Basic Information
ID DDInter1620 and DDInter1518
Interaction Prilocaine can cause dose-related methemoglobin formation via its ortho-toluidine metabolite. Coadministration with other oxidizing agents that can also induce methemoglobinemia including other local anesthetics (e.g., benzocaine, lidocaine),antimalarials (e.g., chloroquine, primaquine, quinine, tafenoquine), nitrates and nitrites, sulfonamides, aminosalicylic acid, dapsone, dimethyl sulfoxide, flutamide, metoclopramide, nitrofurantoin, phenazopyridine, phenobarbital, phenytoin, and rasburicase may increase the risk.
Management Concomitant use of topical lidocaine-prilocaine formulations with other methemoglobin-inducing agents should be avoided in infants younger than 12 months of age. Caution is advised when used in other patients. Signs and symptoms of methemoglobinemia may be delayed some hours after drug exposure. Patients or their caregivers should be advised to seek medical attention if they notice signs and symptoms of methemoglobinemia such as slate-grey cyanosis in buccal mucous membranes, lips, and nail beds; nausea; headache; dizziness; lightheadedness; lethargy; fatigue; dyspnea; tachypnea; tachycardia; palpitation; anxiety; and confusion. In severe cases, patients may progress to central nervous system depression, stupor, seizures, acidosis, cardiac arrhythmias, syncope, shock, coma, and death. Methemoglobinemia should be considered if central cyanosis is unresponsive to oxygen. Calculated oxygen saturation and pulse oximetry are generally not accurate in the setting of methemoglobinemia. The diagnosis can be confirmed by an elevated methemoglobin level of at least 10% using co-oximetry. Methemoglobin concentrations greater than 10% of total hemoglobin will typically cause cyanosis, and levels over 70% are frequently fatal. However, symptom severity is not always related to methemoglobin levels. Mild cases often respond to withdrawal of offending agents and symptomatic support. If patient does not respond to administration of oxygen, clinically significant or symptomatic methemoglobinemia can be treated with methylene blue 1 to 2 mg/kg by slow intravenous injection over 5 to 10 minutes, which may be repeated within 30 to 60 minutes if necessary. Higher dosages of methylene blue (usually greater than 7 mg/kg) should be avoided, as it can paradoxically exacerbate methemoglobinemia. Additionally, methylene blue is ineffective and can cause hemolytic anemia in patients with G6PD deficiency. These patients may be treated with exchange transfusion, dialysis, and/or hyperbaric oxygenation in addition to symptomatic support.
References [1] "Product Information. Emla (lidocaine-prilocaine topical)." Astra-Zeneca Pharmaceuticals (2022): [2] Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0 [3] Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006): [4] Cerner Multum, Inc. "Australian Product Information." O 0 [5] Agencia Espa帽ola de Medicamentos y Productos Sanitarios Healthcare "Centro de informaci贸n online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008): [6] Guay J "Methemoglobinemia related to local anesthetics: a summary of 242 episodes." Anesth Analg 108 (2009): 837-45 [7] Skold A, Cosco DL, Klein R "Methemoglobinemia: pathogenesis, diagnosis, and management." South Med J 104 (2011): 757-61
Alternative for Ropivacaine N01B
Prilocaine Meloxicam Articaine
Alternative for Prilocaine N01B
Tetracaine Ropivacaine Chloroprocaine Etidocaine Meloxicam Procaine
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.