Dextromethorphan/quinidine|
| Dextromethorphan | Sigma-1 receptor agonist, NMDA receptor antagonist |
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| Quinidine | Antiarrhythmic agent (CYP2D6 inhibitor) |
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| Trade names | Nuedexta |
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| Other names | AVP-786, AVP-923 |
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| Main uses | Pseudobulbar affect (PBA)[1] |
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| Side effects | Diarrhea, dizziness, cough, vomiting, peripheral swelling, urinary tract infection[1] |
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Pregnancy category |
- US: C (Risk not ruled out)[2]
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Routes of use | By mouth |
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| AHFS/Drugs.com | Monograph |
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| MedlinePlus | a611048 |
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| License data |
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| Legal status |
- US: ℞-only
- In general: ℞ (Prescription only)
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| Bioavailability | Dextromethorphan 11%, quinidine 70-80%. Food has no effect on absorption. |
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| Metabolism | Liver, extensive. Dextromethorphan is catalyzed by CYP2D6. Quinidine is metabolized by CYP3A4 and competitively inhibits the metabolism of dextromethorphan to increase and prolong plasma concentrations of dextromethorphan |
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| Elimination half-life | Dextromethorphan 13h, quinidine 7h |
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| Excretion | Quinidine 5-20% |
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Dextromethorphan/quinidine, sold under the brand name Nuedexta, is a combination medication used to treat pseudobulbar affect (PBA).[1] This includes PBA that may occur in amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and dementia.[3] It is taken by mouth.[1]
Common side effects include diarrhea, dizziness, cough, vomiting, peripheral swelling, and urinary tract infection.[1] Other side effects may include low platelets, QT prolongation, liver problems, and serotonin syndrome.[1] It contains dextromethorphan, a NMDA receptor antagonist and quinidine, a CYP2D6 inhibitor.[1] Quinidine is used to increase the activity of dextromethorphan.[3]
The combination was approved for medical use in the United States in 2010.[1] While it was approved in Europe in 2013; this approval was subsequently withdrawn.[4] In the United States 60 tablets costs about 1,300 USD as of 2021.[5]
Medical uses
Dosage
It is started at a dose of one pill per day, and than after a week increased to one pill twice per day.[1]
Contraindications
- Atrioventricular (AV) block, complete, without implanted pacemaker or at high risk of complete AV block
- Concomitant use with drugs containing quinidine, quinine, or mefloquine
- Concomitant use with drugs that both prolong the QT interval and are metabolized by CYP2D6 (e.g., thioridazine, pimozide); effects on QT interval may be increased
- Concomitant use with MAOIs or use of MAOIs within 14 days; risk of serious, potentially fatal, drug interactions including serotonin syndrome
- Heart failure
- Hypersensitivity to dextromethorphan
- Hypersensitivity to quinine, mefloquine, quinidine, or dextromethorphan/quinidine with a history of thrombocytopenia, hepatitis, bone marrow depression or lupus-like syndrome induced by these drugs
- QT interval, prolonged or congenital long QT syndrome or a history suggesting torsades de pointes
Side effects
Common risks and side effects include:[1]
Interactions
Research
In June 2012, drug discovery and development magazine reported that Avanir Pharmaceuticals plans to test the drug for the treatment of agitation associated with Alzheimer's disease.[6] The drug is also under investigation for the treatment of major depressive disorder.[1] Archived 2019-03-29 at the Wayback Machine[7] As of May 2021, the drug is also in clinical trial for negative symptoms of schizophrenia.[8]
See also
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 "Nuedexta- dextromethorphan hydrobromide and quinidine sulfate capsule, gelatin coated". DailyMed. 23 June 2019. Archived from the original on 20 October 2020. Retrieved 23 October 2020.
- ↑ "Dextromethorphan / quinidine (Nuedexta) Use During Pregnancy". Drugs.com. 21 August 2019. Archived from the original on 20 January 2021. Retrieved 13 September 2020.
- ↑ 3.0 3.1 "Dextromethorphan and quiNIDine Monograph for Professionals". Drugs.com. Archived from the original on 28 January 2021. Retrieved 23 December 2021.
- ↑ "Nuedexta". Archived from the original on 28 August 2021. Retrieved 23 December 2021.
- ↑ "Nuedexta Prices, Coupons & Savings Tips - GoodRx". GoodRx. Archived from the original on 17 May 2020. Retrieved 23 December 2021.
- ↑ "NNuedexta Testing New Indication". CDrug Discovery and Development Magazine. June 13, 2011. Archived from the original on April 9, 2016. Retrieved May 10, 2021.
- ↑ Nguyen, Linda; Thomas, Kelan L.; Lucke-Wold, Brandon P.; Cavendish, John Z.; Crowe, Molly S.; Matsumoto, Rae R. (2016). "Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders". Pharmacology & Therapeutics. 159: 1–22. doi:10.1016/j.pharmthera.2016.01.016. ISSN 0163-7258. PMID 26826604.
- ↑ Avanir Pharmaceuticals (2021-04-26). "A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-arm Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 (Deudextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Negative Symptoms of Schizophrenia". Archived from the original on 2021-05-10. Retrieved 2021-05-10.
External links
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| mAChRs | | Agonists | |
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| Antagonists |
- 3-Quinuclidinyl benzilate
- 4-DAMP
- Aclidinium bromide (+formoterol)
- Abediterol
- AF-DX 250
- AF-DX 384
- Ambutonium bromide
- Anisodamine
- Anisodine
- Antihistamines (first-generation) (e.g., brompheniramine, buclizine, captodiame, chlorphenamine (chlorpheniramine), cinnarizine, clemastine, cyproheptadine, dimenhydrinate, dimetindene, diphenhydramine, doxylamine, meclizine, mequitazine, perlapine, phenindamine, pheniramine, phenyltoloxamine, promethazine, propiomazine, triprolidine)
- AQ-RA 741
- Atropine
- Atropine methonitrate
- Atypical antipsychotics (e.g., clozapine, fluperlapine, olanzapine (+fluoxetine), rilapine, quetiapine, tenilapine, zotepine)
- Benactyzine
- Benzatropine (benztropine)
- Benzilone
- Benzilylcholine mustard
- Benzydamine
- BIBN 99
- Biperiden
- Bornaprine
- Camylofin
- CAR-226,086
- CAR-301,060
- CAR-302,196
- CAR-302,282
- CAR-302,368
- CAR-302,537
- CAR-302,668
- Caramiphen
- Cimetropium bromide
- Clidinium bromide
- Cloperastine
- CS-27349
- Cyclobenzaprine
- Cyclopentolate
- Darifenacin
- DAU-5884
- Desfesoterodine
- Dexetimide
- DIBD
- Dicycloverine (dicyclomine)
- Dihexyverine
- Difemerine
- Diphemanil metilsulfate
- Ditran
- Drofenine
- EA-3167
- EA-3443
- EA-3580
- EA-3834
- Emepronium bromide
- Etanautine
- Etybenzatropine (ethybenztropine)
- Fenpiverinium
- Fentonium bromide
- Fesoterodine
- Flavoxate
- Glycopyrronium bromide (+beclometasone/formoterol, +indacaterol)
- Hexahydrodifenidol
- Hexahydrosiladifenidol
- Hexbutinol
- Hexocyclium
- Himbacine
- HL-031,120
- Homatropine
- Imidafenacin
- Ipratropium bromide (+salbutamol)
- Isopropamide
- J-104,129
- Hyoscyamine
- Mamba toxin 3
- Mamba toxin 7
- Mazaticol
- Mebeverine
- Meladrazine
- Mepenzolate
- Methantheline
- Methoctramine
- Methylatropine
- Methylhomatropine
- Methylscopolamine
- Metixene
- Muscarinic toxin 7
- N-Ethyl-3-piperidyl benzilate
- N-Methyl-3-piperidyl benzilate
- Nefopam
- Octatropine methylbromide (anisotropine methylbromide)
- Orphenadrine
- Otenzepad (AF-DX 116)
- Otilonium bromide
- Oxapium iodide
- Oxitropium bromide
- Oxybutynin
- Oxyphencyclimine
- Oxyphenonium bromide
- PBID
- PD-102,807
- PD-0298029
- Penthienate
- Pethidine
- pFHHSiD
- Phenglutarimide
- Phenyltoloxamine
- Pipenzolate bromide
- Piperidolate
- Pirenzepine
- Piroheptine
- Pizotifen
- Poldine
- Pridinol
- Prifinium bromide
- Procyclidine
- Profenamine (ethopropazine)
- Propantheline bromide
- Propiverine
- Quinidine
- Revefenacin
- Rociverine
- RU-47,213
- SCH-57,790
- SCH-72,788
- SCH-217,443
- Scopolamine (hyoscine)
- Scopolamine butylbromide (hyoscine butylbromide)
- Silahexacyclium
- Sofpironium bromide
- Solifenacin
- SSRIs (e.g., femoxetine, paroxetine)
- Telenzepine
- Terodiline
- Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin, mirtazapine)
- Tiemonium iodide
- Timepidium bromide
- Tiotropium bromide
- Tiquizium bromide
- Tofenacin
- Tolterodine
- Tricyclic antidepressants (e.g., amitriptyline (+perphenazine), amitriptylinoxide, butriptyline, cidoxepin, clomipramine, desipramine, desmethyldesipramine, dibenzepin, dosulepin (dothiepin), doxepin, imipramine, lofepramine, nitroxazepine, northiaden (desmethyldosulepin), nortriptyline, protriptyline, quinupramine, trimipramine)
- Tridihexethyl
- Trihexyphenidyl
- Trimebutine
- Tripitamine (tripitramine)
- Tropacine
- Tropatepine
- Tropicamide
- Trospium chloride
- Typical antipsychotics (e.g., chlorpromazine, chlorprothixene, cyamemazine (cyamepromazine), loxapine, mesoridazine, thioridazine)
- Umeclidinium bromide (+vilanterol)
- WIN-2299
- Xanomeline
- Zamifenacin
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Precursors (and prodrugs) | |
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See also: Receptor/signaling modulators • Nicotinic acetylcholine receptor modulators • Acetylcholine metabolism/transport modulators |
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| nAChRs | Agonists (and PAMs) |
- 5-HIAA
- 6-Chloronicotine
- A-84,543
- A-366,833
- A-582,941
- A-867,744
- ABT-202
- ABT-418
- ABT-560
- ABT-894
- Acetylcholine
- Altinicline
- Anabasine
- Anatabine
- Anatoxin-a
- AR-R17779
- Bephenium hydroxynaphthoate
- Butinoline
- Butyrylcholine
- Carbachol
- Choline
- Cotinine
- Cytisine
- Decamethonium
- Desformylflustrabromine
- Dianicline
- Dimethylphenylpiperazinium
- Epibatidine
- Epiboxidine
- Ethanol (alcohol)
- Ethoxysebacylcholine
- EVP-4473
- EVP-6124
- Galantamine
- GTS-21
- Ispronicline
- Ivermectin
- JNJ-39393406
- Levamisole
- Lobeline
- MEM-63,908 (RG-3487)
- Morantel
- Nicotine (tobacco)
- NS-1738
- PHA-543,613
- PHA-709,829
- PNU-120,596
- PNU-282,987
- Pozanicline
- Pyrantel
- Rivanicline
- RJR-2429
- Sazetidine A
- SB-206553
- Sebacylcholine
- SIB-1508Y
- SIB-1553A
- SSR-180,711
- Suberyldicholine
- Suxamethonium (succinylcholine)
- Suxethonium (succinyldicholine)
- TC-1698
- TC-1734
- TC-1827
- TC-2216
- TC-5214
- TC-5619
- TC-6683
- Tebanicline
- Tribendimidine
- Tropisetron
- UB-165
- Varenicline
- WAY-317,538
- XY-4083
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Antagonists (and NAMs) | |
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Precursors (and prodrugs) | |
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See also: Receptor/signaling modulators • Muscarinic acetylcholine receptor modulators • Acetylcholine metabolism/transport modulators |
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| AMPAR | |
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| KAR | |
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| NMDAR | |
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- See also: Receptor/signaling modulators
- Metabotropic glutamate receptor modulators
- Glutamate metabolism/transport modulators
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| Group I | |
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| Group II | |
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| Group III | | mGluR4 |
- Antagonists: CPPG
- MAP4
- MPPG
- MSOP
- MTPG
- UBP-1112
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| mGluR6 |
- Antagonists: CPPG
- MAP4
- MPPG
- MSOP
- MTPG
- UBP-1112
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| mGluR7 |
- Antagonists: CPPG
- MAP4
- MMPIP
- MPPG
- MSOP
- MTPG
- UBP-1112
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| mGluR8 |
- Antagonists: CPPG
- MAP4
- MPPG
- MSOP
- MTPG
- UBP-1112
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See also: Receptor/signaling modulators • Ionotropic glutamate receptor modulators • Glutamate metabolism/transport modulators |
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DAT (DRIs) | |
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NET (NRIs) | | | | | | |
- Others: Antihistamines (e.g., brompheniramine, chlorphenamine, pheniramine, tripelennamine)
- Antipsychotics (e.g., loxapine, ziprasidone)
- Arylcyclohexylamines (e.g., ketamine, phencyclidine)
- Dopexamine
- Ephenidine
- Ginkgo biloba
- Indeloxazine
- Nefazodone
- Opioids (e.g., desmetramadol, methadone, pethidine (meperidine), tapentadol, tramadol, levorphanol)
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SERT (SRIs) | | | | |
- Others: A-80426
- Amoxapine
- Antihistamines (e.g., brompheniramine, chlorphenamine, dimenhydrinate, diphenhydramine, mepyramine (pyrilamine), pheniramine, tripelennamine)
- Antipsychotics (e.g., loxapine, ziprasidone)
- Arylcyclohexylamines (e.g., 3-MeO-PCP, esketamine, ketamine, methoxetamine, phencyclidine)
- Cyclobenzaprine
- Delucemine
- Dextromethorphan
- Dextrorphan
- Efavirenz
- Medifoxamine
- Mesembrine
- Mifepristone
- MIN-117 (WF-516)
- N-Me-5-HT
- Opioids (e.g., dextropropoxyphene, methadone, pethidine (meperidine), levorphanol, tapentadol, tramadol)
- Roxindole
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| VMATs | |
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| Others | |
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See also: Receptor/signaling modulators • Monoamine releasing agents • Adrenergics • Dopaminergics • Serotonergics • Monoamine metabolism modulators • Monoamine neurotoxins |
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| σ1 | |
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| σ2 | |
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| Unsorted |
- Antagonists: AHD1
- AZ66
- Lamotrigine
- Naloxone
- SM-21
- UMB-100
- UMB-101
- UMB-103
- UMB-116
- YZ-011
- YZ-069
- YZ-185
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See also: Receptor/signaling modulators |