NIKP-Zolpidem

Zolpidem.

Each tablet contains 10 mg of zolpidem tartrate.
Zolpidem tartrate has a chemical name of N,N,6-Trimethyl-2-(4-methylphenyl)imidazo[1,2-α] pyridine-3-acetamide hemi-(2R,3R)-tartrate. Its molecular formula is (C₁₉H₂₁N₃O)₂·C₄H₆O₆, and the molecular weight is 764.87.
Zolpidem Tartrate occurs as a white crystalline powder. It is freely soluble in acetic acid (100), soluble in N,N-dimethylformamide and in methanol, sparingly soluble in water, and slightly soluble in ethanol (99.5) and in acetic anhydride. It dissolves in 0.1 mol/L hydrochloric acid test solution. It gradually changes to yellow in color on exposure to light.
Excipients/Inactive Ingredients: Lactose, cellulose, sodium starch glycolate, hypromellose, talc, magnesium stearate, macrogol, titanium oxide, yellow ferric oxide, ferric oxide, carnauba wax.

Pharmacology: Pharmacokinetics: Bioequivalence Study: When a single oral dose of one tablet of NIKP-Zolpidem tablet 10 mg or one tablet of the reference product (both tablets contain 10 mg of zolpidem tartrate) was given to healthy male adults during fasting with a cross-over method, the plasma concentrations of zolpidem were measured. In a statistical analysis for the obtained pharmacokinetic parameters (AUC and C_max), calculation results of 90% confidence intervals for the parameters were within a range between log (0.8) and log (1.25), demonstrating the bioequivalence of the two formulations. (See Table 1 and figure.)

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Dissolution Profile: This drug has been shown to meet the dissolution specification for zolpidem tartrate tablets set forth in the Official Monographs of the Japanese Pharmacopoeia.

Short-term treatment of insomnia (excluding insomnia associated with schizophrenia and manic depression).
Precautions: This drug should be administered only after the primary disease causing insomnia has been diagnosed. They are not effective for treating insomnia associated with schizophrenia or manic depression.

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 10 mg dose increase the risk of next day impairment of driving and other activities that require full alterness.
Use the lowest effective dose for the patient.
The total dose of zolpidem should not exceed 10 mg once daily immediately before bedtime.
The recommended dose of zolpidem in elderly patients is 5 mg once daily immediately before bedtime.
The recommended dose of zolpidem in patients with hepatic insufficiency is 5 mg once daily immediately before bedtime.

Symptoms: Disturbances of consciousness ranging from somnolence to coma have been reported after overdose of zolpidem tartrate in monotherapy. Furthermore, severe sypmtoms such as central nervous system depression, hypotension, respiratory depression, and apnea may develop.
Treatment: Respiration, pulse, and blood pressure should be monitored and appropriate therapeutic measures (e.g., induction of emesis, gastric lavage, administration of adsorbents or laxatives, transfusion, airway management) should be taken. Furthermore, if overdose of this drug is confirmed or suspected and flumazenil (a benzodiazepine receptor antagonist) is to be used as a treatment, precautions for using flumazenil (e.g., contraindications, careful administration, and drug interactions) must be read in advance. It should be noted this drug is not dialyzable.

Patients with a history of hypersensitivity to any of the ingredients of this drug.
Patients with severe liver disorder [The blood concentration would rise due to impaired metabolic function, which could strengthen the effects of the drug.]
Patients with myasthenia gravis [The muscle relaxing effects of the drug could exacerbate symptoms.]
Patients with acute narrow-angle glaucoma [The drug could increase intraocular pressure and exacerbate symptoms.]
Relative Contraindications: This drug is generally contraindicated in the following patients, but may be administered with caution if indispensable: Patients with acute pulmonary heart disease, pulmonary emphysema, bronchial asthma, and cerebrovascular disease whose respiratory function is highly compromised [Such patients are prone to carbon dioxide narcosis from respiratory depression.]

Use of this drug may induce twilight states or parasomnias (e.g., sleepwalking) and complex sleep-related behaviours. In addition, the user may not remember activities they do before they fall asleep or during nocturnal awakenings.
Due to the lactose content, this drug is contraindicated in the event of congenital galactosaemia, glucose or galacotse malabsorption syndrome or lactase deficiency.

Careful Administration: This product should be administered with care in the following patients: Debilitated patients [drug effects are strong and thus adverse reactions are more likely]; elderly patients (see Use in Elderly as follows); patients with cardiac disorder [blood pressure may decrease, which could exacerbate symptoms in patients with cardiac disorder]; patients with liver disorder (see Contraindications); patients with kidney disorder [delayed excretion could strengthen the effects of the drug]; patients with organic brain disorder [the effects of the drug could be strengthened.]
Important Precautions: Continuous administration of this drug should be avoided; it should only be administered for a short period of time. If continuous administration is absolutely necessary, it should be done carefully while closely monitoring the patient for any abnormalities in their condition or symptoms on a regular basis.
The effects of this drug may extend past the following morning and result in sleepiness and decreased alertness, concentration, and reflexive motor skills. It is recommended not to drive or perform activities that require mental alertness until 8 hours after taking zolpidem.
Worsening of depression and suicidal thoughts and actions (including completed suicides) reported primarily depressed patients; prescribe the lowest feasible number of tablets at a time.
Other Precautions: If this drug is administered again in a patient who received flumanezil (a benzodiazepine receptor antagonist) before the drug taken was identified, the sedative and anticonvulsive effects of this drug may change or persist for a longer period of time.
Use in Children: The safety of this drug in low birth weight infants, newborns, nursing infants, and children has not been established. (No clinical experience.)
Use in Elderly: Ataxia is common. Furthermore, as elderly patients are prone to adverse reactions, a low dose (5 mg/dose) should be administered at first and no more than 10 mg should be taken at one time.

Use in Pregnancy: This drug should only be administered to pregnant women or women suspected of being pregnant, if the expected therapeutic benefits are evaluated to exceed the possible risks of treatment. [The safety of zolpidem in pregnant women has not been established. Children born to mothers who took a zolpidem tartrate formulation during late pregnancy may develop withdrawal symptoms such as respiratory depression, convulsions, tremors, irritability, and nursing difficulties. These symptoms have presented as birth asphyxia in some cases.]
Use in Lactation: It is desirable to avoid the administration of this drug to nursing mothers. However, if the administration is indispensable, nursing should be discontinued. [Transfer to breast milk has been reported and may lead to lethargy in newborns.]

Surveys or studies that demonstrate frequency of adverse reaction have not been conducted.
Clinically Significant Adverse Reactions (Frequency Unknown): Dependence and Withdrawal Symptoms: Drug dependence may occur with use, so this drug should be administered with caution while carefully monitoring patients. Furthermore, a rapid reduction in dose or discontinuation during use may lead to withdrawal symptoms such as rebound insomnia or irritability. If administration is to be discontinued, it should be done carefully by gradually decreasing the dose.
Psychiatric Symptoms and Disturbances of Consciousness: Psychiatric symptoms and disturbances of consciousness (e.g., delirium, confusion, somnambulism, hallucinations, excitation, disinhibition, depressed level of consciousness) may occur. Patients, hence, should be carefully monitored. If any abnormal findings are observed, administration of this drug should be discontinued and appropriate therapeutic measures should be taken.
Transient Anterograde Amnesia and Twilight States: Sleep walking and other associated behaviours such as “sleep driving”, preparing and eating food, making phone calls or having sex, with amnesia for the event, have been reported in patients who had taken zolpidem and were not fully awake. The use of alcohol and other CNS-depressants with zolpidem appears to increase the risk of such behaviours, as does the use of zolpidem at doses exceeding the maximum recommended dose. Discontinuation of zolpidem should be strongly considered for patients who report such behaviours (for example, sleep driving), due to the risk to the patient and others.
Respiratory Depression: Respiratory depression may occur. Furthermore, carbon dioxide narcosis may occur if this drug are administered to a patient with highly compromised respiratory function. Therefore, in such circumstances, appropriate therapeutic measures such as airway management and ventilation should be taken.
Hepatic Function Disorder, Jaundice: Hepatic function disorder and jaundice accompanied by increased AST (GOT), increased ALT (GPT), increased γ-GTP, and increased Al-P may occur. Patients, hence, should be carefully monitored. If any abnormal findings are observed, administration of this drug should be discontinued and appropriate therapeutic measures should be taken.
Other Adverse Reactions: See Table 2.

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This drug is mainly metabolized by the liver drug metabolizing enzyme CYP3A4 and partially metabolized by CYP2C9 and CYP1A2. Zolpidem should not be taken together with alcohol, other medicines that have an effect on mental function and/or central nervous system. (See Table 3.)

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Store below 25°C.
Shelf-Life: 2 years.

Hypnotics & Sedatives

N05CF02 - zolpidem ; Belongs to the class of benzodiazepine related agents. Used as hypnotics and sedatives.

P₁S₁S₃