Active ingredients: Zolpidem tartrate
SONIREM 10 mg / ml oral drops, solution
Why is Sonirem used? What is it for?
Sonirem contains zolpidem tartrate as the active ingredient. Zolpidem tartrate belongs to a group of medicines called hypnotics. This medicine works on your brain by helping you sleep.
Sonirem is used in adult patients for short-term treatment of severe sleep disorders that cause profound malaise.
Sonirem should not be used every day for long periods of time. Ask your doctor for advice if you are unsure why this medicine has been prescribed for you.
Contraindications When Sonirem should not be used
Do not take Sonirem
- If you are allergic (hypersensitive) to zolpidem tartrate or any other ingredients contained in Sonirem (see section 6). An allergic reaction can include a rash, itching, difficulty breathing, or swelling of the face, lips, throat or tongue.
- If you have severe liver problems or suffer from short breathing stops during sleep (sleep apnea syndrome).
- If you suffer from severe muscle weakness (myasthenia gravis).
- If you have severe and / or acute breathing problems
- If you are under the age of 18.
- If you are pregnant or breastfeeding
Precautions for use What you need to know before you take Sonirem
Before taking your medicine, consult your doctor or pharmacist if:
- He is elderly or weak. If you get up during the night, be careful because there is an increased risk of falling and consequently fracturing the femur due to the relaxing effect of the oral drops.
- You have kidney problems, caution is required although dose adjustment is not necessary.
- A history of breathing difficulties. Your breathing may become more difficult while you are taking Sonirem.
- You have or have had a history of alcohol or drug abuse, extreme caution is required. You should be closely monitored during treatment with Sonirem as you are at risk of physical and psychological dependence.
- You have liver problems as you may be at risk for brain damage (encephalopathy).
- You have a previous history of psychosis, depression or anxiety accompanied by depression. Sonirem may mask or worsen symptoms (suicide risk).
Other considerations
General
Before taking Sonirem
- The cause of sleep disturbances must be identified by your doctor.
- Any other illnesses must be treated before starting treatment with Sonirem.
- If treatment for sleep disorders is unsuccessful after 7-14 days, this could indicate the presence of a psychiatric or physical illness that needs to be identified.
Tolerance
After repeated use for several weeks, some reduction in the hypno-inducing effect of benzodiazepines or other short-lived benzodiazepine-like substances may occur.
Dependence
Physical and psychological dependence may develop as a result of treatment with Sonirem. The risk increases with dose and duration of treatment and is greater in patients with a history of alcohol and drug abuse. If physical dependence develops, abrupt cessation of treatment can cause withdrawal syndrome.
Withdrawal syndrome (Rebound insomnia)
Sonirem should be gradually reduced as the end of your treatment approaches. At the end of treatment, for a short period of time, the original symptoms may return and become worse. They may be accompanied by other reactions such as mood changes, anxiety and restlessness. .
Memory disturbances
Sonirem can cause memory loss (amnesia) in some patients. This condition usually occurs several hours after taking the drops. To minimize this risk, you must make sure that uninterrupted sleep for 7 - 8 hours is possible (see section 4. "Possible side effects").
Psychiatric and paradoxical reactions
Sonirem can cause behavioral undesirable effects such as restlessness, agitation, irritability, aggression, delusions (false beliefs), anger attacks, nightmares, and other nocturnal unconscious behaviors such as eating and driving a car, hallucinations, psychosis, sleepwalking, inappropriate behavior, increased insomnia and other adverse behavioral effects. If these side effects occur, you should stop taking Sonirem and contact your doctor or go to a hospital immediately. The risk of these effects may be higher in the elderly. If you are not sure if the above apply to you, talk to your doctor. doctor or pharmacist before taking Sonirem.
Psychomotor impairment in the next day (see also Driving and using machines)
The day after taking Sonirem, the risk of psychomotor impairment, including impaired ability to drive, may be increased if you:
- take this medicine less than 8 hours before performing activities that require mental alertness
- take a higher dose than recommended
- take zolpidem while already taking other central nervous system depressant drugs or other medicines that increase zolpidem blood levels, or while drinking alcohol, or while taking illicit drugs.
Sleepwalking 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 together with zolpidem, and the use of zolpidem at doses that exceed the maximum recommended dose, increase the risk of such behaviors.
Serious injuries
Zolpidem can cause drowsiness and decreased consciousness, which can lead to falls and consequently serious injuries
Take the single dose immediately at bedtime.
Do not take another dose during the same night.
Special patients
- If you are elderly or debilitated, you should take a lower dose of zolpidem (See section 3). Zolpidem has the effect of relaxing the muscles. For this reason, elderly patients in particular are at risk of falls, and consequent fractures of the "hip, when getting out of bed at night.
- If your kidney function is impaired, elimination of the drug may be reduced. Although a reduction in dosage is not necessary, caution is required. Consult your doctor about this.
- If you have breathing problems, they may get worse with zolpidem.
- If you have abused drugs or alcohol in the past, you should be closely monitored by your doctor during treatment with zolpidem, as you are at risk of addiction and psychological dependence on this drug.
- If you have severe liver disease, you should not take zolpidem, as it risks brain damage (encephalopathy). Consult your doctor on this matter.
- If you suffer from delirium (psychosis), depression or anxiety related to depression, you should combine other medications with zolpidem.
Interactions Which drugs or foods may change the effect of Sonirem
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including those without a prescription or herbal medicines. This is because Sonirem can affect the way some other medicines work. Other medicines can also affect the way Sonirem works.
Tell your doctor if you are taking any of the following medications:
Sonirem may increase the effect of the following drugs:
- Medicines to treat mental disorders (antipsychotics)
- Medicines for depression (antidepressants)
- Medicines for epilepsy (anticonvulsants)
- Medicines used during surgery (anesthetics)
- Medicines to calm or reduce anxiety or for sleep disturbances (anxiolytics / sedatives)
- Medicines for hay fever, rash or other allergies that can make you sleepy (sedative antihistamines)
- Some Medicines for moderate to severe pain (narcotic analgesics) such as codeine, methadone, morphine, oxycodone, pethidine or tramadol.
When taking zolpidem with the following medicines, increased effects of somnolence and psychomotor impairment in the next day, including impaired ability to drive, are possible.
- medicines for certain mental health problems (antipsychotics)
- medicines for insomnia problems (hypnotics)
- medicines to calm or reduce anxiety
- medicines for depression
- medicines for moderate to severe pain (narcotic analgesics)
- medicines for epilepsy
- medicines used for anesthesia
- medicines for hay fever, skin rash (rash) or other allergies, which can make you sleepy (sedative antihistamines)
While you are taking zolpidem with antidepressant medicines, including bupropion, desipramine, fluoxetine, sertraline and venlafaxine, you may see non-existent things (hallucinations).
It is recommended not to take zolpidem with fluvoxamine or ciprofloxacin.
The following medicines may increase the chance of getting side effects when taking Sonirem.
To make this less likely, your doctor may decide to decrease your dose of Sonirem:
- Some antibiotics such as clarithromycin or erythromycin
- Some medicines for fungal infections such as ketoconazole and itraconazole.
- Ritonavir (protease inhibitor) - for HIV infections
The following medicines may reduce the effect of Sonirem:
- Some epilepsy medications such as carbamazepine, phenobarbital or phenytoin
- Rifampicin (an antibiotic) - for infections
- St. John's wort (a herbal medicine) - for mood swings and depression
Taking Sonirem with food and drink
Do not drink alcohol while taking Sonirem as alcohol increases the effects of this drug.
Warnings It is important to know that:
Pregnancy
- Tell your doctor if you plan to become pregnant while taking Sonirem, or if you think you are pregnant, so your doctor can decide whether to change or continue your treatment.
- Sonirem should not be taken during pregnancy, as there are insufficient data to evaluate the safety of Sonirem administration during pregnancy and breastfeeding.
- If Sonirem is taken for a long time during the last months of pregnancy, the newborn may have withdrawal syndrome after birth.
- Taking Sonirem for medical reasons near the end of your pregnancy or during delivery can harm your baby.
Feeding time
- Because zolpidem passes into breast milk in small amounts, Sonirem should not be taken while breastfeeding. Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Sonirem impairs the ability to drive and use machines, for example with the risk of 'falling asleep at the wheel'.
On the day after taking Sonirem (as with other hypnotic medicines), you should be aware that:
- you may feel drowsy, sleepy, dizzy or confused
- it may take longer to make decisions
- vision may be blurred or double
- may feel less alert
A period of at least 8 hours is recommended between taking zolpidem and driving vehicles, using machines and working at height to minimize the effects listed above.
Do not drink alcohol or take other psychoactive substances while taking Sonirem, as the effects listed above may be enhanced.
Dosage and method of use How to use Sonirem: Dosage
Always take Sonirem exactly as your doctor prescribed. If in doubt, you should consult your doctor or pharmacist
The usual dose is
Adults
The recommended dose every 24 hours is 10 mg (25 drops) of Sonirem. A lower dose may be prescribed for some patients. Sonirem must be taken:
- with a single administration,
- just before bedtime
Make sure you have a period of at least 8 hours after taking this medicine before performing any activities that require your vigilance. Do not exceed 10 mg every 24 hours.
Elderly, debilitated patients or patients with liver problems
A lower dose of 12 drops per night can be used. This dose can be increased to 25 drops by your doctor.
Maximum daily dose
The daily dose of 25 drops of Sonirem should not be exceeded.
Use in children and adolescents:
Sonirem should not be given to patients under the age of 18.
25 drops contain 10 mg of zolpidem tartrate and correspond to 1 ml of solution.
Dilute the required number of drops in a glass of water and drink.
It is recommended to take Sonirem just before bedtime.
Duration of treatment with Sonirem
The duration of treatment with Sonirem should be as short as possible. In general it can be a few days up to 2 weeks and should not exceed 4 weeks, including the withdrawal phase. Your doctor will choose the withdrawal phase based on your individual needs.
Some situations may require a longer treatment period. Your doctor will decide on the best course of treatment for your symptoms.
Overdose What to do if you have taken too much Sonirem
If you take more Sonirem than you should
It is important that you do not take more Sonirem drops than prescribed. If you accidentally take too many drops, contact your nearest emergency department or your doctor immediately. Take someone with you as an overdose can make you drowsy very quickly, high doses can lead to a coma.
If you forget to take Sonirem
If you forget to take a dose immediately before going to bed but remember it during the night, take the missed dose if you still have 7-8 hours of uninterrupted sleep. If this is not possible, take the next dose before going to bed the next night. Do not take a double dose to make up for a forgotten dose. If you are concerned, ask your pharmacist or doctor for advice.
If you stop taking Sonirem
Always contact your doctor before stopping treatment with Sonirem as the dose needs to be reduced gradually. This is because abrupt cessation of treatment increases the risk of withdrawal syndrome.
- Treatment should be gradually stopped as the symptoms for which it is being treated will recur and will be worse than before (worsening of insomnia), as well as anxiety, restlessness and mood swings. These effects will disappear over time.
- If you have become physically dependent on Sonirem, abrupt discontinuation of treatment could lead to side effects such as headache, muscle pain, anxiety, tension, restlessness, confusion, irritability and insomnia. In severe cases other effects could appear such as hypersensitivity to light, noise and physical contact, abnormal hearing acuity and painful sensitivity to sound, hallucinations, numbness and tingling of the extremities, detachment from reality (feeling that the world around is not real), depersonalization (feeling the mind separate from the body) or epileptic seizures (violent fits or shaking). These symptoms could also occur between doses, especially if the dose is high.
If you have any further questions on the use of the medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Sonirem
Like all medicines, Sonirem can cause side effects, although not everybody gets them.
Stop taking Sonirem and go to your doctor or hospital directly if:
- He has an allergic reaction. Symptoms may include: a rash, swallowing or breathing problems, swelling of the lips, face, throat or tongue.
- See or hear things that are not real (hallucinations).
If you get any of these symptoms you should stop taking Sonirem and go to your doctor or hospital straight away.
Contact your doctor as soon as possible if you experience any of the following side effects:
Common (present in 1 in 10 patients)
- Memory loss while taking Sonirem (amnesia) and inappropriate behavior during this period. This appears more easily in the first few hours after taking the medicine. If you get 7-8 hours of sleep after taking Sonirem, it is less likely to cause you problems.
- Problems with insomnia that get worse after taking the medicine.
- Sleepiness during the day
Uncommon (present in 1 in 100 patients)
- Blurred vision or double vision
Other effects that have been reported include
- Less attention to the surrounding environment
- Falls, especially in the elderly
Driving while sleeping and other abnormal behaviors
There have been reports of people doing things while they slept that they didn't remember when they got up after taking a sleeping medication. This includes driving while sleeping, walking asleep, and having sex. Alcohol and some medicines for depression or anxiety can increase the chance of these serious effects.
Contact your doctor or pharmacist if any of the following side effects get worse or last longer than a few days:
Common (present in 1 in 10 patients)
- Dizziness, headache, worsening of insomnia, recent memory loss, which may be associated with inappropriate behavior
- Diarrhea, nausea, vomiting, abdominal pain
- Tiredness or agitation
- Back pain
- Hallucinations, nightmares
- Respiratory tract infections
Uncommon (present in 1 in 100 patients)
- Manifestation of pre-existing depression
- Confusion or irritability
- Dependence
Other effects that have been reported, the frequency of which cannot be estimated from the available data, include:
- Itchy skin or rash, excessive sweating
- Reduction of the state of consciousness
- Muscle weakness
- Difficulty in breathing
- Feeling restless, aggressive, angry or showing inappropriate behavior
- Thinking things that are not true (delusion)
- Changes in sexual behavior (libido)
- Changes in the amount of liver enzymes - shown in blood test results
- Alteration of gait
- Sonirem may have less effect than normal
If any of the side effects gets serious or if you notice any other side effects not included in this leaflet, please contact your doctor or pharmacist.
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. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
- Keep this medicine out of the reach and sight of children.
- Do not use Sonirem after the expiry date which is stated on the bottle and carton after EXP. The expiry date refers to the last day of the month.
- This medicine does not require any special storage temperatures
- Store in the original package to keep it away from light.
- Discard the bottle 60 days after opening it, even if there is some solution left
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
What Sonirem contains
The active ingredient is zolpidem tartrate. Each ml (25 drops) contains 10 mg of zolpidem tartrate equivalent to 8.03 mg of zolpidem.
The other ingredients are: Citric acid monohydrate, sodium benzoate E211, purified water, sodium hydroxide (for pH adjustment) and concentrated hydrochloric acid 37% (for pH adjustment).
What Sonirem looks like and contents of the pack
Sonirem 10 mg / ml oral drops, solution, is a clear, colorless or slightly yellowish solution.
It comes in a bottle containing 30 ml of solution with a dropper for administering the medicine.
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
SONIREM 10 MG / ML ORAL DROPS, SOLUTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml (25 drops) contains:
10 mg of zolpidem tartrate equivalent to 8.03 mg of zolpidem.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Oral drops, solution.
Clear, colorless or slightly yellowish solution with a pH range of 3.5 - 4.4.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Sonirem is indicated for the short-term treatment of insomnia in adult patients, in situations where the insomnia is debilitating or causes severe distress to the patient.
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 bottle is supplied with a dropper, 1 ml corresponds to 25 drops equivalent to 10 mg of zolpidem tartrate.
Dosage
The duration of treatment should be as short as possible. Generally, this duration varies from a few days to two weeks and should not exceed four weeks, including the tapering phase of the drug. The tapering phase of the drug should be tailored to the individual patient.
As with all hypnotics, long-term treatment is not recommended and the duration of treatment should not exceed four weeks.
In some cases, it may be necessary to extend the treatment beyond the maximum expected duration; in this case, this should not be done without first re-evaluating the patient's state of health.
Adults
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 (25 drops), to be taken immediately at bedtime. The total daily dose of zolpidem should not exceed 10 mg.
Elderly patients and debilitated patients
For elderly or debilitated patients who may be particularly sensitive to the effects of zolpidem, the recommended daily dose is 5 mg. This dose should only be increased to 10 mg when the clinical response is inadequate and the drug is well tolerated.
Patients with hepatic insufficiency
For patients with hepatic insufficiency who do not clear the drug as quickly as healthy subjects, the recommended dose is 5 mg. This dose should only be increased to 10 mg when the clinical response is inadequate and the drug is well tolerated.
Pediatric population
The use of zolpidem in children and adolescents under 18 years of age is not recommended, as there is a lack of data to support its use in this age group. Available clinical data on this population (placebo-controlled study) are presented in the paragraph 5.1.
Treatment should begin with the lowest effective dose. The total dose of zolpidem should not exceed 10 mg in any patient.
Method of administration
Oral use.
The drops should be taken with liquid (water) just before bedtime.
04.3 Contraindications
Hypersensitivity to zolpidem tartrate or to any of the excipients listed in section 6.1
Sleep apneic syndrome
Myasthenia gravis
Severe hepatic insufficiency
Acute and / or severe respiratory failure.
Children and adolescents under 18 years of age
Pregnancy and breastfeeding
04.4 Special warnings and appropriate precautions for use
General
Whenever possible, the cause of insomnia should be identified. The underlying factors should be treated before a hypnotic is prescribed. Failure to treat insomnia after a period of 7-14 days may indicate the presence of a primary psychiatric disorder or physical disorder to be evaluated.
General information regarding the effects observed after administration of benzodiazepines or other hypnotic substances which must be taken into consideration by the prescribing physician is described below.
Tolerance
After repeated use for several weeks, some reduction in the hypno-inducing effect of benzodiazepines or other short-lived benzodiazepine-like substances may occur.
Dependence
The use of benzodiazepines or benzodiazepine-like substances can lead to physical and psychological dependence on these drugs. The risk of dependence increases with dose and duration of treatment and is also greater in patients with a history of psychiatric and / or psychiatric disorders. alcohol or drug abuse. In cases where physical dependence has developed, abrupt cessation of treatment will cause withdrawal symptoms. These can include: headache, body aches, extreme anxiety and tension, restlessness, 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.
Rebound insomnia
Upon discontinuation of the hypnotic drug, a transient syndrome may occur which consists in the reappearance, in an accentuated form, of the symptoms that led to treatment with a benzodiazepine or with a substance similar to benzodiazepines. This syndrome can be accompanied by other types of reactions such as mood swings, anxiety, sleep disturbances and agitation.
It is important that the patient is informed of the possible occurrence of rebound phenomena, thus minimizing the anxiety related to these symptoms should they occur upon discontinuation of the medicinal product.
It is recognized that in the case of benzodiazepines and benzodiazepine-like substances with a short duration of action, withdrawal symptoms may appear in the dose range, particularly at high doses.
As the risk of withdrawal symptoms / rebound phenomena is more likely to occur after abrupt cessation of treatment, it is recommended to reduce the dose gradually.
Duration of treatment
The duration of treatment should be as short as possible (see section 4.2), but should not exceed 4 weeks including the tapering off phase. An extension of this period should not occur without a reassessment of the patient's status.
It may be useful to inform the patient, when starting the treatment, that it will be of limited duration and to explain precisely how the dosage of the drug will be progressively reduced.
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.
Amnesia
Benzodiazepines or benzodiazepine-like substances can cause anterograde amnesia. Most often this effect occurs several hours after taking the drug. To reduce this risk, patients should ensure that they can sleep continuously for 8 hours (see section 4.8).
Other psychiatric reactions and "paradoxical" reactions
During the use of benzodiazepines or other benzodiazepine-like substances, reactions such as restlessness, agitation, irritability, aggression, delirium, anger, nightmares, hallucinations, psychosis, sleepwalking, and other unconscious nocturnal behaviors such as eating and driving a car may occur , inappropriate behavior, increased insomnia and other adverse behavioral effects. Should this occur, use of the drug should be discontinued. These reactions occur more easily in the elderly.
Sleepwalking 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 together 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.
Serious injuries
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 or debilitated patients
They should take a lower dose: see recommended dose (section 4.2).
Because of the "muscle relaxant effect" there is a risk of falls and consequent hip fractures, especially for elderly patients when they get up during the night.
Patients with renal insufficiency (see section 5.2)
Although no dose adjustment is necessary, caution is still required.
Patients with chronic respiratory insufficiency
Caution is warranted when prescribing zolpidem as benzodiazepines can depress respiratory function. It should be noted that anxiety or agitation have been described as signs of uncompensated respiratory failure.
Patients with severe hepatic insufficiency
Benzodiazepines and benzodiazepine-like substances are not indicated for the treatment of patients with severe hepatic insufficiency, as these can worsen an "encephalopathy".
Use in patients with psychotic illness:
Benzodiazepines and benzodiazepine-like substances are not recommended for primary treatment.
Use in depression
Although important clinical, pharmacokinetic and pharmacodynamic interactions with SSRIs have not been demonstrated, zolpidem should be administered with caution to patients presenting with depressive symptoms. Suicidal tendencies may be present. Given the possibility of intentional overdose by the patient, these patients should be given the lowest possible amount of the drug. Benzodiazepines and benzodiazepine-like substances should not be used as the only treatment for depression or anxiety associated with depression (suicidal tendencies may increase in such patients).
Pre-existing depression may be revealed during the use of benzodiazepines and benzodiazepine-like substances. Since insomnia may be one of the symptoms associated with depression, the patient should be reevaluated if insomnia persists.
Use in patients with a history of alcohol or drug abuse
Benzodiazepines and benzodiazepine-like substances should be used with extreme caution in patients with a history of alcohol or drug abuse. These patients should be closely monitored when receiving zolpidem as they are at risk of addiction and psychic dependence.
04.5 Interactions with other medicinal products and other forms of interaction
Concomitant use with alcohol is not recommended. The sedative effect may increase if the medicinal product is taken in combination with alcohol. This affects the ability to drive and use machines.
Association with CNS depressant drugs
Caution should be exercised when zolpidem is used in combination with other CNS depressant drugs (see section 4.4).
An enhancement of the central depressive effect may occur in the case of concomitant use of antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, muscle relaxants, antidepressants, narcotic analgesics, antiepileptic drugs, anesthetics and sedative antihistamines (see sections 4.8 and 5.1). of narcotic analgesics, an increase in euphoria is also possible, which can lead to an increase in psychological dependence.
Therefore, concomitant use of zolpidem with such drugs may increase somnolence and psychomotor impairment in the next day, including impaired ability to drive (see sections 4.4 and 4.7). In addition, isolated cases of visual hallucinations have been reported in patients. patients taking zolpidem with antidepressants, including bupropion, desipramine, fluoxetine, sertraline and venlafaxine.
Co-administration of fluvoxamine may increase blood levels of zolpidem; concomitant use is not recommended.
CYP450 inhibitors and inducers
Zolpidem is metabolised by certain enzymes of the cytochrome P450 family. The main enzyme is CYP3A4.
Rifampicin induces the metabolism of zolpidem; this results in a reduction in maximum plasma concentration of approximately 60% and a possible decrease in efficacy. Similar effects can also be expected with other strong inducers of cytochrome P450 enzymes.
Substances that inhibit liver enzymes (particularly CYP3A4), such as antibiotics such as clarithromycin or erythromycin and ritonavir (protease inhibitor), may increase the plasma concentration and activity of zolpidem.
Co-administration of ciprofloxacin may increase blood levels of zolpidem; concomitant use is not recommended.
However, when zolpidem is administered with itraconazole (CYP3A4 inhibitors), the pharmacokinetic and pharmacodynamic effects are not significantly different. The clinical relevance of these findings is unknown.
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.
04.6 Pregnancy and lactation
Pregnancy
Insufficient data are available to ascertain the safety of use of zolpidem during pregnancy and lactation. Although animal studies have not shown teratogenic or embryotoxic effects, safety during pregnancy has not been confirmed in humans. Therefore zolpidem should not be used during pregnancy.
If the product is prescribed to a woman of childbearing age, the patient should be advised of the need to contact her doctor to stop treatment in the event of a planned or suspected pregnancy.
If, for absolute medical necessity, zolpidem is administered during the last phase of pregnancy, or during labor, effects on the newborn are foreseeable, such as hypothermia, hypotonia and moderate respiratory depression, due to the pharmacological effect 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 infants born to mothers who have had prolonged use of benzodiazepines or benzodiazepine-like substances in the last months of pregnancy, withdrawal symptoms are possible in the postnatal period due to the development of physical dependence.
Feeding time
Zolpidem tartrate is excreted in breast milk in minimal quantities. Therefore, zolpidem should not be used during breastfeeding as the effects on the newborn have not been studied.
04.7 Effects on ability to drive and use machines
Sonirem 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, morning following 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
The following frequency is the basis for the evaluation of undesirable effects:
Very common (≥1 / 10)
Common (≥1 / 100,
Uncommon (≥1 / 1000,
Rare (≥1 / 10,000,
very rare (
Not known (frequency cannot be estimated from the available data).
With the use of zolpidem there is evidence of the occurrence of dose-related undesirable effects, particularly some CNS and gastrointestinal events. As recommended in section 4.2, these effects should theoretically be minor if zolpidem is administered immediately before bedtime or when already in bed. These effects occur more frequently in elderly patients.
Disorders of the immune system
Not known: angioneurotic edema.
Psychiatric disorders
Common: hallucinations, agitation, nightmares.
Uncommon: confusional state, irritability.
Not known: restlessness, aggression, delirium, anger, psychosis, abnormal behavior, sleepwalking (see section 4.4), dependence (withdrawal syndrome or rebound effects may occur after discontinuation of treatment), libido changes.
Many of these unwanted psychiatric disorders are related to paradoxical reactions.
Depression; pre-existing depression may occur during the use of benzodiazepines or benzodiazepine-like substances.
Nervous system disorders
Common: daytime somnolence, headache, dizziness, increased insomnia, anterograde amnesia (amnesic effects may be associated with inappropriate behavior).
Not known: decreased level of consciousness.
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.
Hepatobiliary disorders
Not known: elevated liver enzymes.
Skin and subcutaneous tissue disorders
Not known: rash, itching, urticaria, hyperhidrosis.
Musculoskeletal and connective tissue disorders
Common: back pain
Not known: muscle weakness.
Infections and infestations
Common: upper respiratory tract infection, lower respiratory tract infection.
General disorders and administration site conditions
Common: tiredness.
Not known: gait changes, drug tolerance, falls (especially in elderly patients and when not taking zolpidem as prescribed).
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 available. at "address: www.aifa.gov.it/responsabili.
04.9 Overdose
Signs and symptoms
In cases of zolpidem overdose, alone or in combination with other CNS depressant agents (including alcohol), impaired consciousness ranges from somnolence to alert coma. Some individuals have recovered completely from overdoses of up to 400 mg of zolpidem tartrate, equal to 40 times the recommended dose.
Treatment
General symptomatic and supportive measures should be used. If the patient is conscious, vomiting must be induced immediately; if he is not conscious, gastric lavage should be performed, protecting the patency of the airways. Administer intravenous fluids if needed. If gastric emptying offers no benefit, activated charcoal should be given to reduce absorption. Control of respiratory and cardiovascular functions should be considered. Sedative drugs should be discontinued even if arousal occurs.
The use of flumazenil should be considered if severe symptoms are observed. In the treatment of overdose of any medicinal product, it should be borne in mind that more substances may have been taken.
Given the high volume of distribution and high protein binding capacity of zolpidem, hemodialysis and induced diuresis are not effective measures.
Hemodialysis studies in patients with renal insufficiency treated with therapeutic doses have shown that zolpidem tartrate is not dialysable.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: hypnotics and sedatives, benzodiazepine analogs.
ATC code: N05CF02.
Zolpidem, an imidazopyridine is a hypnotic substance similar to benzodiazepines.Experimental studies have shown sedative effects at doses lower than those necessary to obtain anticonvulsant, muscle relaxant or anxiolytic effects. These effects are related to a specific agonist action on central receptors belonging to the macromolecular GABA-omega receptor complex (BZ1 and BZ2) which regulates the "opening of the chloride ion channels. Zolpidem acts mainly on the receptors of the omega subtype (BZ1). L" clinical significance of this finding is unknown.
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 population
The safety of use and efficacy of zolpidem have not been demonstrated in patients under the age of 18. A placebo-controlled, randomized clinical study of 201 patients aged 6 to 17 years with insomnia associated with deficit disorder of attention-hyperactivity, showed that zolpidem at doses of 0.25 mg / kg / day (up to a maximum of 10 mg / day) is no more effective than placebo.
The most frequently observed adverse reactions to treatment with zolpidem compared to placebo were psychiatric or neurological: dizziness (23.5% versus 1.5%), headache (12.5% versus 9.2%) and hallucinations (7.4% versus 0%). ) (see sections 4.2 and 4.3).
05.2 Pharmacokinetic properties
Absorption
Zolpidem tartrate is rapidly absorbed and rapidly manifests its hypnotic effect. Bioavailability after oral administration is 70%. Within the therapeutic dose range, the kinetics are linear. The therapeutic plasma level is between 80 and 200 ng / ml. The maximum plasma concentration is reached between 30 minutes and 3 hours after administration.
Distribution
The volume of distribution in adults is 0.54 L / kg and decreases to 0.34 L / kg in elderly patients.
Plasma protein binding is 92%. First pass metabolism through the liver is about 35%. Protein binding is not affected by repeated administration, indicating the lack of a competitive effect between zolpidem tartrate and its metabolites for binding sites.
Elimination
The elimination half-life is short, with an average of 2.4 hours and a duration of action of up to 6 hours.
All metabolites are pharmacologically inactive and are eliminated in the urine (56%) and faeces (37%).
In clinical trials, zolpidem tartrate was shown not to be dialyzable.
Special populations
In patients with renal insufficiency, a moderate reduction in clearance is observed (regardless of any dialysis). The other pharmacokinetic parameters remain unaffected.
In elderly patients and in patients with hepatic insufficiency, the bioavailability of zolpidem tartrate is increased. Clearance is reduced and the elimination half-life prolonged (approximately 10 hours).
A five-fold increase in AUC and a three-fold increase in half-life has been observed in patients with liver cirrhosis.
05.3 Preclinical safety data
Preclinical effects have only been observed at doses well above the maximum human exposure levels and are therefore of little importance for clinical use.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Citric acid monohydrate
Sodium benzoate E211
Sodium hydroxide (for pH adjustment)
Concentrated hydrochloric acid 37% w / w (for pH adjustment)
Purified water
06.2 Incompatibility
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
06.3 Period of validity
2 years.
After first opening: 60 days.
06.4 Special precautions for storage
This medicinal product does not require any special storage temperatures when the medicinal product is stored in its closed original package as well as after first opening.
Keep the medicine in the original package in order to protect it from light and keep the bottle in the carton.
06.5 Nature of the immediate packaging and contents of the package
30ml amber glass bottle (type III), fitted with an LDPE dripper and fitted with a child resistant PP / LDPE screw cap.
06.6 Instructions for use and handling
Unused medicine and waste derived from this medicine must be disposed of in accordance with current legislation.
07.0 MARKETING AUTHORIZATION HOLDER
Italfarmaco S.p.A
Viale F. Testi, 330
20126 Milan
08.0 MARKETING AUTHORIZATION NUMBER
10 mg / ml oral drops, solution 1 glass bottle of 30 ml with dropper
AIC n. 039611013
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Determination n. 1681 of 14/04/2010
10.0 DATE OF REVISION OF THE TEXT
June 2015
