Drug Interactions between AgonEaze and celecoxib

Some of the medication in prilocaine topical is absorbed through the skin into the bloodstream and may cause interactions with other medications such as lidocaine topical. When used together, this combination may increase the risk of methemoglobinemia, a condition that can lead to oxygen deprivation in tissues and vital organs due to reduced oxygen-carrying capacity of the blood. Individuals may be more susceptible to developing methemoglobinemia during treatment with these medications if they are very young (especially neonates and infants) or have anemia, diseases of the heart or lungs, blood circulation disorders, liver cirrhosis, shock, sepsis, and certain genetic predispositions such as NADH cytochrome-b5 reductase deficiency, glucose-6-phosphate dehydrogenase deficiency, and hemoglobin M. In addition, excessive use of prilocaine topical such as application of large doses or on larger than recommended areas, as well as use on inflamed or abraded areas or broken skin, can increase absorption and result in high blood levels of the medication. Close medical supervision is necessary when medications that can cause methemoglobinemia are used together. Signs and symptoms of methemoglobinemia may be delayed by several hours after treatment with prilocaine topical. Patients (or their caregivers) should seek immediate medical attention if they develop a gray discoloration of the skin, mouth, or nail bed; nausea; headache; dizziness; lightheadedness; fatigue; shortness of breath; rapid or shallow breathing; a rapid heartbeat; palpitation; anxiety; or confusion. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Consumer information for this interaction is not currently available.

MONITOR: Some topical anesthetics can be systemically absorbed and cause methemoglobinemia, particularly when applied to mucous membranes. Coadministration with other oxidizing agents that can also induce methemoglobinemia such as injectable local anesthetics, 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. Additional risk factors include very young age (e.g., infants less than 6 months); application to inflamed/abraded areas or broken skin; anemia; cardiac or pulmonary disease; peripheral vascular disease; liver cirrhosis; shock; sepsis; acidosis; and genetic predisposition (e.g., NADH cytochrome-b5 reductase deficiency; glucose-6-phosphate dehydrogenase (G6PD) deficiency; hemoglobin M). There have been rare reports of significant methemoglobinemia associated with administration of topical anesthetics, primarily following application to mucous membranes prior to dental procedures or via the oropharyngeal route prior to procedures such as intubation, laryngoscopy, bronchoscopy, and endoscopy. Very rarely, methemoglobinemia has also been reported with use of anesthetic throat lozenges.

MANAGEMENT: Caution is advised when topical anesthetics are used concomitantly with other methemoglobin-inducing agents. Clinicians should be aware of the potential for methemoglobinemia, particularly when topical anesthetics are applied to mucous membranes or given via the oropharyngeal route. 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. Experts suggest that treatment of methemoglobinemia varies from supplemental oxygen and symptom support to the administration of methylene blue, depending on severity of symptoms and/or the presence of G6PD deficiency. Institutional guidelines and/or individual product labeling should be consulted for further guidance.