DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE

Dextromethorphan hydrobromide and quinidine sulfate contains dextromethorphan and quinidine, both of which are metabolized primarily by liver enzymes. Quinidine’s primary pharmacological action in dextromethorphan hydrobromide and quinidine sulfate is to competitively inhibit the metabolism of dextromethorphan catalyzed by CYP2D6 in order to increase and prolong plasma concentrations of dextromethorphan [see Warnings and Precautions ( 5.4 ), ( 5.8 ), and Clinical Pharmacology ( 12.5 )] . Studies...

The efficacy of dextromethorphan hydrobromide and quinidine sulfate was demonstrated in one trial in patients with pseudobulbar affect (PBA). These patients had underlying amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). Other trials at higher doses (dextromethorphan 30 mg/quinidine 30 mg) provided supportive evidence. In the dextromethorphan hydrobromide and quinidine sulfate trial, patients with PBA were randomized to receive dextromethorphan hydrobromide and quinidine sulfate dextromethorphan 20 mg/quinidine 10 mg, (N=107), dextromethorphan 30 mg/quinidine 10 mg (N=110), or p...

A total of 946 patients participated in four Phase 3 controlled and uncontrolled PBA studies and received at least one dose of the combination product of dextromethorphan/quinidine in various strengths at the recommended or higher than the recommended dose. Of those patients, 393 patients were exposed for at least 180 days and 294 patients were exposed for at least one year. Median exposure was 168 days. Controlled trials enrolled only patients with either ALS or MS. Uncontrolled studies enrolle...

Concomitant use with quinidine, quinine, or mefloquine. ( 4.1 ) Patients with a history of quinidine, quinine or mefloquine-induced thrombocytopenia, hepatitis, or other hypersensitivity reactions. ( 4.2 ) Patients with known hypersensitivity to dextromethorphan. ( 4.2 ) Use with an MAOI or within 14 days of stopping an MAOI. Allow 14 days after stopping dextromethorphan hydrobromide and quinidine...

Thrombocytopenia or other hypersensitivity reactions: Discontinue if occurs. ( 5.1 ) Hepatitis: Discontinue if occurs. ( 5.2 ) QT Prolongation: Monitor ECG if concomitant use of drugs that prolong QT interval cannot be avoided or if concomitant CYP3A4 inhibitors used. ( 5.3 ) Left ventricular hypertrophy (LVH) or left ventricular dysfunction (LVD): Monitor ECG in patients with LVH or LVD. ( 5.3 ) CYP2D6 substrate: Dextromethorphan hydrobromide and quinidine sulfate inhibits CYP2D6. Accumulation ...

7 DRUG INTERACTIONS Desipramine: Exposure increases 8-fold. Reduce desipramine dose and adjust based on clinical response. ( 7.5 , 12.4 ) Paroxetine: Exposure increases 2-fold. Reduce paroxetine dose and adjust based on clinical response. ( 7.5 , 12.4 ) Digoxin: Increased digoxin substrate plasma concentration may occur. ( 7.6 ) 7.1 MAOIs Do not use dextromethorphan hydrobromide and quinidine sulf...