Zoprol Cap 20 mg (Zolpidem): Potential Overview

1. Generic Name: Zolpidem
   Brand Name: Zoprol
   Strength: 20 mg per capsule
   Pack Size: 3 x 5’s (15 capsules)

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Zoprol Cap 20 mg (Zolpidem)

Zoprol 20 mg is a brand name for a medication that contains Zolpidem, a sedative-hypnotic drug commonly used for the treatment of insomnia. Below is a detailed overview of Zoprol 20 mg:

Mechanism of Action:

• Zolpidem is a non-benzodiazepine hypnotic that works by binding to the GABA-A receptors in the brain, specifically to the omega-1 receptor subtype.
• This binding enhances the effect of gamma-aminobutyric acid (GABA), a neurotransmitter that inhibits brain activity. The enhanced GABAergic activity leads to sedation, relaxation, and reduced anxiety.
• Zolpidem induces sleep by reducing the time it takes to fall asleep, increasing sleep duration, and improving sleep quality in individuals with insomnia.

Indications:

Zoprol (Zolpidem) is primarily prescribed for:

1. Short-term treatment of insomnia:
   • To help patients who have difficulty falling asleep (sleep onset insomnia).
   • It may also be prescribed for sleep maintenance insomnia in certain cases.
2. Pre-surgery sedation:
   • Sometimes used as a sedative before surgical or medical procedures (although this use is off-label).

Dosage and Administration:

• Typical dosage: 10 mg once daily, taken just before bedtime (with at least 7-8 hours available for sleep).
• Maximum dosage: For most patients, the maximum recommended dose is 10 mg per day.
• Elderly and patients with liver impairment: Start with 5 mg once daily, as they may be more sensitive to the sedative effects and have slower drug clearance.

Note: Zoprol should be taken only when the patient can commit to 7–8 hours of uninterrupted sleep due to the risk of residual drowsiness and impaired coordination.

Side Effects:

1. Common side effects:
   • Drowsiness, dizziness, headache.
   • Gastrointestinal issues: Nausea, vomiting, diarrhea.
   • Memory problems or amnesia (especially with high doses or prolonged use).
2. Serious side effects (rare but severe):
   • Allergic reactions: Rash, swelling of the face/tongue, difficulty breathing.
   • Sleepwalking, sleep-driving, or performing other activities while not fully awake (without memory of the event).
   • Depression, mood swings, or thoughts of suicide.
   • Hallucinations, confusion, or unusual thoughts.

Precautions and Warnings:

• Allergy: Avoid use in patients with known hypersensitivity to zolpidem or any other ingredients in the product.
• Pregnancy and breastfeeding:
  • Pregnancy: Zolpidem is Category C (may be harmful to the fetus, used only if absolutely necessary).
  • Breastfeeding: Zolpidem is excreted in breast milk, and it is generally advised to avoid use during breastfeeding or to use it with caution.
• Liver or kidney dysfunction:
  • Adjust the dose in patients with liver impairment (start with 5 mg).
  • Use with caution in renal impairment, as it can affect drug clearance.
• Drug interactions:
  • Zolpidem should not be taken with alcohol or other CNS depressants (e.g., benzodiazepines, opioids), as this can enhance sedative effects and increase the risk of respiratory depression, coma, or death.
  • It may interact with CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, grapefruit juice), which can increase zolpidem levels and enhance its effects.
• Use in elderly patients:
  • Elderly patients are at increased risk for falling, sedation, and impaired motor function. Lower doses are recommended (e.g., 5 mg).

Addiction and Dependence:

• Zolpidem has a low potential for abuse compared to benzodiazepines, but prolonged use or misuse may lead to tolerance, dependence, or withdrawal symptoms.
• It is recommended for short-term use (usually no longer than 4 weeks) to minimize the risk of dependence.

Overdose:

• Symptoms of zolpidem overdose can include drowsiness, lethargy, confusion, respiratory depression, and coma.
• In case of overdose, immediate medical attention is necessary. Flumazenil (a benzodiazepine receptor antagonist) may be used in cases of severe toxicity.

Pharmacist Related Data

1. Chemical Name and Formula:

• Generic Name: Zolpidem
• Brand Name: Zoprol
• Chemical Name: N,2,3-Trihydro-1H-imidazo[1,5-a]pyridin-3-yl)-N,N-dimethyl-2-propanamine
• Chemical Formula: C19H21N3O
• Molecular Weight: 307.4 g/mol

2.Pharmacodynamics:

• Zolpidem is a non-benzodiazepine sedative-hypnotic drug that binds to a specific subset of gamma-aminobutyric acid (GABA)-A receptors, particularly the alpha-1 subunit.
• By binding to the GABA-A receptors, zolpidem enhances the effect of GABA, an inhibitory neurotransmitter that suppresses neural activity in the brain, leading to sedation, muscle relaxation, anxiolysis, and hypnosis (sleep).
• Unlike traditional benzodiazepines, zolpidem selectively targets GABA-A receptor subtypes, which may explain its lower potential for abuse and shorter duration of action.
• Zolpidem primarily facilitates sleep initiation, but it is less effective for sleep maintenance (i.e., staying asleep throughout the night).

3. Pharmacokinetics:

Absorption:

• Zolpidem is well absorbed after oral administration, with rapid onset of action.
• Bioavailability: Around 70% after oral administration, though it can be affected by food.
• Peak plasma concentration (Cmax): Achieved within 1.6 hours after oral administration.
• The time to peak is slightly delayed if taken with food (i.e., 3 hours), so it is typically recommended to take zolpidem on an empty stomach for faster onset.

Distribution:

• Zolpidem is widely distributed throughout the body, including the brain, where it exerts its sedative effects.
• It is highly protein-bound (approximately 92%), meaning that only a small fraction of the drug is free or unbound to plasma proteins, and thus pharmacologically active.
• The volume of distribution (Vd) is about 1.0 to 1.3 L/kg, indicating a relatively high distribution into body tissues.

Metabolism:

• Zolpidem is primarily metabolized in the liver via the cytochrome P450 (CYP) system, particularly the CYP3A4 enzyme.
• Its metabolism results in several inactive metabolites, and it has minimal active metabolites, which means its effects are largely due to the parent drug.
• Metabolism is relatively rapid, and zolpidem has a short half-life, contributing to its relatively short duration of action.

Half-life:

• The elimination half-life of zolpidem is relatively short, ranging from 2 to 3 hours in healthy adults.
• The short half-life reduces the risk of daytime sedation or residual drowsiness after waking, though some individuals may still experience hangover effects, especially with higher doses.

Excretion:

• Zolpidem and its metabolites are primarily excreted via the kidneys in the urine (around 70% of the dose).
• Only a small percentage (approximately 10%) of the drug is excreted via feces.
• Renal impairment can affect zolpidem clearance, requiring dose adjustments in patients with severe renal dysfunction.

4. Drug Interactions:

Drug Interactions:

1. CNS Depressants:
   • Combining zolpidem with alcohol, benzodiazepines, opioids, or other CNS depressants can lead to enhanced sedative effects, which can result in respiratory depression, coma, or even death. This combination should be avoided.
2. CYP3A4 Inhibitors:
   • Drugs that inhibit the CYP3A4 enzyme (such as ketoconazole, itraconazole, grapefruit juice, or erythromycin) may increase zolpidem levels in the bloodstream, potentially increasing its sedative effects and the risk of adverse reactions.
   • Dose reduction may be needed when zolpidem is taken with strong CYP3A4 inhibitors.
3. CYP3A4 Inducers:
   • CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine) may reduce zolpidem’s effectiveness by increasing its metabolism, potentially necessitating higher doses to achieve the desired effect.
4. Antihistamines and Other Sedatives:
   • Antihistamines and other sedating drugs (e.g., antidepressants, antipsychotics) can enhance the sedative effects of zolpidem, increasing the risk of drowsiness and impaired motor function.
5. Other Medications for Insomnia:
   • Combining zolpidem with other sleep aids (e.g., benzodiazepines, barbiturates) can increase the risk of serious CNS depression, respiratory depression, and fatal overdose.

Food Interactions:

• Food: The presence of food can delay absorption of zolpidem, leading to a slower onset of action. It is generally recommended to take zolpidem on an empty stomach for the quickest effect, especially in patients needing immediate sleep induction.
• Alcohol: Alcohol can enhance the sedative effects of zolpidem, increasing the risk of severe drowsiness, respiratory depression, or coma.