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Pharmacodynamic properties

Sertraline is an antidepressant, a powerful specific serotonin reuptake inhibitor (5-HT) in neurons. It has a very weak effect on the reuptake of norepinephrine and dopamine. At therapeutic doses, sertraline blocks serotonin uptake in human platelets. It does not have a stimulating, sedative or anticholinergic effect. Due to the selective inhibition of seizure of 5-HT, sertraline does not enhance adrenergic activity. Sertralin has no affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA or benzodiazepine receptors. Sertralin does not cause drug dependence, does not cause an increase in body weight with prolonged use.

Pharmacokinetic properties

Absorption is high (but at a slow rate). Bioavailability increases with food intake by 25%. Food increases the maximum concentration (Cmax) by 25% and shortens the time to reach the maximum concentration (Tcmax). In humans, when treated with sertraline at a dose of 50 to 200 mg once a day for 14 days, the concentration of the drug in plasma reached a peak (Cmax) 4.5–8.4 h after administration. Сmax and the area under the concentration-time curve (AUC) are proportional to the dose within 50-200 mg of sertraline 1 time per day for 14 days, thus revealing the linear nature of the pharmacokinetic dependence. The pharmacokinetic profile in adolescents and the elderly is not significantly different from that in patients aged 18 to 65 years. The average elimination half-life (T1 / 2) of sertraline in young and elderly men and women is 22-36 hours. Accordingly, the final T1 / 2 shows approximately two-fold cumulation of the drug before the onset of equilibrium concentrations after 1 week of treatment (receiving the dose once a day). Plasma protein binding is approximately 98%. The pharmacokinetics of sertraline in children with OCD (see below) have been shown to be similar to those in adults (although sertraline metabolism is slightly more active in children). However, given the lower body weight in children (especially at the age of 6-12 years), the drug is recommended to be used at a lower dose in order to avoid excessive plasma levels.

Sertralin undergoes active biotransformation during the first passage through the liver. The main metabolite found in plasma, N-desmethyl sertraline, is significantly inferior (approximately 20 times) to sertraline in in vitro activity and is actually not active in in vivo depression models. T1 / 2 N-desmethyl sertraline varies in the range of 62-104 hours. Sertralin and N-desmethyl sertraline actively biotransform; The resulting metabolites are excreted in equal amounts with feces and urine. Unchanged sertraline is excreted in the urine in small amounts (<0.2%). In patients with cirrhosis of the liver, the T1 / 2 drug and AUC are increased in comparison with those in healthy people.

Indications for use

• Depression of various etiologies (treatment and prevention)
• Obsessive-compulsive disorders (OCD)
• Panic disorders
• Posttraumatic stress disorder (PTSD)
• Social phobia

Contraindications

Known hypersensitivity to sertraline, children under 6 years of age, pregnancy and breastfeeding period (see section Pregnancy and breastfeeding). The drug should not be prescribed to patients who are simultaneously receiving monoamine oxidase inhibitors (MAO) and pimozide. With care: organic diseases of the brain (including mental retardation), epilepsy, hepatic and / or renal failure, pronounced weight loss.

Pregnancy and breastfeeding

Pregnant women do not have controlled results of sertraline; therefore, it is worthwhile to prescribe the drug only if the expected benefit to the mother outweighs the potential risk to the fetus. Women of reproductive age who are supposed to prescribe sertraline should be advised to use effective contraceptives.

Sertralin is found in breast milk, and therefore, treatment with this drug during breastfeeding is not recommended. There is no reliable data on the safety of its use in this case. If the treatment is still necessary, it is better to stop breastfeeding. If sertraline is used during pregnancy and lactation in some newborns whose mothers took antidepressants from the group of selective serotonin reuptake inhibitors (SSRIs), including serotonin, symptoms similar to the reaction to drug withdrawal may be observed.

Side effect

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

Cardiovascular system: rapid heartbeat, tachycardia, arterial hypertension.

Musculoskeletal system: arthralgia, muscle cramps.

Central and peripheral nervous system: extrapyramidal disorders (dyskinesias, akathisia, gnashing of teeth, gait disturbance), involuntary muscle contractions, paresthesias, fainting, drowsiness, headache, migraine, dizziness, tremor, insomnia, anxiety, agitation, hypoxia, mother's sleep, dizziness, tremor, insomnia, anxiety, agitation, hypoxia, mother's sleep , euphoria, nightmares, psychosis, decreased libido, suicide, coma.

Respiratory system: bronchospasm, yawning.

Urinary system: enuresis, incontinence or urinary retention.

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

Bodies of sight: visual impairment, mydriasis.

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

Hepatobiliary system: hepatitis, jaundice, liver failure.

Allergic reactions: urticaria, pruritus, anaphylactoid reaction.

Other: weakness, reddening of the skin or "flushes" of blood to the face, tinnitus, alopecia, angioedema, swelling of the face, periorbital edema, photosensitivity reaction, purpura, increased sweating, loss of appetite (rarely - increased), up to anorexia, decrease or an increase in body weight, bleeding (including nasal, gastrointestinal, or hematuria), peripheral edema, occasionally Stephen-Johnson syndrome, and epidermal necrolysis.

Data from laboratory tests: rarely, with prolonged use, an asymptomatic increase in serum transaminase activity occurs. Cancellation of the drug in this case leads to the normalization of the activity of enzymes. Perhaps the development of leukopenia and thrombocytopenia, as well as an increase in serum cholesterol levels. When discontinuing treatment with sertraline, rare cases of withdrawal syndrome are described. Paresthesias, hypoesthesia, depression symptoms, hallucinations, aggressive reactions, agitation, anxiety, or symptoms of psychosis, which cannot be distinguished from the symptoms of the underlying disease, may appear.

Overdose

Severe symptoms of sertraline overdose have not been identified even with the administration of the drug in large doses. However, when administered with other drugs or alcohol can cause severe poisoning, even coma and death. An overdose can cause serotonin syndrome with nausea, vomiting, drowsiness, tachycardia, agitation, dizziness, psychomotor agitation, diarrhea, sweating, myoclonus and hyperreflexia. Treatment: there are no specific antidotes. Requires intensive supportive therapy and constant monitoring of vital body functions. Vomiting is not recommended. The introduction of activated carbon may be more effective than gastric lavage. It is necessary to maintain airway patency. Sertraline has a large volume of distribution, therefore, increased diuresis, dialysis, hemoperfusion, or blood transfusion may be unsuccessful.

Interaction with other drugs

Pimozide. With the joint use of sertraline and pimozide, there was an increase in the levels of pimozide with its single appointment in a low dose (2 mg). An increase in pimozide levels was not associated with any changes in the ECG. Since the mechanism of this interaction is not known, and pimozide has a narrow therapeutic index, the simultaneous administration of pimozide and sertraline is contraindicated.

Monoamine oxidase inhibitors (MAOIs). There have been severe complications, while the use of sertraline and MAOIs (including selective effect (selegiline) MAOIs and reversible type of action (moclobemide and linezolid). The development of serotonin syndrome may (hyperthermia, rigidity, myoclonus, the lability of the autonomic nervous system (rapid fluctuations in respiratory parameters and cardiovascular system), changes in mental status, including increased irritability, marked excitement, confusion, which in some cases may or in a delirious state or coma.) Similar complications, sometimes fatal, occur when prescribing an MAO during treatment with antidepressants that suppress the neuronal seizure of monoamines or immediately after their withdrawal.

Drugs that inhibit the central nervous system and ethanol. The combined use of sertraline and substances that depress the central nervous system requires close attention, and the use of alcoholic beverages and drugs containing alcohol during treatment with sertraline is also prohibited. No potentiation of the effect of ethanol, carbamazepine, haloperidol, or phenytoin on cognitive and psychomotor function in healthy people; however, the combined use of sertraline and alcohol is not recommended.

Anticoagulants of indirect action (warfarin). When coadministered with sertraline, there is not a significant but statistically significant increase in prothrombin time - in these cases it is recommended to monitor the prothrombin time at the beginning of treatment with sertraline and after its withdrawal.

Special instructions

Sertralin should not be prescribed in conjunction with an MAOI, and also for 14 days after stopping the treatment of MAOI. Similarly, after the abolition of sertraline within 14 days do not prescribe IMAO.

Serotonin syndrome and neuroleptic malignant syndrome

When using selective serotonin reuptake inhibitors (SSRIs), cases of the development of serotonin syndrome (SS) and malignant neuroleptic syndrome (MNS) are described, the risk of which increases when combined with SSRIs with other serotonergic drugs (including triptans), as well as drugs that affect the metabolism serotonin (including monoamine oxidase inhibitors), antipsychotics and other dopamine receptor antagonists. Signs of SS can be changes in mental status (in particular, agitation, hallucinations, coma), autonomic lability (tachycardia, fluctuations in blood pressure, hyperthermia), changes in neuro-muscular transmission (hyperreflexia, impaired coordination of movements) and / or impaired gastrointestinal intestinal tract (nausea, vomiting and diarrhea). Some manifestations of SS, including hyperthermia, muscle rigidity, vegetative lability with the possibility of rapid fluctuations of parameters of vital functions, as well as changes in mental status, may resemble the symptoms that develop during CSN. It is necessary to monitor patients for the development of clinical manifestations of SS and MNS.

Other serotonergic drugs

Care must be taken when administering sertraline with other drugs that enhance serotonergic neurotransmission, such as tryptophan, fenfluramine or 5-HT agonists. If possible, such a joint appointment should be excluded, given the likelihood of pharmacodynamic interaction.

Transition from other selective serotonin reuptake inhibitors (SSRIs), antidepressants or anti-obsessive drugs

The experience of clinical studies, the purpose of which was to determine the optimal time required for transferring patients from taking other anti-depressive and anti-obsessive drugs to sertraline, is limited. Care must be taken in such a transition, especially with long-acting drugs, such as fluoxetine. The required interval between the cancellation of one selective serotonin reuptake inhibitor and the start of taking another similar drug has not been established. It should be noted that in patients undergoing electroconvulsive therapy, sufficient experience with sertraline is absent.

The possible success or risk of such a combination treatment has not been studied. There is no experience with sertraline in patients with convulsive syndrome, so its use in patients with unstable epilepsy should be avoided, and patients with controlled epilepsy should be carefully monitored during treatment. If seizures occur, the drug should be discontinued. Depressed patients are at risk of suicidal attempts. This danger persists until the development of remission. Therefore, from the start of treatment and until the optimum clinical effect is achieved, patients should be provided with constant medical supervision.

Activation of mania/hypomania

During clinical studies prior to the introduction of sertraline into the market, hypomania and mania were observed in about 0.4% of patients receiving sertraline. Cases of activation of mania/hypomania are also described in a small proportion of patients with manic-depressive psychosis who received other anti-depressive or anti-obsessive drugs.

Use in case of insufficiency of the liver

Sertralin is actively biotransformed in the liver. According to a pharmacokinetic study, with repeated administration of sertraline in patients with stable liver cirrhosis, an increase in the half-life of the drug and an almost threefold increase in AUC (area under the concentration / time curve) and the maximum concentration of the drug compared with those in healthy people were observed. There were no significant differences in plasma binding in the two groups. Caution should be used with sertraline in patients with liver disease. When prescribing a drug to a patient with impaired liver function, it is necessary to discuss the feasibility of reducing the dose or increasing the interval between taking the drug.

Use in renal failure

Sertralin undergoes active biotransformation, therefore, in an unchanged form with urine, it is excreted in small quantities. In patients with mild and moderate renal insufficiency (creatinine clearance 30-60 ml / min) and patients with moderate or severe renal insufficiency (creatinine clearance 10-29 ml / min) sercoralin pharmacokinetic parameters (AUC0-24 and Сmax) with repeated his admission was not significantly different from the control group. In all groups, the half-life of the drug was the same, as well as there were no differences in binding to plasma proteins. The results of this study suggest that, as expected, given the slight renal excretion of sertraline, its dose adjustment depending on the severity of renal failure is not required.

Pathological bleeding / hemorrhage

It is recommended to use caution when prescribing selective serotonin reuptake inhibitors in combination with drugs that have an established ability to alter platelet functions, as well as in patients with a history of hemorrhagic diseases.

Hyponatremia

During treatment with sertraline, transient hyponatremia may occur. This is more common in elderly patients, as well as when taking diuretics or a number of other drugs. This side effect is associated with the syndrome of inadequate secretion of antidiuretic hormone. With the development of symptomatic hyponatremia, sertraline should be discontinued and adequate therapy should be prescribed to correct the sodium level in the blood. Signs and symptoms of hyponatremia include headache, impaired concentration, memory impairment, weakness and instability, which can lead to falls. In more severe cases, hallucinations, syncope, convulsions, coma, respiratory arrest and death may occur.

Influence on ability to drive motor transport and control mechanisms

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