Select a medication above to begin.
Cobenfy
xanomeline/ trospium
Adult Dosing .
Dosage forms: CAP: 50 mg/20 mg, 100 mg/20 mg, 125 mg/30 mg; convenience pack
Special Note
- [convenience pack components]
- Info: 4-wk starter pack contains 50 mg/20 mg cap x4 and 100 mg/20 mg cap x52
schizophrenia
- [100 mg/20 mg-125 mg/30 mg PO bid]
- Start: 50 mg/20 mg PO bid for at least 2 days, then incr. to 100 mg/20 mg PO bid for at least 5 days, then may incr. to 125 mg/30 mg PO bid; Max: 250 mg/60 mg/day; Info: give >1h before or >2h after meal; do not open cap; max 200 mg/40 mg/day in elderly pts
renal dosing
- [see below]
- eGFR <60: avoid use
- HD/PD: not defined
hepatic impairment
- [see below]
- Child-Pugh Class A: avoid use; Child-Pugh Class B or C: contraindicated
Peds Dosing .
Peds dosing is currently unavailable or not applicable for this drug.
Contraindications / Cautions .
- hypersensitivity to drug or ingredient
- urinary retention
- gastric retention
- biliary dz
- angle-closure glaucoma, untreated
- eGFR <60
- hepatic impairment
- caution: elderly pts
- caution: glaucoma risk, angle-closure
- caution: bladder neck obstruction
- caution: GI obstruction disorder
- caution: GI motility disorder
- caution: ulcerative colitis
- caution: intestinal atony
- caution: myasthenia gravis
Drug Interactions .
Overview
trospium
anticholinergic
- anticholinergic effects
- CNS depression
- tachycardia
xanomeline
cholinergic agent
- CYP2D6 substrate
- CYP3A4 inhibitor, weak
- P-gp inhibitor, weak
Contraindicated
- cisapride
- potassium citrate
Avoid/Use Alternative
- aclidinium inhaled
- apixaban
- benztropine
- clonidine
- clozapine
- dabigatran
- eliglustat
- ephedra
- futibatinib
- glycopyrronium topical
- isocarboxazid
- meperidine
- metoclopramide
- midazolam
- neratinib
- olanzapine
- phenelzine
- pimozide
- pramlintide
- propafenone
- relugolix
- repotrectinib
- revefenacin inhaled
- rivaroxaban
- simvastatin
- thalidomide
- tiotropium inhaled
- tranylcypromine
- umeclidinium inhaled
Monitor/Modify Tx
- acalabrutinib
- afatinib
- albuterol inhaled
- aldesleukin
- amiodarone
- amitriptyline
- amphetamine
- arformoterol inhaled
- atomoxetine
- atorvastatin
- avanafil
- avapritinib
- benzphetamine
- brigatinib
- butorphanol
- caffeine
- cannabis
- carbamazepine
- chlordiazepoxide
- clobazam
- clomipramine
- clorazepate
- cocaine
- daridorexant
- dexmedetomidine
- dexmethylphenidate
- dextroamphetamine
- dicyclomine
- diethylpropion
- dihydrocodeine
- disopyramide
- dofetilide
- domperidone
- doxepin
- droperidol
- encorafenib
- entrectinib
- ephedrine oral
- epinephrine
- erythromycin
- esketamine
- estazolam
- ethanol (in some formulations)
- etomidate
- fedratinib
- felodipine
- finerenone
- flibanserin
- flurazepam
- gabapentin
- gabapentin enacarbil
- glycopyrrolate
- hoodia
- hydroxyzine
- hyoscyamine
- ifosfamide
- imipramine
- isoflurane
- isoproterenol
- ivosidenib
- ketamine
- levalbuterol inhaled
- levoketoconazole
- levorphanol
- lifileucel
- lomitapide
- lonafarnib
- lovastatin
- lumateperone
- lurasidone
- mavacamten
- mavorixafor
- methohexital
- methscopolamine
- milnacipran
- mirtazapine
- modafinil
- morphine
- nelarabine
- nifedipine
- nisoldipine
- nortriptyline
- olodaterol inhaled
- opicapone
- orphenadrine
- oxybutynin
- oxymorphone
- pemigatinib
- pentazocine
- perphenazine
- phendimetrazine
- phentermine
- phenylephrine ophthalmic
- pregabalin
- primidone
- protriptyline
- pseudoephedrine
- quinidine (antiarrhythmic)
- red yeast rice
- remifentanil
- ribociclib
- rotigotine transdermal
- selpercatinib
- selumetinib
- sirolimus
- solriamfetol
- suvorexant
- tacrolimus
- talazoparib
- temazepam
- tenofovir alafenamide
- terbutaline
- thioridazine
- tolvaptan
- tramadol
- triazolam
- trimipramine
- ubrogepant
- vilanterol inhaled
- viloxazine
- warfarin
- yohimbe
- zanubrutinib
- ziconotide
Caution Advised
- 5-HTP
- allopurinol
- almotriptan
- alosetron
- amantadine
- apomorphine
- apraclonidine ophthalmic
- aripiprazole bimonthly injection
- aripiprazole lauroxil
- aripiprazole monthly injection
- aripiprazole oral
- asenapine
- atropine ophthalmic
- baclofen
- barium
- belladonna alkaloids
- bethanechol
- botulinum toxin
- brexpiprazole
- brimonidine ophthalmic
- brimonidine topical
- brivaracetam
- bromocriptine
- brompheniramine
- bupropion
- buspirone
- cannabidiol
- carbinoxamine
- cariprazine
- carisoprodol
- cenobamate
- cetirizine
- cevimeline
- chamomile, German
- chlophedianol
- chlorpheniramine
- chlorzoxazone
- citalopram
- clemastine
- clidinium
- cobimetinib
- cyclobenzaprine
- cyclopentolate ophthalmic
- cyclophosphamide
- cyproheptadine
- dacomitinib
- dantrolene
- darifenacin
- darolutamide
- desvenlafaxine
- deutetrabenazine
- dexbrompheniramine
- dexchlorpheniramine
- dichlorphenamide
- difelikefalin
- difenoxin
- dimenhydrinate
- diphenhydramine
- diphenoxylate
- donepezil
- doxazosin
- doxepin topical
- duloxetine
- efavirenz
- eletriptan
- entacapone
- eplerenone
- erenumab
- ergotamine
- escitalopram
- eslicarbazepine acetate
- ethosuximide
- felbamate
- fenfluramine
- fesoterodine
- fexinidazole
- flavoxate
- fluoxetine
- fluvoxamine
- foslevodopa
- fosphenytoin
- frovatriptan
- galantamine
- ganaxolone
- glecaprevir
- glofitamab
- guanfacine
- haloperidol
- homatropine
- hydrochlorothiazide
- iloperidone
- ipratropium nasal
- lacosamide
- lamotrigine
- lasmiditan
- levetiracetam
- levocetirizine
- levodopa
- lofexidine
- loperamide
- loxapine
- meclizine
- melatonin
- meprobamate
- metformin
- methacholine inhaled
- methocarbamol
- methsuximide
- methyldopa
- methylergonovine
- metyrapone
- metyrosine
- mexiletine
- mirabegron
- mitotane
- molindone
- mosunetuzumab
- mycophenolate mofetil
- naldemedine
- naltrexone
- naphazoline ophthalmic
- naratriptan
- nefazodone
- neostigmine
- oxcarbazepine
- oxymetazoline nasal
- paliperidone
- palovarotene
- paroxetine
- passion flower
- perampanel
- pexidartinib
- pheniramine
- phenytoin
- pibrentasvir
- pilocarpine
- pilocarpine ophthalmic
- potassium acid phosphate
- potassium gluconate
- potassium phosphate
- pramipexole
- procainamide
- procarbazine
- prochlorperazine
- pyridostigmine
- pyrilamine
- quetiapine
- quinidine (CYP2D6 inhibitor)
- ramelteon
- rasagiline
- risperidone
- rizatriptan
- roflumilast
- ropinirole
- rufinamide
- safinamide
- scopolamine
- selegiline
- selegiline transdermal
- selinexor
- sertraline
- solifenacin
- stiripentol
- sumatriptan
- tasimelteon
- terbinafine
- tetrabenazine
- tetrahydrozoline ophthalmic
- thiotepa
- tiagabine
- tizanidine
- tolcapone
- tolterodine
- topiramate
- trazodone
- trifluoperazine
- trihexyphenidyl
- triprolidine
- tropicamide ophthalmic
- valbenazine
- valerian
- valproic acid
- venlafaxine
- verapamil
- vibegron
- vigabatrin
- vilazodone
- ziprasidone
- zolmitriptan
- zonisamide
Adverse Reactions .
Serious Reactions
- hypersensitivity rxn
- angioedema
- anaphylaxis
- Stevens-Johnson syndrome
- urinary retention
- gastric retention risk
- hepatic injury
- glaucoma, acute angle-closure
- hallucinations
- rhabdomyolysis
Common Reactions
- nausea
- dyspepsia
- constipation
- vomiting
- HTN
- abdominal pain
- diarrhea
- tachycardia
- dizziness
- GERD
- xerostomia
- urinary retention
- somnolence
- blurred vision
- LFTs elevated
- UTI
- sialorrhea
- orthostatic hypotension
- cough
- extrapyramidal sx, non-akathisia
Safety/Monitoring .
Monitoring Parameters
eGFR at baseline; LFTs, bilirubin before tx start, then as clinically indicated; HR at baseline, then as clinically indicated
Pregnancy/Lactation .
Pregnancy
Clinical Summary
weigh risk/benefit during pregnancy; no human data available; no known risk of teratogenicity, though risk of decr. fetal wt based on animal data w/ xanomeline at >3x MRHD and risk of incr. resorption and post-implantation loss based on animal data w/ xanomeline at >5x MRHD
Pregnancy Registry
encourage pts to enroll in National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or www.womensmentalhealth.org/research/pregnancyregistry/atypicalantipsychotic
Lactation
Clinical Summary
weigh risk/benefit while breastfeeding; no human data available to assess risk of infant harm or effects on milk production
Pharmacology .
Metabolism: for xanomeline: liver; CYP450: 1A2, 2B6, 2C9/19, 2D6 (primary) substrate; for trospium: unknown; CYP450: none
Excretion: for xanomeline: urine 78% (<0.01% unchanged), feces 12%; Half-life: 5h; for trospium: urine (85-90% unchanged); Half-life: 6h; Info: undergoes active tubular secretion
Subclass: Muscarinic Antipsychotics
Mechanism of Action
xanomeline's exact mechanism of action unknown; agonizes M1 and M4 muscarinic acetylcholine receptors in CNS; trospium antagonizes acetylcholine receptors (anticholinergic)
Formulary .
No Formulary Selected
Join Now to View Patient Handouts!
Create a FREE epocrates Online account to access patient medication instructions. Your patients and caregivers will appreciate you printing these friendly handouts, available in English and Spanish. Each handout addresses common concerns such as how to take the medication, and possible side effects.
Current Members: Sign In.
Pill Pictures
Join Now to View Pill Pictures!
Create a FREE epocrates Online account to access full-color images of medications within the drug monograph.
Current Members: Sign In.