Drug Interactions between celecoxib / tramadol and procaine

MONITOR: Coadministration of local anesthetics with other oxidizing agents that can also induce methemoglobinemia such as antimalarials (e.g., chloroquine, quinine), nitrates and nitrites, sulfonamides, aminosalicylic acid, dimethyl sulfoxide (DMSO), metoclopramide, nitrofurantoin, phenazopyridine, phenobarbital, and phenytoin may increase the risk. Additional risk factors include very young age (e.g., infants less than 6 months), cardiac or pulmonary disease, genetic predisposition, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Data surrounding the incidence of methemoglobinemia are agent-specific and, in many instances, have primarily been reported in case reports and/or in overdose situations.

MANAGEMENT: Monitoring for signs and symptoms of methemoglobinemia is recommended if local anesthetics must be used with other methemoglobin-inducing agents. Signs and symptoms of methemoglobinemia may occur immediately or hours after drug exposure. Patients or their caregivers should be advised to seek medical attention if they notice signs and symptoms of methemoglobinemia (e.g., cyanotic skin discoloration, abnormal blood coloration, 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.

MONITOR: Coadministration with celecoxib may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by celecoxib.

MANAGEMENT: Caution is advised if celecoxib must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever celecoxib is added to or withdrawn from therapy.