Active ingredients: Zaleplon
Sonata 5 mg hard capsules
Sonata package inserts are available for packs:- Sonata 5 mg hard capsules
- Sonata 10 mg hard capsules
Why is Sonata used? What is it for?
Sonata belongs to a class of substances called benzodiazepine-related drugs, which consist of preparations with hypnotic action.
Sonata will help you sleep. Sleep disorders generally do not last long and most people only need a short period of treatment. The duration of treatment usually ranges from a few days to two weeks. capsules you still have trouble sleeping, contact your doctor again.
Contraindications When Sonata should not be used
Don't take Sonata
- if you are allergic to zaleplon or any of the other ingredients of this medicine (listed in section 6).
- if you suffer from sleep apnea syndrome (stopping breathing for short periods during sleep).
- if you suffer from severe kidney or liver disease.
- if you suffer from myasthenia gravis (very marked muscle weakness or fatigue).
- if you have severe breathing or chest problems.
If you are unsure about any of these conditions, ask your doctor for advice. Children and adolescents under 18 years of age should not take Sonata.
Precautions for use What you need to know before you take Sonata
Talk to your doctor or pharmacist before taking Sonata.
- Never drink alcohol while being treated with Sonata. Alcohol can increase the side effects of any sleep aid.
- Use the product with extreme caution if you have been addicted to drugs or alcohol.
- If you are taking medicines belonging to the sleep inducing class, which also includes Sonata, there is a possibility that you may become addicted to these medicines. If you develop addiction, abrupt cessation of treatment may be accompanied by withdrawal symptoms. These symptoms can consist of headaches, muscle pain, severe anxiety, tension, confusion, irritability and restlessness.
- Do not use Sonata or any other sleep inducing medicine for longer than your doctor tells you to.
- Do not take another dose of Sonata on the same night.
- If your insomnia persists or worsens, contact your doctor.
- With the intake of sleep medications, there is a possibility that some type of temporary memory loss (amnesia) and loss of coordination may occur. This can usually be ruled out by avoiding any type of activity for at least 4 hours after taking Sonata.
- It is possible that somnambulism (walking while sleeping) may occur, including eating or driving while not fully awake, without having memory of the event. If any of these happen to you, contact your doctor immediately.
- Reactions such as restlessness, agitation, irritability, aggression, altered thinking, delusion, nightmares, depersonalization, hallucinations, psychosis, anger, altered behavior, extroversion, incompatible with character, and other effects on behavior, have been reported following the " use of medicines to treat insomnia, including Sonata. These reactions can be drug-induced, spontaneous in origin, or caused by an underlying psychiatric or physical disorder. They are more common in the elderly. If you experience these reactions, contact your doctor immediately.
- Rare cases of severe allergic reactions have been reported. An allergic reaction may include rash, itching, difficulty breathing, or swelling of the face, lips, pharynx or tongue, or nausea and vomiting. If any of these happen to you, contact your doctor immediately.
Children and adolescents
Do not give this medicine to children and adolescents under 18 years of age.
Interactions Which drugs or foods can change the effect of Sonata
Other medicines and Sonata
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Do not take any other medicines without first checking with your doctor or pharmacist. This also applies to medicines that can be bought without a prescription. Some medications can cause drowsiness and should not be taken while taking Sonata.
If Sonata is taken with other drugs that affect the brain, this combination may make you more sleepy than expected. Keep in mind that these combinations can make you sleepy the next day. These medicines include: substances used in the treatment of mental conditions (antipsychotics, hypnotics, anxiolytics / sedatives, antidepressants), drugs used in the treatment of acute pain (narcotic analgesics), drugs used to treat seizures / convulsions (antiepileptic drugs), anesthetics and drugs used in the treatment of allergies (sedative antihistamines). Drinking alcoholic beverages while taking Sonata may make you feel sleepy the next day. Never drink alcoholic beverages while taking Sonata (see "Warnings and precautions").
Tell your doctor or pharmacist if you are taking cimetidine (a stomach medicine) or erythromycin (an antibiotic).
Sonata with food, drink and alcohol
It is not recommended to take Sonata with or immediately after a large meal as the medicine may work more slowly. Swallow the capsule (s) with a glass of water. Never drink alcohol while being treated with Sonata (see "Warnings and precautions").
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Sonata should not be taken during these times as there are insufficient clinical data available to determine its safety during pregnancy and breastfeeding.
Driving and using machines
Sonata can cause drowsiness, loss of concentration, memory, or muscle weakness. These symptoms may worsen if your sleep duration is less than 7 or 8 hours after taking the medicine or if you are already taking another "central nervous system depressant" or if you are drinking alcohol (see "Other medicines and Sonata "). If these symptoms occur, do not drive or operate machinery.
Sonata contains lactose
If your doctor has told you that you are intolerant to some sugars, contact your doctor before taking this drug.
Dose, Method and Time of Administration How to use Sonata: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
The recommended dose for adults is 10 mg at bedtime or if you have difficulty falling asleep after going to bed. You should not take a second dose on the same night.
There are different dosages for people who are 65 or older and for those who have mild to moderate liver problems:
- 65 years or older: take one 5 mg capsule
- Mild to moderate liver problems: take one 5 mg capsule.
Sonata has been designed in such a way that if the contents of a capsule are dissolved in a liquid, it changes color and becomes opaque.
Overdose What to do if you have taken too much Sonata
If you take more Sonata than you should
Contact a doctor immediately and report how many capsules have been taken. Do not go alone for medical assistance.
If you take a dose higher than that indicated, drowsiness will appear quickly, high doses can probably cause coma.
If you forget to take Sonata
Just take the next dose at the appointed time, then continue as before. Do not try to increase the next dose after the one you missed.
If you stop using Sonata
When treatment is stopped, your initial insomnia may return and you may suffer from conditions such as mood swings, anxiety and agitation. If you experience these symptoms, please ask your doctor about them.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Sonata
Like all medicines, this medicine can cause side effects, although not everybody gets them. If you notice any of the following side effects or any other changes in your health, please tell your doctor as soon as possible.
The frequency with which the side effects listed below occur is as follows:
very common (more than 1 in 10 patients)
common (1 to 10 of 100 patients)
uncommon (1 to 10 of 1000 patients)
rare (1 to 10 in 10,000 patients)
very rare (less than 1 in 10,000 patients)
not known (frequency cannot be estimated from the available data)
Side effects that can commonly appear are: sleepiness; memory difficulties; tingling sensation, for example in the extremities (paraesthesia); painful menstruation.
Uncommon side effects include: dizziness; weakness; reduced coordination of movements; instability and / or falls (ataxia); reduced concentration; apathy; night agitation; depression; agitation; irritability; confusion; altered thinking and behavior (extroversion that does not seem to belong to character, diminished inhibition, aggression, anger; delusion, depersonalization, psychosis); nightmares; hallucinations; double vision or other visual problems; increased sensitivity to noise (hyperacusis); disturbances in smell (parosmia); speech disturbances including blocked speech; numbness, for example in the extremities (hypoesthesia); nausea; decreased appetite; increased sensitivity to light (sunlight, UV light); vague feeling of being unwell (indisposition).
In very rare cases, allergic reactions, some severe, sometimes accompanied by difficulty in breathing have been reported and may require immediate medical attention. An allergic reaction can also include rash, itching, difficulty breathing, or swelling of the face, lips, pharynx or tongue.
If an increase in transaminases (a group of liver enzymes found naturally in the blood) is reported it could be a sign of liver problems.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell 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 listed in Appendix V. 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 sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
If you have any further questions, please consult your doctor or pharmacist.
Do not throw any medicines 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 Sonata contains
The active substance in each Sonata hard capsule is zaleplon 5 mg.
The other ingredients are microcrystalline cellulose, pregelatinised starch, silicon dioxide, sodium lauryl sulfate, magnesium stearate, lactose monohydrate, indigo carmine (E132), titanium dioxide (E171).
Capsule shell ingredients: gelatin, titanium dioxide (E171), red iron oxide (E172), yellow iron oxide (E172), black iron oxide (E172) and sodium lauryl sulfate. contain (SB-3200 gold ink): lacquer, ammonium hydroxide, yellow iron oxide (E172).
Description of what Sonata looks like and contents of the package
Sonata 5 mg hard capsules, which contain a light blue powder, have a light brown cap and a white body with gold imprinted "5 mg". They are packed in blisters. Each pack contains 7, 10 or 14 hard capsules.
Not all pack sizes may be marketed.
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
SONATA 5 MG HARD CAPSULES
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 5 mg of zaleplon.
Excipient with known effect: Lactose monohydrate 54 mg.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Hard capsules.
The capsules have an opaque white and opaque light brown hard shell at the "5 mg" strength.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Sonata is indicated for the treatment of patients with insomnia who have difficulty falling asleep. It is only indicated when the disorder is severe, disabling or causing extremely serious problems.
04.2 Posology and method of administration
In adults, the recommended dose is 10 mg.
Treatment should be as short as possible, with a maximum duration of two weeks.
Sonata can be taken immediately before going to bed or after the patient has gone to bed and is having difficulty falling asleep. Since intake on a full stomach delays the time to reach maximum plasma concentration by approximately 2 hours, Sonata should not be taken with or immediately before food.
The total daily dose of Sonata should not exceed 10 mg in any patient. Patients should be advised not to take a second dose on the same night.
Senior citizens
Elderly patients may be sensitive to the effects of hypnotics; therefore the recommended dose is 5 mg of Sonata.
Pediatric patients
Sonata is contraindicated in children and adolescents below 18 years of age (see section 4.3).
Hepatic insufficiency
Since clearance is reduced, patients with mild to moderate hepatic impairment should be treated with Sonata 5 mg. In case of severe hepatic impairment, see section 4.3.
Kidney failure
No dosage adjustment is required in patients with mild to moderate renal impairment as the pharmacokinetics of Sonata are not altered in these patients. & EGRAVE; contraindicated in severe renal insufficiency (see section 4.3).
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Severe hepatic insufficiency
Severe renal insufficiency
Sleep Apnea Syndrome
Myasthenia gravis
Severe respiratory failure
Children and adolescents (under 18 years of age)
04.4 Special warnings and appropriate precautions for use
Complex behaviors such as driving during sleep (driving during a state of partial wakefulness after ingestion of a hypnotic sedative, with amnesia of the event) have been reported in patients taking sedative-hypnotics. These events can occur in both recent users. time of hypnotic sedatives, both in those who use them for a long time. Although behaviors such as driving during sleep can manifest themselves with the sole use of a hypnotic sedative at therapeutic doses, the intake of alcohol and other depressants of the Central Nervous System (CNS ) concomitant with that of hypnotic sedatives seems to increase the risk of such behaviors, as it can also happen if the maximum recommended dose is exceeded. In patients experiencing sleep driving episodes, discontinuation of Zaleplon is recommended as this poses a risk to the patient and the community. Other complex behaviors have also been reported in patients who are partially awake after taking a hypnotic sedative (e.g. preparing and eating food, making phone calls, having sex).As with sleep driving, patients usually do not remember these events.
Severe anaphylactic / anaphylactoid reactions have been reported with the use of sedative-hypnotics, including Zaleplon. Cases of angioedema involving the tongue, glottis or larynx have been reported in patients after the first or subsequent doses of hypnotic sedatives. including Zaleplon. Some patients taking hypnotic sedatives have experienced additional symptoms such as dyspnoea, pharyngeal occlusion, or nausea and vomiting. Some patients have required emergency medical treatment. If angioedema affects the tongue, glottis or larynx , any airway obstruction can be fatal. Patients who experience angioedema following treatment with Zaleplon should no longer use the drug.
Insomnia may be a symptom of an underlying physical or psychiatric disorder. Insomnia that persists or worsens after a short course of treatment with zaleplon may indicate a need for re-examination.
Due to the short plasma half-life of Zaleplon, alternative therapy should be considered in case of early morning awakening. Patients should be advised not to take a second dose on the same night.
Co-administration of Sonata with medicinal products affecting CYP3A4 causes changes in the plasma concentrations of zaleplon. (see section 4.5).
Concomitant alcohol intake is not recommended. The sedative effect may be enhanced when the product is taken in combination with alcohol, this may affect the ability to drive or use machines the next day (see section 4.7).
Tolerance
After repeated use for a few weeks, a loss of efficacy of the hypnotic effects of the short-acting benzodiazepine and benzodiazepine-like substances may occur.
Dependence
The use of benzodiazepine and benzodiazepine-like substances can lead to physical and psychological dependence. The risk of dependence increases according to the dose and duration of therapy and is greater in patients with a history of alcohol and drug abuse. physical dependence has developed, abrupt discontinuation of treatment will be accompanied by withdrawal symptoms. These can include headache, muscle pain, extreme anxiety, tension, agitation, confusion and irritability. In severe cases the following symptoms may occur: dissociation from reality, depersonalization, hyperacusis, numbness and tingling in the extremities, hypersensitivity to light, noise and physical contact, hallucinations or seizures. Cases of addiction associated with the use of zaleplon, predominantly in combination with other psychotropic agents, have been reported during post-marketing surveillance.
Return of insomnia and anxiety
Upon discontinuation of treatment, 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 benzodiazepine-like substance. This may be accompanied by other reactions which include mood swings, anxiety or sleep disturbances and restlessness.
Duration of treatment
The duration of treatment should be as short as possible (see section 4.2) and should not exceed two weeks. This period should not be extended without a clinical review of the patient.
It may be useful to inform the patient, at the beginning of the treatment, that this will be of limited duration. It is important that the patient is aware of the possibility of the reappearance of the phenomena, thus reducing anxiety in the event of such symptoms occurring upon discontinuation of the treatment.
Memory and psychomotor alterations
Benzodiazepines and benzodiazepine-like substances can induce anterograde amnesia and psychomotor changes. These conditions occur more frequently up to several hours after ingestion of the product. To reduce the risk, patients should not engage in activities that require psychomotor coordination for at least 4 hours or more after taking Sonata (see section 4.7).
Psychiatric and "paradoxical" reactions
It is known that during the use of benzodiazepines or benzodiazepine-like substances reactions such as restlessness, agitation, irritability, reduced inhibition, aggression, altered thinking, delirium, anger, nightmares, depersonalization, hallucinations, psychosis, behavior improper, extraversion that appears not to belong to character and other behavioral effects. These reactions may be drug-induced, spontaneous from origin, or the result of an underlying physical or psychiatric disorder. These reactions are more likely to occur in the elderly. Should this occur, the use of this product should be discontinued. Any new signs or behavioral symptoms require careful and immediate evaluation.
Particular groups of patients
Alcohol and drug abuse
Benzodiazepines and benzodiazepine-like substances should be used with extreme caution in patients with a history of alcohol or drug abuse.
Hepatic insufficiency
Benzodiazepines and benzodiazepine-like substances are not indicated in patients with severe hepatic insufficiency as these drugs can precipitate an "encephalopathy (see section 4.2). In patients with mild to moderate hepatic insufficiency, the bioavailability of zaleplon is increased due to reduced clearance and therefore dose adjustment is required in these patients.
Kidney failure
Sonata is not indicated in patients with severe renal insufficiency as there is a lack of adequate studies in this regard. In patients with mild or moderate renal insufficiency, the pharmacokinetic profile of zaleplon does not differ significantly from that of healthy subjects. Therefore no dosage adjustment is required in these patients.
Respiratory failure
Sedative medicinal products should be prescribed with caution to patients with chronic respiratory failure.
Psychosis
Benzodiazepines and benzodiazepine-like substances are not recommended for the primary treatment of psychotic illness.
Depression
Benzodiazepines and benzodiazepine-like substances should not be used alone to treat depression or anxiety associated with depression (suicides may increase in such patients). Also, due to the increased risk of intentional overdose in patients with depression in In general, the amount of a medicine, including zaleplon, prescribed for these patients should be kept to the minimum necessary.
Sonata contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this drug.
04.5 Interactions with other medicinal products and other forms of interaction
The concomitant intake of alcohol is not recommended. The sedative effect may be enhanced if the drug is used in combination with alcohol which may affect the ability to drive or use machines the next day (see section 4.7).
The combination with other CNS-acting drugs must be taken into account. In case of concomitant use of antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, antidepressant agents, narcotic analgesics, anti-epileptic drugs, anesthetics and sedative antihistamines may occur an increase in central sedation. Taking zaleplon concurrently with these drugs may increase the risk of somnolence the next day, also leading to impaired ability to drive (see section 4.7).
Concomitant administration of a single dose of zaleplon 10 mg and venlafaxine (extended release) 75 mg or 150 mg per day does not affect memory (immediate and delayed verbal recall) or psychomotor performance (digit symbol substitution test). In addition, no pharmacokinetic interactions have been reported between zaleplon and venlafaxine (prolonged release).
In the case of narcotic analgesics, an increase in the sense of euphoria may occur which leads to an increase in physical dependence.
Diphenhydramine is described to be a weak inhibitor of aldehyde oxidase in the rat liver, but its inhibitory effects on the human liver are not known. There are no pharmacokinetic interactions between zaleplon and diphenhydramine following administration of a single dose (10 mg and 50 mg, respectively) of each medicinal product However, as both of these compounds have CNS effects, an additive pharmacodynamic effect is possible.
Cimetidine, a moderate non-specific inhibitor of several liver enzymes including both aldehyde oxidase and CYP3A4, produced an 85% increase in plasma concentrations of zaleplon by inhibiting both the primary (aldehyde oxidase) and secondary enzymes. (CYP3A4) responsible for the metabolism of zaleplon, therefore caution is advised when co-administering cimetidine and Sonata.
Co-administration of Sonata with a single 800 mg dose of erythromycin, a strong selective inhibitor of CYP3A4, resulted in a 34% increase in plasma concentrations of zaleplon. A usual dose adjustment of Sonata is not considered necessary, but patients should be warned that the sedative effects may be enhanced.
In contrast, rifampicin, a strong inducer of several liver enzymes, including CYP3A4, reduced the plasma concentration of zaleplon by a factor of four. Co-administration of Sonata with CYP3A4 inducers such as rifampicin, carbamazepine and phenobarbitone may lead to decreased efficacy of zaleplon.
Sonata did not affect the pharmacokinetic and pharmacodynamic profiles of digoxin and warfarin, two substances with a narrow therapeutic index. Furthermore, ibuprofen, as an example of substances that alter renal excretion, has not shown any interaction with Sonata.
04.6 Pregnancy and lactation
Although animal studies have not shown teratogenic or embryotoxic effects, the clinical data available on Sonata are insufficient to ascertain its safety in pregnancy and lactation. The use of Sonata is not recommended during pregnancy. If the medicine is prescribed to a woman of childbearing potential, she should be advised to contact her doctor about discontinuing the medicine if she intends to become pregnant or suspects that she is pregnant.
If for absolute medical necessities, the drug is administered during the advanced stage of pregnancy or during childbirth at high doses, effects such as hypothermia, hypotonia and moderate respiratory depression, due to the pharmacological action of the compound, can be expected on the newborn.
Babies born to mothers who took benzodiazepines and benzodiazepine-like substances chronically during the latter stages of pregnancy may have developed physical dependence and may be at risk of developing withdrawal symptoms in the postnatal period.
Since zaleplon is excreted in breast milk, Sonata should not be given to mothers who are breastfeeding.
04.7 Effects on ability to drive and use machines
Sonata impairs the ability to drive or use machines.
Sedation, amnesia, difficulty concentrating and changes in muscle function can adversely affect the ability to drive or use machines the next day. In the case of insufficient sleep duration, the likelihood of reduced alertness may increase. In addition, concomitant use of alcohol and other CNS depressant substances may increase this risk (see section 4.5). Caution is advised in patients performing tasks requiring special skill. Patients should be advised not to drive or operate machinery until it is established that their capacity has not diminished.
04.8 Undesirable effects
The most frequently reported undesirable effects are amnesia, paraesthesia, somnolence and dysmenorrhea.
Frequencies are defined as
Very common (> 1/10)
Municipalities (> 1/100,
Uncommon (≥1 / 1000,
Rare (≥1 / 10,000,
Very rare (
Frequency not known (estimate based on available data not possible)
Within each frequency group undesirable effects are presented in order of decreasing severity.
See also below in Depression and psychiatric and "paradoxical" reactions
Amnesia
Anterograde amnesia may occur with recommended therapeutic dosages, the risk increases at higher dosages. Amnesic effects may be associated with improper behavior (see section 4.4).
Depression
Pre-existing depression may occur during the use of benzodiazepines or benzodiazepine-like substances.
Psychiatric and "paradoxical" reactions
It is known that during the use of benzodiazepines or benzodiazepine-like substances, reactions such as restlessness, agitation, irritability, decreased inhibition, aggression, altered thinking, delirium, anger, nightmares, depersonalization, hallucinations, psychosis, improper behavior may occur. , extraversion that does not seem to belong to the character and other adverse behavioral reactions The occurrence of these reactions is more likely in the elderly.
Dependence
Use (even at therapeutic doses) can lead to the development of physical dependence: discontinuation of therapy can cause suspension or rebound phenomena (see section 4.4). Psychic dependence may occur. Cases of benzodiazepine and drug abuse have been reported. benzodiazepine-like drugs.
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.
04.9 Overdose
Clinical experience on the effects of acute overdose with Sonata is limited and the levels of overdose in humans have not been determined.
As with other benzodiazepines or other benzodiazepine-like substances, overdose is not expected to be life threatening unless these have been taken in combination with other CNS depressants (including alcohol).
Symptoms of overdose
Overdose of benzodiazepines or benzodiazepine-like substances usually results in varying degrees of central nervous system depression ranging from somnolence to coma. In mild cases, symptoms include drowsiness, mental confusion and lethargy; in severe cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma, and very rarely death. Chromaturia (discoloration of the urine to blue-green) has been reported with zaleplon overdose.
Treatment of overdose
When treating overdose with any drug, it should be borne in mind that more substances may have been taken.
Treatment of Sonata overdose is largely supportive. It is generally sufficient to pay attention to the patency of the airways and to use supportive strategies for ventilation and hemodynamics. In mild cases, patients must sleep while respiratory and circulatory function is monitored. Induction of vomiting is not recommended. In severe cases, the use of activated charcoal or gastric lavage may be useful when performed close to ingestion. In addition, stabilization of circulatory function and intensive monitoring may be necessary. The value of forced diuresis or hemodialysis in the treatment of overdose has not been determined.
Animal studies suggest that flumazenil is a zaleplon antagonist and should be considered in the treatment of Sonata overdose. However, there is no clinical experience with the use of flumazenil as an antidote to overdose with Sonata.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Benzodiazepine-related drugs, ATC code NO5CF03
Zaleplon is a pyrazolopyrimidine hypnotic with a structure different from that of benzodiazepines and other hypnotics. Zaleplon selectively binds to the benzodiazepine type I receptor.
The pharmacokinetic profile of zaleplon shows rapid absorption and rapid elimination (see section 5.2).The combination of its selective binding characteristics with the receptor subtype, with high selectivity and low affinity for the benzodiazepine type I receptor, is responsible for the overall characteristics of Sonata.
The efficacy of Sonata has been demonstrated both in laboratory sleep studies using objective polysomnography (PSG) measurements and in outpatient studies using sleep assessment questionnaires. In these studies, patients had been diagnosed with "primary (psychophysiological) insomnia."
In studies in non-elderly outpatients using Sonata 10 mg for up to 4 weeks, sleep latency was decreased. In elderly patients, sleep latency was often significantly decreased with Sonata 5 mg and consistently decreased with Sonata 10 mg compared to placebo in 2-week studies. This decrease in sleep latency was significantly different from that seen with placebo. Studies lasting 2 and 4 weeks showed that drug tolerance occurred with no Sonata dosage.
In studies with Sonata, where objective measurements of PSG were used, Sonata 10 mg was more effective than placebo in decreasing sleep latency and increasing sleep duration during the first half of the night. controlled, in which the duration of each phase of sleep was measured in percentage terms, showed that Sonata does not alter the phases of sleep.
05.2 "Pharmacokinetic properties
Absorption
Zaleplon is rapidly and almost completely absorbed following oral administration, and maximum concentrations are reached within approximately 1 hour. At least 71% of the administered oral dose is absorbed. Zaleplon undergoes a presystemic metabolism which leads to an absolute bioavailability of approximately 30%.
Distribution
Zaleplon is lipophilic and has a volume of distribution of approximately 1.4 ± 0.3 L / kg after intravenous administration. In vitro plasma protein binding is approximately 60%, suggesting a low risk of drug interaction due to protein binding.
Metabolism
Zaleplon is metabolised primarily by aldehyde oxidase to 5-oxo-zaleplon. In addition, zaleplon is metabolised from CYP3A4 to the desethylzaleplon form which is further metabolised by aldehyde oxidase to 5-oxy-desethylzaleplon. The oxidative metabolites are further metabolized by conjugation via glucuronidation. All metabolites of zaleplon are inactive both in animal behavioral models and in activity tests performed in vitro.
Plasma concentrations of zaleplon increased linearly with dose and zaleplon showed no signs of accumulation following dosing up to 30 mg / day. The elimination half-life of zaleplon is approximately 1 hour.
Excretion
Zaleplon is excreted as inactive metabolites, mainly in the urine (71%) and faeces (17%). Fifty-seven percent (57%) of the dose is recovered in the urine in the form of 5-oxy-zaleplon and its glucuronic metabolite, and 9% is recovered in the form of 5-oxy-desethylzaleplon and its glucuronic metabolite. The remainder of the urinary excretion is made up of minor metabolites. Most of the faecal excretion is made up of 5-oxo-zaleplon.
Hepatic insufficiency
Zaleplon is metabolised primarily by the liver, and undergoes significant presystemic metabolism. Consequently, the oral clearance of zaleplon was reduced by 70% and 87%, respectively, in compensated and uncompensated cirrhotic patients, which resulted in a marked increase in mean Cmax and AUC (up to 4- and 7-fold in patients compensated and uncompensated, respectively) when compared to those of healthy subjects. The dose of zaleplon should be reduced in patients with mild to moderate hepatic impairment and the use of zaleplon is not recommended in patients with severe hepatic impairment.
Kidney failure
The pharmacokinetics of single-dose administration of zaleplon have been studied in patients with mild (creatinine clearance 40 to 89 ml / min) and moderate (20 to 39 ml / min) renal impairment, and in patients on dialysis. In patients with moderate impairment and in those on dialysis there was an approximately 23% reduction in peak plasma concentration when compared to healthy volunteers. The extent of exposure to zaleplon was similar in all groups. It is not therefore no dose adjustment is required in patients with mild to moderate renal impairment Zaleplon has not been adequately studied in patients with severe renal impairment.
05.3 Preclinical safety data
Repeated dose toxicity
Consistent with the effects seen with other compounds that bind to benzodiazepine receptors, reversible increases in liver and adrenal gland weights were seen only after repeated oral administration of high multiples of the maximum therapeutic dose. At these doses, a significant reduction in the weight of both the prostate and testes was observed in a 3-month study in prepubertal dogs.
Reproductive toxicity
In a fertility and reproductive capacity study in rats, mortality and decreased fertility were observed in males and females at an oral dose of zaleplon of 100 mg / kg / day (equivalent to 49 times the maximum recommended human dose (MRHD). of 20 mg on a mg / m2 basis) Follow-up studies indicated that impaired fertility was due to an effect on the female.
In embryo-fetal development studies, oral administration of zaleplon up to 100 mg / kg / day and 50 mg / kg / day, respectively, to pregnant rats and rabbits (equivalent to 49 (rat) and 48 (rabbit) times the MRHD of 20 mg on a mg / m2 basis) produced no evidence of teratogenicity. The pre- and postnatal growth of rats was reduced at the maternally toxic dose of 100 mg / kg / day. The no-effect dose on offspring growth in the rat was 10 mg / kg (equivalent to 5 times the MRHD on a mg / m2 basis). No adverse effects on embryofoetal development were observed in rabbits.
In a pre- and postnatal development study in rats, increased stillbirth and postnatal mortality, and decreased physical growth and development, were observed in offspring of females treated with doses of 7 mg / kg / day or greater that did not cause toxicity to mothers. The no-effect dose on postnatal development was 1 mg / kg / day (equivalent to 0.5 times the MRHD on a mg / m2 basis). In a subsequent cross-fostering study, adverse effects on the viability and growth of the offspring appeared to result from exposure to zaleplon both in utero and during lactation.
Carcinogenicity
Oral administration of zaleplon to rats for 104 consecutive weeks at dose levels up to 20 mg / kg / day did not result in compound-related tumorigenicity. Oral administration of zaleplon to mice for 65 or 104 consecutive weeks at high dose levels (≥100mg / kg / day) resulted in a statistically significant increase in benign but not malignant liver tumors. The increased incidence of benign liver tumors in mice was likely an adaptive event.
Overall, the results of preclinical studies do not suggest any significant safety risk of using Sonata at the recommended doses in humans.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Nucleus of the capsule
Microcrystalline cellulose,
pregelatinised starch,
silicone dioxide,
sodium lauryl sulfate,
magnesium stearate,
lactose monohydrate,
indigo carmine (E132),
titanium dioxide (E171).
Capsule shell:
jelly,
titanium dioxide (E171),
red iron oxide (E172),
yellow iron oxide (E172),
black iron oxide (E172),
sodium lauryl sulfate,
The printing inks on the housing contain (SB-3002 gold ink):
shellac,
ammonium hydroxide,
yellow iron oxide (E172).
06.2 Incompatibility
Not applicable
06.3 Period of validity
3 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
PVC / PVDC aluminum blisters, of 7, 10 and 14 capsules, with single blisters per capsule. Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
Sonata has been designed in such a way that if the contents of a capsule are dissolved in a liquid, it changes color and becomes opaque.
07.0 MARKETING AUTHORIZATION HOLDER
Meda AB
Pipers väg 2A
170 09 Solna
Sweden
08.0 MARKETING AUTHORIZATION NUMBER
EU / 1/99/102 / 001-003
034386019
034386021
034386033
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 12 March 1999
Renewal date: March 12, 2009
10.0 DATE OF REVISION OF THE TEXT
D.CCE May 2015
