dextromethorphan/quinidine

Contraindicated in:

Hypersensitivity to dextromethorphan;
Hypersensitivity to quinidine, quinine, or mefloquine, including previous hepatitis, bone marrow depression, lupus-like syndrome, or other hypersensitivity reactions;
Concurrent use of quinidine, quinine, or mefloquine;
Use within 14 days of MAO inhibitors;
Prolonged/congenital long QT interval, history suggestive of torsades de pointes, or HF;
Complete heart block (without implanted pacemaker) or risk of heart block.

Use Cautiously in:

CYP2D6 poor metabolizers (quinidine component will not contribute to effectiveness; consider genotyping those at ↑ risk of quinidine toxicity);
Patients with left ventricular hypertrophy or left ventricular dysfunction, history of hypertension, stroke, or coronary artery disease (↑ risk of QT interval prolongation);
Electrolyte abnormalities, especially hypokalemia and hypomagnesemia (↑ risk of QT interval prolongation; correct before use);
Myasthenia gravis (quinidine may worsen condition);
Severe renal impairment;
Severe hepatic impairment;
Other underlying neurologic diseases;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children;
Geri: Appears on Beers list. Limited efficacy in patients with behavioral symptoms of dementia (with exception of pseudobulbar affect). Older adults may have ↑ risk of falls. Use with caution in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema, QT interval prolongation

GI: diarrhea, flatulence, hepatitis, ↑liver enzymes, vomiting

Hemat: thrombocytopenia

Neuro: dizziness, weakness

Resp: cough

Misc: hypersensitivity reactions (including lupus-like syndrome)

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with MAO inhibitors↑ risk of serious adverse reactions, including serotonin syndrome; MAO inhibitor use should be discontinued at least 14 days before/allow 14 days after discontinuing to start MAO inhibitors.
↑levels and risk of adverse reactions from desipramineand paroxetine; ↓ dose of antidepressant and determine dose by clinical response.
Concurrent therapy with strong or moderate CYP3A4 inhibitors, includingaprepitant, atazanavir, clarithromycin, diltiazem, erythromycin, fluconazole, fosamprenavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, and verapamil , ↑ risk of QT interval prolongation; careful monitoring recommended.
Concurrent use with SSRIs or TCAs may result in serotonin syndrome.
Avoid concurrent use with QT interval prolonging drugstogether with CYP2D6 substrates, including thioridazine and pimozide.
When using with QT interval prolonging drugs and moderate/strong CYP3A4 inhibitors ECG monitoring is recommended.
Concurrent use of CYP2D6 substrates, especially those with narrow therapeutic indices should be undertaken with caution, dose modifications or choosing an alternative agent may be necessary, including codeineand hydrocodone.
↑levels and risk of toxicity/adverse reactions from desipramine(daily dose should not exceed 40 mg/day) or paroxetine(dose should not exceed 35 mg/day.
↑levels and the risk of toxicity from digoxin, careful monitoring recommended.
↑risk of CNS depression with other CNS depressants including antihistamines, some antidepressants, sedative/hypnotics and alcohol.

Availability ⬆ ⬇

(Generic available)

Capsules: dextromethorphan 20 mg/quinidine 10 mg

Route/Dosage ⬆ ⬇

PO (Adults ): One capsule once daily for 7 days, then ↑ to one capsule every 12 hr.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Dextromethorphan acts as an N-methyl-D-aspartic acid (NMDA) receptor antagonist and sigma-1 agonist. Quinidine act as an inhibitor of the CYP2D6 isoenzyme, producing a marked increase in dextromethorphan blood levels.

Therapeutic effects:

Decreased emotional lability.

Classifications ⬆ ⬇

Therapeutic Classification: none assigned

Pharmacokinetics ⬆ ⬇

Absorption: Dextromethorphan: well absorbed following oral administration; quinidine: 70–80% absorbed following oral administration.

Distribution: Quinidine: widely distributed to tissues.

Metabolism/Excretion: Both extensively metabolized by the liver (dextromethorphan by the CYP2D6 isoenzyme, quinidine by the CYP3A4 isoenzyme); some metabolites of quinidine have antiarrhythmic activity. The CYP2D6 isoenzyme exhibits genetic polymorphism (7–10% of Caucasians and 3–8% of African Americans may be poor metabolizers and may have significantly ↑ dextromethorphan concentrations and an ↑ risk of adverse effects).5–20% of quinidine excreted unchanged by the kidneys; some renal elimination is pH dependent.

Half-Life: Dextromethorphan: 13 hr; quinidine: 7 hr (↑ in HF and hepatic impairment).

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
dextromethorphan (PO)	15–30 min	unknown	unknown
quinidine (PO)	30 min	1–1.5 hr	unknown

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed, with no more than two capsules daily and approximately 12 hr between doses. Do not double missed doses. Advise patient not to share medication with others, even if they have the same symptoms; may be dangerous.
May cause dizziness. Caution patient to take precautions to prevent falls.
Advise patient to notify health care professional immediately if symptoms of thrombocytopenia, hepatitis, lupus-like syndrome occur.
Instruct patient to notify health care professional if they feel faint or lose consciousness; may be a sign of cardiac effects.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to avoid concurrent use of Rx, OTC, and herbal products without consulting health care professional.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Instruct patient to notify health care professional if symptoms of pseudobulbar affect persist or worsen.

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Indications ⬇

Contraind./Precautions ⬆ ⬇