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Active ingredients
Venlafaxine
Release form
Pills
Composition
Active ingredient: Venlafaxine. Concentration of active ingredient (mg): 75 mg
Pharmacological effect
Pharmacological action - antidepressant.
Pharmacokinetics
After taking Velaxin, the capsules of prolonged action, Cmax of venlafaxine and EFA (the main metabolite) in plasma are achieved within (6.0 ± 1.5) and (8.8 ± 2.2) h, respectively. The rate of absorption of venlafaxine from the capsules of prolonged action is lower than the rate of its elimination. Therefore, the T1 / 2 of venlafaxine after the administration of Velaxin in the form of prolonged-action capsules - (15 ± 6) h - is actually a T1 / 2 of absorption, rather than a T1 / 2 of distribution - (5 ± 2) h - which is observed after the administration of the drug pill form. The binding of venlafaxine and EFA to plasma proteins is respectively 27 and 30%. EFA and other metabolites, as well as non-metabolized venlafaxine, are excreted by the kidneys. With repeated administration of Css, venlafaxine and EFA are achieved within 3 days. In the range of daily doses of 75-450 mg, venlafaxine and EFA have linear kinetics. After taking the drug during a meal, Tmax in the blood plasma increases by 20–30 min, but the values of Cmax and absorption do not change. In patients with liver cirrhosis, plasma concentrations of venlafaxine and EFA are elevated, and their elimination rate is reduced. In moderate to severe renal failure, the total clearance of venlafaxine and EFA decreases, while T1 / 2 increases. A decrease in total clearance is mainly observed in patients with Cl creatinine below 30 ml / min. The age and sex of the patient do not affect the pharmacokinetics of the drug.
Indications
Depression (including with anxiety), treatment and prevention of relapse.
Contraindications
Hypersensitivity to any component of the drug. Simultaneous administration of MAO inhibitors (see also section “Interaction”). Severe dysfunction of the kidneys or liver (GFR less than 10 mlmin, PV over 18 seconds). Age up to 18 years (safety and efficacy for this age group have not been proven). Pregnancy or presumed pregnancy. Lactation period (not enough data from controlled studies). With care: recent myocardial infarction, unstable angina pectoris, heart failure,coronary artery disease, ECG changes, including lengthening the interval QT, electrolyte disturbances, hypertension, tachycardia, cramps in history, ocular hypertension, angle-closure glaucoma, manic state history, a predisposition to bleeding from the skin and mucous membranes, initially reduced body weight.
Precautionary measures
Risk of suicide: Thoughts of suicide or self-harm can be a manifestation of the underlying disease. They may occur or intensify before the development of a pronounced anti-depressive effect. Seek medical attention immediately if you have any thoughts or feelings that are disturbing you.
Use during pregnancy and lactation
If you are pregnant, breastfeeding, suggesting that you are pregnant or planning to become pregnant, tell your doctor or pharmacist. The capsules of the prolonged action of Velaxin should be taken only after a discussion with the doctor of the potential balance of benefits and risks for your unborn child. If you take Velaxin during pregnancy, report it to the obstetrician and / or doctor, as the child may have any of the symptoms after birth. These symptoms usually develop within the first 24 hours after the baby is born. These include poor diet and breathing problems. If the child has these symptoms after birth, and this worries you, consult your doctor and / or obstetrician who can advise you. Make sure your obstetrician and / or doctor know that you are taking Velaxin. In the case of taking similar drugs during pregnancy (specific serotonin reuptake inhibitors), the risk of developing a serious condition in newborns - persistent pulmonary hypertension of the newborn, leading to rapid breathing and cyanosis of the newborn - may increase. These symptoms usually develop within the first 24 hours after the baby is born. In this situation, you should immediately contact your obstetrician and / or doctor. Breastfeeding: Velaxin is excreted in breast milk. There is a risk of exposure to the child.Therefore, this issue should be discussed with the doctor, and he / she will decide whether to stop breastfeeding or treatment with the drug Velaxin. Check with your doctor or pharmacist before taking any medication.
Dosage and administration
Velaxin prolonged-release capsules should be taken with meals. Each capsule should be swallowed whole and washed down with liquid. Capsules must not be divided, crushed, chewed or placed in water. The daily dose should be taken at a time (in the morning or in the evening) at about the same time each time. Depression: The recommended starting dose is 75 mg once a day. If, according to the doctor, a higher dose is necessary (severe depressive disorder or other conditions requiring inpatient treatment), 150 mg can be prescribed immediately once a day. Subsequently, the daily dose can be increased by 75 mg with an interval of two weeks or more (but not more often than after 4 days), until the desired therapeutic effect is achieved. The maximum daily dose of 350 mg. After achieving the desired therapeutic effect, the daily dose can be gradually reduced to the minimum effective level. Supportive therapy and prevention of relapse: Treatment of depression should last at least 6 months. With stabilizing therapy, as well as therapy for the prevention of relapses or new episodes of depression, usually used doses that have demonstrated their effectiveness. The physician should regularly (at least once every 3 months) monitor the effectiveness of long-term therapy with the drug Velaxin. Transfer of patients from Velaxin pills Patients taking the drug Velaxin in the dosage form of a tablet can be transferred to the drug intake in the dosage form of a capsule of prolonged action with the appointment of an equivalent dose once a day. However, an individual dose adjustment may be required. Renal failure: in case of mild renal insufficiency (glomerular filtration rate (GFR) of more than 30 mlmin) correction of the dosing regimen is not required. In moderate renal insufficiency (GFR 10 - 30 mlmin), the dose should be reduced by 50%. In connection with the prolongation of the half-life of venlafaxine and its active metabolite (EFA), such patients should take the entire dose once a day.It is not recommended to use venlafaxine in severe renal failure (GFR less than 10 mlmin), since there is no reliable data on such therapy. Hemodialysis patients can receive 50% of the usual daily dose of venlafaxine after completion of hemodialysis. Hepatic impairment: in case of mild hepatic impairment (prothrombin time (PT) less than 14 sec) correction of the dosing regimen is not required. With moderate liver failure (PF from 14 to 18 seconds), the dose should be reduced by 50%. It is not recommended to use venlafaxine in case of severe hepatic failure, since there is no reliable data on such therapy. Elderly patients: in itself, the elderly patient does not require changing the dose, but (as with the appointment of other drugs), the treatment of elderly patients requires caution, for example, in connection with the possibility of impaired renal function. The smallest effective dose should be applied. At higher doses, the patient must be under close medical supervision. Children and adolescents (under the age of 18): The safety and efficacy of venlafaxine in children and adolescents under 18 years of age has not been established. Cancellation of the drug Velaxin: As with other antidepressants, abrupt withdrawal (especially high doses) of venlafaxine can cause withdrawal symptoms (see sections Side Effects and Special Instructions). Therefore, before the complete abolition of the drug is recommended gradual dose reduction. If high doses have been used for more than 6 weeks, it is recommended to reduce the doses for at least 2 weeks. The duration of the period required to reduce the dose depends on the dose, the duration of therapy, and the patient's reactions.
Side effects
Most of the side effects listed below are dose dependent. With prolonged treatment, the severity and frequency of most of these effects is reduced, and there is no need to cancel therapy. In order of decreasing frequency: frequent (less than 110 and more than 1100). infrequent (less than 1100 and more than 11000). rare (less than 11000). very rare (less than 110000). Common symptoms: weakness, fatigue, headache, abdominal pain, chills, fever. On the part of the gastrointestinal tract: loss of appetite, constipation, nausea, vomiting, dry mouth.infrequent: bruxism, reversible increase in liver enzymes. rare: gastrointestinal bleeding. very rare: pancreatitis. On the part of the nervous system: dizziness, insomnia, agitation, drowsiness. frequent: unusual dreams, anxiety, confused state of consciousness, increased muscle tone, paresthesia, tremor. infrequent: apathy, hallucinations, myoclonus. rare: ataxia, speech disorders, including dysarthria, mania or hypomania (see section Special instructions), manifestations resembling neuroleptic malignant syndrome, convulsive seizures (see section Special instructions), serotonergic syndrome. very rare: nonsense, extrapyramidal disorders, including dyskinesia and dystonia, tardive dyskinesia, psychomotor agitation, katasia (see section Special Instructions). Since the cardiovascular system: arterial hypertension, dilation of blood vessels (rush of blood), heart palpitations. infrequent: orthostatic hypotension, syncope, tachycardia. very rare: pirouette arrhythmia, prolongation of the QT interval, ventricular tachycardia, ventricular fibrillation. From the sense organs: accommodation disturbances, mydriasis, blurred vision, tinnitus. infrequent: violation of taste sensations. On the part of the hematopoietic system: infrequent: hemorrhages into the skin (ecchymosis) and mucous membranes. rare: thrombocytopenia, prolonged bleeding time. very rare: agranulocytosis, aplastic anemia, neutropenia, pancytopenia. On the part of the skin: sweating, itching and rash. infrequent: photosensitivity reactions, angioedema, maculo-papular rash, urticaria. rare: alopecia, erythema multiforme, Stevens-Johnson syndrome. On the part of the urogenital system: impaired ejaculation, erection, anorgasmia. infrequent: decreased libido, menstrual disorders, menorrhagia, urinary retention. rare: galactorrhea. On the part of the metabolism: an increase in serum cholesterol, weight loss. infrequent: hyponatremia, syndrome of insufficient secretion of antidiuretic hormone, impaired laboratory tests of liver function. rarely: hepatitis. very rare: increased prolactin levels. Musculoskeletal system: arthralgia, myalgia. infrequent: muscle spasm. very rare: rhabdomyolysis.In children, the following side effects were observed: abdominal pain, chest pain, tachycardia, refusal to eat, weight loss, constipation, nausea, ecchymosis, nosebleeds, mydriasis, myalgia, dizziness, emotional lability, tremor, hostility and suicidal thoughts. After abrupt cancellation of venlafaxine or a reduction in its dose, there may be: fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, anxiety, anxiety, disorientation, hypomania, paresthesia, sweating. These symptoms are usually mild and go away without treatment. Because of the likelihood of these symptoms, it is very important to gradually reduce the dose of the drug (as well as any other antidepressant), especially after taking high doses. The duration of the period required to reduce the dose depends on the dose, the duration of therapy, as well as the individual sensitivity of the patient.
Overdose
If you have taken more of Velaxin than was prescribed by a doctor, immediately consult a doctor or pharmacist. Symptoms of a possible overdose may include: fast heart rate, changes in the degree of activity (from drowsiness to coma), blurred vision, seizures or convulsions, and vomiting.
Interaction with other drugs
The simultaneous use of MAO inhibitors and venlafaxine contraindicated. Reception of the drug Velaxin can be started no less than 14 days after the end of therapy with MAO inhibitors. If a reversible MAO inhibitor (moccobemide) was used, this interval may be shorter (24 hours). Therapy with MAO inhibitors can begin no less than 7 days after discontinuation of the drug Velaxin. The simultaneous use of venlafaxine with lithium can increase the level of the latter. With simultaneous use with imipramine, the pharmacokinetics of venlafaxine and EFA do not change. At the same time, their simultaneous use enhances the effects of desipramine, the main metabolite of imipramine, and its other metabolite, 2-OH-imipramine, although the clinical significance of this phenomenon is unknown. Haloperidol: combined use increases the level of haloperidol in the blood and enhances its effects. With simultaneous use with diazepam pharmacokinetics of drugs and their major metabolites are not significantly changed.The effect on the psychomotor and psychometric effects of diazepam was also not detected. With simultaneous use with clozapine, an increase in its blood plasma level and the development of side effects (for example, seizures) can be observed. With simultaneous use with risperidone (despite an increase in the AUC of risperidone), the pharmacokinetics of the sum of the active components (risperidone and its active metabolite) do not change significantly. The decrease in mental and motor activity under the influence of alcohol did not increase after taking venlafaxine. Despite this, as in the case of taking other drugs that affect the central nervous system, the use of alcoholic beverages is not recommended during venlafaxine therapy. While taking venlafaxine, special care should be taken with electroconvulsive therapy, since there is no experience with venlafaxine in these conditions. Drugs metabolized by cytochrome P450 isoenzymes: CYP2D6 enzyme of the cytochrome P450 system converts venlafaxine to the active metabolite EFA. Unlike many other antidepressants, the dose of venlafaxine can not be reduced with simultaneous administration with drugs that suppress CYP2D6 activity, or in patients with a genetically determined reduction of CYP2D6 activity, since the total concentration of venlafaxine and EFA will not change. The main route of elimination of venlafaxine involves metabolism involving CYP2D6 and CYP3A4; Therefore, special care should be taken when prescribing venlafaxine in combination with drugs that inhibit both these enzymes. Such drug interactions have not yet been investigated. Venlafaxine is a relatively weak inhibitor of CYP2D6 and does not inhibit the activity of CYP1A2, CYP2C9 and CYP3A4 isoenzymes; therefore, one should not expect its interaction with other drugs, in the metabolism of which these liver enzymes are involved. Cimetidine inhibits first-pass venlafaxine metabolism and does not affect the EFA pharmacokinetics. In the majority of patients, only a slight increase in the total pharmacological activity of venlafaxine and EFA is expected (more pronounced in elderly patients and in impaired liver function). Clinical studies have not found clinically significant interactions with venlafaxine antihypertensive (includingbeta-blockers, ACE inhibitors and diuretics) and antidiabetic drugs. Drugs associated with plasma proteins: plasma binding is 27% for venlafaxine and 30% for EFA, therefore, drug interactions due to protein binding should not be expected. When taken simultaneously with warfarin, the anticoagulant effect of the latter can be enhanced, while the prolonged exposure and increased MHO. When taken simultaneously with indinavir, the pharmacokinetics of indinavir change (with a 28% decrease in AUC and a 36% decrease in Cmax), and the pharmacokinetics of venlafaxine and EFA do not change. However, the clinical significance of this effect is unknown.
special instructions
When depression increases the risk of suicidal thoughts and suicidal attempts. This risk persists until the onset of persistent remission. Therefore, patients should be under constant medical supervision, and they should be given only a small number of capsules of the drug to reduce the risk of possible abuse and / or overdose. Velaxin should not be used in the treatment of children and adolescents under the age of 18 years. An increase in the likelihood of suicidal behavior (suicide attempt and suicidal thoughts), as well as hostility in clinical trials, is more common among children and adolescents receiving antidepressants, compared with groups receiving placebo. It was reported on aggressive behavior while taking venlafaxine (especially at the beginning of the course of treatment and after discontinuation of the drug). The use of venlafaxine can cause psychomotor agitation, which is clinically reminiscent of akathisia, characterized by anxiety with the need to move, often in combination with an inability to sit or stand. This is most often observed during the first few weeks of treatment. If these symptoms occur, increasing the dose may have an adverse effect, and consider the appropriateness of continuing to take the drug. Like all antidepressants, venlafaxine should be administered with caution to patients with a history of mania and / or hypomania, since the drug can cause an increase in their symptoms. In these cases, medical observation is necessary. Caution should be exercised in the treatment of patients with convulsive seizures in history.If you experience convulsive seizures or increase their frequency of treatment with venlafaxine should be interrupted. Like selective serotonin reuptake inhibitors, venlafaxine should be used with caution when used concomitantly with antipsychotic drugs, as symptoms that resemble neuroleptic malignant syndrome may develop. Patients should be warned about the need to immediately consult a doctor if a rash, urticaria or other allergic reactions occur. In some patients, while taking venlafaxine, a dose-dependent increase in blood pressure was observed, and therefore, regular monitoring of blood pressure is recommended, especially at the beginning of a course of treatment or when the dose is increased. While taking venlafaxine, individual cases of orthostatic hypotension are described. Patients, especially the elderly, should be warned about the possibility of dizziness and imbalance. Venlafaxine can cause an increase in heart rate, especially while taking high doses. Special care should be taken when prescribing the drug to patients with conditions that may increase with an increase in heart rate. There have not been sufficient studies on the use of venlafaxine in patients who have recently had a myocardial infarction or have decompensated heart failure, so these patients should be used with caution. Like other serotonin reuptake inhibitors, venlafaxine may increase the risk of hemorrhages in the skin and mucous membranes, so caution is needed when treating patients prone to bleeding. While taking venlafaxine, especially in conditions of dehydration or reduction in blood volume (including in elderly patients and patients taking diuretics), hyponatremia and / or syndrome of insufficient secretion of ADH may occur. While receiving venlafaxine, cases of mydriasis are noted, so patients with a predisposition to increased IOP or who are at risk of angle-closure glaucoma require careful medical observation. For renal and hepatic insufficiency, special care is required. In some cases, a dose reduction is required (see “