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Contrave
naltrexone/ bupropion hydrochloride
Black Box Warnings .
Suicidality
not indicated for major depressive or other psychiatric disorders, but bupropion under other trade names indicated for this use; incr. risk of suicidality in children, adolescents and young adults with major depressive or other psychiatric disorders especially during 1st months of tx with antidepressants vs. placebo; weigh risk vs. benefit; in short-term studies of antidepressants vs. placebo, suicidality risk not incr. in patients >24 yo, and risk decr. in patients 65 yo and older; observe all patients for clinical worsening, suicidality, or unusual behavior changes; not approved for peds use
Adult Dosing .
Dosage forms: ER TAB: 8 mg/90 mg
weight management, chronic
- [2 tabs PO bid]
- Start: 1 tab PO qam x1wk, then 1 tab PO bid x1wk, then 2 tabs PO qam and 1 tab PO qpm x1wk; Max: 4 tabs/day; Info: for obese patients or overweight patients with wt-related comorbidity; D/C if wt loss <5% after 12wk on max dose; do not cut/crush/chew tab; avoid administration with high fat meal
renal dosing
- [see below]
- moderate-severe impairment: max 1 tab bid; ESRD: avoid use
- HD/PD: not defined
hepatic dosing
- [adjust dose amount, frequency]
- hepatic impairment: max 1 tab qam
Peds Dosing .
Peds dosing is currently unavailable or not applicable for this drug.
Contraindications / Cautions .
- hypersensitivity to drug or ingredient
- MAO inhibitor use within 14 days
- ESRD
- HTN, uncontrolled
- seizure disorder
- seizure history
- bulimia
- anorexia nervosa
- opioid use, concurrent
- opioid dependence
- opioid withdrawal, acute
- abrupt alcohol D/C
- abrupt benzodiazepine D/C
- abrupt barbiturate D/C
- abrupt antiepileptic D/C
- avoid: alcohol use
- caution: drug abuse history
- caution: seizure risk
- caution: head injury
- caution: intracranial lesion
- caution: CNS infection
- caution: arteriovenous malformation
- caution: patients <25 yo
- caution: bipolar disorder
- caution: bipolar disorder risk
- caution: hepatic impairment
- caution: renal impairment
- caution: elderly patients
- caution: diabetes mellitus
- caution: HTN
- caution: glaucoma, angle-closure
Drug Interactions .
Overview
bupropion
norepinephrine-dopamine reuptake inhibitor; aminoketone antidepressant
- CYP2B6 substrate
- CYP2D6 inhibitor, strong
- hypertensive effects
- lowers seizure threshold
- caution advised with concomitant drugs if smoking cessation use; dose adjustments may be necessary; smoking cessation may alter pharmacokinetics or pharmacodynamics of certain drugs
- add MAO inhibitor to Interaction Check if recent (14 days) use
naltrexone
opioid antagonist, central
- affected by altered gastrointestinal motility
- CNS depression
- central opioid antagonist
Contraindicated
- acetazolamide
- alfentanil
- brivaracetam
- buprenorphine
- bupropion
- butorphanol
- cannabidiol
- carbamazepine
- cenobamate
- clobazam
- clonazepam
- clorazepate
- codeine
- diazepam
- dihydrocodeine
- eliglustat
- eslicarbazepine acetate
- ethosuximide
- felbamate
- fenfluramine
- fentanyl
- fosphenytoin
- gabapentin
- ganaxolone
- hydrocodone
- hydromorphone
- isocarboxazid
- kratom
- lacosamide
- lamotrigine
- levetiracetam
- levorphanol
- linezolid
- lorazepam
- meperidine
- methadone
- methsuximide
- methylene blue injection
- midazolam
- morphine
- nalbuphine
- oliceridine
- opium
- oxcarbazepine
- oxycodone
- oxymorphone
- pentazocine
- perampanel
- phenelzine
- phenobarbital
- phenytoin
- pimozide
- pregabalin
- primidone
- remifentanil
- rufinamide
- selegiline transdermal
- stiripentol
- sufentanil
- tapentadol
- thioridazine
- tiagabine
- topiramate
- tramadol
- tranylcypromine
- valproic acid
- vigabatrin
- zonisamide
Avoid/Use Alternative
- albuterol
- aldesleukin
- amifampridine
- amphetamine
- aripiprazole bimonthly injection
- aripiprazole lauroxil
- aripiprazole monthly injection
- bremelanotide
- butalbital
- clonidine
- dextroamphetamine
- doxorubicin
- doxylamine
- efavirenz
- epinephrine inhaled
- ethanol (alcoholic beverage)
- ethanol injection
- furosemide
- ginkgo
- haloperidol
- iohexol
- kava
- landiolol
- lisdexamfetamine
- lixisenatide
- lopinavir/ritonavir
- lorlatinib
- metaxalone
- methamphetamine
- methylnaltrexone
- metoclopramide
- midodrine
- naldemedine
- naloxegol
- naltrexone
- oxybate
- pirfenidone
- primaquine
- procarbazine
- promethazine
- propafenone
- rifampin
- ropeginterferon alfa-2b
- scopolamine
- sofpironium topical
- tamsulosin
- thalidomide
- tradipitant
- trimethobenzamide
- zuranolone
Monitor/Modify Tx
- abiraterone acetate
- acebutolol
- acyclovir
- aficamten
- albuterol inhaled
- aliskiren
- almotriptan
- alprazolam
- amiloride
- aminophylline
- amitriptyline
- amlodipine
- amoxapine
- amoxicillin
- ampicillin
- angiotensin II
- apalutamide
- aprocitentan
- arformoterol inhaled
- aripiprazole oral
- armodafinil
- asciminib
- asenapine
- atenolol
- atogepant
- atomoxetine
- atropine ophthalmic
- axicabtagene ciloleucel
- axitinib
- azilsartan medoxomil
- baclofen
- baclofen intrathecal
- benazepril
- benzphetamine
- betamethasone
- betaxolol
- bevacizumab
- bismuth subsalicylate
- bisoprolol
- brexpiprazole
- brexucabtagene autoleucel
- brigatinib
- budesonide
- bumetanide
- busulfan
- cabozantinib
- caffeine
- caffeine citrate
- candesartan cilexetil
- cannabis
- captopril
- carfilzomib
- cariprazine
- carvedilol
- cefazolin
- cefepime
- cefiderocol
- ceftaroline
- ceftazidime
- ceftobiprole
- celecoxib
- chlorambucil
- chlordiazepoxide
- chloroquine
- chlorothiazide
- chlorpheniramine
- chlorpromazine
- chlorthalidone
- ciltacabtagene autoleucel
- ciprofloxacin
- cisatracurium
- citalopram
- clevidipine
- clomipramine
- clopidogrel
- clozapine
- cobicistat
- cocaine
- copanlisib
- corticotropin
- cortisone
- cyclobenzaprine
- cycloserine
- cyclosporine
- dalfampridine
- danazol
- darbepoetin alfa
- daridorexant
- darolutamide
- deflazacort
- delafloxacin
- desflurane
- desipramine
- desmopressin
- desvenlafaxine
- deutetrabenazine
- dexamethasone
- dexmedetomidine
- dexmedetomidine injection
- dexmethylphenidate
- diclofenac
- diclofenac topical
- dicloxacillin
- diethylpropion
- diflunisal
- digoxin
- dihydroergotamine
- diltiazem
- dobutamine
- donepezil
- dopamine
- doxapram
- doxazosin
- doxepin
- dronabinol
- droperidol
- droxidopa
- duloxetine
- eletriptan
- elinzanetant
- elivaldogene autotemcel
- enalapril
- enalaprilat
- enzalutamide
- ephedra
- ephedrine injection
- ephedrine oral
- epinephrine
- eplerenone
- epoetin alfa
- eptinezumab
- erenumab
- ergotamine
- ertapenem
- escitalopram
- esketamine
- esmolol
- estazolam
- estetrol (contraceptive)
- estradiol (contraceptive)
- eszopiclone
- ethacrynic acid
- ethanol (in some formulations)
- ethinyl estradiol (contraceptive)
- etodolac
- etomidate
- etrasimod
- felodipine
- fenoldopam
- fenoprofen
- fingolimod
- flecainide
- fludrocortisone
- fluoxetine
- fluphenazine
- flurazepam
- flurbiprofen
- fluvoxamine
- formoterol inhaled
- foscarnet
- fosinopril
- fostamatinib
- fremanezumab
- frovatriptan
- fruquintinib
- gabapentin enacarbil
- galantamine
- galcanezumab
- ganciclovir
- goserelin
- guanfacine
- histrelin
- hoodia
- hydralazine
- hydrochlorothiazide
- hydrocortisone
- hydroxocobalamin IV
- hydroxychloroquine
- hydroxyzine
- ibrutinib
- ibuprofen
- idecabtagene vicleucel
- ifosfamide
- iloperidone
- imipenem
- imipramine
- indapamide
- indomethacin
- interferon beta 1a
- interferon beta 1b
- iopamidol
- irbesartan
- isoflurane
- isoniazid
- isradipine
- ketamine
- ketoprofen
- ketorolac
- labetalol
- lanreotide
- leflunomide
- lemborexant
- lenvatinib
- leuprolide
- levalbuterol inhaled
- levocarnitine
- levofloxacin
- levoketoconazole
- levomilnacipran
- levothyroxine
- licorice
- lidocaine
- lidocaine topical
- liothyronine
- lisinopril
- lisocabtagene maraleucel
- lithium
- lofexidine
- losartan
- loxapine
- lumacaftor/ivacaftor
- lumateperone
- lurasidone
- luspatercept
- magnesium citrate
- magnesium salicylate
- meclofenamate
- mefenamic acid
- mefloquine
- melatonin
- meloxicam
- meropenem
- methocarbamol
- methohexital
- methotrexate
- methoxy polyethylene glycol-epoetin beta
- methyldopa
- methylene blue oral
- methylergonovine
- methylphenidate
- methylprednisolone
- methyltestosterone
- metolazone
- metoprolol
- metronidazole
- mexiletine
- mifepristone
- milnacipran
- milsaperidone
- minoxidil
- mirabegron
- mirtazapine
- modafinil
- moexipril
- molindone
- moxifloxacin
- nabumetone
- nadolol
- nafarelin nasal
- nafcillin
- naproxen
- naratriptan
- naxitamab
- nebivolol
- nefazodone
- nelarabine
- nicardipine
- nicotine
- nifedipine
- nimodipine
- niraparib
- nisoldipine
- norepinephrine
- nortriptyline
- obecabtagene autoleucel
- obinutuzumab
- ofloxacin
- olanzapine
- olmesartan medoxomil
- olodaterol inhaled
- opicapone
- osilodrostat
- oxacillin
- oxaprozin
- oxazepam
- oxybutynin
- oxymetazoline nasal
- oxytocin
- ozanimod
- paliperidone
- paroxetine
- pazopanib
- peginterferon beta 1a
- penicillin G
- penicillin V
- pentobarbital
- perindopril
- perphenazine
- pexidartinib
- phendimetrazine
- phenoxybenzamine
- phentermine
- phentolamine
- phenylephrine
- phenylephrine injection
- phenylephrine nasal
- phenylephrine ophthalmic
- phenylephrine rectal
- pindolol
- piperacillin
- piroxicam
- pitolisant
- polyethylene glycol
- polyethylene glycol/electrolytes
- ponatinib
- ponesimod
- pralsetinib
- prazosin
- prednisolone
- prednisone
- procainamide
- prochlorperazine
- propofol
- propranolol
- protriptyline
- pseudoephedrine
- pyridostigmine
- pyrimethamine
- quazepam
- quetiapine
- quinapril
- quinine
- ramipril
- ramucirumab
- rasagiline
- regadenoson
- regorafenib
- remimazolam
- rimegepant
- ripretinib
- risperidone
- rivastigmine
- rizatriptan
- ropinirole
- rotigotine transdermal
- safinamide
- salmeterol inhaled
- salsalate
- selegiline
- selpercatinib
- sertraline
- sevoflurane
- siponimod
- sodium picosulfate
- solriamfetol
- sorafenib
- spironolactone
- sulfate bowel prep
- sulindac
- sumatriptan
- sunitinib
- suvorexant
- tacrolimus
- tagraxofusp
- teclistamab
- telmisartan
- temazepam
- terazosin
- terbutaline
- teriflunomide
- testosterone
- tetrabenazine
- theophylline
- thiotepa
- thiothixene
- thyroid
- timolol
- timolol ophthalmic
- tinidazole
- tisagenlecleucel
- tivozanib
- tolmetin
- torsemide
- trametinib
- trandolapril
- tranexamic acid
- trazodone
- treosulfan
- triamcinolone
- triamterene
- triazolam
- trifluoperazine
- trimipramine
- triptorelin
- ubrogepant
- vadadustat
- valacyclovir
- valbenazine
- valganciclovir
- valsartan
- vamorolone
- vandetanib
- varenicline
- vasopressin
- venlafaxine
- verapamil
- vilanterol inhaled
- vilazodone
- viloxazine
- voclosporin
- voriconazole
- vortioxetine
- warfarin
- yohimbe
- zaleplon
- zavegepant
- ziconotide
- ziprasidone
- ziv-aflibercept
- zolmitriptan
- zolpidem
Caution Advised
- 5-HTP
- allopurinol
- amantadine
- apomorphine
- apraclonidine ophthalmic
- brimonidine ophthalmic
- brimonidine topical
- bromocriptine
- brompheniramine
- buspirone
- carbinoxamine
- carisoprodol
- cetirizine
- chamomile, German
- chlophedianol
- chlorcyclizine
- chlorzoxazone
- clemastine
- cyproheptadine
- dantrolene
- darifenacin
- dexbrompheniramine
- dexchlorpheniramine
- dichlorphenamide
- difelikefalin
- difenoxin
- dimenhydrinate
- diphenhydramine
- diphenoxylate
- domperidone
- doxepin topical
- entacapone
- entrectinib
- fesoterodine
- fexinidazole
- flibanserin
- foslevodopa
- gefitinib
- glofitamab
- glycopyrrolate
- hyoscyamine
- isavuconazonium
- levocetirizine
- levodopa
- linvoseltamab
- meclizine
- meprobamate
- metyrapone
- metyrosine
- midostaurin
- mitapivat
- mitotane
- mosunetuzumab
- mycophenolate mofetil
- nevirapine
- orphenadrine
- passion flower
- pheniramine
- pramipexole
- pyrilamine
- ramelteon
- repotrectinib
- ritonavir
- selinexor
- solifenacin
- sparsentan
- tamoxifen
- tasimelteon
- telotristat ethyl
- tizanidine
- tolcapone
- tolterodine
- trihexyphenidyl
- triprolidine
- trospium
- valerian
- xanomeline
Adverse Reactions .
Serious Reactions
- neuropsychiatric disorders
- homicidal ideation
- suicidality
- depression exacerbation
- hypersensitivity reaction
- Stevens-Johnson syndrome
- erythema multiforme
- drug reaction with eosinophilia and systemic symptoms
- acute generalized exanthematous pustulosis
- anaphylaxis
- hepatotoxicity
- MI
- HTN, severe
- Brugada syndrome unmasked
- seizures
- aseptic meningitis
- glaucoma, angle-closure
Common Reactions
- nausea
- vomiting
- constipation
- headache
- dizziness
- insomnia
- xerostomia
- diarrhea
- BP incr.
- HR incr.
- anxiety
- flushing
- fatigue
- tremor
- abdominal pain
- gastroenteritis
- influenza
- tinnitus
- UTI
- HTN
- hyperhidrosis
- irritability
- dysgeusia
- rash
- muscle strain
- palpitations
Safety/Monitoring .
Monitoring Parameters
Cr at baseline, then in elderly patients continue periodically; BP, HR at baseline, then periodically; symptoms of suicidality, clinical worsening, and/or unusual behavior changes, especially during initial tx or after dose changes
Pregnancy/Lactation .
Pregnancy
Clinical Summary
weigh risk/benefit during pregnancy; wt loss during pregnancy offers no benefit and may cause fetal harm; no known risk of teratogenicity based on limited human data
Lactation
Clinical Summary
weigh risk/benefit while breastfeeding; inadequate human data, though possible risk of infant seizures with bupropion; may interfere with infant nutrition based on drug's mechanism of action; no human data available to assess effects on milk production
Pharmacology .
Metabolism: for naltrexone: liver; CYP450: none; Info: active metabolite; for bupropion hydrochloride: liver; CYP450: 2B6 substrate; Info: active metabolites
Excretion: for naltrexone: urine 53-79% (<2% unchanged), feces; Half-life: 4-5h (parent drug), 13-14h (active metabolite); for bupropion hydrochloride: urine 87% (0.5% unchanged), feces 10%; Half-life: 21h (parent drug), 20-51h (active metabolites)
Mechanism of Action
for naltrexone: antagonizes various opioid receptors; for bupropion: inhibits neuronal uptake of norepinephrine and dopamine (aminoketone)
Formulary .
No Formulary Selected
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