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 agoraphobia or without agoraphobia.

One time-delayed capsule contains 75 mg of venlafaxine hydrochloride. The product contains sucrose.

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 has virtually no affinity for cholinergic muscarinic, histamine H receptors₁ and α₁-renergic in the rat's brainin vitro. It does not inhibit MAO activity. There is virtually no affinity for opioid and benzodiazepine receptors. Following oral administration, venlafaxine is extensively metabolised, mainly to the active ODV metabolite. Medium T_0,5 venlafaxine and ODV are 5 ± 2 h and 11 ± 2 h, respectively. Drug concentrations and ODV reach steady state within 3 days of oral repeated administration. After administration of venlafaxine in the form of capsules The maximum plasma concentrations of venlafaxine and ODV occur respectively within 5.5 h and 9 h. The bioavailability is approximately 40-45%, depending on the systemic metabolism. Venlafaxine and ODV bind to plasma proteins in 27% and 30%, respectively. Venlafaxine is extensively metabolised in the liver 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 its metabolites are mainly excreted by the kidneys.

Hypersensitivity to the active substance or any of the excipients. The concomitant use of the drug 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 significant remission occurs. The patient should be closely monitored until the appearance of improvement and in the early stages 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. The drug should not be used to treat children and adolescents under 18 years. In clinical trials, suicide-related behavior and hostility (especially aggression, rebel behavior and anger) were more frequently observed in children and adolescents treated with antidepressants than in the placebo group. If a decision to treat is made based on an existing clinical need, the patient should be carefully monitored for signs of suicide. There are no long-term studies on the safety of children and adolescents regarding growth, maturation, cognitive development and behavioral development. Venlafaxine may potentially lead to life-threatening serotonin syndrome or neuroleptic malignant syndrome (NMS) reactions, especially during concomitant use of serotonergic substances (including serotonin reuptake inhibitors, noradrenaline and serotonin and tryptan reuptake inhibitors, lithium, sibutramine, St. John's wort) normal, fentanyl and its counterparts, tramadol, dextromethorphan, tapentadol, pethidine, methadone and pentazocine), with drugs that disrupt the metabolism of serotonin (such as IMAO, e.g. methylene blue), with serotonin precursors (such as tryptophan supplements) or with antipsychotics, or other dopamine antagonists.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. Close monitoring of patients with elevated intraocular pressure and patients with an increased risk of acute narrow-angle glaucoma (closed-angle glaucoma) is recommended. Because of the risk of increased blood pressure, it is recommended that all patients undergo extensive testing to detect high blood pressure and that pre-existing hypertension should be monitored prior to starting venlafaxine. Blood pressure should be monitored periodically, after starting treatment and after increasing the dose. Caution should be exercised in patients with co-morbid conditions that may be impaired as a result of increased blood pressure, eg in patients with cardiac dysfunction. Special caution should be exercised in patients whose concomitant diseases may deteriorate as a result of an accelerated heart rate. Venlafaxine has not been evaluated in patients with a recent history of myocardial infarction or unstable coronary heart disease. Therefore, caution should be used when using venlafaxine for these patients. Cases of QT interval prolongation, ventricular tachycardia, have been reported post-marketingtorsade de pointes, ventricular tachycardia, and cardiac arrhythmia with fatal outcome when using venlafaxine, especially after overdose or in patients with risk factors. In patients with an increased risk of severe arrhythmia and QT interval prolongation, a benefit / risk ratio should be considered before prescribing venlafaxine. Venlafaxine should be used with caution in patients with a history of seizures. Such patients should be closely monitored. If seizures occur, treatment should be discontinued. Hyponatremia and / or the syndrome of abnormal secretion of antidiuretic hormone (SIADH) may occur during treatment. These cases were more frequently observed in patients with reduced circulating or dehydrated blood volume. The risk of occurrence of the above cases are higher in elderly patients, patients taking diuretics and other patients with decreased volume of circulating blood. The drug should be used with caution in patients with bleeding predisposition, including patients taking anticoagulants and platelet inhibitors. In the case of long-term therapy, serum cholesterol should be measured periodically. Co-administration of venlafaxine and weight loss medicines is not recommended. The drug 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, the drug should be used with caution in patients with a history or family history of bipolar disorder. In patients with an aggressive behavior, the drug should be used with caution. In patients with symptoms of akathisia, increasing the dose may be harmful. Special care should be taken when treating elderly patients (eg due to possible renal dysfunction, possible changes in the sensitivity and affinity of neurotransmitters occurring with age). Caution should be exercised when treating patients with severe hepatic impairment; it is recommended to consider dose reduction by more than 50% and potential risk advantages should be considered. In patients with impaired renal function with GFR from 30 to 70 ml / min, care should be taken; in patients requiring hemodialysis and in patients with severe renal impairment (GFR <30 ml / min), reduce the dose by 50% and take special care. Use of the drug in patients with diabetes can affect the control of blood Glucose - adjustments of insulin dose and / or oral hypoglycaemic agents may be required. The product contains sucrose - should not be used in patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency.

There are no adequate data on the use of the drug in pregnant women. Animal studies have shown deleterious effects on reproduction. During pregnancy, use only if the benefits to the mother outweigh the threat to the fetus. The use of venlafaxine during pregnancy or shortly before delivery may cause withdrawal symptoms in newborns. In some neonates exposed to the drug, complications requiring respiratory support, gavage or long-term hospitalization occurred in the final third trimester of pregnancy; such complications may occur immediately after delivery. 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; in most cases these complications are observed immediately or within 24 hours after delivery. The use of serotonin reuptake inhibitors during pregnancy, especially in the third trimester, may increase the risk of persistent pulmonary hypertension of the newborn (PPHN). Venlafaxine and ODV are excreted in human milk - a decision should be made to continue or terminate breastfeeding or to continue or discontinue treatment, taking into account the benefits of breastfeeding to the child and the benefits of the drug to the woman.

Very common: pain and dizziness, nausea, dry mouth, excessive sweating (including night sweats), problems with passing urine (mainly difficulties with the start of micturition), pollakiuria. Common: decreased appetite, confusion, depersonalization, lack of orgasm, decreased libido, nervousness, insomnia, unusual dreams, drowsiness, tremor, paresthesia, increased muscle tone (hypertonia), blurred vision, blurred vision, mydiasis, accommodation disorders, tinnitus , palpitations, hypertension, vasodilation (mainly redness), yawning, vomiting, diarrhea, constipation, urinary retention, menstrual bleeding disorders associated with increased bleeding or increased irregular bleeding (eg menorrhagia, uterine haemorrhage), ejaculation disorders, orgasmic disorders, asthenia, fatigue, chills, increased cholesterol. Uncommon: hallucinations, feelings of detachment from reality, agitation, orgasm disorders (in women), apathy, hypomania, bruxism, akathisia / psychomotor anxiety, syncope, myoclonic muscle contractions, coordination disorders, balance disorders, taste disorder, tachycardia, orthostatic hypotension, dyspnoea, gastrointestinal bleeding, angioneurotic edema, hypersensitivity reactions, ecchymosis, rash, alopecia, incontinence, weight gain, weight loss. Rare: mania, convulsions. Not known: thrombocytopenia, blood disorders including agranulocytosis, aplastic anemia, neutropenia and pancytopenia, anaphylactic reaction, syndrome of abnormal secretion of antidiuretic hormone (SIADH), hyponatremia, suicidal thoughts and suicidal behavior, delirium, aggression, Neuroleptic Malignant Syndrome (NMS), serotonin syndrome, extrapyramidal reactions including dystonia and dyskinesia, tardive dyskinesia, glaucoma with a closed angle of view, vertigo, ventricular fibrillation, ventricular tachycardia (includingtorsade de pointes), hypotension, bleeding (mucosal bleeding, pulmonary eosinophilia, pancreatitis, hepatitis, abnormalities in liver function tests, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, pruritus, urticaria, rhabdomyolysis, prolongation of QT interval in ECG, prolonged bleeding time, increased prolactin levels in the blood The profile of adverse reactions in children and adolescents (aged 6-17) was generally similar to that seen in adult patients. As observed in adults, decreased appetite, weight loss, increased blood pressure and increased cholesterol in children Suicide thoughts, an increased number of reports of hostility and, especially in cases of depressive disorders, self-harm were observed in children in clinical trials. and undesirable: abdominal pain, agitation, indigestion, petechiae, nosebleeds, muscle aches.Discontinuation of venlafaxine (especially when abrupt) often leads to withdrawal symptoms; the most frequent reports were: dizziness, sensory disturbances (including paraesthesia), sleep disorders (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, convulsions, headache and flu-like symptoms.

Orally.Episodes of major depressionThe recommended starting dose is 75 mg once a day. In patients not responding to the initial dose, it may be beneficial to increase the dose to a maximum dose 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. The dose should only be increased 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 appropriate in preventing the recurrence of major depressive episodes. In the majority of cases, the dose recommended to prevent the recurrence of major depressive episodes is the same as the dose used to treat depressive disorders. The use of antidepressants should be continued for at least 6 months after remission.Generalized anxiety disorderThe recommended starting dose is 75 mg once a day. In patients not responding to the initial dose, it may be beneficial to increase the dose to a maximum dose of 225 mg per day. The dose should be increased gradually at intervals of about 2 weeks or longer. The dose should only be increased 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 phobiaThe recommended starting dose is 75 mg once a day. There is no evidence that higher doses bring additional benefits. However, for patients not reacting to the initial dose, a dose increase up to a maximum dose of 225 mg per day should be considered. Dosage should be increased gradually at intervals of about 2 weeks or longer. The dose should only be increased 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 disorderThe recommended dose is 37.5 mg per day for 7 days. The dose should then be increased to 75 mg / day. In patients not responding to 75 mg / day, it may be beneficial to increase the dose up to a maximum dose of 225 mg / day. Dosage should be increased gradually at intervals of about 2 weeks or longer. The dose should only be increased 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 medicine. 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 typically 50% should be considered. However, due to the variability of the individual clearance values, individual dosage adjustments may be necessary. Data on patients with severe hepatic impairment are limited - a dose reduction of over 50% should be considered in these patients. 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 <30ml / min), the dose should be reduced by 50%. Due to individual variability in the clearance of these patients, individual dosage adjustments may be necessary. Venlafaxine is not recommended for use in children and adolescents under 18 years of age.Way of giving. Take the capsules daily during meals, more or less at the same time, swallowed whole with liquid; they can not be divided, crushed, chewed or dissolved.