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Active ingredients
Zaleplon
Composition
Zaleplon 10 mg Auxiliary substances: colloidal silicon dioxide - 1.1 mg, sodium lauryl sulfate - 1.1 mg, titanium dioxide (CI77891, E171) - 1.1 mg, indigo carmine (CI73015, E132) - 2.2 mg, magnesium stearate - 2.2 mg, microcrystalline cellulose - 45 mg, starlac (lactose monohydrate - 133.7 mg, corn starch - 23.6 mg) - 157.3 mg. The composition of the lid of the gelatin capsule: indigo carmine (C.I.73015, E132) - 0.0471%, titanium dioxide (C.I.77891, E171) - 1%, gelatin - up to 100%. The composition of the body of the gelatin capsule: indigo carmine (C.I.73015, E132) - 0.2513%, titanium dioxide (C.I.77891, E171) - 1.5%, gelatin - up to 100%.
Pharmacological effect
Hypnotic drug pyrazolo-pyrimidine type, the chemical structure differs from benzodiazepines and other hypnotic drugs. Selectively binds to benzodiazepine receptors of type 1 (-1). Significantly reduces the latent time of falling asleep, prolongs the time of sleep (in the first half of the night), does not cause changes in the ratio of different phases of sleep. When used in a dose of 5 mg and 10 mg for 2-4 weeks does not cause pharmacological tolerance. In addition, it has a sedative, slightly pronounced anxiolytic, anticonvulsant and central muscle relaxant effect. It excites benzodiazepine receptors () of GABA type A receptor complexes. Interaction with β-receptors leads to the discovery of neuronal ionoform channels for chlorine ions, the development of hyperpolarization and the enhancement of inhibition processes in the CNS.
Pharmacokinetics
Absorption After ingestion, it is rapidly and almost completely (about 71%) absorbed from the gastrointestinal tract, Cmax in the blood is achieved after 1 h. As a result of systemic metabolism, the absolute bioavailability is 30%. Plasma concentration is directly proportional to the dose. Taking the drug directly after a meal can delay the time to reach Cmax for 2 hours without affecting the absorbability of the drug. Distribution It is a fat soluble compound. Vd after intravenous injection is 1.4 ± 0.3 l / kg. Plasma protein binding is about 60% (the probability of interaction with other drugs is very low). It is excreted in breast milk. Metabolism Aldehyde oxidase is involved in the primary metabolism and leads to the formation of 5-oxazaleplon. CYP3A4 is also involved in the metabolism of zaleplon with the formation of dezetil-zaleplon, which in turn, with the help of aldehyde oxidase turns into 5-oxo-deethyl-zaleplon.Subsequently, the oxidation products are conjugated with glucuronic acid. All metabolites are inactive. When used in doses up to 30 mg / day, no accumulation is observed. T1 / 2 zaleplon - about 1 h. Withdrawal In the form of inactive metabolites, mainly with urine (71%) and feces (17%). Up to 57% of the dose taken is found in the urine as 5-oxazaleplone or its metabolites, 9% of the dose as 5-oxo-dezetil-zaleplon or its metabolites, the remaining part of the dose as less significant metabolites. Among the metabolites excreted through the intestine, 5-oxazaleplone prevails. Quickly excreted from the body. Pharmacokinetics in special clinical situations Pharmacokinetics in elderly patients (including those over 75) does not significantly differ from those in younger patients. The pharmacokinetics of zaleplon in patients with renal insufficiency is not significantly different from that of healthy ones, although the level of inactive metabolites is higher.
Indications
- severe forms of sleep disturbance (difficulty falling asleep), leading to excessive fatigue, hindering daily activity and reducing performance.
Contraindications
- severe liver failure; - sleep apnea syndrome; - severe pulmonary insufficiency; - severe myasthenia gravis; - pregnancy; - lactation period; - children's and teenage age up to 18 years; - hypersensitivity to the drug. With care prescribed for chronic pulmonary insufficiency, liver and / or renal failure, chronic alcoholism, drug dependence (including a history), with depression.
Use during pregnancy and lactation
The drug is contraindicated in pregnancy and lactation (breastfeeding). When prescribing the drug to women of childbearing age, patients should be warned about the need to immediately consult a doctor in the event of conception or when planning a pregnancy. In the case of using zaleplon in the third trimester of pregnancy or when using the drug in high doses of the drug during childbirth in a newborn, hypothermia, muscular hypotension, moderate respiratory failure as a result of the pharmacological action of the drug may develop.Newborns whose mothers regularly took benzodiazepine or a benzodiazepine-like drug in the last weeks of pregnancy may develop physical dependence and the risk of withdrawal symptoms.
Dosage and administration
The duration of therapy should not exceed 2 weeks. The drug should be taken orally just before going to bed, 2 hours after a meal, or after the patient feels that she cannot fall asleep. The recommended dose for adults is 10 mg. The maximum daily dose of 10 mg (the patient must be warned about the dangers of receiving a repeated dose within one night). Elderly patients the drug is prescribed in a dose of 5 mg (due to greater sensitivity to sleeping pills). With mild and moderate hepatic insufficiency, the daily dose is 5 mg (due to delayed elimination from the body). In case of renal failure, mild and moderate doses are not required. Data on the safety of the drug in renal failure severely absent. The safety of the drug in children under the age of 18 years has not been established, therefore, patients in this age group are not prescribed zaleplon.
Side effects
On the part of the digestive system: abdominal pain, nausea, vomiting, diarrhea. On the part of the central nervous system and peripheral nervous system: most often - headache, weakness, increased sleepiness, dizziness, anterograde amnesia (accompanied by behavioral disturbances), depression; paradoxical and mental reactions (most commonly in elderly patients): anxiety, irritability, aggressiveness, paresthesias, bouts of rage, nightmares, hallucinations, psychosis, behavioral disturbances; development of physical dependence with withdrawal symptoms even when used in therapeutic doses (the appearance of the initial symptoms of sleep disturbance in a more severe form, as well as a change in mood, anxiety, anxiety); withdrawal syndrome (headache, myalgia, irritability, confusion); addiction development leading to drug abuse; ataxia, tremor, irritability, disturbances of perception.In severe cases: auto-aggression, depersonalization, hearing loss, increased reaction to light, sound and physical stimuli, epileptic seizures. Allergic reactions: skin rash, itching.
Overdose
There is little data on acute overdose of the drug. The concentration of zaleplon in the blood during overdose was not measured. Like other benzodiazepines and benzodiazepine-like drugs, overdose does not cause life-threatening conditions if zaleplon is not taken in combination with other drugs that depress the central nervous system (including with ethanol). In case of overdose, you should never forget about the possibility of combined poisoning. Symptoms: signs of CNS depression, manifested in drowsiness right up to coma. With an overdose of mild - drowsiness, confusion, lethargy; in more severe cases - ataxia, lowering blood pressure, respiratory failure, less often coma (in very rare cases with a fatal outcome). Treatment: according to preclinical studies, flumazenil is a zaleplon antagonist, although clinical studies do not confirm the efficacy of flumazenil in an overdose of Andante. Flumazenil can be used as an antidote. If the patient is conscious, then vomiting should be induced during the first hour after taking the drug. If the patient is unconscious, then carry out gastric lavage, appoint activated charcoal. Monitoring of cardiac and respiratory activity is carried out in the ICU.
Interaction with other drugs
The simultaneous intake of ethanol or ethanol-containing drugs enhances the sedative effect of zaleplon. The simultaneous use of antipsychotics (neuroleptics), other hypnotics, anxiolytic, sedatives, antidepressants, antiepileptic, antihistamines, anesthesia drugs, opioid analgesics leads to increased sedative action of glaplone. With simultaneous use with opioid analgesics, the euphoric effect of the latter, leading to the development of drug dependence, is possible. With simultaneous use of cimetidine (aldehyde oxidase inhibitor and CYP3A4) increases the concentration of zaleplon in plasma by 85%.With simultaneous use of selective inhibitors of CYP3A4 (ketoconazole, erythromycin) increase the concentration of zaleplon in the plasma and increase its sedative effect (when using this combination, it may sometimes be necessary to adjust the dose of galeplon). With simultaneous use of inducers of CYP3A4 (rifampicin, carbamazepine, derivatives of phenobarbital) can reduce the effectiveness of gluplone by 25%. With simultaneous use, zaleplon does not affect the pharmacodynamics and pharmacokinetics of digoxin and warfarin (dose adjustment of these drugs is not required). Ibuprofen interactions with zaleplon not detected.
special instructions
The patient must be warned that the drug is not intended for long-term therapy and about the possibility of the development of withdrawal syndrome after the end of the use of the drug Andante. The course of the drug should be short and in any case not to exceed 2 weeks. It is possible to prolong the treatment only after a thorough clinical examination of the patient. The drug can be prescribed to elderly patients (including over 75 years). Sleep disturbance can be the result of diseases (including mental ones). If, after short-term use of the drug Andante, sleep does not return to normal or sleep disturbance progresses, the clinical situation should be re-evaluated. If the patient wakes up shortly after midnight (due to the short T1 / 2 of Glaplon), it may be necessary to prescribe another drug with a longer T1 / 2. Patients should be warned about the need to use no more than 1 capsule overnight. Acceptance of benzodiazepines and benzodiazepine-like short-acting drugs for several weeks may be accompanied by a decrease in the hypnotic effect. Acceptance of benzodiazepines and benzodiazepine drugs can lead to the development of physical and mental dependence, the likelihood of which increases when used in high doses, with long-term therapy, chronic alcoholism and drug dependence in the patient's history. With a formed physical dependence, abrupt withdrawal of the drug leads to the development of withdrawal symptoms: headache, myalgia, pronounced anxiety, heightened tension and irritability, psychomotor agitation, confusion.In severe cases, auto-aggression, depersonalization, hearing loss, paresthesia in the extremities, an increased response to light, sound and physical stimuli, hallucinations and epileptic seizures are possible. After stopping the use of benzodiazepines and benzodiazepine-like drugs, transient and more pronounced symptoms of insomnia (withdrawal syndrome) may appear, and are more pronounced than at the beginning of treatment. At the same time, the development of other related phenomena (mood change, anxiety, sleep disturbance or anxiety) is possible Benzodiazepines and benzodiazepine-like drugs can cause the development of anterograde amnesia and impaired psychomotor functions. In order to avoid the development of these symptoms, the drug should be taken only in the case when the patient has the possibility of continuous sleep, at least within 4 hours after taking the drug. Zaleplon treatment should be stopped in case of appearance of increased excitability, irritability, aggressiveness, perception disorders, nightmares, hallucinations, psychotic disorders, and especially behavioral disorders. Children and elderly patients are most likely to develop these symptoms. The drug is not intended to treat depression and / or anxiety, as can be used to implement suicidal intentions, often accompanying depressive disorders. For patients with depression, the drug can be prescribed in a minimum dose in order to avoid a conscious overdose. It is not recommended to prescribe the drug to patients with severe liver failure due to the risk of encephalopathy. In case of lactose intolerance, it should be noted that the composition of the capsule containing 5 mg of glaplone includes 67 mg of lactose, 10 mg -134 mg. Influence on the ability to drive motor vehicles and control mechanisms During the period of use of the drug, it is necessary to refrain from driving motor vehicles and engaging in activities that require high concentration of attention and speed of psychomotor reactions, because sedation, amnesia, loss of concentration and muscle strength adversely affect the ability to such activities.