Lenuxin

Lenuxin contains the component escitalopram, which is an antidepressant from the SSRI subgroup and has a high affinity for the primary site of synthesis.

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

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Indications Lenuxina

It is used in cases of depressive episodes of any intensity, as well as in cases of OCD or panic disorders, with or without agoraphobia.

Release form

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

Pharmacodynamics

Escitalopram has an extremely weak ability to synthesize with some endings (or does not have it at all): 5-HT1A- and 5-HT2 endings of serotonin, D1- and D2 endings of dopamine, α1- with α2-, and β-adrenergic receptors; H1-endings of histamine, opioid or benzodiazepine endings and m-cholinergic receptors.

Pharmacokinetics

Absorption.

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

Distribution processes.

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

Exchange processes.

Escitalopram undergoes intrahepatic metabolism to form demethylated and 2-demethylated metabolic units (both of which have medicinal activity). Nitrogen may be oxidized to form the metabolic component N-oxide.

The unchanged element and its metabolites are partly secreted as glucuronides. With repeated administration, the average level of demethyl and 2-demethyl metabolites is often equal to 28-31% and less than 5% of the escitalopram level, respectively.

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

Excretion.

The half-life after repeated administration of the drug is approximately 30 hours. The clearance rate after oral administration is approximately 0.6 L/minute. The main metabolic components of escitalopram have a longer half-life.

Escitalopram, together with its metabolic components, is excreted via the liver (metabolic process) and kidneys; it is mainly excreted via the kidneys in the form of metabolic components.

Dosing and administration

The medication is taken orally, once a day, without regard to food intake.

Episodes with the development of depression.

Often, 10 mg of the substance is used per day, 1 time. Taking into account the patient's personal reaction, the dose can be increased to the maximum daily dose of 20 mg.

The antidepressant effect often develops after 0.5-1 month from the start of therapy. After eliminating the signs of depression, treatment should be continued for at least another six months - to consolidate the achieved result.

Panic disorders, with or without agoraphobia.

During the first week of therapy, 5 mg of the drug should be taken per day; then the dose is increased to 10 mg. The daily dose can be increased to the maximum permissible (20 mg), taking into account the individual reaction of the person.

It takes approximately 3 months to achieve maximum medicinal effect. The entire course of treatment lasts several months.

Treatment for OCD.

The usual dose is 10 mg per day. It can be increased to a maximum daily dose of 20 mg (depending on the patient's personal response).

Because OCD is chronic, the therapeutic cycle should be long (at least six months) – to completely eliminate all signs of the disease. To prevent relapses, therapy should be carried out for at least 12 months.

Elderly people (over 65 years) should take half the standard dosage – 5 mg per day. The maximum permissible daily dosage for this category of patients is 10 mg.

In case of liver failure, 5 mg should be used per day during the first 14 days of therapy. Taking into account the patient's personal reaction, the dose may be increased to 10 mg.

With reduced activity of the CYP2C19 isoenzyme, 5 mg of the drug per day should be administered during the first 14 days of therapy, and then, taking into account the patient’s tolerance of the drug, the dosage can be increased to 10 mg.

Therapy should be discontinued by gradually reducing the dosage over 7-14 days. This is necessary to prevent the development of withdrawal syndrome.

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Use Lenuxina during pregnancy

Pregnancy.

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

The medication is used during the specified period only under strict indications and after a thorough assessment of all the risks and benefits of its use.

When using escitalopram in late pregnancy (especially in the 3rd trimester), the baby's condition should be closely monitored after birth. If the drug is administered before birth or is discontinued shortly before birth, the baby may experience signs of withdrawal syndrome.

If SSRIs/SNRIs are administered to a woman at a late stage of gestation, the infant may experience the following adverse effects: cyanosis, seizure disorders, respiratory depression, vomiting, apnea, sudden changes in temperature, and hypoglycemia. In addition, problems with breastfeeding, hyperreflexia, lethargy, hypertonicity, drowsiness, muscle hypotonia, tremor, as well as sleep problems, increased neuroreflex excitability, incessant crying, and irritability may occur. These manifestations may develop due to withdrawal syndrome or serotonergic influence. Usually, such complications appear within 24 hours after birth.

Evidence from epidemiological studies suggests that use of SSRIs during pregnancy (especially in the later stages) may increase the risk of developing persistent pulmonary hypertension in the neonate.

Breastfeeding period.

Escitalopram is believed to be excreted in breast milk, which is why breastfeeding is prohibited when using it.

Contraindications

Main contraindications:

• severe intolerance associated with escitalopram and other components of the drug;
• history of prolongation of the QT interval (including congenital prolonged QT syndrome);
• concomitant use with irreversible non-selective MAOIs, as well as with reversible MAOIs, MAO-A (such as moclobemide) or non-selective reversible MAOIs (linezolid);
• combination with medications that can prolong the QT interval (for example, antiarrhythmic drugs of categories IA and III, macrolides and tricyclics);
• administration together with pimozide;
• glucose-galactose malabsorption, hypolactasia and lactase deficiency.

Caution is required when using in cases of the following disorders:

• severe renal failure (creatinine clearance level below 30 ml per minute);
• mania or hypomania;
• epilepsy that cannot be controlled with medication;
• behavior with a pronounced tendency toward suicide;
• diabetes mellitus;
• performing ECT procedures;
• elderly people (over 65 years old);
• tendency to develop bleeding;
• liver cirrhosis;
• combined use with substances that reduce the seizure threshold, MAO-B inhibitors (including selegiline), lithium, serotonergic drugs, medications that contain St. John's wort, as well as with tryptophan, agents that affect blood clotting, orally administered anticoagulants, drugs that provoke hyponatremia, as well as with ethyl alcohol and drugs whose metabolism occurs with the participation of the isoenzyme CYP2C19.

Side effects Lenuxina

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

• damage to the hematopoietic system: thrombocytopenia may develop;
• immune disorders: anaphylactic symptoms occasionally occur;
• problems with the endocrine system: a decrease in the secretion of ADH may be observed;
• Metabolic disorders: weight gain and increased or decreased appetite often occur. Sometimes the patient's weight decreases. Anorexia or hyponatremia may develop;
• Psychiatric problems: anxiety, anorgasmia (women), strange dreams, restlessness, and decreased libido are common. Nervousness, confusion, agitation, bruxism, and panic attacks may occasionally occur. Hallucinations, aggression, or depersonalization may occur. Suicidal thoughts and behavior, as well as mania, may develop. Suicidal thoughts and behavior have been reported with escitalopram and immediately after its withdrawal. Discontinuation of SSRI/SNRI medications (especially if done too abruptly) often causes withdrawal symptoms. These include mainly sensory disturbances (current sensation or paresthesia), dizziness, sleep problems (intense dreams or insomnia), anxiety or agitation, tremor, hyperhidrosis, vomiting or nausea, as well as headaches, confusion, heart palpitations, visual disturbances, diarrhea, irritability and emotional instability. These symptoms are usually mild or moderate in intensity and disappear quickly. However, in some people they may be more severe or last longer. Therefore, the medication should be discontinued by gradually reducing its dosage;
• disorders associated with the functioning of the nervous system: headaches mainly occur. Drowsiness or insomnia, paresthesia, dizziness and tremor are also quite common. Sometimes sleep or taste disorders and fainting are observed. Rarely, serotonin intoxication develops. Convulsive disorders, movement disorders, dyskinesia, akathisia or psychomotor agitation may occur;
• visual disturbances: sometimes problems with vision or mydriasis are observed;
• lesions affecting the labyrinth and auditory system: tinnitus sometimes appears;
• problems arising from the cardiovascular system: tachycardia is sometimes observed. Rarely, bradycardia develops. Orthostatic collapse or prolongation of the QT interval on the ECG is possible. Changes in QT interval values are usually observed in individuals who have a history of cardiovascular diseases;
• respiratory dysfunction: yawning or sinusitis often occur. Sometimes nosebleeds occur;
• digestive disorders: nausea usually occurs. Dryness of the oral mucosa, diarrhea, constipation or vomiting are quite common. Sometimes bleeding inside the gastrointestinal tract (also rectal) develops;
• lesions affecting the biliary tract and liver: possible changes in functional intrahepatic indicators or the development of hepatitis;
• Infections of the subcutaneous layer and epidermis: hyperhidrosis is often observed. Alopecia, itching, urticaria or rashes are sometimes observed. Quincke's edema or ecchymosis may occur;
• disorders of the musculoskeletal system: myalgia or arthralgia often occurs. In people over 50, the use of tricyclics and SSRIs increases the likelihood of fractures;
• disorders of the mammary glands and the reproductive system: impotence or ejaculation disorders often occur. Sometimes menorrhagia or metrorrhagia is observed. Priapism or galactorrhea may develop;
• problems associated with urination: possible delay in urination;
• Systemic symptoms: hyperthermia or weakness are often noted. Sometimes swelling appears.

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Overdose

There is limited information on escitalopram poisoning. Overdose symptoms are often either absent or mild. Administration of 0.4-0.8 g of the drug during monotherapy did not cause clinically significant intoxication.

Manifestations are usually associated with the function of the central nervous system (ranging from tremor and dizziness with agitation to seizure disorders, serotonin intoxication and coma), gastrointestinal tract (vomiting or nausea), cardiovascular system (tachycardia, arrhythmia, decreased blood pressure and prolongation of the QT interval) and salt imbalance (hyponatremia or -kalemia).

Lenuxin has no antidote. Symptomatic and supportive measures are required. It is necessary to ensure free patency of the respiratory tract, as well as pulmonary ventilation and oxygenation. In addition, gastric lavage and activated carbon are used. The stomach must be washed as quickly as possible after poisoning. It is also necessary to monitor cardiac function and the work of other vital systems.

Interactions with other drugs

Drug interactions.

Irreversible non-selective MAOIs.

There are data on the occurrence of severe negative symptoms when combining SSRIs with irreversible non-selective MAOIs, and also when starting therapy with MAOIs in individuals who have recently stopped using SSRIs. Sometimes, patients have noted the occurrence of serotonin intoxication.

Escitalopram should not be used together with irreversible non-selective MAOIs. The first can be started after 2 weeks from the moment of discontinuation of the second. Also, at least 7 days must pass from the moment of discontinuation of escitalopram before starting the use of MAOIs.

Selective reversible MAO-A inhibitors (substance moclobemide).

Due to the high probability of serotonin intoxication, the combined use of Lenuxin with moclobemide is prohibited. If there is a clinical need to use such a combination, treatment should be started with the minimum permissible doses, and at the same time the patient's condition should be constantly monitored.

Escitalopram can be administered after at least 1 day has passed since stopping moclobemide.

Non-selective reversible MAOI drug (linezolid).

Linezolid should not be used in patients taking escitalopram. If there is a strong need to use this combination, the minimum dose should be used and the patient should be closely monitored.

Irreversible MAO-B inhibitor (substance selegiline).

To prevent the possibility of serotonin intoxication, Lenuxin should be combined with the MAO-B selegiline with caution.

Medicines that prolong the QT interval.

Pharmacokinetic and -dynamic tests of the drug in combination with other substances prolonging the QT interval have not been performed. An additive effect can be expected when administering such a combination of drugs. For this reason, the drug is not administered together with tricyclics, class IA and class 3 antiarrhythmic drugs, certain antihistamines (mizolastine or astemizole), neuroleptics (for example, phenothiazine derivatives, haloperidol or pimozide), as well as with certain antimicrobial drugs (including pentamidine, sparfloxacin, erythromycin for intravenous injections, as well as moxifloxacin and antimalarial agents, especially halofantrine).

Serotonergic drugs.

Co-administration with drugs such as sumatriptan or other triptans, as well as tramadol, may cause serotonin intoxication.

Medicines that reduce the seizure threshold.

SSRIs are capable of reducing the seizure threshold, so it is necessary to carefully combine the drug with other substances that have a similar effect (with thioxanthene, tramadol, tricyclics, mefloquine, and also with neuroleptics (phenothiazine derivatives), bupropion or butyrophenone).

Tryptophan and lithium substances.

Combined use of the drug with tryptophan or lithium leads to potentiation of the activity of Lenuxin.

Common St. John's wort (Hypericum perforatum).

The combination of the drug with St. John's wort substances may provoke an increase in the number of negative symptoms.

Anticoagulants and other drugs that affect blood clotting.

The combination of the drug with orally administered anticoagulants and other elements that change blood clotting (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, during the period of initiation or completion of treatment with escitalopram, it is necessary to constantly monitor blood coagulation. Combination with NSAIDs can 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 is the case with other psychotropic drugs, the drug should not be combined with alcoholic beverages.

Pharmacokinetic activity.

The effect of other drugs on the pharmacokinetic properties of the drug.

The metabolic processes of escitalopram are mainly realized by the isoenzyme CYP2C19. Less actively in these processes are involved isoenzymes CYP3A4 with CYP2D6. The process of metabolism of the main metabolic element (demethylated escitalopram) is apparently partially catalyzed by the isoenzyme CYP2D6.

The administration of the drug together with esomeprazole (inhibits the activity of the CYP2C19 isoenzyme) causes a moderate (approximately 50%) increase in plasma values of the former.

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

Therefore, it is necessary to combine the maximum permissible doses of Lenuxin and agents that inhibit the action of the CYP2C19 isoenzyme (for example, fluoxetine, ticlopidine and omeprazole with fluvoxamine, as well as esomeprazole and lansoprazole), as well as cimetidine, very carefully. The administration of the drug together with the above-described substances may require a reduction in the dosage of escitalopram after assessing the clinical picture.

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

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

Also, carefully combine with drugs, the metabolism of which is mainly realized by the action of the isoenzyme CYP2D6, 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, it may be necessary to change the dose.

The introduction of Lenuxin with metoprolol or desipramine causes a twofold increase in the latter's levels.

Escitalopram can slightly slow down the action of the isoenzyme CYP2C19. For this reason, it should be combined with caution with substances whose metabolic processes are associated with the CYP2C19 component.

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Storage conditions

Lenuxin must be stored in a dark place, out of the reach of small children. Temperature indicators for vials are no more than 30°C, and for cell plates – no more than 25°C.

Shelf life

Lenuxin can be used within a 24-month period from the date of sale of the medicinal product.

Application for children

Lenuxin should not be prescribed to persons under 18 years of age (because there is no information regarding its safety and medicinal effectiveness).

Analogues

Analogues of the drug are Miracitol, Cipralex with Sancipam, Elitseya and Selektra with Escitalopram.

Reviews

Lenuxin receives quite mixed reviews. Some patients indicate that the medication helps well, while others claim that it is completely ineffective.

Positive reviews of this medicine note that it quickly eliminates anxiety and improves well-being and mood. In addition, comments say that when using the drug in the indicated dosages, it was possible to get rid of depression, social phobia and panic. Moreover, this effect persisted even after stopping taking Lenuxin.

Negative comments indicate that the medicine causes side effects. Some people developed headaches, others experienced nausea, etc. In addition, there are messages from people who did not find the medicine helpful at all.