dextromethorphan/quinidine (Rx)

Brand and Other Names:Nuedexta
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Dosing & Uses

AdultPediatricGeriatric

Dosing Forms & Strengths

dextromethorphan/quinidine

capsule

  • 20mg/10mg

Pseudobulbar Affect

Indicated for PBA and symptoms associated with a variety of neurological conditions (eg, MS, ALS) that result in involuntary, sudden, and frequent episodes of laughing and/or crying

PBA occurs secondary to a variety of otherwise unrelated neurologic conditions, and is characterized by involuntary, sudden, and frequent episodes of laughing and/or crying; episodes typically occur out of proportion or incongruent to the underlying emotional state

PBA is a specific condition, distinct from other types of emotional lability that may occur in patients with neurological disease or injury

1 capsule PO qDay for 7days, THEN 1 capsule q12h

Dosage Modifications

Renal impairment

  • Mild or moderate: No dose adjustment required
  • Severe: Safety and effaicacy not established

Hepatic impairment

  • Mild or moderate: No dosage adjustment required; increase in adverse reactions possible with moderate impairment
  • Severe: Safety and efficacy not established

Amyotrophic Lateral Sclerosis (Orphan)

Orphan designation for treatment of amyotrophic lateral sclerosis (ALS)

Sponsor

  • Avanir Pharmaceuticals; 30 Enterprise, Suite 400; Aliso Viejo, California 92656

Safety and efficacy not established

Dose selection for elderly should be cautious, usually starting at low end of dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy

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Interactions

Interaction Checker

and dextromethorphan/quinidine

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      Serious - Use Alternative

        Significant - Monitor Closely

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            Contraindicated (7)

            • isocarboxazid

              isocarboxazid and dextromethorphan both increase serotonin levels. Contraindicated.

            • phenelzine

              phenelzine and dextromethorphan both increase serotonin levels. Contraindicated.

            • procarbazine

              procarbazine and dextromethorphan both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.

            • rasagiline

              rasagiline and dextromethorphan both increase serotonin levels. Contraindicated. Risk of psychosis episodes or bizarre behavior.

            • safinamide

              dextromethorphan, safinamide. Other (see comment). Contraindicated. Comment: Coadministration of MAOIs and dextromethorphan has been reported to cause episodes of psychosis or bizarre behavior.

            • selegiline

              selegiline and dextromethorphan both increase serotonin levels. Contraindicated.

            • tranylcypromine

              tranylcypromine and dextromethorphan both increase serotonin levels. Contraindicated.

            Serious - Use Alternative (34)

            • amitriptyline

              amitriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • amoxapine

              amoxapine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • buspirone

              buspirone and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • citalopram

              citalopram and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.

            • clomipramine

              clomipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • desipramine

              desipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • desvenlafaxine

              dextromethorphan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • doxepin

              doxepin and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • duloxetine

              duloxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              duloxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • escitalopram

              escitalopram and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • fluoxetine

              fluoxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              fluoxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • fluvoxamine

              fluvoxamine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • grapefruit

              grapefruit will increase the level or effect of dextromethorphan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • imipramine

              imipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • levomilnacipran

              levomilnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • linezolid

              linezolid and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.

            • lofepramine

              lofepramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • lorcaserin

              dextromethorphan and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

            • maprotiline

              maprotiline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • memantine

              memantine, dextromethorphan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.

            • meperidine

              dextromethorphan and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.

            • methylene blue

              methylene blue and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

            • milnacipran

              milnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • nefazodone

              nefazodone and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • nortriptyline

              nortriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • paroxetine

              paroxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              paroxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • protriptyline

              protriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • selegiline transdermal

              selegiline transdermal and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • sertraline

              sertraline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • St John's Wort

              dextromethorphan and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.

            • trazodone

              trazodone and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • trimipramine

              trimipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • venlafaxine

              venlafaxine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              venlafaxine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • vilazodone

              dextromethorphan, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .

            Monitor Closely (58)

            • 5-HTP

              5-HTP and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • abiraterone

              abiraterone increases levels of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.

            • almotriptan

              almotriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • aripiprazole

              dextromethorphan, aripiprazole. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • artemether/lumefantrine

              artemether/lumefantrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • asenapine

              dextromethorphan, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • bupropion

              bupropion will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • cariprazine

              dextromethorphan, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • clobazam

              clobazam will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.

            • clozapine

              dextromethorphan, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • cocaine

              cocaine and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • desvenlafaxine

              desvenlafaxine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • dexfenfluramine

              dexfenfluramine and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dextroamphetamine

              dextroamphetamine and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dihydroergotamine

              dextromethorphan and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dihydroergotamine intranasal

              dextromethorphan and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.

            • eletriptan

              eletriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • ergotamine

              dextromethorphan and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • fenfluramine

              dextromethorphan and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.

              fenfluramine, dextromethorphan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.

            • fluphenazine

              dextromethorphan, fluphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • frovatriptan

              frovatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • haloperidol

              dextromethorphan, haloperidol. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • iloperidone

              dextromethorphan, iloperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • isoniazid

              dextromethorphan and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.

            • L-tryptophan

              dextromethorphan and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • letermovir

              letermovir increases levels of dextromethorphan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lithium

              dextromethorphan and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.

            • loxapine

              dextromethorphan, loxapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • loxapine inhaled

              dextromethorphan, loxapine inhaled. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • lsd

              dextromethorphan and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lumefantrine

              lumefantrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • lurasidone

              dextromethorphan, lurasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • mirtazapine

              dextromethorphan and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • molindone

              dextromethorphan, molindone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • morphine

              dextromethorphan and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • naratriptan

              naratriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • olanzapine

              dextromethorphan, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • paliperidone

              dextromethorphan, paliperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • panobinostat

              panobinostat will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Panobinostat can increase the levels and effects of sensitive CYP2D6 substrates or those with a narrow therapeutic index CYP2D6.

            • pazopanib

              pazopanib increases levels of dextromethorphan by decreasing metabolism. Use Caution/Monitor.

            • peginterferon alfa 2b

              peginterferon alfa 2b, dextromethorphan. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

            • pentazocine

              dextromethorphan and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • perphenazine

              dextromethorphan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • pimavanserin

              dextromethorphan, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • pimozide

              dextromethorphan, pimozide. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • quetiapine

              dextromethorphan, quetiapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • quinidine

              quinidine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • risperidone

              dextromethorphan, risperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • rizatriptan

              rizatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • rolapitant

              rolapitant will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor for adverse reactions when unable to avoid coadministration with narrow therapeutic index CYP2D6 substrates.

            • SAMe

              dextromethorphan and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.

            • sumatriptan

              sumatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • sumatriptan intranasal

              sumatriptan intranasal and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • thiothixene

              dextromethorphan, thiothixene. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • tramadol

              dextromethorphan and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

            • trifluoperazine

              dextromethorphan, trifluoperazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • ziprasidone

              dextromethorphan, ziprasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • zolmitriptan

              zolmitriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            Minor (22)

            • amiodarone

              amiodarone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • asenapine

              asenapine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • celecoxib

              celecoxib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • chloroquine

              chloroquine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • cimetidine

              cimetidine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • darifenacin

              darifenacin will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • diphenhydramine

              diphenhydramine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • dronedarone

              dronedarone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • haloperidol

              haloperidol will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • imatinib

              imatinib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • maraviroc

              maraviroc will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • marijuana

              marijuana will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • nilotinib

              nilotinib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • parecoxib

              parecoxib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • perphenazine

              perphenazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • propafenone

              propafenone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • quinacrine

              quinacrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • ranolazine

              ranolazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • ritonavir

              ritonavir will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • sertraline

              sertraline will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • thioridazine

              thioridazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • tipranavir

              tipranavir will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

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            Adverse Effects

            >10%

            Diarrhea (13%)

            1-10%

            Dizziness (10%)

            Cough (5%)

            Vomiting (5%)

            Asthenia (5%)

            Peripheral edema (5%)

            Increased gamma-glutamyltransferase (3%)

            Flatulence (3%)

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            Warnings

            Contraindications

            Hypersensitivity

            History of quinine, mefloquine, or quinidine-induced thrombocytopenia, hepatitis, bone marrow depression, or lupus-like syndrome

            Concomitant use with drugs containing quinidine, quinine, or mefloquine

            Coadministration of MAOIs or use within 14 d

            Drugs that both prolong QT interval and are metabolized by CYP2D6 (eg, thioridazine, pimozide)

            Complete AV block (without implanted pacemakers)

            Prolonged QT interval, congenital long QT syndrome, or history of torsades de pointes or heart failure

            Cautions

            Quinidine can cause immune-mediated thrombocytopenia (discontinue if thrombocytopenia occurs)

            Hepatotoxicity reported within first few weeks following initiation of quinidine

            Monitor for QTc prolongation if concomitant use of drugs taht prolong QT interval cannot be avoided or concomitant CYP3A4 used

            Quinidine may cause anticholinergic effects and exacerbate certain conditions (eg, myasthenia gravis)

            Monitor ECG in patients with left ventricular hypertrophy or left ventricular dysfunction

            Dextromethorphan may cause serotonergic effects; monitor for worsening in myasthenia gravis and other sensitive conditions

            Use caution with CYP2D6 poor metabolizers

            CYP3A4 inhibitors may increase quinidine serum levels and risk for QT prolongation

            Coadministration with CYP2D6 substrates other than dextromethorphan that cause accumulation of parent drug and/or failure of metabolite formation may decrease safety and/or efficacy of concomitant CYPD6 metabolized drugs; adjust dose of CYPD6 substrate or use alternative therapy when indicated

            Concomitant use of dextromethorphan with serotonergic drugs (eg, SSRIs, TCAs) may increase risk for serotonin syndrome

            Quinidine may increase digoxin levels (as much as double) by inhibiting P-glycoprotein

            Coadministration with alcohol or other CNS depressants may cause additive effects

            May cause dizziness; use precautions to reduce falls

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            Pregnancy & Lactation

            Pregnancy

            There are no adequate data on the developmental risk associated with use in pregnant women

            Animal studies

            • In oral studies conducted in rats and rabbits, a combination of dextromethorphan/quinidine demonstrated developmental toxicity, including teratogenicity (rabbits) and embryolethality, when given to pregnant animals
            • When administered to female rats during pregnancy and lactation, pup survival and pup weight were decreased at all doses, and developmental delay was observed in offspring at the mid and high doses

            Lactation

            Quinidine is excreted in human milk; unknown whether dextromethorphan is excreted in human milk

            There are no data on the effects of quinidine or dextromethorphan on the breastfed infant or the effects on milk production

            There are no data on effects of quinidine or dextromethorphan on breastfed infant or on milk production

            Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            The mechanism by which dextromethorphan exerts therapeutic effects in patients with pseudobulbar affect is unknown

            Dextromethorphan (DM) is a sigma-1 receptor agonist and an uncompetitive NMDA receptor antagonist

            Quinidine increases plasma levels of dextromethorphan by competitively inhibiting cytochrome P4502D6, which catalyzes a major biotransformation pathway for dextromethorphan

            Pharmacokinetics

            Half-Life: 13 hr (dextromethorphan); 7 hr (quinidine)

            Peak Plasma Time: 3-4 hr (dextromethorphan); 1-2 hr (quinidine)

            Protein Bound: 60-70% ((dextromethorphan); 80-89% (quinidine)

            Metabolism: dextromethorphan by CYP2D6; quinidine’s primary pharmacological action in is to competitively inhibit the metabolism of dextromethorphan catalyzed by CYP2D6 in order to increase and prolong plasma concentrations of dextromethorphan; quinidine metabolized by CYP3A4

            Excretion: Urine

            Pharmacogenomics

            The quinidine component is intended to inhibit CYP2D6 so that higher exposure to dextromethorphan can be achieved compared to when dextromethorphan is given alone

            Approximately 7-10% of Caucasians and 3-8% of African Americans lack the capacity to metabolize CYP2D6 substrates and are classified as poor metabolizers (PMs)

            The quinidine component is not expected to contribute to effectiveness in PMs, but adverse events of the quinidine are still possible

            In those patients who may be at risk of significant toxicity due to quinidine, genotyping to determine if they are PMs should be considered prior to making the decision to treat

            Genetic testing laboratories

            • Genotyping tests for CYP2D6 variants are commercially available through the following companies
            • Applied Biosystems (http://www.appliedbiosystems.com/)
            • GenPath Diagnostics (http://www.genpathdiagnostics.com/)
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            Administration

            Oral Administration

            May take with or without food

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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.