Active ingredients: Zolpidem (zolpidem tartrate)
STILNOX 10 mg film-coated tablets
Indications Why is Stilnox used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Benzodiazepine-related drugs
THERAPEUTIC INDICATIONS
Short-term treatment of insomnia.
Benzodiazepines or benzodiazepine-like substances are only indicated in cases of severe, debilitating, or insomnia that causes profound malaise.
Contraindications When Stilnox should not be used
Hypersensitivity to the active substance (zolpidem) or to any of the excipients.
Myasthenia gravis.
Acute and / or severe respiratory failure.
Sleep apnea syndrome.
Administration to children and adolescents under 18 years.
Severe hepatic insufficiency.
Pregnancy and breastfeeding (see "Special Warnings - Pregnancy and Breastfeeding").
Precautions for use What you need to know before taking Stilnox
Before prescribing a hypnotic, if possible, the cause of insomnia should be identified and the underlying factors treated. A 7-14 day treatment without clinical results may indicate the presence of a primary physical or psychiatric disorder and the patient should be carefully re-evaluated at regular intervals.
Psychomotor impairment on the following day
The risk of psychomotor impairment in the next day, including impaired ability to drive, increases if:
- zolpidem is taken when less than 8 hours remain before performing activities requiring mental alertness (see "Special warnings - Effects on ability to drive and" use machines ");
- a higher dose than recommended is taken;
- zolpidem is co-administered with other central nervous system (CNS) depressant drugs, or other drugs that increase the blood levels of zolpidem, or with alcohol or illicit drugs (see "Interactions").
Zolpidem should be taken as a single administration, immediately at bedtime, and should not be re-administered during the same night.
TOLERANCE:
After repeated use for a few weeks, there may be some reduction in the hypno-inducing effect of benzodiazepines or benzodiazepine-like substances with a short half-life.
DEPENDENCE:
The use of benzodiazepines or benzodiazepine-like substances can lead to physical and psychological dependence on these drugs. The risk of dependence increases according to the dosage and duration of treatment; it is also greater in patients with a history of psychiatric disorders and / or alcohol or drug abuse These patients should be closely monitored when taking benzodiazepines or benzodiazepine-like substances.
In cases where physical dependence has developed, abrupt cessation of treatment will cause withdrawal symptoms, which may include: headache, body aches, extreme anxiety, tension, agitation, confusion and irritability. In severe cases, the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling in the extremities, hypersensitivity to light, noise and physical contact, hallucinations or seizures.
INSOMNIA REBOUND:
When the hypno-inducing drug is discontinued, a transient syndrome may occur which consists in the reappearance, in an accentuated form, of the symptoms that led to treatment with the drug. It may be accompanied by other reactions such as mood swings, anxiety and agitation, or sleep disturbances.
This syndrome is more likely to occur if drug administration is abruptly stopped; therefore treatment should be discontinued gradually.
Furthermore, it is important that the patient is aware of the possibility of rebound phenomena occurring, thus minimizing the anxiety caused by these symptoms should they arise in the withdrawal phase of the drug.
It seems that, in the case of benzodiazepines or benzodiazepine-like substances with a short duration of action, withdrawal phenomena may occur in the interval between two intakes.
DURATION OF TREATMENT:
The duration of treatment should be as short as possible (see "Dose, method and time of administration") and should not exceed 4 weeks including the drug withdrawal phase. The duration of treatment must not be extended beyond this period, without the Doctor having reassessed the patient's situation.
It may be useful to inform the patient at the beginning of the treatment that this will be of limited duration and to explain exactly how the dosage should be progressively reduced.
AMNESIA:
Benzodiazepines or benzodiazepine-like substances can cause anterograde amnesia. Most often this effect occurs several hours after taking the drug.
To reduce the risk, patients should ensure that they can sleep continuously for 8 hours (see "Side Effects").
OTHER PSYCHIATRIC AND "PARADOX" REACTIONS:
Restlessness, aggravation of insomnia, agitation, irritability, aggression, delusions, anger, nightmares, hallucinations, psychosis, abnormal behavior and other behavioral side effects known to occur during the use of benzodiazepines or benzodiazepine-like substances may occur. occur when using hypnotic / sedative agents such as zolpidem.
Should this occur, use of the drug should be discontinued.
These reactions are more likely to occur in children and the elderly.
SLEEP WALKING AND ASSOCIATED BEHAVIORS:
Sleepwalking and other associated behaviors such as sleep driving, preparing and eating food, making phone calls, having sex, with amnesia for the event have been reported in patients taking zolpidem who were not fully awake.
It appears that both the use of alcohol and other CNS depressants in conjunction with zolpidem and the use of zolpidem at doses that exceed the maximum recommended dose increase the risk of such behaviors. Discontinuation of zolpidem treatment in patients exhibiting such behaviors (eg sleep driving) should be carefully considered due to the risks to the patient and others (see "Interactions - Alcohol" and "Undesirable Effects - Psychiatric Disorders") .
SERIOUS INJURY
In relation to its pharmacological properties, zolpidem can cause drowsiness and reduced consciousness, which can lead to falls and consequently serious injuries.
PARTICULAR GROUPS OF PATIENTS:
- Elderly: see "Dose, method and time of administration" - dosage.
- Caution is warranted when prescribing zolpidem to patients with chronic respiratory failure, as benzodiazepines may depress respiratory function (see "Undesirable Effects").
- Benzodiazepines and benzodiazepine-like substances are not indicated for the treatment of patients with severe hepatic insufficiency, as these drugs can precipitate an "encephalopathy".
- Benzodiazepines and benzodiazepine-like substances are not recommended as the primary treatment for psychotic illness.
- Benzodiazepines and benzodiazepine-like substances should not be used alone for the treatment of depression or anxiety associated with depression. Although no clinically significant pharmacokinetic and pharmacodynamic interactions have been demonstrated with SSRI antidepressants (see "Interactions") , zolpidem, like other benzodiazepines and benzodiazepine-like substances, should be administered with caution to patients with symptoms of depression. Suicidal tendencies may occur in such patients and the minimum amount of useful drug should be provided accordingly, due to the possibility of Intentional overdose by the patient. Pre-existing depression may be revealed during the use of zolpidem. Since insomnia can be a symptom of depression, the patient should be reevaluated if insomnia persists.
- Benzodiazepines and benzodiazepine-like substances should be used with extreme caution in patients with a history of alcohol or drug abuse.
Interactions Which drugs or foods can modify the effect of Stilnox
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Alcohol:
concomitant intake of alcohol is not recommended. The sedative effect may be enhanced if the drug is taken concomitantly with alcohol. This adversely affects the ability to drive or use machines.
Association with CNS depressant drugs
An enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, antidepressants, narcotic analgesics, antiepileptic drugs, anesthetics and sedative antihistamines. Therefore, the concomitant use of zolpidem with such drugs. may increase somnolence and psychomotor impairment in the next day, including impaired ability to drive (see "Precautions for use" and "Special warnings - Effects on ability to drive and" use machines "). In addition, there have been isolated reports of visual hallucinations in patients taking zolpidem with antidepressants, including bupropion, desipramine, fluoxetine, sertraline and venlafaxine. In the case of narcotic analgesics, there may also be an "accentuation of the sense of euphoria, which leads to an increase in psychic dependence.
Co-administration of fluvoxamine may increase blood levels of zolpidem; concomitant use is not recommended.
CYP450 inhibitors and inducers
Zolpidem is metabolised by several isoforms of the hepatic cytochrome P450 enzyme: the main enzyme is CYP3A4 with the contribution of CYP1A2.
Substances that inhibit cytochrome P450 may increase the activity of benzodiazepines or benzodiazepine-like substances, such as zolpidem.
Co-administration of ciprofloxacin may increase blood levels of zolpidem; concomitant use is not recommended.
The pharmacodynamic effect of zolpidem decreases when zolpidem is combined with rifampicin (CYP3A4 inducer). However, when zolpidem is administered with itraconazole (CYP3A4 inhibitor) its pharmacokinetics and pharmacodynamics are not significantly affected. The clinical relevance of these results are not significantly affected. it's known.
Concomitant administration of zolpidem and a strong CYP3A4 inhibitor, ketoconazole (200 mg twice daily) prolonged the elimination half-life of zolpidem, increased total AUC and decreased apparent oral clearance compared to zolpidem. plus placebo. The total AUC of zolpidem, when given with ketoconazole, increases by a factor of 1.83 compared to zolpidem alone. It is not considered necessary to adjust the usual dosage of zolpidem, but patients should be advised that the use of zolpidem with ketoconazole may increase the sedative effects.
Other drugs:
No significant pharmacokinetic interactions have been observed when zolpidem is co-administered with warfarin, digoxin or ranitidine.
Warnings It is important to know that:
Important information about some of the ingredients:
This medicinal product contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Pregnancy and breastfeeding
Pregnancy Ask your doctor or pharmacist for advice before taking any medicine. As a precaution zolpidem should be avoided during pregnancy and breastfeeding.
There are no, or very limited, data of zolpidem in pregnant patients. Animal studies do not indicate direct or indirect harmful effects with respect to the development of reproductive toxicity.
The woman of childbearing age who intends to become pregnant or suspects to be pregnant, should contact the doctor to suspend the treatment.
If, for absolute medical necessity, zolpidem has to be administered in late pregnancy, or during delivery, effects on the newborn can be expected such as: hypothermia, hypotonia and moderate respiratory depression, caused by the pharmacological action of the drug. cases of severe neonatal respiratory depression when zolpidem was used with other CNS depressant drugs at term of pregnancy.
In addition, children born to mothers who took benzodiazepines or benzodiazepine-like substances on a chronic basis during the latter stages of pregnancy may develop physical dependence and may be at some risk of experiencing withdrawal symptoms in the postnatal period.
Feeding time
Since benzodiazepines or benzodiazepine-like substances have been found in breast milk, zolpidem should not be given to mothers who are breastfeeding.
Effects on ability to drive and use machines
Stilnox impairs the ability to drive and use machines.
Vehicle drivers and machine operators should be advised that, as with other hypnotics, there is a possible risk of drowsiness, prolonged reaction time, dizziness, drowsiness, confused / double vision and reduced alertness and impaired ability to drive, the morning after treatment (see "Undesirable effects"). To minimize the risk, a rest period of at least 8 hours is recommended between taking zolpidem and driving a vehicle, using machinery and working at height.
Impaired ability to drive and behaviors such as "falling asleep behind the wheel" have occurred with zolpidem alone, at therapeutic doses.
In addition, co-administration of zolpidem with alcohol and other CNS depressant drugs increases the risk of such behaviors (see "Precautions for use" and "Interactions"). Patients should be advised not to use alcohol or other drugs. psychoactive substances while taking zolpidem.
Dosage and method of use How to use Stilnox: Dosage
The duration of treatment should be as short as possible.
Generally, this duration varies from a few days to two weeks with a maximum of four weeks including the drug withdrawal phase.Sometimes it may be necessary to extend the maximum treatment period; in this case, this must not be done without the Doctor having first reassessed the patient's situation.
The drug should be taken at bedtime.
Dosage
The treatment should be taken as a single administration and should not be re-administered during the same night. The recommended daily dose is 10 mg, to be taken immediately at bedtime.
The total daily dose of zolpidem should not exceed 10 mg.
In elderly or debilitated patients who may be particularly sensitive to the effects of zolpidem, a dose of 5 mg (1/2 tablet) is recommended, which will only be exceeded in exceptional cases.
In patients with hepatic insufficiency who do not eliminate the drug as quickly as normal subjects, a dose of 5 mg (1/2 tablet) is recommended, which will only be exceeded in exceptional cases.
However, for any patient, the total dose of zolpidem should not exceed 10 mg.
Overdose What to do if you have taken too much Stilnox
In case of accidental ingestion / intake of an excessive dose of Stilnox, notify your doctor immediately or go to the nearest hospital.
Signs and symptoms
Decreased consciousness up to coma and more severe symptoms including fatal consequences have been reported in cases of overdose with zolpidem alone or in combination with other CNS depressant drugs or substances (including alcohol). .
Treatment
When treating overdose of any medicinal product, it should be borne in mind that more substances may have been taken.
In the event of an overdose of benzodiazepines or benzodiazepine-like substances, induce vomiting (within 1 hour) if the patient is conscious or perform a gastric lavage, with airway protection, if the patient is unconscious.
If stomach emptying is not beneficial, give activated charcoal to reduce absorption. Cardiovascular and respiratory functions should be carefully monitored in the intensive care unit.
Sedative drugs should also be avoided in cases of psychomotor arousal.
Flumazenil may be a useful antidote if severe symptoms have been observed. However, administration of flumazenil may contribute to the onset of neurological symptoms (convulsion).
Zolpidem is not dialysable.
If you have any questions about the use of Stilnox, ask your doctor or pharmacist.
Side Effects What are the side effects of Stilnox
Like all medicines, Stilnox can cause side effects, although not everybody gets them.
Whenever possible, the following CIOMS frequency scale is used: very common> 10%; common> 1 and 0.1 and 0.01 e
There is evidence of dose-related undesirable effects with zolpidem, particularly some CNS events. As recommended under "Dosage", these effects should be less severe if zolpidem is administered immediately before bedtime or when already in bed These effects occur more frequently in elderly patients.
Nervous system disorders
Common: somnolence, headache, dizziness, increased insomnia, anterograde amnesia (amnesic effects may be associated with inappropriate behavior).
Not known: decreased level of consciousness
Psychiatric disorders
Common: hallucinations, agitation, nightmares.
Uncommon: confusional state, irritability.
Not known: restlessness, aggression, delirium, anger, abnormal behavior, sleepwalking (see "Precautions for use - Sleepwalking and associated behaviors"), addiction (drug withdrawal syndrome or rebound effects may occur after discontinuation of treatment), changes libido, depression (see "Precautions for use").
Many of these undesirable psychiatric effects are related to paradoxical reactions.
General disorders and administration site conditions
Common: fatigue
Not known: changes in gait, drug tolerance, falls (especially in elderly patients and when not taking zolpidem as prescribed) (see "Precautions for use")
Eye disorders
Uncommon: diplopia
Respiratory, thoracic and mediastinal disorders
Not known: respiratory depression (see "Precautions for use")
Gastrointestinal disorders
Common: diarrhea, nausea, vomiting, abdominal pain
Musculoskeletal and connective tissue disorders
Common: back pain
Not known: muscle weakness
Infections and infestations
Common: upper respiratory tract infection, lower respiratory tract infection.
Skin and subcutaneous tissue disorders
Not known: rash, itching, urticaria, hyperhidrosis.
Hepatobiliary disorders
Not known: elevated liver enzyme levels
Disorders of the immune system
Not known: angioneurotic edema.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Side effects can also be reported directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on safety of this medicine.
Expiry and Retention
Expiry: see the expiry date printed on the package.
The expiry date refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date indicated on the package.
Keep this medicine out of the sight and reach of children.
Medicines should not be disposed of via wastewater or household waste.
Ask your pharmacist how to throw away medicines you no longer use.
This will help protect the environment.
Composition and pharmaceutical form
COMPOSITION
Each film-coated tablet contains:
Active ingredient: zolpidem tartrate 10 mg.
Excipients: lactose monohydrate; microcrystalline cellulose; hypromellose; sodium carboxymethyl starch (type A); magnesium stearate.
Coating: hypromellose; titanium dioxide (E171); macrogol 400.
PHARMACEUTICAL FORM AND CONTENT
Film-coated tablets.
- 20 film-coated tablets of 10 mg
- 30 film-coated tablets of 10 mg.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
STILNOX 10 MG TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains:
Active principle:
zolpidem tartrate 10 mg.
Excipients:
lactose monohydrate 90.4 mg
For the full list of excipients see section 6.1
03.0 PHARMACEUTICAL FORM
Film-coated, scored tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Short-term treatment of insomnia.
Benzodiazepines or benzodiazepine-like substances are only indicated in cases of severe, debilitating, or insomnia that causes profound malaise.
04.2 Posology and method of administration
The duration of treatment should be as short as possible.
Generally, this duration varies from a few days to two weeks with a maximum of four weeks including the drug withdrawal phase.
Sometimes it may be necessary to extend the maximum treatment period; in this case, this should not be done without first re-evaluating the patient's situation.
The drug should be taken at bedtime.
Dosage
The treatment should be taken as a single administration and should not be re-administered during the same night.
The recommended daily dose is 10 mg, to be taken immediately at bedtime. The total daily dose of zolpidem should not exceed 10 mg.
In elderly or debilitated patients who may be particularly sensitive to the effects of zolpidem a dose of 5 mg is recommended and will only be exceeded in exceptional cases.
In patients with hepatic insufficiency who do not eliminate the drug as quickly as normal subjects, a dose of 5 mg is recommended and will only be exceeded in exceptional cases.
However, for any patient, the total dose of zolpidem should not exceed 10 mg.
04.3 Contraindications
Hypersensitivity to the active substance (zolpidem) or to any of the excipients listed in section 6.1.
Myasthenia gravis.
Acute and / or severe respiratory failure. Sleep apnea syndrome.
Administration to children and adolescents under 18 years.
Severe hepatic insufficiency.
Pregnancy and lactation (see section 4.6).
04.4 Special warnings and appropriate precautions for use
Before prescribing a hypnotic, if possible, the cause of insomnia should be identified and the underlying factors addressed.
A 7-14 day treatment with no clinical results may indicate the presence of a primary physical or psychiatric disorder and the patient should be carefully re-evaluated at regular intervals.
Psychomotor impairment on the following day
The risk of psychomotor impairment in the next day, including impaired ability to drive, increases if:
• zolpidem is taken when less than 8 hours remain before performing activities requiring mental alertness (see section 4.7);
• a higher dose than recommended is taken;
• zolpidem is co-administered with other central nervous system (CNS) depressant drugs, or other drugs that increase the blood levels of zolpidem, or with alcohol or illicit drugs (see section 4.5).
Zolpidem should be taken as a single administration, immediately at bedtime, and should not be re-administered during the same night.
TOLERANCE:
After repeated use for a few weeks, there may be some reduction in the hypno-inducing effect of benzodiazepines or benzodiazepine-like substances with a short half-life.
DEPENDENCE:
The use of benzodiazepines or benzodiazepine-like substances can lead to physical and psychological dependence on these drugs.
The risk of addiction increases according to the dosage and duration of treatment; it is also higher in patients with a history of psychiatric disorders and / or alcohol or drug abuse. These patients should be closely monitored when taking benzodiazepines or benzodiazepine-like substances.
In cases where physical dependence has developed, abrupt cessation of treatment will cause withdrawal symptoms, which may include: headache, body aches, extreme anxiety, tension, agitation, confusion and irritability. In severe cases, the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling in the extremities, hypersensitivity to light, noise and physical contact, hallucinations or seizures.
INSOMNIA REBOUND:
When the hypno-inducing drug is discontinued, a transient syndrome may occur which consists in the reappearance, in an accentuated form, of the symptoms that led to treatment with the drug. It may be accompanied by other reactions such as mood swings, anxiety and agitation, or sleep disturbances.
This syndrome is more likely to occur if drug administration is abruptly stopped; therefore treatment should be discontinued gradually.
Furthermore, it is important that the patient is aware of the possibility of rebound phenomena occurring, thus minimizing the anxiety caused by these symptoms should they arise in the withdrawal phase of the drug.
It seems that, in the case of benzodiazepines or benzodiazepine-like substances with a short duration of action, withdrawal phenomena may occur in the interval between two intakes.
DURATION OF THE TREATMENT:
The duration of treatment should be as short as possible (see section 4.2) and should not exceed 4 weeks including the drug withdrawal phase.
The duration of treatment should not be extended beyond this period without reassessment of the patient's situation.
It may be useful to inform the patient at the beginning of the treatment that this will be of limited duration and to explain exactly how the dosage should be progressively reduced.
AMNESIA:
Benzodiazepines or benzodiazepine-like substances can cause anterograde amnesia. Most often this effect occurs several hours after taking the drug.
To reduce the risk, patients should ensure that they can sleep continuously for 8 hours (see section 4.8).
OTHER PSYCHIATRIC AND "PARADOX" REACTIONS:
Restlessness, aggravation of insomnia, agitation, irritability, aggression, delusions, anger, nightmares, hallucinations, psychosis, abnormal behavior and other behavioral side effects known to occur during the use of benzodiazepines or benzodiazepine-like substances may occur. occur when using hypnotic / sedative agents such as zolpidem.
Should this occur, use of the drug should be discontinued.
These reactions are more likely to occur in children and the elderly.
SLEEPWALKING AND ASSOCIATED BEHAVIOR:
Sleepwalking and other associated behaviors such as sleep driving, preparing and eating food, making phone calls, having sex, with amnesia for the event have been reported in patients taking zolpidem who were not fully awake. It appears that both the use of alcohol and other CNS depressants together with zolpidem, and the use of zolpidem at doses exceeding the maximum recommended dose, increase the risk of such behaviors. Discontinuation of zolpidem treatment in patients exhibiting such behaviors should be carefully considered. (e.g. sleep driving), for the risks to the patient and others (see sections 4.5 and 4.8).
SERIOUS INJURY
In relation to its pharmacological properties, zolpidem can cause drowsiness and reduced consciousness, which can lead to falls and consequently serious injuries.
SPECIAL GROUPS OF PATIENTS:
• Senior citizens: see section 4.2.
• Caution is advised when prescribing zolpidem to patients with chronic respiratory failure, as benzodiazepines can depress respiratory function (see section 4.8).
• Benzodiazepines and benzodiazepine-like substances are not indicated for the treatment of patients with severe liver failure, as these drugs can precipitate an "encephalopathy."
• Benzodiazepines and benzodiazepine-like substances are not recommended as the primary treatment for psychotic illnesses.
• Benzodiazepines and benzodiazepine-like substances should not be used alone for the treatment of depression or anxiety associated with depression (suicidal tendencies may increase in such patients).
Although no clinically significant pharmacokinetic and pharmacodynamic interactions have been demonstrated with SSRI antidepressants (see section 4.5), zolpidem, like other benzodiazepines and benzodiazepine-like substances, should be administered with caution to patients with symptoms of depression. Suicidal tendencies may occur in such patients and consequently the minimum amount of useful drug should be provided due to the possibility of intentional overdose by the patient.
Pre-existing depression may be revealed while using zolpidem. Since insomnia can be a symptom of depression, the patient should be reevaluated if insomnia persists.
• Benzodiazepines and benzodiazepine-like substances should be used with extreme caution in patients with a history of alcohol or drug abuse.
Important information about some of the ingredients
This medicinal product contains lactose.Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose / galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Alcohol:
the simultaneous intake of alcohol is not recommended.
The sedative effect may be enhanced if the drug is taken concomitantly with alcohol. This adversely affects the ability to drive or use machines.
Association with CNS depressant drugs
An enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, antidepressants, narcotic analgesics, antiepileptic drugs, anesthetics and sedative antihistamines. Therefore, the concomitant use of zolpidem with such drugs. may increase somnolence and psychomotor impairment in the next day, including impaired ability to drive (see section 4.4 and section 4.7). In addition, there have been isolated reports of visual hallucinations in patients taking zolpidem with antidepressants, including bupropion, desipramine, fluoxetine, sertraline and venlafaxine.
In the case of narcotic analgesics, there may also be an "accentuation of the sense of euphoria, which leads to an increase in psychic dependence.
Co-administration of fluvoxamine may increase blood levels of zolpidem; concomitant use is not recommended.
CYP450 inhibitors and inducers
Zolpidem is metabolised by several isoforms of the hepatic cytochrome P450 enzyme: the main enzyme is CYP3A4 with the contribution of CYP1A2.
Substances that inhibit cytochrome P450 may increase the activity of benzodiazepines or benzodiazepine-like substances, such as zolpidem.
Co-administration of ciprofloxacin may increase blood levels of zolpidem; concomitant use is not recommended.
The pharmacodynamic effect of zolpidem decreases when zolpidem is combined with rifampicin (CYP3A4 inducer). However, when zolpidem is administered with itraconazole (CYP3A4 inhibitor) its pharmacokinetics and pharmacodynamics are not significantly affected. The clinical relevance of these results are not significantly affected. it's known.
Concomitant administration of zolpidem and a strong CYP3A4 inhibitor, ketoconazole (200 mg twice daily) prolonged the elimination half-life of zolpidem, increased total AUC and decreased apparent oral clearance compared to zolpidem. plus placebo. The total AUC of zolpidem, when given with ketoconazole, increases by a factor of 1.83 compared to zolpidem alone. It is not considered necessary to adjust the usual dosage of zolpidem, but patients should be advised that the use of zolpidem with ketoconazole may increase the sedative effects.
Other drugs:
No significant pharmacokinetic interactions have been observed when zolpidem is co-administered with warfarin, digoxin or ranitidine.
04.6 Pregnancy and lactation
Pregnancy
As a precaution zolpidem should be avoided during pregnancy and breastfeeding.
There are no, or very limited, data of zolpidem in pregnant patients. Animal studies do not indicate direct or indirect harmful effects with respect to the development of reproductive toxicity.
If the drug is prescribed to a woman of childbearing age, she should be advised to contact her doctor to discontinue treatment if she intends to become pregnant or suspects that she is pregnant.
If, for absolute medical necessities, zolpidem has to be administered in the advanced stage of pregnancy, or during childbirth, effects on the newborn can be expected such as: hypothermia, hypotonia and moderate respiratory depression, caused by the pharmacological action of the drug.
Cases of severe neonatal respiratory depression have been reported when zolpidem was used with other CNS depressant drugs in late pregnancy.
In addition, babies born to mothers who took benzodiazepines or benzodiazepine-like substances on a chronic basis during the latter stages of pregnancy may develop physical dependence and may be at some risk of experiencing withdrawal symptoms in the postnatal period.
Feeding time
Since benzodiazepines or benzodiazepine-like substances have been found in breast milk, zolpidem should not be given to mothers who are breastfeeding.
04.7 Effects on ability to drive and use machines
Stilnox impairs the ability to drive and use machines.
Vehicle drivers and machine operators should be advised that, as with other hypnotics, there is a possible risk of drowsiness, prolonged reaction time, dizziness, drowsiness, confused / double vision and reduced alertness and impaired ability to drive, the morning after therapy (see section 4.8). To minimize the risk, a rest period of at least 8 hours is recommended between taking zolpidem and driving a vehicle, using machinery and working at height.
Impaired ability to drive and behaviors such as "falling asleep behind the wheel" have occurred with zolpidem alone, at therapeutic doses.
Furthermore, co-administration of zolpidem with alcohol and other CNS depressant drugs increases the risk of such behaviors (see sections 4.4 and 4.5). Patients should be advised not to use alcohol or other psychoactive substances while taking zolpidem.
04.8 Undesirable effects
Whenever possible, the following CIOMS frequency scale is used: very common> 10%; common> 1 and 0.1 and 0.01 e
Not known: cannot be estimated from the available data.
There is evidence of dose-related undesirable effects with zolpidem, particularly some CNS events. As recommended in section 4.2, these effects should be less severe if zolpidem is administered immediately before bedtime or when in bed. already lying down.
These effects occur more frequently in elderly patients.
Nervous system disorders
Common: somnolence, headache, dizziness, increased insomnia, anterograde amnesia (amnesic effects may be associated with inappropriate behavior).
Not known: decreased level of consciousness.
Psychiatric disorders
Common: hallucinations, agitation, nightmares.
Uncommon: confusional state, irritability.
Not known: restlessness, aggression, delirium, anger, abnormal behavior, sleepwalking (see section 4.4), dependence (drug withdrawal syndrome or rebound effects may occur after discontinuation of treatment), libido changes, depression (see section 4.4).
Many of these undesirable psychiatric effects are related to paradoxical reactions.
General disorders and administration site conditions
Common: fatigue
Not known: changes in gait, drug tolerance, falls (especially in elderly patients and when not taking zolpidem as prescribed) (see section 4.4).
Eye disorders
Uncommon: diplopia.
Respiratory, thoracic and mediastinal disorders
Not known: respiratory depression (see section 4.4)
Gastrointestinal disorders
Common: diarrhea, nausea, vomiting, abdominal pain.
Musculoskeletal and connective tissue disorders
Common: back pain
Not known: muscle weakness.
Infections and infestations
Common: upper respiratory tract infection, lower respiratory tract infection.
Skin and subcutaneous tissue disorders
Not known: rash, itching, urticaria, hyperhidrosis.
Hepatobiliary disorders
Not known: elevated liver enzyme levels.
Disorders of the immune system
Not known: angioneurotic edema.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
04.9 Overdose
Signs and symptoms
Decreased consciousness up to coma and more severe symptoms including fatal consequences have been reported in cases of overdose with zolpidem alone or in combination with other CNS depressant drugs or substances (including alcohol). .
Treatment
When treating overdose of any medicinal product, it should be borne in mind that more substances may have been taken.
In the event of an overdose of benzodiazepines or benzodiazepine-like substances, induce vomiting (within 1 hour) if the patient is conscious or perform a gastric lavage, with airway protection, if the patient is unconscious. If stomach emptying is not beneficial, give activated charcoal to reduce absorption.
Cardiovascular and respiratory functions must be carefully monitored in the intensive care unit.
Sedative drugs should also be avoided in cases of psychomotor arousal.
Flumazenil may be a useful antidote if severe symptoms have been observed. However, administration of flumazenil may contribute to the onset of neurological symptoms (convulsions).
Zolpidem is not dialysable.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Therapeutic drug category: benzodiazepine-related drugs
ATC code: N05CF02
Zolpidem is an imidazopyridine that preferentially binds to the omega-1 receptor subtype (also known as the BZ1 subtype) which is the alpha-1 subunit of the GABA-A receptor complex, while benzodiazepines non-selectively bind to the omega-1 receptor subtypes and omega-2. Modulation of the chlorine anion channel following interaction with this receptor subtype leads to the specific sedative effects demonstrated with zolpidem. These effects are counteracted by benzodiazepine antagonists such as flumazenil.
In animals: the selective binding of zolpidem to the omega-1 receptor may explain the virtual absence of muscle relaxant and anticonvulsant effects at hypnotic doses. These effects are usually present with benzodiazepines, which are not selective for the omega-1 receptor.
In men: zolpidem decreases the sleep latency time and the number of awakenings. It increases the duration and quality of sleep. These effects are associated with a characteristic EEG, different from that caused by the use of benzodiazepines. Zolpidem has been shown to preserve the various stages of sleep in studies evaluating the percentage of time each stage occupies. At the recommended doses zolpidem does not influence the duration of paradoxical sleep (REM). The maintenance of deep sleep stages (stages 3 and 4 or slow wave sleep) can be explained by the selective binding of zolpidem to omega-1 sites. All effects of zolpidem are antagonized by the benzodiazepine antagonist flumazenil.
Randomized trials have shown only convincing evidence of the efficacy of zolpidem 10 mg.
In a randomized double-blind study of 462 healthy volunteers not in old age suffering from transient insomnia, zolpidem 10 mg reduced the mean time to fall asleep by 10 minutes compared to placebo, while in the case of 5 mg zolpidem this time was 10 minutes. 3 minutes.
In a randomized double-blind study of 114 non-elderly patients suffering from chronic insomnia, zolpidem 10 mg reduced the mean time to fall asleep by 30 minutes compared to placebo, while in the case of 5 mg zolpidem this time was 15. minutes.
In some patients, a lower dose of 5 mg may be effective.
Pediatric patients:
The safety and efficacy of zolpidem has not been established in patients younger than 18 years. In an 8-week study in pediatric patients (aged 6-17 years) with insomnia associated with attention deficit hyperactivity disorder (ADHD), psychiatric and nervous system disorders documented the most frequently observed treatment-related adverse events with zolpidem versus placebo, particularly dizziness (23.5% vs. 1.5%), headache (12.5% vs. 9.2%) and hallucinations (7.4% vs. 0%) (see section 4.3).
05.2 Pharmacokinetic properties
Absorption
Zolpidem has rapid absorption and rapid hypnotic action.
After oral administration, the bioavailability of zolpidem is about 70%, in relation to a modest first pass metabolism. The peak plasma concentration is reached between 0.5 and 3 hours after administration.
Distribution
At therapeutic doses, the pharmacokinetic profile of zolpidem is linear and is not affected by repeated administration.
The extent of binding to plasma proteins is approximately 92.5% ± 0.1%.
The elimination half-life is short, with a mean value of 2.4 hours (± 0.2 hours) and a duration of action of up to 6 hours.
The volume of distribution in adults is 0.54 ± 0.02 l / kg and decreases to 0.34 ± 0.05 l / kg in the very elderly patient.
Excretion
Zolpidem is excreted as inactive metabolites, mainly in the urine (56%) and faeces (37%). The metabolites do not interfere with the binding of zolpidem to proteins.
Zolpidem is not dialysable.
Plasma concentrations in the elderly and in hepatopathic patients are increased and consequently the posology may require adjustment. In patients with renal insufficiency, on dialysis and not on dialysis, there is a moderate reduction in clearance. The other pharmacokinetic parameters remain unchanged.
The drug has no inducing effect on liver enzymes.
In elderly patients, clearance is reduced. The peak concentration increased by approximately 50% without significant prolongation of the half-life (approximately 3 hours).
Bioavailability
In patients with hepatic insufficiency the bioavailability of zolpidem is increased, the clearance is reduced and the elimination half-life is prolonged (approximately 10 hours).
05.3 Preclinical safety data
STILNOX showed extremely low acute toxicity in experimental animals.
Numerous tests of subacute and chronic toxicity (up to 52 weeks) conducted on Sprague-Dawley rats and Cynomolgus monkeys (macaca fascicularis) at doses hundreds of times higher than those recommended for the daily dosage in humans, did not show any pathological anomalies. significant nor significant alterations in haematological, haematochemical and urinary parameters.
Reproduction studies (rat, rabbit) and the numerous mutagenesis and carcinogenesis tests performed, both in vivo and in vitro, did not show any teratogenic and / or embryotoxic effect, nor genotoxic, clastogenic and carcinogenic activity.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
lactose monohydrate; microcrystalline cellulose; hypromellose; sodium carboxymethyl starch (type A); magnesium stearate.
Coating: hypromellose; titanium dioxide (E171); macrogol 400.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
4 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Heat-sealed PVC and aluminum / PVC blister
- 20 film-coated tablets of 10 mg
- 30 film-coated tablets of 10 mg
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Sanofi S.p.A. - Viale L. Bodio, 37 / B - Milan
08.0 MARKETING AUTHORIZATION NUMBER
STILNOX 10 mg film-coated tablets, 20 tablets AIC n. 026695027
STILNOX 10 mg film-coated tablets, 30 tablets AIC n. 026695015
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
9/6/2007
10.0 DATE OF REVISION OF THE TEXT
October 2014
