Index of drugs

Treatment of major depressive episodes. Prevention of recurrence of major depressive episodes. Treatment of generalized anxiety disorder. Treatment of social phobia. Treatment of panic disorder with or without accompanying agoraphobia.

1 long-life capsules contain 37.5 mg, 75 mg or 150 mg of venlafaxine as hydrochloride.

Antidepressant. The mechanism of action of venlafaxine is related to its ability to enhance the activity of neurotransmitters in o.u.n. Venlafaxine and its main metabolite - O-desmethylvenlafaxine (ODV) are inhibitors of the reuptake of serotonin and noradrenaline. Venlafaxine is also a weak inhibitor of Dopamine reuptake. Venlafaxine and ODV reduce the β-adrenergic response after both single and long-term administration. Venlafaxine does not show significant affinity for cholinergic muscarinic, histamine H receptors₁ and α₁adrenergic. It does not inhibit MAO activity. There is virtually no affinity for opioid and benzodiazepine receptors. Venlafaxine is absorbed in at least 90% of the gastrointestinal tract. After giving the capsule about release of C_max is achieved after 5.5 h (venlafaxine) and 9 h (ODV). Total bioavailability is 40-45%, which is caused by the first-pass metabolism. Venlafaxine undergoes extensive metabolism in the liver. It is metabolized to the main active metabolite - ODV (with the participation of CYP2D6) and to the less active metabolite - N-desmethylvenlafaxine (with the participation of CYP3A4). Venlafaxine and ODV bind to plasma proteins in 27% and 30%, respectively. Venlafaxine and its metabolites are mainly excreted by the kidneys.

Hypersensitivity to the active substance or to any of the excipients. Concomitant use with irreversible MAO inhibitors is contraindicated due to the risk of serotonin syndrome with symptoms such as agitation, tremor and hyperthermia. Venlafaxine should not be initiated earlier than 14 days after stopping treatment with irreversible MAO inhibitors. Venlafaxine should be discontinued at least 7 days before treatment with irreversible MAO inhibitors.

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide. This risk persists until full remission occurs. The patient should be closely monitored until the appearance of improvement and at an early stage of recovery (increased risk of suicide). In patients treated for other psychiatric disorders, the same precautions should be taken as for patients with major depressive episodes. Patients with a history of suicide-related events or patients exhibiting a significant degree of suicidal ideation prior to commencement of treatment are considered to be at increased risk of suicidal thoughts or suicide attempts and should be closely monitored during treatment, particularly in patients below 25 years of age. During treatment, especially at the beginning and in the event of a change in dose, patients should be closely observed, particularly those at high risk. The drug should not be used to treat children and adolescents under 18 years. In clinical trials in children and adolescents, suicidal behavior (suicide attempts and suicidal thoughts) and hostility (mainly aggression, rebellious behavior and anger) were observed more frequently in the antidepressant group than in the placebo group. If, nevertheless, a treatment decision is made based on clinical indications, the patient should be closely monitored for signs of suicide. In addition, the lack of long-term safety data for children and adolescents with regard to growth, maturation and cognitive and behavioral development. During treatment with venlafaxine, a serotonin syndrome (potentially life-threatening) may occur, especially when other drugs that may affect the system of serotoninergic neurotransmitters (including triptans, SSRI, SNRI, lithium, sibutramine, St. John's wort, fentanyl and its counterparts, tramadol) may be used. , dextromethorphan, tapentadol, pethidine, methadone and pentazocine), with drugs that disrupt the metabolism of serotonin (such as MAO inhibitors, e.g. methylene blue), with serotonin precursors (such as tryptophan supplements) or with antipsychotic drugs or other dopamine antagonists.The most severe form of the serotonin syndrome may resemble NMS, with symptoms of hyperthermia, muscle stiffness, autonomic instability with possible rapid fluctuation of vital signs and changes in the mental state. If the treatment with venlafaxine in combination with another substance that may affect the serotoninergic and / or dopaminergic neurotransmission system is clinically warranted, careful observation of the patient is recommended, especially at the beginning of treatment and after increasing the dose. The concomitant use of venlafaxine with serotonin precursors (such as tryptophan supplements) is not recommended. Elevation of pupils may occur during treatment with venlafaxine. Close monitoring of patients with elevated intraocular pressure and patients with an increased risk of acute narrow-angle glaucoma (closed-angle glaucoma) is recommended. Due to the risk of increased blood pressure in patients treated with venlafaxine, regular monitoring of blood pressure is recommended and venlafaxine should be checked for existing hypertension. Blood pressure should be monitored periodically, after starting treatment and after increasing the dose. Caution should be exercised in patients whose concomitant diseases may deteriorate as a result of increased blood pressure, e.g. patients with cardiac dysfunction. During treatment, cardiac function may increase, especially when using high doses. Special care should be taken in patients whose co-morbid conditions may be exacerbated following an accelerated heart rate. The use of venlafaxine has not been evaluated in patients with a recent history of myocardial infarction or unstable coronary heart disease - these patients should be cautious. In patients at increased risk of severe cardiac arrhythmias and QT prolongation, a benefit / risk ratio should be considered before prescribing venlafaxine. Venlafaxine should be used with caution in patients with a history of seizures - these patients should be closely monitored. If seizures occur, treatment should be discontinued. Venlafaxine may result in cases of hyponatraemia and / or the syndrome of abnormal secretion of antidiuretic hormone (SIADH). These cases were more frequently observed in patients with reduced circulating or dehydrated blood volume. The risk of the above cases are higher in elderly patients, patients taking diuretics and patients with decreased volume of circulating blood. Because of the risk of abnormal bleeding, venlafaxine should be used with caution in people with bleeding predisposition, including those taking anticoagulants and platelet inhibitors. In case of long-term treatment, serum cholesterol should be measured periodically. The safety and efficacy of venlafaxine in combination with weight loss products, including phentermine, has not been established - concomitant use is not recommended. Venlafaxine is not indicated for the treatment of obesity both in monotherapy and in combination therapy with other drugs. Due to the risk of mania or hypomania, venlafaxine should be used with caution in patients with a history or family history of bipolar disorder. Venlafaxine should be used with caution in patients with a history of aggressive behavior. In patients with symptoms of akathisia, increasing the dose may be harmful. In patients with diabetes, treatment with SSRI or venlafaxine may affect glycemic control. Dosage adjustment of insulin and / or oral antidiabetic agents may be necessary.

Venlafaxine may be used in pregnant women only if the expected benefits of treatment outweigh the potential risk. Taking the drug during pregnancy or shortly before delivery may cause withdrawal symptoms in newborns. Some neonates exposed to venlafaxine during the third trimester of pregnancy had complications requiring feeding by gavage, breathing support or long-term hospitalization. Such complications can occur immediately after delivery.The use of serotonin reuptake inhibitors (SSRIs) in pregnant women, especially in the third trimester, may increase the risk of persistent pulmonary hypertension syndrome (PPHN) - this risk can not be excluded when using venlafaxine. If SSRI or SNRI were used at the end of pregnancy, the following symptoms may occur in newborns: irritability, tremor, hypotonia, persistent crying, and difficulty in sucking or sleeping. These symptoms may be due to serotoninergic effects or be symptoms of drug exposure. In most cases, these complications are observed immediately or within 24 hours after delivery. Venlafaxine and its active metabolite ODV are excreted in human milk. There have been reports of crying, irritability and disturbances in sleep rhythm in breast-fed infants after marketing. Following discontinuation of breastfeeding, symptoms consistent with symptoms of discontinuation of venlafaxine have also been reported. The risk of adverse reactions in a breast-fed child can not be excluded. Therefore, a decision should be made to continue or terminate breastfeeding or to continue or discontinue venlafaxine, taking into account the benefits of breastfeeding and the benefits of venlafaxine to a woman.

Very common: dizziness, headache, nausea, dry mouth, excessive sweating (including night sweats). Common: decreased appetite, confusion, depersonalization, lack of orgasm, decreased libido, nervousness, insomnia, abnormal dreams, drowsiness, tremors, paresthesia, hypertension, visual impairment (including blurred vision), mydriasis, accommodation disorders, tinnitus, palpitations, hypertension, vasodilatation (mainly sudden redness), yawning, vomiting, diarrhea, constipation, dysuria (mainly a weak stream of urine), pollakiuria, menstrual bleeding disorders associated with bleeding or irregular bleeding (eg menorrhagia, uterine haemorrhage) ), ejaculation disorders, erectile dysfunction, asthenia, weakness, chills, increased cholesterol in the blood. Uncommon: hallucinations, feelings of detachment (or separation) from reality, agitation, orgasm disorders (women), apathy, hypomania, bruxism, akathisia, syncope, myoclonic muscle contractions, abnormal coordination, balance disorders, taste disorders, tachycardia, orthostatic hypotension, dyspnoea, gastrointestinal bleeding, angioneurotic edema, hypersensitivity reactions to light, bruising, rash, alopecia, urinary retention, weight gain, weight loss. Rare: mania, convulsions, incontinence. Not known: thrombocytopenia, blood disorders (including agranulocytosis, aplastic anemia, neutropenia, pancytopenia), anaphylactic reactions, syndrome of abnormal secretion of antidiuretic hormone (SIADH), hyponatremia, suicidal thoughts and behaviors, delirium, aggression, neuroleptic malignant syndrome ( NMS), serotonin syndrome, extrapyramidal disorders (including dystonia and dyskinesia), tardive dyskinesia, glaucoma with closed-angle glaucoma, dizziness, ventricular fibrillation, ventricular tachycardia (includingtorsade de pointes), hypotension, bleeding (bleeding from mucous membranes), pulmonary eosinophilia, pancreatitis, hepatitis, abnormal liver function tests, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, pruritus, urticaria, rhabdomyolysis, prolongation of the interval QT, prolonged bleeding time, increased prolactin concentration in the blood. Discontinuation of treatment (especially sudden) often leads to withdrawal symptoms: dizziness, sensory disturbances (including paraesthesia), sleep disorders (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, convulsions, dizziness of labyrinthine origin, headache and flu-like symptoms. The profile of adverse reactions observed in children and adolescents (aged 6-17 years) was generally similar to that of adult patients. As in adults, decreased appetite, weight loss, increased blood pressure and increased cholesterol in the blood were observed.In clinical trials, suicidal thoughts, an increased number of reports of hostility and, especially in the case of depressive disorders, self-harm have been observed in children. In children, in particular, the following side effects were observed: abdominal pain, agitation, indigestion, ecchymosis, epistaxis, muscle pain.

Orally. Adults.Episodes of major depression: initially 75 mg once a day. In patients not responding to the initial dose, it may be beneficial to increase the dose to a maximum of 375 mg per day. The dose should be increased gradually at intervals of about 2 weeks or longer. In cases clinically justified by the severity of symptoms, the dose may be increased in shorter intervals, but not shorter than 4 days. Dose escalation should only be carried out after clinical evaluation. The lowest effective dose should be used. Treatment should last long enough, usually a few months or longer. Evaluate the treatment regularly, approaching each patient individually. Long-term therapy may also be suitable for preventing recurrence of major depressive episodes. In most cases, the dose recommended for preventing relapse of major depressive episodes is the same as the dose used for the treatment of the last episode of depression. The use of antidepressants should be continued for at least 6 months after achieving remission.Generalized anxiety disorder: initially 75 mg once a day. In patients not responding to the initial dose, it may be beneficial to increase the dose to a maximum of 225 mg per day. The dose should be increased gradually at intervals of about 2 weeks or longer. Dose escalation should only be carried out after clinical evaluation. The lowest effective dose should be used. Treatment should last long enough, usually a few months or longer. Evaluate the treatment regularly, approaching each patient individually.Social phobia: 75 mg once a day. There is no evidence that higher doses bring additional benefits. However, for patients not responding to the initial dose, a dose increase up to a maximum of 225 mg per day should be considered. Dosage should be increased gradually at intervals of about 2 weeks or longer. Dose escalation should only be carried out after clinical evaluation. The lowest effective dose should be used. Treatment should last long enough, usually a few months or longer. Evaluate the treatment regularly, approaching each patient individually.Panic disorder: 37.5 mg daily for 7 days, then the dose should be increased to 75 mg daily. In patients not responding to 75 mg / day, it may be beneficial to increase the dose to a maximum of 225 mg / day. The dose should be increased gradually at intervals of about 2 weeks or longer. Dose escalation should only be carried out after clinical evaluation. The lowest effective dose should be used. Treatment should last long enough, usually a few months or longer. Evaluate the treatment regularly, approaching each patient individually.Special groups of patients. Elderly patients do not need to modify the dose of the drug; the lowest effective dose should always be used and patients should be closely monitored when an increase in dose is required. In patients with mild and moderate hepatic impairment, a dose reduction of 50% should be considered, and individual dosage adjustments may be necessary. In patients with severe hepatic impairment, a dose reduction of> 50% should be considered. In patients with impaired renal function with GFR from 30 to 70 ml / min, no dose adjustment is necessary. For patients requiring hemodialysis and in patients with severe renal impairment (GFR <30 ml / min), the dose should be reduced by 50%, individual dosage adjustments may be necessary.
Kaps. for extension. release should be taken with a meal, every day at about the same time each day. They should be swallowed whole with liquid; they can not be divided, crushed, chewed or dissolved. Patients treated with venlafaxine in the form of of immediate release may go to the treatment of capsules by the release in the nearest equivalent daily dose, eg venlafaxine in the form of with immediate release 37.5 mg administered twice a day can be converted into capsules.about 75 mg once daily. Individual dose adjustments may be necessary.