Expiration date: 11/2025
Structure and Composition:
The long-acting capsules. 1 capsule contains 75 or 150mg venlafaxine (in the form of venlafaxine hydrochloride)
Other ingredients: sodium chloride, ethyl cellulose, talc MCC dimethicone potassium chloride copovidone Colloidal anhydrous silica Xanthan gum iron oxide yellow
gelatin capsule composition: iron oxide, titanium dioxide, red iron oxide, yellow gelatin
Description pharmaceutical form:
Capsules 75 mg: hard gelatine self-closing, with a colorless, transparent base and cover orange-brown color, containing a mixture of pellets of white and yellow, with little or no odor.
Capsules 150 mg: hard gelatine self-closing, with a colorless, transparent base and cover orange-brown color, containing a mixture of pellets of white and yellow, with little or no odor.
Pharmacokinetics:
Upon receiving Velaksina, long-acting capsules, Cmax venlafaxine and its major metabolite - O-desmethyl venlafaxine (EFA) in plasma reached within (6,0 ± 1,5) and (8,8 ± 2,2) h respectively. The rate of absorption of venlafaxine capsules of long-acting below the rate of its elimination. Therefore, T1 / 2 of venlafaxine after administration Velaksina capsules depot - (15 ± 6) h - is actually T1 / 2 of absorption than T1 / 2 of distribution (5 ± 2) hours, which is observed after administration Velaksin drug in tablet form .
The binding of venlafaxine and EFA to plasma proteins is respectively 27 and 30%. EFA and other metabolites and unmetabolized venlafaxine excreted by the kidneys. Repeated administration of the equilibrium concentrations of venlafaxine and EFA achieved within 3 days. In the range of 75-450 mg daily doses of venlafaxine and EFA have linear kinetics. After taking the drug at meal time achieving increased Cmax for 20-30 minutes in the blood plasma, but Cmax values ??and removals are not changed.
In patients with liver cirrhosis the concentration of venlafaxine blood plasma and increased EFA and their reduced rate of excretion. In moderate or severe renal insufficiency the overall clearance of venlafaxine and EFA is reduced, and the half-life is prolonged. Reducing the total clearance is mainly observed in patients with Cl creatinine below 30 ml / min. Age and sex of the patient did not affect the pharmacokinetics of the drug.
Description of the pharmacological actions:
Venlafaxine - an antidepressant. On chemical structure can not be attributed to any known class of antidepressants (tricyclic, tetracyclic, or other). It has two enantiomeric active racemic forms.
Venlafaxine Antidepressant effect associated with increased activity in the CNS neurotransmitter. Venlafaxine and EFA are potent inhibitors of the reuptake of serotonin and norepinephrine, and weakly inhibit the reuptake of dopamine neurons. Venlafaxine and EFA equally effective influence on the reuptake of neurotransmitters. Venlafaxine and EFA reduce adrenergic & beta-reaction.
Venlafaxine has no affinity for muscarinic, cholinergic, histamine H1- and adrenergic & alpha1-brain receptors. Venlafaxine does not inhibit MAO activity. No affinity for opiate, benzodiazepine, fentsiklidinovym or N-methyl-d-aspartate (NMDA-) receptors.
Testimony:
Depression (including the presence of the alarm), treatment and relapse prevention.
Contraindications:
- Hypersensitivity to any component of the drug
- simultaneous reception of MAO inhibitors (see. also "Interactions" section)
- severe violations of the kidneys and / or liver function (glomerular filtration rate (GFR) - less than 10 ml / min, the PX - more than 18)
- age 18 years (safety and efficacy in this age group have not been proved)
- pregnancy or suspected pregnancy
- Lactation (no controlled trials of sufficient data).
Precautions: recent myocardial infarction, unstable angina, heart failure, coronary artery disease, ECG changes, including lengthening the interval QT, electrolyte disturbances, hypertension, tachycardia, cramps in the history of ocular hypertension, angle-closure glaucoma, manic state in history, predisposition to bleeding from the skin and mucous membranes, weight loss initially.
Application of pregnancy and breastfeeding:
The safety of venlafaxine during pregnancy has not been proven, so use during pregnancy (or suspected pregnancy) is possible only if the potential benefit to the mother outweighs the potential risk to the fetus. Women of childbearing age should be warned about this prior to the start of treatment and should seek medical attention immediately in the event of pregnancy or planning pregnancy during drug treatment.
Venlafaxine and EFA highlighted in the breast milk. The safety of these substances for newborn children is not proven, so taking venlafaxine during breastfeeding is not recommended. If you want to receive the drug during lactation should decide the issue of termination of breastfeeding. If maternal treatment was completed shortly before the birth, the newborn drug withdrawal symptoms may occur.
Side effect:
Most of the following side effects depend on the dose. With long-term treatment of the severity and frequency of most of these effects is reduced, and there is no need for treatment discontinuation.
In decreasing order of frequency: often - <1/10 and> 1/100 infrequently - <1/100 and> rarely 1/1000 - <1/1000 rarely - <1/10000.
Common symptoms include weakness, fatigue, headache, abdominal pain, chills, fever.
On the part of the digestive tract: loss of appetite, constipation, nausea, vomiting, dry mouth, rarely - bruxism, reversible elevation of liver enzymes rarely - gastrointestinal bleeding very rarely - pancreatitis.
From the nervous system: dizziness, insomnia, agitation, drowsiness often - abnormal dreams, anxiety, confused state of mind, increased muscle tone, paraesthesia, tremor rare - apathy, hallucinations, myoclonus rarely - ataxia, speech disorders, including dysarthria, mania or hypomania (see "Special Instructions" section.) manifestations resembling neuroleptic malignant syndrome, seizures (see section "Special Instructions".), serotonergic syndrome rarely - delirium, extrapyramidal disorders, including dyskinesia and dystonia, tardive dyskinesia, psychomotor agitation / akathisia (see. "Special Instructions" section).
Since the cardiovascular system: hypertension, vasodilation (hot flushes), palpitations rarely - orthostatic hypotension, syncope, tachycardia, rarely - arrhythmias of the type "pirouette", lengthening the interval QT, ventricular tachycardia, ventricular fibrillation.
From the senses: accommodation disturbances, mydriasis, blurred vision, tinnitus, rarely - a violation of taste sensations.
Hematopoietic system: rarely - bleeding in the skin (ecchymosis) and mucous membranes rarely - thrombocytopenia, prolonged bleeding is very rare - agranulocytosis, aplastic anemia, neutropenia, pancytopenia.
For the skin: sweating, itching and rashes rarely - photosensitivity reactions, angioedema, rash maculo-papular, rash rare - alopecia, erythema multiforme, Stevens-Johnson syndrome.
With the genitourinary system: ejaculation disorders, erectile dysfunction, anorgasmia infrequently - decreased libido, irregular menstruation, menorrhagia, urinary retention, rarely - galactorrhea.
On the part of metabolism: increased levels of serum cholesterol, decrease in body weight rare - hyponatremia, syndrome of inadequate secretion of antidiuretic hormone, violation of laboratory samples of the liver, rarely - hepatitis is very rare - increase in prolactin levels.
Musculoskeletal system: arthralgia, myalgia, rarely - muscle spasm rarely - rhabdomyolysis.
In children, these side effects were observed: abdominal pain, chest pain, tachycardia, refusal of food, reduction of body weight, constipation, nausea, ecchymosis, epistaxis, mydriasis, myalgia, dizziness, emotional lability, tremor, hostility and suicidal thoughts.
After the abrupt cancellation of venlafaxine or reducing the dose can be observed: fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, restlessness, anxiety, disorientation, hypomania, paraesthesia, sweating. These symptoms are usually mild and go away without treatment. Because of the likelihood of these symptoms it is important to gradually reduce the dose of the drug (or any other antidepressant), especially after high doses. The length of time required to reduce the dose depends on the dose, duration of therapy, as well as individual patient sensitivity.
Drug Interactions:
Concomitant use of monoamine oxidase inhibitors (MAOIs) is contraindicated and venlafaxine. Admission Velaksin drug can be started at least 14 days after the end of therapy MAO inhibitors. If you used a reversible MAO inhibitor (moclobemide), this interval may be shorter (24 h). MAO inhibitor therapy can begin at least 7 days after the cancellation Velaksin drug.
Concomitant use of venlafaxine with lithium may increase the level of the latter.
In an application with imipramine pharmacokinetics of venlafaxine and EFA does not change. At the same time, their simultaneous use enhances the effects of desipramine - the major metabolite of imipramine - and another metabolite - 2-OH- imipramine, although the clinical significance of this phenomenon is unknown.
Haloperidol: combined use enhances haloperidol in blood and increases its effects.
While the use of diazepam pharmacokinetics of drugs and their main metabolites does not change significantly. Also not revealed effects on psychomotor and psihometabolicheskie effects of diazepam.
In an application with clozapine may experience an increase in its level in the blood plasma and the development of side effects (eg seizures).
In an application with risperidone (despite the increase in AUC of risperidone), the pharmacokinetics of the amount of active ingredients (risperidone and its active metabolite) does not change significantly.
Reduced mental and motor activity under the influence of alcohol is not amplified after prima venlafaxine. Despite this, as in the case of reception of other drugs affecting the central nervous system, while venlafaxine therapy is not recommended to consume alcoholic drinks.
In patients receiving venlafaxine should be particularly careful when electroconvulsive therapy, as experience with venlafaxine in these conditions is missing.
Drugs metabolized by cytochrome P450 isoenzymes: CYP2D6 enzyme cytochrome P450 converts to the active metabolite of venlafaxine EFA. Unlike many other antidepressants, venlafaxine dose can not reduce, while administered with drugs that inhibit the activity of CYP2D6, or in patients with a genetically determined reduction in CYP2D6 activity, as the total concentration of venlafaxine and EFA will not change.
The primary route of elimination of venlafaxine includes metabolism by CYP2D6 and CYP3A4 should therefore take special care in prescribing venlafaxine in combination with drugs, depressing both the enzyme. Such drug interactions have not been investigated.
Venlafaxine - a relatively weak inhibitor of CYP2D6 and does not inhibit the activity of isozymes CYP1A2, CYP2C9 and CYP3A4 so do not expect its interaction with other drugs in the metabolism involving the liver enzymes. Cimetidine inhibits first-pass metabolism of venlafaxine and has no effect on the pharmacokinetics of EFA. The majority of patients are expected only a slight increase in the overall pharmacological activity of venlafaxine and EFA (more pronounced in older patients and with abnormal liver function).
Clinical studies have found no clinically significant interactions with antihypertensive venlafaxine (including beta-blockers, ACE inhibitors and diuretics) and antidiabetic drugs.
Medications associated with blood plasma proteins: the binding to plasma proteins is 27% - for venlafaxine and 30% - for the EFA, so do not expect drug-drug interactions due to protein binding.
When concomitantly with warfarin may intensify the anticoagulant effect of the latter, at the same time it lengthens and increases PV MHO. When concomitantly with indinavir changed pharmacokinetics of indinavir (28% decrease in AUC and a 36% decrease in Cmax), and the pharmacokinetics of venlafaxine and EFA does not change. However, the clinical significance of this is unknown effect.
Dosage and administration:
Inside, during a meal. Each capsule should be swallowed whole and washed down with fluid. Capsules can not divide, crush, chew, or put into the water. The daily dose should be taken at one time (morning or evening), each time at about the same time.
Depression. The recommended initial dose - 75 mg 1 time a day.
If the opinion of the physician, a higher dose (major depression or other conditions that require hospital treatment), you can immediately appoint 150 mg 1 time per day. Subsequently, the daily dose may be increased to 75 mg every 2 weeks or more (but not more than 4 days) until the desired therapeutic effect. The maximum daily dose - 350 mg.
After achieving the desired therapeutic effect, the daily dose can be gradually reduced to the minimum effective level.
Supportive therapy and relapse prevention. Treatment for depression should continue for at least 6 months. When a stabilizing treatment and therapy to prevent relapses or new episodes of depression, commonly used dose, demonstrating its effectiveness. The doctor should regularly (at least once every 3 months) to monitor the effectiveness of long-term therapy with Velaksin.
Translation patients Velaksin tablets. Patients taking the drug in tablet form Velaksin can be transferred to the drug as a long-acting capsules, with doses of 1 equivalent appointment times per day. However, the individual may need a dose adjustment.
Renal insufficiency. In mild renal failure (GFR - 30 ml / min), a correction mode is not required. At moderate renal failure (GFR - 10-30 ml / min), the dose should be reduced by 50%. In connection with the elongation of T1 / 2 of venlafaxine and EFA, such patients should take the entire dose one time per day. Not recommended for venlafaxine in severe renal insufficiency (glomerular filtration rate - less than 10 ml / min), since reliable data on such therapy available. Patients on hemodialysis may receive 50% of the usual daily dose of venlafaxine after the completion of hemodialysis.
Liver failure. For mild hepatic insufficiency (PX - less than 14 c) correction mode is not required. At moderate hepatic impairment (MF - from 14 to 18), the dose should be reduced by 50%. Not recommended for venlafaxine in severe hepatic insufficiency, since reliable data on such therapy available.
Elderly patients. By itself, the older age of the patient does not require a change in dose, however (as in the appointment of other drugs) for the treatment of elderly patients need to be careful, for example in connection with renal dysfunction. Use the smallest effective dose. When the dose the patient should be under close medical supervision.
Children and adolescents (under 18 years). The safety and efficacy of venlafaxine in children and adolescents younger than 18 years have not been established.
Cancel the drug Velaksin
As with other antidepressants in the treatment, abrupt withdrawal of reception (especially high-dose) venlafaxine can cause withdrawal symptoms (see. Forums "Side effects" and "Cautions"). Therefore, a gradual reduction in dose is recommended before the complete abolition of the drug. If high doses applied for over six weeks, it is recommended to reduce the dose for at least 2 weeks. The length of time required to reduce the dose depends on the dose and duration of therapy and the patient's reactions.
Overdose:
Symptoms: ECG changes (prolongation of the interval QT, bundle branch block feet blockade, expansion of the QRS complex), sinus and ventricular tachycardia, bradycardia, hypotension, apnea condition, depression of consciousness (decreased level of consciousness). With an overdose of venlafaxine while taking alcohol and / or other psychotropic drugs, reported deaths.
Treatment: symptomatic. Specific antidotes are not known. Recommended continuous monitoring of vital functions (respiration and circulation). Appointment of activated charcoal to reduce absorption of the drug. Do not induce vomiting due to aspiration hazard. Venlafaxine and EFA are not displayed during dialysis.
Special instructions:
When depression increases the risk of suicidal thoughts and suicide attempts. This risk persists until the onset of stable remission. Therefore, patients should be under constant medical supervision, and should issue only a small number of capsules of the drug to reduce the risk of potential abuse and / or overdose.
Velaksin should not be used in the treatment of children and adolescents younger than 18 years. Increase the likelihood of suicidal behavior (suicide attempt and suicidal thoughts), and hostility in clinical trials is more common among children and adolescents treated with antidepressants compared to placebo. It has been reported about the aggressive behavior while receiving venlafaxine (especially at the beginning of treatment and after discontinuation of the drug).
The use of venlafaxine can cause agitation, which clinically resembles akathisia, characterized by a concern with the need to move, often in combination with the inability to sit or stand still. It occurs most often during the first few weeks of treatment. If you have any of these symptoms increase in dose can have an adverse effect, and should consider whether to continue taking the drug.
As with all antidepressants, venlafaxine should be administered with caution to patients with delusions and / or a history of hypomania, as the drug may cause increase in their symptoms. In these cases, medical supervision.
Caution should be exercised when treating patients with a history of seizures. In the event of seizures or increase their frequency of treatment with venlafaxine should be discontinued.
Like the selective serotonin reuptake inhibitors, venlafaxine should be used with caution during concomitant use with antipsychotics because may develop symptoms resembling neuroleptic malignant syndrome.
Patients should be warned of the need to consult a doctor immediately in case of rash, urticaria, or other allergic reactions.
In some patients, while receiving venlafaxine observed a dose-dependent increase in blood pressure, and therefore it is recommended to monitor blood pressure regularly, especially at the beginning of treatment or when increasing the dose.
While receiving venlafaxine individual cases of orthostatic hypotension are described. Patients, especially the elderly, should be alerted to the possibility of dizziness and impaired sense of balance.
Venlafaxine may cause an increase in heart rate, especially in high doses. It should be particularly careful when administering the drug to patients with conditions that may increase with an increase in heart rate. Not conducted adequate trials of venlafaxine in patients with recent myocardial infarction or suffering from decompensated heart failure, so use this drug in these patients with caution.
As with other serotonin reuptake inhibitors, venlafaxine may increase the risk of bleeding in the skin and mucous membranes, so when treating patients predisposed to bleeding, caution is required.
While receiving venlafaxine, especially under conditions of dehydration or reduction of blood volume (including elderly patients and in patients receiving diuretics), hyponatremia can be observed and / or syndrome of inadequate secretion of antidiuretic hormone (SIADH).
While receiving venlafaxine cases marked mydriasis, so patients with a predisposition to increased intraocular pressure, or having a risk of angle-closure glaucoma need careful medical supervision.
In renal and liver failure need special care. In some cases, dose reduction is required (see. "Dosage and Administration" section). Safety and efficacy of venlafaxine with means which reduce body weight, including phentermine, not installed, so their simultaneous application (application venlafaxine as monotherapy for reducing body weight) is not recommended. Clinically significant increases in the level of serum cholesterol was observed in some patients receiving venlafaxine for at least 4 months. Therefore, with a long reception of the drug it is advisable to carry out the control of serum cholesterol level.
After discontinuation of the drug, especially sudden, often have withdrawal symptoms (see. "Side effects" section). The risk of withdrawal symptoms may depend on several factors, including the duration of the course and the dose and dose rate reduction. Withdrawal symptoms such as: dizziness, sensory disturbances (including paraesthesia and feeling of the passage of an electric current), sleep disturbances (including insomnia and abnormal dreams), agitation or anxiety, nausea and / or vomiting, tremor, sweating , headache, diarrhea, palpitations and heart palpitations and emotional instability are usually small or medium severity, but they can be severe in some patients. They usually occur in the first days after discontinuation of the drug, although there have been isolated reports of the occurrence of such symptoms in patients inadvertently missed a dose. Typically, these phenomena are alone for 2 weeks but in some patients they may be more prolonged (2-3 months or more). Therefore, before the abolition of venlafaxine is recommended to gradually reduce the dose over several weeks or months depending on the patient's condition (see. "Dosage and Administration" section).
The ability of driving vehicles. Please note that any medication psychoactive drugs can reduce the ability to make judgments, thinking, or motor function performance. This should warn the patient before treatment. In the event of such effects the extent and duration of the restrictions should be set by your doctor.
