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Klonopin
clonazepam
Black Box Warnings .
Risks from Concomitant Opioid Use
concomitant benzodiazepine use w/ opioids may result in profound sedation, resp. depression, coma, and death; reserve concomitant use for pts w/ inadequate alternative tx options; limit to minimum required dosage and duration; monitor pts for s/sx of resp. depression and sedation
Addiction, Abuse, and Misuse
benzodiazepines expose users to risk of abuse, misuse, and addiction, can lead to overdose or death; commonly involves concomitant use w/ other meds, alcohol, and/or illicit substances, which is assoc. w/ incr. frequency of serious adverse outcomes; assess risk for abuse, misuse, and addiction before prescribing and throughout tx
Dependence and Withdrawal Reactions
cont. benzodiazepine use may lead to clinically significant physical dependence; risk of dependence and withdrawal incr. w/ longer tx duration and higher daily dose; use gradual taper to D/C after cont. use as abrupt D/C or rapid dose reduction may cause acute withdrawal reactions, potentially life-threatening
Adult Dosing .
Dosage forms: TAB: 0.5 mg, 1 mg, 2 mg
seizure disorder
- [individualize dose PO tid]
- Start: up to 0.5 mg PO tid, may incr. by 0.5-1 mg/day q3 days; Max: 20 mg/day; Info: taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
panic disorder
- [0.5-1 mg PO bid]
- Start: 0.25 mg PO bid, may incr. by 0.25-0.5 mg/day q3 days; Max: 4 mg/day; Info: consider lower start dose in elderly pts; taper dose by no more than 0.25 mg/day q3 days to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
anxiety (off-label)
- [0.25-0.5 mg PO bid-tid]
- Start: 0.25 mg PO bid, may incr. by 0.25 mg/day q1-2 days; Max: 4 mg/day; Info: consider lower start dose in elderly pts; taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
restless legs syndrome (off-label)
- [0.5-2 mg PO qhs]
- Start: 30min before bedtime; Info: taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
confusional arousals (off-label)
- [0.5-2 mg PO qhs]
- Info: taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
sleep terrors (off-label)
- [0.5-2 mg PO qhs]
- Info: taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
sleepwalking (off-label)
- [0.5-2 mg PO qhs]
- Info: taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
rapid eye movement sleep behavior disorder (off-label)
- [0.5-1 mg PO qhs]
- Info: taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
burning mouth syndrome (off-label)
- [0.25-2 mg/day PO divided qd-tid]
- Start: 0.25-0.5 mg PO qhs x1wk, may incr. by 0.25-0.5 mg/day qwk; Info: taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
Tourette syndrome (off-label)
- [0.25-3 mg/day PO divided bid-tid]
- Max: 6 mg/day; Info: taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
renal dosing
- [see below]
- renal impairment: no adjustment; Info: metabolite accumulation possible
- HD: no adjustment; no supplement; PD: not defined; Info: metabolite accumulation possible
hepatic dosing
- [see below]
- significant impairment: contraindicated
Peds Dosing .
- Dosage forms: TAB: 0.5 mg, 1 mg, 2 mg
seizure disorder
- [<10 yo or <30 kg]
- Dose: 0.1-0.2 mg/kg/day PO divided bid-tid; Start: 0.01-0.03 mg/kg/day PO divided bid-tid, incr. by up to 0.25-0.5 mg/day q3 days; Max: 0.05 mg/kg/day for initial dose; Info: give largest divided dose qhs; taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
- [10 yo and older or >30 kg]
- Dose: individualize dose PO tid; Start: up to 0.5 mg PO tid, may incr. by 0.5-1 mg/day q3 days; Max: 20 mg/day; Info: taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
sleep terrors (off-label)
- [2 yo and older]
- Dose: 0.125-0.25 mg PO qhs; Info: taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
sleepwalking (off-label)
- [2 yo and older]
- Dose: 0.125-0.25 mg PO qhs; Info: taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
rapid eye movement sleep behavior disorder (off-label)
- [2 yo and older]
- Dose: 0.25-0.5 mg PO qhs; Info: taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
Tourette syndrome (off-label)
- [6 yo and older]
- Dose: 0.25-3 mg/day PO divided bid-tid; Start: 0.25 mg/day PO divided bid-tid, titrate slowly; Max: 6 mg/day; Info: taper dose gradually to D/C; search 'benzodiazepine' for epocrates Benzodiazepine Deprescribing Advice decision tool
renal dosing
- [not defined]
- renal impairment: consider adult renal dosing for guidance
- HD/PD: consider adult renal dosing for guidance
hepatic dosing
- [see below]
- significant impairment: contraindicated
Contraindications / Cautions .
- hypersensitivity to drug or ingredient
- hepatic impairment, severe
- abrupt withdrawal
- caution: hepatic impairment, mild-moderate
- caution: renal impairment
- caution: pulmonary impairment
- caution: sleep apnea
- caution: CNS depression
- caution: alcohol use, concurrent
- caution: alcohol abuse hx
- caution: drug abuse hx
- caution: seizure hx
- caution: elderly pts
- caution: debilitated pts
- caution: depression
- caution: porphyria
Drug Interactions .
Overview
clonazepam
benzodiazepine
- CYP3A4 substrate
- antiepileptic agent
- CNS depression
- hypotensive effects
Contraindicated
- amifampridine
- bupropion
- dalfampridine
- metoclopramide
Avoid/Use Alternative
- alfentanil
- alprazolam
- aripiprazole lauroxil
- buprenorphine
- butalbital
- butorphanol
- chlordiazepoxide
- clobazam
- clonazepam
- clorazepate
- codeine
- diazepam
- dihydrocodeine
- doxylamine
- estazolam
- ethanol
- fentanyl
- ginkgo
- hydrocodone
- hydromorphone
- isocarboxazid
- kava
- kratom
- levorphanol
- lindane topical
- lorazepam
- meperidine
- metaxalone
- methadone
- midazolam
- morphine
- nalbuphine
- oliceridine
- opium
- oxazepam
- oxybate
- oxycodone
- oxymorphone
- pentazocine
- phenelzine
- promethazine
- quazepam
- remimazolam
- ropeginterferon alfa-2b
- tapentadol
- temazepam
- thalidomide
- tramadol
- tranylcypromine
- triazolam
- trimethobenzamide
- zuranolone
Monitor/Modify Tx
- 5-HTP
- adagrasib
- aldesleukin
- allopurinol
- almotriptan
- amantadine
- amitriptyline
- amoxapine
- apomorphine
- apraclonidine ophthalmic
- aprepitant
- aripiprazole
- aripiprazole bimonthly injection
- asenapine
- atazanavir
- baclofen
- baclofen intrathecal
- berotralstat
- brexanolone
- brexpiprazole
- brimonidine topical
- brivaracetam
- bromocriptine
- brompheniramine
- buspirone
- cannabidiol
- cannabis
- carbamazepine
- carbinoxamine
- cariprazine
- carisoprodol
- cenobamate
- ceritinib
- cetirizine
- chamomile, German
- chloramphenicol
- chlorpheniramine
- chlorpromazine
- chlorzoxazone
- ciprofloxacin
- citalopram
- clarithromycin
- clemastine
- clofazimine
- clomipramine
- clonidine
- clozapine
- cobicistat
- conivaptan
- crizotinib
- cyclobenzaprine
- cyclosporine
- cyproheptadine
- danazol
- dantrolene
- daridorexant
- darifenacin
- darunavir
- desflurane
- desipramine
- desvenlafaxine
- deutetrabenazine
- dexchlorpheniramine
- dexmedetomidine
- dexmedetomidine injection
- dichlorphenamide
- difelikefalin
- difenoxin
- diltiazem
- dimenhydrinate
- diphenhydramine
- diphenoxylate
- domperidone
- doxepin
- doxepin topical
- dronabinol
- dronedarone
- droperidol
- duloxetine
- duvelisib
- efavirenz
- eletriptan
- entacapone
- entrectinib
- erythromycin
- escitalopram
- esketamine
- eslicarbazepine acetate
- eszopiclone
- ethanol (in some formulations)
- ethosuximide
- etomidate
- fedratinib
- felbamate
- fenfluramine
- fesoterodine
- flibanserin
- fluconazole
- fluoxetine
- fluphenazine
- fluvoxamine
- fosamprenavir
- fosphenytoin
- frovatriptan
- gabapentin
- gabapentin enacarbil
- ganaxolone
- glofitamab
- glycopyrrolate
- grapefruit
- guanfacine
- haloperidol
- hydroxyzine
- hyoscyamine
- idelalisib
- ifosfamide
- iloperidone
- imatinib
- imipramine
- isavuconazonium
- isoflurane
- itraconazole
- ketamine
- ketoconazole
- lacosamide
- lamotrigine
- lasmiditan
- lefamulin
- lemborexant
- lenacapavir
- letermovir
- levetiracetam
- levocetirizine
- levodopa
- levoketoconazole
- levomilnacipran
- lofexidine
- lonafarnib
- lopinavir/ritonavir
- loxapine
- lumateperone
- lurasidone
- meclizine
- melatonin
- meprobamate
- methocarbamol
- methohexital
- methsuximide
- methyldopa
- metyrapone
- metyrosine
- mifepristone
- milnacipran
- mirtazapine
- mitotane
- molindone
- mosunetuzumab
- mycophenolate mofetil
- naltrexone
- naratriptan
- nefazodone
- nelarabine
- nelfinavir
- netupitant
- nilotinib
- nirogacestat
- nortriptyline
- olanzapine
- opicapone
- orphenadrine
- oxcarbazepine
- oxybutynin
- paliperidone
- paroxetine
- passion flower
- pentobarbital
- perampanel
- perphenazine
- pheniramine
- phenobarbital
- phenylephrine injection
- phenytoin
- pimozide
- posaconazole
- pramipexole
- pregabalin
- primidone
- procarbazine
- prochlorperazine
- propofol
- protriptyline
- pyrilamine
- quetiapine
- ramelteon
- rasagiline
- remifentanil
- repotrectinib
- ribociclib
- risperidone
- ritonavir
- rizatriptan
- ropinirole
- rotigotine transdermal
- rufinamide
- safinamide
- saquinavir
- scopolamine
- selegiline
- selegiline transdermal
- selinexor
- sertraline
- sevoflurane
- solifenacin
- stiripentol
- sufentanil
- sumatriptan
- suvorexant
- tasimelteon
- tetrabenazine
- thioridazine
- thiothixene
- tiagabine
- tipranavir
- tizanidine
- tolcapone
- tolterodine
- topiramate
- trazodone
- trifluoperazine
- trihexyphenidyl
- trimipramine
- triprolidine
- trospium
- tucatinib
- valbenazine
- valerian
- valproic acid
- venlafaxine
- verapamil
- vigabatrin
- vilazodone
- viloxazine
- voriconazole
- zaleplon
- ziconotide
- ziprasidone
- zolmitriptan
- zolpidem
- zonisamide
Caution Advised
- acyclovir
- aminophylline
- amoxicillin
- amphetamine
- ampicillin
- apalutamide
- axicabtagene ciloleucel
- benzphetamine
- betamethasone
- brexucabtagene autoleucel
- brimonidine ophthalmic
- busulfan
- cefazolin
- cefepime
- cefiderocol
- ceftaroline fosamil
- ceftazidime
- chlorambucil
- chloroquine
- ciltacabtagene autoleucel
- cisatracurium
- cocaine
- cortisone
- darbepoetin alfa
- darolutamide
- deflazacort
- delafloxacin
- dexamethasone
- dexmethylphenidate
- dextroamphetamine
- dicloxacillin
- diethylpropion
- donepezil
- elivaldogene autotemcel
- encorafenib
- enzalutamide
- ephedra
- epoetin alfa
- ertapenem
- foscarnet
- galantamine
- ganciclovir
- goserelin
- histrelin
- hydroxychloroquine
- idecabtagene vicleucel
- imipenem
- iohexol
- iopamidol
- isoniazid
- ivosidenib
- ketorolac
- leuprolide
- levocarnitine
- levofloxacin
- lidocaine
- lidocaine topical
- linezolid
- lisdexamfetamine
- lisocabtagene maraleucel
- lithium
- lorlatinib
- lumacaftor/ivacaftor
- magnesium citrate
- mefloquine
- meropenem
- methamphetamine
- methotrexate
- methoxy polyethylene glycol-epoetin beta
- methylphenidate
- metronidazole
- mexiletine
- moxifloxacin
- nafarelin
- nafcillin
- ofloxacin
- oxacillin
- penicillin G
- penicillin V
- phendimetrazine
- phentermine
- piperacillin
- polyethylene glycol
- polyethylene glycol/electrolytes
- pyridostigmine
- pyrimethamine
- quinine
- regadenoson
- rifabutin
- rifampin
- rivastigmine
- sodium phosphate (bowel prep)
- sodium picosulfate
- St. John's wort
- sulfate bowel prep
- tacrolimus
- teclistamab
- terbutaline
- theophylline
- tisagenlecleucel
- tranexamic acid
- triamcinolone
- triptorelin
- valacyclovir
- valganciclovir
- varenicline
Adverse Reactions .
Serious Reactions
- respiratory depression
- dependency
- abuse
- seizures
- suicidality
- hypotension, orthostatic
- tachycardia
- syncope
- blood dyscrasias
- hepatomegaly
- CNS stimulation, paradoxical
- withdrawal sx if abrupt D/C
- protracted withdrawal syndrome
Common Reactions
- drowsiness
- impaired coordination
- dizziness
- depression
- fatigue
- dysarthria
- amnesia
- asthenia
- confusion
- impaired concentration
- disinhibition
- libido changes
- irritability
- dystonia
- diplopia
- appetite changes
- constipation
- incontinence
- urinary retention
- hypotension
- rash
- LFTs elevated
Safety/Monitoring .
Monitoring Parameters
LFTs if long-term tx; s/sx depression, behavior changes, suicidality
Look/Sound-Alike Drug Names
KlonoPIN confused with: cloNIDine
clonazePAM confused with: ALPRAZolam; Ativan; cloBAZam; cloNIDine; clorazepate; cloZAPine; diazePAM; LORazepam; OLANZapine
Pregnancy/Lactation .
Pregnancy
Clinical Summary
weigh risk/benefit during pregnancy; possible risk of teratogenicity based on conflicting human data w/ benzodiazepine class; risk of neonatal respiratory depression, hypotonia, sedation, and withdrawal sx w/ near term use based on human data w/ benzodiazepine class
Pregnancy Registry
encourage pts to enroll in North American Antiepileptic Drug Pregnancy Registry at 1-888-233-2334 or www.aedpregnancyregistry.org
Lactation
Clinical Summary
weigh risk/benefit while breastfeeding; possible risk of infant CNS depression based on limited human data and drug properties; no human data available to assess effects on milk production
Pharmacology .
Metabolism: liver extensively; CYP450: 3A4 partial substrate
Excretion: urine; Half-life: 30-40h
Subclass: Benzodiazepines (BZDs), Long-acting ; Parasomnias ; Seizure Disorders ; Sleep-related Movement Disorders ; Tic Disorders/Tourette Syndrome
Mechanism of Action
binds to benzodiazepine receptors; enhances GABA effects
Formulary .
No Formulary Selected
Manufacturer/Pricing .
Manufacturer: H2-Pharma, LLC
DEA/FDA: Schedule IV
Approximate Retail Price
from http://www.goodrx.com/klonopin
oral tablet:
- 0.5 mg (30 ea): $84.00
- 1 mg (30 ea): $96.00
- 2 mg (60 ea): $257.00
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