Description

Simple

A sedative medication used to help with panic attacks, anxiety, alcohol withdrawals, and seizures.

Clinical

A long-acting benzodiazepine with rapid onset commonly used to treat panic disorders, severe anxiety, alcohol withdrawal, and seizures.

Overview

A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of gamma-aminobutyric acid activity. It is used in the treatment of severe anxiety disorders, as a hypnotic in the short-term management of insomnia, as a sedative and premedicant, as an anticonvulsant, and in the management of alcohol withdrawal syndrome. (From Martindale, The Extra Pharmacopoeia, 30th ed, p589)

Given diazepam's storied history as a commonly used and effective medication for a variety of indications, contemporary advancements in the formulation and administration of the agent include the development and US FDA approval of an auto-injectable formulation for the rapid treatment of uncontrolled seizures in 2015-2016 [7]. Combining diazepam, a proven effective therapy for acute repetitive seizures, with an auto-injector designed for subcutaneous administration that is quickly and easily administered offers the potential for complete, consistent drug absorption and rapid onset of effect [Read more

Pharmacology

Indication

In general, diazepam is useful in the symptomatic management of mild to moderate degrees of anxiety in conditions dominated by tension, excitation, agitation, fear, or aggressiveness such as may occur in psychoneurosis, anxiety reactions due to stress conditions, and anxiety states with somatic expr... Read more

Pharmacodynamic

Diazepam is a benzodiazepine that exerts anxiolytic, sedative, muscle- relaxant, anticonvulsant and amnestic effects [9, 10 Read more

Mechanism of action

Diazepam is a benzodiazepine tranquilliser with anticonvulsant, sedative, muscle relaxant and amnesic properties [9, 10,... Read more

Absorption

After oral administration, it is considered that diazepam is rapidly and completely absorbed from the gastrointestinal tract as >90% of diazepam is absorbed and the average time to achieve peak plasma concentrations is 1 – 1.5 hours with a range of 0.25 to 2.5 hours [ Read more

Protein binding

Despite high binding to plasma proteins (98-99%) - mainly albumin and to a lesser extent α1-acid glycoprotein - diazepam is widely distributed into tissues and crosses the blood-brain barrier and is highly lipid soluble, which causes the initial effects to decrease rapidly as it is redistributed int... Read more

Volume of distribution

In young healthy males, the volume of distribution at steady-state is 0.8 to 1.0 L/kg [9].

Clearance

The clearance of diazepam is 20 to 30 mL/min in young adults [9, 10].

Half life

Diazepam has a biphasic half-life with an initial rapid distribution phase followed by a prolonged terminal elimination phase of 1 or 2 days; its action is further prolonged by the even longer half-life of 2-5 days of its principal active metabolite, desmethyldiazepam (nordiazepam), the relative pro... Read more

Route of elimination

Diazepam and its metabolites are excreted mainly in the urine, predominantly as their glucuronide conjugates [9, 10, Read more

Toxicity

The symptoms of diazepam overdose are mainly an intensification of the therapeutic effects (ataxia, drowsiness, dysarthria, sedation, muscle weakness, profound sleep, hypotension, bradycardia, nystagmus) or paradoxical excitation [ Read more

Adverse Effects

Contraindications

  • Regions: US
  • Below Age:
    • Amount: 6
    • Unit: month
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Sleep Apnea Syndrome
      • Drugbank Id: DBCOND0028401
  • Route:
    • Oral
    • Intravenous
    • Rectal
  • Regions: US
  • Patient Conditions:
      • Name: Acute narrow angle glaucoma
      • Drugbank Id: DBCOND0107878
      • Modification Of:
        • Base:
          • Name: Narrow angle glaucoma
          • Drugbank Id: DBCOND0104923
        • Severity:
          • Includes:
            • acute
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Severe respiratory insufficiency
      • Drugbank Id: DBCOND0107490
      • Modification Of:
        • Base:
          • Name: Respiratory Insufficiency
          • Drugbank Id: DBCOND0029091
        • Severity:
          • Includes:
            • severe
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Severe hepatic insufficiency
      • Drugbank Id: DBCOND0108038
      • Modification Of:
        • Base:
          • Name: Hepatic Insufficiency
          • Drugbank Id: DBCOND0031307
        • Severity:
          • Includes:
            • severe
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Myasthenia Gravis
      • Drugbank Id: DBCOND0028961

Food Interactions

  • Avoid alcohol.
  • Take on an empty stomach. Food may decrease absorption and time to therapeutic effect.

Interactions

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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The serum concentration of (R)-warfarin can be increased when it is combined with Diazepam.
(S)-Warfarin
The serum concentration of (S)-Warfarin can be increased when it is combined with Diazepam.
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of adverse effects can be increased when Diazepam is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthine
The therapeutic efficacy of Diazepam can be decreased when used in combination with 3-isobutyl-1-methyl-7H-xanthine.
3,5-diiodothyropropionic acid
The therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Diazepam.
3,5-Diiodotyrosine
The therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Diazepam.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of adverse effects can be increased when Diazepam is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be decreased when combined with Diazepam.
4-Methoxyamphetamine
The risk or severity of adverse effects can be increased when Diazepam is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of adverse effects can be increased when Diazepam is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanine
The therapeutic efficacy of Diazepam can be decreased when used in combination with 6-O-benzylguanine.
7-Deazaguanine
The therapeutic efficacy of Diazepam can be decreased when used in combination with 7-Deazaguanine.
7-Nitroindazole
The risk or severity of adverse effects can be increased when Diazepam is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
The risk or severity of adverse effects can be increased when Diazepam is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
7,9-Dimethylguanine
The therapeutic efficacy of Diazepam can be decreased when used in combination with 7,9-Dimethylguanine.
8-azaguanine
The therapeutic efficacy of Diazepam can be decreased when used in combination with 8-azaguanine.
8-chlorotheophylline
The therapeutic efficacy of Diazepam can be decreased when used in combination with 8-chlorotheophylline.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be decreased when combined with Diazepam.
9-Deazaguanine
The therapeutic efficacy of Diazepam can be decreased when used in combination with 9-Deazaguanine.
9-Methylguanine
The therapeutic efficacy of Diazepam can be decreased when used in combination with 9-Methylguanine.
11 References
  1. 1 . Mant A, Whicker SD, McManus P, Birkett DJ, Edmonds D, Dumbrell D: Benzodiazepine utilisation in Australia: report from a new pharmacoepidemiological database. Aust J Public Health. 1993 Dec;17(4):345-9.PubMed: 7911332
  2. 2 . 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
  3. 3 . Usami N, Yamamoto T, Shintani S, Ishikura S, Higaki Y, Katagiri Y, Hara A: Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines. Biol Pharm Bull. 2002 Apr;25(4):441-5.PubMed: 11995921
  4. 4 . Oishi R, Nishibori M, Itoh Y, Saeki K: Diazepam-induced decrease in histamine turnover in mouse brain. Eur J Pharmacol. 1986 May 27;124(3):337-42.PubMed: 3089825
  5. 5 . McLean MJ, Macdonald RL: Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture. J Pharmacol Exp Ther. 1988 Feb;244(2):789-95.PubMed: 2450203
  6. 6 . Electronic Medicines Compendium: Diazepam Tablets BP 2mg Monograph Link
  7. 7 . Xeris Pharmaceuticals Awarded Phase I-II NIH SBIR Fast Track Grant to Advance a Stable, Non-Aqueous Diazepam, Subcutaneous Injection for Treatment of Acute Repetitive Seizures in Patients with Epilepsy: Press Release Link
  8. 8 . FDA Approved Drug Products Valtoco Diazepam Nasal Spray Link
  9. 9 . Diazepam FDA Label File
  10. 10 . Diazepam Canadian Product Information File
  11. 11 . WHO Model Prescribing Information: Drugs Used in Anaesthesia, Premedication: Diazepam File