Zolpidem was initially launched in Europe in 1988 by the pharmaceutical company Synthelabo. Through a partnership with Searle, it was subsequently introduced to the U.S. market and approved in 1992. The medication became available in generic form in 2007. Zolpidem is a medication used to treat insomnia by helping you fall asleep more quickly.
BRAND NAMES
Ambien, Ambien CR, Edluar, Intermezzo, and Zolpimist.
This medication is mainly prescribed for the short-term treatment of insomnia. The standard dose is a 10 mg tablet taken just before going to bed. It takes around 30 minutes to work.
MECHANISM OF ACTION
Zolpidem is a non-benzodiazepine hypnotic agent that acts as a modulator and agonist of gamma-aminobutyric acid (GABA) receptor chloride channels, enhancing GABA’s inhibitory effects and resulting in sedation. It specifically targets the GABA receptor, also known as the GABA-BZ receptor, which is widely distributed throughout the brain, including the sensorimotor cortex, globus pallidus, inferior colliculus, pons, ventral thalamic complex, olfactory bulb, cerebellum, and substantia regions. By enhancing the activity of these receptors, zolpidem produces sedative effects and supports the maintenance of deep sleep.
PHARMACOKINETICS
Absorption
Zolpidem is rapidly absorbed from the gastrointestinal tract. In a single-dose crossover study with 45 healthy participants given 5 mg and 10 mg zolpidem tartrate tablets, the mean peak plasma concentrations (Cmax) observed were 59 ng/mL and 121 ng/mL, respectively, the peak concentrations were reached at an average time (Tmax) of 1.6 hours for both doses.
Distribution
Both formulations of zolpidem demonstrate a high degree of protein binding, with an average of 92.5 ± 0.1%.
Metabolism
Zolpidem is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system, with CYP3A4 being the primary isoenzyme involved. This process produces three pharmacologically inactive metabolites, which are predominantly excreted by the kidneys. In healthy adults, the drug has a short elimination half-life of approximately 2 to 3 hours.
Excretion
Around 56% of the administered dose is excreted in the urine.
A significant portion of the inactive metabolites is also eliminated in the feces, accounting for about 34% of the dose.
PHARMACODYNAMICS
Zolpidem is a short-acting nonbenzodiazepine hypnotic that binds to gamma-aminobutyric acid (GABA)–benzodiazepine receptor complexes and exhibits some pharmacological effects similar to those of benzodiazepines.
ADMINISTRATION
In addition to standard oral tablets, zolpidem can be administered as a spray directed onto the tongue or as a tablet that dissolves under it. The standard oral dosage is 5 mg or 10 mg, based on the patient's sleep requirements.
DOSAGE AND STRENGTHS
Zolpidem is available in oral formulations as both a standard tablet and an extended-release tablet. Additionally, it comes as an oral spray sprayed onto the tongue and as a sublingual tablet placed under the tongue. Depending on the patient’s sleep needs, it is typically given orally in 5 mg or 10 mg doses. For both Ambien and Edluar, the standard nightly dosage is 5 mg to 10 mg, taken once before going to bed. The typical dosage of Ambien CR is 6.25 mg to 12.5 mg once per night.
DRUG INTERACTIONS
Combining zolpidem with alcohol, opioids, and other central nervous system (CNS) depressants such as antidepressants, anti-anxiety medications, or sedating antihistamines can cause extreme drowsiness, slowed breathing, and potentially fatal overdose. Other drug interactions can increase zolpidem's sedative effects or decrease its effectiveness.
FOOD INTERACTIONS
Taking zolpidem with or shortly after a meal can significantly delay its absorption, which may reduce its effectiveness and postpone the onset of sleep. For this reason, it is recommended to take it on an empty stomach to ensure it works quickly and effectively. Food can also increase the risk of next-day drowsiness and impairment.
CONTRAINDICATIONS
Zolpidem is contraindicated in individuals with a history of hypersensitivity to the medication or who have experienced complex sleep-related behaviors after taking it. It should be used with caution, and sometimes avoided, in patients with severe liver disease, respiratory issues like sleep apnea, mental health conditions including depression, or a history of substance abuse. Additionally, it carries risks for the elderly, pregnant or breastfeeding individuals, and should not be combined with alcohol or other central nervous system depressants due to increased risk of excessive sedation and dangerous side effects.
SIDE EFFECTS
Daytime drowsiness, dizziness, or a "drugged feeling".
Headache.
Nausea, stomach pain, or constipation.
Diarrhea.
Memory problems or amnesia.
Unusual dreams.
Pain in the back, muscles, or joints.
OVER DOSE
Excessive and severe drowsiness.
Confusion and impaired judgment.
Loss of balance or motor coordination.
Slurred speech.
Difficulty breathing or shallow breathing.
Becoming unconscious or entering a deep sleep.
Coma.
In rare, severe cases, death.
TOXICITY
Zolpidem toxicity, often resulting from an overdose, is characterized by central nervous system (CNS) depression and can range in severity from mild drowsiness to coma and even death. The risk of severe toxicity is significantly increased when zolpidem is combined with other CNS depressants, such as alcohol or opioids.
