Aleval, tablets 50 mg, 28 pcs.

An antidepressant, selective serotonin reuptake inhibitor (5-NT). It has a very weak effect on norepinephrine and dopamine reuptake. In therapeutic doses, sertraline blocks serotonin uptake by human platelets.

It has no stimulant, sedative, or anticholinergic effects. Sertraline has no affinity for m-cholinoreceptors, adrenoreceptors, serotonin, dopamine, histamine receptors, GABA- or benzodiazepine receptors.

Antidepressant effect is noted by the end of the second week of regular use of Sertraline, while the maximum effect is achieved only after 6 weeks. Sertraline does not cause mental or physical drug dependence.

Indications

Active ingredient

Composition

1 tablet contains:

The active ingredient: sertraline hydrochloride (which is equivalent to sertraline) – 56 mg (50 mg).

Auxiliary substances: calcium hydrophosphate dihydrate, microcrystalline cellulose, corn starch, hypromellose 2910, purified talc, magnesium stearate, colloidal silicon dioxide, crosspovidone, indigo carmine; coating composition: hypromellose 2910, macrogol 6000, refined talc, titanium dioxide, indigo carmine.

How to take, the dosage

Sertraline is prescribed orally, once a day, in the morning or evening. Sertraline tablets can be taken regardless of meals.

Depression and OCD

Adults

The starting dose is 50 mg of Sertraline once daily. The daily dose can be gradually increased at weekly intervals up to a maximum daily dose of 200 mg.

The initial therapeutic effect may occur within 7 days, but full effect is usually achieved in 2-4 weeks (or even longer in OCD). The maintenance dose in long-term treatment should be the minimum effective dose – with adjustments depending on the therapeutic effect.

Panic Disorders and PTSD

In panic disorder and PTSD, the drug is indicated for adults. The starting dose is 25 mg of Sertraline once daily, in the morning or evening. With tolerance, the dose can be gradually increased to a maximum daily dose of 200 mg, no more than once a week by 25 mg, until the desired therapeutic effect is achieved.

Satisfactory therapeutic results are usually achieved in 7 days from the start of treatment. However, regular use of the drug for 2-4 weeks is required to achieve full therapeutic effect. The minimum dose that provides a therapeutic effect is maintained thereafter as a maintenance dose.

Children with OCD

For children 6 to 12 years of age, the starting dose is 25 mg of sertraline once daily, morning or evening. After a week, you can increase the dose to 50 mg once a day.

For children 12 to 17 years of age, the starting dose is 50 mg once daily, morning or evening. The daily dose can be gradually increased from 50 mg to a maximum daily dose of 200 mg, at the earliest after a week. To avoid overdose, the lower body weight in children compared to adults should be taken into account, and if the dose is increased beyond 50 mg/day, this category of patients should be closely monitored and the drug should be discontinued at the first signs of overdose.

There is no need for special dose selection in elderly patients.

Patients with hepatic dysfunction require special attention during treatment with sertraline. If liver function is severely impaired, the dose of the drug should be reduced or the intervals between doses should be increased. In patients with impaired renal function there is no need to specifically adjust the dose.

Interaction

In coadministration of sertraline and pimozide, there was an increase in pimozide concentrations when administered once at a low dose (2 mg). The increase in pimozide concentration was not associated with any ECG changes. Since the mechanism of this interaction is not known and pimozide has a narrow therapeutic index, concomitant administration of pimozide and sertraline is contraindicated.

Severe complications have been reported with concomitant use of sertraline and MAOI inhibitors (including the selectively acting selegiline, the MAOI inhibitor with reversible type of action moclobemide, and linezolid). Serotonin syndrome may develop (hyperthermia, rigidity, myoclonus, vegetative nervous system lability (rapid fluctuations of respiratory and cardiovascular system parameters), mental status changes, including increased irritability, pronounced agitation, confusion, which in some cases may progress to delirium or coma). Similar complications, sometimes fatal, occur when IMAO is prescribed as a concomitant treatment with antidepressants that inhibit monoamine reuptake or immediately after their withdrawal.

The combined use of sertraline and CNS depressant medications requires close monitoring. Alcohol consumption is prohibited during treatment. No potentiation of the effects of carbamazepine, haloperidol or phenytoin, and ethanol on cognitive and psychomotor function has been noted in healthy subjects.

In coadministration of indirect anticoagulants (warfarin) with sertraline, a small but statistically significant increase in prothrombin time has been noted – in these cases, it is recommended that prothrombin time be monitored at the start of treatment with sertraline and after discontinuation.

When changing from one serotonin uptake inhibitor to another, a “washout period” is not necessary. However, caution is required when altering the course of treatment. Co-prescribing tryptophan or fenfluramine with sertraline should be avoided.

Sertraline causes minimal induction of microsomal liver enzymes. Concomitant administration of sertraline and phenazone at a dose of 200 mg results in a significant decrease in T1/2 phenazone, although this occurs in only 5% of cases.

When administered together, sertraline does not alter the beta-adrenoblocking effect of atenolol.

There are no drug interactions with glibenclamide and digoxin when sertraline is administered at a daily dose of 200 mg.

In long-term use, Sertraline at a dose of 200 mg/day has no clinically significant effect and does not inhibit metabolism of phenytoin. Despite this, careful monitoring of plasma phenytoin concentrations is recommended from the start of treatment with sertraline, with appropriate adjustment of the phenytoin dose.

In extremely rare cases of weakness, increased tendon reflexes, confusion, anxiety, and agitation have been reported in patients taking sertraline and sumatriptan concomitantly. Follow-up of patients with appropriate clinical reasons for concomitant administration of sertraline and sumatriptan is recommended.

Pharmacokinetic interaction

Sertraline binds to plasma proteins. Therefore, the possibility of its interaction with other drugs that bind to plasma proteins (e.g., diazepam and tolbutamide) must be considered.

Concomitant use with cimetidine significantly reduces the clearance of sertraline.

Prolonged treatment with sertraline at a dose of 50 mg/day increases plasma concentrations of concomitant drugs which are metabolized by CYP2D6 isoenzyme (tricyclic antidepressants, antiarrhythmic drugs of class I C – propafenone, flecainide).

In experimental studies of interaction in vitro have shown that beta-hydroxylation of endogenous cortisol, which occurs with the participation of CYP3A3/4 isoenzymes, as well as metabolism of carbamazepine and terfenadine do not change with long-term use of Sertraline at a dose of 200 mg/day. Plasma concentrations of tolbutamide, phenytoin and warfarin also do not change with long-term administration of sertraline at the same dose. Therefore, it is believed that sertraline does not inhibit the CYP2C9 isoenzyme.

Sertraline decreases the clearance of tolbutamide when taken concomitantly (blood glucose control is necessary).

Sertraline has no effect on the serum concentration of diazepam, indicating no inhibition of the CYP2C19 isoenzyme. According to in vitro studies, Sertraline has little or no effect on the CYP1A2 isoenzyme.

The pharmacokinetics of lithium are not altered by concomitant administration of sertraline. However, tremor is observed more frequently when they are used together. Particular caution is required when coadministering sertraline (like other SSRIs) with drugs that affect serotonergic transmission (e.g., lithium).

Special Instructions

Aleval should not be administered together with MAO inhibitors and also within 14 days after stopping treatment with MAO inhibitors. Similarly, no MAOI inhibitors should be prescribed for 14 days after withdrawal of Aleval.

When using selective serotonin reuptake inhibitors (SSRIs), there have been cases of serotonin syndrome and MNS, the risk of which increases when combining SSRIs with other serotonergic agents (including triptans).including triptans), as well as drugs that affect serotonin metabolism (including MAO inhibitors), antipsychotics, and other dopamine receptor antagonists. Manifestations of serotonin syndrome may include changes in mental status (particularly agitation, hallucinations, coma), autonomic instability (tachycardia, BP fluctuations, hyperthermia), changes in neuromuscular transmission (hyperreflexia, movement coordination disorders) and/or GI disorders (nausea, vomiting and diarrhea). Some manifestations of serotonin syndrome, including hyperthermia, muscle stiffness, autonomic instability with possible rapid fluctuations of parameters of vital functions, and changes in mental status, may resemble the symptomatology that develops in MNS.

Caution should be exercised when concomitantly prescribing sertraline with other drugs that enhance serotonergic neurotransmission, such as, tryptophan, phenfluramine, or serotonin 5-NT receptor agonists. Such co-administration should be avoided if possible, given the possibility of pharmacodynamic interactions.

There is limited experience in clinical studies to determine the optimal time to switch patients from other antidepressants and OCD medications to sertraline. Caution must be exercised when making this transition, especially from long-acting medications such as fluoxetine. The necessary interval between withdrawal of one SSRI and initiation of another similar medication has not been established.

It should be noted that there is insufficient experience with Sertraline in patients undergoing electroconvulsive therapy. The possible success or risk of this combination treatment has not been studied.

There is no experience with the use of sertraline in patients with seizure syndrome, so the drug should be avoided in patients with unstable epilepsy, and patients with controlled epilepsy should be closely monitored during treatment. If seizures occur, the drug should be discontinued.

In clinical trials prior to the introduction of sertraline to the market, manic disorders were observed in about 0.4% of patients taking sertraline. Cases of manic activation have also been described in a small proportion of patients with manic-depressive psychosis who were receiving other antidepressants or OCD medications.

Sertraline is actively biotransformed in the liver. According to a pharmacokinetic study, repeated administration of sertraline in patients with stable mild cirrhosis showed an increase in T1/2 drug and an increase in Cmax and AUC almost 3-fold compared to these figures in healthy subjects. There were no significant differences in binding to plasma proteins in the two groups. Sertraline should be used with caution in patients with liver disease. When prescribing the drug to a patient with hepatic impairment, the advisability of reducing the dose or increasing the interval between doses of the drug should be discussed.

Sertraline is excreted in small amounts unchanged in the urine. In patients with mild to moderate renal impairment (CKR 30-60 ml/min) and in patients with severe renal impairment (CKR ≤10-29 ml/min or less) the pharmacokinetic parameters (Cmax and AUC0-24) of Sertraline when taken repeatedly were not significantly different from control group. In all groups, the T1/2 drug was the same, nor were there differences in binding to plasma proteins. The results of this study suggest that, as expected given the insignificant renal excretion of sertraline, no dose adjustment depending on the severity of renal impairment is required.

We recommend caution when prescribing SSRIs in combination with drugs with an established ability to alter platelet function and in patients with a history of hemorrhagic disease.

Transient hyponatremia may occur during treatment with sertraline. This occurs more often in elderly patients, as well as when taking diuretics or a number of other drugs. Such side effect is associated with inadequate ADH secretion syndrome. If symptomatic hyponatremia develops, sertraline should be discontinued and adequate therapy should be prescribed to correct blood sodium concentration. Signs and symptoms of hyponatremia include headache, impaired concentration, memory disturbances, weakness and unsteadiness, which may lead to falls. In more severe cases, hallucinations, fainting, seizures, coma, respiratory failure, and death may occur.

The risk of suicide attempts

Patients with depression, are at risk for suicide attempts. This risk persists until remission develops. Therefore, ongoing medical monitoring of patients should be established from the initiation of treatment until optimal clinical effect is achieved.

In children, adolescents, and young adults younger than 24 years of age with depression and other psychiatric disorders, antidepressants increase the risk of suicidal ideation and suicidal behavior compared to placebo. Therefore, when prescribing Aleval or any other antidepressant medication in children, adolescents, and young adults younger than 24 years of age, the risk of suicide and the benefits of its use should be weighed. In short-term studies, the risk of suicide was not increased in people over 24 years of age, and was slightly decreased in people over 65 years of age. Any depressive disorder itself increases the risk of suicide. Therefore, all patients should be monitored during antidepressant treatment for early detection of impairment or behavioral changes as well as suicidal tendencies.

Impact on driving and operating machinery

Patients should not drive vehicles, operate special equipment, or engage in high-risk activities during treatment with Aleval.

Contraindications

Side effects

Digestive system: dyspeptic symptoms (flatulence, nausea, vomiting, diarrhea), abdominal pain, pancreatitis, dry mouth, hepatitis, jaundice, liver failure, decreased appetite up to anorexia; rarely – increased appetite.

Cardiovascular system disorders: palpitations, tachycardia, decreased blood pressure.

Muscular system disorders: arthralgia, muscle cramps.

CNS and peripheral nervous system disorders: Extrapyramidal disorders (dyskinesia, akathisia, teeth grinding, gait disturbance), involuntary muscle contractions, paresthesias, fainting, drowsiness, headache, migraine, dizziness, tremor, insomnia, anxiety, agitation, tremor, seizures, manic disorders, hallucinations, euphoria, nightmares, psychosis, decreased libido, suicide, coma.

Respiratory system: bronchospasm, yawning.

Urinary system disorders: enuresis, urinary incontinence or retention.

Reproductive system disorders: sexual dysfunction (delayed ejaculation, decreased potency), galactorrhea, gynecomastia, menstrual cycle disorders, priapism.

Sensory system disorders: visual impairment, mydriasis, periorbital edema, tinnitus.

Endocrine system disorders: hyperprolactinemia, hypothyroidism, ADH inadequate secretion syndrome.

Dermatological reactions: skin redness or flushing of the face, alopecia, photosensitization, purpura, increased sweating; Stevens-Johnson syndrome and toxic epidermal necrolysis are rare.

Allergic reactions: urticaria, pruritus, anaphylactoid reaction, angioedema, facial edema.

Laboratory data: rarely, with long-term use – asymptomatic increase in serum transaminase activity occurs. Withdrawal of the drug in this case leads to normalization of the enzyme activity. Leukopenia and thrombocytopenia may develop, as well as increased serum cholesterol concentration.

Others: weakness, weight loss or increase in body weight, bleeding (including nasal, gastrointestinal or hematuria), peripheral edema.

When discontinuing treatment with sertraline in rare cases – withdrawal syndrome: paresthesias, hypoesthesias, symptoms of depression, hallucinations, aggressive reactions, psychomotor agitation, anxiety or symptoms of psychosis which cannot be distinguished from symptoms of the underlying disease are possible

Overdose

Symptoms: Severe symptoms of Sertraline overdose have not been found, even when administered in high doses. However, when administered simultaneously with other drugs or ethanol, severe poisoning is possible, up to coma and death. Overdose may cause serotonin syndrome with nausea, vomiting, somnolence, tachycardia, agitation, dizziness, psychomotor agitation, diarrhea, increased sweating, myoclonus and hyperreflexia.

Treatment: there are no specific antidotes. Intensive supportive therapy and constant monitoring of vital body functions is required. Inducing vomiting is not recommended. Ingestion of activated charcoal may be more effective than gastric lavage. Airway patency should be maintained. Sertraline has a large Vd, so increasing diuresis, performing dialysis, hemoperfusion, or blood transfusion may not be effective.

Pregnancy use

The use of the drug is contraindicated in pregnancy and lactation (breastfeeding).

There are no controlled effects of Sertraline in pregnant women.

Women of reproductive age who are expected to be prescribed sertraline should use effective contraceptive methods.

Sertraline is excreted with breast milk. There are no reliable data on the safety of using the drug during breastfeeding. If it is necessary to use the drug during lactation, breastfeeding should be stopped.

In the case of sertraline during pregnancy and during breastfeeding, some infants whose mothers have taken antidepressants from the group of selective serotonin reuptake inhibitors, including serotonin, may have symptoms similar to those seen during withdrawal of the drug.

Similarities