Valdoxan tablets 25mg, no. 28

Inside. ValdoxanЃ tablets can be taken with or without food. The tablet should be swallowed whole without chewing.

If you skip the next dose of the drug, during the next dose, ValdoxanЃ is taken in the usual dose (you should not take the missed dose).

To improve patient control of drug intake, a calendar is printed on the blister containing the tablets.

The recommended dose is 25 mg (1 tab.) 1 time / day before bedtime. In the absence of clinical dynamics after a two-week treatment, the dose can be increased to 50 mg (2 tablets, 25 mg each) 1 time / day before bedtime.

The decision to increase the dose should be made taking into account the increasing risk of increased transaminase activity. Any dose increase to 50 mg should be made on the basis of an assessment of the benefits and risks for the individual patient and with close monitoring of liver function tests.

Functional liver function tests should be performed in all patients before starting therapy. Therapy cannot be started in patients with transaminase levels more than 3 times higher than ULN (see sections 'Contraindications' and 'Special instructions'). During treatment, liver function should be monitored periodically, after about 3 weeks, after about 6 weeks (the end of the stopping period of therapy), after about 12 weeks and 24 weeks (the end of the maintenance period of therapy) after the start of therapy, and thereafter in accordance with the clinical situation (see the section 'Special instructions'). If the activity of transaminases is more than 3 times higher than VGN, the drug should be discontinued (see sections 'Contraindications' and 'Special instructions').

With an increase in the dose, liver function should be monitored with the same frequency as at the beginning of the drug.

Duration of treatment

Drug therapy for depression should be administered for at least 6 months until the symptoms of depression have completely disappeared.

Switching from SSRI / SNRI therapy to agomelatine

Possible withdrawal syndrome after discontinuation of SSRIs / SNRIs.

To reduce the risk of withdrawal symptoms after stopping treatment with previously prescribed SSRIs / SNRIs, you must follow the instructions for medical use of these drugs.

Agomelatine can be started on day 1 of a gradual reduction in the dose of SSRI / SNRI antidepressants (see the Pharmacodynamics section).

Termination of treatment

In case of discontinuation of treatment, there is no need for a gradual dose reduction.

Elderly patients

The efficacy and safety of agomelatine (at a dose of 25-50 mg / day) has been confirmed in elderly patients with depression under 75 years of age. In patients aged 75 years and older, there is no confirmed evidence of a significant effect. In this regard, ValdoxanЃ should not be prescribed to patients of this age group (see sections 'Special instructions' and 'Pharmacological action'). No dose adjustment depending on age is required (see section 'Pharmacological action').

Patients with renal impairment

In patients with severe renal impairment, no significant changes in pharmacokinetic parameters were observed. The experience of using ValdoxanЃ for major depressive episodes in patients with moderate and severe renal failure is limited. When prescribing ValdoxanЃ to such patients, care should be taken (see the section 'Special instructions').

Patients with hepatic impairment

ValdoxanЃ is contraindicated in patients with hepatic impairment (see sections 'Contraindications', 'Special instructions' and 'Pharmacokinetics').

Film-coated tablets, oblong, biconvex, orange-yellow in color.

1 tab.

agomelatine 25 mg

Excipients: lactose monohydrate - 61.84 mg, magnesium stearate - 1.3 mg, corn starch - 26 mg, Povidone-K30 - 9.1 mg, colloidal silicon dioxide anhydrous - 0.26 mg, sodium carboxymethyl starch (type A) - 3.9 mg, stearic acid - 2.6 mg.

• hypersensitivity to agomelatine and / or any of the excipients of the drug (see the section 'Composition');

• liver failure (for example, cirrhosis or liver disease in the active phase) or an increase in the level of transaminases by more than 3 times relative to VGN (see sections 'Dosage regimen' and 'Special instructions');

• simultaneous use of powerful inhibitors of the isoenzyme CYP1A2 (such as fluvoxamine, ciprofloxacin) (see the section 'Drug Interactions');

• children under 18 years of age (due to the lack of sufficient experience in clinical use). In children and adolescents, while taking other antidepressants, suicidal behavior (attempts at suicide and suicidal thoughts) and hostility (mainly aggressiveness, conflict behavior, irritation) were observed more often compared with the placebo group.

The drug should not be used in patients with lactose intolerance: lactase deficiency, galactosemia and glucose-galactose malabsorption.

Care should be taken to prescribe the drug to patients with moderate to severe renal failure in the treatment of major depressive episodes, while concomitant administration of agomelatine with moderate inhibitors of the CYP1A2 isoenzyme (such as propranolol, enoxacin), patients with a history of manic or hypomanic episodes, patients with a history of events associated with suicide, as well as patients who had suicidal intentions before starting therapy.

Care should be taken when prescribing the drug to patients who abuse alcohol or take drugs that can cause liver dysfunction.

pharmachologic effect

Pharmacodynamics

Agomelatine is an agonist of melatonergic MT1 and MT2 receptors and an antagonist of serotonin 5-HT2C receptors. Agomelatine is an antidepressant active in validated models of depression (test of acquired helplessness, test of despair, chronic stress of moderate severity), as well as in models with desynchronization of circadian rhythms, as well as in experimental situations of anxiety and stress. It has been shown that agomelatine does not affect the uptake of monoamines and has no affinity for alpha-, beta-adrenergic, histaminergic, cholinergic, dopaminergic and benzodiazepine receptors.

Agomelatine enhances the release of dopamine and norepinephrine, especially in the prefrontal cortex and does not affect the concentration of extracellular serotonin. In experiments on animals with desynchronization of circadian rhythms, it was shown that agomelatine restores the synchronization of circadian rhythms by stimulating melatonin receptors.

Agomelatine helps restore normal sleep patterns, lower body temperature and release melatonin.

The efficacy of short-term use of agomelatine (therapy for 6-8 weeks) at doses of 25-50 mg in patients with major depressive episodes has been shown.

The efficacy of the use of agomelatine in patients with more severe forms of depressive disorder has also been shown (Hamilton's score is 25).

Agomelatine was also effective in initially high levels of anxiety, as well as in a combination of anxiety and depressive disorders.

The supportive antidepressant effect of agomelatine (with a study duration of 6 months) at a dose of 25-50 mg 1 time / day was confirmed. The results of the study confirmed the anti-relapse efficacy of agomelatine, which was assessed by the time to disease recurrence (p = 0.0001). The recurrence rate in the agomelatine group was 22%, and in the placebo group - 47%.

The efficacy of agomelatine has been demonstrated in six of seven clinical studies (advantage (2 studies), or comparable efficacy (4 studies)) in heterogeneous populations of depressed adult patients compared with SSRIs / SNRIs (sertraline, escitalopram, fluoxetine, venlafaxine, or duloxetine) ... The antidepressant effect was assessed on the Hamilton scale (17-point version) as either the primary or secondary endpoint.

Agomelatine does not have a negative effect on mindfulness and memory; in patients with depression, agomelatine at a dose of 25 mg increases the duration of slow wave sleep without changing the number and duration of REM sleep. Taking agomelatine at a dose of 25 mg also promotes a faster onset of sleep with a decrease in heart rate and an improvement in the quality of sleep (starting from the first week of treatment); at the same time, lethargy in the daytime is not noted.

While taking agomelatine, there was a tendency towards a decrease in the frequency of sexual dysfunction (effect on arousal and orgasm).

Taking agomelatine does not affect heart rate and blood pressure, does not cause sexual dysfunction, does not cause withdrawal syndrome (even with abrupt cessation of treatment) and addiction syndrome.

The efficacy of agomelatine at a dose of 25-50 mg 1 time / day was confirmed in elderly patients with depression under 75 years of age during an 8-week clinical study. In patients aged 75 years and older, there is no confirmed evidence of a significant effect.

The tolerability of agomelatine in elderly patients is comparable to that in younger patients.

In a 3-week, controlled study involving patients with major depressive disorder and insufficient therapeutic effect from taking paroxetine (SSRI) or venlafaxine (SNRI), withdrawal symptoms were observed when switching from therapy with these antidepressants to treatment with agomelatine. Withdrawal syndrome appeared both after a one-step cessation of treatment with previously prescribed SSRIs / SNRIs, and with their gradual cancellation, which could be mistaken for a manifestation of low efficacy of agomelatine at the initial stage of treatment.

The number of patients who had at least one withdrawal symptom a week after stopping the SSRI / SNRI was lower in the group with long-term dose reduction (gradual reduction of the SSRI / SSRI dose over 2 weeks) than in the group with a rapid decrease dosage (gradual reduction in the dose of SSRIs / SNRIs within 1 week), and than with a one-time cancellation: 56.1%, 62.6% and 79.8% of patients, respectively.

Pharmacokinetics

Suction

After oral administration, agomelatine is rapidly (?80%) absorbed. Cmax in plasma is achieved within 1-2 hours after oral administration. Absolute bioavailability after taking a therapeutic dose is low (<5%); interindividual variability is significant. Bioavailability in women is higher than in men. Bioavailability increases with oral contraceptives and decreases with smoking.

With the appointment of therapeutic doses, Cmax increased in proportion to the dose. At higher doses, there was a more pronounced 'first pass' effect through the liver. Food intake (both regular and high-fat) did not affect either bioavailability or absorption. Interindividual variability increased with high-fat meals.

Distribution

Vd in the equilibrium phase was about 35 liters. Plasma protein binding - 95%, regardless of the concentration of the drug, age or the presence of renal failure.

In liver failure, a twofold increase in the free fraction of the drug was noted.

Metabolism

After oral administration, agomelatine undergoes rapid oxidation, mainly due to the isoenzymes CYP1A2 and CYP2C9. The isoenzyme CYP2C19 is also involved in the metabolism of agomelatine, but its role is less significant.

The main metabolites in the form of hydroxylated and demethylated agomelatine are inactive, quickly bound and excreted by the kidneys.

Withdrawal

Removal is fast. T1 / 2 from plasma is from 1 to 2 hours. Metabolic clearance is about 1100 ml / min. Excretion occurs mainly by the kidneys (80%) in the form of metabolites. The amount of unchanged drug in the urine is insignificant. With repeated administration of the drug, the kinetics does not change.

Pharmacokinetics in special patient groups

Renal failure In patients with severe renal failure, the pharmacokinetic parameters did not significantly change with a single dose of agomelatine at a dose of 25 mg. Due to limited clinical experience, caution should be exercised when prescribing agomelatine in patients with moderate to severe renal impairment.

Liver failure. When agomelatine was prescribed at a dose of 25 mg to patients with mild (class A according to the Child-Pugh classification) and moderate (class B according to the Child-Pugh classification) chronic hepatic failure against the background of liver cirrhosis, an increase in its plasma concentration was noted by 70 and 140 times , respectively, compared with volunteers matched for sex, age and smoking habits, but without liver failure.

Elderly patients. When agomelatine was prescribed at a dose of 25 mg to elderly patients (aged 65 years and older), it was noted that the average AUC and average Cmax were 4 times and 13 times higher, respectively, in patients aged 75 years and older compared to patients under 75 years of age. The total number of patients who received 50 mg was too low to draw any conclusions. No dose adjustment depending on age is required.

Racial affiliation. There are no data on racial differences in pharmacokinetic parameters.

Side effect

More than 8000 depressed patients have received ValdoxanЃ in clinical trials. Side effects were most often mild or moderate and were observed in the first 2 weeks of treatment. The most common were headache, nausea and dizziness. The noted side effects, as a rule, were transient and, in general, did not require discontinuation of treatment.

Below are data on side effects observed in placebo-controlled and comparative clinical studies.

The frequency of side effects of agomelatine is given as the following gradation: very often (? 1/10), often (? 1/100, <1/10), infrequently (? 1/1000, <1/100), rarely (? 1 / 10,000, <1/1000); very rare (<1/10 000), unspecified frequency.

From the side of the central nervous system: very often - headache; often - dizziness, drowsiness, insomnia; infrequently - migraine, paresthesia, restless legs syndrome ; rarely - akathisia .

From the gastrointestinal tract: often - nausea, diarrhea, constipation, abdominal pain, vomiting *.

From the liver and biliary tract: often - an increase in the activity of ALT and / or ACT (more than 3 times compared with VGN in 1.2% of patients receiving agomelatine at a dose of 25 mg per day and in 2.6% of patients taking agomelatine at a dose 50 mg daily versus 0.5% with placebo in clinical trials); infrequently - an increase in the activity of ?-glutamyl transferase (GGT) (more than 3 times compared with VGN); rarely - hepatitis, increased ALP activity (more than 3 times compared with VGN), liver failure (1), jaundice .

On the part of the skin and subcutaneous tissue: infrequently - sweating, eczema, pruritus , urticaria ; rarely - erythematous rash, facial edema and angioedema *.

On the part of the organ of hearing: infrequently - tinnitus *.

From the side of the organ of vision: infrequently - blurred vision.

From the musculoskeletal system: often - back pain.

From the side of the kidneys and urinary tract: rarely - urinary retention *.

General disorders: often - fatigue.

Mental disorders: often - anxiety, unusual dreams ; infrequently - suicidal thoughts or suicidal behavior (see the section 'Special instructions'), agitation and related symptoms (such as irritability and anxiety), aggressiveness , nightmares , mania / hypomania (these symptoms may also be a manifestation of the underlying disease (see . section 'Special instructions')), confusion ; rarely - hallucinations *.

Data from (additional) examinations: often - an increase in body weight ; infrequently - weight loss .

* Estimation of the frequency of adverse reactions identified by spontaneous messages was based on data from clinical studies.

(1) Only a few cases of death or liver transplantation have been reported in patients with pre-existing risk factors for liver damage.

Application during pregnancy and lactation

Pregnancy

Data on the use of agomelatine during pregnancy are lacking or limited (less than 300 pregnancy outcomes).

Animal studies have not revealed direct or indirect harmful effects on pregnancy, embryo and fetal development, labor and postnatal development. As a precautionary measure, it is recommended to avoid prescribing ValdoxanЃ during pregnancy.

Breast-feeding

It is not known whether agomelatine passes into breast milk in women during lactation.

In animal experiments, it was shown that agomelatine and its metabolites pass into breast milk. The risk to the newborn / child cannot be excluded. It is necessary to evaluate the significance of breastfeeding for the child and therapy for the mother and make a decision to stop breastfeeding or to stop taking the drug.

Fertility

Reproductive studies in rats and rabbits have shown no effect of agomelatine on fertility.

Application for violations of liver function

The drug is contraindicated in liver failure.

Application for impaired renal function

In patients with severe renal impairment, no significant changes in pharmacokinetic parameters were observed. The experience of using ValdoxanЃ for major depressive episodes in patients with moderate and severe renal failure is limited. When prescribing Valdoxan to such patients, caution should be exercised.

Application in children

Contraindicated in children and adolescents under 18 years of age (due to lack of sufficient clinical experience).

Use in elderly patients

The efficacy and safety of agomelatine (at a dose of 25-50 mg / day) has been confirmed in elderly patients (under 75 years of age) with depression. In patients aged 75 years and older, there is no confirmed evidence of a significant effect. In this regard, ValdoxanЃ should not be prescribed to patients of this age group. No dose adjustment depending on age is required.

special instructions

Monitoring liver function indicators

—ообщалось о случа¤х поражени¤ печени, включа¤ печеночную недостаточность (приводившие в исключительных случа¤х к летальному исходу или требовавшие трансплантации печени у пациентов с ранее имеющимис¤ факторами риска поражени¤ печени), повышение уровн¤ печеночных ферментов более чем в 10 раз относительно ¬vЌ, гепатит и желтуху у пациентов, принимавших ¬альдоксанЃ, в пострегистрационный период (см. раздел 'ѕобочное действие'). Ѕольшинство этих нарушений возникало в первые мес¤цы лечени¤. ’арактер поражени¤ печени представл¤етс¤ главным образом гепатоцеллюл¤рным.  ак правило, после прекращени¤ терапии уровни трансаминаз возвращались к нормальным значени¤м.

—ледует про¤вл¤ть осторожность перед началом лечени¤ и вести тщательное наблюдение в процессе лечени¤ дл¤ всех пациентов, особенно имеющих факторы риска развити¤ заболеваний печени или получающих сопутствующую терапию препаратами, которые могут вызвать поражение печени.

?о начала терапии

Ћечение препаратом ¬альдоксанЃ должно быть назначено только после тщательной оценки соотношени¤ ожидаемой пользы к возможному риску у пациентов с факторами риска развити¤ нарушений функции печени, такими как:

• ожирение/избыточна¤ масса тела/неалкогольный жировой гепатоз, диабет;

• алкоголизм и/или злоупотребление алкоголем;

• прием препаратов, способных вызвать нарушение функции печени.

ѕеред началом терапии функциональные печеночные пробы должны быть проведены у всех пациентов, и терапи¤ не может быть начата, если уровень печеночных ферментов јЋ“ и/или ACT более чем в 3 раза превышает ¬vЌ (см. раздел 'ѕротивопоказани¤'). —ледует соблюдать осторожность при назначении препарата ¬альдоксанЃ пациентам с исходно повышенной активностью трансаминаз (выше ¬vЌ, но не более чем в 3 раза относительно ¬vЌ).

ѕериодичность проведени¤ функциональных печеночных проб:

• до начала терапии;

• и далее:

  • приблизительно через 3 недели,

  • приблизительно через 6 недель (окончание купирующего периода терапии),

  • приблизительно через 12 и 24 недели (окончание поддерживающего периода терапии),

  • в дальнейшем - в соответствии с клинической ситуацией.

ѕри увеличении дозы следует контролировать функцию печени с той же частотой, что и в начале терапии.

ѕри повышении активности трансаминаз в сыворотке крови, следует провести повторное исследование в течение 48 ч.

¬ процессе лечени¤

Ћечение препаратом ¬альдоксанЃ следует немедленно прекратить в случае:

• по¤влени¤ симптомов и признаков возможного нарушени¤ функции печени (таких как темна¤ моча, обесцвеченный стул, желтизна кожи/глаз, боль в правой верхней части живота, недавно по¤вивша¤с¤ посто¤нна¤ и необъ¤снима¤ утомл¤емость);

• повышени¤ уровн¤ трансаминаз более чем в 3 раза, по сравнению с ¬vЌ.

ѕосле отмены терапии препаратом ¬альдоксанЃ следует регул¤рно проводить функциональные печеночные пробы до нормализации уровн¤ трансаминаз.

ѕациенты пожилого возраста

Ёффективность применени¤ препарата у пожилых пациентов (в возрасте 75 лет и старше) не установлена. ¬ св¤зи с этим, ¬альдоксанЃ не следует назначать пациентам этой возрастной группы (см. разделы '–ежим дозировани¤' и '‘армакологическое действие').

ѕациенты пожилого возраста с деменцией

Ќе следует назначать ¬альдоксанЃ дл¤ лечени¤ больших депрессивных эпизодов у пожилых пациентов с деменцией (из-за отсутстви¤ данных об эффективности и безопасности применени¤ препарата у данной группы пациентов).

ѕациенты с почечной недостаточностью

” пациентов с т¤желой почечной недостаточностью значимого изменени¤ фармакокинетических параметров не отмечалось. ќднако опыт применени¤ препарата ¬альдоксанЃ при больших депрессивных эпизодах у пациентов со средней и т¤желой степенью почечной недостаточности ограничен. ѕри назначении препарата ¬альдоксанЃ таким пациентам следует соблюдать осторожность.

Ѕипол¤рные расстройства/мани¤/гипомани¤

—ледует соблюдать осторожность при применении препарата ¬альдоксанЃ у пациентов с бипол¤рными расстройствами, маниакальными или гипоманиакальными эпизодами в анамнезе. ѕри по¤влении симптомов мании следует прекратить прием препарата (см. раздел 'ѕобочное действие').

—уицид/суицидальное поведение

ѕри депрессивном состо¤нии повышен риск суицидальных мыслей, самоповреждений и суицида (событий, св¤занных с суицидом). –иск сохран¤етс¤ до наступлени¤ отчетливой ремиссии. ѕациенты должны находитьс¤ под медицинским наблюдением вплоть до улучшени¤ состо¤ни¤ (после начала терапии может пройти несколько недель, прежде чем состо¤ние улучшитс¤).  линический опыт свидетельствует, что риск суицида может увеличиватьс¤ на ранних этапах наступлени¤ ремиссии.

ѕациенты, в анамнезе которых имелись событи¤, св¤занные с суицидом, а также пациенты, имевшие суицидальные намерени¤ до начала терапии, относ¤тс¤ к группе риска и во врем¤ проведени¤ терапии должны находитьс¤ под пристальным медицинским наблюдением.

–езультаты мета-анализа клинических исследований антидепрессантов у пациентов с психическими расстройствами свидетельствуют о повышенном риске суицидального поведени¤ у пациентов в возрасте до 25 лет на фоне приема антидепрессантов по сравнению с плацебо.

¬ период лечени¤ пациенты, особенно относ¤щиес¤ к группе риска, должны находитьс¤ под пристальным медицинским наблюдением, особенно в начале терапии и при изменении дозы препарата. ѕациенты (и лица, осуществл¤ющие уход за ними) должны быть информированы о необходимости немедленного обращени¤ к врачу при ухудшении состо¤ни¤, суицидальном и необычном поведении, а также при по¤влении суицидальных мыслей.

—овместное применение с ингибиторами изофермента CYP1A2

—ледует соблюдать осторожность при одновременном применении агомелатина с умеренными ингибиторами изофермента CYP1ј2 (такими как пропранолол, эноксацин) из-за возможности повышени¤ концентрации агомелатина (см. разделы 'ѕротивопоказани¤' и 'Ћекарственное взаимодействие').

ѕациенты с непереносимостью лактозы

Ќе следует примен¤ть препарат у пациентов с непереносимостью лактозы: лактазной недостаточностью, галактоземией и глюкозо-галактозной мальабсорбцией (см. раздел 'ѕротивопоказани¤').

¬ли¤ние на способность к вождению автотранспорта и управлению механизмами

»сследований по изучению вли¤ни¤ препарата ¬альдоксанЃ на способность управл¤ть автомобилем и другими механизмами не проводилось. —ледует помнить о том, что головокружение и сонливость - частые побочные эффекты агомелатина.

ѕередозировка

?анные о передозировке агомелатина ограничены.

—имптомы: сонливость, боль в эпигастрии, беспокойство, слабость, тревога, ажитаци¤, напр¤жение, головокружение, цианоз, недомогание. ѕри приеме пациентом агомелатина в дозе 2450 мг состо¤ние нормализовалось самосто¤тельно, без нарушений со стороны сердечно-сосудистой системы или изменени¤ лабораторных показателей.

Ћечение: специфические антидоты дл¤ агомелатина не известны; симптоматическое лечение и мониторинг в специализированных отделени¤х с последующим наблюдением.

Ћекарственное взаимодействие

ѕотенциально возможное вли¤ние других лекарственных средств

јгомелатин на 90% метаболизируетс¤ в печени с участием цитохрома –450 1ј2 (CYP1A2) и на 10% - с помощью CYP2—9/19. ѕоэтому любые препараты, метаболизм которых зависит от этих изоферментов, могут увеличивать или снижать биодоступность агомелатина.

‘лувоксамин, ¤вл¤етс¤ сильным ингибитором изофермента CYP1A2 и умеренным ингибитором изофермента CYP2C9 и существенно замедл¤ет метаболизм агомелатина, при этом концентраци¤ агомелатина увеличиваетс¤ примерно в 60 (12-412) раз. ѕоэтому одновременное применение агомелатина и сильных ингибиторов изофермента CYP1A2 (таких как флувоксамин, ципрофлоксацин) противопоказано.

ќдновременное назначение агомелатина и эстрогенов, которые ¤вл¤ютс¤ умеренными ингибиторами изофермента CYP1A2, приводит к увеличению концентрации агомелатина в несколько раз. ’от¤ комбинированное применение агомелатина и эстрогенов не сопровождалось ухудшением профил¤ безопасности проводимой терапии, следует соблюдать осторожность при одновременном назначении агомелатина с другими умеренными ингибиторами изофермента CYP1A2 (такими как пропранолол, эноксацин) до накоплени¤ достаточного клинического опыта (см. раздел 'ќсобые указани¤').

–ифампицин, как индуктор обоих цитохромов, участвующих в метаболизме агомелатина, может понижать биодоступность агомелатина.

ѕоказано, что курение, индуциру¤ изофермент CYP1A2, понижает биодоступность агомелатина, особенно у пациентов, злоупотребл¤ющих курением (?15 сигарет/день) (см. раздел '‘армакокинетика').

ѕотенциально возможное вли¤ние агомелатина на другие лекарственные средства

In vivo агомелатин не индуцирует изоферменты цитохрома –450. јгомелатин не ингибирует изофермент CYP1A2 in vivo и другие изоферменты цитохрома –450 in vitro. ѕоэтому агомелатин не вли¤ет на концентрацию лекарственных средств, метаболизм которых св¤зан с этими изоферментами.

ѕрепараты, в значительной степени св¤зывающиес¤ с белками плазмы

јгомелатин не измен¤ет свободную концентрацию препаратов, которые в значительной степени св¤зываютс¤ с белками плазмы и, в свою очередь, они не вли¤ют на концентрацию агомелатина.

?ругие лекарственные средства

There were no pharmacokinetic and pharmacodynamic interactions between agomelatine and drugs commonly used in the target patient population: benzodiazepines, lithium drugs, paroxetine, fluconazole and theophylline.

Alcohol

The use of agomelatine in conjunction with alcohol is not recommended.

Electroconvulsive therapy (ECT)

There are no data on the use of agomelatine concomitantly with electroconvulsive therapy (ECT). Since agomelatine did not contribute to the onset of seizures in animal studies, the undesirable effects of the combined use of agomelatine and ECT seem unlikely.