Zolpidem: Sedative, Ambinox, Jonfa, Stilnox, Zoltsan

2021-06-11 05:40 PM

Zolpidem is quick and short-acting, with normal doses inducing sleep in humans, zolpidem shortens the time to onset of sleep and prolongs the duration of sleep, maintaining deep sleep.

International generic name: Zolpidem.

Type of drug: Sedative to induce sleep.

Drug form and content

Tablets, film-coated tablets 5 mg and 10 mg (zolpidem tartrate).

6.25 mg and 12.5 mg delayed-release tablets (zolpidem tartrate).

Pharmacology and mechanism of action

Zolpidem tartrate is a derivative of imidazopyridine with strong sedative effects causing sleep. Although zolpidem is structurally unrelated to benzodiazepines, zolpidem has some of the pharmacological properties of benzodiazepines and has interacted with the Cl channel complex - GABA receptors (gamma-aminobutyric acid) in the central nervous system at benzodiazepine (BZ) receptors. , omega). Unlike some benzodiazepines, which nonselectively act on type 1 (BZ1, omega1), type 2 (BZ2, omega2) receptors in the central nervous system as well as peripheral type 3 (BZ3, omega3) receptors. , leading to nonspecific pharmacological effects, zolpidem binds selectively to BZ1 receptors with a high affinity for the alpha1/alpha2 subunit, so zolpidem has little muscle relaxant, anxiolytic, and anti-inflammatory effects. seizures compared with benzodiazepines. Zolpizem is also a bit forgetful. Zolpidem is quick and short-acting. At doses normally inducing sleep in humans, zolpidem shortens the time to onset of sleep and prolongs the duration of sleep, maintaining deep sleep (stages 3 and 4). The selective binding of zolpidem to the BZ1 receptor may reduce the abuse potential and reduce the development of tolerance, but has not been recognized. The selectivity of zolpidem for pharmacology and toxicology may be dose and species-dependent. In addition, the EEG changes during sleep with zolpidem were similar to those observed with benzodiazepines. Current evidence suggests the little risk of daytime sleepiness and effects on mental and psychological functioning.

Clinical studies have shown that zolpidem has a greater sedating effect than placebo and is generally comparable to benzodiazepines by comparison. There have been reports of drug abuse. In terms of residual post-day effects, withdrawal symptoms or dependence, zolpidem is not superior to short-acting benzodiazepines.

A study in children and adolescents 6-17 years of age with insomnia with decreased attention/hyperactivity showed that zolpidem was no more effective than placebo, in addition to some ADRs such as dizziness, headache. , illusion. Therefore, this medicine should not be given to children and adolescents.

Pharmacokinetics

Absorption:

Zolpidem is rapidly and almost completely absorbed from the gastrointestinal tract. Food slows and reduces drug absorption. After oral administration from 30 minutes to 2 hours, the drug reaches maximum plasma concentration (after 30 minutes when taking a dose of 20 mg zolpidem, the peak blood concentration is about 200 nanograms/ml). Zolpidem undergoes first-pass metabolism, with an absolute bioavailability of about 70%.

Distribution:

The volume of distribution is about 0.54 liters/kg. Zolpidem passes into breast milk (3 hours after a 20 mg dose, concentrations in milk range from 0.004 to 0.019%). Binding to plasma proteins is about 92%.

It is not known whether zolpidem crosses the placenta.

Elimination and metabolism:

The drug is metabolized mainly in the liver by cytochrome P450 to an inactive metabolite. Inactive metabolites are eliminated mainly by the kidneys (48-67% in the urine) and feces (29-42%). Zolpidem has a mean elimination half-life of 2.5 hours (range 1.4 to 4.5 hours); The elimination half-life of the drug is prolonged in the elderly, longer in patients with hepatic impairment (9.9 hours), and renal failure. Zolpidem cannot be removed by hemodialysis.

Indications

Short-term correction of frequent insomnia (such as when traveling).

Short control takes time to sleep (makes stress).

Contraindications

Hypersensitivity to the drug or to any of its ingredients.

Sleep apnea. Acute respiratory failure. Computational network congestion disease.

Basic disadvantages.

Liver failure, severe renal failure.

Deity.

Pregnant and lactating women.

Cautions

Since insomnia can be a manifestation of a physical and/or mental illness, a careful examination of the patient should be made before insomnia is valid. If after 7 - 10 days of the value by zolpidem that is not supported, must be marketing, can do a disease center or a content disease to must have a value.

Do not use sleeping pills for more than 2-3 weeks.

Narcotics and psychotropic drugs including zolpidem have the potential to alter processing importance and mood abnormalities such as driving while asleep (i.e., driving while not fully awake after taking a sedative). . without the event occurring).

When this drug is used in combination with alcohol or other central nervous system depressants, depression may develop or worsen (suicidal ideation), anxiety, amnesia. Because that, when the output is any new processing at the people are being used to zolpidem must also be polled and reevaluated. Since some accessories are dose-related, it is important to try to use the lowest effective dose, especially for the elderly.

Because zolpidem is fast-acting, it should be taken just before bedtime.

It is necessary to warn the patient about the impact on functional activities, dexterity, and coordination requirements such as driving a car, operating machinery. Patients also should not use the drug if they cannot sleep enough nights continuously for many hours (7 - 8 hours) and the drug is excreted from the body before returning to work and returning to work because it may occur during periods. forget.

Caution should be exercised in combination with central nervous system depressants and alcohol because of community or potentiating effects.

Discontinuing or decelerating zolpidem too quickly in people taking the drug for a long time (eg, more than 1 - 2 weeks) because may promote symptoms of drug addiction. This certificate of the same as when COMBINED WITH DIFFERENT MEDICINE. Withdrawal symptoms associated with medications ranging from irritability, insomnia to withdrawal syndrome include stiff muscles and abdomen, heat, sweating, running and convulsions or fatigue, boredom, red face, face, crying uncontrollably, in pain, panicking within 48 hours of the last fever.

The drug should be used with caution in patients with impaired respiratory function due to sedating sedatives with the potential for respiratory depression.

The drug must be discontinued in the event of an allergic reaction such as rash, urticaria, especially angioedema.

Use the drug with caution in people with depression, people with a history of drug addiction, patients with compromised respiratory function, alcoholism, liver failure (not used in severe cases), kidney failure and the elderly.

Avoid prolonged use of the drug. It is necessary to clearly explain the time of taking the drug to the patient, depending on the type of insomnia. When taking the drug for 1-2 weeks or more, the dose must be reduced gradually before stopping to avoid withdrawal syndrome.

Pregnancy

Pregnant women should not take zolpidem at any time.

Breastfeeding

Zolpidem is distributed into breast milk in small amounts; the effect of the drug on the nursing infant is unknown. However, in order to avoid ADRs in the infant, the mother should not take this drug during breastfeeding or discontinue breastfeeding when the benefits of taking the drug to the mother have been considered.

Adverse Effects (ADRs)

Zolpidem is generally well tolerated at therapeutic doses. ADR tends to increase with the dose and duration of drug use, especially in the elderly. ADR is mainly related to the central nervous system and digestive system such as drowsiness, dizziness, diarrhea.

Common, ADR > 1/100

Nervous: Drowsiness, lethargy, headache, dizziness, weakness, confusion, forgetfulness, anxiety, difficulty concentrating, loss of coordination, sweating.

Gastrointestinal: Diarrhea, nausea, vomiting, dyspepsia, constipation, abdominal pain, loss of appetite.

Muscle: Muscle and joint pain.

Uncommon, 1/1 000 < ADR < 1/100

Psychiatric depression, anxiety, nervousness, sleep disturbance, paresthesia, migraine, apathy, neuralgia, neuritis, cerebral palsy, decreased libido, migraine, tremor, difficulty speaking.

Also may experience: Difficulty swallowing, taste disturbance, flatulence, cough, shortness of breath, cramps, bronchitis.

Rarely, ADR < 1/1 000

Neurological: Hallucinations, irritability, insomnia, suicidal tendencies, convulsions, sciatica.

Allergic reactions: Anaphylaxis, skin allergy, and photosensitivity.

Other: Intestinal obstruction, rectal bleeding, epistaxis, bronchospasm, muscle weakness, tendonitis, arthritis, increased liver enzymes, hypotension.

Instructions on how to handle ADR

Because the drug causes drowsiness, dizziness, and memory loss, the drug should be taken at night when going to bed; Do not drink while working, especially when driving a vehicle or operating machinery.

Although clinical trials of zolpidem have not demonstrated the potential for dependence, there have been some reports of zolpidem withdrawal syndrome. Therefore, after long-term or high-dose use, the dose should be reduced gradually before stopping completely.

Dosage and Administration

Indications

Take the medicine right before going to bed. The delayed-release tablets must be swallowed whole and must not be chewed or divided.

Dosage

Dosage varies from person to person, one must use the smallest effective dose (especially for the elderly, debilitated people, people with liver disease). Avoid prolonged treatment.

Adults: Usual dose: Regular tablets: 10 mg at bedtime. Or extended-release tablet: 12.5 mg. In all cases, the dose of 10 mg per day should not be exceeded.

Elderly, debilitated people: Starting dose of 5 mg (regular tablet) or 6.25 mg (extended-release tablet) at bedtime; Adjust dose if necessary.

Hepatic impairment: Starting dose of 5 mg (regular tablet) or 6.25 mg (extended-release tablet) at bedtime; Adjust dose if necessary.

People with kidney failure: Opinions are not unanimous. The manufacturer claims that no adjustment is required but must be closely monitored. Others have suggested that dose reduction is necessary because of the slower elimination rate of zolpidem and other changes in pharmacokinetics in patients with renal failure who are not on hemodialysis and on hemodialysis.

Duration of treatment: As short as possible, if possible, from a few days to 4 weeks, including dose reduction. It is necessary to guide the treatment time for patients such as occasional insomnia (eg travel): 2 - 5 days; Temporary insomnia (mental stress): 2-3 weeks. If treatment is very short, there is no need to gradually reduce the dose. If long-term treatment is required, it is necessary to repeatedly and accurately assess the patient's condition.

Dosage should be reduced in patients receiving other CNS depressants concurrently due to increased potency.

Dosage should also be reduced in patients with hepatic impairment: The initial oral dose is 5 mg at bedtime, the dose may be increased to 10 mg, if necessary, in subjects under 65 years of age.

The safety and efficacy of the drug in children under 18 years of age have not been established; There are no recommendations for use of this medicine in children.

Drug interactions

Zolpidem is majorly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6.

Drugs that affect liver microglial enzymes: Potential for pharmacokinetic interactions.

The antifungal azoles (ketoconazole, fluconazole...) inhibit metabolism, increase the concentration and increase the effect of zolpidem. Therefore, when used concomitantly with antifungal azoles, the dose of zolpidem should be reduced.

Rifampicin: Increases cytochrome P450 CYP3A4 metabolism, reduces plasma concentrations, and reduces the effect of zolpidem. Therefore, when co-administered with rifampicin, the dose of zolpidem should be increased.

Ritonavir and other drugs in the same class: Inhibits hepatic metabolism, increasing the concentration of zolpidem leading to strong sedation and respiratory depression. Therefore, manufacturers advise against taking these two drugs at the same time.

Serotonin absorption inhibitors (fluoxetin, paroxetin ...) inhibit metabolism and increase the effect of zolpidem.

Flumazepine: Reverses the sedative effects of zolpidem.

Stability and preservation

Unless otherwise indicated by the manufacturer, the drug should be stored at a temperature of 15 - 25 degrees Celsius; in sealed packaging.

Overdose and treatment

Symptoms: Life can be threatened, especially with multiple medications including CNS depressants (including alcohol). With single toxicity of zolpidem, the prognosis is generally good with doses up to 400 mg. The signs of overdose (single or multidrug zolpidem) are primarily CNS depression, ranging from somnolence to coma, depending on the amount taken. Mild cases: Confusion, lethargy. More severe cases: Loss of coordination, decreased muscle tone, hypotension, respiratory failure, rarely death.

Treatment: If overdose due to oral administration 1 hour before, induce vomiting if the patient is awake, if comatose, perform gastric lavage with respiratory protection. Beyond that time, giving activated charcoal may reduce absorption. The cardio-respiratory function should be specially monitored in the intensive care unit. Flumazenil may be used to diagnose and/or treat intentional or accidental overdose of benzodiazepines. The antagonism of flumazepine to the effects of benzodiazepines can lead to the development of neurological disorders (convulsions), mainly in people with epilepsy. Failed to dialyzate zolpidem.

Trade names

Ambinox; Jonfa; Stilnox; Zoltsan.

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