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);
Left ventricular hypertrophy, left ventricular dysfunction, or history of hypertension, stroke, or coronary artery disease (↑ risk of QT interval prolongation);
Electrolyte abnormalities, especially hypokalemia and hypomagnesemia (↑ risk of QT interval prolongation);
Myasthenia gravis (quinidine may worsen condition);
Other underlying neurologic diseases;
Severe renal impairment;
Severe hepatic impairment;
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: 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: ↑liver enzymes, diarrhea, flatulence, hepatitis, 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 ≥14 days before/allow 14 days after discontinuing to start MAO inhibitor.
Desipramineand paroxetine may ↑ levels and risk of toxicity of dextromethorphan; ↓ dose of antidepressant and determine dose by clinical response.
Strong or moderate CYP3A4 inhibitors, includingaprepitant, atazanavir, clarithromycin, diltiazem, erythromycin, fluconazole, fosamprenavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, and verapamil may ↑ risk of QT interval prolongation.
SSRIs or TCAs may ↑ risk of serotonin syndrome.
Avoid concurrent use with QT interval prolonging drugstogether with CYP2D6 substrates, including thioridazine and pimozide.
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.
May ↑ levels and risk of toxicity of desipramineor paroxetine; do not exceed desipramine dose of 40 mg/day or paroxetine dose of 35 mg/day.
May ↑ levels and the risk of toxicity of digoxin.
↑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: Acts as CYP2D6 inhibitor, producing a marked increase in plasma concentrations of dextromethorphan.

Therapeutic effects:

Decreased emotional lability.

Classifications ⬆ ⬇

Therapeutic Classification: none assigned

Pharmacologic Classification: n methyl d aspartate antagonist

Pharmacokinetics ⬆ ⬇

Dextromethorphan

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP2D6 isoenzyme; 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).

Half-Life: 13 hr.

Quinidine

Absorption: 70–80% absorbed following oral administration.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme; some metabolites have antiarrhythmic activity. 5–20% excreted unchanged by the kidneys; some renal elimination is pH dependent.

Half-Life: 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 ⬆ ⬇

Explain purpose and side effects of dextromethorphan/quinidine. 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. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
Instruct patient to notify health care professional if symptoms of pseudobulbar affect persist or worsen.
May cause dizziness. Caution patient to take precautions to prevent falls.
Advise patient to notify health care professional immediately if signs/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 women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Excessive doses of quinidine may lead to premature labor. Breastfeeding newborn infants should be monitored for quinidine toxicity.

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Indications ⬇

Contraind./Precautions ⬆ ⬇