Estazolam

Small or debilitated older patients: Consider an initial dose of 0.5 mg at bedtime.

Estazolam May be taken with or without food.

Concomitant use with itraconazole or ketoconazole.

Patient with history of alcoholism or substance abuse, history of psychiatric or personality disorder; depression, respiratory disease (e.g. COPD, sleep apnoea). Patient at risk of falls. Concomitant use with opioids. Avoid abrupt withdrawal. Not recommended for prolonged use. Renal and hepatic impairment. Elderly and small or debilitated older patients. Pregnancy and lactation.

Significant: Anterograde amnesia, paradoxical reactions (including hyperactive or aggressive behaviour), hazardous sleep-related activities (e.g. sleep-driving, making phone calls, cooking and eating food while asleep), CNS depression; risk of physical dependence (prolonged use).
Gastrointestinal disorders: Constipation, xerostomia.
General disorders and administration site conditions: Hangover effect.
Musculoskeletal and connective tissue disorders: Leg pain, stiffness.
Nervous system disorders: Drowsiness, dizziness, ataxia, hypokinesia.
Psychiatric disorders: Abnormal thinking, confusion, anxiety.
Skin and subcutaneous tissue disorders: Pruritus.
Potentially Fatal: Risk of abuse, misuse and addiction; may precipitate acute withdrawal reactions (following abrupt discontinuation or rapid dose reduction after continued use). Rarely, anaphylaxis and angioedema (involving the tongue, glottis or larynx).

PO: Z (Use in late pregnancy may cause neonatal sedation and withdrawal symptoms. Monitor neonates for adverse effects (sedation, respiratory depression, poor feeding) and withdrawal symptoms.)

This drug may impair mental or physical abilities, if affected, do not drive or operate machinery.

Monitor CBC, electrolytes, and urinalysis (periodically during prolonged use); respiratory and CV status, daytime alertness, and behaviour profile. Observe for signs and symptoms of hypersensitivity reaction.

Symptoms: Mild to moderate cases: Drowsiness, ataxia, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, hypotonia; rarely, paradoxical or disinhibitory reactions (e.g. agitation, irritability, violent behaviour, excitement). Severe cases: Respiratory depression and coma. Management: Supportive treatment. Administer IV fluids and implement airway management. Consider flumazenil as an adjunct to supportive management for the complete or partial reversal of the sedative effect.

May reduce serum concentration with strong CYP3A inducers (e.g. carbamazepine, rifampicin, phenytoin).
Potentially Fatal: Concurrent use with opioids may result in profound sedation, respiratory depression and coma. May increase serum concentration with ketoconazole and itraconazole.

Increased CNS depressant effect with alcohol. May increase serum concentration with grapefruit juice.

Description:
Mechanism of Action: Estazolam, a triazolobenzodiazepine derivative, binds to the stereospecific benzodiazepine receptors on the postsynaptic gamma-aminobutyric acid (GABA) neuron at various sites within the CNS (including limbic system and reticular formation). Increased permeability of neural membrane to chloride ions enhances the inhibitory effect of GABA on neuronal excitability, leading to hyperpolarisation (less excitable state) and stabilisation.
Pharmacokinetics:
Absorption: Rapidly and well absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 2 hours (range: 0.5-6 hours).
Distribution: Widely distributed into most body fluids and tissues. Plasma protein binding: 93%.
Metabolism: Extensively metabolised in the liver into inactive metabolites, including 1-oxo-estazolam and 4-hydroxy-estazolam; CYP3A catalyses the metabolism to 4-hydroxy-estazolam.
Excretion: Via urine (>70% as inactive metabolites, <5% as unchanged drug); faeces (4%). Elimination half-life: 10-24 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3261, Estazolam. https://pubchem.ncbi.nlm.nih.gov/compound/Estazolam. Accessed May 28, 2024.

Store between 20-25°C. Protect from light.

Hypnotics & Sedatives

N05CD04 - estazolam ; Belongs to the class of benzodiazepine derivatives. Used as hypnotics and sedatives.

Anon. Estazolam. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 06/05/2024.

Buckingham R (ed). Estazolam. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/05/2024.

Estazolam Tablet (Dr. Reddy's Laboratories Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/05/2024.

Estazolam Tablet (Mayne Pharma). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 15/05/2024.

Estazolam. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 15/05/2024.

Estazolam. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 06/05/2024.