Drug Interactions between MY-E and Nuedexta

GENERALLY AVOID: Coadministration of quinidine with some macrolide antibiotics (e.g., clarithromycin, erythromycin, troleandomycin) may increase the risk of ventricular arrhythmias including torsade de pointes and sudden death due to additive effects on the QT interval. In addition, the clearance of quinidine may be reduced. Data are available for erythromycin. In six healthy male volunteers, erythromycin 250 mg given orally four times a day reduced the median total clearance and peak plasma concentration (Cmax) of a single 200 mg oral dose of quinidine sulfate by 34% and 39%, respectively. The mechanism may involve enhanced absorption as well as reduced clearance of quinidine due to inhibition of both intestinal P-glycoprotein efflux transporter and hepatic/intestinal CYP450 3A4 isoenzyme by erythromycin. A case report describes a 74-year-old patient whose serum trough quinidine levels increased by 50% two days after starting erythromycin lactobionate 500 mg every 6 hours with ceftriaxone 1 gram daily. The patient later developed torsades de pointes arrhythmia when the erythromycin dosage was doubled and metronidazole was added. A 25% reduction in the quinidine dose was required, and erythromycin and metronidazole were subsequently replaced with doxycycline and ciprofloxacin. Another case of torsades de pointes, followed by cardiac arrest, was reported in a 95-year-old patient receiving quinidine and erythromycin orally.

MANAGEMENT: The use of quinidine in combination with macrolide antibiotics should be avoided. Patients treated with these agents should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitations, irregular heartbeat, shortness of breath, or syncope.

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GENERALLY AVOID: Coadministration with potent CYP450 2D6 inhibitors (e.g., quinidine, terbinafine) may significantly increase the plasma concentrations of dextromethorphan in patients who are extensive metabolizers of this isoenzyme (approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent). The proposed mechanism is inhibition of the CYP450 2D6-mediated O-demethylation of dextromethorphan. Studies in humans have shown an increase in systemic exposure of dextromethorphan of up to 43-fold when given concurrently with quinidine. Increased plasma concentrations increase the risk of dextromethorphan-related adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome. However, this interaction has also been used clinically, with dextromethorphan in combination with quinidine indicated by some authorities for the treatment of pseudobulbar affect. Data evaluating the impact of this interaction in patients who are poor metabolizers of CYP450 2D6 are limited; most studies include extensive metabolizers of this isoenzyme. It is expected that poor metabolizers would have elevated dextromethorphan levels without concurrent quinidine

MANAGEMENT: The combination of dextromethorphan with potent CYP450 2D6 inhibitors should be generally avoided. Some manufacturers consider the concomitant use of dextromethorphan and selective serotonin reuptake inhibitors contraindicated. If use is considered necessary, the patient should be monitored for signs of dextromethorphan adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome, and advised to notify their health care professional if these adverse effects develop or worsen. Dose reduction of dextromethorphan may also be required.

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