Diazepam

Diazepam is a 1,4-benzodiazipine. A substituent in the 7th position such as halogen or a nitro group is required for its sedative, hypnotic activity. Benzdiazipines are the most widely used anxiolytic drugs. The benzodiazipines are more effective and safer. They have largely replaced barbiturates and meprobamate in the treatemnt of anxiety. Diazepam is also useful in reducing muscletone in spasticity and as an anticonvulsant.


Adult Dose
Dose: 2 to 10 mg
Single Dose: 6 (6)
Frequency: 12 hourly
Route: PO,PR,IM,Slow IV
Instructions: or frequency may be increased to 3 times a day.
Neonatal
Dose: 0.2 to 0.3 mg/kg
Single Dose: 0.25 (0.25)
Frequency: As recommended.
Route: Slow intravenous
Instructions: Single dose
Paedriatic
Dose: 0.25 mg/kg
Single Dose: 0.25 (0.25)
Frequency: As recommended.
Route: Intra Rectal
Instructions: Single Dose
Characteristics
. It is of Synthetic origin and belongs to Benzodiazepine. It belongs to Chloride Channel Potentiater (GABA operated) pharmacological group on the basis of mechanism of action and also classified in Benzodiazepine pharmacological group.The Molecular Weight of Diazepam is 284.70. Its pKa is 3.7.
Contraindications
Diazepam is contraindicated in conditions like Myasthenia gravis.
Effects
Diazepam produces potentially life-threatening effects which include Blood dyscrasias, Respiratory arrest, Cardiac Arrest. which are responsible for the discontinuation of Diazepam therapy.The signs and symptoms that are produced after the acute overdosage of Diazepam include Apnea, Coma, Drowsiness, Confusion, Areflexia, Reduced reflexes, Cardiorespiratory depression.The symptomatic adverse reactions produced by Diazepam are more or less tolerable and if they become severe, they can be treated symptomatically, these include Dizziness, Headache, Fatigue, Excitement, Ataxia, Nausea, Anxiety, Tachycardia, Skin rashesX, Constipation, Insomnia, Blurred vision, Urinary retensionX, Confusion, Hematuria, VertigoX, Hallucination, Sleep disturbance, Hypotension, Depression, Flushing, Muscle weakness, Tremor, Diplopia, Phlebitis, SomnolenceX, Slurred speech, Euphoria, Faintness, Hypoactivity, Dysarthria, Impairment of memory, Changes in libido, Pain at injection site, Poor appetite.
Indications
Diazepam is primarily indicated in conditions like Agitation, Alcohol withdrawal, Amnesia induction, Anxiety, Chloroquine overdose, Dyspnoea associated with anxiety in palliative care, Flare with initial gonadorelin therapy, Herpes zoster, Insomnia, Minor surgical and medical procedures, Muscle spasm (acute), Muscle spasm in palliative care, Muscular spasm, Partial seizures, Premedication, Sedation induction, Severe acute anxiety, Severely emetognic chemotherapy, Status epilepticus, Tetanus, Tonic-clonic seizures, Treatment of acute migraine attacks, and can also be given in adjunctive therapy as an alternative drug of choice in Acute diarrhoea, All forms of epilepsy, Bone pain in neoplastic disease, Hypercalcaemia of malignancy, Influenza A, Muscle spasm of varied aeitology, Myoclonus, Prevention and treatment of corticosteroid-induced osteoporosis.
Interactions
Diazepam is known to interact with other drugs, the details of drug interactions is as follows:DrugDetailsSeverityOnsetManagementAlcoholAdditive CNS depressant activity. Ethanol increases Rate of GI absorption of DiazepamAmprenavirIncreased risk of prolonged sedation and respiratory depression when Amprenavir given with Diazepam.MajorAntazolineIncreased antimuscarinic and sedative effects when antihistamines (e.g Antazoline) given with anxiolytics (e.g Diazepam).AtenololAtenolol may increase the serum concentration of Diazepam.MinorNo action required.Azelastine (HCl) Increased sedative effects when antihistamines (e.g Azelastine) given with anxiolytics and hypnotics (e.g Diazepam).BaclofenEnhanced sedative effects when Baclofen given with anxiolytics and hypnotics (e.g Diazepam).CaffeineCarbamazepineCimetidine (HCl)Cimetidine reduce metabolism and increase plasma concentration of diazepam through CYP450 inhibitionthus enhance sedation and it delays clearance of Diazepam.MinorPatient response and tolerance should be monitor and diazepam dose is adjusted.ClozapineBoth agents have additive effects on respirstory and cardiovascular system.MajorClosely monitor for vital signs.DiazoxideEnhanced hypotensive effect when Diazoxide given Diazepam.DigoxinDiazepam may increase the serum concentration of digoxin.ModerateNo action required.EnfluraneFluoxetine (HCl)fluoxetine prolong the half life of diazepamFluvoxamine (Maleate)HalothaneInterferon AlphaIprindoleTheoretical potential for DIAZEPAM increasing the SEDATIVE effect of IPRINDOLE. ModerateIproniazid PhosphateInfrequent reports of DIAZEPAM increasing the EXTRAPYRAMIDAL side effects of IPRONIAZID. ModerateIsoniazidLevodopaDetoriation of Parkinsonism occurs in patients when take diazepamLithiumWhen both drugs given in combination cause HypothermiaMirtazapineNefopam (HCl)Omeprazoleomeperzole decrease the clearance of diazepamPemolinePemoline may decrease seizure threshold. Efficacy of anticonvulsants may be decreased PericyazineThese drugs shouldnot be taken concurrently without doctors prescription.PhenobarbitoneBarbiturates (e.g. Phenobarbitone) potentiate the action of Diazepam and should not be given concurrentlyPhenytoin (Na)Metabolic elimination of phenytoin is altered by DiazepamPropranolol (HCl)RifampicinRizatriptanConcurrent use may increase drowsiness.SertindoleSertindole has the potential of causing drowsiness, thus in combination Diazepam sedation may result. SilymarinSilymarin may interfere with Diazepam because both drugs are broken down by the same liver enzymes.Terpin HydrateShould not use concurretly without doctors prescription.Verapamil (HCl)VORICONAZOLEVoriconazole may increase the serum concentration of diazepam by decreasing its metabolism. Monitor for diazepam toxicity if voriconazole is initiated or dose increased.Zotepine These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.
Interfrence
Slight reddish coloration in Ferrocitrate paper strip test for Levodopa
Risks
Drug should not be given to Pregnant Mothers, and Neonates.If prescribing authority justifies the benefits of the drug against the possible damages he/she should reevaluate them and consult the reference material and previous studies.
Storage
Inj, Oral Soln, Rectal Gel Store Between 15°C-25°C. Do not Freeze. Protect from Sunlight. Tab, Caps Store in a well closed container, Between 20°C-25°C. Protect from Sunlight and Moisture.
Warnings
Perform periodic blood counts and liver function tests during long term therapy with diazepam. Diazepam should be used with caution in patients if increased salivation cause respiratory difficulty, because it may produce an increase in salivation. Give least amount of drug to patients in whom depression accompanies anxiety and suicidal tendencies may be present. It should be used with caution (if it contains tartrazine) in patients with aspirin hypersensitivity because it may cause allergic reaction (including bronchial asthma).
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