Stilnox瑞樂時

Stilnox

zolpidem

Manufacturer:

Sanofi

Distributor:

DCH Auriga - Healthcare
/
Four Star
Full Prescribing Info
Contents
Zolpidem tartrate.
Description
Each scored film-coated tablet contains: Zolpidem tartrate 10 mg.
Action
Pharmacotherapeutic group: Hypnotics and sedatives. ATC code: N05CF02 (N: Central Nervous System).
Pharmacology: Pharmacodynamics: Zolpidem is a hypnotic imidazopyridine related to benzodiazepines with pharmacodynamic effects that are qualitatively similar to that of other compounds in the same class, i.e.: muscle relaxant, anxiolytic, sedating, hypnotic, anticonvulsant, amnesic.
Experimental studies have demonstrated a sedative effect at doses lower than those required to obtain anticonvulsant, muscle-relaxant or anxiolytic effects.
These effects are related to a specific agonist action on a central receptor belonging to the "GABA-OMEGA" macromolecular receptor complex, also known as BZ1 and BZ2, modulating the opening of the chloride ion channel.
Zolpidem preferentially binds to the omega-1 receptor subtype (or BZ1).
In man, zolpidem decreases sleep latency, reduces the number of nocturnal awakenings, and increases total sleep duration and sleep quality. These effects are associated with a characteristic EEG profile, different from that of benzodiazepines. Studies recording night-time sleep have shown that zolpidem prolongs both stage II sleep and deep sleep stages (III and IV). At the recommended dose, zolpidem has no influence on total paradoxical sleep duration (REM).
In randomized trials, zolpidem was shown to be effective only at the 10 mg dose.
In a randomized double-blind study in 462 healthy volunteers under 65 years of age with transient insomnia, sleep latency was decreased by 10 minutes in the zolpidem 10 mg group and by 3 minutes in the 5 mg group compared to placebo.
In a randomized double-blind study in 114 patients under 65 years of age with chronic insomnia, mean sleep latency was decreased by 30 minutes in the zolpidem 10 mg group and by 15 minutes in the 5 mg group compared to placebo.
In some patients, a dose of 5 mg may prove to be effective.
Children and adolescents: Randomized placebo-controlled study in 201 children and adolescents aged 6-17 years with insomnia associated with Attention Deficit Hyperactivity Disorder (ADHD) failed to demonstrate efficacy of zolpidem 0.25 mg/kg/day (with a maximum of 10 mg/day) compared to placebo. Psychiatric and neurological disorders were the adverse events most frequently observed in patients treated with zolpidem compared to placebo and included dizziness (23.5% versus 1.5%), headache (12.5% versus 9.2%), and hallucinations (7.4% versus 0%).
Consequently, and in the absence of any new studies, zolpidem must not be prescribed in this population. (See Dosage & Administration.)
Pharmacokinetics: Absorption: After oral administration, the bioavailability of zolpidem is approximately 70% and peak plasma concentrations are reached in 0.5 to 3 hours.
Distribution: The pharmacokinetic pattern of the drug is linear at therapeutic doses. Zolpidem is approximately 92% bound to plasma proteins. The volume of distribution in adults is 0.54 ± 0.02 l/kg.
Metabolism and elimination: Zolpidem is eliminated as inactive metabolites (via liver metabolism), primarily in the urine (approximately 60%) and feces (approximately 40%). It does not have a liver enzyme-inducing effect.
Mean plasma elimination half-life is 2.4 hours (0.7 to 3.5 hours).
At-risk populations: Liver clearance is reduced in elderly patients. Peak plasma concentrations are approximately 50% higher in this population and the half-life is not significantly prolonged (mean of 3 hours). The volume of distribution is reduced to 0.34 ± 0.05 l/kg.
Renal clearance is moderately decreased in patients with kidney failure, regardless of whether they are dialyzed or not. The other kinetic parameters remain unchanged. Zolpidem is not dialyzable.
In patients with liver failure, bioavailability of zolpidem is increased. Clearance is substantially reduced and elimination half-life prolonged (approximately 10 hours).
Indications/Uses
Use of zolpidem is limited to the treatment of severe sleep disorders in adults with: Transient insomnia, Short-term insomnia.
Dosage/Direction for Use
Dose: The treatment should be taken as a single dose and not be re-administered during the same night.
The recommended daily dose for adults is 10 mg, to be taken immediately at bedtime.
Treatment should always be initiated at the lowest effective dose and the maximum dosage must not exceed 10 mg.
Elderly or debilitated subjects: As elderly or debilitated patients are especially sensitive to the effects of zolpidem, the recommended dose in this population is 5 mg (i.e. half a tablet).
Liver failure: As the clearance and metabolism of zolpidem are reduced in liver failure, treatment should be initiated at 5 mg per day in these patients, with particular caution being exercised in elderly patients.
Under no circumstances should the daily dose exceed 10 mg.
Stilnox may be prescribed for use continuously or as required, depending on the signs and symptoms.
Paediatric population: The safety and efficacy of zolpidem in children and adolescents under 18 years of age have not been demonstrated. Therefore, use of zolpidem is not recommended in this population. The available evidence from placebo-controlled clinical trials is presented in Pharmacology: Pharmacodynamics under Actions.
Treatment duration: The duration of treatment should be as short as possible, from a few days to four weeks, including the tapering off period (see Warnings and Precautions).
The duration of treatment must be explained to the patient: 2 to 5 days for transient insomnia (when traveling, for example); 2 to 3 weeks for short-term insomnia (following a serious event, for example).
Very short-term treatments do not require discontinuation tapering-off period.
In some cases, it may be necessary to extend treatment beyond the recommended durations. This requires detailed and repeated reassessment of the patient's condition.
Overdosage
Overdose can be life-threatening, particularly multiple overdose involving other central nervous system depressants (including alcohol). In the case of zolpidem, the prognosis has always been positive for single-agent intoxication with doses of zolpidem of up to 400 mg.
If massive amounts of zolpidem are taken alone or concomitantly with other central nervous system depressants (including alcohol), the main sign of overdose is central nervous system depression, which may range from drowsiness to coma, depending on the amount ingested.
In non-serious cases of overdose, symptoms include confusion and lethargy.
In more serious cases, signs include ataxia, hypotonia, hypotension, respiratory depression and, in very rare cases, death.
If oral overdose occurred less than one hour before, vomiting should be induced in conscious patients; otherwise gastric lavage must be performed with protection of the airways. After this time point, administration of activated charcoal may be useful in reducing absorption.
Specific monitoring of cardiac and respiratory functions in a specialized setting is recommended.
Administration of flumazenil may be useful for diagnosis and/or treatment of accidental or intentional overdose with benzodiazepines.
Antagonism of the effects of benzodiazepines by flumazenil may promote neurological disorders (seizures), particularly in epileptic patients.
Zolpidem is not dialyzable.
Contraindications
This medicinal product must never be used in patients with: hypersensitivity to the active substance or any of the excipients in the product; severe respiratory failure; sleep apnoea syndrome; severe, acute or chronic hepatic failure (due to risk of encephalopathy); myasthenia.
Warnings
This medicinal product contains lactose. It is not recommended for use in patients with galactose intolerance, Lapp lactase deficiency or glucose and galactose malabsorption syndrome (rare hereditary diseases).
Pharmacological Tolerance: The sedative or hypnotic effect of benzodiazepines and related drugs may gradually decrease, despite using the same dose, if administered over several weeks.
Dependence: Any treatment with benzodiazepines and related drugs, particularly over long periods, may lead to the development of physical or psychological drug dependence.
Various factors seem to promote dependence: treatment duration; dosage; history of other addictions, to medicinal products or other substances,including alcohol.
Drug dependence may occur at therapeutic doses and/or in patients with no specific risk factors.
Cases of zolpidem dependence have been reported very rarely when administered at therapeutic doses.
This state may cause a withdrawal syndrome on treatment discontinuation.
Some symptoms are frequent and may appear to be unremarkable: insomnia, headache, extreme anxiety, myalgia, muscle tension and irritability.
Other symptoms occur more rarely: agitation or even episodes of confusion, paresthesia of the extremities, hypersensitivity to light, noise or physical contact, depersonalization, derealization, hallucinations and convulsions.
Withdrawal symptoms may appear within days of treatment discontinuation.
For short-acting benzodiazepines, and particularly when given at high doses, symptoms may even occur between two doses.
Concomitant use of several benzodiazepines, whether for treatment of anxiety or sleep disorders, may increase the risk of drug dependence.
Cases of drug abuse have been reported.
Rebound effect: This transient syndrome may occur as an exacerbation of the insomnia which was the initial reason for treatment with benzodiazepines and related drugs.
Psychomotor function disorders: Psychomotor function disorders may occur within hours of administration.
The risk of psychomotor function disorders, including impaired driving ability, is increased if: this medicine is taken less than 8 hours before performing activities that require alertness (see Effects on ability to drive and use machines as follows); a dose higher than the recommended dose is taken; the medicine is co-administered with other CNS depressants or with other drugs that increase zolpidem blood levels, or with alcohol or illicit drugs (see Interactions).
Zolpidem should be taken as a single dose immediately at bedtime and not be readministered during the same night.
Amnesia: Anterograde amnesia may occur within hours of administration.
In order to reduce these risks, patients should ensure that they will be able to sleep uninterrupted for 8 hours (see Adverse Reactions).
Behavioral disturbances: In some subjects, benzodiazepines and related drugs may cause a syndrome combining varying degrees of impaired consciousness with behavioral and memory disorders.
The following may be observed: exacerbated insomnia, nightmares, agitation, nervousness; delirium, hallucinations, confusion and oneirism, psychotic symptoms; loss of inhibition with impulsiveness; euphoria, irritability; anterograde amnesia; suggestibility.
This syndrome may be accompanied by disorders potentially dangerous to the patient and others, such as: abnormal behavior for the patient; aggressiveness to self and others, especially if those around the patient try to prevent the patient from doing what he/she wants; automatic behavior with post-event amnesia.
These symptoms require treatment discontinuation.
Somnambulism and associated behavior: Complex behavior such as sleep driving (i.e. driving while not completely awake after intake of a hypnotic-sedative agent), with post-event amnesia, has been reported in patients who had taken zolpidem. Although behavior associated with somnambulism may occur during zolpidem monotherapy at therapeutic doses, concomitant intake of alcohol and other central nervous system depressants appears to increase the risk of such behavior, as does intake of zolpidem at doses exceeding the maximum recommended dose.
Discontinuation of zolpidem treatment is strongly recommended in patients who have experienced somnambulism-related behaviours, due to the risk to the patient and others (see Interactions and Adverse Reactions).
Risk of accumulation: Benzodiazepines and related drugs (like any medicinal products) remain in the body for a period of about five elimination half-lives (see Pharmacology: Pharmacokinetics under Actions).
In elderly patients or patients with renal or hepatic failure, the elimination half-life maybe considerably longer. After repeated administration, steady-state concentrations of the drug or its metabolites are achieved much later and are much higher. The efficacy and safety of the drug can only be evaluated once steady-state concentrations have been achieved.
Dose adjustment may be necessary (see Dosage & Administration).
This is not expected with zolpidem in patients with renal failure given the metabolic profile of the drug (see Pharmacology: Pharmacokinetics under Actions).
Risk in case of concomitant use with opioids: Concomitant use of zolpidem with other opioids can cause sedation, respiratory depression, coma and death. Given these risks, concomitant prescription of opioids and sedatives, e.g. benzodiazepines and other related drugs such as zolpidem, should be limited to patients for whom there are no alternative treatment options.
If zolpidem and opioids have been prescribed concomitantly, the lowest effective dose should be prescribed and duration of treatment should be as short as possible (see Dosage & Administration). Patients must be closely monitored for any signs and symptoms of respiratory depression and sedation. Therefore, it is highly recommended that patients and those around them be made aware of these symptoms (see Interactions).
Elderly subjects: Benzodiazepines and related drugs should be used with caution in elderly subjects since there is a risk of sedation and/or muscle relaxant effects which may lead to falls, which often have serious consequences in this population, and because the incidence of behavioral disturbances is higher in these patients.
Liver failure: Dose adjustment is required due to the risk of accumulation (see Dosage & Administration).
Zolpidem should not be used in patients with severe liver failure due to the risk of encephalopathy (see Dosage & Administration, Contraindications and Adverse Reactions).
Special Precautions
Extreme caution is recommended in patients with a history of alcoholism or other addictions, whether to medicinal products or other substances (see Interactions).
In all cases, insomnia should be assessed routinely, and the underlying causes treated, before prescribing a hypnotic agent.
Insomnia may be a sign of an underlying physical or psychiatric disorder. The clinical diagnosis should be re-evaluated if insomnia persists or worsens after a short period of treatment.
Treatment duration: The patient must be clearly informed of the duration of treatment depending on the type of insomnia (see Dosage & Administration).
Suicide - Patients with depression - Patients with a major depressive episode: Several epidemiological studies demonstrate an increase in the incidence of suicide and attempted suicide in patients with or without depression treated with benzodiazepines and other hypnotic agents, including zolpidem. No causal relationship has been established.
Insomnia may be a symptom of depression; depression must therefore be treated. If insomnia persists, the patient should be re-evaluated.
In subjects with a major depressive episode: Benzodiazepines and related drugs should not be prescribed alone since this allows the depression to progress independently, along with persistent or enhanced risk of suicide.
Since there is a risk of suicide in these patients, the lowest amount of zolpidem must be prescribed and supplied to them in order to limit the possibility of intentional overdose.
Tapering-off methods: Patients should be clearly instructed on how to gradually discontinue treatment.
In addition to the need to taper the doses, patients should be warned of the risk of rebound insomnia, so as to minimize any insomnia which may arise because of the symptoms resulting from discontinuation, even if it is gradual.
Patients must be informed of possible discomfort during the tapering-off period.
Patients with respiratory failure: The depressant effect of benzodiazepines and related drugs should be taken into account when prescribed to patients with respiratory failure (particularly since anxiety and restlessness may be warning signs of respiratory decompensation, requiring transfer to an intensive care unit).
Effects on ability to drive and use machines: Stilnox can have a major influence on the ability to drive and use machines.
Patients who drive and use machines should be warned that, as with other hypnotics, there may be a possible risk of drowsiness, longer reaction time, dizziness, torpor, blurred/double vision and reduced alertness as well as impaired driving ability the morning after administration (see Adverse Reactions).
In order to minimize this risk, at least 8 hours of uninterrupted sleep is recommended between taking zolpidem and driving, using machinery and working at heights.
Impairment of driving ability and behavior such as falling asleep while driving have occurred in patients taking zolpidem alone at therapeutic doses.
Furthermore, co-administration of zolpidem with alcohol and other CNS depressants increases the risk of such behaviors (see Warnings, Precautions and Interactions).
Patients should be warned not to drink alcohol or take other psychoactive substances during treatment with zolpidem.
Use in Children: In the absence of clinical studies, STILNOX should not be given to children aged under the age of 18 years.
Use in Elderly: Dose adjustment is required due to the risk of accumulation (see Warnings).
Use In Pregnancy & Lactation
Pregnancy: There is no evidence from extensive data collected during cohort studies that exposure to benzodiazepines during the first trimester of pregnancy results in any malformative effects. However, in some epidemiological case-control studies, an increased incidence of cleft lip and palate was observed with benzodiazepines. According to these data, the incidence of cleft lip and palate would seem to be less than 2 per 1000 in neonates exposed to benzodiazepines in utero, compared to an expected ratio of 1 per 1000 in the general population.
Decreased fetal movement (DMF) and fetal heart rate changes have been described with administration of high benzodiazepine doses during the second and/or third trimester of pregnancy. Benzodiazepine treatment at the end of pregnancy, even at low doses, may cause signs of exposure in the neonate, such as axial hypotonia and difficulty suckling, leading to poor weight gain. Although these signs are reversible, they may last for 1 to 3 weeks depending on the half-life of the benzodiazepine prescribed. At high doses, respiratory depression/apnea or hypothermia may occur in the neonate. Furthermore, neonatal withdrawal syndrome may occur, even if there are no signs of exposure. This is characterized in particular by overexcitability, agitation and tremor in the neonate, occurring some time after delivery. The time to onset depends on the elimination half-life of the medicinal product, and may be significant if the elimination half-life is long.
Based on these data, as a precautionary measure, use of zolpidem is not recommended during pregnancy, regardless of the trimester.
Women of child-bearing potential receiving zolpidem treatment should be instructed to contact their physician if they plan a pregnancy or if they are in the early stages of pregnancy, in order to reassess the need for treatment.
At term, if zolpidem treatment is absolutely necessary, high doses should be avoided and the effects described above taken into account during neonatal monitoring.
Breastfeeding: Use of this medicinal product is not recommended in breastfeeding women.
Adverse Reactions
Adverse reactions are classified based on incidence using the following classification: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to <1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).
These effects are related to the dose administered and the individual sensitivity of each patient.
Immune system disorders: Frequency not known: angioedema.
Psychiatric disorders (see Warnings and Precautions): Common: hallucinations, agitation, nightmares.
Uncommon: confusion, irritability.
Frequency not known: behavioral disturbances, aggressiveness, nervousness, delirium, anger, somnambulism (see Warnings and Precautions), physical and psychological dependence even at therapeutic doses with withdrawal syndrome or rebound effect on treatment discontinuation, changes in libido, depression, euphoria.
Nervous system disorders (see Warnings and Precautions): Common: impaired alertness or even drowsiness (particularly in the elderly), headache, lightheadedness, insomnia, cognitive disorders such as anterograde amnesia, which may occur at therapeutic doses, the risk increasing in proportion to the dose.
Uncommon: paresthesia, tremor.
Frequency not known: changes in consciousness, attention and speech disorders, ataxia, tension.
Eye disorders: Uncommon: diplopia, blurred vision.
Very rare: vision impairment.
Respiratory, thoracic and mediastinal disorders: Frequency not known: dyspnea.
Gastrointestinal disorders: Common: diarrhea, nausea, vomiting, abdominal pain.
Hepatobiliary disorders: Frequency not known: elevated liver enzymes, hepatocellular lesions, cholestatic or mixed liver injury (see Dosage & Administration, Contraindications, Warnings and Precautions).
Metabolism and nutrition disorders: Uncommon: appetite disorders.
Skin and subcutaneous tissue disorders: Frequency not known: skin rash, pruritus, urticaria.
Musculoskeletal and systemic disorders: Uncommon: arthralgia, myalgia, muscle spasm.
Frequency not known: muscle hypotonia.
Infections and infestations: Common: upper and lower respiratory tract infections.
General disorders and administration site conditions: Common: asthenia.
Frequency not known: balance disorders or even falls.
Drug Interactions
Hypnotic agents: Currently-prescribed hypnotic agents are either benzodiazepines and related drugs (zolpidem, zopiclone) or H1 antihistamines. In addition to increased sedation when prescribed with other CNS depressants, or in the event of alcohol intake, the possible increase in the respiratory depressant effect when co-administered with morphine-like substances, other benzodiazepines, or phenobarbital should also be taken into account for benzodiazepines, especially in the elderly.
Central nervous system depressants: The fact that many drugs or substances can have additive depressant effects on the central nervous system and contribute to a decrease in alertness must be taken into account. These drugs include morphine derivatives (analgesic agents, antitussive agents and replacement therapies), neuroleptic agents, barbiturates, benzodiazepines, anxiolytic agents other than benzodiazepines (such as meprobamate), hypnotic agents, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1-antihistamines, centrally-acting antihypertensive agents, baclofen, thalidomide, antiepileptic drugs and anesthetics.
Inadvisable combination: Alcohol (beverage or excipient): Alcohol enhances the sedative effect of benzodiazepines and related drugs. Impaired alertness may make driving vehicles or using machines dangerous.
Patients should not consume alcoholic beverages or medicinal products containing alcohol.
Fluvoxamine: Co-administration of fluvoxamine may increase blood levels of zolpidem.
Concomitant use is not recommended.
CYP450 inhibitors and inducers: Co-administration of ciprofloxacin may increase blood levels of zolpidem.
Concomitant use is not recommended.
St. John's Wort: St. John's Wort has been shown to have a pharmacokinetic interaction with zolpidem. Mean zolpidem Cmax and AUC levels are lower (by 33.7% and 30.0% respectively) when co-administered with St. John's Wort, compared to the levels with single dose administration.
Co-administration of St. John's Wort may decrease blood levels of zolpidem. Concomitant use is not recommended.
Combinations requiring precautions for use: Rifampicin: Co-administration of zolpidem with rifampicin decreases plasma concentrations and efficacy of zolpidem due to increased hepatic metabolism. Clinical monitoring is required. If necessary, another hypnotic agent may be used.
Combinations to be taken into consideration: Other central nervous system depressants: Co-administration of zolpidem with other central nervous system depressants may increase next-day drowsiness and psychomotor impairment. Impaired alertness may make driving vehicles and using machines dangerous (see Warnings, Precautions and Effects on ability to drive and use machines).
Isolated cases of visual hallucinations have been reported in patients taking zolpidem with antidepressants including bupropion, fluoxetine, sertraline and venlafaxine.
Barbiturates: Co-administration of zolpidem with barbiturates or morphine derivatives increases the risk of respiratory depression, which may be fatal in the event of an overdose.
Buprenorphine: Co-administration of buprenorphine as replacement therapy with zolpidem increases the risk of potentially fatal respiratory depression. The benefit/risk balance of this combination should be carefully assessed. Patients must be informed of the need to comply with prescribed doses.
Clozapine: Co-administration of zolpidem with clozapine increases the risk of collapse with respiratory and/or cardiac arrest.
Opioids: Concomitant use of opioids and sedatives, e.g. benzodiazepines and related drugs such as zolpidem, increases the risk of sedation, respiratory depression, coma and death due to the increased central nervous system depressant effect.
Doses and duration of concomitant treatment must be limited (see Warnings and Precautions).
Clarithromycin, erythromycin, telithromycin: Co-administration of zolpidem with clarithyromycin, erythromycin or telithromycin slightly increases the sedative effects of zolpidem.
Ketoconazole, itraconazole, voriconazole: Co-administration of zolpidem with ketaconazole, itraconazole or voriconazole slightly increases the sedative effects of zolpidem.
Nelfinavir, ritonavir-boosted protease inhibitors: Co-administration of zolpidem with nelfinavir or ritonavir-boosted protease inhibitors slightly increases the sedative effects of zolpidem.
When zolpidem was administered with ranitidine, no significant pharmacokinetic interactions were observed.
ATC Classification
N05CF02 - zolpidem ; Belongs to the class of benzodiazepine related agents. Used as hypnotics and sedatives.
Presentation/Packing
FC tab (scored) 10 mg x 20's.
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