Valdoxan pills 25mg №14

Indications

- treatment of major depressive disorder in adults.

Dosage and administration

The drug is prescribed inside. Valdoxan ^® can be taken regardless of the meal. pills should be swallowed whole, without chewing.

The recommended dose is 25 mg (1 tab.) 1 time per day in the evening. In the absence of clinical dynamics after two weeks of treatment, the dose can be increased to 50 mg (2 tab.) 1 time per day in the evening. The decision to increase the dose should be made in view of the increasing risk of increased transaminase activity. Increase the dose to 50 mg should be after assessing the benefits and risks for a particular patient and under the strict control of liver samples.

It is recommended to monitor liver function at the start of therapy and then periodically, after 3 weeks, after 6 weeks (the end of the stopping period of therapy), 12 weeks and 24 weeks (end of the supporting period of therapy) after the start of therapy, and further according to the clinical situation. With increasing doses should be monitored liver function with the same frequency as at the beginning of the drug.

Drug treatment of depression should be carried out for at least 6 months to completely stop the symptoms.

If treatment is discontinued, there is no need to gradually reduce the dose.

When skipping the next doseduring the next dose of Valdoxan^® take in the usual dose (do not take the missed dose of the drug).

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

The efficacy and safety of agomelatine (at a dose of 25-50 mg / day) was confirmed in elderly patients (younger than 75 years old) with depression. Have patients aged 75 and over no confirmed evidence of significant effect. In this regard, Valdoxan^® should not be prescribed to patients of this age group. Dose adjustment depending on age is not required.

Adverse effects

In clinical studies Valdoxan^® more than 7,900 depressed patients were treated. Side effects were most often mild or moderate and were observed in the first 2 weeks of treatment. The most frequently observed nausea and dizziness. The observed side effects, as a rule, were transient and, in general, did not require cessation of treatment.

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 rarely (<1/10 000), unspecified frequency.

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

Psychological: often - anxiety; infrequently - agitation and associated symptoms *, such as irritability and anxiety,aggressiveness *, nightmares *, unusual dreams *; rarely - mania / hypomania * (these symptoms may also be a manifestation of the underlying disease), hallucinations *; unspecified frequency - suicidal thoughts or suicidal behavior.

Gastrointestinal: often - nausea, diarrhea, constipation, abdominal pain, vomiting *.

From the hepatobiliary system: often - an increase in the activity of ALT and / or ACT (more than 3 times as compared with VGN in 1.4% of patients while receiving agomelatine in a dose of 25 mg / day and in 2.5% of patients while taking agomelatine in a dose of 50 mg / day, compared with 0.6% against placebo in clinical trials); rarely - hepatitis, increased activity of GGT * (more than 3 times compared with VGN), increased activity of alkaline phosphatase * (more than 3 times compared to VGN), liver failure * (1), jaundice *.

From the skin and subcutaneous tissue: often - sweating; infrequently - eczema, pruritus *, urticaria *; rarely - erythematous rash, swelling of the face and angioedema *.

From the organ of hearing: infrequently - tinnitus.

Special senses: infrequently - blurry vision.

Musculoskeletal system: often - back pain.

Other: often - fatigue.

Additional survey data: rarely - weight gain, weight loss.

* - assessment of the frequency of adverse reactions identified by spontaneous reports, conducted on the basis of clinical studies.

(1) Only a few deaths or liver transplants were reported in patients with previously existing risk factors for liver damage.

Contraindications

- liver failure (for example, cirrhosis or liver disease in the active phase) or an increase in the level of transaminases more than 3 times relative to VGN;

- simultaneous use of strong inhibitors of the isoenzyme CYP1A2 (such as fluvoxamine, ciprofloxacin);

- children's age up to 18 years (due to the lack of sufficient experience of clinical use). In children and adolescents, while taking other antidepressants, suicidal behavior (suicide attempts and suicidal thoughts) and hostility (mainly aggressiveness, conflict behavior, irritation) were observed more often than in the placebo group;

- lactose intolerance (lactase deficiency, galactosemia and glucose / galactose malabsorption syndrome);

- hypersensitivity to agomelatine and / or any of the excipients of the drug.

WITH caution the drug should be prescribed for major depressive episodes in patients with moderate and severe renal insufficiency; while administering agomelatine with moderate inhibitors of the CYP1A2 isoenzyme (such as propranolol, grepafloxacin, enoxacin); patients with a history of manic or hypomanic episodes, patients with a history of suicide, as well as patients who had suicidal intent before the start of therapy.

Should be respected caution when prescribing the drug to patients who consume significant amounts of alcohol or take drugs that can cause impaired liver function.

Use during pregnancy and lactation

Data on the use of agomelatine during pregnancy are not available or are limited (less than 300 pregnancy outcomes).

Animal studies have not revealed any direct or indirect effects on pregnancy, embryo and fetus development, generic activity and postnatal development. As a precautionary measure, it is recommended to avoid the prescription of Valdoxan.^® during pregnancy.

It is not known whether agomelatine passes into breast milk in women during lactation. AT experimental research in animals, agomelatine and its metabolites have been shown to pass into breast milk. If treatment with agomelatine is necessary, breastfeeding should be discontinued.

Application for violations of the liver

The drug is contraindicated in severe hepatic failure. Patients with mild to moderate liver failure the drug is recommended to be administered in a daily dose of 25 mg (1 tab.).

Application for violations of kidney function

Patients with renal insufficiency do not require dose adjustment.

Use in children

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

Use in elderly patients

WITH caution the drug should be prescribed to elderly patients (65 years and older).

Special notes

Monitoring of liver function

Reported cases of liver damage, including liver failure (resulting in exceptional cases of death or requiring liver transplantation in patients with previously existing risk factors for liver damage), elevated levels of liver enzymes by more than 10 times relative to HCH, hepatitis and jaundice in patients taking Valdoxan^®in the post-registration period. Most of these disorders occurred in the first months of treatment. The nature of the damage to the liver is mainly hepatocellular. As a rule, after cessation of therapy, transaminase levels returned to normal values.

It is recommended to monitor liver function at the start of therapy and then periodically, after 3 weeks, after 6 weeks (the end of the stopping period of therapy), 12 weeks and 24 weeks (end of the supporting period of therapy) after the start of therapy, and further according to the clinical situation. With increasing doses should be monitored liver function with the same frequency as at the beginning of the drug.

With an increase in the activity of transaminases in the serum, a repeated study should be conducted within 48 hours. If the activity of transaminases is more than 3 times higher than VGN, the administration of the drug should be stopped.In the future, you should regularly monitor the functional state of the liver to normalize the activity of transaminases.

If symptoms and signs of possible impaired liver function appear (such as dark urine, discolored stools, yellow skin / eyes, pain in the right upper abdomen, recently appeared constant and unexplained fatigue), Valdoxan should be stopped immediately.

Care should be taken when prescribing the drug Valdoxan^® in patients with increased transaminase activity prior to the start of therapy (higher than VGN, but not more than 3 times relative to VGN).

Care should be taken when prescribing the drug Valdoxan^® patients with risk factors for liver dysfunction, such as obesity / overweight / non-alcoholic fatty hepatosis, diabetes mellitus, drinking large amounts of alcohol or taking drugs that can cause liver dysfunction.

Elderly patients

The efficacy of the drug in elderly patients (75 years and older) has not been established. Therefore, Valdoxan should not be prescribed.^® patients of this age group.

Elderly patients with dementia

Do not appoint Valdoscan^® for the treatment of major depressive episodes in elderly patients with dementia (due to the lack of data on the efficacy and safety of the drug in this group of patients).

Patients with renal failure

In patients with severe renal insufficiency, no significant change in pharmacokinetic parameters was observed. However, experience with the use of the drug in major depressive episodes in patients with moderate or severe renal insufficiency is limited. When prescribing the drug Valdoxan^® such patients should be careful.

Bipolar disorders / mania / hypomania

Caution must be exercised when using the drug Valdoxan.^® in patients with bipolar disorders, manic or hypomania episodes in history. If you experience symptoms of mania, you should stop taking the drug.

Suicide / suicidal behavior

In the depressed state, the risk of suicidal thoughts, self-harm and suicide (suicidal events) is increased. The risk persists until a distinct remission occurs. Patients must be kept under medical supervision until the condition improves (after the start of therapy it may take several weeks before the condition improves). Clinical experience suggests that the risk of suicide may increase in the early stages of remission.

Patients with a history of suicide-related events, as well as patients who had suicidal intentions prior to treatment, are at risk and should be under close medical supervision during treatment.

The results of a meta-analysis of clinical trials of antidepressants in patients with mentalDisorders indicate an increased risk of suicidal behavior in patients under the age of 25 years while receiving antidepressants compared with placebo.

During treatment, patients, especially those at risk, should be under close medical supervision, especially at the beginning of therapy and when changing the dose of the drug. Patients (and their caregivers) should be informed of the need for immediate medical attention in case of deterioration, suicidal and unusual behavior, as well as suicidal thoughts.

Combined use with inhibitors of an isoenzyme CYP1A2

Caution should be exercised with the simultaneous use of agomelatine with moderate inhibitors of the CYP1A2 isoenzyme (such as propranolol, grepafloxacin, enoxacin) due to the possibility of increasing the concentration of agomelatine.

Influence on ability to drive motor transport and control mechanisms

Studies on the effect of Valdoxan^® on the ability to drive a car and other mechanisms was not carried out. It should be remembered that dizziness and drowsiness are frequent side effects of agomelatine.

Overdose

Data on agomelatine overdose is limited.

Symptoms: drowsiness, epigastric pain, anxiety, weakness, anxiety, agitation, tension, dizziness, cyanosis, malaise. When the patient was taking agomelatine at a dose of 2450 mg, the state returned to normal on its own, without disturbances of the cardiovascular system or changes in laboratory parameters.

Treatment: The specific antidote for agomelatine is not known.Carry out symptomatic treatment and monitoring in specialized departments with the subsequent supervision.

Drug interaction

Potential interaction

Agomelatine is 90% metabolized in the liver with the participation of the CYP1A2 isoenzyme and 10% by CYP2C9 / 19. Therefore, any drugs whose metabolism depends on these isoenzymes may increase or decrease the bioavailability of agomelatine.

Fluvoxamine is a strong inhibitor of the isoenzyme CYP1A2 and a moderate inhibitor of the isoenzyme CYP2C9 and significantly slows down the metabolism of agomelatine, while the concentration of agomelatine increases approximately 60 (12-412) times. Therefore, the simultaneous use of agomelatine and strong inhibitors of the isoenzyme CYP1A2 (such as fluvoxamine, ciprofloxacin) is contraindicated.

The simultaneous appointment of agomelatine and estrogen, which are mild inhibitors of the CYP1A2 isoenzyme, leads to an increase in the concentration of agomelatine several times. Although the combined use of agomelatine and estrogen has not been accompanied by a deterioration in the safety profile of the therapy, caution should be taken with the simultaneous administration of agomelatine with other moderate inhibitors of the CYP1A2 isoenzyme (such as propranolol, grepafloxacin, enoxacin) until sufficient clinical experience has been gained.

Rifampicin, as an inducer of both cytochrome P450 isoenzymes involved in the metabolism of agomelatine, can reduce the bioavailability of agomelatine.It has been shown that smoking, inducing CYP1A2 isoenzyme, reduces the bioavailability of agomelatine, especially in patients who abuse smoking (more than 15 cigarettes / day).

Probability of action of agomelatine on other drugs

In vivo, agomelatine does not induce cytochrome P450 isoenzymes. Agomelatine does not inhibit the isoenzyme CYP1A2 in vivo and other cytochrome P450 isoenzymes in vitro. Therefore, agomelatine does not affect the concentration of drugs whose metabolism is associated with these isoenzymes.

Agomelatine does not change the free concentration of drugs that are largely associated with plasma proteins and, in turn, they do not affect the concentration of agomelatine.

The absence of pharmacokinetic and pharmacodynamic interactions of agomelatine and drugs commonly used in the target patient population: benzodiazepines, lithium preparations, paroxetine, Fluconazole and theophylline was detected.

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

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

Terms and conditions of storage

The drug should be kept out of the reach of children. Special conditions for storage of the drug is not required.