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

Before using Relador (lidocaine 2.5%/prilocaine 2.5% topical cream), it's important to tell your healthcare provider about all the medications, supplements, and herbal products you take. While Relador is generally used once before a procedure and does not have the same interaction concerns as a daily prescription drug, some medications can dangerously increase your risk of a serious reaction called methemoglobinemia. Here's what you need to know.

The Most Important Category: Methemoglobin-Inducing Drugs

Methemoglobinemia is the most serious risk associated with Relador. It occurs when the iron in hemoglobin is oxidized to a form (ferric/Fe3+) that cannot carry oxygen. Both lidocaine and prilocaine can cause this, with prilocaine carrying the higher methemoglobin-forming potential. Combining Relador with other drugs that also promote methemoglobin formation multiplies this risk significantly.

Drugs with major interaction potential (significantly increased methemoglobinemia risk):

Dapsone: An antibiotic used for leprosy, dermatitis herpetiformis, and acne. Dapsone is a potent methemoglobin inducer — the combination with Relador carries significant risk of serious methemoglobinemia.

Nitrofurantoin: A common urinary tract infection antibiotic. Concurrent use with Relador can increase methemoglobin levels.

Sulfasalazine: Used for inflammatory conditions like ulcerative colitis and rheumatoid arthritis. Additive methemoglobin risk with prilocaine.

Aminosalicylic acid (para-aminosalicylic acid): An antibiotic used for tuberculosis.

Chloroquine and primaquine: Antimalarial drugs with known methemoglobin-inducing potential.

Quinine: Used for malaria and leg cramps. Moderate methemoglobin-inducing potential.

Seizure Medications That Interact With Relador

Certain anti-epileptic drugs can interact with Relador both through methemoglobin mechanisms and CNS effects:

Phenobarbital: Increases methemoglobin formation when used with prilocaine.

Phenytoin (Dilantin): Additive methemoglobin potential; may also compound central nervous system depression if systemic lidocaine toxicity occurs.

Valproic acid: Some evidence of additive methemoglobin effects.

Cardiac Medications: Additive Effects

Lidocaine is also a Class Ib antiarrhythmic drug. When used topically, systemic absorption is minimal with correct application. However, if combined with cardiac medications that affect heart rhythm, there is a theoretical risk of additive effects:

Class III antiarrhythmics (amiodarone, sotalol): Additive cardiac electrophysiology effects; clinically relevant mainly with excessive absorption.

Nitroglycerin: Nitrates have methemoglobin-inducing potential and can combine with prilocaine to elevate methemoglobin levels.

Other Local Anesthetics

Combining Relador with other local anesthetics (such as injectable lidocaine, bupivacaine, or topical benzocaine/tetracaine used at the same time) can result in additive systemic toxicity. This is most relevant in procedural settings where your doctor may also use an injectable anesthetic in addition to your Relador prep. Always inform all providers about any topical anesthetics you've applied before a procedure.

Chemotherapy Agents

Several chemotherapy drugs have methemoglobin-inducing properties and should be flagged when using Relador:

Cyclophosphamide and ifosfamide: alkylating agents with methemoglobin potential

Flutamide: an anti-androgen used for prostate cancer

Hydroxyurea: used for sickle cell disease and some leukemias

Metoclopramide

Metoclopramide (Reglan), a medication used for nausea and gastroparesis, has methemoglobin-inducing properties. Patients on metoclopramide should inform their provider before Relador application.

Acetaminophen (Tylenol)

Acetaminophen (Tylenol) has a minor interaction — some evidence that concurrent use may slightly increase methemoglobin formation. This is generally considered a low-risk interaction for standard doses, but it is listed as an interaction to be aware of.

What to Tell Your Provider Before Using Relador

Before using Relador, tell every healthcare provider who will be involved in your care:

All prescription and OTC medications you take

Any herbal supplements, vitamins, or natural remedies

History of G6PD deficiency, methemoglobinemia, or anemia

Any heart or lung conditions

Pregnancy or breastfeeding status

For a complete overview of Relador side effects, see Relador side effects: what to expect. And for general information on how Relador works and how to use it, see what is Relador.