Retre-Gel Side Effects: What to Expect and When to Call Your Doctor

Retre-Gel contains 20% benzocaine, a topical local anesthetic used to numb oral tissue before dental procedures and to relieve minor mouth pain. For most people, it works quickly and causes only mild or no side effects. However, benzocaine carries a serious safety warning from the FDA regarding a rare but potentially fatal condition called methemoglobinemia. This guide explains what side effects to expect, which warning signs require immediate medical attention, and who should avoid benzocaine entirely.

Common Side Effects of Retre-Gel

Most people who use Retre-Gel experience minimal side effects. The most common reactions are local and mild:

Mild stinging or burning at the site of application — this is normal and usually passes within seconds to a minute.

Temporary numbness extending slightly beyond the application area — expected and usually brief.

Redness, mild swelling, or irritation at the application site — more common with repeated use.

Skin tenderness or itching — especially in people with sensitive skin or mild PABA sensitivity.

These side effects do not typically require treatment and resolve on their own. If any persist longer than a few hours, contact your healthcare provider.

The Most Serious Risk: Methemoglobinemia

Methemoglobinemia is a rare but serious condition in which the blood cannot carry enough oxygen. The FDA has documented over 400 cases of benzocaine-associated methemoglobinemia since 1971, with more than 75% involving life-threatening or serious outcomes. This can occur even with small amounts of benzocaine and even if the product has been used before without problems.

Signs and symptoms of methemoglobinemia typically appear within minutes to 2 hours after benzocaine use. Call 911 immediately if you notice:

Pale, gray, or blue-colored skin, lips, or nail beds

Shortness of breath or difficulty breathing

Confusion or altered mental status

Headache, lightheadedness, or dizziness

Unusually fast heartbeat (tachycardia)

Extreme fatigue or weakness

Treatment for severe methemoglobinemia requires IV methylene blue administered in an emergency setting. Do not wait — call 911 immediately if any of these symptoms appear.

Who Is at Highest Risk for Serious Side Effects?

Certain groups face a significantly higher risk of serious adverse events from benzocaine:

Infants and children under 2 years — The FDA has contraindicated benzocaine topical use in this age group. Do not use Retre-Gel for infant teething.

Elderly patients — Age-related changes in red blood cell function increase susceptibility.

Patients with G6PD deficiency, hemoglobin-M disease, or NADH-methemoglobin reductase deficiency — These inherited conditions impair the body's ability to reduce methemoglobin levels.

Patients with heart disease, asthma, COPD, or emphysema — Reduced oxygen-carrying capacity makes methemoglobinemia more dangerous.

Smokers — Smoking reduces baseline oxygen saturation and increases risk.

Allergic Reactions to Benzocaine

Benzocaine is an ester-type local anesthetic derived from para-aminobenzoic acid (PABA). People with known PABA sensitivity or allergies to other ester-type anesthetics (such as procaine or tetracaine) may experience:

Contact dermatitis (rash, redness, blistering at application site)

Hives or widespread itching

Anaphylaxis (rare but possible — swelling of throat, difficulty breathing, drop in blood pressure)

If you have had a reaction to a dental anesthetic or a topical pain reliever in the past, tell your provider before using Retre-Gel. Patients who are PABA-allergic can usually tolerate amide-type anesthetics like lidocaine.

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When to Call Your Doctor vs. Call 911

Call 911 immediately: Blue or gray lips/nails/skin; difficulty breathing; severe confusion; loss of consciousness.

Call your doctor or pharmacist: Persistent rash or irritation; symptoms that don't improve within 7 days; sore throat with fever, headache, or swollen glands.

Normal — no action needed: Brief stinging at application, temporary numbness, mild tingling.

For a full list of drug interactions to be aware of when using Retre-Gel, see our guide on Retre-Gel drug interactions. For general information about this medication, see what is Retre-Gel and how is it used.