Expiration date: 11/2025
Active substance: Sertraline
Pharmacokinetics:
Absorption - high (but at a slow speed). Bioavailability increased food intake during 25%. Food increases the Cmax by 25% and shorten Tmax. In humans, the treatment of sertraline in a dosage of 50 to 1 200 mg once a day for 14 days in plasma Cmax achieved through 4,5-8,4 h after administration. Cmax and AUC are proportional in the range of 50-200 mg sertraline dose one time a day for 14 days, and the pharmacokinetic revealed linear dependence. The pharmacokinetic profile of adolescent and older people do not differ from those patients age 18 to 65 years. The average T1 / 2 of sertraline for young and elderly men and women is 22-36 hours, respectively the final T1 / 2 occurs in about two-time accumulation of the drug to the onset of CSS after 1 week of treatment. (Dosing - 1 time per day). Plasma protein binding is approximately 98%. It has been shown that the pharmacokinetics of sertraline in children with obsessive-compulsive disorder (OCD cm. Below) similar to that of adults (children although sertraline metabolism is somewhat more active). However, given the lower body weight in children (especially those aged 6-12 years), the drug is recommended at a lower dose to avoid excessive levels in plasma.
Active sertraline undergoes biotransformation in the first pass through the liver. The main metabolite, found in plasma, - N-desmetilsertralin - significantly inferior (about 20 times) for sertraline in vitro activity, and in fact is not active in vitro models of depression. T1 / 2 N-desmetilsertralina varies from 62-104 hours. Sertraline and N-desmetilsertralin actively biotransformed formed metabolites are excreted in equal amounts in the faeces and urine. Unchanged sertraline is excreted in the urine in small amounts (<0.2%). In patients with cirrhosis are increased T1 / 2 and AUC of the drug as compared to those of healthy people.
Description of the pharmacological actions:
Sertraline - antidepressant, a powerful specific inhibitor of the reuptake of serotonin (5-HT) neurons. He has very little effect on the reuptake of noradrenaline and dopamine. At therapeutic doses, sertraline blocks uptake of serotonin in human platelets. He has no stimulating, sedative or anticholinergic action. Due to the selective inhibition of 5-HT capture, sertraline does not enhance adrenergic activity. Sertraline has no affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA or benzodiazepine receptors.
Sertraline not cause drug dependence, and weight gain during chronic administration.
Testimony:
- Depression different etiology (treatment and prevention)
- obsessive-compulsive disorder (OCD)
- panic disorder
- post-traumatic stress disorder (PTSD)
- social phobia.
Contraindications:
- known hypersensitivity to sertraline
- simultaneous use of MAO inhibitors and pimozide
- pregnancy
- breastfeeding (see. "Pregnancy and breast-feeding" section)
- Children up to age 6 years.
Carefully:
- organic brain disease (including mental retardation)
- epilepsy
- liver and / or kidney failure
- marked reduction in body weight.
Application of pregnancy and breastfeeding:
Monitored results of the application of sertraline in pregnant women do not have, so the drug should assign them only if the expected benefit to the mother outweighs the potential risk to the fetus. Women of reproductive age, which is supposed to appoint sertraline should be advised to use effective contraception.
Sertraline is found in breast milk, therefore the treatment with this drug is not recommended during breast-feeding. No reliable data on safety of its use in this case. If treatment is necessary, it is better to stop breast-feeding. In the case of sertraline during pregnancy and lactation in some newborns whose mothers took antidepressants of the SSRI group, including serotonin, may experience symptoms similar to the reaction to the abolition of the drug.
Side effect:
From the digestive system: dyspepsia (bloating, nausea, vomiting, diarrhea, constipation), abdominal pain, pancreatitis, dry mouth.
From the CCC: palpitations, tachycardia, hypertension.
From the musculoskeletal system: arthralgia, muscle cramps.
From the central and peripheral nervous system: extrapyramidal disorder (dyskinesia, akathisia, gnashing of teeth, gait disturbance), involuntary muscle contractions, paresthesia, syncope, somnolence, headache, migraine, dizziness, tremor, insomnia, anxiety, agitation, hypomania, mania , hallucinations, euphoria, nightmares, psychosis, decreased libido, suicide, coma.
From the respiratory system: bronchospasm, yawning.
From the urinary system: bedwetting, incontinence or urinary retention.
Reproductive system and breast: sexual dysfunction (delayed ejaculation, decreased potency), galactorrhea, gynaecomastia, menstrual disorders, priapism.
On the part of the organs of vision: blurred vision, mydriasis.
From endocrine system: hyperprolactinemia, hypothyroidism, syndrome of inappropriate secretion of ADH.
On the part of the hepatobiliary system: hepatitis, jaundice, hepatic failure.
Allergic reactions: urticaria, pruritus, anaphylactoid reactions.
Other: weakness, skin redness or flushing, tinnitus, alopecia, angioedema, face edema, periorbital edema, reaction fotosensebilizatsii, purpura, increased sweating, decreased appetite (rarely - increased) up to anorexia, decreased or increased body weight, bleeding (including nasal, gastrointestinal or hematuria), peripheral edema occasionally Stevens-Johnson syndrome, epidermal necrolysis.
These laboratory tests: rare, long-term use there is asymptomatic increase of transaminases in blood serum. Removal of the drug, in this case leads to a normalization of enzyme activity.
Perhaps the development of leukopenia and thrombocytopenia, as well as increase the level of cholesterol in the blood serum.
When stopping treatment with sertraline described rare cases of withdrawal. May appear paresthesia, hypoesthesia, depressive symptoms, hallucinations, aggressive reaction, agitation, anxiety or psychotic symptoms that are indistinguishable from symptoms of the underlying disease.
Drug Interactions:
Pimozide. When the joint application of sertraline and pimozide pimozide levels showed an increase when administered in a single low dose (2 mg). Increased pimozide levels were not associated with any ECG changes. Since the mechanism of this interaction is unknown, and pimozide different narrow therapeutic range, concomitant use of pimozide and sertraline is contraindicated.
MAO inhibitors. There have been severe complications, while the use of sertraline and MAO inhibitors (including the selective MAO inhibitors - selegiline and reversible type of action - moclobemide and linezolid). Perhaps the development of serotonin syndrome (hyperthermia, rigidity, myoclonus, lability of the autonomic nervous system (rapid fluctuations of breathing parameters and cardiovascular) changes in mental status, including increased irritability, marked agitation, confusion, which in some cases can go into delirious state or coma). Similar complications, sometimes fatal, occur in the appointment of MAO inhibitors during treatment with antidepressants, depressing neuronal uptake of monoamines, or immediately after their withdrawal.
LC, depressing the central nervous system, and ethanol. The combined use of sertraline and substances which depress the central nervous system, requires close attention is also prohibited the use of alcohol and drugs containing alcohol during treatment with sertraline. There was no potentiation of ethanol effects, carbamazepine, haloperidol or phenytoin on cognitive and psychomotor performance in healthy people but not recommended sertraline and alcohol combined use.
Anticoagulants of indirect action (warfarin). At their joint appointment with sertraline been a slight but statistically significant increase in PV (in these cases it is recommended to control the PV at the beginning of treatment with sertraline and after its cancellation).
Pharmacokinetic interactions
Sertraline is bound to plasma proteins. It is therefore necessary to consider the possibility of interaction with other drugs that bind to the protein (eg diazepam and tolbutamide).
Cimetidine. Simultaneous application substantially reduces the clearance of sertraline.
Drugs metabolized isoenzyme cytochrome P450 2D6. Long-term treatment with sertraline 50 mg / day increases the plasma concentration of both drugs used in the metabolism which takes part this enzyme (tricyclic anti-depressants, anti-arrhythmic drugs class IC - propafenone, flecainide).
Drugs metabolized by cytochrome P450 other enzyme systems. Experiments on the interaction in vitro showed that the isoenzymes carried CYP 3A3 / 4 beta-hydroxylation of endogenous cortisol, as well as the metabolism of carbamazepine and long-term administration of terfenadine with sertraline at a dose of 200 mg / day does not change. Tolbutamide concentration in the plasma (but while taking tolbutamide reduces clearance - is necessary to monitor blood glucose, while the application), warfarin and phenytoin prolonged assignment of sertraline in the same dose also varies. Thus, we can conclude that sertraline does not inhibit CYP 2C9 isoenzyme.
Sertraline has no effect on the concentration of diazepam in blood serum, which indicates the absence of inhibition of isoenzymes CYP 2C19. According to studies in vitro, sertraline has virtually no effect or minimally inhibits isoenzyme CYP 1A2.
Lithium. The pharmacokinetics of lithium is not changed by concomitant administration of sertraline. However, the tremor occurs more often when they are used together. As well as the appointment of other SSRIs, concomitant use of sertraline with drugs that affect the serotonergic transmission (eg lithium), requires increased caution.
Agents acting on serotonergic transmission. When replacing one inhibitor of neuronal uptake of serotonin on the other in a period of no need of laundering. However, you want to be careful with changes in the course of treatment. Avoid concomitant administration of tryptophan or fenfluramine with sertraline.
The induction of microsomal liver enzymes. Sertraline causes minimal induction of liver enzymes. Co-administration of sertraline at a dose of 200 mg and a flame retardant results in a small (5%) but statistically significant decrease in T1 / 2 of antipyrine.
Atenolol. If co-administration of sertraline does not change its beta-adrenoceptor blocking action.
Glibenclamide and digoxin. With the introduction of sertraline in a daily dose of 200 mg of 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. Although it is recommended that careful monitoring of phenytoin levels in blood plasma of the designation of sertraline with a corresponding adjustment of phenytoin doses.
Sumatriptan. There have been very rare cases of weakness, increased tendon reflexes, confusion, anxiety and agitation in patients concurrently treated with sertraline and sumatriptan. It is recommended to monitor the patients, who have the relevant clinical reasons for the simultaneous reception of sertraline and sumatriptan.
Dosage and administration:
Inside, 1 time a day, morning or evening, regardless of the meal.
The initial dose
Depression and OCD. Treatment with sertraline should start with a dose of 50 mg / day.
Panic Disorder, PTSD, and social phobia. Treatment is initiated with a dose of 25 mg / day, which increased after 1 week to 50 mg / day. Use of the drug for such a scheme to reduce the frequency of early treatment of adverse effects characteristic of panic disorder.
dose selection
Depression, OCD, panic disorder, PTSD, and social phobia. With little effect in patients applying the sertraline dose of 50 mg / day, its daily dose may be increased. The dose should be increased with the interval of no more than once per week to a maximum recommended dose of 200 mg / day.
Some therapeutic effect may occur within 7 days, but the overall effect is usually achieved after 2-4 weeks (or even for a longer time in OCD).
Supportive therapy. Maintenance dose by prolonged treatment should be minimal effective - with its respective changes depending upon the therapeutic effect.
Application for the treatment of children
The safety and efficacy of sertraline established in children with OCD (aged 6 to 17 years). In adolescents (aged 13-17 years), suffering from OCD, sertraline treatment should be started at a dose of 50 mg / day. In children (aged 6-12 years) OCD therapy is started with a dose of 25 mg / day, 1 week, it increased to 50 mg / day. Subsequently, with little effect of the dose can be increased by steps of 50 mg / day to 200 mg / day, as needed. In clinical trials in patients with depression, OCD and aged 6 to 17 years it has shown that the pharmacokinetic profile of sertraline is similar to that of adults. However, to avoid overdosing with increasing doses of 50 mg to take into account the smaller body weight in children as compared to adults.
Selection of doses in children and adolescents. T1 / 2 of sertraline is approximately 1 day, so the dose changes should occur at intervals of not less than 1 week.
Use for treating the elderly. In old age, the drug is used in the same dose range as that of younger people.
The use in patients with liver failure. Sertraline should be used with caution in patients with liver disease. Patients with hepatic insufficiency should use lower doses or increase the interval between doses of the drug (See. "Special Instructions").
The use in patients with renal insufficiency. Sertraline largely metabolized in the body. In unaltered with urine output only a small amount of the drug. As expected, given the slight renal excretion of sertraline, the dose correction, depending on the severity of renal failure, it is not required (See. "Special instructions").
Overdose:
Symptoms: severe symptoms of an overdose of sertraline is not revealed even in the appointment of the drug in high doses. However, severe poisoning can occur when administered simultaneously with other drugs or alcohol, up to coma and death.
Overdose can cause serotonin syndrome with nausea, vomiting, somnolence, tachycardia, agitation, dizziness, agitation, diarrhea, sweating, myoclonus and hyperreflexia.
Treatment: No specific antidote. It requires intensive supportive care and constant monitoring of vital body functions. Induce vomiting is not recommended. Appointment of activated charcoal may be more effective than gastric lavage. It is necessary to maintain airway patency. In a large Vd sertraline, in this regard, increased diuresis, dialysis, hemoperfusion or blood transfusion may be inconclusive.
Special instructions:
Sertraline should not be administered together with MAO inhibitors and within 14 days after discontinuation of treatment MAO inhibitors. Similarly, after the abolition of sertraline for 14 days did not prescribe MAOIs.
Serotonin syndrome (SS), and neuroleptic malignant syndrome (NMS)
If SSRIs are described cases of SS and NMS, the risk of which is increased when combining SSRIs with other serotonergic agents (including triptans), as well as drugs that affect the metabolism of serotonin (including MAOIs), antipsychotics and other dopamine receptor antagonists. Manifestations of SS can be mental status changes (eg agitation, hallucinations, coma), autonomic lability (tachycardia, blood pressure fluctuations, hyperthermia), changes in neuromuscular transmission (hyperreflexia, incoordination) and / or disorders of the gastrointestinal tract (nausea, vomiting and diarrhea). Some manifestations of the SS, including hyperthermia, muscle rigidity, autonomic lability with rapid fluctuations of vital signs parameters, and changes in mental status, may resemble symptoms, develops at NSA. Required monitoring patients for the development of clinical manifestations of NMS and SS.
Other serotonergic agents. Caution should be exercised with concomitant administration of sertraline with other drugs which increase cerotoninergicheskuyu neurotransmission, such as tryptophan, fenfluramine or 5-HT agonists. This joint appointment if possible should be avoided, given the likelihood of a pharmacodynamic interaction.
Go with other SSRIs, antidepressants or drugs antiobsessivnye
Experience in clinical research, whose purpose was to determine the optimal time required to transfer patients taking other antidepressant and antiobsessivnye funds for sertraline is limited. Care must be taken in such a transition, particularly with long-acting drugs such as fluoxetine. The required interval between the cancellation of SSRIs and start taking a similar drug is not installed.
In patients undergoing electroconvulsive therapy, sufficient experience with sertraline is not. The possible success or the risk of such combined treatment has not been studied.
No experience with sertraline in patients with convulsive disorders, so avoid its use in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored during treatment. When the seizure medication should be discontinued.
Patients with depression are at risk for suicide attempts. This risk persists until the development of remission. Therefore, from the beginning of the treatment and to achieve optimal clinical response for patients should establish a permanent medical supervision.
Activation of mania / hypomania. During clinical trials before the introduction on the market of sertraline, hypomania and mania occurred in approximately 0.4% of patients treated with sertraline. Cases of activation of mania / hypomania have also been described in a small proportion of patients with manic-depressive psychosis treated with other antidepressant or antiobsessivnye funds.
Use in liver function failure. Sertraline actively biotransformed in the liver. According to pharmacokinetic study at repeated sertraline in patients with stable hepatic cirrhosis, lung flow increase observed T1 / 2 of the drug and almost threefold increase in AUC and Cmax of the drug as compared to those of healthy people. There were no significant differences in plasma protein binding was not in the two groups. Use of sertraline in patients with liver disease should be cautious. In appointing the drug to patients with impaired liver function is necessary to discuss the feasibility of reducing the dose or increase the interval between administration of the drug.
Use in renal failure
Sertraline undergoes biotransformation active, therefore unchanged in the urine, he appears in a minor amount. In patients with mild to moderate renal insufficiency (Cl creatinine 30-60 ml / min) and in patients with moderate or severe renal impairment (Cl creatinine 10-29 ml / min), the pharmacokinetic parameters (AUC0-24 and Cmax) of sertraline with repeated its admission did not differ significantly from the control group. In all groups, T1 / 2 was the same preparation, as there was no difference in the binding to plasma proteins. The results of this study indicate that, as expected based on small sertraline renal excretion, its dose correction depending on the severity of renal failure, is not required.
Abnormal bleeding / hemorrhage. It is recommended to be careful in appointing an SSRI in combination with drugs having established the capacity for change of platelet function, and in patients with bleeding disorders in history.
Hyponatremia. During treatment with sertraline may occur transient hyponatremia. It occurs more frequently in elderly patients, as well as when taking diuretics or several other drugs. This side effect associated with the syndrome of inappropriate secretion of antidiuretic hormone. With the development of symptomatic hyponatremia sertraline should be discontinued and adequate therapy aimed at correcting sodium levels in the blood. Signs and symptoms of hyponatremia include headache, impaired concentration, impaired memory, weakness and instability, which can lead to falls. In more severe cases may experience hallucinations, fainting, seizures, coma, respiratory arrest and death.
Effects on ability to drive vehicles and management mechanisms. Appointment of sertraline is usually not accompanied by violation of psychomotor functions. However, its use in conjunction with other drugs may impair attention and motor coordination. Therefore, during treatment with sertraline drive vehicles, special equipment or practice associated with an increased risk of the activity is not recommended.
