Index of drugs

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

One extended-release capsule contains 75 mg or 150 mg of venlafaxine hydrochloride.

Antidepressant. The mechanism of action of venlafaxine is associated with increased 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 reactivity of the β-adrenergic receptor after both single and repeated 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 about 40-45%. 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 to any of the excipients. Simultaneous use of irreversible MAO inhibitors, due to the risk of serotonin syndrome with symptoms such as agitation, tremor or hyperthermia. Venlafaxine should not be initiated until at least 14 days after discontinuation of irreversible MAO inhibitors. Venlafaxine therapy should be discontinued for at least 7 days before starting MAO inhibitor therapy.

Depression is associated with an increased risk of suicidal thoughts, self-injuries and suicides (suicide related events). This risk persists until significant remission is achieved. Patients should be closely monitored until recovery and in the initial phase of recovery (increased risk of suicide). In patients treated for other psychiatric disorders, the same precautions should be taken as in patients with severe depressive disorder. Patients with a history of suicidal ideation or patients exhibiting a significant suicidal tendency before commencing treatment have a higher risk of suicidal thoughts or attempts, and should be closely monitored during treatment, especially patients under 25 years of age. Pharmacological treatment, especially in patients at high risk and in the initial phase and during dose escalation, should be accompanied by careful observation of patients. The preparation should not be used to treat children and adolescents under 18 years of age. In the course of clinical trials, suicide (suicide attempts and suicidal thoughts), hostility (especially aggression, rebel behavior and anger) were more frequently observed in children and adolescents treated with antidepressants than in the placebo group. If, based on the existing clinical need, however, a decision to treat is made, the patient should be carefully monitored for suicidal tendencies. In addition, the lack of long-term data on the safety of the medicine in children and adolescents regarding development, maturation and cognitive and behavioral development.Venlafaxine may be potentially life-threatening with serotonin syndrome and neuroleptic malignant syndrome (NMS), especially when co-administered with venlafaxine with other serotonergic agents such as SSRIs, serotonin and noradrenaline reuptake inhibitors (SNRIs, triptans), with medicinal products that may affect the metabolism of serotonin such as MAO inhibitors, with antipsychotic drugs or other dopamine antagonists. If the concomitant use of venlafaxine and another drug affecting serotoninergic and dopaminergic neurotransmitters is clinically warranted, careful monitoring of the patient is recommended, particularly when starting treatment and increasing the dose. Co-administration of venlafaxine and serotonin precursors (such as tryptophan supplements) is not recommended. It is recommended to monitor patients with elevated intraocular pressure or patients who are at risk of acute occlusive glaucoma (narrow-angle glaucoma). Before initiating treatment, the hypotension in the patient should be compensated and all patients should be carefully monitored for high blood pressure during treatment. Blood pressure should be checked regularly after starting treatment and after increasing the dose. Caution should be exercised in patients with symptoms of underlying disease that may get worse due to elevated pressure, for example those associated with impaired cardiac function. Caution should be exercised in patients with symptoms of underlying disease that may get worse due to increased heart rate. In patients with recent myocardial infarction or unstable cardiac disease, care should be taken. The benefit / risk ratio should be considered before prescribing venlafaxine to patients at high risk of severe arrhythmia. Venlafaxine therapy should be introduced with caution in all patients with a history of convulsions, and patients should be closely monitored. In all patients who experience convulsions, treatment should be discontinued. When using venlafaxine, there is a risk of hyponatraemia and / or syndrome of abnormal secretion of antidiuretic hormone (SIADH); most often in patients with deficient fluids in the body or in dehydrated patients; older people, patients receiving diuretics and patients with low body fluids due to a different cause are at higher risk. Due to the increased risk of bleeding into the skin and mucous membrane bleeding (including gastrointestinal haemorrhage), caution should be exercised in patients prone to bleeding, including those taking anticoagulant and antiplatelet agents. Due to the risk of clinically significant increase in serum cholesterol level, serum cholesterol measurements should be considered during long-term treatment. Co-administration of venlafaxine hydrochloride with slimming drugs (including with phentermine) is not recommended. Venlafaxine used alone or in combination with other medicines is not indicated for the treatment of overweight. Due to the risk of mania and / or hypomania, venlafaxine should be used with caution in patients with a bipolar disorder or a history of a family history. Caution should be exercised when venlafaxine is administered to patients with a history of aggression. In patients who develop symptoms of akathisia, increasing the dose may be harmful. Dry mouth mucosa was observed in 10% of patients treated with venlafaxine. This may increase the risk of tooth decay and patients should be informed about the need to maintain proper oral hygiene. In diabetic patients, administration of SSRIs or venlafaxine may change glycemic control - you may need to adjust your insulin dose and / or oral hypoglycaemic agents. Caution should be exercised when treating elderly patients (eg due to possible impairment of renal function, possible changes in affinity and sensitivity to neurotransmitters). Caution should be exercised when treating patients with severe hepatic impairment; It is recommended to consider a dose reduction of more than 50% and potential risk advantages should be considered.In patients with impaired renal function with GFR 30-70 ml / min, care should be taken; in patients requiring hemodialysis and in patients with severe renal impairment (GFR <30 ml / min), the dose should be reduced by 50% and caution should be exercised.

There are no adequate data on the use of the drug in pregnant women. Animal studies have shown toxic effects on reproduction. Venlafaxine can be used in pregnant women only if the expected benefits outweigh the potential risk. In newborns, withdrawal symptoms may occur if the mother uses venlafaxine during pregnancy. Some neonates treated with venlafaxine at the end of the third trimester of pregnancy had complications requiring probe feeding, breathing support or prolonged hospitalization. Such complications can occur immediately after birth. The use of SSRIs during pregnancy, especially at a later time, may increase the risk of persistent neonatal hypertension (PPHN). The following symptoms can be seen in newborns if the mother used SSRI / SNRIs in late pregnancy: irritability, tremor, hypotension, persistent crying, and problems with sucking or sleeping. These symptoms may be caused by serotoninergic effects or symptoms associated with the use of the drug. In most cases, the above complications were observed immediately or within 24 hours after birth. Venlafaxine and its active metabolite - ODV are excreted in breast milk. There have been cases of crying, irritability and disturbances of sleep rhythm in breastfed infants whose mothers used venlafaxine after the product was placed on the market. In these children, symptoms similar to symptoms after discontinuation of the drug were observed. The risk for a breast-fed baby can not be ruled out. Therefore, a decision should be made whether to continue breastfeeding or to continue treatment / discontinue treatment, taking into account the benefits of breastfeeding for the child and the benefits of treatment for the mother.

Very common: pain and dizziness, nausea, dry mouth, excessive sweating (also at night). Common: decreased appetite, confusion, depersonalization, anorgasmia, decreased libido, nervousness, insomnia, unusual dreams, drowsiness, tremors, paresthesia, hypertension, blurred vision (including blurred vision), mydriasis, accommodation disturbances, tinnitus, palpitations, hypertension, vasodilatation (mainly facial flushing), yawning, vomiting, diarrhea, constipation, dysuria (painful urination, mainly difficulty in initiating micturition), pollakiuria, menstrual disorders associated with severe bleeding or irregular bleeding (eg metrorrhagia, menorrhagia) , ejaculation disorders, erectile dysfunction, asthenia, fatigue, chills, increased cholesterol in the blood. Uncommon: hallucinations, derealization, agitation, unnatural orgasms (in women), apathy, hypomania, bruxism, akathisia / psychomotor agitation, syncope, muscle clonic convulsions, coordination and balance disorders, taste disorders, tachycardia, orthostatic hypotension, gastric bleeding and intestinal angioedema, hypersensitivity to light, ecchymosis, rash, alopecia, urinary retention, weight gain or loss. Rare: mania, convulsions, incontinence. Not known: thrombocytopenia, abnormal blood composition (including agranulocytosis, aplastic anemia, neutropenia and pancytopenia), anaphylactic reaction, abnormal vasopressin secretion syndrome - SIADH), hyponatremia, suicidal thoughts and behaviors, delirium, aggression, neuroleptic malignant syndrome, serotonin syndrome, extrapyramidal reactions (including dystonia and dyskinesia), tardive dyskinesia, glaucoma with closed-angle glaucoma, dizziness, ventricular fibrillation, ventricular tachycardia (includingtorsade de pointes), hypotension, bleeding (bleeding from the mucous membrane), pulmonary eosinophilia, pancreatitis, hepatitis, abnormal liver function tests, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, pruritus, urticaria, rhabdomyolysis, QT prolongation on the electrocardiogram, prolonged bleeding time, increased prolactin in the blood.The profile of side effects in children and adolescents (6-17 years) was similar to that seen in adults. As with adults, decreased appetite, weight loss, increased blood pressure and increased serum cholesterol were observed. Suicidal thoughts have been observed in pediatric clinical trials. There was also an increased number of cases of hostility and, especially in severe depressive disorders, self-injury. The most common symptoms in children and adolescents were abdominal pain, agitation, indigestion, petechiae, nosebleeds and muscular pains. Discontinuation of treatment (especially sudden) usually leads to withdrawal symptoms; the most common are: dizziness, sensory disturbances (including paraesthesia), sleep disorders (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, tremor, dizziness, headache and flu-like symptoms.

Orally. Adults.Episodes of severe depression. The recommended starting dose is 75 mg once a day. For patients who do not respond to the initial 75-mg daily dosage, it may be beneficial to increase the dose up to a maximum dose of 375 mg / day. The dose should be increased at intervals of 2 weeks or longer. Due to the severity of symptoms, it may be advisable to increase the dose faster, but at intervals of not less than 4 days. Due to the risk of side effects associated with increasing the dose, the dose should be increased only after prior clinical evaluation of the patient. The lowest effective dose should be used. Treatment should last for a long time, usually a few months or longer. Periodic evaluation of individual cases should be carried out. Long-term treatment may also be recommended to prevent the recurrence of major depressive episodes. In most cases, the same dose that is used to treat the current episode is recommended in preventing relapses of major depressive episodes. The use of antidepressants should be continued for at least 6 months after remission.Generalized anxiety disorder. The recommended starting dose is 75 mg once a day. For patients who do not respond to treatment with the initial 75-mg dose per day, the dose may be increased up to a maximum dose of 225 mg / day. The dose should be increased at intervals of 2 weeks or longer. Due to the risk of side effects associated with increasing the dose, the dose should be increased only after prior clinical evaluation of the patient. Treatment should be continued with the lowest effective dose. Treatment should last for a long time, usually a few months or more. The effects of treatment should be assessed regularly, in each case individually.Social anxiety disorder. The recommended dose is 75 mg once a day. There is no evidence that higher doses bring any additional benefits. However, in some patients who do not respond to initial 75 mg treatment, dose titration up to a maximum dose of 225 mg per day may be considered. The dose should be increased at intervals of 2 weeks or longer. Due to the risk of side effects associated with increasing the dose, the dose should be increased only after prior clinical evaluation of the patient. Treatment should be continued with the lowest effective dose. Treatment should last for a long time, usually a few months or more. The effects of treatment should be assessed regularly, in each case individually.Panic disorder syndrome. The recommended dose is 37.5 mg per day for 7 days. The dose should then be increased to 75 mg / day. For patients who do not respond to 75 mg daily, the benefit may be increased by up to a maximum dose of 225 mg / day. The dose should be increased at intervals of 2 weeks or longer. Due to the risk of side effects associated with increasing the dose, the dose should be increased only after prior clinical evaluation of the patient. Treatment should be continued with the lowest effective dose. Treatment should last for a long time, usually a few months or more. The effects of treatment should be assessed regularly, in each case individually.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 the dose should be increased. 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, caution should be exercised and a dose reduction of over 50% should be considered. In patients with impaired renal function with GFR 30-70 ml / min, no dosage 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. The preparation should be taken with a meal every day at about the same time every day. Kaps. should be swallowed whole with liquid; they must 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 replaced with a capsule. 75 mg once daily. Individual dose adjustments may be necessary.