Drug Interactions between AccessPak for HIV PEP Expanded with Viracept and Nuedexta

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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CONTRAINDICATED: Coadministration with nelfinavir may significantly increase the plasma concentrations of amiodarone and quinidine. The proposed mechanism is nelfinavir inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of these antiarrhythmic agents. Although clinical data are lacking, the interaction could conceivably lead to serious and/or life-threatening reactions including QT interval prolongation and ventricular arrhythmias such as ventricular tachycardia and torsade de pointes.

MANAGEMENT: The use of nelfinavir with amiodarone or quinidine is considered contraindicated.

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MONITOR: Coadministration of tenofovir with other drugs that are also eliminated by active tubular secretion may result in increased plasma concentrations of tenofovir and/or the coadministered drug(s) due to competition for renal excretion. Drugs that are thought to undergo active tubular secretion include acyclovir, amiloride, cidofovir, cimetidine, flecainide, ganciclovir, metformin, midodrine, procainamide, quinidine, ranitidine, triamterene, valacyclovir, and valganciclovir.

MANAGEMENT: Patients receiving tenofovir in combination with other drugs that undergo active tubular secretion should be monitored for excessive pharmacologic effects of all drugs, and the dosages adjusted as necessary. Because tenofovir is associated with dose-related nephrotoxicity, especially proximal renal tubulopathy, renal function tests including serum creatinine, serum phosphorous, estimated creatinine clearance, urine glucose, and urine protein should be performed prior to and during therapy. Patients with renal insufficiency at baseline or during treatment may require dosage adjustment in accordance with the manufacturer's product labeling. Persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may also be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in at-risk patients.

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