DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE
Clinical safety rating: safe
Inhibits CYP2D6 and CYP3A4 increasing levels of many drugs Can cause cinchonism and thrombocytopenia.
Dextromethorphan is an uncompetitive NMDA receptor antagonist and sigma-1 receptor agonist; quinidine is a CYP2D6 inhibitor that increases dextromethorphan bioavailability.
| Metabolism | Dextromethorphan is primarily metabolized by CYP2D6 to dextrorphan; quinidine is a potent CYP2D6 inhibitor at low doses. |
| Excretion | Renal: quinidine 15-25% unchanged, dextromethorphan <1% unchanged; biliary/fecal: quinidine metabolites ~5%, dextromethorphan metabolites ~60-80% as dextrorphan conjugates |
| Half-life | Dextromethorphan: 2-4 hours (extensive metabolizers); quinidine: 6-8 hours (inhibits CYP2D6, prolonging dextromethorphan half-life in poor metabolizers to >20 hours) |
| Protein binding | Dextromethorphan: ~60-70% (albumin); quinidine: 80-90% (albumin, alpha-1-acid glycoprotein) |
| Volume of Distribution | Dextromethorphan: 5-6 L/kg; quinidine: 2-3 L/kg |
| Bioavailability | Oral: dextromethorphan ~11% (extensive first-pass metabolism; increased to >50% when coadministered with quinidine); quinidine ~70-80% |
| Onset of Action | Oral: pseudobulbar affect symptom relief within 1-2 weeks; central effects (cough suppression) in 15-30 minutes |
| Duration of Action | Pseudobulbar affect: sustained during chronic dosing; cough suppression: 3-6 hours |
One capsule (dextromethorphan 20 mg/quinidine 10 mg) orally once daily, with a maximum dose of two capsules per day.
| Dosage form | CAPSULE |
| Renal impairment | For creatinine clearance (CrCl) 30–59 mL/min: reduce dose to one capsule once daily. For CrCl <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B or C: not recommended (quinidine is extensively metabolized by the liver). |
| Pediatric use | Safety and efficacy in pediatric patients have not been established; not recommended for use in children. |
| Geriatric use | Initiate at one capsule once daily; titrate cautiously. Monitor for QT prolongation and anticholinergic effects. Lower doses may be required due to age-related renal and hepatic decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Inhibits CYP2D6 and CYP3A4 increasing levels of many drugs Can cause cinchonism and thrombocytopenia.
| FDA category | Animal |
| Breastfeeding | Dextromethorphan: Likely excreted in breast milk in low amounts; M/P ratio not reported. Quinidine: Excreted in breast milk; M/P ratio approximately 0.71. Potential for infant quinidine toxicity (cinchonism, arrhythmias). Avoid breastfeeding during maternal quinidine therapy. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show quinidine sulfate associated with increased risk of fetal malformations at high doses. Second/third trimester: Dextromethorphan hydrobromide not associated with major malformations; quinidine sulfate may cause fetal bradycardia and hypoglycemia due to quinidine's antiarrhythmic effects. Overall: No adequate human studies; use only if benefit outweighs risk. |
■ FDA Black Box Warning
None.
| Common Effects | GI upset |
| Serious Effects |
["Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days.","Concomitant use with other drugs that prolong QT interval.","Known hypersensitivity to dextromethorphan or quinidine.","Complete atrioventricular block without pacemaker.","History of drug-induced torsades de pointes."]
| Precautions | ["CNS depression: may cause dizziness, somnolence; avoid alcohol.","Cardiotoxicity: quinidine may cause QT prolongation; monitor ECG.","Serotonin syndrome: risk with concurrent serotonergic drugs.","Hepatic impairment: use with caution.","Renal impairment: not recommended in severe renal disease."] |
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| Fetal Monitoring | Monitor maternal heart rate, blood pressure, and electrocardiogram (ECG) for quinidine-related arrhythmias. Fetal monitoring for bradycardia and hypoglycemia with prolonged use. Assess maternal renal and hepatic function. |
| Fertility Effects | No known effects on human fertility. Animal studies: Dextromethorphan showed no adverse effects; quinidine sulfate at high doses caused decreased spermatogenesis and fertility in male rats. |