Nafarelin Nasal Spray

Nafarelin nasal spray (brand name Synarel) is approved for two distinct conditions:

• Endometriosis (adults): Synarel nasal spray is used to relieve pain and reduce endometriotic lesions in women 18 years and older. The recommended treatment course is 6 months; retreatment is not routinely recommended.
• Central precocious puberty (CPP) in children: Synarel nasal spray is used to treat gonadotropin-dependent early puberty in children of both sexes — girls showing signs before age 8, boys before age 9. Treatment continues until the resumption of puberty is desired.

Nafarelin is a GnRH agonist — a synthetic version of the hormone the brain uses to signal the pituitary gland to release sex hormones. When used continuously, nafarelin overstimulates that signaling pathway until the pituitary gland essentially stops responding. The result is a dramatic drop in the sex hormones estrogen and testosterone. In endometriosis, lower estrogen starves the abnormal tissue causing pain. In central precocious puberty, it puts early hormonal development on pause, allowing bone growth to normalize.

Synarel nasal spray is used twice daily for endometriosis — one spray into one nostril in the morning, one spray into the other nostril in the evening. For central precocious puberty in children, it is used more frequently throughout the day, with multiple sprays into each nostril as directed by the prescriber. There are no food restrictions, but timing and technique matter:

• Tilt your head back slightly before spraying
• Wait 30 seconds between sprays
• Try not to sneeze right after using it — this reduces absorption
• If a nasal decongestant is needed, use it at least 2 hours after Synarel, not before

If you miss doses, contact your prescriber — consistent daily use is essential for the medication to work properly.

The most common side effects are largely due to the drop in sex hormone levels that the medication intentionally causes:

• Hot flashes
• Vaginal bleeding or discharge
• Mood changes — irritability, emotional swings, crying
• Acne and oily skin
• Nasal irritation or runny nose
• In children: transient breast enlargement, temporary increase in pubic hair, and body odor during the first few weeks
• Decreased bone density with extended use

Seek medical care right away for severe skin reactions (blistering or peeling rash), sudden severe headache with vomiting or vision changes, new-onset seizures, or significant worsening of depression.

• Bone loss: Synarel lowers estrogen, which reduces bone density. After 6 months of endometriosis treatment, bone density can decrease by measurable amounts. Full recovery after stopping is not guaranteed, especially with longer use or other bone-thinning risk factors.
• Psychiatric effects: Depression, mood swings, irritability, and — rarely — suicidal thoughts have been reported. Anyone with a history of depression should be closely monitored. Children treated for CPP have also experienced these effects.
• Seizures: Convulsions have been reported in some patients taking GnRH agonists, including those with no prior seizure history.
• Severe skin reactions: Rare but serious skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, AGEP) have been reported with this class of drugs. Stop Synarel and get medical care immediately if a severe rash develops.
• Increased intracranial pressure (pseudotumor cerebri): Reported in pediatric patients — watch for persistent headache, blurred or double vision, eye pain, tinnitus, or dizziness.
• Pituitary apoplexy: Rare but serious bleeding in the pituitary gland has been reported, often within the first two weeks of treatment. Symptoms include sudden severe headache, vomiting, vision changes, and confusion — seek emergency care immediately.

Formal drug interaction studies have not been conducted with nafarelin. Because nafarelin is broken down by enzymes called peptidases (not by the liver's cytochrome P-450 system), major drug interactions are not expected. However, a few practical points apply:

• Nasal decongestants: Using a decongestant within 2 hours of Synarel may reduce how much of the drug is absorbed through the nasal lining — wait at least 2 hours after Synarel before using one
• Drugs associated with seizures (e.g., bupropion, SSRIs): Postmarketing reports note that convulsions have occurred in patients on these medications alongside GnRH agonists — inform your prescriber of all medications you take

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Pregnancy: Do not use Synarel if you are pregnant or may become pregnant — it can cause fetal harm. Rule out pregnancy before starting. Synarel is not a reliable contraceptive, so use a nonhormonal birth control method during treatment.
• Breastfeeding: Synarel is contraindicated while breastfeeding.
• Undiagnosed vaginal bleeding: Do not use until the cause of any unexplained vaginal bleeding is identified.
• Allergy to GnRH or GnRH analogs: Do not use if you have a known hypersensitivity to this drug class.
• History of depression or psychiatric illness: Tell your doctor — depression can worsen during treatment, and close monitoring is recommended.
• History of seizures or brain/nervous system conditions: Tell your doctor before starting, as seizure risk may be increased.
• Children: Diagnosis of CPP must be confirmed thoroughly before starting Synarel. Compliance is critical, especially in the first 6–8 weeks; caregivers are often asked to administer the doses.
• Bone health: If you have risk factors for bone loss, discuss this with your doctor before starting — and if retreatment is ever considered after endometriosis therapy, bone density should be assessed first.

In animal studies, very large doses of nafarelin did not cause harmful effects. There is currently no clinical evidence of dangerous effects from accidental overdose of GnRH analogs in humans. If you suspect an overdose, contact your local poison control center or seek medical attention.

Nafarelin initially triggers a brief spike in pituitary hormones (LH and FSH), which can temporarily stimulate the sex glands — this is why some children experience a short-lived increase in pubic hair or vaginal bleeding in the first few weeks of treatment. With continued use, however, the pituitary gland stops responding, and sex hormone levels fall to prepubertal or near-menopausal ranges within about 4 weeks. In children with CPP, this results in a halt to premature secondary sexual development and a slowing of abnormal bone age advancement. In women with endometriosis, the low-estrogen state shrinks endometriotic tissue and reduces pain.

Nafarelin is absorbed quickly after nasal administration — peak blood levels are typically reached within 10 to 45 minutes. The drug has a short half-life of roughly 2.5 to 3 hours, meaning it clears the body relatively quickly, which is why twice-daily (or more frequent) dosing is needed. It is broken down mainly by peptide-cleaving enzymes rather than the liver, and its byproducts are eliminated through both urine and feces. Nasal congestion does not significantly affect how much of the drug is absorbed.

Store upright at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) . Protect from light.