Index of drugs

Treatment of major depressive episodes. Prevention of recurrence of major depressive episodes.

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

Antidepressant. The mechanism of action of venlafaxine is to increase the activity of neurotransmitters within o.u.n. Venlafaxine and its active 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 the muscarinic, cholinergic and 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 or benzodiazepine receptors. Following oral administration, venlafaxine is extensively metabolised, mainly to the active ODV metabolite. Venlafaxine and ODV levels 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 absolute bioavailability is approximately 40-45% due to the first pass 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. T_0,5 venlafaxine is 5 ± 2 h; OVD - 11 ± 2 h. In patients on dialysis and in patients with mild or moderate hepatic impairment, the clearance of venlafaxine and ODV is reduced and T_0,5 it is elongated. Data on patients with severe hepatic impairment are limited.

Hypersensitivity to venlafaxine or other ingredients of the preparation. Do not use simultaneously with 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 harm and suicide. This risk persists until full remission occurs. The patient should be closely monitored until improvement occurs and during dose escalation. The risk of suicide may increase in the initial periods of recovery. 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 suicidal ideation or patients exhibiting a significant degree of suicidal tendency before commencing treatment are considered to be at increased risk of suicidal thoughts or suicide attempts and should be closely monitored during treatment, particularly patients under 25 years of age. Close monitoring of patients with elevated intraocular pressure and patients with an increased risk of acute angle-retracting glaucoma (narrow-angle glaucoma) is recommended. Before initiating therapy, 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, such as those associated with impaired cardiac function.Special care should be taken in patients with symptoms of underlying disease that may get worse due to accelerated heart rate. Venlafaxine has not been evaluated in patients with recent myocardial infarction or unstable cardiac disease, therefore caution should be exercised in these patients. Patients at high risk of severe arrhythmia should take into account the risk-benefit ratio (fatal cases of arrhythmia have been reported with venlafaxine, especially in overdose). 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. 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 fluid deficiencies in the body or in dehydrated patients. The risk of occurrence of the above cases are greater: in elderly patients, patients taking diuretics and patients with a deficiency of fluid in the body resulting from a different cause. The drug should be used with caution in patients with bleeding predisposition, including patients taking anticoagulants and platelet inhibitors. Due to the risk of a significant increase in blood cholesterol levels, it should be periodically measured in blood during long-term treatment. Co-administration of venlafaxine and weight loss medicines is not recommended. The drug is not indicated for the treatment of overweight, 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 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. Dryness of oral mucosa during treatment with the product may increase the risk of tooth decay - patients should be informed about the need to maintain proper oral hygiene. In patients with diabetes, venlafaxine may change glycemic control. Caution should be exercised when treating elderly patients (eg due to possible renal dysfunction, possible changes in sensitivity and affinity of neurotransmitters getting worse with age) and in patients with impaired liver or kidney function. The drug should not be used to treat children and adolescents under 18 years of age. In clinical trials, suicide (suicide attempts and suicidal thoughts) 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, however, a decision about treatment is made based on the existing clinical need, the patient should be closely monitored for signs of suicide. In addition, there are no data on the safety of long-term use in children and adolescents regarding the effects on growth, maturation, cognitive and behavioral development. The product contains pellets, which slowly releases the active substance into the gastrointestinal tract. The insoluble part of these pellets is excreted and can be seen in the faeces.

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 expected benefits of treatment outweigh the potential risks. Epidemiological studies have shown that the use of SSRIs during pregnancy, especially in late-onset, may increase the risk of persistent neonatal hypertension (PPHN). The use of venlafaxine in pregnancy may cause withdrawal symptoms in newborns. In some neonates exposed to the drug, complications requiring breathing support, probe feeding or prolonged hospitalization occurred in the final third trimester of pregnancy; such complications may occur immediately after delivery. If SSRIs or SNRIs were used at the end of pregnancy, the following symptoms may occur in newborns: irritability, tremor, hypotension, persistent crying and disturbances of sucking or sleep; in most cases these complications are 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 continue or discontinue treatment, taking into account the benefits of breastfeeding and the benefits of venlafaxine to a woman.

Very common: dryness of the oral mucosa, headache, nausea, sweating (including night sweats). Common: increase in blood cholesterol, weight loss, unusual dreams, decreased sex drive, dizziness, increased muscle tone (hypertonia), insomnia, nervousness, paresthesia, sedation, trembling, confusion, depersonalization, accommodation disorders, mydriasis, visual impairment, hypertension, vasodilatation (mainly facial flushing), palpitations, yawning, decreased appetite (anorexia), constipation, vomiting, ejaculation disorders (orgasm) in men, lack of orgasm, impotence, impaired urination (mainly difficulty in the beginning of micturition), menstrual bleeding disorders associated with the severity of bleeding or the severity of irregular bleeding (eg metrorrhagia, menorrhagia), pollakiuria, asthenia, chills. Uncommon: ecchymosis, gastrointestinal bleeding, weight gain, apathy, hallucinations, muscle clonic convulsions, agitation, disturbances of coordination and balance, disturbed taste, tinnitus, orthostatic hypotension, syncope, tachycardia, bruxism, diarrhea, rash, alopecia, orgasmic disorders in women, urinary retention, angioneurotic edema, hypersensitivity reactions to light. Rare: akathisia, convulsions, manic reactions, urinary incontinence. Not known: bleeding from mucous membranes, prolonged bleeding time, thrombocytopenia, abnormal blood composition (including agranulocytosis, aplastic anemia, neutropenia, pancytopenia), abnormal liver function tests, hepatitis, antidiuretic hormone deficiency syndrome (SIADH), increased concentration prolactin in the blood, neuroleptic malignant syndrome, serotonin syndrome, delirium, extrapyramidal reactions (including dystonia and dyskinesia), tardive dyskinesia, suicidal thoughts and suicidal behavior, dizziness, aggression, narrow-angle glaucoma, hypotension, QT prolongation, flicker chambers, ventricular tachycardia (incltorsade de pointes), pulmonary eosinophilia, pancreatitis, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, pruritus, urticaria, rhabdomyolysis, anaphylaxis. The profile of side effects in children and adolescents (6-17 years) was similar to that seen in adult patients. As in adults, decreased appetite, weight loss, increased blood pressure and increased cholesterol in the blood 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 muscle aches. Discontinuation of venlafaxine (especially when abrupt) usually results in 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 dizziness and flu-like symptoms.

Orally. Adults. Major depressive episodes: the 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. Due to the risk of dose-related adverse reactions, the dose should be increased only after clinical evaluation. The lowest effective dose should be used. Treatment should last long enough, usually a few months or longer. Periodically evaluate the treatment, approaching each patient individually. Long-term therapy may be appropriate in preventing the recurrence of major depressive episodes.In most cases, the dose recommended for preventing relapse of episodes of depression is the same as the dose used to treat the current episode. The use of antidepressants should be continued for at least 6 months after remission.
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 dose adjustments may be necessary. Data on patients with severe hepatic impairment are limited - in these patients a dose reduction of over 50% should be considered, taking into account the potential benefits and risks of treatment. 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 <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 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.
The capsules should be taken with a meal at approximately the same time. Swallow whole with liquid; they should not be divided, crushed, chewed or dissolved.