2010/09/20

Andante

Composition, structure and packing

Hard gelatin capsules with opaque blue cap and light blue opaque body, the contents of capsules - powder light blue with a grayish tint.

1 capsule. zaleplon 5 mg.

Excipients: starlak (a mixture of lactose and corn starch), microcrystalline cellulose, magnesium stearate, indigo, titanium dioxide, sodium lauryl sulfate, colloidal silicon dioxide.

The composition of the shell capsules: indigo, titanium dioxide, gelatin. Hard gelatin capsules with opaque blue cap and blue opaque body, the contents of capsules - powder light blue with a grayish tint.

1 capsule. zaleplon 10 mg.

Excipients: starlak (a mixture of lactose and corn starch), microcrystalline cellulose, magnesium stearate, indigo, titanium dioxide, sodium lauryl sulfate, colloidal silicon dioxide.

The composition of the shell capsules: indigo, titanium dioxide, gelatin.

Clinico-pharmacological group: sleeping pills.

Pharmacological action

Sleeping pills pyrazolo-pyrimidine type, the chemical structure differs from the benzodiazepines and other hypnotics. Selectively binds to benzodiazepine receptors type 1 (ω-1). Significantly reduces the latency time of falling asleep, prolongs sleep (in the first half of the night), does not cause changes in the ratio of the 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, has sedative, slightly pronounced anxiolytic, anticonvulsant and central miorelaksiruyuschee action. Excited benzodiazepine receptor (ω) GABA receptor complexes of type A.

Interaction with ω-receptors leads to the discovery of neuronal ionoformnyh channels for chloride ions, the development of hyperpolarization and increase of inhibitory processes in the CNS.

Pharmacokinetics

Absorption

Once inside quickly and almost completely (about 71%) absorbed from the gastrointestinal tract, Cmax in the blood is achieved after 1 h. As a result presistemnogo metabolism absolute bioavailability of 30%. Plasma concentration is directly proportional to the dose. Acceptance of the drug immediately after a meal may, at 2 h delay the time to reach Cmax, without affecting the absorbability of the drug. Distribution is fat-soluble compound. Vd after i / v administration of 1.4 ± 0.3 L / kg. Plasma protein binding of about 60% (the probability of interaction with other drugs is very low). Provided with breast milk.

Metabolism

In the primary metabolism involved aldegidoksidaza and leads to the formation of 5-oksozaleplona. CYP3A4 is also involved in the metabolism zaleplona with the formation dezetil-zaleplona, which in turn, with the help aldegidoksidazy transformed into 5-oxo-dezetil-zaleplon. Further oxidation products are subjected to conjugation with glucuronic acid. All metabolites are inactive. When used in doses of 30 mg / day accumulation is not observed. T1 / 2 zaleplona - about 1 h.

Withdrawal

Outputs in the form of inactive metabolites mainly in urine (71%) and feces (17%). Up to 57% of applied dose found in urine in the form of 5-oksozaleplona or its metabolite, 9% of the dose - in the form of 5-oxo-dezetil zaleplona or its metabolites, the remainder of the dose - as less important metabolites. Among the metabolites that are derived through the intestine, the prevailing 5-oksozaleplon. Rapidly excreted from the body.

Pharmacokinetics in special clinical situations

Pharmacokinetics in elderly patients (including older than 75 years) is not significantly different from that of younger persons. Zaleplona pharmacokinetics in patients with renal failure is not significantly different from that of healthy, although the level of inactive metabolites is higher. Indications - severe sleep disturbances (difficulty falling asleep), leading to excessive fatigue, hindering daily activities and reduce efficiency.

Dosage regimen

Duration of therapy should not exceed 2 weeks. The drug, taken orally immediately before bedtime, after 2 hours after meals or after the patient feels that he can not sleep. The recommended dose for adults - 10 mg. The maximum daily dose of 10 mg (patients should be alert about the dangers of taking repeated doses in one night). Elderly drug administered in a dose of 5 mg (for greater sensitivity to the soporific).

When liver failure light and moderate daily dose is 5 mg (due to delayed removal from the body).

In renal insufficiency, mild and moderate dose adjustment is required. Data on the safety of the drug in renal failure severe absent. Safety of the drug in children under the age of 18 is not installed, so the patients in this age group, zaleplon is not indicated.

Side effect

On the part of the digestive system: stomach pain, nausea, vomiting, diarrhea.

From the side of the central nervous system and peripheral nervous system: the most common - headache, fatigue, increased sleepiness, dizziness, anterograde amnesia (accompanied by a breach of conduct), depression, paradoxical and mental reactions (mostly elderly patients): anxiety, irritability, aggressiveness, paresthesia, rage, nightmares, hallucinations, psychosis, behavioral disorders, the development of physical dependence with withdrawal symptoms, even when used in therapeutic doses (the appearance of initial symptoms of sleep disturbance in a more severe form, as well as changes in mood, anxiety, agitation), withdrawal syndrome (headache, myalgia, irritability, confusion), the development of psychological dependence, leading to drug abuse, ataxia, tremor, irritability, violations of perception. In severe cases: autoaggression, depersonalization, hearing loss, increased reaction to visual, auditory and physical stimuli, seizures. Allergic reactions: skin rash, itching.

Contraindications
severe hepatic impairment;
sleep apnea syndrome;
severe pulmonary insufficiency;
severe myasthenia gravis;
Pregnancy
lactation;
children's age (18 years);
Hypersensitivity to any component of the drug.

With caution is prescribed for chronic obstructive pulmonary disease, hepatic and / or renal failure, chronic alcoholism, drug dependence (including history), and depression.

Pregnancy and lactation

The drug is contraindicated during pregnancy and lactation (breastfeeding). In the appointment of the drug to women of childbearing age should warn patients about the need for immediate treatment to the doctor in case of conception or when planning pregnancy.

In the case of zaleplona in the III trimester of pregnancy or use of the drug at high doses of the drug during delivery of the newborn may develop hypothermia, muscular hypotonia, mild respiratory insufficiency resulting from the pharmacological action of the drug. Babies whose mothers regularly took benzodiazepines or benzodiazepinopodobny drug in the last weeks of pregnancy may develop physical dependence and the risk of withdrawal symptoms.

Application for violations of liver function

When liver failure light and moderate daily dose is 5 mg (due to delayed removal from the body). Contraindicated in severe liver failure due to the risk of encephalopathy

Application for violations of renal function

In renal insufficiency, mild and moderate dose adjustment is required. Data on the safety of the drug with severe renal insufficiency are absent. Cautions Patients must notify that the drug is not intended for long-term therapy and the possibility of withdrawal symptoms after the drug Andante. The course is taking the drug should be short and in no case exceed 2 weeks. To extend the treatment is possible only after a thorough clinical examination of the patient.

The drug can be considered in patients older (including older than 75 years). Sleep disturbance may be the result of disease (including mental health). If, after a brief use of the drug Andante sleep is normal, or sleep disturbance progresses, you should re-evaluate the clinical situation. If the patient wakes up shortly after midnight (because of the short T1 / 2 zaleplona) may require the appointment of another drug with a longer T1 / 2.

It should warn patients about the need for no more than 1 tab. overnight. Acceptance of benzodiazepines and short-acting drugs benzodiazepinopodobnyh within a few weeks may be accompanied by lower soporific effect. Acceptance of benzodiazepines and benzodiazepinopodobnyh drugs may lead to the development of physical and psychic dependence, the probability of which increases with the use of high-dose, prolonged therapy, chronic alcoholism and drug addiction in the history of the patient.

When formed of physical dependence abrupt withdrawal of the drug leads to development of withdrawal symptoms: headache, myalgia, a pronounced anxiety, increased tension and irritability, psychomotor agitation, confusion. In severe cases, possible autoaggression, depersonalization, hearing loss, paresthesia in the extremities, increased reaction to visual, auditory and physical stimuli, hallucinations and seizures.

After the cessation of the use of benzodiazepines and benzodiazepinopodobnyh drug may cause transient and more pronounced than at the beginning of treatment, symptoms of insomnia (withdrawal symptoms). It is possible to develop other related phenomena (change of mood, anxiety, sleep disorders or anxiety). Benzodiazepines and benzodiazepinopodobnye drugs can cause the development of anterograde amnesia and a violation of psychomotor functions. In order to avoid the development of these symptoms the drug should be taken only when the patient can sleep uninterrupted, at least within 4 h after administration of the drug.

Zaleplonom Treatment should be discontinued in case of increased excitability, irritability, aggressiveness, disorders of perception, nightmares, hallucinations, psychotic disorders, particularly behavioral disorders.

Children and elderly patients are more likely to develop such symptoms. The product is not intended to treat depression and / or anxiety, because can be used for the implementation of suicidal intent, often accompany depressive disorders. Patients with depression drug can be given a minimum dose to avoid deliberate overdose. Do not appoint a drug to patients with severe hepatic insufficiency due to the risk of encephalopathy. If lactose intolerance should be noted that in the tablet containing 5 mg zaleplona, comprises 67 mg of lactose, 10 mg -134 mg. Effects on ability to drive vehicles and management mechanism during use of the drug should refrain from driving motor vehicles, and training activities that require high concentration and quickness of psychomotor reactions, because sedative effect, amnesia, reduced concentration and muscle strength may adversely affect the ability to engage in such activities.

Overdose

Data on acute drug overdose a bit. Zaleplona concentration in the blood of an overdose was not measured. Like other benzodiazepines and benzodiazepinopodobnym drug overdose does not cause life-threatening conditions, when zaleplon was not taken in combination with other drugs, depressant drug (including ethanol). In case of overdose should never forget about the possibility of combined poisoning.

Symptoms: symptoms of CNS depression, manifested in sleepiness until coma. In case of overdose mild - drowsiness, confusion, lethargy, in more severe cases - ataxia, decrease blood pressure, respiratory failure, rarely coma (in very rare cases, fatal).

Treatment: According to preclinical studies flumazenil is an antagonist zaleplona, although clinical studies did not confirm the efficacy of flumazenil in overdose Andante. Flumazenil can be used as an antidote.

If the patient is conscious, then during the first hour after taking the drug should induce vomiting. If the patient is unconscious, then carry out gastric lavage, activated charcoal designate. Monitoring of cardiac and respiratory activity conducted in the intensive care unit.

Drug Interactions

Simultaneous reception of ethanol or etanolsoderzhaschih drugs increases sedative effect zaleplona.

The simultaneous use of antipsychotic (neuroleptics), other hypnotics, anxiolytic, sedative, antidepressant, antiepileptic, antihistamine drugs, means for anesthesia, opioid analgesics leads to increased sedative effect zaleplona. With the simultaneous use of opioid analgesics may be a manifestation of euphoric effect of the latter, leading to the development of drug dependence.

With simultaneous application of cimetidine (an inhibitor of aldegidoksidazy and CYP3A4) increases the concentration of zaleplona in plasma by 85%. With simultaneous application of selective inhibitors of CYP3A4 (ketoconazole, erythromycin) increase the concentration of zaleplona in plasma and enhance its sedative effect (when using this combination can sometimes require dosage adjustment zaleplona).

With simultaneous application of inducers of CYP3A4 (rifampicin, carbamazepine, phenobarbital derivatives) may reduce the effectiveness of zaleplona by 25%. With simultaneous use of zaleplon did not affect the pharmacodynamics and pharmacokinetics of digoxin and warfarin (dosage adjustment of these drugs is not required). Interactions of ibuprofen with zaleplonom not revealed.

Terms and Conditions of storage

The drug should be stored in their original packaging away from children at a temperature of 15 ° to 30 ° C. Shelf life - 2 years.