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.

1 long-life capsules contain 37.5 mg, 75 mg or 150 mg of venlafaxine as hydrochloride. Kaps. 37.5 mg contain sucrose and cochineal red. Kaps. 75 mg and 150 mg contain sucrose and sunset yellow.

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 venlafaxine or other components of the drug. Do not use simultaneously with irreversible MAO inhibitors and for 14 days after discontinuation. Venlafaxine therapy 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 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. During therapy, especially at the beginning of therapy and after dose adjustment, patients should be closely monitored, particularly those at high risk. During treatment with venlafaxine, as with other serotoninergic substances, a serotonin syndrome may occur, potentially life threatening, especially when other substances such as MAO inhibitors are used that may affect the serotoninergic transmission system. Close monitoring of patients with elevated intraocular pressure and patients with an increased risk of acute narrow-angle glaucoma (closed-angle glaucoma) is recommended. 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. Caution should be exercised in patients with recent myocardial infarction or unstable coronary heart disease. In patients with an increased risk of severe arrhythmia, a benefit / risk ratio should be considered before treatment. 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. Patients taking venlafaxine may have an increased risk of bleeding in the skin and mucous membranes, including gastrointestinal bleeding. The drug should be used with caution in patients with bleeding predisposition, including patients taking anticoagulants and platelet inhibitors. 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. 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 and behavioral development. The drug contains sucrose - should not be used in patients with rare inherited disorders associated with fructose intolerance, malabsorption of glucose-galactose and sucrase-isomaltase deficiency. Dyes contained in capsule shells can cause allergic reactions.

There are no adequate data on the use of the drug in pregnant women. Animal studies have shown reproductive toxicity. 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. The use of serotonin reuptake inhibitors during pregnancy, particularly late, may increase the risk of persistent pulmonary hypertension of the newborn (PPHN).If serotonin reuptake inhibitors are 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 are usually observed immediately or within 24 hours after delivery. 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: dry mouth, headache, nausea, sweating (including night sweats). Common: increased cholesterol in the blood, weight loss, unusual dreams, decreased libido, dizziness, increased muscle tone (hypertonia), insomnia, nervousness, paresthesia, sedation, tremors, confusion, depersonalization, accommodation disorders, pupil dilation, visual impairment, palpitations, hypertension, vasodilation (mainly blood clots to the head, sudden redness), yawning, decreased appetite (anorexia), constipation, vomiting, difficult urination (mainly difficulties with the onset of micturition), pollakiuria, ejaculation disorders (orgasm) in men, lack of orgasm, erectile dysfunction (impotence), menstrual bleeding disorders associated with increased or increased irregular bleeding (eg menorrhagia, uterine hemorrhage), weakness, chills. Uncommon: ecchymosis, gastrointestinal bleeding, weight gain, apathy, hallucinations, myoclonic muscle contractions, agitation, impaired coordination and balance, taste disturbances, fainting, tinnitus, tachycardia, orthostatic hypotension, bruxism, diarrhea, rash, alopecia, hypersensitivity reactions to light, urinary retention, and orgasm disorders in women. Rare: akathisia (psychomotor restlessness), convulsions, manic reactions. Frequency unknown: mucosal disorders, prolonged bleeding time, thrombocytopenia, abnormal blood composition (including agranulocytosis, aplastic anemia, neutropenia, pancytopenia), anaphylaxis, abnormal liver function tests, hyponatremia, hepatitis, antidiuretic hormone deficiency syndrome (SIADH) , increased levels of prolactin in the blood, neuroleptic malignant syndrome, serotonin syndrome, delirium, extrapyramidal reactions (including dystonia and dyskinesia), tardive dyskinesia, suicidal thoughts and behaviors, glaucoma with closed-angle glaucoma, prolongation of QT interval, ventricular fibrillation, ventricular tachycardia ( includingtorsade de pointes), hypotension, pulmonary eosinophilia, pancreatitis, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, pruritus, urticaria, rhabdomyolysis. 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 serum cholesterol were observed. In clinical trials, suicidal thoughts, an increased number of reports of hostility and, especially in the case of depressive disorders, self-harm were observed in children. In children, in particular, the following side effects were observed: abdominal pain, agitation, indigestion, ecchymosis, epistaxis, muscle pain. 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, tremor, headache and flu-like symptoms.

Orally.Major depressive episodesThe 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. 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. Patients receiving venlafaxine in the form of tablets of immediate release, can be switched to venlafaxine in the form of capsules about the release, after choosing an equivalent dose. For example, patients taking venlafaxine in the form of tablets with an immediate release of 37.5 mg 2 times a day, can be switched to venlafaxine in the form of a capsule. 75 mg once a day. Dosage should be adjusted individually.
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.