Aleval - instructions for use, dose, side effects, contraindications

calcium hydrophosphate dihydrate, microcrystalline cellulose, corn starch, hypromellose 2910, talc purified, magnesium stearate, silicon dioxide colloid, crospovidone, indigocarmine; shell composition: hypromellose 2910, macrogol 6000, talcum cleaned, titanium dioxide, indigocarmine.

Description:

Round biconvex tablets covered with a film coating of blue color, with a risk on one side. View of the break: The core of the tablet is white.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.X Other antidepressants

N.06.A Antidepressants

N.06.A.B Selective serotonin reuptake inhibitors

Pharmacodynamics:

Sertralin is a selective serotonin reuptake inhibitor (5-HT).It has very little effect on the re-uptake of norepinephrine and dopamine. In therapeutic doses sertraline blocking the seizure of serotonin by human platelets. It has no stimulating, sedative or anticholinergic action. Sertraline does not have a similarity to muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA or benzodiazepine receptors. The antidepressant effect is noted towards the end of the second week of regular sertraline intake, whereas the maximum effect is achieved only after 6 weeks. Sertraline does not cause mental or physical drug dependence.

Pharmacokinetics:

Absorption of sertraline from the gastrointestinal tract is significant, but it is slow. The maximum concentration in the blood plasma is reached after 4,5-8,4 hours after taking the drug inside. The equilibrium concentration of sertraline in blood plasma is reached within a week with a single daily intake. Bioavailability during meals increases by 25%, while the time to reach maximum concentration is shortened.

Distribution. The total binding of sertraline to plasma proteins is 98%. The volume of distribution is> 20 l / kg.

Metabolism and excretion. Sertraline is subjected to intensive metabolism during the first passage through the liver, undergoing N-demethylation. Its main metabolite, N-desmethylsertralin, is less active than the parent compound. Metabolites are separated with urine and feces in equal amounts. About 0.2% sertraline is excreted in the urine unchanged. The half-life of the drug is 22-36 hours and does not depend on age or sex. For N-desmethylsertraline, this indicator is 62-104 hours.

The half-life of sertraline and the area under the concentration-time curve (AUC) increase with liver function impairment. Regardless of the severity of renal failure, the pharmacokinetics of sertraline does not change with its constant application. Sertraline penetrates into breast milk. Data on its ability to pass through the hematoplacental barrier is not present.

Sertraline is not dialyzed.

Indications:

Depression of various etiologies (treatment and prevention)
Obsessive-compulsive disorder (OCD)
Panic disorders (with or without agoraphobia)
Post-traumatic stress disorder (PTSD)

Contraindications:

Hypersensitivity to the active substance or other ingredients included in the preparation;
joint use of sertraline with monoamine oxidase (MAOI) inhibitors and pimozide. When replacing one drug with another, one should refrain from taking antidepressants within 14 days;
joint use of sertraline with tryptophan or fenfluramine;
uncontrolled epilepsy;
children under 6 years of age with depression and OCD;
children under 18 years of age with panic disorder and PTSD;
pregnancy and lactation (see the section "Pregnancy and lactation").

Carefully:

Organic diseases of the brain (including mental retardation), manic conditions, epilepsy, hepatic and / or renal insufficiency, weight loss, in children older than 6 years with depression and OCD.

Pregnancy and lactation:

There are no controlled results of the use of sertraline in pregnant women, so it is necessary to prescribe them only if the expected benefit for the mother exceeds the potential risk for the fetus. Women of reproductive age who are supposed to be appointed sertraline, effective methods of contraception should be used. Sertraline is found in breast milk, and therefore treatment with this drug during breastfeeding is not recommended. In this case there are no reliable data on the safety of its application. If treatment is still necessary, then breast-feeding should be stopped. In the case of the use of sertraline during pregnancy and lactation in some newborns whose mothers took antidepressants from the group of selective serotonin reuptake inhibitors (SSRIs), including serotonin, there may be symptoms similar to the response to drug withdrawal.

Dosing and Administration:

Sertraline is administered orally, once a day in the morning or in the evening. Sertraline tablets can be taken regardless of food intake.

Depression and OCD

Adults

The initial dose is 50 mg sertraline once a day. The daily dose can be gradually increased at intervals not more than once a week to a maximum daily dose of 200 mg.

The initial therapeutic effect may appear within 7 days, but the overall effect is usually achieved in 2-4 weeks (or even for a longer time with OCD).The maintenance dose for long-term treatment should be minimal effective - with its corresponding changes depending on the therapeutic effect.

Panic disorder and PTSD

For panic disorders and PTSD, the drug is prescribed to adults. The initial dose is 25 mg sertraline once a day, in the morning or in the evening. Taking into account the tolerability, the dose can be gradually increased to a maximum daily dose of 200 mg, not more often than once a week by 25 mg, until the desired therapeutic effect is achieved.

A satisfactory therapeutic result is achieved usually after 7 days from the start of treatment. However, in order to achieve the full therapeutic effect, a regular intake of the drug is required within 2-4 weeks. The minimum dose providing the therapeutic effect is preserved as a supporting one in the future.

Children with OCD

For children from 6 to 12 years, the initial dose is 25 mg sertraline once a day, in the morning or in the evening. After a week, you can increase the dose to 50 mg once a day.

For children from 12 to 17 years, the initial dose is 50 mg once a day, in the morning or in the evening. The daily dose can be gradually, not earlier than a week, increase from 50 mg to a maximum daily dose of 200 mg.To avoid an overdose, you should take in withdrawing a smaller body weight in children compared with adults, and with an increase in the dose of more than 50 mg / day, careful monitoring of this category of patients and at the first signs of an overdose to cancel the drug.

In elderly patients there is no need for a special dose selection.

Patients with impaired hepatic function require special attention in the treatment of sertraline. In case of severe impairment of liver function, the dose of the drug should be reduced or the intervals between doses should be increased. In patients with impaired renal function, no special dose is required (see "Special instructions").

Side effects:

From the digestive system: dyspeptic symptoms (flatulence, nausea, vomiting, diarrhea), abdominal pain, pancreatitis, dry mouth, hepatitis, jaundice, liver failure, decreased appetite right up to anorexia; rarely - increased appetite.

From the cardiovascular system: heart palpitations, tachycardia, lowering blood pressure.

From the musculoskeletal system: arthralgia, muscle cramps.

From the side of the central nervous system and the 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, tremor, convulsions, manic disorders, hallucinations, euphoria, nightmares, psychosis, decreased libido, suicide, coma.

From the respiratory system: bronchospasm, yawning.

From the urinary system: enuresis, incontinence or urinary 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: impaired vision, mydriasis, periorbital edema, ringing in the ears.

From the endocrine system: hyperprolactinemia, hypothyroidism, ADH inadequate secretion syndrome.

Dermatological reactions: redness of the skin or flushes of blood to the face, alopecia, photosensitivity, purpura, increased sweating; rarely Stevens-Johnson syndrome, toxic epidermal necrolysis.

Allergic reactions: urticaria, itching, anaphylactoid reaction, angioedema, edema of the face.

Laboratory test data: 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. Possible development of leukopenia and thrombocytopenia, as well as an increase in the concentration of cholesterol in the serum.

Other: weakness, decrease or increase in body weight, bleeding (including nasal, gastrointestinal or hematuria), peripheral edema.

When discontinuing sertraline treatment in rare cases - withdrawal syndrome:possible 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

Overdose:

Severe symptoms with an overdose of sertraline was not detected even with the administration of the drug in large doses. However, with simultaneous administration with other drugs or ethanol, severe poisoning can occur, up to coma and death.Overdose can cause serotonin syndrome with nausea, vomiting, drowsiness, tachycardia, agitation, dizziness, psychomotor agitation, diarrhea, increased sweating, myoclonus and hyperreflexia.

Treatment: there are no specific antidotes. It requires intensive maintenance therapy and constant monitoring of vital body functions. It is not recommended to induce vomiting. The introduction of activated carbon can be more effective than gastric lavage. It is necessary to maintain airway patency. Sertraline has a large volume of distribution, in connection with this, increased diuresis, dialysis, hemoperfusion or blood transfusion may not be successful.

Interaction:

Pimozide. With the joint use of sertraline and pimozide, an increase in the concentration of pimozide with its single administration in a low dose (2 mg) was noted. An increase in the concentration of pimozide 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, simultaneous administration of pimozide and sertraline is contraindicated.

Inhibitors of monoamine oxidase (MAOI). Serious complications are noted with simultaneous use of sertraline and MAO inhibitors (including selective selegiline, an MAO inhibitor with a reversible type of action moclobemide, and linezolid). Perhaps the development of serotonin syndrome (hyperthermia, rigidity, myoclonus, the lability of the autonomic nervous system (rapid fluctuations in the parameters of the respiratory and cardiovascular system), mental status changes, including increased irritability, expressed agitation, confusion, which in some cases can go into delirious state or to whom). Similar complications, sometimes fatal, occur in the appointment of MAOI antidepressants during treatment, depressing reverse neuronal capture of monoamines or immediately after their withdrawal.

Drugs that depress the central nervous system, and ethanol. The combined use of sertraline and drugs that exert a depressing effect on the central nervous system requires careful monitoring. During the period of treatment, alcohol is not allowed.Potentiation of the action of carbamazepine, haloperidol or phenytoin, as well as ethanol, on cognitive and psychomotor function in healthy people has not been noted.

In the joint appointment of anticoagulants of indirect action (warfarin) with sertraline there is a slight but statistically significant increase in prothrombin time - in these cases it is recommended to monitor prothrombin time at the beginning of treatment with sertraline and after its withdrawal.

When replacing one inhibitor of neuronal seizure of serotonin with another, there is no need for a "period of washing". However, care must be taken when changing the course of treatment. Tryptophan or fenfluramine should be avoided together with sertraline.

Sertraline causes minimal induction of microsomal liver enzymes. Simultaneous administration of sertraline and phenazone at a dose of 200 mg leads to a significant decrease in T_1/2phenazone, although this occurs in only 5% of cases.

When co-introduced sertraline does not change the beta-adrenergic blocking effect of atenolol.

With the introduction of sertraline in a daily dose of 200 mg drug interaction with glibenclamide and digoxin is not revealed.

With prolonged use sertraline in a dose of 200 mg / day has no clinically significant effect and does not suppress the metabolism of phenytoin. Despite this, careful monitoring of the concentration of phenytoin in the blood plasma is recommended from the beginning of treatment with sertraline with appropriate correction of the dose of phenytoin.

There are extremely rare cases of weakness, increased tendon reflexes, confusion, anxiety and arousal in patients simultaneously taking sertraline and sumatriptan. It is recommended to monitor patients who have the appropriate clinical grounds for simultaneous administration of sertraline and sumatriptan.

Pharmacokinetic interaction

Sertraline binds to blood plasma proteins. Therefore, it is necessary to consider the possibility of its interaction with other drugs that bind to plasma proteins (for example, diazepam and tolbutamide).

When used simultaneously with cimetidine, simultaneous use significantly reduces the clearance of sertraline.

Long-term treatment with sertraline at a dose of 50 mg / day increases the concentration in the plasma of concomitant medications,in the metabolism of which the isozyme CYP2D6 (tricyclic antidepressants, antiarrhythmic drugs I C class - propafenone, flecainide).

In experimental studies on in vitro interaction, it has been shown that beta-hydroxylation of endogenous cortisol, which occurs with the participation of CYP3A3 / 4 isozymes, as well as the metabolism of carbamazepine and terfenadine, does not change with prolonged use of sertraline at a dose of 200 mg / day. The concentration in the blood plasma of tolbutamide, phenytoin and warfarin in the long-term administration of sertraline in the same dose also does not change. Therefore, it is considered that sertraline does not inhibit the isoenzyme CYP2C9.

At simultaneous reception sertraline reduces the clearance of tolbutamide (blood glucose control is necessary).

Sertraline does not affect the concentration of diazepam in the serum, indicating that there is no inhibition of the isoenzyme CYP2C19. According to in vitro studies sertraline practically does not influence or minimally inhibits the isoenzyme CYP1A2.

The pharmacokinetics of lithium does not change with the concomitant administration of sertraline. However, tremor is observed more often when they are used together.Special care is required in the joint use of sertraline (like other SSRIs) with drugs that affect serotonergic transmission (eg, lithium).

Special instructions:

Aleval should not be administered together with MAO inhibitors, and also within 14 days after discontinuation of treatment with MAO inhibitors. Similarly, after the withdrawal of the drug Aleval within 14 days, MAO inhibitors are not prescribed.

With the use of selective serotonin reuptake inhibitors (SSRIs), cases of the development of serotonin syndrome and ZNS have been described, the risk of which increases when SSRIs are combined with other serotonergic agents (including triptans), as well as drugs that affect serotonin metabolism (v. including MAO inhibitors), antipsychotics and other dopamine receptor antagonists. Manifestations of serotonin syndrome may include changes in mental status (in particular, agitation, hallucinations, coma), autonomic instability (tachycardia, blood pressure fluctuations, 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, autonomic instability with the possibility of rapid fluctuations in the parameters of vital functions, as well as changes in mental status, can resemble the symptoms that develop in the NSA.

Care should be taken when concurrently administering sertraline with other drugs that enhance serotonergic neurotransmission, such as tryptophan, fenfluramine or serotonin 5-HT receptor agonists. Such a joint appointment should, if possible, be deleted, given the likelihood of pharmacodynamic interaction.

The experience of clinical studies, the purpose of which was to determine the optimal time required for transferring patients from taking other antidepressants and funds used in ROC 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, sufficient experience with sertraline is absent. 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, the use of the drug in patients with unstable epilepsy should be avoided, and patients with controlled epilepsy should be carefully observed during treatment. When the seizures appear, the drug should be discontinued.

During clinical trials prior to the introduction of sertraline on the market, manic disorders were observed in approximately 0.4% of patients taking sertraline. Cases of activation of manic disorders are also described in a small proportion of patients with manic-depressive psychosis who received other antidepressant drugs or agents used in OCD.

Sertralin is actively biotransformed in the liver. According to the pharmacokinetic study, with repeated administration of sertraline in patients with stable cirrhosis of the lung of the lung, there was an increase in T_1/2and increase in C_max and AUC almost 3 times compared with these indicators in healthy people.There were no significant differences in binding to plasma proteins in the two groups. Use sertraline patients with liver disease should be treated with caution. When appointing a drug to a patient with a violation of liver function, it is necessary to discuss the advisability of reducing the dose or increasing the interval between doses of the drug.

Sertraline in a small amount in unchanged form is excreted in the urine. In patients with mild to moderate renal insufficiency (CK 30-60 ml / min) and patients with severe renal insufficiency (CK <10-29 ml / min or less), the pharmacokinetic parameters (C_max and AUC_0-24) sertraline with multiple admission did not differ significantly from the control group. In all groups T_1/2of the drug was the same, as well as there was no difference in binding to plasma proteins. The results of this study suggest that, as expected with the slight renal excretion of sertraline, correction of its dose depending on the severity of renal failure is not required.

It is advisable to use caution when prescribing SSRIs in combination with drugs with established ability to change the functions of platelets, as well as in patients with hemorrhagic diseases in the anamnesis.

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 hyponatraemia sertraline should be abolished and an appropriate therapy aimed at correcting the concentration of sodium 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.

Risk of suicide attempts

Patients with depression are a risk group for suicidal 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.

Have children, adolescents and young people under 24 years of age with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal ideation and suicidal behavior.Therefore, when prescribing Aleval or any other antidepressant drugs in children, adolescents and young people under 24, it is necessary to correlate the risk of suicide and the benefits of their use. In short-term studies in people over 24 years of age, the risk of suicide did not increase, but in people older than 65 years, it declined slightly. Any depressive disorder in itself increases the risk of suicide. Therefore, during treatment with antidepressants, all patients should be monitored for early detection of abnormalities or behavioral changes, as well as suicidal tendencies.

Effect on the ability to drive transp. cf. and fur:During treatment with Aleval, patients are not advised to drive vehicles, special equipment or engage in activities involving increased risk.

Form release / dosage:

Film coated tablets, 25 mg, 50 mg and 100 mg.

Packaging:

For 14 tablets in a strip of aluminum foil. For 1 or 2 strips in a cardboard box with instructions for use.

Storage conditions:

Keep in dry the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-003615/10

Date of registration:30.04.2010

Expiration Date:Unlimited

The owner of the registration certificate:San Pharmaceutical Industries Co., Ltd.San Pharmaceutical Industries Co., Ltd. India

Manufacturer: & nbsp

Sun Pharmaceutical Industries, Ltd. India

Information update date: & nbsp20.09.2015

Illustrated instructions

Instructions

Aleval (Aleval)