Trade names
Asentra. Zoloft. Serlift. Sertralin. Stimuloton. Torino.
Composition
50 mg and 100 mg.
Subgroup
Selective serotonin inhibitors reverse the seizure.
Action
Pharmacological Effects - antidepressive. It provides stimulating, sedative or antiholinergicheskogo action and no cardiotoxicity in animals. In tests the drug in healthy volunteers did not have sedative effects and do not modify the psychomotor function. Unlike tricyclic antidepressants, in treating depression or obsessive-compulsive disorders (obsessive state) sertralinom increase in body weight does not happen, in some cases it even decreases.
Mechanism of Action
Selectively blocks the reverse capture presinapticheskoy membrane serotonin neurons of brain and platelets, slightly affects the level of others neuromediators (noradrenaline and dofamina) in the synaptic fissure. It reinforces kateholaminergicheskuyu activity. It has affinity to muskarinovym holinoretseptoram, serotoninovym, dopaminovym, gistaminovym, GABA, benzodiazepinovym and adrenergic receptors. With long-term use reduces the number of adrenergic receptors in the CNS, have a similar effect of other clinically effective antidepressive drugs and antiobsessivnye.
Pharmacokinetics
The man in the treatment of sertralinom in a dose of 50 to 200 mg 1 time per day within 14 days, Cmax was achieved after 4.5-8.4 h after administration. Consequently, T1 / 2 (young and older men and women is 22-36 h) is approximately double accumulation of the drug to achieve Css after 1 week of treatment (receiving doses of 1 times / day). Eating does not have a significant influence on the bioavailability sertralina tablets. Binding to plasma proteins is about 98%. Sertralin actively biotransformiruetsya in the first passage through the liver. The main metabolite found in plasma, - N-desmetilsertralin - significantly less activity sertralinu (approximately 20-fold) in vitro, and in fact is not active in models of depression in vivo. The average T1 / 2 sertralina in young and elderly men and women is 22-36 h. T1 / 2 N-desmetilsertralina the range of 62-104 h. Sertralin and N-desmetilsertralin actively biotransformiruyutsya in humans, occurring metabolites derived from faeces and urine in equal amounts. Only a small fraction of the drug (less than 0.2%) derived from the urine in unchanged form.
Indications
* Treatment of depressive states (including the accompanying feelings of anxiety) in the presence and absence of mania in history;
* Treatment of obsessive-compulsive disorder (ROC) in children and adults;
* Treatment of panic disorder, accompanied or not by agoraphobic;
* Post-traumatic stress disorder (PTSD).
Contraindications
* Joint appointment of MAO inhibitors;
* Hypersensitivity to the drug.
Side Effects
In controlled tests of the re-taking the medication at different doses compared to placebo sertralin often leads to the following adverse reactions:
On the part of the digestive system: nausea, diarrhea, unsteady stool, anorexia, dyspepsia, xerostomia. Asymptomatic increase of aminotransferase activity (AST and ALT) in the treatment of sertralinom met infrequently (approximately 0.8% of cases). These violations are usually observed during the first 1-9 weeks of treatment and rapidly disappeared after the abolition of the drug.
From CNS: tremor, dizziness, insomnia, drowsiness.
From the water-electrolyte balance: in some cases - hyponatremia (after cessation of treatment, sodium levels returned to normal) and in some cases, hyponatremia may have been linked to inadequate secretion antidiureticheskogo hormone. The reduction of sodium in most cases observed in patients with older age, as well as patients receiving diuretics and other medications.
On the part of blood clotting: transient thrombocytopenia, atypical bleeding and haemorrhagic rash, causal connection with the admission that the drug has not been established.
Other: increased sweating, violation of sexual function in men (mostly delayed ejaculation).
Profile of adverse events encountered during the double-blind placebo-controlled trials in patients with intrusive state, was similar to that in patients with depression.
After the introduction of the drug on the market before the records were the following side effects, which sometimes occurred when using the drug, but can not be associated with him: vomiting, abdominal pain, disturbance of motor activity (ekstrapiramidnye symptoms and violations of gait), convulsions, disturbance of menstrual cycle giperprolaktinemiya, galaktoreya, rash (including rare cases of erythema multiformnoy), rarely - pancreatitis and severe violations of the functions of the liver (including hepatitis, jaundice and liver failure). We describe the rare cases of the syndrome cancel. In rare cases, there were the following side effects, which could not be distinguished from the natural flow of the main manifestations of the disease: paresthesia, gipesteziya, symptoms of depression, hallucinations, aggressive reaction, agitation, anxiety and psychosis.
Dependence syndrome and the abolition of
Sertralin does not cause physical or psychological dependence.
Interaction
We describe cases of serious adverse reactions in patients receiving sertralin in combination with MAO inhibitors, including selective MAO inhibitors (selegiline) and reversible inhibitors of MAO (moklobemid). Symptoms of this collaboration include: hyperthermia, rigidity, muscle cramps, changes in mental status, which include confusion, irritability and excessive excitation to the development of deliriya and coma.
Simultaneous reception of the drug at a dose of 200 mg / day did not influence ethanol increases, carbamazepine, haloperidol or phenytoin on cognitive and psychomotor function in healthy people.
Sertralin associated with plasma proteins, so it is necessary to take into account the possibility of its interaction with other drugs, have been linked to proteins. However, during the 3 formal studies on interaction with diazepam, tolbutamidom and warfarin, a significant influence on the binding of drugs to proteins have been identified.
Simultaneous reception of the drug at a dose of 200 mg / day of diazepam or tolbutamidom led to a small but statistically significant change in some pharmacokinetic parameters. Tsimetidin caused a significant reduction in clearance sertralina co-application with the drug. If you are applying sertralin no effect on beta-adrenoblokiruyuschuyu activity of atenolol. Signs drug interactions 200 mg / day with glibenklamidom and digoxin were not found. If you are taking 200 mg / day with warfarin, there was a small but statistically significant increase in prothrombin time. In this regard, should closely monitor the rate of prothrombin time at the beginning of therapy sertralinom and after its repeal.
Many antidepressants, such as selective serotonin inhibitors reverse the seizure, including sertralin, and most tricyclic antidepressants, inhibit a biochemical activity of the enzyme, metabolized drugs - cytochrome P450 2D6 (debrizokvingidroksilaza) and thus may increase the plasma concentrations of other drugs that biotransformiruyutsya 2D6 and have a narrow therapeutic index, such as tricyclic antidepressants and drugs antiaritmicheskie class 1c (propafenon and flekainid). With simultaneous application of the drug, subjected to biotransformation P450 2D6, and sertralina first may need to assign to a lower dose than usual. In addition, when you cancel sertralina may require increased doses of other drugs.
In placebo-controlled trials in healthy volunteers sertralin do not affect the pharmacokinetics of lithium, but in comparison with placebo, increased tremor, indicating a possible pharmacodynamic interaction. In this regard, while treating sertralinom, like other selective serotonin inhibitors reverse the seizure, in combination with other drugs type of lithium, which may act through mechanisms serotoninergicheskie, be careful.
Dosing and Administration in Adults
Appoints 1 time / day morning or evening. Tablets can be taken irrespective of food intake. When depression and begin treatment with the ROC dose of 50 mg / day. When the effect of daily low dose can be increased gradually (50 mg), in a few weeks to a maximum dose of 200 mg / day. The initial effect may occur within 7 days after the start of treatment, but the full effect is usually achieved within 2-4 weeks.
Treatment of panic disorder and PTSD beginning with doses of 25 mg / day, which increased after 1 week to 50 mg / day. The use of drugs under the scheme will reduce the frequency of unwanted effects of early treatment, which are typical for panic disorder.
In a long-term maintenance therapy medication designate the minimum effective dose, which subsequently changed depending on the clinical effect. In old age, drug use in the same doses as in younger patients.
Dosing and Administration in pediatric practice
In children and adolescents aged 13-17 years suffering from ROC, treatment should begin with a dose of 50 mg / day. In children aged 6-12 years of therapy to begin with ROC dose 25 mg / day, after 1 week it increased to 50 mg / day. Later, with little effect of the dose can be increased in steps of 50 mg / day to 200 mg / day as needed. However, to avoid overdosing, with increasing doses over 50 mg should be taken into account the smaller body weight in children than adults. You may change the dose should be at intervals of not less than 1 week.
In completed and ongoing studies sertralin received more than 250 children with the ROC. Safety sertralina in these studies was comparable to that in studies of adult patients with ROC. Effectiveness sertralina with depression or panic disorder in children in controlled studies has not been established. The safety and efficacy sertralina in children aged less than 6 years of age are not proven.
Pregnancy and lactation
When pregnancy sertralin should be appointed only if the expected benefits outweigh the risks, because Adequate well-controlled testing of the drug in pregnant women.
Information about the intrusion sertralina in breast milk are not available and therefore is not recommended to assign the drug during lactation.
Women of childbearing age during treatment sertralinom must use appropriate methods of contraception.
In experimental studies, with the introduction sertralina rats and rabbits at doses approximately 20 and 10 times the maximum daily dose for humans (in mg / kg), signs of teratogenic action have been identified. Sertralin do not have mutagenic action. Nevertheless sertralin in doses of about 2.5-10 times the maximum daily dose for humans (in mg / kg) caused a delay of ossification of bone tissue fetus, possibly as a result of the impact on the parent species. When you enter sertralina at doses approximately 5 times the maximum dose for humans (in mg / kg), resulted in the decreased survival of newborns.
Overdosage
Toxicological studies in various animal species demonstrated good portability sertralina. Available data indicate a wide range of security sertralina with his overdose. Reported cases of overdose with sertralinom monotherapy at a dose of up to 13.5 g. There have been reports of fatal overdose sertralina when combined with other drugs and / or alcohol. In this regard, in all cases of overdose requires intensive treatment.
Treatment. Recommendations for specific therapy of drug overdoses, as well as specific antidotes are not available. There should be a normal adequate airway, oxygenation and ventilation of the lungs. Activated charcoal, which can be used in combination with sorbitol, may be even more effective than emesis or gastric lavage. Advisable to monitor the performance of the heart and other vital organs and the conduct symptomatic and supportive therapy. The use of forced diuresis and hemodialysis impractical because of the large volume of distribution of the drug.
Cautions
Sertralin can be used no earlier than 14 days after the lifting of MAO inhibitors. MAO inhibitors also can be used no earlier than 14 days after lifting sertralina.
You must be careful while appointing sertralina with other drugs, reinforcing serotoninergicheskuyu neyrotransmissiyu, such as tryptophan or fenfluramin. Pending receipt of additional data serotoninergicheskie funds should not be used in combination with sertralinom.
Experience of clinical trials aimed at determining optimal time required for transfer of patients to receive other funds to antidepressive sertralin is limited. You must be careful with such a transition, especially with long-acting drugs. The required interval between the cancellation of a selective inhibitor of serotonin and a capture start receiving a similar drug is not installed.
Sertralin exposed to an active metabolism in the liver. According to the pharmacokinetic study, with acute administration sertralina in patients with stable hepatic cirrhosis easy flow increase in T1 / 2 drug, and AUC (area under the curve concentration-time ") were compared with those in healthy people. Apply sertralin in patients with liver disease should be with caution, it is necessary to discuss the desirability of reducing the dose or increasing the interval between taking the medication. Sertralin unchanged output of urine in small amounts. In patients with primary and Moderate renal insufficiency (CC 20-50 ml / min) and patients with severe renal insufficiency (CC less than 20 ml / min) pharmacokinetic parameters at single sertralina his admission did not differ significantly from controls. However, pharmacokinetics sertralina in the equilibrium state of this category of patients studied is insufficient, therefore, in the treatment of patients with renal insufficiency should be careful.
In patients with convulsive syndrome certralina application is not examined, therefore, should avoid its use in unstable epilepsy and patients with controlled epilepsy require careful monitoring during treatment. If you have seizures in all cases, the drug should be abolished.
When testing sertralina gipomaniya and mania occurred in about 0.4% of patients receiving sertralin. Cases activate mania / gipomanii described as a small portion of patients with major depression who received other antidepressive or antiobsessivnye funds.
The risk or benefit of combined use of Electro-therapy and sertralina in clinical trials not been studied. Patients depression inherent propensity to attempt suicide, which persists until the onset of significant improvement in their condition as a result of treatment. In this regard, the early treatment of patients must be carefully monitored. In clinical studies on the effectiveness of sertralina in the elderly its effectiveness in patients of this group has been demonstrated in more than 700 patients over 65 years. Profile and frequency of adverse reactions in patients older and younger age were the same. Against the background of the reception sertralina not to drink alcohol.
Studies have shown that sertralin no effect on psychomotor function. Nevertheless, antidepressive or antiobsessivnye could impair mental or physical activity necessary to perform the functions of the type of potentially dangerous driving, or management arrangements, as necessary to warn the patient.
