Synarel Drug Interactions: What to Avoid and What to Tell Your Doctor

Before starting Synarel (nafarelin acetate), it's essential to review all medications, supplements, and over-the-counter products you currently take. While Synarel has fewer pharmacokinetic drug-drug interactions than many medications (because it's a peptide degraded by enzymes, not the cytochrome P-450 system), it still has important clinical interactions that can affect safety or effectiveness.

Nasal Decongestant Sprays (Oxymetazoline, Xylometazoline, etc.)

Interaction type: Reduced absorption

The most directly relevant interaction for Synarel is with topical nasal decongestant sprays (such as Afrin/oxymetazoline). These products can affect the nasal mucosa in ways that reduce Synarel's absorption — meaning you may not get the full dose.

What to do: If you need a nasal decongestant spray, use it at least 2 hours after your Synarel dose — not before. This allows Synarel to be absorbed first. Oral decongestants (pills) are generally not affected by this interaction.

SSRIs (Selective Serotonin Reuptake Inhibitors)

Interaction type: Increased seizure risk

Postmarketing reports have linked GnRH agonists including nafarelin to convulsions, particularly when used alongside SSRIs such as fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), or escitalopram (Lexapro). The precise mechanism isn't fully understood, but both classes of drugs affect neurological function in ways that may lower the seizure threshold.

What to do: Tell your doctor if you are taking any SSRI antidepressant before starting Synarel. This does not necessarily mean you can't take both — many patients do — but your doctor needs to know and will monitor you more closely for any neurological symptoms.

Bupropion (Wellbutrin, Aplenzin, Zyban)

Interaction type: Increased seizure risk

Bupropion (an antidepressant and smoking-cessation medication) is specifically mentioned in the Synarel prescribing information as a medication that, when combined with GnRH agonists, has been associated with reports of convulsions. Bupropion itself lowers the seizure threshold, and this risk may be additive with Synarel.

What to do: Inform your doctor if you are taking bupropion for depression, SAD, or to quit smoking. They will evaluate the risk-benefit ratio and may recommend an alternative antidepressant during Synarel treatment.

Hormonal Contraceptives

Interaction type: Reduced contraceptive efficacy

Synarel suppresses the hormonal system that hormonal contraceptives (pills, patches, rings, implants, injections) depend on to work. As a result, hormonal contraceptives may not be effective for preventing pregnancy while you are taking Synarel.

What to do: Use a non-hormonal form of contraception during Synarel treatment — such as condoms, a copper IUD (Paragard), a diaphragm, or a cervical cap with spermicide. Do not rely on oral contraceptive pills, the patch, the ring, or Depo-Provera for pregnancy prevention during treatment.

Other Medications and Lab Tests

Synarel can interfere with certain lab tests, including tests for pituitary gonadotropic and gonadal functions. Always tell lab personnel and all your doctors that you are taking Synarel before any hormonal testing.

Additionally, if you are prescribed any new medication while on Synarel — including over-the-counter products — always mention that you are taking nafarelin. Because it's an intranasal specialty drug, prescribers who are not familiar with your full medication list may not know to check for interactions.

What to Tell Your Doctor Before Starting Synarel

Before your first Synarel dose, tell your prescribing doctor about:

All prescription medications, including antidepressants (SSRIs, SNRIs, bupropion), hormonal contraceptives, and any seizure medications

All over-the-counter medications, including nasal decongestant sprays (Afrin, Flonase, Nasacort)

All vitamins, minerals, herbal supplements, and dietary supplements

Any personal or family history of seizures or epilepsy

Known allergies to GnRH analogs (goserelin, leuprolide, histrelin, triptorelin)

For more details on what to watch for during treatment, see our complete guide to Synarel side effects.

For a full overview of the medication, see our complete Synarel guide.