Composition, form of production and packaging
The tablets covered with a cover of white color, oblong, with the squeezed out inscription "Pfizer" on the one hand, with the risk and the squeezed out inscription "ZLT50" on the other side of the tablet.
1 tab.
sertraline (in the form of hydrochloride) 50 mg
Excipients: calcium phosphoric acid, microcrystalline cellulose, hydroxypropyl cellulose, sodium starch glycolate, magnesium stearate, hydroxypropylmethylcellulose, polyethylene glycol, polysorbates, titanium dioxide (E171).
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
The tablets covered with a cover of white color, oblong, with the squeezed out inscription "Pfizer" on one side and "ZLT100" on the other side of the tablet.
1 tab.
sertraline (in the form of hydrochloride) 100 mg
Excipients: calcium phosphoric acid, microcrystalline cellulose, hydroxypropyl cellulose, sodium starch glycolate, magnesium stearate, hydroxypropylmethylcellulose, polyethylene glycol, polysorbates, titanium dioxide (E171).
14 pcs. - blisters (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
Antidepressant, a powerful specific inhibitor of reuptake of serotonin (5-HT) in neurons. Has a very weak effect on the re-uptake of norepinephrine and dopamine. In therapeutic doses, it blocks the seizure of serotonin in human platelets. Does not have a stimulating, sedative or anticholinergic action. Due to selective inhibition of 5-HT capture, sertraline does not increase adrenergic activity. Sertraline does not have an affinity for muscarinic cholinergic receptors, serotonin, dopamine, histamine, GABA-, benzodiazepine and adrenoreceptors.
Sertraline does not cause drug dependence, does not cause an increase in body weight with prolonged admission.
PHARMACOKINETICS
Suction
Absorption is high, but at a slow rate. When taking the drug simultaneously with food bioavailability increases by 25%, C max increases by 25% and T max decreases.
At the person at reception sertralina in a dose from 50 to 200 mg 1 times / sut for 14 days C max it was reached through 4.5-8.4 hours after reception. Cmax and AUC are proportional to the dose in the range of 50-200 mg sertraline 1 time / day for 14 days, with the linear character of the pharmacokinetic dependence being revealed.
Distribution
Binding to plasma proteins is about 98%.
Approximately twofold cumulation of the drug before the equilibrium concentrations after 1 week of treatment (taking the dose 1 time / day) is observed corresponding to the final T 1/2 .
Metabolism
Sertraline undergoes active biotransformation at the "first pass" through the liver. The main metabolite found in plasma, N-desmethylsertralin, is significantly inferior (about 20 times) to sertraline by in vitro activity and is in fact not active on in vivo depression models.
Sertraline and N-desmethylsertralin are actively biotransformed.
Excretion
The mean T 1/2 sertraline in young and elderly men and women is 22-36 h. T 1/2 N-desmethylsertraline varies within the range of 62-104 h. Metabolites are excreted in feces and urine in equal amounts. Only a small part of the drug (less than 0.2%) is excreted in the urine unchanged.
Pharmacokinetics in special clinical cases
The pharmacokinetic profile in adolescents and elderly patients is not significantly different from that in patients aged 18 to 65 years.
It is shown that the pharmacokinetics of sertraline in children with OCD is similar to that in adults (although in children the metabolism of sertraline is somewhat more active). However, given the lower body weight in children (especially at the age of 6-12 years), the drug is recommended to be used in a smaller dose to avoid excessive levels of it in the plasma.
In patients with liver cirrhosis, T 1/2 of the drug and AUC are increased compared to those in healthy people.
INDICATIONS
- Depression of various etiologies (treatment and prevention);
- obsessive-compulsive disorder (OCD);
- panic disorder;
- post-traumatic stress disorder (PTSD);
- Social phobia.
DOSING MODE
The drug is administered orally, 1 time / day in the morning or in the evening. Tablets can be taken regardless of food intake.
With depression and OCD treatment is started with a dose of 50 mg / day.
Treatment of panic disorders, PTSD and social phobia begin with a dose of 25 mg / day, which is increased after 1 week to 50 mg / day. The use of the drug in this scheme allows you to reduce the frequency of early undesirable effects of treatment, characteristic of panic disorder.
With an insufficient effect of sertraline in patients at a dose of 50 mg / day, the daily dose can be increased. The dose should be increased at intervals not more than once a week to the maximum recommended dose of 200 mg / day.
The initial effect can be observed 7 days after the start of treatment, but the overall effect is usually achieved in 2-4 weeks (or even for a longer time with OCD).
In the case of prolonged maintenance therapy, the drug is administered at the lowest effective dose, which is subsequently changed depending on the clinical effect.
In children and adolescents aged 13-17 years with OCD, treatment with Zoloft В® should be started at a dose of 50 mg / day. In children aged 6-12 years, OCD is started with a dose of 25 mg / day, after 1 week it is increased to 50 mg / day. In the following, if the effect is insufficient, the dose can be increased stepwise by 50 mg / day to 200 mg / day as needed. In clinical trials in patients with depression and OCD at the age of 6 to 17 years, it was shown that the pharmacokinetic profile of sertraline was similar to that in adults. To avoid an overdose, with a dose increase of more than 50 mg, it is necessary to take into account the smaller body weight in children compared to adults.
T 1/2 sertraline is approximately 1 day, therefore, the dose change should occur at intervals of not less than 1 week.
In elderly patients, the drug is used in the same doses as in younger patients.
The drug should be used with caution in patients with liver disease . In patients with hepatic insufficiency , lower doses should be used or the interval between doses should be increased.
The drug is largely metabolized in the body. In an unchanged form, only a small amount of the drug is excreted in the urine. As expected, taking into account the minor renal excretion of sertraline, correction of its dose, depending on the severity of renal failure is not required.
SIDE EFFECT
From the digestive system: dyspeptic symptoms (flatulence, nausea, vomiting, diarrhea, constipation), abdominal pain, pancreatitis, dry mouth, hepatitis, jaundice, liver failure, decreased appetite (rarely - increase), up to anorexia; rarely, with prolonged use - there is an asymptomatic increase in the activity of transaminases in the blood serum. The abolition of the drug in this case leads to a normalization of the activity of the enzymes.
From the cardiovascular system: a feeling of palpitations, tachycardia, arterial hypertension.
From the musculoskeletal system: arthralgia, muscle cramps.
From the central nervous system and peripheral nervous system: extrapyramidal disorders (dyskinesias, akathisia, gnashing of teeth, gait disturbance), involuntary muscular contractions, paresthesia, fainting, drowsiness, 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: enuresis, urinary incontinence or retention.
On the part of the reproductive system: violation of sexual function (delay ejaculation, decreased potency), galactorrhea, gynecomastia, menstrual disorder, priapism.
From the sense organs: visual impairment, mydriasis, ringing in the ears.
On the part of the endocrine system: giperprolaktinemiya, hypothyroidism, syndrome of inadequate secretion of ADH.
Dermatological reactions: reddening of the skin or "tides" of blood to the face, alopecia, photosensitivity reaction, purpura, increased sweating.
Allergic reactions: urticaria, itching, anaphylactoid reaction, angioedema, periorbital edema, facial edema, occasionally Stevens-Johnson syndrome and epidermal necrolysis.
On the part of the hematopoiesis system: development of leukopenia and thrombocytopenia is possible.
Other: decreased or increased body mass, peripheral edema, increased serum cholesterol, weakness, bleeding (including nasal, gastrointestinal or hematuria). When treatment with sertraline is discontinued, rare cases of withdrawal syndrome are described. There may be paresthesia, hypoesthesia, symptoms of depression, hallucinations, aggressive reactions, psychomotor agitation, anxiety or symptoms of psychosis that can not be distinguished from the symptoms of the underlying disease.
CONTRAINDICATIONS
simultaneous administration of MAO inhibitors and pimozide;
- Pregnancy;
- the period of lactation (breastfeeding);
- children's age till 6 years;
- Hypersensitivity to sertraline.
With caution should be used in cases of organic brain diseases (including mental retardation), epilepsy, hepatic and / or renal insufficiency, a marked decrease in body weight.
PREGNANCY AND LACTATION
Controlled results of the use of sertraline in pregnant women do not exist, therefore Zoloft В® can be prescribed during pregnancy only if the expected benefit for the mother exceeds the potential risk for the fetus.
Female reproductive age during treatment with sertraline should use effective methods of contraception.
Sertraline is found in breast milk, and therefore the use of Zoloft В® during lactation is not recommended. In this case there are no reliable data on the safety of its application. If the purpose of the drug is necessary, then breastfeeding should be discontinued.
In the case of sertraline during pregnancy and during breastfeeding, some newborns whose mothers were taking antidepressants from the group of selective serotonin reuptake inhibitors, including serotonin, may have symptoms similar to the response to drug withdrawal.
APPLICATION FOR FUNCTIONS OF THE LIVER
Given the slight renal excretion of sertraline, correction of its dose, depending on the severity of renal failure is not required.
With caution should prescribe the drug for kidney failure.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug should be used with caution in patients with liver disease . In patients with hepatic insufficiency , lower doses should be used or the interval between doses should be increased.
With caution should prescribe the drug for liver failure.
APPLICATION FOR CHILDREN
Contraindicated the use of the drug in childhood to 6 years.
In children and adolescents aged 13-17 years suffering from OCD, treatment with Zoloft В® should be started at a dose of 50 mg / day. In children aged 6-12 years,OCD is started with a dose of 25 mg / day, after 1 week it is increased to 50 mg / day. In the following, if the effect is insufficient, the dose can be increased stepwise by 50 mg / day to 200 mg / day as needed. To avoid an overdose, with an increase in the dose of more than 50 mg, it is necessary to take into account the smaller body weight in children compared to adults. Change the dose should be at intervals of not less than 1 week.
APPLICATION IN ELDERLY PATIENTS
In elderly patients, the drug is used in the same doses as in younger patients.
SPECIAL INSTRUCTIONS
Sertraline should not be administered together with MAO inhibitors, but also within 14 days after discontinuation of treatment with MAO inhibitors. Similarly, after the withdrawal of sertraline within 14 days, MAO inhibitors are not prescribed.
Serotonin syndrome and malignant neuroleptic syndrome
With the use of selective serotonin reuptake inhibitors (SSRIs), cases of the development of serotonin syndrome and malignant neuroleptic syndrome (SNS) are described, the risk of which increases when SSRIs are combined with other serotonergic agents (including triptans), as well as drugs affecting serotonin metabolism (including MAO inhibitors), antipsychotic agents and other antagonists of dopamine receptors. The manifestations of serotonin syndrome may be changes in mental status (in particular, agitation, hallucinations, coma), autonomic lability (tachycardia, fluctuations in blood pressure, hyperthermia), changes in neuromuscular transmission (hyperreflexia, impaired coordination of movements) and / or gastrointestinal disturbances nausea, vomiting and diarrhea). Some manifestations of serotonin syndrome, incl. hyperthermia, rigidity of muscles, vegetative lability with the possibility of rapid fluctuations in the parameters of vital functions, as well as changes in mental status, can resemble the symptoms developing in the NSA. It is necessary to monitor patients for the development of clinical manifestations of serotonin syndrome and ZNS.
Other serotonergic agents
Care should be taken when concurrently administering sertraline with other drugs that enhance serotonergic neurotransmission, such as tryptophan, fenfluramine, or 5-HT agonists. Such a joint appointment, if possible, should be ruled out, given the likelihood of pharmacodynamic interaction.
Transition from other 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 antidepressant and anti-obsessive agents to sertraline, is limited. Care must be taken in this transition, especially with long-acting drugs, for example, with fluoxetine. The necessary interval between the cancellation of one SSRI and the start of taking another similar drug is not established. It should be noted that in patients undergoing electroconvulsive therapy, there is no sufficient experience with sertraline.
The possible success or risk of such a combined treatment has not been studied. There is no experience with sertraline in patients with convulsive syndrome, therefore, it should be avoided in patients with unstable epilepsy, and patients with controlled epilepsy should be carefully observed during treatment. When the seizures appear, the drug should be discontinued.
Patients with depression are at risk for suicide attempts. This danger persists until the development of remission. Therefore, from the beginning of treatment and until the optimal clinical effect is achieved, patients should be provided with permanent medical supervision.
Activation of mania / hypomania
During clinical trials before the introduction of sertraline on the market, hypomania and mania were observed in approximately 0.4% of patients receiving sertraline.The cases of activation of mania / hypomania are also described in a small part of patients with manic-depressive psychosis receiving other antidepressant or anti-obsessional drugs.
Application in case of insufficiency of liver function
Sertralin is actively biotransformed in the liver. According to the pharmacokinetic study, with multiple sertraline administration in patients with stable cirrhosis of the liver of the lung course, an increase in T 1/2 of the drug was observed and an almost triple increase in the AUC and C max of the drug compared with that in healthy individuals. There were no significant differences in binding to plasma proteins in the two groups. Use sertralin in patients with liver disease with caution. When appointing a drug to a patient with impaired liver function, it is necessary to discuss the advisability of reducing the dose or increasing the interval between taking the drug.
Application for renal failure
Sertraline undergoes active biotransformation, so in unchanged form with urine it is excreted in a small amount. In patients with mild and moderate renal insufficiency (CK 30-60 ml / min) and patients with moderate or severe renal failure (CK 10-29 ml / min) pharmacokinetic parameters (AUC 0-24 and C max ) of sertraline at multiple his reception did not differ significantly from the control group. In all groups, T 1/2 of the drug was the same, as well as there was no difference in binding to plasma proteins. The results of this study indicate that, as expected, taking into account the minor renal excretion of sertraline, correction of its dose depending on the severity of renal failure is not required.
Pathological hemorrhages / hemorrhages
It is advisable to use caution in the appointment of selective serotonin reuptake inhibitors in combination with drugs with established ability to change the functions of platelets, as well as in patients with hemorrhagic diseases in the anamnesis.
Hyponatremia
During treatment with sertraline, transient hyponatremia may occur. It often develops in elderly patients, as well as when taking diuretics or a number of other drugs.Such a side effect is associated with the syndrome of inappropriate ADH secretion. With the development of symptomatic hyponatremia, sertraline should be abolished and an adequate therapy aimed at correcting the sodium level in the blood should be prescribed. Signs and symptoms of hyponatremia include headache, impaired concentration, memory impairment, weakness and instability, which can lead to falls. In more severe cases, hallucinations, fainting, convulsions, coma, respiratory arrest and death may occur.
Impact on the ability to drive vehicles and manage mechanisms
Appointment, sertraline, are generally not accompanied by a breach of psychomotor functions. However, its use in conjunction with other medications may impair attention and coordination of movements. Therefore, during treatment with sertraline drive vehicles, special equipment or practice associated with an increased risk of the activity is not recommended.
OVERDOSE
Symptoms: severe symptoms are observed with an overdose of sertraline even when using the drug at high doses. However, severe poisoning can occur when simultaneous administration with other drugs or alcohol up to coma and death.
When possible overdose manifestations serotonin syndrome (nausea, vomiting, drowsiness, tachycardia, agitation, dizziness, agitation, diarrhea, excessive 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. Introduction of activated carbon may be more effective than gastric lavage. It is necessary to maintain airway patency. In sertraline big the V d , in this regard, increased diuresis, dialysis, hemoperfusion or blood transfusion may be inconclusive.
DRUG INTERACTION
Pimozide
When combined sertraline and pimozide pimozide levels showed an increase when it is administered in a single low dose (2 mg). Increasing the levels of pimozide it was not associated with any changes in EKG. Since the mechanism of this interaction is not known, 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 effect (selegiline), MAO inhibitors, 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 parameters of the respiratory and cardiovascular system), mental status changes, including increased irritability, expressed agitation, confusion, which in a certain cases one can go to the delirious state or anyone). Similar complications, sometimes fatal, occur in the appointment of MAO inhibitors during treatment with antidepressants, depressing the neuronal uptake of monoamines or immediately after their withdrawal.
Medicaments, CNS depressants, and the ethanol
combined use of sertraline and substances depressing the central nervous system requires attention. No alcohol and drugs containing ethanol during treatment with sertraline. There was no potentiation of ethanol effects, carbamazepine, haloperidol or phenytoin on cognitive and psychomotor performance in healthy subjects; however it is not recommended sertraline and alcohol combined use.
Anticoagulants of indirect action (warfarin)
In their joint appointment with sertraline been a slight 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 cancellation.
Pharmacokinetic interaction
Sertraline binds to plasma proteins. It is therefore necessary to consider the possibility of interaction with other drugs that bind to the protein (e.g., diazepam and tolbutamide).
Cimetidine
simultaneous use greatly reduces the clearance of sertraline.
Drugs metabolized isoenzyme CYP2D6
Prolonged treatment with sertraline at a dose of 50 mg / day increases the plasma concentration of both drugs used in metabolism which participates this enzyme (tricyclic antidepressant, antiarrhythmic drugs class IC - propafenone, flecainide).
Drugs metabolized by other cytochrome P450 enzyme systems
Experiments to study the in vitro interaction showed that carried isoenzyme CYP3A3 / 4 beta-hydroxylation of endogenous cortisol, as well as the metabolism of carbamazepine and terfenadine during long-term administration of sertraline at a dose of 200 mg / day are not changed. plasma concentration of tolbutamide (while receiving clearance reduces tolbutamide - 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 CYP2C9 isozyme.
Sertraline has no effect on the concentration of diazepam in blood serum, which indicates the absence of inhibition of the isozyme CYP2C19. According to in vitro studies, sertraline has virtually no effect or minimally inhibits the CYP1A2 isoenzyme.
Formulations lithium
lithium Pharmacokinetics not changed by concomitant administration of sertraline. However, the tremor occurs more often in their joint application. As well as administration of other selective inhibitors of reverse neuronal uptake of serotonin, sertraline combined use with drugs that affect serotonergic transmission (e.g., lithium preparations) requires precautionary.
Agents acting on serotonergic transmission
When replacing one inhibitor of neuronal uptake of serotonin on the other there is no need to "washout period". However, you must be careful when changing the course of treatment. Avoid concomitant administration of tryptophan or fenfluramine with sertraline.
Induction of hepatic enzymes mikrosomalnyh
Sertraline causes minimal induction of liver enzymes. Simultaneous administration of sertraline at a dose of 200 mg and antipyrine leads to a small (5%) but significant decrease in T 1/2 antipyrine.
Atenolol is
the co-administration of sertraline does not change its beta-adrenoceptor blocking action.
Glibenclamide and digoxin
When administered sertraline in a daily dose of 200 mg of drug interactions with these drugs is not revealed.
Phenytoin
Prolonged use of sertraline at a dose of 200 mg / day has no clinically significant impact and does not inhibit the metabolism of phenytoin. In spite of this, we recommend careful monitoring of phenytoin plasma levels of the appointment of sertraline with a corresponding correction of the dose of phenytoin.
Sumatriptan
There have been very rare cases of weakness, increased tendon reflexes, confusion, anxiety and agitation in patients concurrently treated with sertraline and sumatriptan. If necessary, the simultaneous use of sertraline and sumatriptan recommended monitoring of patients.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored out of reach of children at a temperature of no higher than 30 В° C. Shelf life - 5 years.
