Bupivacaine and epinephrine and Lidocaine and prilocaine interaction

Bupivacaine and epinephrine and Lidocaine and prilocaine: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Bupivacaine and epinephrine (Marcaine) label · effective 2026-05-29

Major

If coadministration of other local anesthetics with MARCAINE / MARCAINE WITH EPINEPHRINE cannot be avoided, monitor patients for neurologic and cardiovascular effects related to local anesthetic systemic toxicity [see Dosage and Administration (2.1) , Warnings and Precautions (5.2) ] .

Drug interactionsby drug classView label on DailyMed
Moderate

…Methemoglobinemia: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic…

Drug interactionsnames Lidocaine and prilocaineView label on DailyMed
Moderate

Monitor for neurologic and cardiovascular effects when additional local anesthetics are administered.

Drug interactionsby drug classView label on DailyMed
Moderate

Drugs Associated with Methemoglobinemia Patients who are administered MARCAINE / MARCAINE WITH EPINEPHRINE are at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics [see Warnings and Precautions (5.3) ] .

Drug interactionsby drug classView label on DailyMed

From the Lidocaine and prilocaine (Oraqix) label · effective 2026-04-21

Moderate

…Examples of Drugs Associated with Methemoglobinemia: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, isofamide, rasburicase Antibiotics…

Drug interactionsnames Bupivacaine and epinephrineView label on DailyMed
Moderate

Other Local Anesthetics or Agents Structurally Related to Local Anesthetics Oraqix should be used with caution in combination with dental injection anesthesia, other local anesthetics, or agents structurally related to local anesthetics, e.g., Class 1 antiarrhythmics such as tocainide and mexiletine, as the toxic effects of these drugs are likely to be additive…

Drug interactionsby drug classView label on DailyMed
Minor

Other local anesthetics or agents structurally related to local anesthetics ( 7.1 )

Drug interactionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.