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.

Zolpidem is indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. Zolpidem has been shown to decrease sleep latency for up to 35 days in controlled clinical studies 

The clinical trials performed in support of efficacy were 4-5 weeks in duration with the final formal assessments of sleep latency performed at the end of treatment.

Dosage In Adults: Use the lowest effective dose for the patient. The recommended initial dose is 5 mg for women and either 5 or 10 mg for men, taken only once per night immediately before bedtime with at least 7–8 hours remaining before the planned time of awakening. If the 5 mg dose is not effective, the dose can be increased to 10 mg. In some patients, the higher morning blood levels following use of the 10 mg dose increase the risk of next day impairment of driving and other activities that require full alertness. The total dose of Zolpidem should not exceed 10 mg once daily immediately before bedtime. Zolpidem should be taken as a single dose and should not be readministered during the same night.

The recommended initial doses for women and men are different because zolpidem clearance is lower in women.

Special Populations: Elderly or debilitated patients may be especially sensitive to the effects of zolpidem tartrate. The recommended dose of Zolpidem in these patients is 5 mg once daily immediately before bedtime

Patients with mild to moderate hepatic impairment do not clear the drug as rapidly as normal subjects. The recommended dose of Zolpidem in these patients is 5 mg once daily immediately before bedtime. Avoid Zolpidem use in patients with severe hepatic impairment as it may contribute to encephalopathy

Use With CNS Depressants: Dosage adjustment may be necessary when Zolpidem is combined with other CNS depressant drugs because of the potentially additive effects

Administration

The effect of Zolpidem may be slowed by ingestion with or immediately after a meal.

Severe hepatic impairment.

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.

Overdose Effects

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.

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.

Use in Special Populations

Pediatric Use: Zolpidem is not recommended for use in children. Safety and effectiveness of zolpidem in pediatric patients below the age of 18 years have not been established.

Pregnancy & Lactation

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.