pharmachologic effect
Antidepressant, a powerful specific inhibitor of serotonin (5-HT) reuptake in neurons.
It has a very weak effect on the reuptake of norepinephrine and dopamine. In therapeutic doses, it blocks the uptake of serotonin in human platelets. Does not have a stimulating, sedative or anticholinergic effect. Due to the selective inhibition of 5-HT uptake, sertraline does not enhance adrenergic activity. Sertraline has no affinity for muscarinic cholinergic receptors, serotonin, dopamine, histamine, GABA, benzodiazepine and adrenergic receptors. Sertraline does not cause drug dependence and does not cause weight gain with long-term use.
Pharmacokinetics
Suction
Absorption is high, but at a slow rate. When taking the drug simultaneously with food, bioavailability increases by 25%, Cmax increases by 25% and Tmax decreases.
In humans, when taking sertraline at a dose of 50 to 200 mg 1 time / day for 14 days, Cmax was achieved 4.5-8.4 hours after administration. Cmax and AUC are proportional to the dose within the range of 50-200 mg of sertraline 1 time / day for 14 days, while the linear nature of the pharmacokinetic dependence is revealed.
Distribution
Plasma protein binding is about 98%.
According to the final T1/2, an approximately twofold cumulation of the drug is observed until the onset of equilibrium concentrations after 1 week of treatment (dose 1 time/day).
Metabolism
Sertraline undergoes active biotransformation during the “first pass” through the liver. The main metabolite found in plasma, N-desmethylsertraline, is significantly inferior (about 20 times) to sertraline in activity in vitro and is virtually inactive in in vivo models of depression.
Sertraline and N-desmethylsertraline are actively biotransformed.
Removal
The average T1/2 of sertraline in young and elderly men and women is 22-36 hours. T1/2 of N-desmethylsertraline varies between 62-104 hours. Metabolites are excreted in feces and urine in equal quantities. Only a small part of the drug (less than 0.2%) is excreted unchanged in the urine.
Pharmacokinetics in special clinical situations
The pharmacokinetic profile in adolescents and elderly patients does not differ significantly from that in patients aged 18 to 65 years.
The pharmacokinetics of sertraline in children with OCD have been shown to be similar to those in adults (although the metabolism of sertraline is somewhat more active in children). However, given the lower body weight in children (especially those aged 6-12 years), it is recommended to use the drug in a lower dose to avoid excessive plasma levels.
In patients with liver cirrhosis, T1/2 of the drug and AUC increase compared to those in healthy people.
How is Triazavirin good for COVID-19?
According to the mechanism of action, the drug is active against RNA viruses. The COVID-19 genome consists of a single strand of RNA.
The drug is recommended for use for preventive purposes. It allows you to stop the proliferation of microorganisms that have penetrated the host cells. The medication is especially recommended for people who are in contact with patients with COVID-19 (relatives of coronavirus patients, doctors, nurses, etc.).
Triazavirin for moderate coronavirus can be used as part of complex therapy. The drug reduces the severity of symptoms and shortens the duration of therapy. Can be used as monotherapy for mild forms of coronavirus infection.
Dosage
The drug is administered orally, 1 time/day in the morning or evening. The tablets can be taken regardless of meals.
For depression and OCD
treatment begins with a dose of 50 mg/day.
Treatment of panic disorders, PTSD and social phobia
start with a dose of 25 mg/day, which is increased after 1 week to 50 mg/day. The use of the drug according to this regimen can reduce the incidence of early undesirable treatment effects characteristic of panic disorder.
If the effect of using sertraline in patients at a dose of 50 mg/day is insufficient, the daily dose can be increased. The dose should be increased at intervals no more than once per week to a maximum recommended dose of 200 mg/day.
Initial effects may be seen within 7 days of starting treatment, but full effects are usually achieved within 2-4 weeks (or even longer for OCD).
During long-term maintenance therapy
the drug is prescribed in the minimum effective dose, which is subsequently changed depending on the clinical effect.
In children and adolescents aged 13-17 years
with
OCD,
treatment with Zoloft should begin with a dose of 50 mg/day.
In children aged 6-12 years,
treatment for OCD begins with a dose of 25 mg/day, after 1 week it is increased to 50 mg/day. Subsequently, if the effect is insufficient, the dose can be increased in steps of 50 mg/day up to 200 mg/day as needed. In clinical trials in patients with depression and OCD aged 6 to 17 years, it was shown that the pharmacokinetic profile of sertraline was similar to that in adults. To avoid overdose, when increasing the dose above 50 mg, it is necessary to take into account the lower body weight in children compared to adults.
T1/2 of sertraline is approximately 1 day, so dose changes should occur at intervals of at least 1 week.
In elderly patients
the drug is used in the same doses as in younger patients.
The drug should be used with caution in patients with liver disease
.
In patients with liver failure
, use lower doses or increase the interval between doses of the drug.
The drug is largely metabolized in the body. Only a small amount of the drug is excreted unchanged in the urine. As expected given the negligible renal excretion of sertraline, its dose was adjusted depending on the severity of renal failure
not required.
USE OF ANTIDEPRESSANTS in cardiology
Most often, cardiologists have to use antidepressants for various depressive conditions. According to foreign authors, the frequency of depressive disorders among hospitalized therapeutic patients is 15-36%, among patients with coronary heart disease (CHD) - 16-23%. In the post-infarction period, with relapses of angina pectoris, as well as in connection with coronary artery bypass grafting, anxiety and cardiophobia often arise, and in the future secondary depression often develops.
Depression (regardless of its origin), which develops against the background of a severe somatic illness, significantly complicates its course and the patient’s rehabilitation. A number of studies have found that depressive symptoms are reliable predictors of mortality from cardiovascular diseases after myocardial infarction. According to N. Frasure-Smith et al. (1991, 1993), depressive symptoms identified after myocardial infarction significantly increase the risk of death or recurrent myocardial infarction, even when other risk factors are taken into account (in particular, left ventricular dysfunction, a history of myocardial infarction, and the frequency of ventricular extrasystoles).
On the other hand, sometimes with depression, somatic complaints and functional symptoms are so prevalent in the clinical picture that the internist does not even assume that the patient has a mental disorder. According to WHO, more than half of patients with depression are treated by general practitioners and do not come to the attention of psychiatrists. Such depressions, called larved or somatized, occur under the guise of various somatovegetative symptoms, and the actual manifestations of depression turn out to be atypical. This often leads to errors in diagnosis, and grueling additional examinations and long-term ineffective treatment disappoint both the patient and the doctor. These somatovegetative equivalents are extremely diverse and include various pain syndromes (cardialgia, headaches, neuralgia, etc.), often imitating serious pathology; decreased or increased appetite and, accordingly, weight loss or gain, sleep disorders, autonomic paroxysms and a number of other disorders.
The main signs of depression include low mood, lack of interests or feelings of satisfaction, increased fatigue; Additional ones include decreased ability to concentrate, low self-esteem and self-doubt, feelings of guilt, self-deprecation, a gloomy pessimistic vision of the future, suicidal thoughts or actions, sleep disturbances (usually early awakenings), and appetite. In case of long-term chronic diseases, the etiology of which cannot be identified, occurring with periodic spontaneous exacerbations, the doctor should always think about the presence of masked depression.
Among the conditions requiring the use of psychotropic drugs, in particular antidepressants, it is necessary to highlight vegetative crises (panic attacks). In the practice of general practitioners and cardiologists, paroxysmal conditions are often encountered, accompanied by anxiety, fear of death, cardialgia, palpitations, a feeling of lack of air, and other mental and somatic manifestations. Such patients are often hospitalized in cardiology departments of hospitals with the erroneous diagnosis of “angina pectoris.” First of all, it is necessary to clearly establish whether the patient has a disease of the internal organs with a tendency to paroxysmal manifestations (for example, paroxysmal tachycardia, atrial fibrillation, pheochromocytoma, bronchial asthma, etc.) or whether we are talking about panic attacks with a variety of somatic symptoms associated with increased activity autonomic nervous system. If organic pathology is excluded, one should think that the patient has a mental disorder, manifested in the form of panic attacks. Such attacks rarely occur in isolation, and then they are considered within the framework of panic disorder. Much more often they occur against a background of depression and are combined with various phobias - pronounced and persistent or unmotivated fears, for example, fear of open (agoraphobia) or closed (claustrophobia) spaces, fear of social situations, public speaking (social phobia), etc.
Finally, antidepressants are used for some sleep disorders. Traditionally, sleep time (about a third of a patient's life) does not fall into the scope of analysis and diagnosis by a doctor. However, sleep is not just a state of reduced activity: it plays a unique role in maintaining the vital functions of a living organism. A.I. Barder (1975) in the course of special studies identified a group of diseases, including angina pectoris, myocardial infarction, arterial hypertension, strokes and some other diseases that are reliably associated with sleep disorders. According to Mittlmen et al. (1999), 20% of myocardial infarctions and 15% of sudden deaths occur during sleep (between midnight and 6 a.m.). In addition, nocturnal myocardial infarctions are more severe and more often fatal.
On the other hand, angina attacks also often occur at night and in turn cause sleep disturbance. In the works of O. Masagtur et al. (1995) demonstrated that emotional stress in patients with coronary heart disease increases noticeably in the evening and night hours due to the fear of a recurrence of an anginal attack and death during sleep.
In addition, according to Hung et al. (1993), 5-9% of the working age population experiences complete cessation of breathing during sleep lasting 10 seconds or more - obstructive sleep apnea. These attacks play a certain role in the development of myocardial infarction and sudden death in coronary artery disease, since the resulting hypoxemia can provoke myocardial ischemia. Convincing evidence of this was obtained by researchers from the Stanford group. Angina pectoris and changes in the QT segment coincide in time with periods of severe obstructive sleep apnea, accompanied by episodes of blood desaturation. All this adversely affects the rehabilitation process of patients with myocardial infarction.
Thus, the main indications for the use of antidepressants in cardiological practice are depressive disorders, as well as vegetative crises (panic attacks) and sleep disorders.
The need for treatment of minor depression by general practitioners is due, on the one hand, to the high prevalence of these diseases, and on the other, to the persistent reluctance of many patients to go to psychoneurological institutions. When deciding on the issue of independent supervision of a patient with depression, a general practitioner must exclude the following conditions that require mandatory specialized psychiatric care: suicidal thoughts, which may not be actively expressed by patients, but upon questioning they are revealed in an active or passive form (for example, “it would be better to get under the car and suffer”); delusions (usually guilt, hypochondriacal or accusations), hallucinations; indications of a history of mental illness; severe somatic condition requiring special care when selecting psychotropic therapy; pregnancy.
After an exhaustive somatic examination, the doctor must carefully analyze the psychopathological features of the condition in order to choose the most adequate therapy. Treatment of depression in the general medical network is carried out mainly with the help of medications, but a simple explanatory conversation can not only reassure the patient, but also ensure his adherence to the recommended therapy.
Contraindications for the prescription of antidepressants are acute diseases of the liver and kidneys (taking into account their biotransformation and excretion), hematopoietic organs, cerebrovascular accidents, decompensated heart defects, seizures and some other severe somatic diseases.
Safety of therapy
Currently, there is already a huge selection of different antidepressants, and their range continues to expand steadily. Today there are quite a lot of different classifications of antidepressants. These classifications are based on the characteristics of the chemical structure, metabolism, mechanisms of action on the neurotransmitter system, etc. In the most general form, antidepressants can be divided into two groups: classical antidepressants (amitriptyline, ludiomil, melipramine, etc.) and modern ones (Prozac, Coaxil, lerivon, etc.).
Classical antidepressants (tricyclic, tetracyclic) have the greatest therapeutic effect, but at the same time they have the widest and most pronounced range of side effects (associated mainly with the anticholinergic effect). In this regard, it is often necessary to refuse therapy; in many patients it is impossible to achieve a sufficient therapeutic dose. Due to their pronounced anticholinergic effect, tricyclic antidepressants can cause constipation, difficulty urinating, and blurred vision (accommodation disorders). When using these drugs in patients with cardiovascular diseases, it should be taken into account that tricyclic antidepressants tend to accumulate in the heart muscle, where their concentration is more than 100 times higher than in the blood plasma. Overdose of tricyclic antidepressants is associated with an increase in mortality from cardiovascular disorders; in therapeutic doses they can cause prolongation of the PQ, QRS, QT intervals, which is explained by their quinidine-like activity.
Irreversible MAO inhibitors (nialamide) are currently used extremely rarely due to the high risk of drug interactions, tyramine, or “cheese” reactions, and the development of serious complications.
Modern antidepressants are comparable to traditional ones in effectiveness, but have significantly fewer side effects, they are much safer and easier to use. These include selective serotonin reuptake inhibitors (SSRIs) - fluoxetine (Prozac), citalopram (Cipramil), fluvoxamine (Fevarin), sertraline (Zoloft), paroxetine (Paxil), as well as drugs with another mechanism of action - tianeptine (Coaxil), mianserin (lerivon), moclobemide (Aurorix), bupropion, etc. When treating with serotonergic antidepressants, the most serious complication, especially when high doses are used, is the development of serotonin syndrome. The initial manifestations of the syndrome affect mainly the gastrointestinal tract and nervous system. Characterized by seething and colic in the abdomen, diarrhea, nausea and other dyspeptic complaints. Neurological symptoms include tremor, dysarthria, muscle hypertonicity and myoclonic jerks. The main symptoms are reversible and quickly disappear after reducing the dose or discontinuing antidepressants.
In cardiological practice, the use of SSRIs is certainly preferable due to their greater selectivity and better tolerability. However, here too there are some differences in the tolerability of these drugs, due primarily to the selectivity of the main action. In this subgroup, citalopram (cipramil), which is the safest drug to use, has the highest selectivity. For example, the effects of citalopram on cardiac conduction and repolarization were assessed in a randomized, double-blind, placebo-controlled trial involving 23 participants. In addition, Soren LR et al. (1999) retrospectively assessed more than 6000 ECGs performed on 1460 patients between 1978 and 1996 during three randomized, double-blind studies; of these, 1789 ECGs were taken during citalopram therapy. The results of the studies showed that the effect of citalopram on electrocardiographic parameters was manifested only in the form of a slight decrease in heart rate (less than 8 beats per minute). No significant effect of the drug on the duration of the PQ, QRS and QT intervals was detected, that is, citalopram does not have a noticeable effect on cardiac conduction and repolarization processes.
Another important advantage of modern antidepressants is their minimal interaction with other drugs, including those used in the treatment of cardiovascular diseases. The most important role is played by cytochrome P450, which is involved in the metabolism of various drugs (Table 1).
Drugs that inhibit more than one cytochrome P450 isomer are more likely to interact with other drugs. The effect of SSRIs on various isomers of cytochrome P450 is presented in table. 2. Based on these data, it can be argued that the lowest likelihood of drug interactions occurs when using citalopram.
The basic principles of antidepressant therapy are valid for both classical and new modern antidepressants
- It is necessary to use adequate therapeutic doses, which for classical (tricyclic, four-cyclic) antidepressants are up to 150-300 mg per day. Treatment with these antidepressants begins with small doses (25-50 mg per day); if well tolerated, the dose is gradually increased until a positive effect or a side effect occurs. In general somatic practice, it is not recommended to use a dose of more than 75-100 mg per day, since with a subsequent increase in the dose, the risk of various complications increases - both somatic and neuropsychiatric (for example, the danger of anticholinergic delirium in the elderly). If treatment with the indicated dose is ineffective, consultation with a psychiatrist is necessary. For modern antidepressants, doses are usually fixed and vary depending on the type of drug.
- The effect of antidepressant therapy does not appear immediately, but within 1-3 weeks from the start of treatment.
- If by the fourth week of treatment there is no effect from the therapy, first of all it is necessary to ensure that the therapeutic dose has been achieved. Only in this case can we assume that the drug is ineffective and, therefore, should be replaced with another (in this case, consultation with a psychiatrist is necessary).
- Treatment of depression should be long-term, from 4-6 months to several years, depending on the characteristics of the course of the disease; early discontinuation of the drug, even against the background of clinical well-being, can lead to relapse of the disease. The dose of the drug should remain at the same level and only if necessary (side effects) can be reduced, but not more than 25-30%.
The drugs of choice for the treatment of depression with somatic symptoms are those with the least severity of side effects. These drugs include selective serotonin reuptake inhibitors, in particular citalopram (cipramil) at a dose of 20 mg per day, sertraline (Zoloft) at a dose of 50-100 mg per day, as well as drugs of a different chemical structure: coaxil at a dose of 25-37 .5 mg per day, mianserin (Lerivon) at a dose of up to 100 mg per day and doxepin (Sinequan) at a dose of up to 150 mg per day.
For anxiety depression, drugs that have a sedative or anxiolytic effect are used: amitriptyline at a dose of up to 75-100 mg per day, citalopram (cipramil) at a dose of 20 mg per day, coaxil at a dose of 37.5 mg per day, mianserin (lerivon) at a dose up to 100 mg per day; or balanced drugs: ludiomil at a dose of up to 100 mg per day, fevarin at a dose of 50-100 mg per day, Zoloft at a dose of 50-100 mg per day, Paxil at a dose of 20 mg per day.
If depression is accompanied by anxiety, irritability, vegetative paroxysms (panic attacks), it is advisable to combine antidepressants with tranquilizers or use combination drugs, for example amixide (amitriptyline + chlordiazepoxide). Tranquilizers are not prescribed if the patient has suicidal thoughts, as this makes suicide easier.
If apathy and anergy predominate in the structure of depression, it is advisable to use drugs with an activating effect: melipramine at a dose of up to 100 mg per day, Prozac at a dose of 20 mg per day, moclobemide (Aurorix) at a dose of 300 mg per day. For apathoadynamic depression with signs of asthenia, difficulties concentrating attention and thinking, it is advisable to add nootropics.
In the treatment of panic attacks, especially if they develop against the background of depression, in combination with phobias, the use of antidepressants is also of great importance. Treatment for these disorders takes a long time. The most effective is the use of antidepressants in combination with psychotherapy. To choose the right therapeutic tactics, a consultation with a psychiatrist is necessary. In such a situation, it is advisable to use cipramil, imipramine, anafranil, Zoloft, fevarin, fluoxetine and other drugs; tranquilizers are assigned a supporting role. The presence of a distinct anxiolytic effect in tsipramil makes it most effective for panic attacks.
Cipramil is one of the drugs that can be used to correct sleep disturbances in patients with myocardial infarction, especially in middle age. Its advantages include the absence of a negative effect on the patient’s breathing, which seems important in connection with the possibility of obstructive sleep apnea. Moreover, as shown in some studies, antidepressants - serotonin reuptake inhibitors can slightly reduce the sleep apnea index. Tsipramil has the ability to normalize sleep structure, increase its efficiency and reduce the time it takes to fall asleep, which makes this drug very promising for drug correction of sleep disorders in myocardial infarction.
A. L. Vertkin , Doctor of Medical Sciences, Professor A. V. Topolyansky O. V. Lyubshina
Side effects
From the digestive system:
dyspeptic symptoms (flatulence, nausea, vomiting, diarrhea, constipation), abdominal pain, pancreatitis, dry mouth, hepatitis, jaundice, liver failure, decreased appetite (rarely increased), even anorexia; rarely, with long-term use - an asymptomatic increase in transaminase activity in the blood serum occurs. Discontinuation of the drug in this case leads to normalization of enzyme activity.
From the cardiovascular system:
palpitations, tachycardia, arterial hypertension.
From the musculoskeletal system:
arthralgia, muscle cramps.
From the central nervous system and peripheral nervous system:
extrapyramidal disorders (dyskinesia, akathisia, teeth grinding, gait disturbance), involuntary muscle contractions, paresthesia, fainting, drowsiness, headache, migraine, dizziness, tremor, insomnia, anxiety, agitation, hypomania, mania, hallucinations, euphoria, nightmares, psychosis, decreased libido, suicide, coma.
From the respiratory system:
bronchospasm, yawning.
From the urinary system:
enuresis, incontinence or urinary retention.
From the reproductive system:
sexual dysfunction (delayed ejaculation, decreased potency), galactorrhea, gynecomastia, menstrual irregularities, priapism.
From the senses:
blurred vision, mydriasis, ringing in the ears.
From the endocrine system:
hyperprolactinemia, hypothyroidism, syndrome of inappropriate ADH secretion.
Dermatological reactions:
redness of the skin or flushing of the face, alopecia, photosensitivity reaction, purpura, increased sweating.
Allergic reactions:
urticaria, pruritus, anaphylactoid reaction, angioedema, periorbital edema, facial edema, rarely Stevens-Johnson syndrome and epidermal necrolysis.
From the hematopoietic system:
possible development of leukopenia and thrombocytopenia.
Other:
weight loss or gain, peripheral edema, increased serum cholesterol levels, weakness, bleeding (including nasal, gastrointestinal or hematuria). Rare cases of withdrawal syndrome have been described when stopping treatment with sertraline. Paresthesia, hypoesthesia, symptoms of depression, hallucinations, aggressive reactions, psychomotor agitation, anxiety, or symptoms of psychosis may appear that cannot be distinguished from the symptoms of the underlying disease.
Serenata tablets ppo 100 mg No. 30
Compound
Active substance: sertraline (in the form of hydrochloride) 100 mg.
Excipients: microcrystalline cellulose, sodium carboxymethyl starch, calcium hydrogen phosphate dihydrate, hydroxypropylcellulose, polysorbate, magnesium stearate.
Shell composition: hypromellose, propylene glycol, titanium dioxide.
Pharmacokinetics
Suction
After taking the drug orally, the absorption of sertraline from the gastrointestinal tract is significant, but occurs slowly. Cmax in blood plasma is achieved after 4.5-8.4 hours. Bioavailability during meals increases by 25%, while the time to reach Cmax is shortened.
Distribution
With a single daily dose, Css in blood plasma is achieved within a week. The binding of sertraline to plasma proteins is 98%. Vd >20 l/kg.
Sertraline is excreted in breast milk. There is no data on its permeability through the placental barrier.
Metabolism and excretion
Sertraline is extensively metabolized during the “first pass” through the liver, undergoing N-demethylation. Its main metabolite, N-desmethylsertraline, is less active than the parent compound. Metabolites are excreted in urine and feces in equal quantities. About 0.2% of sertraline is excreted unchanged by the kidneys. T1/2 is 22-36 hours and does not depend on age or gender. For N-desmethylsertraline this figure is 62-104 hours.
Pharmacokinetics in special clinical situations
If liver function is impaired, T1/2 and AUC increase.
Regardless of the severity of renal failure, the pharmacokinetics of sertraline does not change with its continuous use.
Sertraline is not dialyzable.
Indications for use
- Depression of various etiologies (treatment and prevention);
- obsessive-compulsive disorders (OCD);
- panic disorder (with or without agoraphobia);
- post-traumatic stress disorder (PTSD).
Contraindications
- Unstable epilepsy;
- children under 6 years of age;
- pregnancy;
- lactation period;
- combined use of sertraline and MAO inhibitors (when replacing one drug with another, you should refrain from taking antidepressants for 14 days);
- combined use of sertraline with tryptophan or fenfluramine;
- hypersensitivity to the components of the drug.
The drug should be used with caution in case of organic diseases of the brain (including mental retardation), manic states, epilepsy, liver and/or kidney failure, and weight loss.
Directions for use and doses
For adults with depression and OCD, the drug is prescribed at an initial dose of 50 mg 1 time / day in the morning or evening. The daily dose can be gradually, no earlier than a week later, increased from 50 mg to a maximum daily dose of 200 mg.
For panic disorders and PTSD, the initial dose is 25 mg 1 time / day in the morning or evening. After a week, you can increase the dose to 50 mg 1 time / day, and then gradually, no earlier than a week later, the daily dose can be increased from 50 mg to a maximum daily dose of 200 mg.
A satisfactory therapeutic result is usually achieved within 7 days from the start of treatment. However, to achieve the full therapeutic effect, regular use of the drug is required for 2-4 weeks. When treating OCD, it may take 8-12 weeks to achieve good results. The minimum dose that provides a therapeutic effect is subsequently maintained as a maintenance dose.
For children with OCD, the drug is prescribed depending on age. For children aged 6 to 12 years, the initial dose is 25 mg 1 time / day in the morning or evening. After a week, the dose can be increased to 50 mg 1 time / day. For children and adolescents aged 12 to 17 years, the initial dose is 50 mg 1 time / day, in the morning or evening. The daily dose can be gradually, no earlier than a week later, increased from 50 mg to a maximum daily dose of 200 mg. To avoid overdose, one should take into account the lower body weight in children compared to adults, and when increasing the dose to more than 50 mg/day, it is necessary to carefully monitor this category of patients and, at the first signs of an overdose, discontinue the drug.
In elderly patients, no special dose selection is required.
In case of severe liver dysfunction, the dose of the drug should be reduced or the intervals between doses increased.
In patients with impaired renal function, no special dose selection is required.
Storage conditions
The drug should be stored out of the reach of children, at a temperature below 25°C.
Best before date
2 years. Do not use after the expiration date stated on the packaging.
special instructions
Sertraline should not be administered within 14 days of stopping treatment with MAO inhibitors. MAO inhibitors are not prescribed within 14 days after discontinuation of sertraline.
Patients receiving electroconvulsive therapy do not have sufficient experience with the use of the drug Serenata. The possible success or risk of this combination treatment has not been studied.
Patients suffering from depression are at risk for suicide attempts. This danger persists until remission develops. Therefore, from the start of treatment until the optimal clinical effect is achieved, patients should be under constant medical supervision.
When using the drug Serenata simultaneously with drugs that have a depressant effect on the central nervous system, special caution and careful monitoring of the patient's condition are required.
Description
Antidepressant.
Use in children
The drug is contraindicated in children under 6 years of age.
The drug should be used with caution in children over 6 years of age.
For children with OCD, the drug is prescribed depending on age. For children aged 6 to 12 years, the initial dose is 25 mg 1 time / day in the morning or evening. After a week, the dose can be increased to 50 mg 1 time / day. For children and adolescents aged 12 to 17 years, the initial dose is 50 mg 1 time / day, in the morning or evening. The daily dose can be gradually, no earlier than a week later, increased from 50 mg to a maximum daily dose of 200 mg. To avoid overdose, one should take into account the lower body weight in children compared to adults, and when increasing the dose to more than 50 mg/day, it is necessary to carefully monitor this category of patients and, at the first signs of an overdose, discontinue the drug.
Pharmacodynamics
Antidepressant. Selective serotonin reuptake inhibitor (5-HT). It has a weak effect on the reuptake of norepinephrine and dopamine. At therapeutic doses, sertraline blocks the uptake of serotonin by human platelets. Sertraline has no affinity for muscarinic, serotonin, dopamine, adrenergic, histamine, GABA or benzodiazepine receptors. Does not have a stimulating, sedative or anticholinergic effect.
The antidepressant effect is observed by the end of the second week of regular use of sertraline, while the maximum effect is achieved only after 6 weeks.
Unlike tricyclic antidepressants, sertraline does not cause weight gain. Sertraline does not cause mental or physical drug dependence.
Side effects
From the digestive system: dry mouth, decreased appetite (rarely increased), up to anorexia, dyspeptic disorders (flatulence, nausea, vomiting, diarrhea), abdominal pain; with long-term use in 0.8% of cases - an asymptomatic increase in transaminase activity in the blood serum (when the drug is discontinued, enzyme activity normalizes).
From the central nervous system and peripheral nervous system: drowsiness, headache, dizziness, tremor, insomnia, anxiety, agitation, hypomania, mania, gait disturbances, weakness. During treatment with sertraline, extrapyramidal disorders, dyskinesias, tremor, convulsions, and visual disturbances were noted. Motor disorders were more often observed in patients with indications of their presence in the anamnesis or with concomitant use of antipsychotic drugs.
From the endocrine system: ejaculation disorders, decreased libido, menstrual irregularities, hyperprolactinemia, galactorrhea.
Metabolism: increased sweating, weight loss; 0.8% (more often in elderly patients, as well as when taking diuretics or a number of other drugs) - transient hyponatremia (this side effect is associated with the syndrome of inappropriate ADH secretion).
Dermatological reactions: redness of the skin, skin rash; rarely - erythema multiforme.
When stopping treatment: rarely - withdrawal syndrome: possible paresthesia, hypoesthesia, symptoms of depression, hallucinations, aggressive reactions, psychomotor agitation, anxiety or symptoms of psychosis that cannot be distinguished from the symptoms of the underlying disease.
Use during pregnancy and breastfeeding
Adequate and strictly controlled clinical studies of the safety of Serenata during pregnancy have not been conducted. Prescribing the drug to pregnant women is contraindicated.
Women of reproductive age who are expected to undergo treatment with Serenata should use effective methods of contraception.
Sertraline is excreted in breast milk. There are no reliable data on the safety of sertraline use during lactation. Therefore, if it is necessary to prescribe the drug, breastfeeding should be stopped.
Interaction
With the simultaneous use of the drug Serenata and MAO inhibitors, both selectively acting (selegiline) and with a reversible type of action (moclobemide), severe complications may develop, including serotonin syndrome. Similar complications, sometimes fatal, occur when MAO inhibitors are prescribed during treatment with antidepressants that inhibit the neuronal uptake of monoamines or immediately after their withdrawal. With the simultaneous use of selective neuronal reuptake inhibitors of serotonin and MAO inhibitors, the following occur: hyperthermia, rigidity, myoclonus, lability of the autonomic nervous system (rapid fluctuations in the parameters of the respiratory and cardiovascular system), changes in mental status, including increased irritability, severe agitation, confusion, which in some cases can progress to delirium or coma.
When coumarin derivatives and sertraline are administered together, a significant increase in prothrombin time is observed (it is recommended to monitor the prothrombin time at the beginning of treatment with Serenata and after its discontinuation).
Pharmacokinetic interaction
Sertraline binds to plasma proteins. Therefore, the possibility of its interaction with other protein-binding drugs (for example, diazepam, tolbutamide and warfarin) should be considered.
When used simultaneously with cimetidine, a significant decrease in the clearance of sertraline is observed. With long-term treatment with sertraline at a dose of 50 mg/day, in case of simultaneous use, an increase in the plasma concentration of desipramine, which is metabolized with the participation of the CYP2D6 isoenzyme, is observed.
In vitro experimental studies of drug interactions have shown that metabolic processes occurring with the participation of CYP3A3/4 isoenzymes - beta-hydroxylation of endogenous cortisol and metabolism of carbamazepine and terfenadine - do not change with long-term administration of sertraline at a dose of 200 mg / day. The plasma concentrations of tolbutamide, phenytoin and warfarin also do not change with long-term administration of sertraline at the same dose. Thus, we can conclude that sertraline does not inhibit the activity of the CYP2C9 isoenzyme.
Sertraline does not affect the concentration of diazepam in the blood serum, which indicates the absence of inhibition of the CYP2C19 isoenzyme.
According to in vitro studies, sertraline has virtually no effect or minimal inhibition of the CYP1A2 isoenzyme.
The pharmacokinetics of lithium does not change with simultaneous use of sertraline, however, in such cases, tremor is more often observed. As with the administration of other selective neuronal serotonin reuptake inhibitors, the combined use of sertraline with drugs that affect serotonergic transmission (for example, lithium) requires increased caution. When replacing one neuronal serotonin uptake inhibitor with another, there is no need for a washout period. However, caution is required when changing the course of treatment.
Co-administration of tryptophan or fenfluramine with sertraline should be avoided.
Sertraline causes minimal induction of liver microsomal enzymes. The simultaneous administration of sertraline and antipyrine at a dose of 200 mg leads to a significant decrease in T1/2 of antipyrine, although this occurs in only 5% of cases.
With simultaneous use, sertraline does not change the beta-adrenergic blocking effect of atenolol.
When simultaneous use of sertraline at a dose of 200 mg/day with glibenclamide or digoxin, no drug interactions were detected.
Overdose
Symptoms: no severe symptoms of sertraline overdose were detected even when the drug was prescribed in high doses. However, when taken simultaneously with other drugs or ethanol, severe poisoning may occur. Overdose can cause serotonin syndrome with nausea, vomiting, drowsiness, tachycardia, agitation, dizziness, psychomotor agitation, diarrhea, increased sweating, myoclonus and hyperreflexia.
Treatment: There are no specific antidotes. Intensive supportive care and constant monitoring of vital body functions are required. Inducing vomiting is not recommended. The administration of activated carbon may be more effective than gastric lavage. The airway must be maintained. Sertraline has a large Vd, so increasing diuresis, dialysis, hemoperfusion, or blood transfusion may not be effective.
Impact on the ability to drive vehicles and operate machinery
The administration of sertraline, as a rule, is not accompanied by impairment of psychomotor functions. However, its use simultaneously with other drugs can lead to impairment of attention and coordination of movements. Therefore, during treatment with sertraline, driving vehicles, special equipment or engaging in activities associated with increased risk is not recommended.
Overdose
Symptoms:
no severe symptoms were detected in case of an overdose of sertraline even when using the drug in high doses. However, when administered simultaneously with other drugs or alcohol, severe poisoning can occur, including coma and death.
In case of overdose, manifestations of serotonin syndrome are possible (nausea, vomiting, drowsiness, tachycardia, agitation, dizziness, psychomotor agitation, diarrhea, increased sweating, myoclonus and hyperreflexia).
Treatment:
There are no specific antidotes. Intensive supportive care and constant monitoring of vital body functions are required. Inducing vomiting is not recommended. The administration of activated carbon may be more effective than gastric lavage. The airway must be maintained. Sertraline has a large Vd, and therefore increased diuresis, dialysis, hemoperfusion or blood transfusion may be ineffective.
