Identification

Name

Clonazepam

Accession Number

DB01068

Description

A benzodiazepine used to treat various seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop ^{Label 11,12,13,14}. The agent has also been indicated for treating panic disorder ^{Label 7,11,12,13,14}. The mechanism of action appears to involve the enhancement of gamma-aminobutyric acid receptor responses ^{Label 7,8,11,12,13,14}.

Since being first patented in 1960 and then released for sale from Roche in the US in 1975 ^9,10, clonazepam has experienced a storied history in the treatment of the aforementioned medical conditions. Now available as a generic medication, the agent continues to see exceptionally high use as millions of prescriptions are written for the medication internationally every year. Unfortunately, however, like most benzodiazepines, clonazepam use has also been associated with recreational use and drug abuse ^{Label 11,12,13,14}.

Type

Small Molecule

Groups

Approved, Illicit

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Clonazepam (DB01068)

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Weight

Average: 315.711
Monoisotopic: 315.041068908

Chemical Formula

C₁₅H₁₀ClN₃O₃

Synonyms

• 1,3-dihydro-7-nitro-5-(2-chlorophenyl)-2H-1,4.benzodiazepin-2-one
• 5-(2-chloro-phenyl)-7-nitro-1,3-dihydro-benzo[e][1,4]diazepin-2-one
• 5-(2-chlorophenyl)-7-nitro-1H-benzo[e][1,4]diazepin-2(3H)-one
• 5-(o-chlorophenyl)-7-nitro-1,3-dihydro-2H-1,4-benzodiazepin-2-one
• Clonazepam
• Clonazepamum

External IDs

• RO 5-4023
• RO-5-4023

Pharmacology

Indication

Clonazepam is indicated as monotherapy or as an adjunct in the treatment of Lennox-Gastaut syndrome (petit mal variant), akinetic, and myoclonic seizures ^{Label 13}. Furthermore, clonazepam may also be of some value in patients with absence spells (petit mal) who have failed to respond to succinimides ^{Label 13}. Additionally, clonazepam is also indicated for the treatment of panic disorder, with or without agoraphobia, as defined in the DSM-V ^Label.

Alternatively, some regional prescribing information note that clonazepam is indicated for all clinical forms of epileptic disease and seizures in adults, especially absence seizures (petit mal) including atypical absence; primary or secondarily generalised tonic-clonic (grand mal), tonic or clonic seizures; partial (focal) seizures with elementary or complex symptomatology; various forms of myoclonic seizures, myoclonus and associated abnormal movements ^11,14. Such regional label data also has clonazepam indicated for most types of epilepsy in infants and children, especially absences (petit mal), myoclonic seizures and tonic-clonic fits, whether due to primary generalized epilepsy or to secondary generalization of partial epilepsy ¹⁴.

Associated Conditions

• Akinetic seizures
• Burning Mouth Syndrome
• Gilles de la Tourette's Syndrome
• Lennox-Gastaut Syndrome (LGS)
• Mixed manic depressive episode
• Panic Disorders
• Rapid Eye Movement Sleep Disorder
• Restless Legs Syndrome (RLS)
• Tardive Dyskinesia (TD)
• Tremor, Essential
• Acute Manic episode
• Myoclonic seizures
• Refractory absence Seizures

Contraindications & Blackbox Warnings

Learn about our commercial Contraindications & Blackbox Warnings data.

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Pharmacodynamics

The pharmacodynamic properties of clonazepam are common among benzodiazepines and include anticonvulsive, sedative, muscle relaxing and anxiolytic effects ^6,11,12,13. Animal data and electroencephalographic investigations in man have shown that clonazepam rapidly suppresses many types of paroxysmal activity including the spike and wave discharge in absence seizures (petit mal), slow spike wave, generalized spike wave, spikes with temporal or other locations, as well as irregular spikes and waves ^{Label 6,11,12,13}. Moreover, the agent can also decrease the frequency, amplitude, duration, and spread of discharge in minor motor seizures ^{Label 12}.

Generalized EEG abnormalities are more readily suppressed by clonazepam than are focal EEG abnormalities such as focal spikes ¹¹. Clonazepam has beneficial effects in generalized and focal epilepsies ¹¹.

Mechanism of action

Gamma-Aminobutyric acid (GABA) is considered the principal inhibitory neurotransmitter in the human body ^6,7,8. When GABA binds to GABA(a) receptors found in neuron synapses, chloride ions are conducted across neuron cell membranes via an ion channel in the receptors ^6,7,8,13. With enough chloride ions conducted, the local, associated neuron membrane potentials are hyperpolarized - making it more difficult or less likely for action potentials to fire, ultimately resulting in less excitation of the neurons ^6,7,8,13.

Subsequently, benzodiazepines like clonazepam can bind to benzodiazepine receptors that are components of various varieties of GABA(a) receptors ^{6,7,8,13,11,12}. This binding acts to enhance the effects of GABA by increasing GABA affinity for the GABA(a) receptor, which ultimately enhances GABA ligand binding at the receptors ^{6,7,8,13,11,12}. This enhanced ligand binding of the inhibitory neurotransmitter GABA to the receptors increases the aforementioned chloride ion conduction (perhaps reportedly via an increase in the frequency of the chloride channel opening), resulting in a hyperpolarized cell membrane that prevents further excitation of the associated neuron cells ^{6,7,8,13,11,12}. Combined with the notion that such benzodiazepine receptor associated GABA(a) receptors exist both peripherally and in the CNS, this activity consequently facilitates various effects like sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action ^{6,7,8,13,11,12}.

In particular, when out of the ordinary rapid and repetitive electrical signals are released in the CNS, it is proposed that the brain can become over-stimulated and ordinary functions are disrupted - resulting in seizure activity ⁸. By enhancing the neuro-inhibitory activity of GABA, it is believed that clonazepam can facilitate in decreasing any excessive electrical nerve activity in the CNS that might be contributing to seizures ⁸. Concurrently, it is also believed that clonazepam's actions in enhancing GABA effects may inhibit neuronal activity proposed to occur in amygdala-centered fear circuits - therefore assisting in the management of anxiety or panic ⁷.

Target	Actions	Organism
AGABA(A) Receptor	positive allosteric modulator	Humans
AGABA(A) Receptor Benzodiazepine Binding Site	ligand	Humans
UNuclear receptor subfamily 1 group I member 2	partial agonist	Humans

Absorption

Clonazepam is rapidly and almost entirely absorbed after oral administration as tablets ^{Label 12,14}. Peak plasma concentrations of clonazepam administered by the oral route are reached within 1-4 hours and the associated absorption half-life is about 25 minutes ^{Label 12,14}. The absolute bioavailability is approximately 90% - but with substantially large differences between individuals ^{Label 12,14}.

Volume of distribution

Clonazepam distributes very rapidly to various organs and body tissues with preferential uptake by brain structures ^12,14. The apparent volume of distribution has been documented as approximately 3 L/kg ^12,14.

Protein binding

The recorded plasma protein binding of clonazepam ranges between 82–86% ^12,14.

Metabolism

Clonazepam is metabolized principally in the liver ^12,14. The metabolic pathways include hydroxylation, reduction of the nitro groups to amine groups, and the addition of acetate to the amino grouping ^12,14. In particular, clonazepam is extensively metabolized by reduction to 7-amino-clonazepam and by N-acetylation to 7-acetamido-clonazepam ^12,14. Hydroxylation at the C-3 position also occurs ^12,14. Hepatic cytochrome P450 3A4 is implicated in the nitroreduction of clonazepam to pharmacologically inactive metabolites ^12,14.

Hover over products below to view reaction partners

• Clonazepam
  • 7-amino-clonazepam
    • 7-acetamido-clonazepam

Route of elimination

Approximately 50-70% of a clonazepam dose is excreted in the urine and 10-30% is excreted in the feces as metabolites ^12,14. The excretion of unchanged clonazepam in the urine is typically less than 2% of the administered dose ^12,14. Metabolites of clonazepam are present in urine as both free and conjugated (glucuronide and sulfate) compounds ^12,14.

Half-life

The mean elimination half-life determined for clonazepam is independent of the dose given and has been documented as being about 30-40 hours ^12,14.

Clearance

The documented clearance for clonazepam is approximately 55 ml/min regardless of gender ¹². Nevertheless, clearance values normalized by weight decline with increasing body weight ¹².

Adverse Effects

Learn about our commercial Adverse Effects data.

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Toxicity

Benzodiazepines like clonazepam commonly cause drowsiness, ataxia, dysarthria, and nystagmus. Overdose with clonazepam is generally not life-threatening if the drug is taken alone, but may lead to areflexia, apnea, hypotension, cardiorespiratory depression, and coma. Coma, if it does occur, usually lasts a few hours but it can become more protracted and cyclical, especially in elderly patients. Increased frequency of seizures may occur in patients at supratherapeutic plasma concentrations. Benzodiazepine respiratory depressant effects are more serious when compounded in patients with respiratory disease.

An increased risk of congenital malformations associated with the use of benzodiazepine drugs like clonazepam has been suggested in several studies ^{Label 12,14}. There may also be non-teratogenic risks associated with the use of benzodiazepines during pregnancy ^{Label 12,14}. There have been reports of neonatal flaccidity, respiratory and feeding difficulties, and hypothermia in children born to mothers who have been receiving benzodiazepines late in pregnancy ^{Label 12,14}. In addition, children born to mothers receiving benzodiazepines late in pregnancy may be at some risk of experiencing withdrawal symptoms during the postnatal period ^{Label 12,14}. In general, it is best for patients who are of childbearing potential and also use benzodiazepines like clonazepam to discuss such matters with their health care professionals as careful consideration must be undertaken regarding the intersection of the risks of untreated seizure potential in the patient and any possible toxicity to the fetus ^{Label 12,14}.

Although the active ingredient of clonazepam has been found to pass into the maternal milk in small amounts only, mothers receiving clonazepam should not breast-feed their infants ^{Label 12,14}.

Since the possibility that adverse effects on the physical or mental development of the child could become apparent only after a number of years, the risk-benefit consideration of the long-term use of clonazepam in pediatric patients younger than five years of age is important ^{Label 12,14}.

The pharmacological effects of benzodiazepines like clonazepam appear to be greater in elderly patients than in younger patients even at similar plasma benzodiazepine concentrations, possibly because of age-related changes in drug-receptor interactions, post-receptor mechanisms, and organ function ^{Label 12,14}. In general elderly patients should be started on the lowest possible dose of clonazepam and observed closely ^{Label 12,14}. There is an increased risk for falls and fractures among elderly and debilitated benzodiazepine users ^{Label 12,14}. The risk is increased in those taking concomitant sedatives, including substances like benzodiazepines, alcoholic beverages, and so on ^{Label 12,14}.

Some oral LD50 values documented are >4000 mg/kg for the mouse model, >4000 mg/kg for the adult rat model, and >2000 mg/kg for the rabbit model ¹².

Affected organisms

• Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
Unlock Additional Data
Abacavir	Abacavir may decrease the excretion rate of Clonazepam which could result in a higher serum level.
Abametapir	The serum concentration of Clonazepam can be increased when it is combined with Abametapir.
Acarbose	Acarbose may decrease the excretion rate of Clonazepam which could result in a higher serum level.
Aceclofenac	Aceclofenac may decrease the excretion rate of Clonazepam which could result in a higher serum level.
Acemetacin	Acemetacin may decrease the excretion rate of Clonazepam which could result in a higher serum level.
Acetaminophen	The metabolism of Clonazepam can be increased when combined with Acetaminophen.
Acetazolamide	The risk or severity of adverse effects can be increased when Acetazolamide is combined with Clonazepam.
Acetophenazine	The risk or severity of adverse effects can be increased when Acetophenazine is combined with Clonazepam.
Acetylsalicylic acid	Acetylsalicylic acid may decrease the excretion rate of Clonazepam which could result in a higher serum level.
Aclidinium	Clonazepam may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.

Additional Data Available

Extended Description
Extended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
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Severity
Severity
A severity rating for each drug interaction, from minor to major.
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Evidence Level
Evidence Level
A rating for the strength of the evidence supporting each drug interaction.
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Action
Action
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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Food Interactions

• Avoid alcohol.
• Limit caffeine intake.
• Take with or without food. The absorption is unaffected by food.

Products

Product Images

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International/Other Brands

Antelepsin (AWD) / Iktorivil (Roche) / Rivotril (Roche)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Unlock Additional Data
Clonapam	Tablet		Oral	Valeant Canada Lp Valeant Canada S.E.C.	1997-01-31	Not applicable
Clonapam	Tablet		Oral	Valeant Canada Lp Valeant Canada S.E.C.	1997-01-31	Not applicable
Clonapam	Tablet		Oral	Valeant Canada Lp Valeant Canada S.E.C.	1997-02-28	Not applicable
Clonazepam	Tablet	1 mg	Oral	Meliapharm Inc	2010-10-20	2014-06-25
Clonazepam	Tablet	2 mg	Oral	Sivem Pharmaceuticals Ulc	2015-07-09	2018-07-11
Clonazepam	Tablet	1 mg/1	Oral	Vintage Pharmaceuticals, LLC	2006-10-18	2006-10-18
Clonazepam	Tablet	1 mg/1	Oral	Watson Pharmaceuticals	2008-03-18	Not applicable
Clonazepam	Tablet	1 mg	Oral	Sivem Pharmaceuticals Ulc	2015-07-09	2017-12-19
Clonazepam	Tablet	0.25 mg	Oral	Sivem Pharmaceuticals Ulc	2015-07-09	2017-07-12
Clonazepam	Tablet	2 mg	Oral	Meliapharm Inc	2010-10-20	2014-06-25

Additional Data Available

Application Number
Application Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
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Product Code
Product Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Unlock Additional Data
Accel-clonazepam	Tablet		Oral	Accel Pharma Inc	Not applicable	Not applicable
Accel-clonazepam	Tablet		Oral	Accel Pharma Inc	Not applicable	Not applicable
Accel-clonazepam	Tablet		Oral	Accel Pharma Inc	Not applicable	Not applicable
Apo-clonazepam - Tab 0.5mg	Tablet		Oral	Apotex Corporation	1995-12-31	Not applicable
Apo-clonazepam - Tab 2mg	Tablet		Oral	Apotex Corporation	1995-12-31	Not applicable
Clonazepam	Tablet	2 mg/1	Oral	REMEDYREPACK INC.	2019-07-23	Not applicable
Clonazepam	Tablet	2 mg/1	Oral	A S Medication Solutions	2006-06-28	Not applicable
Clonazepam	Tablet	1 mg/1	Oral	A-S Medication Solutions	2011-06-03	Not applicable
Clonazepam	Tablet	2 mg/1	Oral	Actavis Pharma, Inc.	1997-02-12	2022-01-31
Clonazepam	Tablet	0.5 mg/1	Oral	Qualitest Pharmaceuticals	2006-06-28	2019-09-30

Additional Data Available

Application Number
Application Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more
Product Code
Product Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
Learn more

Categories

ATC Codes

N03AE01 — Clonazepam

• N03AE — Benzodiazepine derivatives
• N03A — ANTIEPILEPTICS
• N03 — ANTIEPILEPTICS
• N — NERVOUS SYSTEM

Drug Categories

• Anticonvulsants
• Benzazepines
• Benzodiazepines and benzodiazepine derivatives
• Benzodiazepinones
• Central Nervous System Agents
• Central Nervous System Depressants
• Cytochrome P-450 CYP2E1 Inhibitors
• Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Substrates
• Drugs that are Mainly Renally Excreted
• GABA Agents
• GABA Modulators
• Heterocyclic Compounds, Fused-Ring
• Muscle Relaxants
• Muscle Relaxants, Centrally Acting Agents
• Nervous System

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as 1,4-benzodiazepines. These are organic compounds containing a benzene ring fused to a 1,4-azepine.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Benzodiazepines

Sub Class

1,4-benzodiazepines

Direct Parent

1,4-benzodiazepines

Alternative Parents

Nitroaromatic compounds / Chlorobenzenes / Aryl chlorides / Cyclic carboximidic acids / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Organic oxoazanium compounds / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organochlorides / Organic zwitterions / Organic oxides / Hydrocarbon derivatives

show 4 more

Substituents

1,4-benzodiazepine / Allyl-type 1,3-dipolar organic compound / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / C-nitro compound / Chlorobenzene / Cyclic carboximidic acid / Halobenzene / Hydrocarbon derivative / Imine / Ketimine / Monocyclic benzene moiety / Nitroaromatic compound / Organic 1,3-dipolar compound / Organic nitro compound / Organic nitrogen compound / Organic oxide / Organic oxoazanium / Organic oxygen compound / Organic zwitterion / Organochloride / Organohalogen compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Propargyl-type 1,3-dipolar organic compound

show 19 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

monochlorobenzenes, 1,4-benzodiazepinone (CHEBI:3756)

Chemical Identifiers

UNII

5PE9FDE8GB

CAS number

1622-61-3

InChI Key

DGBIGWXXNGSACT-UHFFFAOYSA-N

InChI

InChI=1S/C15H10ClN3O3/c16-12-4-2-1-3-10(12)15-11-7-9(19(21)22)5-6-13(11)18-14(20)8-17-15/h1-7H,8H2,(H,18,20)

IUPAC Name

5-(2-chlorophenyl)-7-nitro-2,3-dihydro-1H-1,4-benzodiazepin-2-one

SMILES

[O-][N+](=O)C1=CC2=C(NC(=O)CN=C2C2=CC=CC=C2Cl)C=C1

References

Synthesis Reference

Kariss, J. and Newmark, H.L.; US. Patents 3,116,203; December 31, 1963; and 3,123,529; March 3, 1964; both assigned to Hoffmann-LaRoche, Inc. Keller, O., Steiger, N. and Sternbach, L.H.; U S . Patents 3,121,114; February 11, 1964; and 3,203990; August 31, 1965; both assigned to Hoffmann-LaRoche, Inc. Focella, A. and Rachlin, A.I.; U.S. Patent 3,335,181; August 8, 1967; assigned to Hoffmann- LaRoche. Inc.

General References

1. Dreifuss FE, Penry JK, Rose SW, Kupferberg HJ, Dyken P, Sato S: Serum clonazepam concentrations in children with absence seizures. Neurology. 1975 Mar;25(3):255-8. [PubMed:1089913]
2. Robertson MD, Drummer OH: Postmortem drug metabolism by bacteria. J Forensic Sci. 1995 May;40(3):382-6. [PubMed:7782744]
3. Rosen GM, Turner MJ 3rd: Synthesis of spin traps specific for hydroxyl radical. J Med Chem. 1988 Feb;31(2):428-32. [PubMed:2828624]
4. Rosen GM, Demos HA, Rauckman EJ: Not all aromatic nitro compounds form free radicals. Toxicol Lett. 1984 Aug;22(2):145-52. [PubMed:6089382]
5. Earley JV, Fryer RI, Ning RY: Quinazolines and 1,4-benzodiazepines. LXXXIX: Haptens useful in benzodiazepine immunoassay development. J Pharm Sci. 1979 Jul;68(7):845-50. [PubMed:458601]
6. DeVane CL, Ware MR, Lydiard RB: Pharmacokinetics, pharmacodynamics, and treatment issues of benzodiazepines: alprazolam, adinazolam, and clonazepam. Psychopharmacol Bull. 1991;27(4):463-73. [PubMed:1687613]
7. Nardi AE, Machado S, Almada LF, Paes F, Silva AC, Marques RJ, Amrein R, Freire RC, Martin-Santos R, Cosci F, Hallak JE, Crippa JA, Arias-Carrion O: Clonazepam for the treatment of panic disorder. Curr Drug Targets. 2013 Mar;14(3):353-64. [PubMed:23256724]
8. Jenner P, Pratt JA, Marsden CD: Mechanism of action of clonazepam in myoclonus in relation to effects on GABA and 5-HT. Adv Neurol. 1986;43:629-43. [PubMed:2418652]
9. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. [ISBN:9783527607495]
10. Shorter, Edward (2005). A Historical Dictionary of Psychiatry. Oxford University Press. [ISBN:9780190292010]
11. Electronic Medicines Compendium: Clonazepam Rosemont 2mg/5ml Oral Solution [Link]
12. Rivotril (Clonazepam) 0.5 mg and 2 mg Tablets Canadian Product Monograph [File]
13. Clonazepam Fact Sheet from http://cdn.neiglobal.com/content/pg/live/clonazepam.pdf [File]
14. Rivotril (Clonazepam) Australian Product Information [File]

External Links

Human Metabolome Database

HMDB0015201

KEGG Drug

D00280

PubChem Compound

2802

PubChem Substance

46507677

ChemSpider

2700

BindingDB

50019213

RxNav

2598

ChEBI

3756

ChEMBL

CHEMBL452

ZINC

ZINC000003813003

Therapeutic Targets Database

DAP000259

PharmGKB

PA449050

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Clonazepam

AHFS Codes

• 28:12.08 — Benzodiazepines

FDA label

Download (513 KB)

MSDS

Download (74.3 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Treatment	Fear of open spaces / Panic Disorders	1
4	Completed	Treatment	Post Traumatic Stress Disorder (PTSD)	1
4	Completed	Treatment	Social Phobia	1
4	Recruiting	Diagnostic	Severe Major Depression Disorder	1
4	Recruiting	Treatment	Burning Mouth Syndrome	1
4	Recruiting	Treatment	Epilepsies	1
4	Unknown Status	Treatment	Cardiac Arrest (CA)	1
4	Withdrawn	Treatment	Burning Mouth Syndrome	1
4	Withdrawn	Treatment	Schizoaffective Disorders / Schizophrenia / Schizophreniform Disorder	1
3	Completed	Treatment	Epilepsies / Refractory seizure disorders	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

• Actavis Group
• Aidarex Pharmacuticals LLC
• Alphapharm Party Ltd.
• Apotex Inc.
• Apotheca Inc.
• A-S Medication Solutions LLC
• Barr Pharmaceuticals
• Bryant Ranch Prepack
• Caraco Pharmaceutical Labs
• Cardinal Health
• Caremark LLC
• Catalent Pharma Solutions
• Cebert Pharmaceuticals Inc.
• Centaur Pharmaceuticals Pvt Ltd.
• Comprehensive Consultant Services Inc.
• Corepharma LLC
• Coupler Enterprises Inc.
• Direct Dispensing Inc.
• Dispensing Solutions
• Diversified Healthcare Services Inc.
• Eon Labs
• F Hoffmann-La Roche Ltd.
• Golden State Medical Supply Inc.
• Goldline Laboratories Inc.
• H.J. Harkins Co. Inc.
• Heartland Repack Services LLC
• Innoviant Pharmacy Inc.
• Kali Laboratories Inc.
• Keltman Pharmaceuticals Inc.
• Lake Erie Medical and Surgical Supply
• Liberty Pharmaceuticals
• Major Pharmaceuticals
• Mckesson Corp.
• Murfreesboro Pharmaceutical Nursing Supply
• Mylan
• Novopharm Ltd.
• Nucare Pharmaceuticals Inc.
• Palmetto Pharmaceuticals Inc.
• Par Pharmaceuticals
• PD-Rx Pharmaceuticals Inc.
• Physicians Total Care Inc.
• Preferred Pharmaceuticals Inc.
• Prepackage Specialists
• Prepak Systems Inc.
• Qualitest
• Rebel Distributors Corp.
• Recalcine Laboratorios
• Redpharm Drug
• Remedy Repack
• Sandhills Packaging Inc.
• Sanofi-Aventis Inc.
• Southwood Pharmaceuticals
• St Mary's Medical Park Pharmacy
• Stat Rx Usa
• Syntex SA
• Teva Pharmaceutical Industries Ltd.
• Torpharm Inc.
• UDL Laboratories
• Va Cmop Dallas
• Vintage Pharmaceuticals Inc.

Dosage Forms

Form	Route	Strength
Tablet	Oral	0.25 mg
Tablet	Oral	0.5 mg/1
Tablet	Oral	1 mg
Tablet	Oral	1 mg/1
Tablet	Oral	2 mg/1
Tablet, orally disintegrating	Oral	.25 mg/1
Tablet, orally disintegrating	Oral	.5 mg/1
Tablet, orally disintegrating	Oral	0.125 mg/1
Tablet, orally disintegrating	Oral	0.25 mg/1
Tablet, orally disintegrating	Oral	0.5 mg/1
Tablet, orally disintegrating	Oral	1 mg/1
Tablet, orally disintegrating	Oral	2 mg/1
Tablet	Oral	2 mg
Solution	Oral	2.5 mg
Tablet	Oral	.5 mg/1
Wafer	Oral	0.125 mg/1
Wafer	Oral	0.25 mg/1
Wafer	Oral	0.5 mg/1
Wafer	Oral	1 mg/1
Wafer	Oral	2 mg/1
Tablet	Oral
Solution / drops	Oral	2.5 mg/1ml
Solution / drops	Oral	2.5 MG/ML
Injection, solution	Intravenous	1 mg/1ml
Tablet		2 mg
Solution / drops		2.5 mg/1ml
Tablet
Tablet	Oral	0.5 mg

Prices

Unit description	Cost	Unit
Klonopin 2 mg tablet	2.85USD	tablet
Klonopin 1 mg tablet	2.17USD	tablet
Klonopin 0.5 mg tablet	1.91USD	tablet
ClonazePAM ODT 2 mg Dispersible Tablet	1.67USD	dispersible tablet
ClonazePAM ODT 0.25 mg Dispersible Tablet	1.22USD	dispersible tablet
ClonazePAM ODT 0.5 mg Dispersible Tablet	1.18USD	dispersible tablet
ClonazePAM ODT 0.125 mg Dispersible Tablet	1.17USD	dispersible tablet
ClonazePAM ODT 1 mg Dispersible Tablet	1.1USD	dispersible tablet
Clonazepam 2 mg tablet	0.81USD	tablet
Clonazepam 1 mg tablet	0.63USD	tablet
Clonazepam 0.5 mg tablet	0.61USD	tablet
Rivotril 2 mg Tablet	0.38USD	tablet
Rivotril 0.5 mg Tablet	0.22USD	tablet
Apo-Clonazepam 2 mg Tablet	0.21USD	tablet
Co Clonazepam 2 mg Tablet	0.21USD	tablet
Mylan-Clonazepam 2 mg Tablet	0.21USD	tablet
Novo-Clonazepam 2 mg Tablet	0.21USD	tablet
Phl-Clonazepam 2 mg Tablet	0.21USD	tablet
Pms-Clonazepam 2 mg Tablet	0.21USD	tablet
Ratio-Clonazepam 2 mg Tablet	0.21USD	tablet
Sandoz Clonazepam 2 mg Tablet	0.21USD	tablet
Co Clonazepam 1 mg Tablet	0.19USD	tablet
Phl-Clonazepam 1 mg Tablet	0.19USD	tablet
Pms-Clonazepam 1 mg Tablet	0.19USD	tablet
Sandoz Clonazepam 1 mg Tablet	0.19USD	tablet
Apo-Clonazepam 0.5 mg Tablet	0.12USD	tablet
Co Clonazepam 0.5 mg Tablet	0.12USD	tablet
Mylan-Clonazepam 0.5 mg Tablet	0.12USD	tablet
Novo-Clonazepam 0.5 mg Tablet	0.12USD	tablet
Phl-Clonazepam 0.5 mg Tablet	0.12USD	tablet
Phl-Clonazepam-R 0.5 mg Tablet	0.12USD	tablet
Pms-Clonazepam 0.5 mg Tablet	0.12USD	tablet
Pms-Clonazepam-R 0.5 mg Tablet	0.12USD	tablet
Ratio-Clonazepam 0.5 mg Tablet	0.12USD	tablet
Sandoz Clonazepam 0.5 mg Tablet	0.12USD	tablet
Pms-Clonazepam 0.25 mg Tablet	0.07USD	tablet

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Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	238-240	Kariss, J. and Newmark, H.L.; US. Patents 3,116,203; December 31, 1963; and 3,123,529; March 3, 1964; both assigned to Hoffmann-LaRoche, Inc. Keller, O., Steiger, N. and Sternbach, L.H.; U S . Patents 3,121,114; February 11, 1964; and 3,203990; August 31, 1965; both assigned to Hoffmann-LaRoche, Inc. Focella, A. and Rachlin, A.I.; U.S. Patent 3,335,181; August 8, 1967; assigned to Hoffmann- LaRoche. Inc.
water solubility	100 mg/L (at 25 °C)	MERCK INDEX (1996)
logP	2.41	HANSCH,C ET AL. (1995)

Predicted Properties

Property	Value	Source
Water Solubility	0.0106 mg/mL	ALOGPS
logP	2.76	ALOGPS
logP	3.15	ChemAxon
logS	-4.5	ALOGPS
pKa (Strongest Acidic)	11.89	ChemAxon
pKa (Strongest Basic)	1.86	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	87.28 Å2	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	84.02 m3·mol-1	ChemAxon
Polarizability	29.59 Å3	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9946
Blood Brain Barrier	+	0.9718
Caco-2 permeable	+	0.5313
P-glycoprotein substrate	Substrate	0.5594
P-glycoprotein inhibitor I	Non-inhibitor	0.8474
P-glycoprotein inhibitor II	Non-inhibitor	0.9157
Renal organic cation transporter	Non-inhibitor	0.8179
CYP450 2C9 substrate	Non-substrate	0.7777
CYP450 2D6 substrate	Non-substrate	0.8934
CYP450 3A4 substrate	Substrate	0.7295
CYP450 1A2 substrate	Inhibitor	0.7646
CYP450 2C9 inhibitor	Inhibitor	0.5213
CYP450 2D6 inhibitor	Non-inhibitor	0.8271
CYP450 2C19 inhibitor	Inhibitor	0.7441
CYP450 3A4 inhibitor	Inhibitor	0.5565
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.7255
Ames test	Non AMES toxic	0.6778
Carcinogenicity	Non-carcinogens	0.6417
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	1.6422 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9821
hERG inhibition (predictor II)	Non-inhibitor	0.8734

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Mass Spectrum (Electron Ionization)	MS	splash10-02a9-2492000000-109e2626e8a128b9e433
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

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Drug created on June 13, 2005 07:24 / Updated on September 22, 2020 02:11