Overview of Zolpidem
Zolpidem is a non-benzodiazepine sedative and hypnotic drug but mainly produces hypnotic effect-decreases sleep latency & duration of sleep time increases in insomnia. It is classified as an imidazopyridine.
Mechanism of action
The non-benzodiazepine hypnotics bind selectively to BZD binding site on GABAa receptors and facilitate GABA-mediated neuronal inhibition ( due to enhance membrane hyperpolarization) and finally produce CNS depression.
- Atypical thinking & behavior
- Rebound insomnia
- Amnesia (memory loss)
- GI disturbance (diarrhea)
- Upper and lower respiratory tract infection
- Visual disturbance
- Increased ALT serum concentrations
- Abnormal liver function test
- Anaphylactic reactions
Uses of zolpidem
- Short-term management of insomnia
- In adults: as immediate release tab: 5-10 mg immediately before bedtime. Maximum 10 mg/day. The maximum duration of time is 4 weeks including tapering
- In elderly: as immediate release tab: 5 mg immediately before bedtime. The maximum duration of time is 4 weeks including tapering
- Renal impairment: 5 mg immediately before bedtime.
- Hepatic impairment (mild to moderate): 5 mg immediately before bedtime.
- Sedative and hypnotic
- Absorption: Rapidly absorbed from the GI tract when a drug is taken orally.
- Distribution: widely distributed and enters the breast milk, the protein binding capacity ranges from 45% to 80%.
- Metabolism: Extensively hepatic; converted to less active N-oxide and inactive N-desmethylzolpidem. Undergoes decarboxylation to inactive metabolites. The plasma half-life is around 2 hours and has a short duration of action.
- Excretion: urine, feces (as unchanged drug and metabolites), and lungs and saliva have a little role for excretion.
- Severe hepatic impairment
- Myasthenia gravis
- Respiratory failure
- Severe sleep apnea syndrome
- Pregnancy and lactation
Interaction of Zolpidem
- Flumazenil reverses the sedative and hypnotic effects of zolpidem
- Increased depressant effects with CNS depressants agents such as sedatives, alcohol, antihistamines.
- Additive effect on decreased alertness & psychomotor performance with drugs imipramine and chlorpromazine.
- Increased plasma concentration with itraconazole, ketoconazole & other CYP3A4 inhibitors.
- May decrease plasma concentration with CYP3A4 inducers e.g. carbamazepine.
- Reduced hypnotic effects with Rifampicin
- Increased risk of prolonged sedation and respiratory depression with ritonavir.