Drug Interactions between fentanyl / ropivacaine and Metozolv ODT

MONITOR: By diminishing gastrointestinal motility, narcotic analgesics may antagonize the pharmacologic effects of gastrointestinal prokinetic agents. In addition, concomitant use may increase central nervous system effects such as sedation, dizziness, confusion, and mental depression.

MONITOR: Gastrointestinal prokinetic agents may alter the absorption characteristics of some controlled release narcotic analgesic preparations. In a study of 20 patients undergoing surgery, peak plasma concentration (Cmax) of morphine was reached more quickly in patients who received a 20 mg dose of sustained-release morphine with 20 mg metoclopramide compared to patients who received morphine alone, although the actual Cmax and systemic exposure (AUC) were not significantly altered. Both the degree and the rate of onset of sedation were also increased in the metoclopramide group, which may have been partially due to additive pharmacodynamic effects of the drugs. During chronic administration, however, the clinical relevance of this interaction may be diminished due to tolerance.

MANAGEMENT: The potential for reduced efficacy of gastrokinetic agents should be considered during coadministration with opioid analgesics. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their doctor if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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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.

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