DEXTROMETHORPHAN HYDROBROMIDE AND QUINIDINE SULFATE
Clinical safety rating
safeInhibits CYP2D6 and CYP3A4 increasing levels of many drugs Can cause cinchonism and thrombocytopenia.
Inhibits CYP2D6 and CYP3A4 increasing levels of many drugs Can cause cinchonism and thrombocytopenia.
Pseudobulbar affect (PBA) - FDA approved
GI upset
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 |
| Molecular Weight | Dextromethorphan HBr: 370.33 Da; Quinidine sulfate: 746.97 Da |
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 | Limited data; avoid use due to potential teratogenic effects (quinidine sulfate associated with fetal harm). |
| 2nd trimester | Use only if benefit outweighs risk; monitor for maternal arrhythmias. |
| 3rd trimester | Avoid near term due to risk of neonatal arrhythmias and respiratory depression. |
Clinical note
Inhibits CYP2D6 and CYP3A4 increasing levels of many drugs Can cause cinchonism and thrombocytopenia.
| FDA category | Animal |
| Placental transfer | Both drugs cross the placenta; quinidine achieves fetal serum levels 50-90% of maternal levels. |
| Breastfeeding | Both dextromethorphan and quinidine are excreted into breast milk. Quinidine levels may cause cardiac effects in the infant. Avoid breastfeeding. |
| Lactation Rating | L4 |
| 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. |
| 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. |
■ FDA Black Box Warning
None.
| Common Effects | GI upset |
| Serious Effects |
Hypersensitivity to any componentHistory of drug-induced QT prolongationConcurrent use of MAOIs or within 14 daysComplete AV blockMyasthenia gravis
| 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. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase plasma levels of quinidine, raising risk of toxicity including QT prolongation. Avoid excessive alcohol consumption as it may exacerbate CNS depression. |
| Clinical Pearls | Monitor for QT prolongation with baseline and periodic ECG, especially in patients with hypokalemia, hypomagnesemia, or bradycardia. Avoid use with CYP3A4 inhibitors (e.g., ketoconazole) or CYP2D6 inhibitors (e.g., paroxetine) due to quinidine metabolism. Quinidine is a potent CYP2D6 inhibitor; caution with concurrent CYP2D6 substrates like tricyclic antidepressants. Onset of pseudobulbar affect improvement may take weeks; titrate dose gradually. |
| Patient Advice | Take this medication exactly as prescribed; do not double doses if missed. · Avoid grapefruit juice as it may increase side effects. · Report any signs of irregular heartbeat (palpitations, dizziness, fainting) or allergic reactions (rash, difficulty breathing). · May cause dizziness or blurred vision; avoid driving until you know how it affects you. · Do not stop abruptly; dose reduction should be gradual under medical supervision. · Inform all healthcare providers about this medication, especially before any surgery or dental procedure. |
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