Vyleesi Side Effects: What to Expect and When to Call Your Doctor

Before starting any new medication, knowing what side effects to expect — and which ones require medical attention — is essential. Vyleesi (bremelanotide) has a well-documented side effect profile from its clinical trials, and most side effects are manageable. But there are a few important warnings worth knowing upfront.

Here's everything you need to know about Vyleesi side effects in plain language.

Most Common Side Effects of Vyleesi

These are the side effects reported most frequently in clinical trials (more than 4% of patients):

• Nausea (40%): The most common side effect, especially with the first injection. Nausea can last 2 hours or more. Importantly, nausea usually improves significantly with the second dose. An anti-emetic (nausea medication) can be prescribed by your doctor to help if needed.
• Flushing (20%): A warm, reddening sensation in the face, neck, or chest. Usually mild and temporary.
• Injection site reactions (13%): Redness, bruising, or mild pain at the site of the injection in the abdomen or thigh. Rotating injection sites can help.
• Headache (11%): Mild to moderate headache following injection. Typically resolves on its own.
• Vomiting: Occurs in some patients, often alongside nausea. If severe or persistent, contact your provider.

Serious Side Effects to Know About

While most Vyleesi side effects are manageable, there are three important warnings from the official prescribing information:

• Transient increase in blood pressure / decrease in heart rate: Vyleesi temporarily raises blood pressure and lowers heart rate after each dose, with effects usually resolving within 12 hours. For this reason, Vyleesi is NOT recommended in patients at high risk for cardiovascular disease and is CONTRAINDICATED in patients with uncontrolled hypertension or known cardiovascular disease.
• Focal hyperpigmentation (1%): About 1% of patients who received up to 8 doses per month developed darkening of the skin (particularly the face, gums/gingiva, and breasts). Those with darker skin complexions are at higher risk. The darkening may not fully resolve after stopping Vyleesi. If you notice skin color changes, contact your doctor.
• Liver injury (rare): Rare cases of clinically apparent liver injury have been reported in patients using bremelanotide. Seek care if you develop yellowing of the skin/eyes, dark urine, or significant fatigue — these could indicate liver problems.

Who Should NOT Use Vyleesi

Vyleesi is contraindicated (should not be used) in patients who have:

• Uncontrolled hypertension (high blood pressure)
• Known cardiovascular disease
• Pregnancy — Vyleesi may cause fetal harm, and effective contraception is required while using it

How to Manage Nausea (the Most Common Problem)

Since nausea is the leading reason patients discontinue Vyleesi, here are practical tips to manage it:

• Ask your doctor to prescribe an anti-emetic (such as ondansetron/Zofran) to take before your first few doses
• Eat a light snack before injecting — an empty stomach can worsen nausea
• Stay hydrated and rest after injection while the medication takes effect
• Give it at least 2–3 uses before deciding it's not tolerable — most patients report nausea improves with subsequent doses

When to Call Your Doctor

Contact your healthcare provider if you experience:

• Severe or persistent nausea that doesn't improve after 2–3 uses
• New or worsening darkening of skin on your face, gums, or breasts
• Chest pain, severe headache, or shortness of breath following injection
• Yellowing of skin or eyes, dark urine, or significant fatigue (possible liver symptoms)
• Missed period or suspected pregnancy — discontinue Vyleesi immediately if pregnancy is suspected

For a full list of medications to avoid while taking Vyleesi, see our guide to Vyleesi drug interactions.

Once you're comfortable with the side effect profile and ready to fill your prescription, medfinder can help you find a specialty pharmacy near you that stocks Vyleesi.