Clonazepam (Klonopin®) versus Diazepam (Valium®)
Both clonazepam and diazepam are long-acting benzodiazepines. Two benzodiazepines differ in their effects on GABA-A receptors, route of metabolism, and elimination half-life.
|Brand name/Year of initial approval||Klonopin®, 1975||Valium®, 1963|
|Formulations||Oral tablets, oral disintegrating wafers||Oral tablets, oral solution, intramuscular, injectable solution, rectal gel|
|Legal status||Schedule IV
|Drug class||Benzodiazepine, long acting|
|FDA-approved Indications||• Panic disorder
• Lennox-Gastaut syndrome
• Akinetic seizure
• Myoclonic seizure
• Acute mania
• Acute psychosis
| • Anxiety disorder
• Symptoms of anxiety
• Alcohol withdrawal
• Skeletal muscle spasms and spasticity
• Adjunctively in convulsive disorders
• Anxiety relief prior to cardioversion
|Off-label uses||• Insomnia5
|• Restless legs syndrome6||• Anesthetic premedication7|
|Mechanism of action||• Prominent anticovulsant activity
• Anxiolytic, sedative, muscle- relaxant, effects
Benzodiazepines work by facilitation of the action of gamma aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS.
Clonazepam has higher affinity for the GABA-A receptor site than diazepam2. Clonazepam is 10–20 times more potent than diazepam.
|Clonazepam has more selective anticonvulsant activity8.||• I.V. diazepam produces analgesia
• Decreases nocturnal gastric secretion and prevents stress ulcers
|Half-life||30-40 hours||20-50 hours (mean half-life 48 hours)|
|Metabolism, Elimination||Clonazepam is metabolized in the liver (CYP3A4). The drug is metabolized principally by reduction of the nitro group to produce inactive 7-amino derivatives. Less than 1% of the drug is excreted unchanged in the urine.||Metabolized by CYP2C19 and CYP3A4 to an active metabolite desmethyldiazepam.
Diazepam and its metabolites are excreted mainly in the urine, predominantly as their glucuronide conjugates.
|Contraindications||• History of sensitivity to benzodiazepines
||• Hypersensitivity to diazepam
• Children under 6 months of age
• Myasthenia gravis
• Severe respiratory insufficiency
• Sleep apnea
|• Acute narrow angle glaucoma
• Significant liver disease
|Warnings & precautions||• Abuse, physical dependence, tolerance
• Impairment of cognitive and motor skills9
• Abnormal thinking or behavioral changes
|Side effects|| • Drowsiness
|Drug interactions||• Increased depressive effects when taken with other CNS depressants or alcohol|
|Onset of effect||Rapid onset of action, 1-5 min. Both benzodiazepines are highly lipid-soluble and penetrate rapidly into the brain.|
|Advantages||• Broad anti-seizure properties
• One of the most useful benzodiazepines for preventing recurrent seizures1
• Has a role in long-term treatment of epilepsy
|• The first choice for emergency management of convulsions, e.g. status epilepticus, tetanus, eclampsia, convulsant drug poisoning, ongoing acute seizures.
• Various dosage formulations allow more flexibility of administration
|Disadvantages||• Rapid development of tolerance to the antiepileptic effect3. Not useful as an oral anticonvulsant.|
|Both drugs are quickly redistributed to lipid stores. This may cause recurrence of seizures, and necessitate co-administration of a long-acting anticonvulsant.|
In contrast to diazepam, which is used mainly for treatment of acute seizures, clonazepam is also useful for long-term treatment of refractory, chronic epilepsy.
Clonazepam is superior to diazepam in suppressing focal seizures and focal spiking4.
- 1. C.P. Panayiotopoulos The Epilepsies: Seizures, Syndromes and Management. Ch.14 Pharmacopoeia of Prophylactic Antiepileptic Drugs. Oxford , U.K. , 2005
- 2. Juan G. Ochoa, Selim R. Benbadis. Antiepileptic Drugs. Available at: http://emedicine.medscape.com/article/1187334-overview
- 3. Rosenberg HC, Tietz EI, Chiu TH. Tolerance to anticonvulsant effects of diazepam, clonazepam, and clobazam in amygdala-kindled rats. Epilepsia. 1989 May-Jun;30(3):276-85. PubMed
- 4. van Duijn H. Superiority of clonazepam over diazepam in experimental epilepsy. Epilepsia. 1973 Jun;14(2):195-202.
- 5. Sastre Hernández MS, Hentschel HD, Fichte K. Comparative efficacy of lormetazepam (Noctamid) and diazepam (Valium) in 100 out-patients with insomnia. J Int Med Res. 1981;9(3):199-202. PubMed
- 6. Montagna P, Sassoli de Bianchi L, Zucconi M, Cirignotta F, Lugaresi E. Clonazepam and vibration in restless legs syndrome. Acta Neurol Scand. 1984 Jun;69(6):428-30.
- 7. Dionne RA, Goldstein DS, Wirdzek PR. Effects of diazepam premedication and epinephrine-containing local anesthetic on cardiovascular and plasma catecholamine responses to oral surgery. Anesth Analg. 1984 Jul;63(7):640-6.
- 8. Voronina TA, von Littrow K. Comparative experimental characteristics of clonazepam and diazepam. Farmakol Toksikol. 1980 May-Jun;43(3):296-9. PubMed
- 9. Gagnon MA, Langlois Y, Boghen DR, Verdy M. Effects of halazepam and diazepam on the motor coordination of geriatric subjects. Eur J Clin Pharmacol. 1977 Jul 19;11(6):443-8.
Published: December 02, 2016
Last updated: December 02, 2016