Zoloft, 100 mg 28 pcs

Zoloft is an antidepressant.

Pharmacodynamics

Sertraline is an antidepressant, a potent specific inhibitor of serotonin reuptake (5-NT) in neurons. It has a very weak effect on norepinephrine and dopamine reuptake. At therapeutic doses, sertraline blocks serotonin uptake in human platelets. It has no stimulant, sedative or anticholinergic effects. Due to its selective inhibition of 5-NT uptake, sertraline does not increase adrenergic activity. Sertraline has no affinity for muscarinic (cholinergic), serotoninergic, dopaminergic, adrenergic, histaminergic, GABA or benzodiazepine receptors.

Sertraline does not cause drug dependence and weight gain with prolonged use.

Pharmacokinetics

Absorption is high (but at a slow rate). Bioavailability is increased with food by 25%. Food increases C_max by 25% and shortens T_max. In humans, when treated with sertraline at a dose of 50 to 200 mg once daily for 14 days, the T_max in plasma is 4.5-8.4 h after ingestion. C_max and AUC are proportional over a dose range of 50-200 mg of sertraline once daily for 14 days, with a linear pharmacokinetic relationship. The pharmacokinetic profile in adolescents and the elderly does not differ from that in patients aged 18 to 65 years. The mean T_1/2 of sertraline in young and elderly men and women is 22-36 h. Corresponding to the final T_1/2 there is approximately double cumulation of the drug before the onset of C_SS after 1 week of treatment (once-daily dose). Binding to plasma proteins is approximately 98%. It has been shown that the pharmacokinetics of sertraline in children with obsessive-compulsive disorder (OCD, see below) are 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), a lower dose of the drug is recommended to avoid excessive plasma levels.

Sertraline undergoes active biotransformation on first passage through the liver. The major metabolite found in plasma, N-desmethylsertraline, is significantly inferior (approximately 20-fold) to sertraline in in vitro activity and is virtually inactive in in vivo models of depression. The T_1/2 of N-desmethylsertraline varies from 62-104 h. Sertraline and N-desmethylsertraline are actively biotransformed; the resulting metabolites are excreted in equal amounts in the feces and urine. Unchanged sertraline is excreted in insignificant amounts in the urine (1/2 of the drug and AUC compared to those of healthy subjects.

Indications

Active ingredient

Composition

Active substance:

Sertraline (as hydrochloride)100 mg;

Auxiliary substances:

Calcium phosphate;

MCC;

hydroxypropylcellulose;

sodium starch glycolate;

magnesium stearate;

hydroxypropyl methylcellulose;

polyethylene glycol;

polysorbates;

titanium dioxide (E171)

How to take, the dosage

Overly, once daily, in the morning or evening, regardless of meals.

The initial dose

Depression and OCD. Treatment with sertraline should be started with a dose of 50 mg/day.

Panic disorder, PTSD, and social phobia. Treatment begins with a dose of 25 mg/day, which is increased after 1 week to 50 mg/day. Use of the drug on such a regimen reduces the incidence of early unwanted effects of treatment typical of panic disorder.

Dose selection

Depression, OCD, panic disorder, PTSD, and social phobia. If the effect of Sertraline in patients at a dose of 50 mg/day is insufficient, the daily dose may be increased. The dose should be increased at weekly intervals up to a maximum recommended dose of 200 mg/day.

The initial therapeutic effect may be seen within 7 days, but full effects are usually achieved within 2-4 weeks (or even longer for OCD).

Supportive therapy

The maintenance dose in long-term treatment should be the minimum effective dose – with adjustments accordingly, depending on the therapeutic effect.

Therapeutic use in children

Safety and efficacy of sertraline have been established in children with OCD (ages 6 to 17 years). In adolescents (ages 13-17) with OCD, treatment with sertraline should be started at a dose of 50 mg/day. In children (at the age of 6-12 years), treatment of OCD should begin with a dose of 25 mg/day, increasing to 50 mg/day after 1 week. Later, if the effect is insufficient, the dose can be increased in steps, 50 mg/day, up to 200 mg/day, as required. In clinical trials in depressed and OCD patients aged 6 to 17 years, it has been shown that the pharmacokinetic profile of sertraline is similar to that of adults. However, to avoid overdose, the lower body weight in children compared to adults must be taken into account when increasing doses over 50 mg.

Dose selection in children and adolescents. T1/2 Sertraline is approximately 1 day, so dose changes should be at least 1 week apart.

Particular patient groups

Elderly people. In the elderly, the drug is used in the same dose range as in younger people.

Hepatic impairment. Sertraline should be used with caution in patients with liver disease. In patients with hepatic impairment, lower doses should be used or the interval between doses should be increased.

Kidney function impairment. Sertraline is largely metabolized in the body. Only a small amount of the drug is excreted unchanged in the urine. As expected, in view of insignificant renal excretion of Sertraline, no dose adjustment, depending on the severity of renal impairment, is required.

Interaction

Pimozide. When sertraline and pimozide were used together, there was an increase in pimozide levels when administered once at a low dose (2 mg). The increase in pimozide levels was not associated with any ECG changes. Because the mechanism of this interaction is unknown and pimozide has a narrow therapeutic index, concomitant administration of pimozide and sertraline is contraindicated.

MAO inhibitors. Severe complications have been reported with concomitant use of sertraline and MAO inhibitors (including selectively acting ones – selegiline and with reversible type of action – moclobemide, as well as linezolid). Serotonin syndrome (SS) may develop (hyperthermia, rigidity, myoclonus, vegetative nervous system lability (rapid fluctuations in respiratory and CSF parameters), changes in mental status, including increased irritability, marked agitation, confusion, which in some cases may progress to delirium or coma). Similar complications, sometimes fatal, occur when prescribing MAO inhibitors during treatment with antidepressants that inhibit monoamine neuronal uptake, or immediately after their withdrawal.

CNS depressants and ethanol. The combined use of sertraline and CNS-depressant drugs requires close attention, and the use of alcoholic beverages and drugs containing alcohol during treatment with sertraline is also prohibited. No potentiation of the effects of ethanol, carbamazepine, haloperidol, or phenytoin on cognitive and psychomotor function has been noted in healthy subjects; however, co-administration of sertraline and alcohol is not recommended.

The indirect-acting anticoagulants (warfarin). A small but statistically significant increase in PV has been observed when coadministered with sertraline (in these cases, it is recommended to monitor PV at the beginning of treatment with sertraline and after its withdrawal).

Pharmacokinetic interaction

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

Cimetidine. Simultaneous use significantly reduces the clearance of sertraline.

The drugs metabolized by cytochrome P450 isoenzyme 2D6. Long-term treatment with sertraline at a dose of 50 mg/day increases plasma concentrations of concomitantly used drugs metabolized by this enzyme (tricyclic antidepressants, antiarrhythmic drugs of class IC – propafenone, flecainide).

The drugs metabolized by other enzyme systems of cytochrome P450. Experiments on study of interaction in vitro have shown that beta-hydroxylation of endogenous cortisol, as well as metabolism of carbamazepine and terfenadine by CYP3A3/4 isoenzyme do not change with long-term administration of sertraline at a dose of 200 mg/day. Plasma concentrations of tolbutamide (but concomitant administration reduces tolbutamide clearance – blood glucose control is required for concomitant use), phenytoin and warfarin also do not change with long-term administration of Sertraline at the same dose. Thus, it can be concluded that sertraline does not inhibit CYP2C9 isoenzyme.

The serum concentration of diazepam is not affected by Sertraline, which suggests that there is no inhibition of CYP2C19 isoenzyme. According to in vitro studies, Sertraline has little or no effect on the CYP1A2 isoenzyme.

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

Drugs that affect serotonergic transmission. A washout period is not necessary when replacing one serotonin neuronal takeover inhibitor with another. However, caution is required when altering the course of treatment. Co-prescribing tryptophan or fenfluramine with sertraline should be avoided.

Induction of microsomal liver enzymes. Sertraline causes minimal induction of hepatic enzymes. Concomitant administration of Sertraline at a dose of 200 mg and antipyrine results in a small (5%) but significant decrease in T1/2 of antipyrine.

Athenololol. When co-administered, sertraline does not alter its beta-adrenoblocking effect.

Glybenclamide and digoxin. When sertraline is administered in a daily dose of 200 mg, no drug interactions with these drugs have been identified.

Phenytoin. Long-term use of sertraline at a dose of 200 mg/day has no clinically significant effect and does not inhibit the metabolism of phenytoin. Despite this, close monitoring of plasma phenytoin levels is recommended from the time of administration of sertraline, with appropriate adjustments in phenytoin doses.

Sumatriptan. Very 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.

Special Instructions

Sertraline should not be coadministered with MAO inhibitors, or for 14 days after stopping treatment with MAO inhibitors. Similarly, no MAOI inhibitors should be prescribed for 14 days after withdrawal of Sertraline.

CS and malignant neuroleptic syndrome (MNS). There are cases of SS and MNS when using SSRIs, the risk of which is increased when combining SSRIs with other serotonergic agents (including triptans), as well as with drugs that affect serotonin metabolism (including MAO inhibitors), antipsychotics and other dopamine receptor antagonists. Manifestations of SS can be changes in mental status (in particular agitation, hallucinations, coma), autonomic lability (tachycardia, BP fluctuations, hyperthermia), changes in neuromuscular transmission (hyperreflexia, movement coordination disorders) and/or GI disorders (nausea, vomiting and diarrhea). Some manifestations of SS, including hyperthermia, muscle stiffness, autonomic lability with possible rapid fluctuations of vital functions, and changes in mental status may resemble the symptomatology developing in MNS. It is necessary to monitor patients for development of clinical manifestations of SS and MNS.

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

Transition from other SSRIs, antidepressants, or antiobesity drugs. There is limited experience with clinical studies that have sought to determine the optimal time to switch patients from other antidepressants and antipsychotics to sertraline. Caution should 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.

In patients undergoing electroconvulsive therapy, there is insufficient experience with sertraline. The possible success or risk of this combination treatment has not been studied.

There is no experience with sertraline in patients with a seizure syndrome, so it 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.

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

The activation of mania/hypomania. During clinical trials prior to the introduction of sertraline on the market, hypomania and mania were observed in approximately 0.4% of patients receiving sertraline. Mania/hypomania activation has also been described in a small proportion of manic-depressive psychosis patients receiving other antidepressants or antipsychotics.

The use in liver function insufficiency. Sertraline is actively biotransformed in the liver. According to a pharmacokinetic study, repeated administration of sertraline in patients with stable mild cirrhosis showed increased T1/2 of the drug and nearly a threefold increase in AUC and Cmax of the drug compared to those 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 impaired liver function, it is necessary to discuss the advisability of reducing the dose or increasing the interval between doses of the drug.

The use in renal failure. Sertraline undergoes active biotransformation, therefore in unchanged form it is excreted in small amounts in the urine. In patients with mild to moderately expressed renal insufficiency (Cl creatinine 30-60 ml/min) and in patients with moderate or severe renal failure (Cl creatinine 10-29 ml/min) pharmacokinetic parameters (AUC0-24 and Cmax) of Sertraline in repeated use were not significantly different from control group. In all groups, the T1/2 of the 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.

Pathological bleeding/hemorrhage. Caution is recommended when prescribing SSRIs in combination with drugs with an established ability to alter platelet function, as well as in patients with a history of hemorrhagic disease.

Hyponatremia. Transient hyponatremia may occur during treatment with sertraline. This develops 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 levels. Signs and symptoms of hyponatremia include headache, impaired concentration, impaired memory, weakness and unsteadiness, which may lead to falls. In more severe cases, hallucinations, fainting, seizures, coma, respiratory failure, and death may occur.

The effect on the ability to drive and operate machinery.The prescription of Sertraline is generally not accompanied by impairment of psychomotor functions. However, its use simultaneously with other drugs may lead to impairment of attention and coordination of movements. Therefore, during treatment with sertraline, it is not recommended to drive vehicles, operate special machinery, or engage in activities associated with increased risk.

Contraindications

With caution: organic brain disease (including mental retardation); epilepsy; hepatic and/or renal insufficiency; marked weight loss.

Side effects

Digestive system: dyspeptic disorders (flatulence, nausea, vomiting, diarrhea, constipation), abdominal pain, pancreatitis, dry mouth.

Systemic diseases: palpitations, tachycardia, arterial hypertension.

Motor 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, vertigo, tremor, insomnia, anxiety, agitation, hypomania, mania, hallucinations, euphoria, nightmares, psychosis, decreased libido, suicide, coma.

Respiratory system: bronchospasm, yawning.

Urinary system disorders: enuresis, urinary incontinence or retention.

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

Visual organs: visual impairment, mydriasis.

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

Hepatobiliary system disorders: hepatitis, jaundice, liver failure.

Allergic reactions: urticaria, pruritus, anaphylactoid reaction.

Others: weakness, skin redness or flushing, tinnitus, alopecia, angioedema, facial edema, periorbital edema, photosensitization reaction, purpura, increased sweating, decreased appetite (rarely increased), up to anorexia, weight loss or increase in body weight, bleeding (including nasal and gastrointestinal bleeding).including nasal, gastrointestinal or hematuria), peripheral edema, occasionally Stevens-Johnson syndrome and epidermal necrolysis.

Data of laboratory tests: rarely, with long-term use, asymptomatic increase in serum transaminase activity occurs. Withdrawal of the drug in this case leads to normalization of enzyme activity.

Overdose

Symptoms: Severe symptoms of Sertraline overdose have not been identified even when administered in high doses. However, when administered simultaneously with other drugs or alcohol, severe poisoning may occur, up to and including coma and death.

Overdose may cause SS with nausea, vomiting, somnolence, tachycardia, agitation, dizziness, psychomotor agitation, diarrhea, increased sweating, myoclonus and hyperreflexia.

Treatment: There is no specific antidote to the drug. Intensive supportive therapy and constant monitoring of vital body functions is required. Inducing vomiting is not recommended. Administration 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

Zoloft is contraindicated in pregnancy and lactation.

Similarities