Zolpidem

Zolpidem is a nonbenzodiazepine receptor modulator that is primarily used in the FDA-approved short-term treatment of insomnia in patients with difficulty falling asleep. It improves sleep latency, sleep duration, and reduces awakenings in patients with transient insomnia. It also improves sleep quality in patients with chronic insomnia and may act as a minor muscle relaxant. This article reviews the indications for zolpidem, including pharmacology, side effects, dosage, contraindications.

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Indications Zolpidem

Studies also show that it quickly and effectively restores brain function in patients who are in a vegetative state after a brain injury, as the drug can completely or partially reverse the abnormal metabolism of damaged brain cells. Patients usually recover if the injury is not in the brain stem areas. [ 3 ], [ 4 ], [ 5 ]

Release form

The main active ingredient of the drug is zolpidem tartrate, which, in order to maintain its high pharmacological effectiveness, is combined with some other excipients.

Along with zolpidem, the tablet form contains: 55 mg lactose monohydrate, 42.4 mg microcrystalline cellulose, 4.8 mg sodium carboxymethyl starch, 1.8 mg povidone, 0.4 mg colloidal silicon dioxide and 0.6 mg magnesium stearate.

The protective shell is represented by such chemical compounds as macrogol, hyprolose, hypromellose, titanium dioxide, carnauba wax and special dyes.

The drug is available in one form - tablets covered with a dense protective shell. The tablet has a slightly convex shape on both sides, with a dividing strip visible on one side of the plane.

Pharmacodynamics

Zolpidem, a nonbenzodiazepine hypnotic agent, acts as a gamma-aminobutyric acid (GABA) chloride channel receptor modulator/agonist, which enhances the inhibitory effects of GABA, resulting in sedation. It also has anticonvulsant, anxiolytic, and mild muscle relaxant properties. The GABAa receptor, also called GABA-BZ, is found in the sensorimotor areas of the cortex, globus pallidus, inferior colliculus, pons, ventral thalamic complex, olfactory bulb, cerebellum, and largely in the cerebrum. The drug activates these receptors, producing a sedative effect that leads to the maintenance of deep sleep.[ 6 ],[ 7 ]

Unlike benzodiazepines, which non-selectively bind to and activate all benzodiazepine (BZ) receptor subtypes, zolpidem binds the BZ1 receptor preferentially in vitro with a high alpha1/alpha5 subunit affinity ratio. The selective binding of zolpidem to the BZ1 receptor may explain the relative lack of muscle relaxant and anticonvulsant effects. Overall, zolpidem is not recommended as a first-line treatment in the general population due to its high abuse liability. Medications such as controlled-release melatonin and doxepin may be used as first-line treatment in addition to proper sleep hygiene and cognitive behavioral therapy for patients with insomnia.

Pharmacokinetics

The elimination half-life of 5 mg zolpidem was 2.6 hours. Accordingly, the elimination for patients administered 10 mg zolpidem is 2.5 hours with a range of 1.4 to 3.8 hours. Zolpidem undergoes linear kinetics when the drug dose range is from 5 to 20 mg. The drug was also found to be primarily protein bound and remains unchanged in concentration, which is subsequently extracted through the renal system.

Patients experience anterograde amnesia after taking the drug if plasma concentrations are high at the time of exposure. This is due to either inattention or consolidation of the memory process.

This drug may cause excessive use and daily dependence. Patients who use drugs for several weeks have low behavioral dependence on zolpidem. Patients who have used zolpidem in higher single doses or have a history of drug abuse should be closely monitored when using zolpidem or any other sleep aid.

Dosing and administration

Zolpidem is rapidly absorbed from the gastrointestinal tract and has a short half-life in healthy patients. Oral zolpidem is available as tablets and extended-release tablets. Zolpidem is also available as an oral spray, which is sprayed into the mouth over the tongue, and a sublingual tablet, which is placed under the tongue. It is administered in tablets of 5 or 10 mg orally, depending on the patient's sleep quality. Zolpidem is then converted to an inactive metabolite and excreted by the kidneys. Tablets do not count. Swallowing with or immediately after meals may delay the action of this drug.

Elderly patients should receive a 5 mg dose because their concentrations were higher than those in younger adults during clinical trials. In patients with liver dysfunction, the dosage should be adjusted because the half-life of zolpidem is many times longer than in healthy patients. The recommended starting dose is 5 mg for women and 5 or 10 mg for men, taken only once per night immediately before bedtime, with at least 7 to 8 hours before the scheduled time of awakening. Zolpidem clearance is lower in women. [ 11 ], [ 12 ], [ 13 ]

Patients with end-stage renal disease undergoing dialysis do not require dosage adjustments, as they were not significantly different from patients with renal impairment. However, zolpidem concentrations should be closely monitored on a daily basis.

Zolpidem should not be prescribed to pediatric patients because its effectiveness has not yet been established. In addition, a study has shown that hallucinations may occur in a small percentage of pediatric patients treated with zolpidem.

Use Zolpidem during pregnancy

Do not take zolpidem if you are pregnant because it may harm your baby. There is some evidence that taking zolpidem may increase the risk of your baby being born prematurely (before 37 weeks) and having a lower birth weight.

Taking zolpidem right before labor starts may increase your baby's chances of having withdrawal symptoms right after birth.

There is little information on the use of zolpidem during breastfeeding. Some experts believe that zaleplon is not recommended during breastfeeding.[ 8 ],[ 9 ] Because of the low levels of zolpidem in breast milk and its short half-life, the amounts ingested by the infant are small and are not expected to cause any adverse effects in older breastfed infants. Monitor infants for excessive sedation, hypotension, and respiratory depression.

Five lactating mothers who were 3 to 4 days postpartum were given a single 20 mg oral dose of zolpidem. Milk collected 3 hours after dosing contained 0.76 to 3.88 mcg of zolpidem. This corresponded to 0.004 to 0.019% of the maternal dose. The drug was undetectable (<0.5 mcg/L) in milk at 13 and 16 hours postdose.[ 10 ]

Contraindications

Zolpidem is contraindicated only in patients with a known allergy to the drug or inactive ingredients in the formula. In addition, other causes of sleep deprivation, such as any existing medical or psychiatric history, should be assessed before administering zolpidem.

Caution should be exercised in patients also taking drugs that affect drug metabolism via cytochrome P450. Consider prescribing a lower dosage of zolpidem, as patients have shown increased sedation. Zolpidem should be avoided in patients taking imipramine and chlorpromazine. When combined, these drugs cause decreased alertness and psychomotor performance.

Side effects Zolpidem

Some side effects include anaphylaxis, behavioral changes, withdrawal symptoms, and central nervous system (CNS) depression.

In rare cases, patients have reported swelling of the tongue, larynx, or glottis in the form of angioedema. In addition, patients have reported shortness of breath, airway closure, nausea, and vomiting. If patients report this, do not re-administer the drug to the patient. Patients who experience closure of the throat, glottis, or larynx should be referred to the emergency department.

Changes in behavior and abnormal thinking have also been reported. In addition, patients have been found to exhibit aggressiveness and extroversion, which are abnormal for normal human behavior. Patients suffering from alcohol or drug poisoning experience auditory and visual hallucinations associated with strange behavior and agitation.

The patient has also been found to exhibit a behavior called sleep driving, in which the patient drives while not fully awake after taking a sedative-hypnotic, without any memory of the event. The use of alcohol or any other CNS depressant has been found to enhance these phenomena, as the combination increases the sedative effect. In these cases, the drug should be discontinued. Patients who are depressed should also not take zolpidem, as it worsens depression and suicidal thoughts and actions.

Overdose

Zolpidem overdose causes CNS depression, cognitive impairment leading to drowsiness or coma, cardiovascular and respiratory depression, and other fatal outcomes. The acute toxicity of zolpidem is less severe than that of other short-acting benzodiazepines such as triazolam and midazolam. However, in combination intoxication with other CNS depressants, zolpidem can cause coma even at low concentrations. Single-drug poisoning is benign and does not require therapeutic intervention.

If the patient develops any symptoms, gastric lavage should only be attempted if the benefits outweigh the risks within one hour of ingestion and if the patient is conscious with a gag reflex or is intubated. Patients may also benefit from flumazenil and intravenous fluids. Flumazenil is a known antagonist of benzodiazepine toxicity; however, it may exacerbate other neurological symptoms such as seizure activity.

In case of drug toxicity, the patient's respiratory function, oxygen saturation, blood pressure, pulse and other vital signs should be monitored. [ 14 ]

Interactions with other drugs

Some medications and zolpidem may interfere with each other and increase the chance of side effects. Some medications may increase the sleep-inducing (sedative) effects of zolpidem.

Before taking zolpidem, talk to your doctor or pharmacist if you are taking any of the following:

1. drowsy antihistamines such as chlorphenamine or promethazine;
2. medications for the treatment of schizophrenia and bipolar disorder;
3. medications for the treatment of depression;
4. anti-epilepsy medications;
5. medications to calm or reduce anxiety;
6. medications for sleep problems;
7. medicines used to treat fungal infections (such as ketoconazole and itraconazole);
8. ritonavir (a drug used to treat HIV infection);
9. strong painkillers (such as codeine, methadone, morphine, oxycodone, pethidine, or tramadol).

• Mixing Zolpidem with Herbs and Supplements

Do not take any herbal remedies that make you sleepy while taking zolpidem. They may increase the sleep-inducing (sedative) effects of your medicine.

Storage conditions

The storage conditions for Zolpidem are not much different from the classic set of recommendations:

1. The medicine should be stored throughout the entire period of permitted use in a cool place where the temperature does not exceed +25 degrees.
2. Keep Zolpidem out of the reach of small children.
3. The medicine should not be exposed to direct sunlight.
4. The humidity of the room where the drug is stored should be low.

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Shelf life

When buying any medication, the first thing you need to pay attention to is its expiration date. The packaging of the drug must reflect both the production date and the recommended end time of administration. For Zolpidem, the expiration date is three years. If the end use date on the packaging has already passed, then such a drug is not recommended for further use.