Zolpidem

Zolpidem Uses, Dosage, Side Effects, Food Interaction and all others data.

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.

Effects on the central nervous system (CNS)

This drug has CNS depressant effects, which may include somnolence, decreased alertness, sedation, drowsiness, dizziness, and other changes in psychomotor function . Due to the above effects, the FDA has recommended an initial dose of zolpidem (immediate-acting) is a single dose of 5 mg for women and a single dose of 5 or 10 mg for men, immediately before bedtime with at least 7-8 hours remaining before the planned time of awakening . Refer to product labeling for detailed information , .

Effects on memory

Trade Name Zolpidem
Availability Prescription only
Generic Zolpidem
Zolpidem Other Names Zolpidem, Zolpidemum
Related Drugs amitriptyline, lorazepam, melatonin, diphenhydramine, Ativan, Ambien
Type
Formula C19H21N3O
Weight Average: 307.3895
Monoisotopic: 307.168462309
Protein binding

92.5 ± 0.1%

Groups Approved
Therapeutic Class Miscellaneous sedatives & hypnotics
Manufacturer Mylan
Available Country United Kingdom, United States, Portugal, Switzerland
Last Updated: September 19, 2023 at 7:00 am
Zolpidem
Zolpidem

Uses

Zolpidem is used 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.

Zolpidem is also used to associated treatment for these conditions: Insomnia

How Zolpidem works

Zolpidem, the active moiety of zolpidem tartrate, is a hypnotic substance with a chemical structure that is not related to the structure benzodiazepines, barbiturates, pyrrolopyrazines, pyrazolopyrimidines or other drugs exerting hypnotic effects. It interacts with a GABA-BZ receptor complex and shares various pharmacological properties with the benzodiazepine class of drugs .

Subunit binding of the GABAA receptor chloride channel macromolecular complex is thought to lead to the sedative, anticonvulsant, anxiolytic, and myorelaxant drug effects of zolpidem. The main regulatory site of the GABAA receptor complex can be found on its alpha (α) subunit and is called the benzodiazepine (BZ) or omega (ω) receptor. At least three different subtypes of the (ω) receptor have been identified to this date .

In contrast to benzodiazepine drugs, which are found to modulate all benzodiazepine receptor subtypes in a non-selective fashion, zolpidem binds the (BZ1) receptor specifically with a potent affinity for the alpha 1/alpha 5 subunits (in vitro) . More recent studies suggest that zolpidem binds primarily to the alpha 1, 2, and 3 subunits of the GABA receptor , , , and not the alpha 5 subunit.

The (BZ1) receptor is found primarily on the Lamina IV of the brain sensorimotor cortical regions, substantia nigra (pars reticulata), cerebellum molecular layer, olfactory bulb, ventral thalamic complex, pons, inferior colliculus, and globus pallidus. Specific and selective binding of zolpidem on the (BZ1) receptor is not considered absolute, however, this binding could potentially explain the relative lack of myorelaxant and anticonvulsant activity in animal studies in addition to the preservation of deep sleep (stages 3 and 4) in human studies of zolpidem at hypnotic doses .

Dosage

Zolpidem dosage

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

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

Side Effects

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.

Toxicity

Oral (male rat) LD50 = 695 mg/kg .

Overdose

Symptoms of overdose include impairment of consciousness ranging from somnolence to light coma, in addition to cardiorespiratory collapse resulting in fatal outcomes have been reported .

Withdrawal effects

Following rapid decreases in dose or abrupt discontinuation of zolpidem and other sedative/hypnotics, reports of signs and symptoms similar to those associated with withdrawal from other CNS-depressant drugs have been made .

Carcinogenesis

Zolpidem was administered to rats and mice over a span of 2 years at dietary dosages of 4, 18, and 80 mg/kg/day. In mice, these doses are considered 26 to 520 times or 2 to 35 times the maximum 10 mg human dose, respectively. In rats, these doses are 43 to 876 times or 6 to 115 times the maximum 10 mg human dose. No evidence of carcinogenicity was seen in mice. Renal liposarcomas were observed in 4/100 rats (3 males, 1 female) receiving 80 mg/kg/day, and a renal lipoma was observed in one male rat at the 18 mg/kg/day dose. Incidence rates of lipoma and liposarcoma for zolpidem were similar to those seen in historical control cases, and the tumor findings are presumed to be a spontaneous occurrence, not causally related to zolpidem .

Mutagenesis

Zolpidem did not show mutagenic activity in several tests including the Ames test, genotoxicity in mouse lymphoma cells in vitro, chromosomal aberrations in cultured human lymphocytes, abnormal DNA synthesis in rat hepatocytes in vitro, and the micronucleus test performed in mice .

Impairment of fertility

In a rat reproduction study, the high dose (100 mg base/kg) of zolpidem lead to irregular estrus cycles and prolonged precoital intervals, however, there was no effect on male or female fertility after daily oral doses comparable to 5 to 130 times the recommended human dose. No effects on any other fertility parameters were observed .

Use in pregnancy

This drug is considered a pregnancy category C drug. There are currently no sufficient conclusive studies completed in pregnant women to determine the safety of zolpidem use during pregnancy. Zolpidem should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.

Use in nursing

From 0.004% to 0.019% of the total administered zolpidem dose is excreted into milk. The effect of zolpidem on the nursing infant is unknown at this time. Caution should be observed when zolpidem is administered to a nursing mother .

Precaution

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.

Interaction

Co-administration of zolpidem with other CNS depressants increases the risk of CNS depression. Concomitant use of zolpidem with these drugs may increase drowsiness and psychomotor impairment, including impaired driving ability. Zolpidem tartrate was evaluated in healthy volunteers in single-dose interaction studies for several CNS drugs.Imipramine, Chlorpromazine: Imipramine in combination with zolpidem produced no pharmacokinetic interaction other than a 20% decrease in peak levels of imipramine, but there was an additive effect of decreased alertness. Similarly, chlorpromazine in combination with zolpidem produced no pharmacokinetic interaction, but there was an additive effect of decreased alertness and psychomotor performance Haloperidol: A study involving haloperidol and zolpidem revealed no effect of haloperidol on the pharmacokinetics or pharmacodynamics of zolpidem. The lack of a drug interaction following single-dose administration does not predict the absence of an effect following chronic administration Alcohol: An additive adverse effect on psychomotor performance between alcohol and oral zolpidem was demonstrated Sertraline: Concomitant administration of zolpidem and sertraline increases exposure to zolpidemFluoxetine: After multiple doses of zolpidem tartrate and fluoxetine an increase in the zolpidem half-life (17%) was observed. There was no evidence of an additive effect in psychomotor performance

Food Interaction

  • Avoid alcohol.
  • Take separate from meals. This drug should not be administered with or immediately after a meal.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of zolpidem.

Use in combination may result in additive central nervous system depression and
ADJUST DOSING INTERVAL: Administration of zolpidem with food may delay the onset of hypnotic effects.

In 30 healthy subjects, administration of zolpidem 20 minutes after a meal resulted in decreased mean peak plasma drug concentration (Cmax) and area under the concentration-time curve (AUC) by 25% and 15%, respectively, compared to fasting.

The time to reach peak plasma drug concentration (Tmax) was prolonged by 60%, from 1.4 to 2.2 hours.



MANAGEMENT: Patients receiving zolpidem should be advised to avoid the consumption of alcohol.

For faster sleep onset, zolpidem should not be administered with or immediately after a meal.

Volume of Distribution

0.54 to 0.68 L/kg (in humans) . In patients with long term renal insufficiency who were not yet on hemodialysis, the volume of distribution was found to increase significantly, AUC increased by 60%, and half-life nearly doubled .

Elimination Route

Zolpidem is rapidly absorbed from the gastrointestinal tract. In a single-dose crossover study in 45 healthy subjects given 5 and 10 mg zolpidem tartrate tablets, the average peak zolpidem concentrations (Cmax) were 59 and 121 ng/mL, respectively, occurring at a mean time (Tmax) of 1.6 hours for both doses .

Half Life

The average zolpidem elimination half-life was 2.6 and 2.5 hours, for the 5 and 10 mg tablets, respectively .

Clearance

In a clinical trial, after a 20mg dose, total clearance of zolpidem 0.24 to 0.27 ml/min/kg .

Elimination Route

Zolpidem tartrate tablets are converted to inactive metabolites that are eliminated mainly by renal excretion .

Pregnancy & Breastfeeding use

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.

Contraindication

Severe hepatic impairment.

Special Warning

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.

Acute Overdose

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.

Storage Condition

Store between 20-25° C.

Innovators Monograph

You find simplified version here Zolpidem

Zolpidem contains Zolpidem see full prescribing information from innovator Zolpidem Monograph, Zolpidem MSDS, Zolpidem FDA label

FAQ

What is Zolpidem used for?

Zolpidem is a sleeping pill. It's used to treat insomnia.when you might have trouble getting to sleep and staying asleep.Zolpidem helps you fall asleep more quickly and makes you less likely to wake up during the night.

What are the effects of Zolpidem?

Commonly reported side effects of Zolpidem include:dizziness and drowsiness.Other side effects include:

  • myalgia, 
  • visual 
  • hallucination, 
  • anxiety, 
  • hallucination, 
  • and nausea

How safe is Zolpidem?

Zolpidem can be taken by most adults aged 18 and over. Zolpidem not suitable for some people. To make sure Zolpidem is safe for you, tell a doctor if you: have had an allergic reaction toZolpidemor any other medicines in the past.

When should I take Zolpidem?

Zolpidem should be taken as a single intake just before bedtime. Make sure you have a period of at least 8 hours after taking this medicine before performing activities that require your alertness.

Is Zolpidem a good sleeping pill?

Zolpidem helps improve your sleep by boosting a chemical in your brain called gamma-aminobutyric acid (GABA). GABA blocks some of the neurotransmitters that send messages in the brain. This has a calming effect on the brain, which helps you get to sleep.

Is Zolpidem used for anxiety?

Zolpidem extended-release improves sleep and next-day symptoms in comorbid insomnia and generalized anxiety disorder.

What can't i take with Zolpidem?

A product that may interact with this drug is: sodium oxybate. Other medications can affect the removal of Zolpidem from your body, which may affect how Zolpidem works.

Is Zolpidem safe during pregnancy?

Zolpidem is an FDA pregnancy category C drug. The FDA categories are based on research currently available, including research from animal studies and human research. Category A drugs are considered the safest to take during pregnancy.

Is Zolpidem safe during breastfeeding?

Because of the low levels of Zolpidem in breastmilk and its short half-life, amounts ingested by the infant are small and would not be expected to cause any adverse effects in older breastfed infants.

Can Zolpidem cause heart problems?

Zolpidem users have a tendency for decreased risk of heart disease.

Can Zolpidem cause weight gain?

Yes,Zolpidem can be cause weight gain. Although this is somewhat old news, it is important to be reminded of this side effect of ambien.

Can Zolpidem raise blood pressure?

No changes in systolic blood pressure or heart rate were found with Zolpidem in comparison to placebo.

Is Zolpidem hard on kidneys?

Moderate Potential Hazard, Low plausibility.Zolpidem is extensively metabolized by the liver and subsequently excreted in the urine, primarily as metabolites.

Does Zolpidem cause memory loss?

The most frequent adverse effects associated with Zolpidem are nausea, headache, dizziness, drowsiness, hallucination, and short-term memory loss.

Is it safe to take Zolpidem every night?

Most experts agree that sleep aids should not be used long-term. Sleeping pills are best used for short-term stressors, jet lag, or similar sleep problems.

Can Zolpidem cause nightmares?

Side effects are not uncommon with Zolpidem use. patients developed delirium, nightmares and hallucinations during treatment with Zolpidem.

Can I drink alcohol with Zolpidem?

You should avoid the use of alcohol while being treated with Zolpidem. Alcohol can increase the nervous system side effects of Zolpidem such as dizziness, drowsiness, and difficulty concentrating.

Can I drive after taking Zolpidem?

More than 8 hours from the time you take the medication to the time you drive. Remember, being under the influence of these medications while driving is no safer than driving after drinking alcohol.

*** Taking medicines without doctor's advice can cause long-term problems.
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