Zolpidem

Oral
Short-term management of insomnia

No dosage adjustment needed.

As immediate release tab: 5 mg immediately before bedtime. As extended release tab: 6.25 mg immediately before bedtime. Max duration of treatment: 4 wk including tapering. Severe: Contraindicated.

Should be taken on an empty stomach. Do not take w/ or immediately after a meal.

Severe hepatic impairment.

Obstructive sleep apnoea, myasthenia gravis, compromised respiratory function. Patients exhibiting symptoms of depression. History of drug or alcohol abuse. Avoid abrupt withdrawal and rapid dose reduction after prolonged therapy. Re-evaluate if insomnia fail to remit after 7-10 days as this may indicate the presence of underlying psychiatric and/or medical condition. Pregnancy, lactation, childn <18 yr.

Atypical thinking and behaviour, hallucination, nightmare, somnolence, somnambulism, headache, nausea, vomiting, dizziness, vertigo, drowsiness, asthenia, ataxia, rebound insomnia, amnesia, GI disturbances, upper and lower respiratory tract infection, fatigue, visual disturbances, increased ALT serum concentrations, abnormal LFT.
Potentially Fatal: Hepatitis, anaphylactic reactions, angioedema, sleep-driving (driving while not fully awake after drug intake, w/ no recollection of the event).

PO: C

Patients should be warned about performing activities involving mental alertness or physical coordination after drug intake.

Symptoms: Drowsiness, impairment of consciousness from somnolence to coma, compromised CV and respiratory function. Management: Treatment is largely symptomatic and supportive. IV fluids should be administered as needed. Activated charcoal may be given if presented w/in 1 hr of ingestion of >1 mg/kg zolpidem in adults or childn. Gastric lavage may be considered if presented w/in 1 hr of ingestion of >100 mg zolpidem and monitor for at least 12 hr. Flumazenil may be used if there is severe CNS depression, but generally not needed. Haemodialysis is unlikely to be useful.

Flumazenil reverses the sedative/hypnotic effect of zolpidem. Increased depressant effects w/ CNS depressants (e.g. sedatives, antihistamines, alcohol). Additive effect on decreased alertness and psychomotor performance w/ imipramine and chlorpromazine. Increased plasma concentration w/ itraconazole, ketoconazole and other CYP3A4 inhibitors. May decrease plasma concentration w/ CYP3A4 inducers (e.g. carbamazepine). Reduced hypnotic effect w/ rifampicin.
Potentially Fatal: Increased risk of prolonged sedation and respiratory depression w/ ritonavir.

Avoid combination w/ St John's wort, alcohol and grapefruit juice.

Description:
Mechanism of Action: Zolpidem is an imidazopyridine derivative that acts by binding to the benzodiazepine (BZD) receptors of the GABA receptor complex resulting in neuronal hyperpolarisation, action potential inhibition, increased in chloride conductance and decreased in neuronal excitability. It has strong sedative action but only minimal anxiolytic, myorelaxant and anticonvulsant properties due to its selectivity for the BZ₁-receptor over the BZ₂-receptor. Zolpidem has a rapid onset but short duration of hypnotic action.
Onset: Immediate release: 30 min.
Duration: Immediate release: 6-8 hr.
Pharmacokinetics:
Absorption: Rapidly absorbed from GI tract. Food reduces both the rate and extent of GI absorption. Absolute bioavailability: Approx 70%. Time to peak plasma concentration: Immediate release: 1.6 hr; extended release: 1.5 hr.
Distribution: Distributed into breast milk. Volume of distribution: 0.54 kg/L. Plasma protein binding: Approx 92%.
Metabolism: Undergoes first pass metabolism, metabolised primarily by CYP3A4 isoenzyme.
Excretion: Via urine (48-67%) and faeces (29-42%) as inactive metabolites. Elimination half-life: Approx 2.5 hr.

Store between 20-25°C.

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