Zoloft - instructions for use, doses, side effects, contraindications

Excipients: calcium hydrogen phosphate dihydrate 24.0 mg or 48.0 mg, microcrystalline cellulose 44.925 mg or 89.85 mg, giprolose 4.5 mg or 9.0 mg, sodium carboxymethyl starch 18.75 mg or 37.5 mg, magnesium stearate 1,875 or 3.75 mg.

Film sheath:

Fill white with 4,125 mg or 8.25 mg (hypromellose 2.465 mg or 4.93 mg, titanium dioxide 1.289 mg or 2.578 mg, macrogol 0.33 mg or 0.66 mg, nolisorbate 80 0.041 mg or 0.082 mg). Fill transparent with 0.375 mg or 0.75 mg (hypromellose 0.341 mg or 0.682 mg, macrogol 0.034 mg or 0.068 mg).

Description:

Dosage 50 mg: white oval biconvex tablets covered with a film sheath, with engraving "Pfizer" on one side and "ZLT-50", separated by a risk, on the other.

Dosage of 100 mg: white, oval, biconvex tablets coated with a film sheath, engraved with "Pfizer" on one side and "ZI / G-100" on the other.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.X Other antidepressants

N.06.A Antidepressants

N.06.A.B Selective serotonin reuptake inhibitors

Pharmacodynamics:

Sertraline is an antidepressant, a potent selective serotonin reuptake inhibitor (5-HT) (SSRI). Has a very weak effect on the reverse capture of norepinephrine and dopamine. When used in therapeutic doses sertraline blocking the re-uptake of serotonin in human platelets. In controlled clinical trials, no stimulating, sedative or anticholinergic action was observed, nor were psychomotor functions disturbed in volunteers. Sertraline does not cause drug dependence, does not cause an increase in body weight with prolonged admission.

In animal models, it has been shown that, due to the selective inhibition of 5-HT capture, sertraline does not enhance catecholamine activity, does not have an affinity for muscarinic (cholinergic), serotonergic, dopamypergic, adrenergic, histaminergic, GABA or benzodiazepine receptors. In animal models it was shown that sertraline also has no cardiotoxic effect. Long-term use in animals was associated with the regulation of norepinephrine receptors in the brain according to the type of negative feedback that is characteristic of other antidepressants and anti- bessiviral drugs.

Sertraline does not lead to abuse of the drug. 13 placebo-controlled, double-blind, comparative study that examined the ability of sertraline, alprazolam and dextroamphetamine to develop abuse, sertraline did not have this ability. In contrast to this observation, patients who received alprazolam and dextramphetamine, showed a greater propensity to develop drug abuse, compared with placebo. The degree of propensity to abuse was based on measuring such indicators as the ability of the drug to cause positive emotions, euphoria and abuse. In rhesus monkeys, accustomed to the independent administration of cocaine, sertraline did not act as a positive stimulus, unlike phenobarbital and dextramphetamine.

Pharmacokinetics:

Absorption

The maximum concentration (C_max) and the area under the curve "concentration-time" (AUC) are proportional to the dose in the range of 50-200 mg, while the linear character of the pharmacokinetic dependence is revealed. When sertraline was used at a dose of 50 mg to 200 mg once a day for 14 days, the concentration of sertraline in the blood plasma reached C_max in 4,5-8,4 hours after administration. Absorption is high, at a slow rate. During food intake, bioavailability changes insignificantly (by 25%).

Distribution

Approximately 98% of sertraline binds to plasma proteins.

Metabolism

Sertraline undergoes active biotransformation when it first passes through the liver. The main pathway of metabolism is N-demethylation. The main metabolite found in plasma, N-desmethylsertraline, is significantly inferior (about 20-fold) to sertraline by in vitro activity and is in fact not active on in vivo depression models. The half-life of N-desmstilsertralin ranges from 62 to 104 hours. And sertraline and N-desmethylsertraline undergo oxidative deamination and subsequent reduction, hydroxylation and glucuroidation. When labeled sertraline was administered to healthy volunteers, less than 5% of radioactive sertraline was detected in the blood plasma.About 40 - 45% of the dose administered after nine days was found in the urine. Unchanged sertraline not excreted through the kidneys. During the same period, about 40 - 45% of the injected sertraline was found in feces, including 12-14% of unchanged sertraline.

AUC (0-24 h), C_max and C_m_indesmugil sertraline increases depending on the dose and time approximately 5 to 9 times from the 1st day to the 14th.

Excretion

Mean half-life (T_1/2) sertraline in young and elderly patients is 22-36 hours. Corresponding to the final T_1/2 there is approximately a two-fold cumulation of the drug before the onset of equilibrium concentrations after 1 week of treatment (taking the dose once a day). T_1/2 N-desmethylsertraline varies within the range of 62-104 h. Sertraline and N-desmethylsertralin are actively biotransformed; the resulting metabolites are excreted in equal amounts by the kidneys and through the intestine. Sertraline in unchanged form is excreted by the kidneys in an insignificant amount (<0.2%). The pharmacokinetic profile in adolescents and elderly people does not differ from that of the nation of gov at the age of 18 to 65 years.

Special patient groups

Use in children

It was shown that the pharmacokinetics of sertraline in children with obsessive-compulsive disorder (OCD) is similar to that in adults(although in children the metabolism of sertraline is somewhat more active). However, given the lower body weight in children (especially at the age of 6-12 years), the drug is recommended to use in a smaller dose to avoid excessive concentrations of sertraline in the blood plasma (see section "Method of administration and dose").

Adolescents and elderly patients

The pharmacokinetic profile in adolescents and the elderly does not differ from the pharmacokinetic profile in patients aged 18 to 65 years.

Application in case of insufficiency of liver function

With repeated admission of the sertralip in patients with cirrhosis of the liver of the lung, there is an increase T_1/2 and a nearly triple increase in AUC and C_max compared with those of healthy people. There are no significant differences in binding to plasma proteins in the two groups. When sertraline is used in patients with impaired liver function, it is necessary to discuss the advisability of reducing the dose or increasing the interval between taking the drug.

Application for renal failure

Sertraline undergoes active biotransformation, so the kidneys in unchanged form it is displayed in a small amount.In patients with mild and moderate renal failure (creatinine clearance 30-60 ml / min) and patients with moderate or severe renal failure (QC 10-29 ml / min), the pharmacokinetic parameters (AUC₀_-₂₄and C_max) sertraline with multiple admission did not differ significantly from the control group. In all groups T_1/2 sertraline was the same, just as there was no difference in binding to plasma proteins. It was found that, as expected, taking into account the insignificant renal excretion of sertraline, correction of its dose depending on the severity of renal failure is not required.

Indications:

Major depressive episodes. Prevention of major depressive episodes.

Obsessive-compulsive disorder in adults and children aged 6-17 years. Panic disorders (with or without agoraphobia).

Post-traumatic stress disorder (PTSD).

Contraindications:

Known hypersensitivity to sertraline and other components of the drug; children under 6 years of age (with a disabling-compulsive disorder (OCD)), for other indications, the drug is contraindicated in patients under 18 years of age;
the use of sertraline with monoamine oxidase inhibitors (MAOI) irreversible is contraindicated in connection with the risk of developing delayed sleep and a new syndrome manifested by agitation, tremor and hyperthermia. Do not start ssrtralin for 14 days after the abolition of irreversible MAOI, and sertraline therapy should be discontinued 7 days before the start of therapy with irreversible MAOIs (see "Interactions with Other Drugs" and "Special Advice");
simultaneous application with pimozide (see section "Interaction with other medicinal products").

Carefully:

Caution should be exercised when using sertraline in patients with organic brain diseases (including mental retardation), epilepsy, hepatic and / or renal insufficiency, expressed by a decrease in body weight.

Also, use caution when using sertraline with other drugs that enhance serotonergic neurotransmission (see "Interactions with Other Drugs").

Care should be taken when prescribing SSRIs in combination with drugs that have proven ability to influence platelet function (see section "Special instructions").

Caution should be exercised while simultaneously using sertraline and tricyclic antidepressants (see section "Interaction with other medicinal products").

Caution should be exercised when using sertraline in patients with risk factors for prolonging the QTc interval on the ECG or arrhythmia of the ventricular tachysystolic type "pirouette" (torsade de pointes).

Pregnancy and lactation:

Pregnancy

Controlled studies of the use of sertraline in pregnant women have not been carried out, so use the drug in this category of patients is only if the expected benefit for the mother exceeds the potential risk to the fetus.

However, in a significant amount of data, there was no evidence of induction of congenital malformations with sertraline. Studies in animals have shown the possible effect of sertraline on reproductive function. This effect is probably related to maternal toxicity caused by the pharmacodynamic effects of sertraline on the fetus.

Some newborns whose mothers have been taking sertraline During pregnancy, symptoms similar to withdrawal reactions were observed.This phenomenon was also observed with the use of other antidepressants of the SSRI group.

Women of reproductive age who are expected to use sertraline, should be recommended to use effective contraception.

Lactation

In breast milk a small amount is found sertraline and its metabolite N-desmethylsertralin. Insignificant amounts of sertraline were found in the blood plasma of the newborn, except for one case when 50% of the concentration in the blood plasma of the mother was detected in the plasma of the newborn (without a noticeable effect on the state of the newborn's health). Treatment with this drug during breastfeeding ns is recommended. If treatment is still necessary, then breast-feeding should be stopped.

In newborns whose mothers took the Zoloft drug and other SSRIs or SIOZ during pregnancy, complications requiring additional hospitalization, support of the respiratory system and feeding through the probe were observed, and neonates whose mothers were taken carefully sertraline late stages of pregnancy, especially in the third trimester.Such newborns may have the following symptoms: respiratory distress, cyanosis, apnea, convulsions, instability of body temperature, feeding difficulties, vomiting, hypoglycemia, hypotension, hypertropus, hyperreflexia, tremor, muscle twitching, increased excitability, lethargy, prolonged crying, drowsiness and difficulty falling asleep. These symptoms can be associated with immediate serotoninergic effects or may be symptoms of drug withdrawal. In most cases, such complications begin immediately or soon (<24 h) after birth. It should be borne in mind that in some cases the clinical picture may be similar to the symptoms of a serotonergic syndrome.

In newborns whose mothers took SSRIs during pregnancy, the risk of developing pulmonary neonatal pulmonary hypertension may also be increased. PLNG is 5 cases per 1000 pregnancies and is one of the causes of morbidity and mortality of newborns. Several recent epidemiological studies indicate a link between SSRIs (including Zolof g) and PGHN.

Fertility

In one of the two studies in mice, there was a decrease in fertility with the use of sertraline at a dose of 80 mg / kg (this is 4 times the maximum recommended dose for humans when calculating mg / m).

According to the described clinical cases, the intake of some SSRIs affects the quality of sperm, this effect is reversible.

Dosing and Administration:

Sertraline is administered orally, once a day in the morning or in the evening, regardless of the meal.

Initial dose

Depression and OCD: the initial dose is 50 mg / day.

Panic disorders, PTSD and social phobia: treatment starts with a dose of 25 mg / day, which is increased in one short time to 50 mg / day. The use of the drug in this scheme allows you to reduce the frequency of early undesirable effects of treatment, characteristic of panic disorder.

Dose selection

Depression, OCD, panic disorder, PTSD and social phobia: if the effect of sertraline at a dose of 50 mg / day is insufficient, the daily dose may be increased in increments of not more than 50 mg / day and at intervals not more than once a week (taking into account the 24-hour terminal half-life) to the maximum recommended dose, which is 200 mg / day.

The initial therapeutic effect may appear within 7 days, but the overall effect is usually achieved in 2-4 weeks (or even for a longer time with OCD).

Supportive therapy: the maintenance dose for long-term treatment should be minimal effective, with appropriate correction depending on the therapeutic effect.

For large depressive episodes, therapy should be continued for at least 6 months. In OCD and panic disorder, the need to continue therapy should be regularly evaluated, since in these conditions, the prevention of relapse is not indicated.

Use in children

Safety and efficacy of sertraline have been established in children with OCD (aged 6 to 17 years).

For adolescents (aged 13-17 years) with OCD, the initial dose is 50 mg / day.

For children (aged 6-12 years old), OCD therapy starts at a dose of 25 mg / day, followed by a dose increase of one week to 50 mg / day. In the future, with an insufficient dose effect of 50 mg, a further dose increase is possible in a few weeks. The maximum dose is 200 mg / day. Do not change the dose more than once a week.It was shown that in patients with depression and OCD at the age of 6 to 17 years, the pharmacokinetic profile of sertraline is similar to that of adults. However, in order to avoid an overdose, with an increase in the dose of more than 50 mg, it is necessary to take into account the smaller body weight in children, but in comparison with adults.

The safety and effectiveness of the drug in children with major depressive disorder has not been identified.

Selection of dose in children and adolescents

The half-life of sertraline is approximately 1 day, so the dose change should occur at intervals of not less than 1 week.

Application in elderly patients

In the elderly, the drug should be used with caution because of the increased risk of developing hyponatremia. The drug is used in the same dose range as in younger people.

Use in patients with liver failure

In patients with hepatic insufficiency, lower doses should be used or the interval between doses should be increased (see section "Special instructions"). Do not use sertraline in patients with severe hepatic insufficiency (nc has clinical data).

Use in patients with kidney failure

Given the slight renal excretion of sertraline, a one hundred dose correction depending on the severity of renal insufficiency ns is required (see section "Special instructions").

The withdrawal syndrome

It should be avoided abrupt withdrawal of Zoloft. If necessary, cancel therapy, you should gradually reduce the dose of sertraline for at least 1-2 weeks in order to minimize the risk of developing symptoms of withdrawal syndrome. In the case of intolerable adverse reactions during the period of dose reduction or after drug discontinuation, consideration should be given to the possibility of resuming therapy at the previous dose. In the future, the doctor may resume the dose reduction, but with longer intervals.

Side effects:

The most common side effect is nausea. In the treatment of social phobia, a violation of sexual function (ejaculation abnormality) in men in 14% of cases with sertraline was noted, compared with 0% when taking placebo. These adverse events depend on the dose and often go away with the continuation of therapy. The adverse events observed in patients with OCD,panic disorder, PTSD and social phobia do not differ from those with a major depressive disorder.

Table 1 provides information on adverse reactions observed with the use of sertraline, based on data obtained during post-marketing (frequency unknown) and placebo-controlled clinical trials (studies were conducted with the participation of 2542 patients receiving sertraline, and 2,145 patients receiving a placebo). These studies were conducted in patients with depression, OCD, panic disorder, PTSD, or social phobia.

Some of the undesirable reactions listed in Table 1 while continuing therapy may decrease in intensity and frequency and generally do not lead to discontinuation of therapy.

Very Frequent	≥ 10%
Frequent	≥ 1% and <10%
Infrequent	≥ 0.1% and <1%
Rare	> 0.01% and <0.1%
Very rare	<0,01 %
Frequency unknown	It is impossible to determine from the available data

Table number 1

System of organs	Undesirable Reactions
Heart Disease
Frequent	heart palpitations *
Infrequent	tachycardia
Rare	Myocardial infarction, bradycardia, heart disease
Frequency unknown	the development of arrhythmia of the ventricular tachysystolic type "pirouette" (torsade de poinles), interval lengthening QTc on the ECG
Vascular disorders
Frequent	"tides" of blood to the skin of the face *
Infrequent	increased blood pressure *, hyperemia
Rare	peripheral ischemia, hematuria
Frequency unknown	bleeding (eg, bleeding from the gastrointestinal tract)
Violations of the blood and lymphatic system
Rare	lymphadenopathy
Frequency unknown	leukopenia, thrombocytopenia
Hearing disorders and labyrinthine disorders
Frequent	tinnitus*
Infrequent	ear pain
Disturbances from the liver and bile ducts
Rare	abnormal liver function
Frequency unknown	serious violations of the liver (including, hepatitis, jaundice, liver failure)
Disturbances on the part of the organ of sight
Frequent	visual impairment
Infrequent	mydriasis *
Rare	glaucoma, lacrimal disorders, scotoma, diplopia, photophobia, anterior eye hemorrhage
Frequency unknown	impaired vision, different pupil size
Disorders from the gastrointestinal tract
Very Frequent	diarrhea (18%), nausea (24%), dryness of the oral mucosa (14%)
Frequent	vomiting , abdominal pain , constipation *, indigestion, flatulence
Infrequent	esophagitis, dysphagia, hemorrhoids, increased salivation, lesions of the tongue, eructation
Rare	melena, blood in the stool, stomatitis, ulcerative lesion of the tongue, tooth loss, glossitis, ulcerative lesion of the oral mucosa
Frequency unknown	pancreatitis
Common disorders and disorders together
Very Frequent	increased fatigue (10%) *
Frequent	chest pain *, weakness
Infrequent	chills, fever , asthenia , thirst, peripheral swelling
Rare	hernia, decreased drug tolerance, gait disorder
Benign, malignant and unspecified neoplasms (including cysts and polyps)
Rare	neoplasms ↑
Immune system disorders
Infrequent	hypersensitivity
Rare	anaphylactoid reactions
Frequency unknown	allergy
Laboratory and instrumental data
Infrequent	decrease * or increase * of body weight, increased activity of "liver" transaminases (alanine aminotransferase (ALT) , aspartate aminotransferase (ACT) ) in blood serum
Rare	a violation of the properties of the semen, an increase in the concentration of cholesterol in the blood plasma
Frequency unknown	deviations from the norm of the results of laboratory tests, a violation of the function of platelets
Disorders from the endocrine system
Infrequent	hypothyroidism
Frequency unknown	hyperprolactinemia, inadequate secretion of antidiuretic hormone
Disorders from the metabolism and nutrition
Frequent	decrease or increase * of appetite
Rare	diabetes mellitus, hypoglycemia, hypercholesterolemia
Frequency unknown	hyponatremia, hyperglycemia
Disturbances from musculoskeletal and connective tissue
Frequent	myalgia, arthralgia
Infrequent	osteoarthritis, muscle weakness, back pain, muscle spasms
Rare	disorders of the bone
Frequency unknown	muscle cramps
Disturbances from the nervous system
Very Frequent	headache (21%) *, dizziness (11%), drowsiness (13%)
Frequent	paresthesia *, tremor, hypertonus, dysgeusia, attention disorder
Infrequent	convulsions , involuntary muscle contraction , impaired coordination, hyperkinesia, amnesia, hypoesthesia , speech disorders, postural dizziness, migraine , fainting
Rare	coma *, horsoatstosis, dyskinesia, hyperesthesia, sensory disorders
Frequency unknown	impaired motor function (including extra-nerve disorders, such as hyperkinesia, hypertonia, dystonia, gnashing of teeth or gait disturbance). Also reported the development of symptoms of serotonin syndrome or malignant neuroleptic syndrome: in some cases, associated with the simultaneous use of serotonergic drugs. They included the following symptoms: anxiety, impaired consciousness, diaphoresis, diarrhea, fever, increased blood pressure, muscle stiffness, tachycardia; akathisia and psychomotor agitation (see section "Special instructions"); cerebrovascular spasm (including reversible vasoconstriction of cerebral vessels and the Coll-Fleming syndrome)
Disorders of the psyche
Very Frequent	Insomnia (19%)
Frequent	depressive symptoms , decreased libido , depersonalization, anxiety , nightmares, agitation , gnashing of teeth in sleep, increased excitability
Infrequent	euphoria , hallucinations , aggressive behavior *, apathy, thinking disorder
Rare	conversion disorder, drug dependence, psychotic disorders , paranoid behavior, suicidal ideation / behavior **, walking in a dream, premature ejaculation
Frequency unknown	painful dreams
Disorders from the kidneys and urinary tract
Infrequent	nocturia, urinary retention , polyuria, frequent urination, urination disorders, urinary incontinence
Rare	oliguria, urinary retention
From the side of the reproductive system **
Very Frequent	violation of ejaculation (14%)
Frequent	erectile disfunction
Infrequent	vaginal bleeding, sexual dysfunction, sexual dysfunction in women, menstrual irregularities
Rare	menorrhagia, atrophic vulvovaginig, balanoposgit, discharge from genital organs, priapism , galactorrhea
Frequency unknown	gynecomastia
Disturbances from the respiratory system, chest and mediastinal organs
Frequent	yawn*
Infrequent	bronchospasm *, shortness of breath, nosebleeds
Rare	laryngospasm, hyperventilation, hypoventilation, stridor, dysphonia, hiccough
Frequency unknown	interstitial lung disease
Disturbances from the skin and subcutaneous tissues
Frequent	rash *, increased sweating
Infrequent	periorbital edema , face swelling , purpura , alopecia , cold notes, dry skin, urticaria *, itchy skin
Rare	dermatitis, bullous dermatitis, follicular rash, hair texture disorder, skin odor change
Frequency unknown	rare cases of severe skin reactions, such as toxic epidermal necrolysis, Stevens-Johnson syndrome,
	angioedema, skin reaction, photosensitivity
Infectious and parasitic diseases
Frequent	pharyngitis
Infrequent	upper respiratory tract infection, rhinitis
Rare	diverticulitis, gastroenteritis, otitis media
Trauma, intoxication and complications of manipulation
Rare	injuries
Surgical and therapeutic manipulations
Rare	vasodilation procedure

When registering an adverse event in patients with depression, OCD, panic disorder, PTSD, and social anxiety disorder, an undesirable phenomenon is referred to the class of organs that was used to classify this undesirable phenomenon in studies in patients with depression.

↑ one case of neoplasm development was reported compared with patients in the placebo group.

* These adverse affects were also observed in post-marketing studies.

** The number of patients grouped according to gender is used as a denominator: sertraline therapy (1118 men, 1424 women), placebo therapy (926 men, 1219 women).

*** There have been cases of suicidal thoughts and suicidal behavior in patients receiving sertraline therapy or in the early period after the withdrawal of therapy (see section "Special instructions").

Class Effects

According to epidemiological studies, conducted mainly with the participation of patients aged 50 years and older, there was an increased risk of bone fractures in patients taking SSRIs and tricyclic antidepressants. The mechanism of this side effect is unknown.

The withdrawal syndrome

Termination of sertraline treatment (especially acute) often leads to the development of withdrawal syndrome. The most commonly reported symptoms are: dizziness, sensitivity disorders (including paresthesia), sleep disorders (including, insomnia and bright dreams), agitation or psychomotor agitation, nausea and / or vomiting, tremor and headache.In general, these symptoms are mild, moderate and limited; nevertheless, in some patients they can be severe and persist for a long time. In this regard, in the event that a patient does not need to continue treatment with sertraline, the drug should be gradually phased out by a smooth dose reduction.

Elderly patients

The use of SSRIs or selective norepinephrine reuptake inhibitors (SSRIs), including sertraline, in some cases has been associated with the development of severe hyponatremia in elderly patients, which may be characterized by an increased risk of developing such a complication.

Children

The profile of adverse reactions with sertraline in children was generally similar to the safety profile in adult patients. In clinical studies in children, the following adverse reactions were noted:

Very frequent (≥1 / 10): headache (22%), insomnia (21%), diarrhea (11%), nausea (15%).

Frequent (≥1 / 100 and <1/10): pain in the chest, mania, pyrexia, vomiting, anorexia, affective lability, aggressive behavior, agitation, increased excitability, attention disturbance, dizziness, hyperkinesia, migraine, snotty,tremor, visual impairment, dryness of the oral mucosa, dyspepsia, nightmares, increased fatigue, urinary incontinence, rash, acne, epistaxis, flatulence.

Infrequent (≥1 / 1000 and <1/100): prolongation of QT interval on ECG, suicide attempts, seizures, extraniramide disorders, paresthesia, depressive symptoms, hallucinations, purpura, hyperventilation, anemia, impaired liver function, increased ALT activity, cystitis, herpes simplex, otitis media, pain in the ears, pain in the eyes apples, mydriasis, malaise, hematuria, pustular rash, rhinitis, injuries, weight loss, involuntary muscle contractions, atypical dreams, apathy, albuminuria, pollakiuria, noliuria, chest pain, menstrual irregularities, alopecia, dermatitis, pores zheniya skin, skin odor, rash, gnashing his teeth in his sleep, "tides" of blood to the skin.

Frequency unknown: enuresis.

Overdose:

It is possible to develop severe poisoning, up to coma and legal outcome with simultaneous administration with other drugs and / or alcohol or when used in monotherapy. In this regard, it is necessary to carry out intensive therapy with any overdose of sertraline.

Overdose can cause serotonin syndrome with prolongation of the QT interval, the development of torsade de pointes, nausea, vomiting, drowsiness, tachycardia, agitation, dizziness, tremor, psychomotor agitation, diarrhea, increased sweating, myoclonus and hyperreflexia. In some cases, coma development was noted.

The safety of the drug depends on the patient population and concomitant therapy.

Treatment: there are no specific antidotes. Intensive supportive therapy and constant monitoring of vital body functions are required (including ECG monitoring, in connection with the possibility of prolongation of QT interval with sertraline intake). It is not recommended to induce vomiting. The introduction of activated carbon together with a laxative can be more effective than gastric lavage. It is necessary to maintain airway patency. Sertraline has a large volume of distribution, due to this, forced diuresis, dialysis, hemoperfusion or blood transfusion may be ineffective.

Interaction:

Simultaneous use of sertralny and the following drugs is contraindicated in IAO

Irreversible MAOIs (for example, selegiline)

Sertraline can not be used concomitantly with irreversible (nonselective) MAOIs, such as selegiline. Sertraline It is impossible to apply for a minimum of 14 days after the cancellation of irreversible (nonselective) MAOIs. It should stop taking sertraliya at least 7 days before the start of therapy with irreversible (nonselective) MAOI.

Reversible selective MAOA-A (moclobemide)

Due to the risk of developing serotonin syndrome, it is not recommended to take reversible selective MAOIs simultaneously, such as moclobemide, and sertraline. After the application of reversible MAOIs, a shorter than 14 days can be maintained before the onset of sertraline administration. The intake of sertraline should be discontinued at least 7 days before therapy is initiated with irreversible (nonselective) MAOIs.

Reversible non-selective MAOIs (linezolid and methylene blue)

Antibiotic linezolid is a weak reversible non-selective MAOI. It should not be used in patients receiving sertraline therapy.

Severe adverse reactions in patients were noted,who have recently stopped therapy with MAOI and started taking sertraline or who have recently canceled sertraline and started MAOI therapy. These reactions included tremor, myoclonus, diaphoresis, nausea, vomiting, stiffness, "flushes" of blood to the skin of the face, dizziness and hyperthermia with symptoms reminiscent of malignant neuroleptic syndrome, lability in the autonomic nervous system (rapid fluctuations in the parameters of the respiratory and cardiovascular system ), changes in mental status, including increased irritability, marked agitation, confusion (which in some cases can go into a delirious state and to whom), seizures and, in separate x cases, death.

Pimozide

With the simultaneous use of sertraline (at a dose of 200 mg per day) and pimozide (2 mg once), an increase in the concentration of pimozide (approximately 35%) was noted, which was not associated with any changes in the ECG. Since the mechanism of this interaction is unknown, and pimozide has a narrow therapeutic index, simultaneous administration of pimozide and sertraline is contraindicated.

Simultaneous use of sertraline and the following drugs is not recommended

Ethanol

Despite the fact that with the simultaneous use of sertraline in a dose of 200 mg daily and ethanol ns potentiation of the effect of ethanol is noted, the use of alcoholic beverages and preparations containing alcohol during treatment with sertraline is not recommended.

Drugs that depress the central nervous system

Simultaneous use of sertraline and substances that depress the central nervous system requires close attention. Potentiation of the effect with the simultaneous use of sertraline in a dose of 200 mg daily and carbamazepine, halonidol or phenytoin for cognitive and psychomotor function in healthy people has not been noted.

Drugs affecting serotonergic transmission

Caution should be exercised while simultaneously applying sertraline to other drugs that enhance serotonergic neurotransmission, such as tryptophan, fenfluramine, 5-HT agonists, tramadol or St. John's Wort. Such a joint application but the possibility should be ruled out, given the probability of pharmacodynamic interaction.

Caution should also be exercised while using fentanyl, other serotonergic agents (including serotonergic antidepressants, tryptanes), other opioids and sertraline.

Simultaneous use of sertraline and the following drugs should be performed with caution

Lithium

The pharmacokinetics of lithium does not change with simultaneous use with sertraline. However, there was an increase in tremor, which may indicate a possible pharmacodynamic interaction. With the simultaneous use of sertraline with lithium preparations, patients should be monitored continuously, and the concentration of lithium in the blood plasma should be monitored in order to correct the dose of the drug.

Phenytoin

Long-term use of sertraline at a dose of 200 mg per day does not have a clinically significant effect on the metabolism of phenytoin. There are some reports of an increase in the concentration of phenytoin when used simultaneously with sertraline. In this regard, it is recommended to carefully monitor the concentration of phenytoin in the blood plasma (especially in patients with concomitant diseases or at the same time receiving another therapy) from the time of sertraline administration withappropriate dose adjustment of phenytoin. Besides, phenytoin can reduce the concentration of sertraline in the blood plasma.

It is also impossible to exclude the ability of other inductors of CYP3A4 isoferme (for example, phenobarbital, carbamazepine, St. John's Wort, rifampicin) reduce the concentration of sertraline in the blood plasma.

Triptans

There are rare cases of weakness, increased tendon reflexes, impaired coordination of movements, confusion, anxiety and agitation in patients simultaneously taking sertraline and sumatriptan. Symptoms of serotonin syndrome can also occur with the simultaneous use of sertraline with other drugs of the same class (tryptans). If simultaneous use of sertraline and tryptanes is required, monitoring of patients is recommended.

Anticoagulants of indirect action (warfarin)

With the simultaneous use of indirect anticoagulants with sertraline (at a dose of 200 mg / day), there is a slight but statistically significant increase in the urothrombin time (see the "Specific guidance" section), which in some cases may lead to an imbalance in the values of the International Normalized Relationship (INR) .In this regard, prothrombin time should be carefully monitored during the initiation of sertraline therapy and during drug withdrawal.

Atenolol

With simultaneous application sertraline does not change the β-adrenergic blocking effect of atenolol.

Glibenclamide and digoxin

With the introduction of sertraline in a daily dose of 200 mg of drug interaction with these drugs is not revealed.

Cimetidine

Simultaneous use significantly reduces the clearance of sertraline.

Drugs affecting the function of platelets

With simultaneous use of SSRIs, including sertraline, and drugs that affect the function of thromboses (for example, non-steroidal anti-inflammatory drugs (PPAP), acetylsalicylic acid and ticlopidine) or drugs that may increase the risk of bleeding, there may be an increased risk of bleeding.

Drugs that increase the QTc interval

With the simultaneous use of sertraline and drugs increasing the QTc interval, the risk of prolonging the QTc interval and the development of torsade de pointes ventricular tachycystolic type increases.

Other

Sertraline binds to blood plasma proteins.Therefore, it is necessary to take into account the possibility of its interaction with other drugs that bind to proteins (for example, diazepam, tolbutamide and warfarin), although no interaction was noted in the studies.

Drugs metabolized by the CYP2D6 cytochrome P450 isoenzyme

Prolonged treatment with sertraline at a dose of 50 mg per day increases (averaging 23% - 37%) of the equilibrium concentration in the blood plasma desipramine (isoenzyme activity marker CYP2D6). Clinically significant interaction is also noted while the use of drugs with a narrow therapeutic index, in which metabolism is involved isoenzyme CYP2D6 (tricyclic antidepressants, typical antipsychotic drugs, antiarrhythmic drugs of class 1c - propafenone, flecainide) (see section "Special instructions").

Drugs metabolized by other cytochrome P450 (CYP3A3 / 4, CYP2C9, CYP2C19, CYP1A2)

Sertraline does not clinically significantly inhibit the isoenzymes CYP3A4, CYP2C9, CYP2C19 and CYP1A2.

Isozyme CYP3A3 / 4

It has been shown in vino that with prolonged simultaneous application at a dose of 200 mg per day sertraline does not inhibit the metabolism of carbamazepine, terfenadine, as well as beta-hydroxylation of endogenous cortisol, carried out by the isoenzyme CYP3A3 / 4. Besides, sertraline in a dose of 50 mg per day does not inhibit the metabolism of alprazolam.

It was found that the intake of three glasses of grapefruit juice daily increases the concentration of sertraline in the blood plasma by approximately 100%. Thus, simultaneous administration of sertraline and grapefruit juice should be avoided.

Based on studies of the interaction of sertraline and grapefruit juice, it can not be ruled out that the simultaneous use of sertraline and potent inhibitors of the CYP3A4 isoenzyme (eg, protease inhibitors, ketoconazole, itraconazole, posaconazole, voriconazole, clarygromycin, telithromycin and nefazodone) may lead to an even greater increase in sertraline exposure. This also applies to moderate inhibitors of the CYP3A4 isoenzyme (eg, aprepitant, erythromycin, fluconazole, verapamil and diltiazem). It is necessary to avoid the use of potent inhibitors of the isoenzyme CYP3A4 during the treatment with ssrtraline.

Isozyme CYP2C9

With simultaneous application sertraline reduces the clearance of tolbutamide.but sertraline does not affect the degree of binding of tolbutamide to plasma proteins and the volume of distribution. It is assumed that the change in the clearance of tolbutamide is associated with a change in the metabolism of the drug. Thus, it can be concluded that sertraline does not inhibit the isoenzyme CYP2C9.

Isozyme CYP2C19

Sertraline does not affect the concentration of diazepam in the serum, indicating that there is no inhibition of the isoenzyme CYP2C19.

In patients slowly metabolizing the isoenzyme CYP2C19, an increase in sertraline concentration in the blood plasma is observed to be 50% higher than in patients rapidly metabolizing this isoenzyme. It is impossible to exclude the interaction between potent inhibitors of the isoenzyme CYP2C19 (for example, omeprazole, lansoprazole, nantoprazole, rabeprazole, fluoxetine, fluvoxamine) and sertraline.

Isozyme CYP1A2

According to in vitro studies sertraline practically does not influence or minimally inhibits the isoenzyme CYP1A2.

Induction of microsomal liver enzymes

Sertraline causes minimal induction of liver enzymes. Simultaneous use of sertraline in a dose of 200 mg and antipyrin results in a small (5%), but significant decrease in the half-life of the antipyrine.

Special instructions:

Sertraline should not be administered in conjunction with MAOI, within 14 days before the initiation of admission to the AO, and within 14 days after their withdrawal.

Monitor the concentration of tricyclic antidepressants in the blood to assess the need for dose adjustment.

With the simultaneous use of sertraline and golbutamide, it is necessary to monitor the blood glucose level (see the section "Interaction with other medicinal products").

Serotonin syndrome

When using SSRIs, cases of development of serotonin syndrome (SS) and malignant neuroleptic syndrome (CNS) are described. Risk Data complications increases with simultaneous application of SSRIs with other serotonergic agents (including trintanami and fentanyl and its analogs, tramadol deksomstorfanom, tapentadolom, meperedinom, methadone, pentazocine) as well as drugs affecting the serotonin metabolism (including monoamine oxidase inhibitors ), antipsychotic agents and other dopamine receptor antagonists. Manifestations of the SS can be changes in mental status (in particular, agitation, hallucinations, coma), autonomic lability (tachycardia,fluctuations in blood pressure, hyperthermia), changes in neuromuscular transmission (hyperreflexia, impaired coordination of movements) and / or disorders of the gastrointestinal tract (nausea, vomiting and diarrhea). Some manifestations of SS, including hyperthermia, rigidity of muscles, vegetative lability with possible rapid fluctuations in the parameters of vital functions, as well as changes in mental status, can resemble the symptoms developing in the NSA. It is necessary to observe patients for the development of clinical manifestations of SS and ZPS.

Lengthening of the OTT interval or arrhythmia ventricular tachysystolic type "pirouette" (torsade de pointes)

During the postmarketing use of sertraline, cases of prolongation of the QTc interval on the ECG and the development of torsade de pointes ventricular tachysystolic type arrhythmia were reported. Most cases were noted in patients with risk factors for developing such conditions. Therefore, caution should be exercised in the use of sertraline in patients with risk factors for prolonging the QTc interval on the ECG or for the development of torsade dc pointes in the ventricular tachysystolic type.

Transition from other SSRIs, antidepressants or anti-obsessive drugs

The necessary interval between the cancellation of one SSRI and the start of taking another similar drug is not established. Care must be taken when moving to sertraline with other SSRIs, antidepressants or anti-obsessive drugs, especially with long-acting drugs, for example, with fluoxetine.

When replacing one inhibitor of neuronal seizure of serotonin with another, there is no need for a "period of washing". However, care must be taken when changing the course of treatment.

Other serotonergic drugs, for example, tryptophan, (fenfluramine and 5-HT-agonists

Simultaneous use of sertraline with other drugs with a pronounced effect on neurotransmitter transmission (such as tryptophan, fenfluramine, 5-HT-agonists or herbal medicine, St. John's wort) should be carried out with caution and, if possible, avoided, given the potential pharmacodynamic interaction.

Suicidal behavior

Depression is associated with an increased risk of suicidal thoughts, a propensity for self-harm and suicide. This risk persists until a stable remission.Given that improvements in the patient's condition may not occur within the first few weeks of therapy or longer, careful monitoring of the patients should be made before such an improvement. It is also common to increase the risk of suicide in the early stages of recovery.

Other diseases that can be prescribed sertraline, may also be associated with an increased risk of suicidal events. In addition, these diseases can accompany a major depressive disorder. In this regard, the same precautions should be taken as in the treatment of a large depressive disorder.

In patients with a history of suicidal tendencies or patients prone to suicidal thinking prior to therapy, a higher risk of suicidal thoughts or suicide attempts is noted. Such patients should also be kept under close medical supervision during therapy.

All patients, especially those at risk, who are receiving sertraline therapy, should be carefully monitored to identify the development or worsening of symptoms of suicidal behavior.Patients, their relatives and guardians should be warned about the need to monitor the condition for the appearance or deterioration of depression, the appearance of suicidal thoughts or behavior, as well as for any changes in behavior, especially at the beginning of therapy and with any change in the dose of the drug. It should also be borne in mind the risk of suicide attempts, especially in patients with depression. In this regard, in order to reduce the risk of overdose, it is necessary to take a minimal dose of the drug, providing a sufficient therapeutic effect.

Patients with depression and other mental disorders have a risk of suicidal behavior. By themselves, these diseases are strong predisposing factors of such behavior. It has been found that in children, adolescents and young people (aged 18-24 years) with depression or other mental disorders, antidepressants (SSRIs and others), compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when using sertraline or any other antidepressant drugs in children, adolescents and young people (younger than 24 years), the risk of suicide and the benefits of their use should be correlated.In addition, there was no increase in the risk of suicidal behavior in adults over 24 years of age, and in patients aged 65 and older, a reduction in this risk was noted.

Use in children and adolescents under 18 years of age

Sertraline should not be used to treat children and adolescents under the age of 18, except for patients with OCD aged 6-17 years. Suicidal tendencies (suicide attempts or suicidal thoughts) and hostility (mainly aggressiveness, opposition behavior and anger) were more often observed in patients receiving antidepressant therapy than in patients receiving placebo. If, on the basis of a clinical assessment of the patient, a decision was made to conduct therapy, the patient's condition should be carefully monitored for symptoms of suicidal behavior. In addition, it should be taken into account that data on the effect of the drug on growth, puberty and cognitive and behavioral development of the child are limited. With long-term therapy of pediatric patients, doctors should monitor for abnormalities in development.

The withdrawal syndrome

When withdrawal of the drug often there are withdrawal symptoms, especially in the case of a sharp withdrawal of the drug. Symptoms of withdrawal were observed in 23% of patients who stopped taking sertraline and 12% of patients who continued the drug. The risk of developing these symptoms depends on several factors, including the duration of therapy and dosage, as well as the rate of dose reduction. The most frequent reactions are dizziness, sensitivity disorders (including paresthesia), sleep disturbances (including insomnia and deep sleep), agitation or anxiety, nausea and / or vomiting, and death and headache. Usually these symptoms are mild and moderate; nevertheless, in some cases they can be heavy. Typically, these symptoms occur during the first few days of treatment discontinuation, but there are very few reports of the development of such symptoms in patients who inadvertently missed the dose. Usually these manifestations are not aggravated and take place within two weeks, with the exception of some cases when they can last longer (2-3 months or more). In this regard, it is recommended to cancel the drug gradually, reducing the dose for several weeks or months, depending on the patient's condition.

Akathisia / nonsihomotor excitation

The use of sertraline may be associated with the development of akathisia, characterized by a subjective feeling of discomfort or anxiety and the need to move, accompanied by an inability to sit or stand still. Most often, such symptoms are observed in the first weeks of treatment. Increasing the dose in such patients can be harmful.

Impaired liver function

If it is necessary to use sertraline in patients with impaired liver function, consider reducing the dose of the drug or the frequency of admission. Do not take sertraline in patients with severe impairment of liver function.

Impaired renal function

It was found that. as expected, taking into account the slight renal excretion of sertraline, correction of its dose depending on the severity of renal failure is not required.

Electroconvulsive therapy

The possible success or risk of such a combination treatment has not been studied (no clinical data are available).

Convulsions

Experience with sertraline in patients with convulsive syndrome is not present, therefore, it should be avoided in patients with unstable epilepsy,and patients with controlled epilepsy should be carefully observed during treatment. When the seizures appear, the drug should be discontinued.

Activation of mania / hypomania

During clinical trials before the introduction of sertraline on the market, hypomania and mania were observed in approximately 0.4% of patients who received sertraline. The cases of activation of mania / hypomania are also described in a small part of patients with manic-depressive psychosis receiving other anti-depressive or anti-obsessional drugs. In patients with mania or hypomania in history, apply sertraline with caution. Careful observation of the physician is necessary and sertraline should be withdrawn if the patient exhibits any signs of a manic condition.

Schizophrenia

In patients with schizophrenia, there may be an exacerbation of psychotic symptoms.

Pathological hemorrhages / hemorrhages

There are reports of bleeding or hemorrhage from ecchymoses and purpurae of life-threatening bleeding / hemorrhage) against the background of SSRIs. Care should be taken when prescribing SSRIs in combination with drugs,having the established ability to influence the function of platelets (for example, atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory drugs), as well as in patients with hemorrhagic diseases in history.

In addition, when using sertraline with anticoagulants of indirect action, it is recommended to monitor prothrombin time at the beginning of treatment with sertraline and after its withdrawal.

Hyponatremia

Transient hyponatremia often develops in elderly patients, in patients with dehydration or with the administration of diuretics. This side effect is associated with the syndrome of inadequate secretion of antidiuretic hormone. There were reports of a decrease in the concentration of sodium in the blood plasma below 110 mmol / l. With the development of automatic gyniatrics sertraline should be abolished and an appropriate therapy aimed at correcting the concentration of sodium in the blood should be prescribed. Signs and symptoms of hyponatremia include headache, impaired concentration, memory impairment, weakness and instability, which can lead to falls.In more severe cases, hallucinations, fainting, convulsions, coma, respiratory arrest and death may occur.

In connection with the fact that there is a clear relationship between the development of depression and OCD, depression and panic disorders, depression and PTSD. depression and social phobia, when treating patients with OCD, panic disorder, PTSD and social phobia, the same precautions should be followed as in the treatment of depression.

Fractures

Based on epidemiological studies, it was found that when serotonin reuptake inhibitors are used, including sertraline, the risk of fractures increases. The mechanism leading to increased risk is not fully understood.

Elderly patients

The profile of adverse reactions in elderly and younger patients is different. In the elderly, the drug should be used with caution because of the increased risk of developing hyponatremia.

Diabetes mellitus / impaired glucose control When SSRIs, including Zoloft®, were used, there were cases of exacerbation of diabetes mellitus and / or impaired glucose control (hyperglycemia and hypoglycemia) in patients with or without diabetes mellitus.In this regard, it is necessary to monitor the level of glucose. Particular attention is required for patients with diabetes mellitus, as they may need to adjust the dose of hypoglycemic agents for ingestion and / or insulin.

Closed-angle glaucoma

SSRIs, including sertraline, affect the size of the pupil, which leads to mydriasis. At the same time, the angle of the eye is narrowed, which leads to an increase in intraocular pressure and the development of closed-angle glaucoma, especially in patients with a predisposition. It should be used with caution in patients with angle-closure glaucoma or with glaucoma in the anamnesis.

Laboratory methods

In patients who took sertraline, noted false positive results of immunological tests of urine on benzodiazepines. This is due to the low specificity of screening tests. Also, false positive results can be noted within a few days after the withdrawal of sertraline therapy. Additional tests, such as gas chromatography and mass spectrometric method, will help to distinguish sertraline from benzodiazepines.

Grapefruit juice

The simultaneous use of sertraline and grapefruit juice is not recommended.

Effect on the ability to drive transp. cf. and fur:

The use of sertraline, as a rule, is not accompanied by a violation of psychomotor functions. However, its use simultaneously with other drugs can lead to disruption of attention and coordination of movements. Therefore, during the treatment with sertraline, it is not recommended to drive vehicles, special equipment or engage in activities involving an increased risk.

Form release / dosage:

Film-coated tablets, 50 mg and 100 mg.

Packaging:

For 14 tablets in a blister of PVC / aluminum foil.

1 or 2 blisters together with instructions for use in a cardboard pack with the control of the first opening.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013622 / 01

Date of registration:18.07.2008 / 07.05.2015

Expiration Date:Unlimited

The owner of the registration certificate: Pfizer Inc. Pfizer Inc. USA

Manufacturer: & nbsp

HAUPT PHARMA LATINA, S.R.L. Italy

Representation: & nbspPfizer LtdPfizer LtdUSA

Information update date: & nbsp17.10.2017

Illustrated instructions

Instructions

Zoloft® (Zoloft®)