Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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.
Adverse Effects
>10%
Diarrhea (13%)
1-10%
Dizziness (10%)
Cough (5%)
Vomiting (5%)
Asthenia (5%)
Peripheral edema (5%)
Increased gamma-glutamyltransferase (3%)
Flatulence (3%)
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
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.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/)
Administration
Oral Administration
May take with or without food
Images
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
