Lidocaine + Prilocaine + Tropicamide + Phenylephrine + Lidocaine

3 documented mechanisms

This source documents more than one distinct mechanism for this pair. Each is shown with its own effect, advice and sources rather than merged into one.

1. Mechanism 1: Synergy

   Major

   via Lidocaine and Prilocaine

   What happens

   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, acetaminophen, aminosalicylic acid, dapsone, dimethyl sulfoxide, flutamide, metoclopramide, nitrofurantoin, phenazopyridine, phenobarbital, phenytoin, and rasburicase may increase the risk.

   What to do

   Prilocaine should be used with caution in the presence of other methemoglobin-inducing drugs. Patients should be closely monitored to ensure adequate perfusion and oxygenation during treatment with prilocaine. Methemoglobin levels should be monitored and oxygen administered whenever possible. 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.

   6 sources

   1. "Product Information. Citanest Plain (prilocaine)" Astra-Zeneca Pharmaceuticals, Wilmingtoon, DE.
   2. Cerner Multum, Inc. "Australian Product Information." O 0
   3. Skold A, Cosco DL, Klein R "Methemoglobinemia: pathogenesis, diagnosis, and management." South Med J 104 (2011): 757-61
   4. Guay J "Methemoglobinemia related to local anesthetics: a summary of 242 episodes." Anesth Analg 108 (2009): 837-45
   5. Agencia Española de Medicamentos y Productos Sanitarios Healthcare "Centro de información online de medicamentos de la AEMPS - CIMA. Available from: URL: https://cima.aemps.es/cima/publico/home.html." ([2018]):
   6. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

2. Mechanism 2: Synergy

   Major

   via Lidocaine and Prilocaine

   What happens

   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.

   What to do

   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.

   7 sources

   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

3. Mechanism 3: Unknown

   Listed, not described

   via Lidocaine and Tropicamide

   The source lists this pair here and publishes no description, mechanism or citation for it.

   No sources recorded

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• Everything for Lidocaine + Prilocaine
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