Lenuxin

Lenuxin contains the component Escitalopram, which is an antidepressant from the SSRI subgroup, and has a high affinity relative to the primary synthesis site.

In addition, escitalopram is synthesized with the allosteric region of protein transporter synthesis, whose affinity is 1000 times lower. Moreover, the allosteric modulation of this protein potentiates the synthesis of escitalopram within the primary binding zone, due to which a more complete slowdown of the processes of reverse serotonin uptake occurs.

[1]

Indications Lenuksina

It is used in case of episodes of depression of any intensity, and besides with OCD or panic disorders, accompanied by agoraphobia or not.

Release form

The release of drugs is produced in tablets - 14 pieces inside the cell plate (1 or 2 plates in a box) or 14 or 28 pieces inside the bottle.

Pharmacodynamics

Escitalopram has an extremely weak ability to synthesize with some endings (or does not have it at all): 5-HT1A- and 5-НТ2 endings of serotonin, D1- and D2 dopamine endings, α1- with α2-, and also β-adrenergic receptors; Histamine H1 endings, opioid or benzodiazepine endings and m-cholinergic receptors.

Pharmacokinetics

Absorption.

Absorption is almost complete and is not tied to the use of food. The average term for achieving plasma Cmax is 4 hours with reusable use. The absolute bioavailability level of the element is approximately 80%.

Distribution processes.

Values of apparent Vd (Vd, β / F) when consumed inside are in the range of 12-26 l / kg. Synthesis of escitalopram and its main metabolic elements with intraplasma protein is less than 80%. The pharmacokinetics of escitalopram has a linear structure. Css values are observed approximately after 7 days. The average Css level is 50 nmol / l (in the range of 20-125 nmol / l) and is noted when using a daily dose of 10 mg.

Exchange processes.

Escitalopram undergoes intrahepatic metabolism with the formation of demethylated as well as 2-demethylated metabolic elements (they both possess medicinal activity). Nitrogen can participate in the oxidation with the formation of the metabolic component of the N-oxide.

The unchanged element with its metabolites is partially secreted as glucuronides. With repeated administration, the average index of demethyl- and 2-demethylmetabolites often equals, respectively, 28–31% and less than 5% of the level of escitalopram.

The active component is biotransformed into a demethylated metabolic substance mainly with the participation of CYP2C19 isoenzyme; CYP3A4 isoenzymes with CYP2D6 can also be involved in this process.

Excretion.

The term half-life after multiple use of a drug is approximately 30 hours. The level of clearance after ingestion is about 0.6 l / min. The main metabolic components of escitalopram have a longer term half-life.

Escitalopram along with its metabolic elements is excreted with the participation of the liver (metabolic process) and kidneys; mainly excreted through the kidneys in the form of metabolic components.

Dosing and administration

The drug is administered orally, 1 time a day, without reference to food intake.

Episodes with the development of depression.

Often, they use 10 mg of a substance per day, 1-fold. Taking into account the personal response of the patient, the portion can be increased to a maximum daily - 20 mg.

An antidepressant effect often develops after a period of 0.5–1 months since the start of therapy. After the elimination of signs of depression, treatment should be continued for at least six months, in order to consolidate the achieved result.

Panic disorders, which are accompanied by agoraphobia or not.

During the 1st week of therapy, you need to take 5 mg of medication per day; further the portion rises to 10 mg. Portion per day can increase to the maximum allowable (20 mg), taking into account the personal response of the person.

It takes about 3 months to achieve maximum drug exposure. The entire treatment course lasts several months.

Treatment for OCD.

Basically, they take 10 mg per day. An increase to a maximum daily portion of 20 mg is possible (taking into account the personal response of the person being treated).

Because OCD has a chronic course, the therapeutic cycle must be long (at least six months) in order to completely eliminate all signs of the disease. To prevent the occurrence of relapses, therapy should be carried out for at least 12 months.

Older people (over 65 years) need to apply half the standard dosage - 5 mg per day. The maximum allowable daily dosage for this category of treatment is 10 mg.

In case of insufficiency of the liver, it is necessary to use 5 mg per day for the first 14 days of therapy. Given the personal response of the patient, the portion is allowed to increase to 10 mg.

With a reduced activity of CYP2C19 isoenzyme, in the first 14 days of therapy, 5 mg of the drug should be administered per day, and then, given the patient's tolerance of the drug, you can increase the dosage to 10 mg.

Cancellation of therapy is required by gradual reduction of the dosage for 7-14 days. This is necessary to prevent the development of withdrawal syndrome.

[3]

Use Lenuksina during pregnancy

Pregnancy.

There is limited information regarding the use of escitalopram during pregnancy. Preclinical drug tests have shown that it has reproductive toxicity.

The drug is used in the specified period only with strict indications and after careful assessment of all risks and benefits of its use.

When using escitalopram at a late stage of pregnancy (especially in the 3rd trimester), after the birth of the child, his condition should be carefully monitored. With the introduction of drugs before the birth or its cancellation shortly before them, the baby may experience signs of the syndrome of "cancellation."

In case of introduction of a SIOZS / SIOZSN to a woman at a late stage of gestation, the infant may experience the following negative signs: cyanosis, convulsive disorders, respiratory depression, vomiting, apnea, sudden changes in temperature and hypoglycemia. In addition, there are problems with breastfeeding, hyperreflexion, lethargy, hypertonia, drowsiness, muscle hypotension, tremor, as well as sleep problems, increased neuronal reflex excitability, incessant crying and irritability. These manifestations may develop due to withdrawal syndrome or serotonergic effects. Usually such complications appear after 24 hours after birth.

Information obtained during epidemiological testing suggests that using SSRIs during pregnancy (especially in the later stages) may increase the likelihood of sustained lung hypertension in the newborn.

Lactation period.

It is believed that escitalopram can be eliminated with mother's milk, which is why breastfeeding is prohibited during its use.

Contraindications

The main contraindications:

• severe intolerance associated with escitalopram and other elements of the drug;
• prolongation of QT-interval values, available in history (among them, prolonged QT-interval syndrome of a congenital character);
• combined use with irreversible non-selective substances of MAOI, and also with reversible MAOI, MAO-A (such as moclobemide) or non-selective reversible MAOI (linezolid);
• combination with drugs that can prolong the QT-gap (for example, antiarrhythmic substances of categories IA and III, macrolides and tricyclics);
• administration with pimozide;
• glucose-galactose malabsorption, hypolactasia and lactase deficiency.

Caution is required when used for such disorders:

• severe degree of kidney failure (the level of QC below 30 ml per minute);
• mania or hypomania;
• epilepsy, which cannot be controlled by medication;
• behavior with a pronounced suicidal tendency;
• diabetes;
• ECT procedures;
• elderly people (over 65 years);
• tendency to develop bleeding;
• hepatic cirrhosis;
• combined use with substances that weaken the convulsive threshold, IMAO-B (among them selegilin), lithium, serotonergic drugs, medicines, which include common St. John's wort, and in addition with tryptophan, means acting on blood circulation, taken by anticoagulants, drugs, provoking hyponatremia, as well as with ethyl alcohol and drugs, whose metabolism proceeds with the participation of CYP2C19 isoenzyme.

Side effects Lenuksina

Negative manifestations often develop during the 1st or 2nd week of therapy, after which their intensity and frequency decrease. Among the side effects:

• damage to the hematopoietic system: possible development of thrombocytopenia;
• immune disorders: occasionally anaphylactic symptoms occur;
• problems with the work of the endocrine system: there may be a decrease in the release of ADH;
• metabolic disorders: weight gain and appetite are often increased or weakened. Sometimes the weight of the patient is reduced. Anorexia or hyponatremia may develop;
• mental problems: anxiety, anorgasmia (women), strange dreams, anxiety and weakened libido are often observed. Sometimes there is nervousness, confusion, agitation, bruxism and panic attacks. Occasionally, hallucinations, aggression or depersonalization appear. Perhaps the development of thoughts of suicide and appropriate behavior, as well as mania. Behavior and thoughts related to suicide are observed when using escitalopram, as well as immediately after its abolition. The discontinuation of drugs from the SSRIs / SSRIs (especially too sharp) often causes signs of cancellation. Mainly, there is a sensitivity disorder (feeling of passing through or paresthesia), dizziness, sleep problems (intense dreams or insomnia), anxiety or agitation, tremor, hyperhidrosis, vomiting or nausea, and in addition, headaches, confusion, heartbeat, visual disturbances, diarrhea, irritability and emotional lability. Typically, these signs have a weak or moderate intensity and quickly disappear. But in some people may have a stronger severity or increased duration. Therefore, it is necessary to cancel the medication, gradually lowering its dosage;
• violations associated with the work of the National Assembly: mainly there are headaches. Also, drowsiness or insomnia, paresthesia, dizziness and tremor are often noted. Sometimes there are disorders of sleep or taste and fainting. Occasionally serotonin intoxication develops. The appearance of convulsive disorders, movement disorders, dyskinesias, akathisia, or psychomotor agitation is possible;
• visual disorders: vision problems or mydriasis are sometimes noted;
• lesions affecting the labyrinth and the auditory system: tinnitus sometimes appears;
• problems arising from the cardiovascular system: tachycardia is sometimes noted. Occasionally, bradycardia develops. The appearance of an orthostatic collapse or prolongation of the QT-gap on the ECG may occur. Changes in the values of the QT-interval is usually observed in individuals who have a history of diseases associated with cardiovascular disease;
• impaired respiratory function: yawning or sinusitis often occurs. Sometimes there is a nosebleed;
• digestive disorders: nausea usually occurs. Quite often there is dryness of the oral mucous membranes, diarrhea, constipation or vomiting. Sometimes bleeding inside the digestive tract (also rectal) develops;
• lesions affecting the gallstones and liver: possible change in functional intrahepatic indications or the appearance of hepatitis;
• infection of the subcutaneous layer and the epidermis: hyperhidrosis is often noted. Sometimes there is alopecia, pruritus, urticaria, or rash. Perhaps the occurrence of angioedema or ecchymosis;
• dysfunction of the musculoskeletal structure: often myalgia or arthralgia. In people over the age of 50, the use of tricyclics and SSRIs leads to an increased likelihood of fractures;
• disorders of the breast and reproductive system: often impotence or ejaculation disorder occurs. Sometimes there is menorrhagia or metrorrhagia. Perhaps the development of priapism or galactorrhea;
• problems associated with urination: possible delay of the process of urination;
• systemic signs: often marked hyperthermia or weakness. Sometimes puffiness appears.

[2]

Overdose

There is only limited information regarding escitalopram poisoning. Often, overdose symptoms are absent or have a weak intensity. The introduction of the drug in portions of 0.4-0.8 g during monotherapy did not cause clinically significant manifestations of intoxication.

Manifestations are usually associated with the central nervous system function (starting with tremor and dizziness with agitation, and ending with convulsive disorders, serotonin intoxication and coma), gastrointestinal tract (vomiting or nausea), cardiovascular disease (tachycardia, arrhythmia, decrease in blood pressure and prolongation of QT-interval) salt balance disorder (hyponatremia or -caliemia).

Lenuxin does not have an antidote. Symptomatic and supportive actions are required. It is necessary to provide free passability of the respiratory tract, as well as pulmonary ventilation and oxygenation. In addition, gastric lavage and the use of activated carbon. The stomach must be washed as quickly as possible after poisoning. It is also required to monitor cardiac function and the work of other vital systems.

Interactions with other drugs

Drug interaction.

Irreversible indiscriminate IMAO.

There is evidence of the occurrence of severe negative symptoms when SSRIs are combined with irreversible non-selective MAOIs, and, moreover, when starting therapy with the introduction of MAOIs to individuals who have recently stopped using SSRIs. Occasionally, patients experienced a serotonin intoxication.

Escitalopram cannot be used together with irreversible non-selective MAOIs. You can start the introduction of the first after 2 weeks from the moment of cancellation of the second. A minimum of 7 days should also pass from the moment of termination of the use of escitalopram before the start of the use of MAOI

Electoral reversible IMAO-A (substance moclobemide).

Due to the high probability of serotonin intoxication, the combined use of Lenuxin with moclobemide is prohibited. With the clinical need to use such a combination, treatment should begin with the minimum allowable portions, and at the same time constantly monitor the patient's condition.

It is possible to enter escitalopram after at least 1 day from the moment of cessation of use of moclobemide.

Indiscriminate reversible drug MAOI (substance linezolid).

Linezolid is forbidden to use in persons who take escitalopram. If there is a strict need to use this combination, you need to use minimal portions and carefully monitor the patient's condition.

Irreversible IMAO-B (substance selegilin).

To prevent the possibility of serotonin intoxication, it is necessary to carefully combine Lenuxin with MAOI-B selegilinom.

Medicines prolonging the QT-interval indicators.

Pharmacokinetics and drug dynamics tests in combination with other substances prolonging the QT-interval were not performed. We can expect the development of additive effects with the introduction of such a combination of drugs. Because of this, the drug is not administered together with tricyclics, antiarrhythmic substances of IA and Class 3, separate antihistamine drugs (mizolastine or astemizole), neuroleptics (for example, phenothiazine derivatives, haloperidol or pimozide), as well as with individual antimicrobial drugs (among pentamidine, sparfloxacin, erythromycin for IV injection, and besides, moxifloxacin and antimalarial substances, especially halofantrine).

Serotonergic medicines.

Administration with agents such as sumatriptan or other triptans, as well as tramadol, can cause the appearance of serotonin intoxication.

Medications that weaken the convulsive threshold.

SSRIs can weaken the convulsive threshold, so it is necessary to carefully combine the drug with other substances with similar effects (with thioxanthene, tramadol, tricyclics, mefloquine, and besides with antipsychotics (phenothiazine derivatives), bupropion or butyrophenone).

Tryptophan and lithium substances.

The combined use of the drug with tryptophan or lithium leads to a potentiation of Lenuxin activity.

Common Hypericum (Hypericum perforatum).

Combination of medication with substances of Hypericum can cause an increase in the number of negative symptoms.

Anticoagulants and other medications that affect blood coagulation.

Combining the drug with ingested anticoagulants and other elements that alter blood circulation (among these are most tricyclics, atypical neuroleptics, and phenothiazine derivatives, NSAIDs with aspirin, dipyridamole, and ticlopidine) can lead to disorders of this process.

With such combinations, in the period of beginning or end of treatment with the introduction of escitalopram, it is required to constantly monitor blood coagulation. Combination with NSAIDs may increase the frequency of bleeding.

Drugs that cause hypomagnesemia or -kalemia.

It is necessary to carefully combine Lenuxin with the above-mentioned substances, because such disorders increase the likelihood of malignant arrhythmias.

Ethanol.

Although escitalopram does not interact with ethyl alcohol, as in the situation with other psychotropic drugs, it is not necessary to combine medicine and alcoholic beverages.

Pharmacokinetic activity.

The effects of other medicines on the pharmacokinetic characteristics of the drug.

The exchange processes of escitalopram are mostly realized with CYP2C19 isoenzyme. CYP3A4 isoenzymes with CYP2D6 are less active in these processes. The exchange process of the main metabolic element (demethylated escitalopram) seems to be partially catalyzed by CYP2D6 isoenzyme.

Drug administration along with esomeprazole (slows down the activity of CYP2C19 isoenzyme) causes a moderate (approximately 50%) increase in plasma values of the first.

Use in combination with cimetidine (slows down the action of CYP2D6 isoenzymes with CYP3A4, as well as CYP1A2) in a portion of 0.4 g 2-fold per day causes an increase in plasma level of escitalopram (approximately 70%).

Therefore, it is necessary to very carefully combine the maximum allowable dosages of Lenuxin and agents that slow down the effect of CYP2C19 isoenzyme (for example, fluoxetine, ticlopidine and omeprazole with fluvoxamine, and in addition, esomeprozole and lansoprazole), as well as cimetidine. The introduction of the drug together with the above substances may require a reduction in the dosage of escitalopram after evaluation of the clinical picture.

The effect exerted by escitalopram on the pharmacokinetic parameters of other drugs.

Escitalopram slows down the effect of CYP2D6 isoenzyme. It is necessary to very carefully combine it with drugs, whose metabolic processes are carried out with the participation of this isoenzyme, and whose drug index is very low. Among them is propafenone with flekainid and metoprolol (use in CH).

Also carefully combined with drugs, the exchange process which is mainly implemented under the action of CYP2D6 isoenzyme, and which affect the function of the central nervous system. Among them are neuroleptics (thioridazine, risperidone and haloperidol) and antidepressants (clomipramine and desipramine with nortriptyline). With such combinations, you may need to change portions.

The introduction of Lenuksin with metoprolol or desipramine causes the latter to double.

Escitalopram is capable of slightly slowing down the effects of CYP2C19 isoenzyme. Because of this, you need to carefully combine it with substances whose metabolic processes are associated with the component CYP2C19.

[4], [5]

Storage conditions

Lenuksin is required to be kept in a dark and closed place from small children. Temperature indicators for vials - no more than 30 ° С, and for cell plates - no more than 25 ° С.

Shelf life

Lenuxin can be used within a 24-month term from the time a drug product is sold.

Application for children

Lenuksin should not be administered to persons under the age of 18 (because there is no information regarding the safety of its action and drug efficacy).

Analogs

Analogs of drugs are means Miracitol, Cipralex with Sancipam, Elycea and Selectra with Escitalopram.

Reviews

Lenuxin receives rather ambiguous reviews. Some patients indicate that the drug helps well, while others argue that it is completely ineffective.

In the positive reviews regarding this medication, it is noted that it quickly removes anxiety and improves well-being with mood. In addition, the comments state that when using drugs in the indicated dosages, it was possible to get rid of depression, social phobia and panic. At the same time, this effect persisted even after the cessation of Lenuxin intake.

Negative comments indicate that the drug causes the appearance of side symptoms. Individuals developed headaches, someone had nausea, etc. In addition, there are messages from people whom the drug did not help at all.