Valdoxan®
Liver function monitoring
Cases of liver damage (including liver failure, increases in liver enzyme levels more than 10 times the ULN, hepatitis and jaundice) have been reported in patients taking Valdoxan® in the post-marketing period. Most of these disorders occurred in the first months of treatment. The nature of liver damage appears to be primarily hepatocellular. As a rule, after cessation 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 relief period of therapy), 12 weeks and 24 weeks (end of the maintenance period of therapy) after the start of therapy, and thereafter in accordance with the clinical situation. When increasing the dose, liver function should be monitored at the same frequency as at the beginning of the drug.
If the activity of transaminases in the blood serum increases, a repeat test should be performed within 48 hours. If the activity of transaminases is more than 3 times higher than the ULN, the drug should be discontinued. In the future, the functional state of the liver should be regularly monitored until transaminase activity normalizes.
If you experience symptoms and signs of possible liver dysfunction (such as dark urine, discolored stools, yellow skin/eyes, pain in the right upper abdomen, new persistent and unexplained fatigue), Valdoxan should be stopped immediately.
Caution should be exercised when prescribing Valdoxan® to patients with elevated transaminase activity before starting therapy (above the ULN, but not more than 3 times the ULN).
Caution should be exercised when prescribing Valdoxan® to patients with risk factors for developing liver dysfunction, such as obesity/overweight/non-alcoholic fatty liver disease, diabetes mellitus, drinking significant amounts of alcohol, or taking medications that can cause liver dysfunction.
Elderly patients
The effectiveness of the drug in elderly patients (aged 65 years and older) has not been established. There is limited data on the use of Valdoxan® for major depressive episodes in patients aged 65 years and older. When prescribing the drug to elderly patients, caution should be exercised.
Patients with kidney failure
In patients with severe renal failure, no significant changes in pharmacokinetic parameters were observed. However, experience with the use of the drug for major depressive episodes in patients with moderate or severe renal failure is limited. When prescribing Valdoxan® to such patients, caution should be exercised.
Bipolar disorders/mania/hypomania
Caution should be exercised when using Valdoxan® in patients with a history of bipolar disorders, manic or hypomanic episodes. If symptoms of mania appear, you should stop taking the drug.
Suicide/suicidal behavior
People who are depressed have an increased risk of suicidal ideation, self-harm, and suicide (suicide-related events). The risk remains until a clear remission occurs. Patients should be under medical supervision until the condition improves (after starting therapy, it may take several weeks for the condition to improve). Clinical experience suggests that the risk of suicide may increase in the early stages of remission.
Patients with a history of events associated with suicide, as well as patients who had suicidal intentions before starting therapy, are at risk and should be under close medical supervision during therapy.
The results of a meta-analysis of clinical trials of antidepressants in patients with mental disorders indicate an increased risk of suicidal behavior in patients under the age of 25 years while 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 their caregivers) should be advised to seek immediate medical attention if their condition worsens, if they experience suicidal or unusual behavior, or if they experience suicidal thoughts.
Combined use with CYP1A2 isoenzyme inhibitors
Caution should be exercised when using agomelatine simultaneously 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 operate machinery
No studies have been conducted to study the effect of Valdoxan® on the ability to drive a car or use other mechanisms. It should be remembered that dizziness and drowsiness are common side effects of agomelatine.
Valdoxan tablet p/pl/o 25 mg N14 (Servier)
Elderly patients The effectiveness of the drug in elderly patients (aged 65 years and older) has not been established. There is limited data on the use of Valdoxan® for major depressive episodes in patients aged 65 years and older. When prescribing the drug to elderly patients, caution should be exercised (see section "Special Instructions"). Patients with renal failure In patients with severe renal failure, no significant changes in pharmacokinetic parameters were observed. However, experience with the use of Valdoxan® for major depressive episodes in patients with moderate to severe renal failure is limited. When prescribing Valdoxan® to such patients, caution should be exercised. Bipolar disorders/mania/hypomania Caution should be exercised when using Valdoxan® in patients with a history of bipolar disorders, manic or hypomanic episodes. If symptoms of mania appear, you should stop taking the drug. Suicide/suicidal behavior When you are depressed, there is an increased risk of suicidal ideation, self-harm and suicide (suicide-related events). The risk remains until a clear remission occurs. Patients should be under medical supervision until the condition improves (after starting therapy, it may take several weeks for the condition to improve). Clinical experience suggests that the risk of suicide may increase in the early stages of remission. Patients with a history of events associated with suicide, as well as patients who had suicidal intentions before starting therapy, are at risk and should be under close medical supervision during therapy. The results of a meta-analysis of clinical trials of antidepressants in patients with mental disorders indicate an increased risk of suicidal behavior in patients under the age of 25 years while 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 their caregivers) should be advised to seek immediate medical attention if their condition worsens, if they experience suicidal or unusual behavior, or if they experience suicidal thoughts. Concomitant use with inhibitors of the CYP1A2 isoenzyme Caution should be exercised when 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 (see section “Interaction with other drugs and other types of interactions”). . Increased transaminase activity in the blood serum In studies while taking the drug Valdoxan®, especially at a dose of 50 mg, an increase in transaminase activity in the blood serum was noted (more than 3 times compared to the upper limit of normal) (see section “Side effects”) . As a rule, after cessation of therapy, these indicators 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 relief period of therapy), 12 weeks and 24 weeks (end of the maintenance period of therapy) after the start of therapy, and thereafter in accordance with the clinical situation. If transaminase activity in the blood serum increases, a repeat test should be performed within 48 hours. If transaminase activity is more than 3 times the upper limit of normal, the drug should be discontinued. In the future, the functional state of the liver should be regularly monitored until transaminase activity normalizes. Caution should be exercised when prescribing Valdoxan® to patients with elevated transaminase activity before starting therapy (above the upper limit of normal, but not more than 3 times the upper limit of normal). If symptoms of liver dysfunction develop, liver function tests should be performed. Taking into account laboratory data and the clinical picture, a decision should be made to discontinue or continue therapy with Valdoxan®. If jaundice develops, it is necessary to discontinue therapy. Caution should be exercised when prescribing Valdoxan® to patients with risk factors for developing liver dysfunction, such as obesity/overweight/non-alcoholic fatty liver disease, patients who drink alcohol in significant quantities or are taking drugs that can cause impairment liver functions.
VALDOXAN
special instructions
Liver function monitoring:
Cases of liver damage, including liver failure (leading in exceptional cases to death or requiring liver transplantation in patients with pre-existing risk factors for liver damage), elevated liver enzymes more than 10 times the upper limit of normal, have been reported. , hepatitis and jaundice in patients taking Valdoxan® during the post-registration period (see section “Side effects”).
Most of these disorders occurred in the first months of treatment. The nature of liver damage appears to be primarily hepatocellular. As a rule, after cessation of therapy, transaminase levels returned to normal values. Caution should be exercised before starting treatment and close monitoring during treatment in all patients, especially those with risk factors for liver disease or those receiving concomitant therapy with drugs that can cause liver damage. — Before starting therapy,
treatment with Valdoxan® should be prescribed only after a careful assessment of the expected benefit to possible risk in patients with risk factors for liver dysfunction, such as obesity/overweight/non-alcoholic fatty liver disease, diabetes, alcohol abuse and drug use that can cause liver dysfunction. Before starting therapy, liver function tests should be performed in all patients, and therapy cannot be started if the level of liver enzymes ALT and/or AST is more than 3 times the upper limit of normal (see section "Contraindications"). Caution should be exercised when prescribing Valdoxan® to patients with initially elevated transaminase activity (above the upper limit of normal, but not more than 3 times the upper limit of normal).
— Frequency of liver function tests
- Before starting therapy
- And further:
- in approximately 3 weeks,
- after approximately 6 weeks (end of the stopping period of therapy),
- after approximately 12 and 24 weeks (end of the maintenance period of therapy) in the future - in accordance with the clinical situation.
- When increasing the dose, liver function should be monitored at the same frequency as at the beginning of therapy. If the activity of transaminases in the blood serum increases, a repeat test should be performed within 48 hours.
— During treatment
Treatment with Valdoxan® should be stopped immediately if:
- the appearance of symptoms and signs of possible liver dysfunction (such as dark urine, discolored stools, yellow skin/eyes, pain in the right upper abdomen, new persistent and unexplained fatigue).
- increase in transaminase levels by more than 3 times, but compared with the upper limit of normal.
After discontinuation of therapy with Valdoxan®, liver function tests should be performed regularly until transaminase levels normalize.
Elderly patients
The effectiveness of the drug in elderly patients (aged 75 years and older) has not been established. In this regard, Valdoxan® should not be prescribed to patients in this age group (see sections “Dosage and Administration” and “Pharmacological Properties”).
Elderly patients with dementia
Valdoxan® should not be prescribed for the treatment of major depressive episodes in elderly patients with dementia (due to the lack of data on the effectiveness and safety of the drug in this group of patients).
Patients with kidney failure
In patients with severe renal failure, no significant changes in pharmacokinetic parameters were observed. However, experience with the use of Valdoxan® for major depressive episodes in patients with moderate to severe renal failure is limited. When prescribing Valdoxan® to such patients, caution should be exercised.
Bipolar disorders/mania/hypomania
Caution should be exercised when using Valdoxan® in patients with a history of bipolar disorders, manic or hypomanic episodes. If symptoms of mania appear, you should stop taking the drug.
Suicide/suicidal behavior
People who are depressed have an increased risk of suicidal ideation, self-harm, and suicide (suicide-related events). The risk remains until a clear remission occurs. Patients should be under medical supervision until the condition improves (after starting therapy, it may take several weeks for the condition to improve). Clinical experience suggests that the risk of suicide may increase in the early stages of remission.
Patients with a history of events associated with suicide, as well as patients who had suicidal intentions before starting therapy, are at risk and should be under close medical supervision during therapy.
The results of a meta-analysis of clinical trials of antidepressants in patients with mental disorders indicate an increased risk of suicidal behavior in patients under the age of 25 years while 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 their caregivers) should be advised to seek immediate medical attention if their condition worsens, if they experience suicidal or unusual behavior, or if they experience suicidal thoughts.
Concomitant use with inhibitors of
the CYPIA 2
isoenzyme Caution should be exercised when using agomelatine simultaneously with moderate inhibitors of the CYP1A2 isoenzyme (such as propranolol, enoxacin) due to the possibility of increasing the concentration of agomelatine (see sections “Contraindications” and “Interaction with other drugs and other types of interactions”) ").
Patients with lactose intolerance
The drug should not be used in patients with lactose intolerance: lactase deficiency, galactosemia and glucose-galactose malabsorption (see section “Contraindications”).
VALDOXAN film-coated tablets 25 mg No. 14
Elderly patients The effectiveness of the drug in elderly patients (aged 65 years and older) has not been established. There is limited data on the use of Valdoxan® for major depressive episodes in patients aged 65 years and older. When prescribing the drug to elderly patients, caution should be exercised (see section "Special Instructions"). Patients with renal failure In patients with severe renal failure, no significant changes in pharmacokinetic parameters were observed. However, experience with the use of Valdoxan® for major depressive episodes in patients with moderate to severe renal failure is limited. When prescribing Valdoxan® to such patients, caution should be exercised. Bipolar disorders/mania/hypomania Caution should be exercised when using Valdoxan® in patients with a history of bipolar disorders, manic or hypomanic episodes. If symptoms of mania appear, you should stop taking the drug. Suicide/suicidal behavior When you are depressed, there is an increased risk of suicidal ideation, self-harm and suicide (suicide-related events). The risk remains until a clear remission occurs. Patients should be under medical supervision until the condition improves (after starting therapy, it may take several weeks for the condition to improve). Clinical experience suggests that the risk of suicide may increase in the early stages of remission. Patients with a history of events associated with suicide, as well as patients who had suicidal intentions before starting therapy, are at risk and should be under close medical supervision during therapy. The results of a meta-analysis of clinical trials of antidepressants in patients with mental disorders indicate an increased risk of suicidal behavior in patients under the age of 25 years while 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 their caregivers) should be advised to seek immediate medical attention if their condition worsens, if they experience suicidal or unusual behavior, or if they experience suicidal thoughts. Concomitant use with inhibitors of the CYP1A2 isoenzyme Caution should be exercised when 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 (see section “Interaction with other drugs and other types of interactions”). . Increased transaminase activity in the blood serum In studies while taking the drug Valdoxan®, especially at a dose of 50 mg, an increase in transaminase activity in the blood serum was noted (more than 3 times compared to the upper limit of normal) (see section “Side effects”) . As a rule, after cessation of therapy, these indicators 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 relief period of therapy), 12 weeks and 24 weeks (end of the maintenance period of therapy) after the start of therapy, and thereafter in accordance with the clinical situation. If transaminase activity in the blood serum increases, a repeat test should be performed within 48 hours. If transaminase activity is more than 3 times the upper limit of normal, the drug should be discontinued. In the future, the functional state of the liver should be regularly monitored until transaminase activity normalizes. Caution should be exercised when prescribing Valdoxan® to patients with elevated transaminase activity before starting therapy (above the upper limit of normal, but not more than 3 times the upper limit of normal). If symptoms of liver dysfunction develop, liver function tests should be performed. Taking into account laboratory data and the clinical picture, a decision should be made to discontinue or continue therapy with Valdoxan®. If jaundice develops, it is necessary to discontinue therapy. Caution should be exercised when prescribing Valdoxan® to patients with risk factors for developing liver dysfunction, such as obesity/overweight/non-alcoholic fatty liver disease, patients who drink alcohol in significant quantities or are taking drugs that can cause impairment liver functions.
How to take it correctly
Grandaxin is a small, round, disc-shaped tablet with the GRANDAX logo. They are white or gray in color and have virtually no odor. Located on a blister of 10 pieces.
The dosage of 1 tablet is 50 mg. The package contains 20 or 60 tablets.
Once in the digestive tract, Grandaxin is quickly absorbed into it. Undergoing transformation in the liver, it enters the blood. Here it reaches its maximum concentration 2 hours after administration. It is excreted by the kidneys and does not accumulate in the body.
The dose of the drug depends on the severity of the condition. It is calculated and prescribed only by a doctor. Self-medication is unacceptable. Usually the scheme is as follows: 1–2 tablets. from 1 to 3 times a day.
The maximum dose per day is 300 mg, in children – 200 mg.
Due to the fact that the drug accumulates in the liver and is evacuated through the kidneys, the drug is prescribed to patients with renal and liver failure with caution. In such patients, the severity and duration of the effect may change, as well as the development of side effects. In this regard, their dose is reduced by half. The same scheme is used for elderly people.
In case of an overdose of the drug, complications such as vomiting, changes in consciousness, coma, seizures and impaired respiratory function are possible.
Grandaxin is not used in parallel with cyclosporine and immunosuppressants such as tacrolimus, sirolimus.
Tablets can intensify the effect of drugs that depress the activity of the central nervous system: analgesics, sedatives and hypnotics, etc.
The use of Grandaxin along with alcohol, smoking, barbiturates, along with antiepileptic therapy reduces its activity.
It is strongly recommended to take Grandaxin before 17.00 to avoid insomnia.
The drug is available with a doctor's prescription. The average cost of 20 tablets is 400 rubles, 60 tablets - 900 rubles.
