Is it Safe to Take Zolpidem in Pregnancy?

Sinuosi (Zolpidem Tartrate), the indication is limited to the treatment of severe sleep disorders in the following cases: occasional insomnia temporary insomnia

Drug Name: Zolpidem Tartrate
Whether prescription drugs: prescription
Drug Name: Snos

Drug type: Prescription drugs, medicines for medical workers' injuries
Special medicine: Psychotropic drugs
Use classification: Cyclopyrrolidone

Sinuosi ingredients

Chemical name: bis [N, N-dimethyl-2- [6-methyl-2- (4-methylphenyl) imidazo [1,2-] pyridin-3yl] -acetamide] (2R , 3R) -2,3-dihydroxysuccinate.
Chemical Structure:

Molecular formula: (C ₁₉ H ₂₁ N ₃ O ₂ ) ₂ · C ₄ H ₆ O ₆
Molecular weight: 765

Sinos traits

This product is a white scoring coated tablet.

Sinos indications

This product is limited to the treatment of severe sleep disorders in the following cases:
· Occasional insomnia · Temporary insomnia

Sinoth Specifications

10mg.

Sinos Usage and Dosage

Oral dose [u] dose [/ u]
The general population < br Using this product for treatment should usually use the lowest effective dose, which should not exceed the maximum therapeutic dose.
Usual adult dose: 10 mg / tablet / day.
This product should be taken before going to bed or after going to bed.
Special populations < br Elderly people < br Elderly patients or patients with liver dysfunction: the dose should be halved to 5 mg.
The daily dose should not exceed 10 mg.
Children < br Because of the lack of corresponding clinical research data, this product should not be used in patients under 18 years of age.
Impaired liver function < br Because the clearance and metabolism of Zolpidem are reduced in patients with liver damage, these patients should be started with a dose of 5ml, especially in elderly patients. In adults (under 65 years), the dose can be increased to 10 mg only if the clinical effect is insufficient and the drug is well tolerated.
[u] Duration of treatment [/ u] :
The treatment time of this product should be as short as possible, the shortest is a few days, the longest does not exceed 4 weeks, including the gradual reduction period (see [Cautions]).
Patients should be advised to:
For occasional insomnia (eg during travel), treat for 2-5 days.
· For temporary insomnia (such as during annoyance), treat for 2-3 weeks.
Patients treated for very short periods of time do not need to stop the drug gradually.
It may take more than 4 weeks for some patients, but the patient's condition must be evaluated carefully and carefully before making a decision.

Sinorth adverse reactions

Appropriate use of the following CIOMS (Council of International Medical Organizations) frequency grading:
Very common 10%: common 1% and <10%; uncommon 0.1% and <1%; rare 0.01% and <0.1%; very rare <0.01%;
Unknown: Evaluation cannot be based on available information.
There is evidence that adverse reactions are dose-related to zolpidem use, especially for certain CNS (central nervous system) events. Theoretically, taking zolpidem before bedtime or already at bedtime can reduce such events. Such events are most common in elderly patients.
The occurrence of these adverse effects depends on the dose of the drug and the sensitivity of the individual patient.
Immune system abnormalities < br Unknown: Anaphylactic shock (severe allergic reaction) and angioedema (severe facial edema) may occur in the initial period of taking this product.
Mental disorders < br Common: hallucinations, excitement, nightmares are uncommon: confusion, irritability, unknown: restlessness, aggressiveness, delusion, anger, abnormal behavior, sleepwalking (taking this product may cause sleep syndrome behavior, Including potentially dangerous behaviors such as sleepwalking while driving, sleepwalking cooking, and eating. For details, see [Caution] Sleepwalking and related behaviors. These psychotic reactions are related to abnormal reactions.
Nervous system abnormalities < br Common: drowsiness, headache, dizziness, exacerbation of insomnia, anterograde amnesia (amnesia may cause inappropriate behavior)
Unknown: Decreased consciousness Unknown: Increased liver enzymes Systemic abnormalities < br Common: Fatigue is unknown: Gait disorder, drug tolerance, falls (mainly in elderly patients and patients taking zolpidem not prescribed)

Sinos taboo

The following conditions should be contraindicated:
· When you are allergic to Zolpidem or any of the ingredients of this product,
· Severe respiratory insufficiency,
· Sleep apnea syndrome,
Severe, acute or chronic liver insufficiency (at risk for hepatic encephalopathy),
Muscle weakness.

Precautions

Special warnings < br As this product contains lactose, it is contraindicated in cases of congenital galactosemia, glucose or galactose malabsorption syndrome, or lactase deficiency.
Warnings Zolpidem should be used with caution in patients with sleep apnea syndrome and respiratory insufficiency.
Because sleeping pills can inhibit respiratory motility, caution should be exercised when prescribing zolpidem to patients with respiratory insufficiency.
For patients with respiratory insufficiency, the sedative effect of benzodiazepines and related drugs must be considered (especially because anxiety and emotional agitation may be signs of respiratory decompensation, and patients with respiratory decompensation need to live in intensive care treatment).
Patients with liver dysfunction See [Usage and Dosage]
Precautions < br Patients with a history of alcoholism or other substance dependence (whether or not related to drugs) need to be more cautious (see [Drug Interactions]).
Before prescribing sleeping pills, the cause of insomnia should be determined as much as possible and its cause treated. When insomnia cannot be alleviated after 7-14 days of treatment, this indicates that there may be a primary mental or physical disorder and the diagnosis should be re-evaluated.
Duration of treatment < br The patient should be clearly informed that the length of treatment depends on the type of insomnia (see [Dosage and Administration]).
Mental Illness < The pyrazolidine sleeping pills are not recommended for the initial treatment of mental illness.
Amnesia < br Sedative / hypnotic drugs, such as Zolpidem, may cause anterograde amnesia. This happens most often a few hours after taking the medication, so to reduce the risk, patients should ensure that they can sleep for 7-8 hours.
Depression < br Although zolpidem and SSRI (selective serotonin reuptake inhibitors) have not been proven to have clinically significant pharmacokinetic and pharmacodynamic interactions, like other sedative / hypnotic drugs, It should also be used with caution in patients with depressive symptoms. Because suicidal tendencies are likely, these patients should be provided with a reasonable minimum amount of Zolpidem to avoid intentional overdose. The use of Zolpidem may cause preexisting depression. Because insomnia can be a symptom of depression, patients should be re-evaluated if insomnia persists.
[u] Other mental illnesses and "abnormal" behaviors [/ u]
It is known that other mental illnesses and "abnormal" reactions may occur when using sedative / hypnotic drugs such as Zolpidem,
The following can be observed:
-Worsening of insomnia, nightmares, excitement, nervousness,
-Illusions, hallucinations, confusion and delirium, symptoms of psychosis,
-Impulsiveness out of control,
-Euphoria, irritability,
-Anterograde oblivion,
-Susceptible to suggestiveness.
The syndrome can be accompanied by abnormal behaviors that are potentially dangerous to the patient or others, such as:
-The patient behaves abnormally,
-Self-attack or attack others, especially if the patient is prevented from doing what he / she wants to do by a family member or friend.
-Unconscious behaviors that are forgotten after the fact.
If these symptoms occur, you should stop using this product.
[u] These symptoms are more commonly observed in elderly patients. [/ u]
[u] Sleepwalking and related behaviors [/ u]
Sleepwalking and other related behaviors have been reported in patients who are taking zolpidem and are not fully awake, such as "driving while sleeping", making food and eating, making phone calls or having sex, and losing memory of an event. Concomitant use of zolpidem with alcohol and other central nervous system (cNS) inhibitors, or use of zolpidem over the recommended maximum dose, can increase the risk of these behaviors, taking into account the risks to the patient and others It is strongly recommended to discontinue zolpidem [u] (see [Drug Interactions] and [Adverse Reactions]) [/ u] for patients who have reported such behaviors (such as driving while sleeping).
[u] Tolerance [/ u]
After repeated use of this product for more than a few weeks, the sedative or hypnotic effects of Zolpidem and related drugs may gradually decrease.
[u] dependency [/ u]
The use of zolpidem sedative / hypnotic drugs can lead to physical and mental dependence. The risk of dependence increases with dose and duration of treatment; the risk may be higher in patients with mental disorders and / or a history of alcohol or drug dependence. These patients should be carefully monitored when using sleeping pills.
Once physical dependence occurs, sudden withdrawal of treatment may cause withdrawal symptoms. These symptoms may include headache or muscle pain, extreme anxiety and tension, restlessness, confusion, and irritability. In severe cases, the following symptoms may occur: loss of realism, disintegration of personality, hearing allergies, numbness and tingling of limbs, allergies to light, sound and physical contact, hallucinations or seizures.
Bounce insomnia:
This transient symptom has previously led to sedative / hypnotic treatment and may recur in a stronger form when hypnotic treatment is withdrawn. Other accompanying reactions may occur, such as mood changes, anxiety, and restlessness. It is important that patients understand that rebound may occur and that these symptoms can minimize anxiety if they occur when the drug is stopped. When using short-acting sedative / hypnotic drugs, the withdrawal may occur in the interval between dosing.
[u] accumulated risk [/ u]
Benzodiazepines and related drugs (like all pharmaceutical products) can retain 5 half-lives in the human body (see [Pharmacokinetics]).
In elderly patients or patients with liver and kidney dysfunction, the half-life can be significantly extended. After multiple doses, the drug or metabolite reaches a steady state much later, and the steady state concentration is higher. It is only possible to evaluate the efficacy and safety of a drug under steady state conditions.
It may be necessary to adjust the dose of the drug (see [Dosage and Administration]).
Considering the metabolic pathway of Zolpidem, in patients with renal insufficiency, no dose adjustment is expected (see [Pharmacokinetics]).
Elderly patients < br When taking benzodiazepines and related drugs to the elderly, special care should be taken because it has a sedative and / or muscle relaxation effect, which may cause falls with serious consequences in the elderly.
Gradual withdrawals < br These methods should be explained to patients in detail.
In addition to the need to gradually reduce the dose, patients should also be warned that a rebound effect may occur in order to minimize any symptoms of insomnia. As stopping the drug may cause some symptoms to appear, insomnia may recur, even in In case of gradual withdrawal.
Patients should be warned that this stage of treatment may be unpleasant.
Driving a motor vehicle or performing other hazardous work Warn motor vehicle drivers and machine operators: Like other sleeping pills, there may be a risk of sleepiness the next morning after treatment. To minimize risk, it is recommended to sleep all night (7-8 hours).
This product belongs to the second category of psychotropic drugs. Please take medicine as prescribed by your doctor.
It is strictly prohibited for food and feed processing.

Medication for pregnant women and lactating women

Pregnancy < br As a precaution, it is best to avoid using Zolpidem during pregnancy.
There is little or no data on zolpidem use in pregnant patients. Animal studies have not shown direct or indirect harmful effects on reproductive toxicity.
If the drug is prescribed to a woman of childbearing age, the patient should be warned to contact a physician when she plans or suspects pregnancy to discuss the withdrawal.
If Zolpidem is used in the late stages of pregnancy or during childbirth, depending on the pharmacological effects of the product, it is expected that it may affect the newborn, such as hypothermia, hypotonia, and moderate respiratory depression. [u] Severe neonatal respiratory depression has been reported with zolpidem concurrently with other CNS inhibitors during late pregnancy. [/ u]
In addition, babies born to mothers after long-term use of sedatives / sleeping pills during the later part of pregnancy may develop physical dependence and may be at risk for drug withdrawal syndrome during the postpartum period.
Nursing < br There is a small amount of Zolpidem in breast milk. Therefore, zolpidem is not recommended when the mother is breastfeeding.

Sinuo Si medication

The safety and efficacy of Zolpidem have not been established in patients under the age of 18. In an 8-week study of children (6-17 years) with insomnia associated with attention deficit / hyperactivity disorder (ADHD), zolpidem is the most common compared to placebo for psychiatric disorders and neurological disorders Treatment-related adverse events included dizziness (23.5% vs. 1.5%), headache (12.5% vs. 9.2%), and hallucinations (7.4% vs. 0%). (See [Usage and dosage])

Sinuosi elderly medicine

Elderly patients take it with caution, refer to [Usage and Dosage]), [Precautions] or follow the doctor's advice.
The dose in elderly patients should be halved to 5 mg.

Sinoth drug interactions

Alcohol :
It is not recommended to take alcohol at the same time. The simultaneous use of drugs and alcohol may enhance sedation. This affects the ability to drive or operate machinery.
CNS inhibitor :
Aggravation of central inhibitory effects may occur when combining antipsychotics (sedatives), sleeping pills, anxiolytic / sedatives, antidepressants, narcotic analgesics, antiepileptics, narcotics and sedative antihistamines. However, if SSRI antidepressants (fluoxetine and sertraline) were used, no clinically significant pharmacokinetics or pharmacodynamic interactions were observed. Increased euphoria may also occur when using narcotic sedatives, leading to increased mental dependence.
CYP450 inhibitor [u] and inducer [/ u] :
Compounds that inhibit cytochrome P450 may enhance the activity of sleeping pills such as Zolpidem. Zolpidem is metabolized by some liver cytochrome P450 enzymes. The main enzymes are CYP3A4 and CYP1A2. When administered concurrently with rifampicin, a CYP3A4 inducer, the pharmacodynamic effects of Zolpidem are reduced. However, when zolpidem was administered concurrently with itraconazole, a CYP3A4 inhibitor, its pharmacokinetics and pharmacodynamics did not change significantly. The clinical relevance of these results is unclear, and the simultaneous use of Zolpidem with ketoconazole (a CYP3A4 inhibitor) (200 mg twice daily) and Zolpidem plus placebo delayed the elimination half-life and increased Total AUC and reduced apparent oral clearance. Compared with Zolpidem alone, the combined AUC of Zolpidem increased 1.83 times. Routine dose adjustments for zolpidem are generally not considered necessary, but patients should be advised that sedation may be enhanced when zolpidem and ketoconazole are used simultaneously.
Other drugs :
No significant pharmacokinetic interactions were observed when Zolpidem was co-administered with warfarin, digoxin, ranitidine, or cimetidine.

Sinos overdose

Signs and symptoms :
When zolpidem is used alone or in combination with other CNS inhibitors, including alcohol, overdose has been reported to cause consciousness until coma and more severe symptoms, including fatal results.
Processing :
General symptomatic and supportive measures should be used. If gastric emptying is ineffective, activated carbon should be given to reduce absorption. Sedatives should be discontinued even if excitement occurs. Consider flumazenil when severe symptoms are observed. However, administration of flumazenil may trigger neurological symptoms (epilepsy).
Zolpidem cannot be dialyzed.

Sinoth Pharmacology and Toxicology

Pharmacological effects Zolpidem is an imidazolidine hypnotic drug related to benzodiazepines. Its pharmacodynamic activity is essentially similar to that of other similar compounds: muscle relaxation, anxiolytic, sedative, hypnotic , Anti-convulsions, cause forgetfulness.
Experimental studies have demonstrated that the dose required for sedation is lower than the dose required for anticonvulsant, muscle relaxation, and anxiolytic effects. These effects are related to specific agonistic effects on central receptors, which belong to the GABA-Omega (BZ1 and BZ2) macromolecular receptor complex and have a role in regulating the opening of chloride ion channels.
Zolpidem binds selectively to the Omega (or BZ1) subtype receptor.
In humans, Zolpidem shortens the time required to fall asleep, reduces the number of waking up at night, increases the total duration of sleep and improves sleep quality. These effects are accompanied by characteristic EEG waveforms, which are different from those induced by benzodiazepines. Nocturnal sleep recording studies have demonstrated that Zolpidem prolongs stage II and deep sleep (stages III and IV). At the recommended dose, zolpidem does not affect the total duration of heterogeneous sleep (rapid eye movement sleep).

Toxicological studies <br Genetic toxicity: Zolpidem Ames test, mouse lymphoma cell genotoxicity test, human lymphocyte chromosome aberration test, rat liver cell extra-programmed DNA synthesis test and mouse micronucleus test results are all negative.
Reproductive toxicity: In general reproductive toxicity tests in rats, rats in the high-dose group (100 mg alkali / kg) showed irregular estrus and prolonged intervals before mating, but were administered orally at 4-100 mg / kg (in mg / m [ When calculated by sup] 2 [/ sup], which is equivalent to 5-130 times the recommended dosage for humans), it has no effect on fertility and other reproduction parameters of female and male rats. In the teratogenicity test, zolpidem 20 and 100 mg / kg had adverse effects on both mother and fetus, including maternal lethargy, ataxia, and fetal skull ossification, which were dose-dependent. Poor ossification of the fetus indicates delayed maturity, which is often seen in rats given sedative / hypnotic drugs. No teratogenic effect was seen. Zolpidem has no effect on the mother and fetus at a dose of 4 mg base / kg (equivalent to 5 times the recommended human dose based on mg / m [sup] 2 [/ sup]). Pregnant rabbits showed dose-related sedation and weight loss at various doses studied. The incidence of ossification of the sternum of the sternum of surviving fetuses after implantation at high doses (16 mg base / kg) increased, and these changes in fetuses were secondary to maternal weight loss. No teratogenic effect was seen. The non-toxic effect of Zolpidem on fetal rabbits is 4 mg base / kg (equivalent to 7 times the maximum human dose calculated as mg / m [sup] 2 [/ sup]).
Carcinogenicity: Zolpidem was administered to rats and mice for 2 consecutive years at doses of 4, 18, and 80 mg / kg / day. Calculated as mg / kg or mg / m [sup] 2 [/ sup], this dose is equivalent to 26-520 times or 2-35 times the maximum human dose of 10 mg in mice, respectively, and is equivalent in rats, respectively. At 43-876 times or 6-115 times. No increase in tumor incidence was seen in rats. Among rats, renal liposarcoma appeared in 4/100 rats (male: 3, female: 1) at a dose of 80 mg / kg / day, and 1 male rat in the 18 mg / kg / day dose group Renal lipomas appear. The incidence of lipomas and liposarcomas in the zolpidem-administered group was comparable to historical control data and was considered spontaneous.

Sinoth Pharmacokinetics

[u] absorption [/ u]
The bioavailability of oral zolpidem is approximately 70%, and the peak plasma drug concentration time is between 0.5 and 3 hours.
[u] distribution [/ u]
At the therapeutic dose, the pharmacokinetics are linear. The plasma protein binding rate is about 92%. The volume of distribution in an adult human body is 0.54 ± 0.02 L / kg.
[u] metabolism and elimination [/ u]
Zolpidem is metabolized by the liver as an inactive metabolite, mainly excreted in urine (about 60%) and feces (about 40%). It does not induce liver enzymes.
The plasma elimination half-life is approximately 2.4 hours (0.7-3.5 hours).
[u] Dangerous people [/ u]
-Decreased liver clearance is observed in elderly patients. The peak concentration increased by approximately 50%, while the half-life (average 3 hours) did not increase significantly. The distribution volume was reduced to 0.34 ± 0.05 L / kg.
-In patients with renal insufficiency, a moderate reduction in clearance can be observed regardless of whether dialysis is performed. Other kinetic parameters remain unchanged. Zolpidem cannot be cleared by dialysis.
-Increased bioavailability of Zolpidem in patients with liver dysfunction. Its clearance is reduced and its elimination half-life is extended (approximately 10 hours).

Snoth Storage

Store at room temperature.
Avoid high-temperature and high-humidity storage, and do not use medicines beyond the expiration date.
Keep this medicine in a safe place to avoid accidental ingestion by children.

Sinoth Packaging

Aluminum plastic packaging, 7 pieces / box, 20 pieces / box, 21 pieces / box.

Syros Validity Period

48 months.

Sinoth Standards

Import drug registration standard: JX20100222

Sinoth Approval Number

Import Drug Registration Certificate Number: H20090001
Psychotropic substance import permit number: TPI20090302
Sub-packaging approval number for imported drugs: National Drug Standard J20090050

Sinos production company

Sanofi Winthrop Industrie

Sinoth Entrusted Enterprise

Sanofi-Aventis France

Sinos Packaging

Sanofi (Hangzhou) Pharmaceutical Co., Ltd.

Sinoth Approval Date

March 12, 2007

Sinoth Revision Date

September 19, 2007 April 17, 2009 November 10, 2009 December 13, 2009 December 27, 2010 June 22, 2011 July 4, 2011 August 10, 2011