Валокордин®-Доксиламин

General characteristics. Structure:

Active ingredient: 2,5 g of a doksilamin of succinate.

Excipients: ethanol of 96%, the water purified oil mint.

Pharmacological properties:

Pharmacodynamics. Doksilamina succinate is an antihistaminic drug (derivative monoethanol amine) with sedative properties. Antihistaminic drugs which are also called antagonists of H1 receptors are well-known the fact that they have the calming effect on the person. Doksilamin weakens many effects of an endogenous histamine, blocking H1 receptors. The oppressing action on TsNS most likely is caused by its high affinity to H1-retseptoramv a brain.

Doksilamina succinate, thanks to its sedative properties, is used for short-term treatment of sleep disorders. Doksilamina succinate improves a dream, duration of backfilling decreases, and duration of a dream increases.

Many antagonists of H1 receptors inhibit action of acetylcholine on muskarinovy receptors. Anticholinergic properties do not play a role in efficiency of a doksilamin.

Pharmacokinetics. After intake доксиламин it is quickly and almost completely soaked up. Effect of drug begins to be shown within 30 minutes, the maximum concentration in blood serum of 99 ng/ml is found in 2,4 hours after oral administration of a dose of 25 mg. Duration of action makes from 3rd to 6 hours.

Doksilamin is metabolized preferential in a liver. N-desmetil доксиламин, by N, N-didesmetil доксиламин and their N-atsetilkonjyugaty were found. The elimination half-life of initial connection fluctuates in limits ot10,1 till 12 o'clock. The most part of the accepted dose (apprx. 60%) is removed the extra changed view with urine, and the rest eliminirutsya in various metabolic ways.

Indications to use:

Symptomatic treatment of periodic sleep disorders (disturbances of backfilling and maintenance of a dream) at adults.

Route of administration and doses:

For intake. If the doctor did not appoint differently, the single dose of the drug Valokordin®-Doksilamin for adults makes 22 drops (that sootvetstvuyet25 mg of a doksilamin of succinate). At persistent sleep disorders, the patient can accept up to 44 drops of Valokordina®-Doksilamina (50 mg of a doksilamin of succinate) – the maximum dose. It is not necessary to exceed the maximum daily dose.

To patients with disturbances of functions of kidneys or a liver, the elderly and weakened patients who can be more sensitive to action of a doksilamin it is necessary to reduce a drug dose.

Drops should be accepted with enough liquid (water) in ½ hours – 1 hour of a dosn. After administration of drug Valokordin®-Doksilamin it is important to provide the necessary duration of a dream that will allow to avoid decrease in speed of reaction in the morning. At acute disorders of a dream it is necessary to be limited to single doses.

Not later than in 14 days after the beginning of daily use it is necessary to begin to reduce a drug dose gradually.

Features of use:

Not all frustration of a dream demand medicamentous therapy. Often frustration of a dream are connected with an aggravation of symptoms of health or mental derangements and can be eliminated in other ways or treatment of a basic disease. It is not necessary to carry out prolonged treatment of chronic sleep disorders (including disturbances of backfilling and maintenance of a dream) by the drug Valokordin®-Doksilamin without consultation of the doctor.

Валокордин®-Доксиламин it is necessary to apply with care at:
- abnormal liver functions
- heart failure and hypertension
- to a chronic asthma and asthma
- gastroesophageal (gastroesophagal) reflux
- pylorostenosis
- cardia achalasias

Валокордин®-Доксиламин patients need to apply with extra care with focal damages of a cerebral cortex or convulsive attacks in the anamnesis as even small doses of drug can provoke toniko-clonic epileptic attacks.

It is necessary to take into account that even rather low doses of a doksilamin of succinate can provoke spasms at patients with organic lesions of a brain and spasms in the anamnesis. It is recommended to carry out EEG (electroencephalography). Anticonvulsant therapy should not be interrupted during drug Valokordin®-Doksilamin use.

During treatment antihistaminic drugs recommend to carry out regular control of function of heart as there are messages on changes of an ECG, in particular changes of a phase of repolarization. It is especially important for patients of advanced age and patients with heart failure. Extra care needs to be shown at treatment of patients with arterial hypertension as antihistaminic drugs can increase blood pressure.

Sharp drug withdrawal after prolonged use can lead to aggravation of sleep disorders.

At use of a doksilamin of succinate, as well as at use of other hypnagogues, physical and mental dependence can develop. The risk of emergence of dependence increases with increase in a dose and increase in duration of treatment above at patients with alcohol, medicinal or drug addiction in the anamnesis.

The sharp termination of reception of a doksilamin of succinate even of a postshort course of treatment can be followed by temporary sleep disorders. Therefore it is recommended to complete, in case of need, treatment, gradually reducing a dose.

Валокордин®-Доксиламин do not appoint to children and teenagers.

Валокордин®-Доксиламин contains 55 about. % of ethanol (alcohol). What makes to 0,9 g of alcohol in one dose of drug (there correspond 21,87 ml of beer or 9,11 ml of wine). Drug can be dangerous to the people having alcoholism. Content of alcohol should be taken into account to pregnant women and the feeding women, children, patients from risk groups, for example, with diseases of a liver or epilepsy.

Pregnancy and lactation. Валокордин®-Доксиламин during pregnancy it is necessary to apply only when the estimated advantage exceeds possible risk. As active ingredient gets into breast milk, feeding by a breast during treatment has to be stopped.

Features of influence of medicine on ability to manage the vehicle or potentially dangerous mechanisms. Drug can exert negative impact on speed of reaction, ability to drive the car and to work with mechanisms. In particular at the simultaneous use of medicine and alcohol. Therefore it is necessary to avoid driving of the car, work with mechanisms and other potentially dangerous types of activity, at least, during the first phase of treatment.

Side effects:

Frequency of emergence of side reactions is estimated as follows:
very often (³ 1/10)
often (³ 1/100 to <1/10)
infrequently (³ 1/1.000 to <1/100)
seldom (³ 1/10.000 to <1/1.000)
very seldom (<1/10.000),
it is unknown (frequency cannot be established on the basis of the available data)

From hemopoietic and lymphatic system: in exceptional cases after use of antihistaminic drugs changes of a picture of blood can take place: leukopenia, thrombocytopenia and hemolitic anemia. Aplastic anemia and an agranulocytosis were seldom or never observed.

From endocrine system: at patients with a pheochromocytoma reception of antihistaminic drugs can lead to increase in emission of catecholamines.

Mental disorders: treat the side effects depending on an individual chuvstvitelnostiya of the accepted dose: the slowed-down reaction, concentration disturbance, a depression. Besides, development of so-called "paradoxical" reactions (concern, excitement, tension, sleeplessness, nightmares, confusion of consciousness, a hallucination, a tremor) is possible.

Sharp drug withdrawal after prolonged use can lead to aggravation of sleep disorders.

Dependence. At use of a doksilamin of succinate, as well as at use of other hypnagogues, physical and mental dependence can develop. The risk of emergence of dependence increases with increase in a dose and increase in duration of treatment above at patients with alcohol, medicinal or drug addiction in the anamnesis.

Rebound-sleeplessness (strengthening of initial symptoms). The sharp termination of reception of a doksilamin of succinate even after a short course of treatment can be followed by temporary sleep disorders. Therefore it is recommended to complete, in case of need, treatment, gradually reducing a dose.

Ecmnesia. Hypnagogues even in therapeutic doses can cause an ecmnesia, especially during the first hours after reception. The risk increases with increase in a dose, however can be reduced thanks to a long and continuous dream (7-8 hours).

From a nervous system: dizziness, headache, drowsiness. Cerebral spasms are in rare instances possible.

From organs of sight: disorder of accommodation, increase in intraocular pressure.

From an ear and ear labyrinth: sonitus.

From cardiovascular system: tachycardia, disturbance of a cordial rhythm, hypotension, gipertenziya dekompensirovanny heart failure. Changes of an ECG were in certain cases observed.

From respiratory tracts, bodies of a thorax of an isredosteniye: the secret condensation, a bronkhoobstruktion and a bronchospasm can lead to dysfunction of lungs.

From digestive tract: vegetative side effects can be shown: dryness vorta, lock, nausea, vomiting, diarrhea, loss or increase in appetite, epigastric pains; seldom or never - life-threatening paralytic intestinal impassability.

From a liver and gall bladder: there are messages on abnormal liver functions (cholestatic jaundice) against the background of antihistaminic therapy.

From skin and hypodermic cellulose: there are data on allergic skin reactions, fotosensibilizatsiiya disturbance of thermal control during treatment by antihistaminic drugs.

From skeletal muscles and connecting fabric: muscular weakness.

From kidneys and urinary tract: disturbance of an urination.

The general frustration and reactions in a drug injection site: feeling of a congestion of a nose, weariness, weakness.

Accustoming development: long reception sedative and (or) hypnagogues of a mozhetprivesta to efficiency loss - tolerance.

Note: careful individual selection of a dosage allows to reduce the frequency and expressiveness of side reactions. The probability of emergence of side effects at elderly patients is higher. At this group of patients the risk of a loss of consciousness (faint) is also increased.

Interaction with other medicines:

Use of Valokordina®-Doksilamina along with medicines the oppressing TsNS (for example, neuroleptics, tranquilizers, antidepressants, hypnagogues, analgetics, anesthetics, antiepileptic means) can strengthen effect of these drugs. It is necessary to be careful at a combination to Procarbazinum or other antihistaminic drugs because of possible mutual strengthening of the oppressing action on TsNS. During treatment by the drug Valokordin®-Doksilamin it is not necessary to take alcohol as alcohol can it is unpredictable to strengthen action of a doksilamin of succinate.

Results of an experiment on mice show dozozavisimy increase in enzymatic activity of P450 (CYP450) cytochrome in a liver. Use of a doksilamin led to considerable induction of CYP2B enzymes and moderate induction of CYP3A and CYP2A. It is impossible to exclude interactions with medicines which are metabolized with the participation of these Cypfermentov (for example, antiarrhytmic means, protease inhibitors, neuroleptics, beta adrenoblockers, immunodepressants, antiepileptic means).

The anticholinergic effect of a doksilamin of succinate can be unpredictable is increased and prolonged at a concomitant use with other medicines possessing anticholinergic action (for example, atropine, Biperidinum, tricyclic antidepressants). Doksilamin succinate cannot be combined with monoamine oxidase inhibitors. Anticholinergic action of a doksilamin of succinate at a concomitant use with monoamine oxidase inhibitors can amplify that can be shown by life-threatening paralytic intestinal impassability, a delay of an urination or acute glaucoma, etc. Besides, interaction between doksilaminy and monoamine oxidase inhibitors can lead to hypotension and oppression of the central nervous system. In need of performing short-term therapy, it is necessary to take a small break between two courses of treatment.

At simultaneous use of Valokordina®-Doksilamina with hypotensive drugs of the central action (for example, гуанабенз, a clonidine, alpha Methyldopum) strengthening of sedative action is possible.

(Such kakaminoglikozida, salicylates, diuretics), their concomitant use with antihistaminic drugs can disguise signs of the beginning damage of the inner ear (a sonitus, dizziness, stupefaction) caused by reception of ototoksichny drugs.

After treatment doksilaminy succinate results of skin tests can be false-negative.

The patients accepting доксиламинасукцинат cannot apply Epinephrinum (adrenaline) because in this case Epinephrinum (adrenaline) can strengthen hypotension to treatment of hypotonia. At serious depressed cases it is possible to apply Norepinephrinum (noradrenaline).

The concomitant use of the medicines possessing the photosensitizing action and antihistaminic drugs can lead to strengthening of a photosensitization.

Contraindications:

- hypersensitivity (allergy) to active ingredient or other components of drug
- hypersensitivity (allergy) to antihistaminic drugs
- bad attack of asthma
- закрытоугольнаяг laukoma
- an inborn syndrome of the extended QT interval
- pheochromocytoma
- a prostatauxe with urine outflow disturbance
- ostryeotravleniya alcohol, sedative, soothing or psychotropic drugs (neuroleptics, tranquilizers, antidepressants, lithium drugs)
- epilepsy
- lecheniye monoamine oxidase ngibitor

The patients having bronchial asthma or other respiratory diseases which are characterized by hypersensitivity of respiratory tracts should not apply Valokordin®-Doksilamin because it contains mint oil which inhalation can cause a bronchial spasm.

Overdose:

Intoxication symptoms:
- from drowsiness to a coma, sometimes with nervous excitement and a delirium
- antikholinergicheskiyeeffekta: indistinct sight, acute glaucoma, oppression of a vermicular movement of intestines, urination delay
- cordial сосудистаясистема: hypotension, tachycardia or bradycardia, ventrikulyarny tachyarrhythmia, cardiac standstill
- hypothermia or hyperthermia
- tserebralnyesudorog
- respiratornyeoslozhneniya: cyanosis, respiratory depression, apnoea, aspiration

Cases of development of a rabdomioliz as a result of poisoning doksilaminy are known for succinate. Lee and Lee (2002) reported about a case when as a result of reception by the patient because of persistent sleeplessness of 500 mg of a doksilamin acute pancreatitis and an acute renal failure developed.

The symptomatic treatment is also based on the general principles of treatment of poisonings with the following features:
- at intake of a large amount of drug carry out a gastric lavage or artificially cause vomiting;

- analeptics are contraindicated as because of possible decrease in the convulsive threshold caused by administration of drug Valokordin®-Doksilamin the risk of developing of cerebral spasms increases;

- prigipotoniya because of paradoxical strengthening of action do not appoint the means operating on cardiovascular system as Epinephrinum (adrenaline), and apply means like Norepinephrinum (noradrenaline), for example, slow drop infusion of Norepinephrinum (noradrenaline) or Angiotensinamidum. It is necessary to avoid use of beta-agonists as they can strengthen a vazodilatation at a serious poisoning (a loss of consciousness, cardiac arrhythmia) or emergence of an anticholinergic syndrome in the conditions of an intensive care (control of an ECG) it is possible to apply a physostigmine antidote salicylate;

- at the repeating epileptic attacks appoint anticonvulsant drugs, but, because of the increased risk of respiratory depression, only in that case when there is an opportunity to carry out artificial ventilation of the lungs.

The hemodialysis, haemo filtering and peritoneal dialysis were not studied in overdose cases doksilaminy and can be hardly effective in view of the large volume of distribution. Efficiency of an artificial diuresis is not established.

Storage conditions:

To store at a temperature not above 25 °C. To store in the place, unavailable to children! Period of storage 4 years. The use period after opening of a bottle of 6 months. Not to apply after expiry date!

Issue conditions:

Without recipe

Packaging:

On 20 ml and 50 ml of drug spill in bottles from brown glass, with a vertical dropper from polyethylene and the screwing-up cover from polypropylene.

On one bottle together with the instruction on a medical use in the state and Russian languages place in a cardboard pack.