogen production, Synarela effectively starves the endometriotic tissue of its hormonal fuel. This causes the ectopic endometrial implants to shrink or become inactive, leading to a reduction in pain symptoms such as dysmenorrhea (painful periods), pelvic pain, and dyspareunia (pain during intercourse). Menstruation typically ceases during treatment but returns after Synarela is discontinued. Treatment for endometriosis should not exceed 6 months due to the potential impact on bone mineral density.
Pre-Treatment for In Vitro Fertilization (IVF)
In assisted reproductive technology, Synarela plays a crucial role as a pituitary suppression agent. During IVF protocols, it is important to prevent the body's natural hormonal surge that triggers spontaneous ovulation, which would release eggs prematurely before they can be collected. Synarela's suppressive effect on LH ensures that the timing of egg retrieval can be precisely controlled by the fertility specialist using exogenous gonadotropins. This controlled ovarian stimulation approach significantly improves the success rates of IVF cycles by allowing multiple mature eggs to develop simultaneously without the risk of premature luteinization or spontaneous ovulation.
What Should You Know Before Taking Synarela?
Quick Answer: Synarela must not be used during pregnancy or if you have unexplained vaginal bleeding. Non-hormonal contraception is required during treatment. Discuss all medications with your doctor, particularly nasal decongestants, which should be used at least 30 minutes after Synarela.
Contraindications
Synarela should not be used if any of the following conditions apply to you. It is essential to discuss these with your prescribing physician before starting treatment:
- Allergy or hypersensitivity: Do not use Synarela if you are allergic to nafarelin, GnRH, GnRH analogues, or any of the inactive ingredients in the formulation, including benzalkonium chloride and sorbitol.
- Pregnancy: Synarela is absolutely contraindicated during pregnancy. Limited clinical data on use in pregnant women suggest a potential risk to fetal development. A pregnancy test should be performed before initiating treatment.
- Undiagnosed vaginal bleeding: If you experience abnormal vaginal bleeding for which the underlying cause has not been determined, Synarela should not be started until a thorough gynecological evaluation has been completed.
Warnings and Precautions
Depression, including severe cases, has been reported in patients taking Synarela. Inform your doctor immediately if you experience feelings of depression, persistent sadness, or significant mood changes during treatment. Your healthcare provider may recommend discontinuing therapy or initiating appropriate support.
During treatment with Synarela, you must use a non-hormonal method of contraception such as condoms or a diaphragm. Hormonal contraceptives (pills, patches, rings) should not be used as they may interfere with the mechanism of action of nafarelin. While this requirement may seem contradictory for patients undergoing IVF treatment, the goal is to prevent pregnancy during the suppression phase, with conception being achieved only after planned embryo transfer following treatment completion.
When Synarela is used in combination with gonadotropins for fertility treatment, there is a risk of ovarian hyperstimulation syndrome (OHSS). Symptoms of OHSS include abdominal pain, bloating, nausea, vomiting, and in severe cases, difficulty breathing and fluid accumulation. Contact your healthcare provider immediately if you experience any of these symptoms. Your doctor will monitor your response through blood tests and ultrasound examinations during treatment.
Prolonged use of Synarela (beyond 6 months) can lead to a decrease in bone mineral density (osteoporosis). Clinical studies have shown that bone density typically returns to pre-treatment levels within approximately 6 months after completing therapy. Patients with existing risk factors for osteoporosis should discuss these concerns with their physician, and calcium and vitamin D supplementation may be recommended during treatment.
Pregnancy and Breastfeeding
Synarela must not be used during pregnancy. Although clinical experience with nafarelin during pregnancy is limited, the pharmacological action of the drug poses a theoretical risk of harm to the developing fetus. If pregnancy is suspected during treatment, Synarela should be stopped immediately and the patient should contact their healthcare provider.
It is currently unknown whether nafarelin is excreted in human breast milk. Therefore, breastfeeding is not recommended during treatment with Synarela. If you are breastfeeding, discuss alternative treatment options with your doctor before starting therapy.
Driving and Operating Machinery
No direct effects on the ability to drive or operate machinery have been observed with Synarela. However, patients should be aware that side effects such as headache, dizziness, or mood changes could potentially affect concentration and reaction time. Each individual should assess their own fitness before engaging in activities requiring alertness.
Synarela contains 0.01 mg of benzalkonium chloride per nasal spray dose. This preservative may cause irritation and swelling inside the nose, particularly with prolonged use. If you experience significant nasal irritation, inform your prescribing physician.
How Does Synarela Interact with Other Drugs?
Quick Answer: The most important interaction to be aware of is with nasal decongestants — these should be administered at least 30 minutes after Synarela to avoid reduced absorption. Hormonal contraceptives may interfere with nafarelin's therapeutic effect.
Although nafarelin has relatively few documented drug interactions compared to many other medications, it is essential to inform your doctor or pharmacist about all medicines you are taking, have recently taken, or plan to take, including over-the-counter products and herbal supplements. The most clinically significant interactions involve medications that are administered nasally or that affect hormonal pathways.
| Interacting Drug | Type | Effect | Recommendation |
|---|---|---|---|
| Nasal decongestants (e.g., oxymetazoline, xylometazoline) | Absorption interference | May reduce nasal absorption of nafarelin, leading to subtherapeutic drug levels | Administer decongestants at least 30 minutes after Synarela |
| Hormonal contraceptives (combined oral, patches, rings) | Pharmacodynamic antagonism | May counteract the hormonal suppression achieved by nafarelin | Use only non-hormonal contraception during treatment |
| Nasal corticosteroid sprays (e.g., fluticasone, mometasone) | Potential absorption interference | May alter nasal mucosa and affect nafarelin absorption | Separate administration by at least 30 minutes; consult your doctor |
| Gonadotropins (FSH, hMG) | Intentional co-administration (IVF) | Combined use increases risk of OHSS | Use only under specialist supervision with regular monitoring |
The relatively limited interaction profile of nafarelin is partly explained by its route of administration (nasal) and its highly specific mechanism of action on GnRH receptors. Unlike orally administered drugs, nafarelin does not undergo significant first-pass hepatic metabolism, reducing the potential for cytochrome P450-mediated drug interactions. However, any medication that alters nasal blood flow, mucosal integrity, or produces excessive nasal secretions has the theoretical potential to affect nafarelin absorption and efficacy.
If you are prescribed a new medication while using Synarela, always inform the prescribing physician and your pharmacist that you are on nafarelin therapy. This is particularly important if the new medication is administered nasally or has hormonal effects.
What Is the Correct Dosage of Synarela?
Quick Answer: For endometriosis: 1 spray (200 mcg) in one nostril morning and 1 spray in the other nostril evening = 400 mcg/day for up to 6 months. For IVF: 1 spray in each nostril morning and evening = 800 mcg/day. Always follow your doctor's individual instructions.
Always use Synarela exactly as your doctor has prescribed. The dosage is determined individually by your physician based on your specific condition and treatment goals. Never change your prescribed dose without first consulting your doctor.
| Indication | Dosage | Schedule | Duration |
|---|---|---|---|
| Endometriosis | 1 spray (200 mcg) in one nostril morning, 1 spray in the other nostril evening | Start on day 2 or day 4 of menstrual cycle; twice daily (morning and evening) | Up to 6 months |
| IVF pre-treatment | 1 spray (200 mcg) in each nostril morning and evening (total 4 sprays/day = 800 mcg) | Twice daily (morning and evening), both nostrils each time | As directed by fertility specialist |
How to Use the Nasal Spray
Correct technique is essential for Synarela to work effectively. The pump must deliver a fine spray mist — if it produces a thin stream of liquid instead, the spray device is not functioning correctly and you should contact your pharmacy for assistance.
Before using a new Synarela bottle for the first time, you must prime the spray pump. Hold the bottle upright, away from your face, with two fingers on the "shoulders" and your thumb on the base. Press the pump firmly and evenly 5–7 times until a fine, even mist appears. You only need to prime the pump once per bottle — re-priming each time wastes medication.
Step-by-step administration:
- Blow your nose gently to clear both nostrils.
- Remove the protective cap and safety clip. Keep them safe for replacement after use.
- Clean the spray tip by holding the bottle horizontally and rinsing the tip with warm water while rubbing gently with your finger or a clean, soft cloth for 15 seconds. Do not use sharp objects to clean the tip, as this may enlarge the nozzle hole and result in inaccurate dosing. Do not remove the pump from the bottle as this releases the required internal pressure.
- Tilt your head slightly forward. Close one nostril and insert the spray tip into the other, directing it backward and toward the outer wall of the nose.
- Press the bottle firmly upward between your thumb and fingers once while gently breathing in through the nostril. If your doctor has prescribed 4 sprays per day, spray into the other nostril as well at this time.
- Tilt your head back for a few seconds to allow the solution to spread across the nasal lining.
- Clean the spray tip again with warm water and a soft cloth, then dry thoroughly.
- Replace the safety clip and protective cap to prevent the tip from becoming clogged.
If you sneeze during or immediately after spraying, the dose may be insufficient. In this case, administer one additional spray to ensure you receive the complete therapeutic dose.
Missed Dose
If you forget to take your dose at the scheduled time, take it as soon as you remember and then continue with your regular dosing schedule. Do not take a double dose to compensate for a missed one. Consistent timing of doses (morning and evening) is important for maintaining stable drug levels and optimal therapeutic effect. If you frequently forget doses, consider setting reminders on your phone or associating your doses with daily routines such as brushing your teeth.
Overdose
If you have taken too much Synarela or if a child has accidentally ingested the medication, contact your doctor, hospital emergency department, or poison control center immediately for risk assessment and advice. Based on the pharmacological profile of nafarelin, an acute overdose is unlikely to cause serious harm, but medical evaluation is recommended to monitor for any unexpected effects.
What Are the Side Effects of Synarela?
Quick Answer: Most side effects result from lowered estrogen levels and include hot flashes, mood swings, headache, and vaginal dryness. These are typically reversible after treatment ends. Serious but uncommon effects include bone density loss, depression, and ovarian hyperstimulation syndrome (when used with gonadotropins).
Like all medicines, Synarela can cause side effects, although not everyone experiences them. The majority of reported side effects are a direct consequence of the medication's therapeutic action — the suppression of estrogen production. These effects are generally reversible after treatment is discontinued and the body's natural hormonal balance is restored.
Very Common
May affect more than 1 in 10 users
- Hot flashes (vasomotor symptoms)
- Rapid mood swings and emotional changes
- Decreased libido (reduced sexual desire)
- Headache
- Runny nose (rhinorrhea)
- Acne
- Muscle pain (myalgia)
- Vaginal dryness
- Decreased breast size
- Weight gain
- Seborrhoeic eczema (seborrhoea)
- Edema (swelling)
Common
May affect up to 1 in 10 users
- Insomnia (difficulty sleeping)
- Weight loss
- Bone density loss (usually reversible within ~6 months after stopping)
- Nasal mucosa irritation
- Depression (with long-term treatment)
- Emotional instability (with long-term treatment)
- Estrogen deficiency symptoms
- Breast gland reduction
- Increased libido
- Hypersensitivity reactions (chest pain, breathing difficulties, urticaria, rash, itching)
- Paraesthesia (tingling or "pins and needles")
- Blood pressure changes (hypertension or hypotension)
- Premature menopause symptoms
- Uterine bleeding (breakthrough bleeding)
- Hirsutism (increased body hair growth)
Uncommon
May affect up to 1 in 100 users
- Depression (with short-term treatment)
- Emotional instability (with short-term treatment)
- Breast enlargement
- Ovarian cysts
- Hair loss (alopecia)
- Joint pain (arthralgia)
Rare
May affect up to 1 in 1,000 users
- Visual disturbances
- Joint inflammation (arthritis)
Frequency Not Known
Cannot be estimated from available data
- Ovarian hyperstimulation syndrome (OHSS) — symptoms include abdominal pain, bloating, fluid accumulation, nausea, vomiting, and diarrhea (primarily when used with gonadotropins for IVF)
- Interstitial pneumonia and pulmonary fibrosis (causal relationship not established)
Understanding the underlying mechanism helps put these side effects in context. Hot flashes, vaginal dryness, mood changes, and bone density loss are all characteristic features of estrogen deficiency — essentially the same symptoms experienced during natural menopause. The key difference is that Synarela-induced estrogen suppression is temporary and reversible. Once treatment is discontinued, the pituitary-ovarian axis gradually recovers, menstruation returns, and estrogen levels normalize, typically within 4 to 8 weeks.
Bone mineral density changes deserve particular attention. Clinical studies have demonstrated that the degree of bone loss during a 6-month course of nafarelin treatment is generally modest and reversible. Bone density measurements usually return to pre-treatment baseline values within approximately 6 months after completing therapy. This is one of the primary reasons that treatment duration for endometriosis is limited to a maximum of 6 months.
Seek immediate medical attention if you experience severe allergic reactions (breathing difficulties, swelling of face or throat, severe rash), signs of OHSS (significant abdominal pain and bloating), or symptoms of severe depression. Report any persistent or troublesome side effects to your healthcare provider, who can advise on appropriate management strategies.
How Should You Store Synarela?
Quick Answer: Store upright at room temperature (below 25°C/77°F), in the original carton. Do not freeze. Always replace the safety clip and cap after use. Keep out of reach of children.
Proper storage of Synarela is important to maintain the medication's stability and ensure accurate dosing throughout the treatment period. Improper storage conditions can degrade the active ingredient or damage the spray pump mechanism.
- Temperature: Store the bottle upright at a temperature not exceeding 25°C (77°F). Do not refrigerate or freeze the medication, as freezing can damage the pump mechanism and alter the spray characteristics.
- Light protection: Keep the bottle in its original outer carton when not in use to protect it from light exposure.
- After use: Always replace the safety clip and protective cap on the spray tip after each use. This prevents the spray nozzle from becoming clogged with dried medication residue, which could result in inaccurate dosing.
- Expiry date: Do not use Synarela after the expiry date printed on the packaging. The expiry date refers to the last day of the stated month.
- Children: Keep this medication out of the sight and reach of children at all times.
- Disposal: Do not dispose of unused medication via household waste or wastewater. Return unused or expired medication to your pharmacy for environmentally safe disposal.
What Does Synarela Contain?
Quick Answer: The active substance is nafarelin acetate (equivalent to nafarelin 2 mg/mL). Inactive ingredients include sorbitol, benzalkonium chloride (preservative), acetic acid, sodium hydroxide and/or hydrochloric acid, and purified water.
Understanding the complete composition of Synarela is important, particularly for patients with known allergies or sensitivities to specific pharmaceutical excipients. The formulation has been designed to maintain the chemical stability of nafarelin while ensuring optimal nasal absorption and long-term product shelf life.
Active Ingredient
Each milliliter of Synarela nasal spray solution contains nafarelin acetate in an amount equivalent to 2 mg of nafarelin. Each metered spray delivers approximately 200 micrograms (mcg) of nafarelin. Nafarelin is a synthetic decapeptide analogue of natural GnRH, modified to have a significantly longer duration of action and greater potency than the endogenous hormone.
Inactive Ingredients (Excipients)
- Sorbitol: Used as a stabilizing agent to maintain the physicochemical properties of the solution.
- Benzalkonium chloride: A preservative included at a concentration of 0.01 mg per spray dose. While effective at preventing microbial contamination, this ingredient may cause nasal irritation in some patients, particularly with prolonged use (see Warnings section).
- Acetic acid: Used for pH adjustment to ensure optimal nasal absorption and chemical stability.
- Sodium hydroxide and/or hydrochloric acid: Used for precise pH adjustment during manufacturing.
- Purified water: Serves as the base solvent for the formulation.
Appearance and Pack Sizes
Synarela solution is a clear, colorless to slightly yellow liquid. It is available in spray bottles with a metered-dose pump in the following pack sizes:
- 4 mL bottle (providing approximately 30 metered doses)
- 2 × 4 mL bottles (2 × 30 doses)
- 8 mL bottle (providing approximately 60 metered doses)
Not all pack sizes may be marketed in every country. Your pharmacist can advise you on the sizes available in your region.
Frequently Asked Questions About Synarela
Synarela (nafarelin) nasal spray is used for two main purposes: treating endometriosis by reducing estrogen-dependent endometrial tissue growth, and as a pre-treatment in IVF (in vitro fertilization) to suppress spontaneous ovulation and premature corpus luteum formation. For endometriosis, treatment typically lasts up to 6 months. For IVF, the duration is determined by your fertility specialist based on your individual protocol.
For endometriosis: 1 spray in one nostril in the morning and 1 spray in the other nostril in the evening (total 2 sprays per day = 400 mcg). For IVF: 1 spray in each nostril morning and evening (total 4 sprays per day = 800 mcg). The spray pump must be primed before first use by pressing 5–7 times until a fine mist appears. Always clean the spray tip before and after each use with warm water and a soft cloth to prevent clogging.
Very common side effects (affecting more than 1 in 10 users) include hot flashes, mood swings, decreased libido, headache, runny nose, acne, muscle pain, vaginal dryness, decreased breast size, weight gain, seborrhoeic eczema, and edema. Most of these are a consequence of the estrogen-suppressing effect and typically resolve after treatment is discontinued.
No. Synarela must not be used during pregnancy as there is a risk of harm to the developing fetus. Non-hormonal contraception (condoms or diaphragm) must be used throughout the treatment period. If you suspect you are pregnant, stop taking Synarela immediately and contact your doctor. It is also unknown whether nafarelin passes into breast milk, so breastfeeding is not recommended during treatment.
Treatment of endometriosis with Synarela should not exceed 6 months. This time limit exists because prolonged estrogen suppression can lead to a clinically significant decrease in bone mineral density. Studies have shown that bone density typically returns to pre-treatment levels within approximately 6 months after completing therapy. Your doctor will assess whether re-treatment is appropriate after a suitable recovery period.
If you sneeze during or immediately after spraying Synarela, the dose may have been expelled from the nasal cavity and may be insufficient. In this case, administer one additional spray to ensure you receive the complete therapeutic dose. Do not take a double dose at the next scheduled time to compensate.
References
This article is based on the following international medical guidelines, regulatory documents, and peer-reviewed sources:
- European Medicines Agency (EMA). Nafarelin – Summary of Product Characteristics. Updated 2024. Available at: www.ema.europa.eu
- U.S. Food and Drug Administration (FDA). Synarel (nafarelin acetate) Prescribing Information. Reference ID: FDA-approved labeling. Available at: www.accessdata.fda.gov
- Brown J, Crawford TJ, Datta S, Prentice A. Oral contraceptives for pain associated with endometriosis. Cochrane Database of Systematic Reviews. 2018;5(5):CD001019. doi:10.1002/14651858.CD001019.pub3
- European Society of Human Reproduction and Embryology (ESHRE). Endometriosis Guideline. 2022. Available at: www.eshre.eu
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List (2023). Geneva: World Health Organization; 2023.
- British National Formulary (BNF). Nafarelin. National Institute for Health and Care Excellence. Available at: bnf.nice.org.uk
- Dlugi AM, Miller JD, Knittle J, et al. Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Fertility and Sterility. 1990;54(3):419-427.
- Surrey ES, Hornstein MD. Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up. Obstetrics & Gynecology. 2002;99(5 Pt 1):709-719.
- Olive DL, Lindheim SR, Pritts EA. GnRH agonists and antagonists in reproductive medicine. Expert Opinion on Pharmacotherapy. 2003;4(5):727-741.
- Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis: a committee opinion. Fertility and Sterility. 2014;101(4):927-935.
Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians in gynecology, reproductive medicine, and clinical pharmacology. Our editorial process follows the GRADE evidence framework, and all medical content is independently reviewed according to international clinical guidelines from the WHO, EMA, ESHRE, and FDA.
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