Valdoksan - instructions for use, reviews, analogs and formulations (25 mg tablets) of an antidepressant drug for the treatment of depression in adults, children and pregnancy. Composition and interaction with alcohol
In this article, you can read the instructions for using the drug Valdoxane. Presented are reviews of visitors to the site - consumers of this medication, as well as opinions of physicians specialists on the use of Valdoxane in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Valdoxan in the presence of existing structural analogs. Use to treat depression in adults, children, as well as during pregnancy and lactation.Composition and interaction with alcohol.
Valdoxane - an antidepressant, a melatonin MT1- and MT2-receptor agonist and a serotonin 5-HT2c receptor antagonist.
Agomelatine (active ingredient of the drug Valdoxan) is active on validated depression models (test of acquired helplessness, despair test, chronic stress of moderate severity), as well as on models with desynchronization of circadian rhythms, and also in experimental situations of anxiety and stress. It has been shown that agomelatine does not affect the capture of monoamines and has no affinity for alpha, beta adrenoreceptors, histamine receptors, cholinergic receptors, dopamine 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 experimental studies on animals with simulated desynchronization of circadian rhythms, it was shown that agomelatine restores the synchronization of circadian rhythms through the stimulation of melatonin receptors.
Valdoxan helps restore normal sleep patterns, reduce body temperature and release melatonin.
The effectiveness of short-term use of agomelatine (therapy 6-8 weeks) in doses of 25-50 mg in patients with large depressive episodes is shown.
The effectiveness of agomelatine in patients with more severe forms of depressive disorder is also shown (an estimate on the Hamilton scale is greater than 25).
Agomelatine was also effective at initially high levels of anxiety, as well as in the combination of anxiety and depressive disorders.
A supportive antidepressant effect of agomelatine (with a duration of 6 months) at a dose of 25-50 mg once a day is confirmed. The results of the study confirmed the anti-relapse efficacy of agomelatine, which was evaluated before the onset of relapse (p = 0.0001). The recurrence rate in the group of patients taking agomelatine was 22%, in the placebo group - 47%.
Valdoxane does not adversely affect care and memory; in patients with depression, agomelatine 25 mg increases the duration of the slow-sleep phase without changing the amount and duration of fast-sleep phases. Taking agomelatine in a dose of 25 mg also contributes to a faster onset of sleep withdecreased heart rate and improved sleep quality (from the first week of treatment); at the same time there is no slowing down in the daytime.
Against the background of taking agomelatine, there was a tendency to decrease the frequency of sexual dysfunction (effect on excitement and orgasm).
Admission of agomelatine does not affect the heart rate and blood pressure, does not cause sexual disorders, does not cause withdrawal syndrome (even with a sharp cessation of treatment) and addiction.
Composition
Agomelatine + excipients.
Pharmacokinetics
After oral administration of Valdoxane quickly and well (more than 80%) is absorbed from the digestive tract. Absolute bioavailability after taking a therapeutic dose is low (less than 5%); interindividual variability is considerable. Bioavailability in women is higher than in men. Bioavailability increases with oral contraceptives and decreases with smoking. Binding to plasma proteins is 95% regardless of drug concentration, age or presence of renal insufficiency. In liver failure, there was a twofold increase in the free fraction of the drug. The main metabolites in the form of hydroxylated and demethylated agomelatine are inactive,quickly bind and excreted by the kidneys. Excretion occurs quickly. The metabolic clearance is about 1100 ml / min. Excretion occurs mainly in 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.
Indications
- treatment of major depressive disorder in adults.
Forms of release
The tablets covered with a cover of 25 mg.
Instructions for use and dosing regimen
The drug is prescribed inside.
The recommended dose is 25 mg (1 tablet) 1 time per day in the evening. In the absence of clinical dynamics after a two-week treatment, the dose may be increased to 50 mg (2 tablets) once a day in the evening.
It is recommended to monitor liver function at the beginning of therapy and then periodically, after 3 weeks, after 6 weeks (end of the period of therapy), 12 weeks and 24 weeks (end of maintenance period) after initiation of therapy, and subsequently in accordance with the clinical situation. With increasing doses, liver function should be monitored at the same frequency as at the beginning of the drug.
Drug therapy for depression should be performed for at least 6 months to completely stop the symptoms.
In the event of discontinuation of treatment, there is no need for a gradual dose reduction.
Valdoxane can be taken regardless of food intake. Tablets should be swallowed whole, without chewing.
In case of missed intake of the next dose, during the next dose, take Valdoxane in the usual dose (do not take the missed dose of the drug).
To improve the control of taking the drug on a blister containing tablets, a calendar is printed.
Side effect
- headache;
- dizziness;
- drowsiness;
- insomnia;
- migraine;
- anxiety;
- agitation;
- irritability;
- anxiety;
- aggressiveness;
- nightmarish dreams;
- unusual dreams;
- hallucinations;
- suicidal thoughts or suicidal behavior;
- nausea, vomiting;
- diarrhea;
- constipation;
- abdominal pain;
- liver failure;
- jaundice;
- sweating;
- eczema;
- itching;
- erythematous rash;
- blurred vision;
- backache;
- fatigue;
- increase in body weight;
- decrease in body weight.
Contraindications
- hepatic insufficiency (eg, cirrhosis or liver disease in the active phase);
- simultaneous use of strong inhibitors of the isoenzyme CYP1A2 (such as fluvoxamine, ciprofloxacin);
- children's age till 18 years;
- lactose intolerance (lactase deficiency, galactosemia and glucose malabsorption / galactose syndrome);
- hypersensitivity to agomelatine and / or any of the excipients of the drug.
Application in pregnancy and lactation
Data on the use of Valdoxan in pregnancy are absent or limited (less than 300 pregnancy outcomes).
Studies in animals have not revealed direct or indirect adverse effects on the course of pregnancy, embryo and fetus development, labor activity and postnatal development. Care should be taken when prescribing pregnant women.
It is not known whether agomelatine penetrates breast milk in women during lactation. In experimental studies in animals, it has been shown that agomelatine and its metabolites penetrate into breast milk. If treatment with agomelatine is necessary, breastfeeding should be discontinued.
Use in children
Contraindicated in children and adolescents under the age of 18 (due to lack of sufficient clinical experience). In children and adolescents, when taking other antidepressants, suicidal behavior (suicide attempts and suicidal ideation) and hostility (predominantlyaggressiveness, conflict behavior, irritation) were noted more often compared with the placebo group.
special instructions
Monitoring of liver function
There have been reports of liver damage (including liver failure, elevation of hepatic enzyme levels by more than 10 times relative to IGN, hepatitis and jaundice) in patients taking Waldoxan in the post-marketing period. Most of these disorders occurred during the first months of treatment. The nature of the liver lesion is mainly hepatocellular. As a rule, after discontinuation of therapy, transaminase levels returned to normal values.
It is recommended to monitor liver function at the beginning of therapy and then periodically, after 3 weeks, after 6 weeks (end of the period of therapy), 12 weeks and 24 weeks (end of maintenance period) after initiation of therapy, and subsequently in accordance with the clinical situation. With increasing doses, liver function should be monitored at the same frequency as at the beginning of the drug.
With an increase in the activity of transaminases in serum, a re-examination should be carried out within 48 hours.If the activity of transaminases is more than 3 times higher than UGN, the drug should be discontinued. In the future, it is necessary to regularly monitor the functional state of the liver prior to the normalization of transaminase activity.
If symptoms and signs of possible violations of the liver function (such as dark urine, discolored stool, yellowness of the skin / eye, pain in the right upper abdomen, recently appeared permanent and unexplained fatigue), the use of Valdoxan should be stopped immediately.
Caution should be exercised in prescribing the drug Valdoxane to patients with increased activity of transaminases prior to initiation of therapy (higher than IGN, but no more than 3 times the IGN).
Caution should be exercised when administering the drug Valdoxane to patients with risk factors for liver dysfunction, such as obesity, overweight, non-alcoholic fatty hepatosis, diabetes mellitus, the consumption of alcohol in significant quantities, or taking medications that can cause liver dysfunction.
Elderly patients
The effectiveness of the drug in elderly patients (aged 65 years and older) is not established.There are limited data on the use of the drug Valdoxane in large depressive episodes in patients aged 65 years and older. Care should be taken when prescribing elderly patients.
Patients with renal insufficiency
In patients with renal insufficiency, no significant change in pharmacokinetic parameters was noted. However, the experience of using the drug in large depressive episodes in patients with moderate or severe renal insufficiency is limited. Caution should be exercised when administering the drug Valdoxane to such patients.
Bipolar disorder / mania / hypomania
Care should be taken when using the drug Valdoxane in patients with bipolar disorders, manic or hypomanic episodes in the anamnesis. When symptoms of mania appear, stop taking the drug.
Suicide / suicidal behavior
In a depressed state, the risk of suicidal thoughts, self-harm and suicide (events associated with suicide) is increased. The risk persists until a distinct remission occurs.Patients should be under medical supervision until the condition improves (after the start of therapy, it may take several weeks before the condition improves). Clinical experience indicates that the risk of suicide may increase in the early stages of the onset of remission.
Patients who had a history of suicidal events, as well as patients who had suicidal intent before initiating therapy, are at risk and should be closely monitored during therapy.
The results of the meta-analysis of clinical trials of antidepressants in patients with mental disorders indicate an increased risk of suicidal behavior in patients under 25 years of age when taking antidepressants compared with placebo.
During the treatment period, 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 caregivers) should be informed of the need for immediate medical attention if the condition worsens, suicidal and unusual behavior, and when suicidal thoughts occur.
Combined use with inhibitors of the isoenzyme CYP1A2
Caution should be exercised while using agomelatine with moderate inhibitors of the CYP1A2 isoenzyme (such as propranolol, grepafloxacin, enoxacin) due to the possibility of increasing the concentration of agomelatine.
Impact on the ability to drive vehicles and manage mechanisms
Studies to study the effect of the drug Valdoxane on the ability to drive and other mechanisms were not carried out. It should be remembered that dizziness and drowsiness are frequent side effects of agomelatine.
Drug Interactions
Potentially possible interaction
Agomelatine is 90% metabolized in the liver with the participation of the CYP1A2 isoenzyme and 10% with 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 CYP1A2 isoenzyme and a moderate inhibitor of the CYP2C9 isoenzyme and significantly slows 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.
Simultaneous administration of agomelatine and estrogen that are moderate inhibitors of isoenzyme CYP1A2, leads to an increase in the concentration of the agomelatine several times. Although the combined use of estrogen and agomelatine not accompanied by the deterioration of the profile of the therapy safety caution while appointing agomelatine with other moderate inhibitors isoenzyme CYP1A2 (such as propranolol, grepafloksatsin, enoxacin) until a sufficient accumulation of clinical experience.
Rifampicin as inducer of both isozymes of cytochrome P450, involved in the metabolism of agomelatine, can reduce the bioavailability of agomelatine. It has been shown that smoking induce isoenzyme CYP1A2, it reduces the bioavailability of agomelatine, especially in patients who abuse tobacco (more than 15 cigarettes / day).
The likelihood of the action of agomelatine on other drugs
Valdoxane does not induce cytochrome P450 isoenzymes. Agomelatine does not inhibit the isoenzyme CYP1A2 and other isoenzymes of cytochrome P450.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, which largely bind to plasma proteins and, in turn, they do not affect the concentration of agomelatine.
The absence of pharmacokinetic and pharmacodynamic interaction of agomelatine and drugs often used in the target population of patients: benzodiazepines, lithium preparations, paroxetine, Fluconazole and theophylline has been revealed.
It is not recommended to use Valdoxan together with alcohol.
There is no data on the use of agomelatine concomitantly with electroconvulsive therapy (ECT). Since agomelatine has not contributed to the occurrence of seizures in animal experiments, the undesirable consequences of the combined use of agomelatine and ECT seem unlikely.
Analogues of the drug Valdoxane
Structural analogs for the active substance:
- Agomelatine.
Analogues for the pharmacological group (antidepressants):
- Adress;
- Azafen;
- Amizole;
- Amitriptyline;
- Anaphranil;
- Velaxin;
- Velafax;
- Venlafaxine;
- Heptral;
- Depres;
- Depenone;
- Deprim;
- Duloxetine;
- Zoloft;
- Clomipramine;
- Coaxyl;
- Lenuksin;
- Maprotiline;
- Mirzaten;
- Mirtazapine (hemihydrate);
- Nerustin;
- Neuroplant;
- Newvelong;
- Oprah;
- Paxil;
- Paroxetine;
- Pirazidol;
- Plizil;
- Prozac;
- Rexetin;
- Seralin;
- Stimuloton;
- Trittico;
- Umorap;
- Févarine;
- Floxet;
- Fluoxetine;
- Citalopram;
- Elivel;
- Ephevelone;
- Epevelon retard.
Similar medicines:
Other medicines:
- Femoden - instructions for use, analogs, reviews and release forms (birth control pills) of a drug for contraception in women, including during pregnancy and lactation. Composition and Contraindications
- Ultraproject - instructions for use, analogs, reviews and release forms (ointment or cream and rectal suppositories) drugs for the treatment of hemorrhoids and proctitis in adults, children and pregnancy. Composition
- Flavamed - instructions for use, analogs, reviews and release forms (solution or syrup 15 mg, tablets 30 mg, 60 mg Forte) drug for coughing with bronchitis, pneumonia in adults, children and pregnancy. Composition