Pharmacological properties of the drug Velaxin
Venlafaxine ((±)-1-[dimethylamino-1-(methoxy-phenyl)-ethyl] cyclohexanol hydrochloride) is an antidepressant with a new chemical structure that cannot be classified as tricyclic, tetracyclic or other known antidepressants. It is a racemic mixture of two active enantiomers. The mechanism of the antidepressant effect of venlafaxine is associated with increased neurotransmitter activity of the central nervous system. Venlafaxine and its main metabolite O-desmethyl venlafaxine (ODV) are potent inhibitors of neuronal reuptake of serotonin and norepinephrine, and also inhibit dopamine reuptake. In addition, both single and chronic administration of venlafaxine and EDV attenuates β-adrenergic reactions. They are equally effective in influencing the reuptake of neurotransmitters. Venlafaxine does not inhibit MAO activity. Venlafaxine has no affinity for opiate, benzodiazepine, phencyclidine, or N-methyl-d-aspartate (NMDA) receptors; it also does not affect the release of norepinephrine from brain tissue. With repeated use of the drug, equilibrium concentrations of venlafaxine and its only active metabolite in the blood plasma are achieved within 3 days. Venlafaxine and EDV have linear pharmacokinetics with total daily doses ranging from 75 to 450 mg. Absorption of venlafaxine after taking a single dose of the drug orally is almost 92%, absolute bioavailability is about 45%. After administration of Velaxin extended-release capsules, maximum plasma concentrations of venlafaxine and its active metabolite EDV are achieved within approximately 6 and 8 hours, respectively. The rate of absorption of venlafaxine released from extended-release capsules is less than the rate of its elimination. Therefore, the average half-life of venlafaxine from the body after taking Velaxin (15±6 hours) is actually the half-life in the absorption phase, and not the half-life in the distribution phase (5±2 hours), which is observed after the use of tablets. After administration of venlafaxine in equivalent doses in tablet or extended-release capsule form, venlafaxine AUC exposure and EDV were similar in both dosage forms, and their plasma concentrations were slightly lower after administration of venlafaxine in capsule form. Thus, extended-release capsules provide slower absorption but the same extent of absorption (i.e., AUC) as Velaxin tablets. Venlafaxine is extensively metabolized during the initial passage through the liver, mainly with the participation of CYP 2D6, with the formation of the main metabolite EDV. It is also metabolized to N-desmethyl venlafaxine and some other metabolites with the participation of CYP 3A3/4. Venlafaxine and its metabolites are excreted mainly by the kidneys. Approximately 78% of the administered dose of venlafaxine is determined in the urine over 48 hours in the form of unchanged venlafaxine, unconjugated EDV, conjugated EDV or other metabolites. In case of renal and hepatic insufficiency, the half-life of venlafaxine and its active metabolite EDV increases. Taking the drug with food does not affect the absorption of venlafaxine and the further formation of EDV. The age and gender of the patient do not affect the pharmacokinetics of the drug. The drug does not accumulate in the body. Velaxin extended-release capsules contain microspheres that, when entering the gastrointestinal tract, slowly release the active component. The insoluble part of these microspheres is excreted in the feces.
Compound
The main active ingredient of the drug is venlafaxine . This is an antidepressant from the group of selective serotonin and norepinephrine reuptake inhibitors. Venlafaxine is an international name that is produced by different companies under different trade names, one of which is Velaxin. The dosage of the drug is calculated based on the active substance.
Additional substances are necessary to give the drug the required form. Velaxin contains the following substances: cellulose and its compounds, talc, dimethicone, sodium, cadmium, potassium, silicon and iron compounds. The capsules also contain gelatin and food coloring.
Use of the drug Velaxin
Capsules should be taken whole with a meal with liquid. Capsules should not be divided, crushed, chewed or dissolved. The daily dose should be taken in one dose (morning or evening) at the same time. Depression The recommended dose is 75 mg/day in one dose. If, taking into account the course of the disease, a higher dose is necessary, for example, in case of severe depression or inpatient treatment of the patient, the recommended initial dose may be 150 mg/day in one dose. After this, the daily dose can be increased by 37.5–75 mg at intervals of ≥2 weeks, but not less than 4 days until the required therapeutic effect is achieved. The recommended maximum dose of Velaxin is 225 mg/day for moderate depression and 350 mg for severe depression. After achieving the desired therapeutic effect, the dose should be gradually reduced to the minimum effective, taking into account the individual response and tolerability of each patient. When used in high doses, the risk of developing side effects of the drug increases. Generalized anxiety disorders and social anxiety disorders (social phobia) The recommended dose of Velaxin is 75 mg/day in one dose. If after 2 weeks of treatment there is no noticeable improvement in the condition, the daily dose can be increased to 150 mg/day in one dose. When used in a daily dose of 75 mg, an anxiolytic effect is observed after 1 week. Prevention of relapses or new episodes The effectiveness of venlafaxine has been established with long-term therapy (up to 12 months for depression and social phobia; up to 6 months for generalized anxiety disorders). Treatment of acute episodes of depression must be continued for at least 6 months. The doses typically used to prevent a relapse or new episode are similar to those used to treat patients with a primary episode. It is necessary to regularly (at least once every 3 months) examine the patient to monitor the effectiveness of long-term therapy with Velaxin. Transfer of patients receiving therapy with Velaxin in the form of tablets to taking a capsule form of the drug Patients with depression receiving Velaxin tablets in a therapeutic dose can be transferred to taking the drug in the form of long-acting capsules with the appointment of the nearest equivalent dose. Sometimes individual dose adjustment may be required. Renal failure When the glomerular filtration rate is 30 ml/min, no dose adjustment is required. With a glomerular filtration rate of 10–30 ml/min, the dose should be reduced by 50%. Due to the increased half-life of venlafaxine and its active metabolite in these patients, the daily dose should be taken in one dose. It is not recommended to use venlafaxine if the glomerular filtration rate is ≤10 ml/min, since there is insufficient data on therapy in these patients. For patients on hemodialysis, the daily dose of the drug should be reduced by 50% and, if possible, used after completion of the hemodialysis procedure. Liver failure In mild liver failure (prothrombin time ≤14 s), no dose adjustment is required. In case of moderately severe liver failure (prothrombin time - 14–18 s), the dose should be reduced by 50%. It is not recommended to use venlafaxine in severe hepatic impairment (prothrombin time 18 s), as there is insufficient data on this therapy. Elderly patients Caution should be exercised when prescribing the drug to elderly patients (due to the possibility of renal dysfunction), and the drug is prescribed in the minimum effective dose. When increasing the dose, the patient should be under regular medical supervision. Cancellation of Velaxin Abrupt cessation of Velaxin therapy, especially after taking the drug in high doses, can cause the development of withdrawal syndrome, and therefore a gradual dose reduction is recommended before complete discontinuation of the drug. If the drug has been used in high doses for 6 weeks, a dose reduction period of at least 2 weeks is recommended. The length of the period required to reduce the dose depends on the dose size, duration of therapy, as well as the individual sensitivity of the patient.
Pharmacokinetics
Venlafaxine after oral administration is almost completely metabolized in the liver. 16% is converted to N-didesmethylvenlafaxine (DDV) and 56% is metabolized to O-desmethylvenlavaxine (ODV). Among all metabolites, ODV is pharmacologically more active with a higher concentration and longer half-life than the parent compound (4-9 hours vs. 11-13 hours) and therapeutically contributes significantly to the effects of VEN. Therapeutic plasma concentration levels for VEN typically range from 30 to 200 ng/mL, while ODV levels range from 50 to 500 ng/mL.
The figure shows the concentration profile of Venlafaxine (VEN), O-desmethylvenlavaxine (ODV) and N-didesmethylvenlafaxine (DDV) after a single dose of 75 mg. volunteer. After half an hour, the plasma concentration of ODV significantly exceeded the plasma concentration of the parent compound. However, the maximum concentration was recorded almost after 1 hour in plasma. Thus, the maximum concentrations of compounds in the blood plasma were 141.2, 268.7 and 47.0 ng/ml, which were observed almost 1.5, 2.5 and 2.5 hours after administration of VEN, ODV and DDV, respectively . The half-lives of VEN, ODV and DDV were approximately 5.1, 8.2 and 5.4 hours, respectively.
Contraindications to the use of the drug Velaxin
Hypersensitivity to any component of the drug. Simultaneous use of any antidepressant from the MAO inhibitor group, as well as for 14 days after discontinuation of irreversible MAO inhibitors. After complete discontinuation of venlafaxine, therapy with MAO inhibitors can be started no earlier than 7 days later. Diseases of the cardiovascular system (heart failure, coronary artery disease, ECG changes - pre-existing increase in the QT on the ECG), hypertension (arterial hypertension), electrolyte imbalance. Age up to 18 years. During pregnancy and breastfeeding.
Side effects of the drug Velaxin
Side effects are divided by body system and frequency of occurrence: very often (1/10); often (≤1/10, but 1/100); sometimes (≤1/100, but 1/1000); rare (≤1/1000); very rare (≤1/10,000). General symptoms: very often - asthenia, headache; often - abdominal pain, chills, increased body temperature; rarely - anaphylaxis. Gastrointestinal tract: very often - constipation, nausea; often - loss of appetite, diarrhea, vomiting; sometimes - bruxism, reversible increase in the activity of liver enzymes; rarely - gastrointestinal bleeding; very rarely - pancreatitis. Cardiovascular system: often - tachycardia, hypertension (arterial hypertension), dilatation of blood vessels; sometimes - hypotension/orthostatic hypotension, loss of consciousness, arrhythmias, tachycardia; very rarely - pirouette-type tachycardia, increased QT on ECG, ventricular tachycardia, ventricular fibrillation. Respiratory system: often - difficulty breathing, yawning; very rarely - eosinophilic infiltrates in the lungs. Nervous system: very often - dizziness, dry mouth, insomnia, anxiety, drowsiness; often - unusual dreams, agitation, anxiety, confusion, increased muscle tone, paresthesia, tremor; sometimes - apathy, hallucinations, myoclonus; rarely - ataxia with impaired balance and coordination of movements, speech impairment, including dysarthria, mania or hypomania, as well as manifestations that resemble neuroleptic malignant syndrome (NMS), seizures, serotonergic syndrome; very rarely - delirium, extrapyramidal disorders, including dyskinesia and dystonia, psychomotor agitation/akathisia. Genitourinary system: very often - anorgasmia, erectile dysfunction, impaired ejaculation and orgasm; often - frequent urination, decreased libido, menstrual irregularities; sometimes - urinary retention, menorrhagia; rarely - galactorrhea. Sense organs: often - blurred vision and accommodation, mydriasis, noise and ringing in the ears; sometimes - a change in taste sensations. Skin: very often - sweating; often - skin rashes and itching; sometimes - angioedema, maculopapular rash, urticaria, photosensitivity, alopecia; rarely - erythema multiforme, Stevens-Johnson syndrome. Blood system: sometimes - ecchymosis, bleeding from the mucous membrane; rarely - increased bleeding time, hemorrhage, thrombocytopenia; very rarely - agranulocytosis, aplastic anemia, neutropenia, pancytopenia. Metabolism: often - increased cholesterol levels in the blood serum, increase or decrease in body weight; sometimes - hyponatremia, increased activity of liver transaminases; rarely - hepatitis; very rarely - increased prolactin levels. Musculoskeletal system: often - arthralgia, myalgia; sometimes - muscle spasms; very rarely - rhabdomyolysis.
Venlafaxine (Velaxin) tablets 75 mg No. 30
A country
Russia
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Active substance
Venlafaxine
Compound
1 tablet contains: venlafaxine (in the form of hydrochloride) 75 mg.
Excipients: microcrystalline cellulose 134.62 mg, pregelatinized starch 99.00 mg, colloidal silicon dioxide (aerosil) 1.64 mg, talc 6.60 mg, magnesium stearate 3.30 mg. Flat-cylindrical tablets with a chamfer and a score, white or white with a yellowish tint. Light marbling is allowed.
pharmachologic effect
Venlafaxine is an antidepressant that does not chemically belong to any class of antidepressants (tricyclic, tetracyclic or others) and is a racemate of two active enantiomers. Venlafaxine and its main metabolite, O-desmethylvenlafaxine (ODV), are potent serotonin and norepinephrine reuptake inhibitors (abbreviated as SNRIs or SNRIs) and weak dopamine reuptake inhibitors. The mechanism of antidepressant action is associated with the ability of the drug to enhance the activity of neurotransmitters during the transmission of nerve impulses in the central nervous system (CNS). Venlafaxine and EDV are equally effective in influencing the reuptake of the above-mentioned neurotransmitters, while they do not have an affinity (studied in vitro) for cholinergic (muscarinic), histamine (H1), alpha1-adrenergic, opioid and benzodiazepine receptors, and do not suppress the activity of monoamine oxidase (MAO) . In terms of inhibition of serotonin reuptake, venlafaxine is inferior to selective serotonin reuptake inhibitors (SSRIs).
Indications for use
Depression: prevention and treatment.
Mode of application
Inside. Venlafaxine is taken with food, preferably at the same time, without chewing and with liquid. The recommended starting dose is 75 mg in two divided doses daily (37.5 mg 2 times a day). Depending on tolerability and effectiveness, the dose may be gradually increased to 150 mg/day. If necessary, the dose is increased to 225 mg/day. Dose increases of 75 mg/day can be made at intervals of 2 weeks or more; if clinically necessary, due to the severity of symptoms, it is possible to increase the dose in a shorter period of time, but not less than 4 days. Higher doses (up to a maximum daily dose of 375 mg/day in 2-3 doses) require inpatient monitoring of patients. After achieving the required therapeutic effect, the daily dose can be gradually reduced to the minimum effective level. Maintenance therapy and relapse prevention: Maintenance treatment can last 6 months or more. The minimum effective doses used in the treatment of a depressive episode are prescribed. Renal failure: in case of mild renal failure (glomerular filtration rate (GFR) more than 30 ml/min), no dosage adjustment is required. In case of moderate renal failure (GFR 10-30 ml/min), the dose should be reduced by 25-50%. Due to the prolongation of T1/2 of venlafaxine and its active metabolite (EAM), such patients should take the entire dose once daily. It is not recommended to use venlafaxine in severe renal failure (GFR less than 10 ml/min), since reliable data on such therapy are lacking. During hemodialysis, the daily dose should be reduced by 50%; the drug should be taken after the end of the hemodialysis session. Liver failure: in case of mild liver failure (prothrombin time (PT) less than 14 seconds), no dosage adjustment is required. In case of moderate liver failure (PT 14 to 18 seconds), the daily dose should be reduced by 50% or more. It is not recommended to use venlafaxine in severe liver failure, since reliable data on such therapy are lacking. Elderly patients: the elderly age of the patient in the absence of any acute or chronic diseases does not require a change in dose, however (as when prescribing other drugs) caution is required when treating elderly patients. Elderly patients should use the lowest effective dose. When increasing the dose, the patient should be under close medical supervision. Discontinuation of the drug Discontinuation of the drug should be done gradually to minimize the risk associated with drug withdrawal. With a course of treatment of 6 weeks or more, the period of gradual withdrawal of the drug should be at least 2 weeks and depends on the dose, duration of therapy and the individual characteristics of the patient.
Interaction
Venlafaxine, which itself does not have increased binding to plasma proteins, practically does not increase the concentration of concomitantly taken drugs, which are characterized by high binding to plasma proteins. No clinically significant interaction with antihypertensive (many pharmacological groups, including beta blockers, ACE inhibitors and diuretics) and antidiabetic drugs was detected. Caution should be exercised when co-administered with other drugs that affect the central nervous system, since combinations of venlafaxine with all such drugs have not been studied. MAO inhibitors The simultaneous use of venlafaxine with MAO inhibitors, as well as within 14 days after their discontinuation, is contraindicated (the risk of severe side effects, including death, is likely). Therapy with MAO inhibitors can be prescribed no less than 7 days after discontinuation of the drug Venlafaxine. Venlafaxine should be discontinued at least 7 days before starting reversible selective MAO inhibitors (moclobemide). The weakly reversible and non-selective MAO inhibitor linezolid (an antimicrobial drug) and methylene blue (IV dosage form) are also not recommended for concomitant use with venlafaxine. Serotonergic drugs Caution should be exercised in the simultaneous use of drugs that affect the serotonin system of mediators, such as triptans (sumatriptan, zolmitriptan, etc.), selective serotonin reuptake inhibitors (SSRIs) and SNRIs (prolonged convulsions have been reported), tricyclic antidepressants, lithium, sibutramine or fentanyl (and its analogues dextromethorphan, tramadol, etc.), as well as excess sources of tryptophan due to the increased potential risk of serotonin syndrome. Alcohol During treatment with venlafaxine, alcohol (ethanol) should be completely avoided. Alcohol increases the psychomotor dysfunction that venlafaxine can cause. Lithium Lithium preparations do not have a significant effect on the pharmacokinetics of venlafaxine. Diazepam There was no effect of orally administered diazepam on the pharmacokinetics of venlafaxine and EDV, and, conversely, venlafaxine did not change the pharmacokinetics of diazepam and its metabolite desmethyldiazepam. In addition, the administration of both of these drugs does not impair the psychomotor and psychometric effects caused by diazepam. Cimetidine The simultaneous administration of cimetidine and venlafaxine resulted in a delay in metabolism during the “first pass” of venlafaxine. The oral clearance of venlafaxine decreased by 43%, and the area under the pharmacokinetic curve (AUC) and Cmax for this drug increased by 60%. However, no similar impact was found for EFA. Since the total activity of venlafaxine and EFA is expected to increase only slightly, no dose adjustment will be required for most normal patients. However, in patients with existing (detected) hypertension, elderly patients and those with impaired liver or kidney function, the dose of venlafaxine may be adjusted. Haloperidol In a study where venlafaxine was administered at steady state at a dose of 150 mg/day, a 42% decrease in total oral haloperidol clearance was observed following a 2 mg oral dose; while AUC increased by 70%, and Cmax increased by 88%, while T1/2 of haloperidol did not change. This should be taken into account when choosing the correct dose of haloperidol. Imipramine Venlafaxine does not impair the pharmacokinetics of imipramine and 2-hydroxyimipramine. However, the AUC, Cmax and Cmin of desipramine (the active metabolite of imipramine) increased by approximately 35% when co-administered with venlafaxine. The concentration of 2-hydroxydesipramine also increases from 2.5 to 4.5 times (depending on the dose of venlafaxine: 37.5 mg for 12 hours or 75 mg for 12 hours), but the clinical significance of this fact is not known. Metoprolol When using metoprolol and venlafaxine simultaneously, caution should be exercised, since due to pharmacokinetic interaction, the concentration of metoprolol in the blood plasma increases by approximately 30-40%, without changing the concentration of its active metabolite β-hydroxymetoprolol. The clinical significance of this interaction has not been studied. Metoprolol does not affect the AUC of venlafaxine and EDV. Risperidone When used concomitantly with risperidone (despite an increase in the AUC of risperidone), the pharmacokinetics of a pair of active molecules (risperidone and 9-hydroxyrisperidone) do not change significantly when combined with venlafaxine. Clozapine During post-marketing studies of venlafaxine, it was found that when used simultaneously with clozapine, its concentration in the blood plasma increases. This was manifested by an increase in the side effects of clozapine, especially in relation to the incidence of seizures. Indinavir With simultaneous use, the pharmacokinetics of indinavir changes (AUC decreases by 28% and Cmax decreases by 36%). For venlafaxine, no changes in pharmacokinetics are observed. The clinical significance of this fact is unknown. Ketoconazole A pharmacokinetic study when combined with ketoconazole showed an increase in plasma concentrations of venlafaxine and EDV in subjects with both good (X-Met) and poor (P-Met) metabolism by CYP2D6. In particular, the Cmax of venlafaxine increased by 26% for X-Met and by 48% for P-Met. EFA Cmax values increased by 14% and 29% in X-Met and P-Met subjects, respectively. The AUC of venlafaxine increased by 21% in X-Met and by 70% in P-Met. EFA AUC values increased by 23% and 33% in X-Met and P-Met subjects, respectively. Drugs that affect blood clotting and platelet function (NSAIDs, acetylsalicylic acid preparations and other anticoagulants) Serotonin, released by platelets, plays an important role in hemostasis (stopping bleeding). Epidemiological studies demonstrate an association between the use of psychotropic medications that interfere with serotonin reuptake and the incidence of upper gastrointestinal bleeding. This relationship is enhanced if NSAIDs, drugs containing acetylsalicylic acid or other anticoagulants are used simultaneously. The risk of bleeding has been shown to increase when SSRIs and SNRIs (including venlafaxine) are prescribed concomitantly with warfarin. Patients prescribed warfarin should be closely monitored for prothrombin time and/or partial thromboplastin time, especially when co-administration with venlafaxine is started or stopped. Interaction with other drugs at the level of the studied metabolism with cytochrome P450 isoenzymes The main routes of metabolism of venlafaxine include isoenzymes CYP2D6 and CYP3A4: the first of them converts venlafaxine into its active metabolite EDV, and the second is less important in the metabolism of venlafaxine compared to CYP2D6 and forms the product N -desmethylvenlafaxine with little pharmacological activity. Preclinical studies have shown, and subsequently confirmed clinically, that venlafaxine is a relatively weak inhibitor of CYP2D6. Therefore, even when prescribed with drugs that moderately suppress the activity of this enzyme (see the example with imipramine above), or in the case of patients with a genetically determined decrease in CYP2D6 function, no dose adjustment of venlafaxine is required, since the total concentration of the active substance and active metabolite (venlafaxine and EFA) does not change significantly. This characterizes venlafaxine positively when compared with other antidepressants. Caution should be exercised when co-administered with CYP2D6 inhibitors such as quinidine, paroxetine, fluoxetine, haloperidol, perphenazine, levomepromazine, as venlafaxine may potentially increase the plasma concentrations of these CYP2D6 substrates. In combination with drugs that inhibit both enzymes (CYP2D6 and CYP3A4), special caution is required. Such drug interactions have not yet been sufficiently studied, and in this case this combination of drugs is not recommended. In addition, venlafaxine does not inhibit the activity of the enzymes CYP3A4, CYP1A2 and CYP2C9, therefore, no significant interaction is observed with drugs such as alprozolam, caffeine, carbamazepine, diazepam, tolbutamide, terfenadine. Interaction with ketoconazole is described above. CYP3A3/4 inhibitors such as itraconazole and ritonavir can have a similar effect. Other interactions with various concomitant therapeutic factors and food When using venlafaxine, special caution should be used during electroconvulsive therapy, as there is no experience with the use of venlafaxine in these conditions. There was no significant effect of different types of food on the absorption of venlafaxine and its subsequent conversion to EDV. Foods (usually high in protein, for example: hard cheeses, fish roe, turkey), as well as nutritional supplements and fitness diets, which are an increased source of tryptophan, potentially contribute to greater production of serotonin in the body, which may increase serotonergic side effects. effects of venlafaxine. Undesirable pharmacodynamic interactions may occur when Venlafaxine is taken simultaneously with the medicinal plant St. John's wort (herb or various preparations made from it); such a combination is not recommended. There are reports of false-positive results of the immunochromatographic rapid urine test (test strip) for phencyclidine and amphetamines in patients taking venlafaxine, even several days after discontinuation of venlafaxine. This may be explained by the lack of specificity of this test. Only a confirmatory test in a specialized anti-doping laboratory can distinguish venlafaxine from phencyclidine and amphetamines. According to the data available to date, venlafaxine has not shown itself to be a drug that causes drug abuse or addiction (both in preclinical receptor affinity studies and in clinical practice).
Side effect
Frequency of side effects: very often (? 1/10), often (? 1/100 to General symptoms: - often - weakness, fatigue, chills; - infrequently - Quincke's edema, photosensitivity reactions; - frequency not established - anaphylactic reactions. From the nervous system: - very often - dry mouth, headache; - often - unusual dreams, decreased libido, dizziness, insomnia, increased excitability, paresthesia, stupor, confusion, depersonalization, increased muscle tone, tremor; - infrequently - apathy, agitation, hallucinations, myoclonus, impaired coordination of movements and balance; - rarely - akathisia, psychomotor agitation, epileptic seizures, manic reactions; - frequency not established - dizziness, neuroleptic malignant syndrome (NMS), serotonin syndrome, delirium, extrapyramidal reactions ( including dystonia and dyskinesia), tardive dyskinesia, suicidal thoughts and behavior, aggression. From the gastrointestinal tract: - very often - nausea; - often - loss of appetite (anorexia), constipation, vomiting; infrequently - bruxism, diarrhea; - rarely - hepatitis; - frequency not established - pancreatitis. From the respiratory system: - often - yawning, bronchitis, shortness of breath; - rarely - interstitial lung diseases and eosinophilic pneumonia, chest pain. From the cardiovascular system: - often - arterial hypertension, hyperemia of the skin; - uncommon - postural hypotension, tachycardia, fainting; - frequency not established - hypotension, QT interval prolongation, ventricular fibrillation, ventricular tachycardia (including bidirectional tachycardia). From the hematopoietic system: - infrequently - hemorrhages into the skin (ecchymosis), gastrointestinal bleeding; - frequency not established - hemorrhages in the mucous membranes, prolongation of bleeding time, thrombocytopenia, pathological changes in the blood (including agranulocytosis, aplastic anemia, neutropenia and pancytopenia). From the metabolic side: - often - increased cholesterol levels in the blood serum, decreased body weight; - uncommon - weight gain; - very rarely - increase in prolactin levels; frequency not established - changes in laboratory tests of liver function, hepatitis, hyponatremia, syndrome of insufficient secretion of antidiuretic hormone. From the genitourinary system: - often - ejaculation/orgasm disorders (in men), erectile dysfunction (impotence), anorgasmia, dysuric disorders (mainly difficulties at the beginning of urination), pollakiuria, menstrual disorders associated with increased bleeding or increased irregular bleeding (menorrhagia, metrorrhagia); - infrequently - orgasm disturbances (in women), urinary retention; rarely - urinary incontinence. From the senses: - often - disturbances of accommodation, mydriasis, blurred vision; - infrequently - disturbance of taste, noise or ringing in the ears; — frequency not established — angle-closure glaucoma. From the skin: - very often - sweating; - infrequently - alopecia, rapidly passing rash; - frequency not established - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, itching, urticaria. From the musculoskeletal system: frequency not established - rhabdomyolysis. When you stop taking venlafaxine, abruptly stop or reduce the dose, symptoms may be observed that relate to the so-called withdrawal syndrome: increased fatigue, asthenia, headache, dizziness, sleep disturbances (drowsiness or insomnia, difficulty falling asleep, the appearance of unusual dreams), hypomania, anxiety, agitation (increased nervous excitability and irritability), confusion, paresthesia (spontaneously occurring unpleasant sensation of numbness, tingling, burning, crawling, etc.), increased sweating, dry mouth, decreased appetite, nausea, vomiting, diarrhea (most of these reactions are mild and do not require treatment).
Contraindications
- hypersensitivity to venlafaxine or any of the excipients;
- simultaneous use with MAO inhibitors; - severe renal dysfunction (glomerular filtration rate (GFR) less than 10 ml/min); - severe liver dysfunction; - taking the drug under the age of 18 years; - during pregnancy and lactation. With caution: recent myocardial infarction, unstable angina, arterial hypertension, arrhythmias (especially tachycardia), history of convulsive syndrome, increased intraocular pressure, closed-angle glaucoma, history of manic states, suicidal tendencies, predisposition to bleeding from the skin and mucous membranes , initially reduced body weight, hyponatremia, dehydration, simultaneously with diuretics or drugs used to treat obesity. Use during pregnancy and breastfeeding Venlafaxine should not be prescribed to pregnant and breastfeeding women, because The safety of the drug during pregnancy and lactation in women has not been sufficiently established, due to the fact that there are no adequately controlled clinical studies on a sufficiently large sample of such patients. This concerns the health of both the mother and, to a greater extent, the fetus/child. Women of childbearing age should be warned about this before starting treatment and should immediately consult a doctor if they become pregnant or plan to become pregnant during treatment with the drug. Venlafaxine and its metabolite (EFV) are excreted into breast milk. If it is necessary to take the drug during lactation, breastfeeding must be stopped. In practice, there are cases of prescribing venlafaxine to mothers during pregnancy and shortly before childbirth, when in a particular situation the expected benefit to the mother outweighs the potential risk to the fetus. In these cases, newborns often experienced complications that required: increased hospitalization, maintenance of breathing and tube feeding. These complications can develop immediately after childbirth and are also typical when taking other antidepressants from the SNRI group or SSRIs (not containing venlafaxine). In such cases, the following clinical symptoms in newborns have been reported: respiratory disorders, cyanosis, apnea, convulsions, temperature instability, feeding difficulties, vomiting, hypoglycemia, muscle hypertension or hypotonia, hyperreflexia, tremor, trembling, irritability, lethargy, constant crying, drowsiness or insomnia. Such disturbances may indicate the serotonergic effects of the drug Venlafaxine. If venlafaxine was used during pregnancy and maternal treatment was completed shortly before delivery, the newborn may experience withdrawal symptoms. In such a newborn, the presence of serotonin syndrome or neuroleptic malignant syndrome should be excluded. Epidemiological evidence suggests that use of SSRIs during pregnancy, especially late in pregnancy, may increase the risk of persistent neonatal pulmonary hypertension.
Overdose
Symptoms of overdose: impaired consciousness (from drowsiness to coma), agitation, possible vomiting, diarrhea; tremor, decrease or (mild) increase in blood pressure, dizziness, mydriasis, convulsive states, sinus or ventricular tachycardia or bradycardia; changes on the ECG (prolongation of the QT interval, bundle branch block, widening of the QRS complex). Post-marketing experience indicates that the most common overdose of venlafaxine occurred with concomitant use of alcohol and/or other psychotropic drugs. There are repeated reports of deaths. Published literature on retrospective studies of venlafaxine overdoses report that this increased risk of fatal outcomes may be inherent in venlafaxine when compared with commercially available SSRI antidepressants, but this risk is lower than the risk inherent in tricyclic antidepressants. Epidemiological studies have shown that those patients treated with venlafaxine have a greater risk of suicide compared with those patients treated with SSRIs (other than venlafaxine). However, it remains unclear to what extent these high rates of death (due to venlafaxine overdose) are due to the toxic properties of the drug itself or the special characteristics of the group of patients treated with venlafaxine. According to clinical experience, it is recommended that prescriptions for venlafaxine prescribe the minimum possible amount of the drug, sufficient only until the patient's next visit, in order to reduce the risk of intentional overdose. Treatment: symptomatic and supportive therapy is provided. Specific antidotes are unknown. Continuous monitoring of vital functions (respiration, circulation and heart rate) is recommended. In case of overdose, it is recommended to immediately lavage the stomach and take activated charcoal to reduce the absorption of the drug. Inducing vomiting is not recommended if there is a risk of aspiration of vomit. Forced diuresis, dialysis, and blood transfusion are ineffective.
special instructions
Suicide and suicidal behavior Depression is associated with an increased risk of suicidal ideation, self-harm, and suicide (suicidal behavior). This risk persists until significant remission occurs. Since improvement may not be observed during the first few weeks of therapy or even longer, patients should be closely monitored until such improvement occurs. Based on accumulated clinical experience, the risk of suicide may increase in the early stages of recovery. Patients with a history of suicide attempts or high levels of suicidal ideation prior to treatment are at greater risk for suicidal ideation or suicide attempts and should be closely monitored. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with mental disorders found that antidepressants were at increased risk of suicidal behavior compared with placebo in patients under 25 years of age. Drug treatment of these patients, and in particular those at high risk of suicide, should be accompanied by careful monitoring, especially early in therapy and during dose adjustment. Patients (and caregivers of such patients) should be warned to monitor for any signs of clinical worsening, suicidal behavior or ideation, or unusual changes in behavior, and to seek immediate medical attention if these symptoms occur. In a small number of patients taking antidepressants, incl. venlafaxine, aggression may occur during initiation of treatment, dose changes, or discontinuation of treatment. Clinical studies conducted to date have not revealed tolerance or dependence to venlafaxine. Despite this, as with other drugs that act on the central nervous system, the physician should closely monitor patients for signs of drug abuse, as well as patients with a history of such symptoms. Special Populations Venlafaxine is not approved for use in children. In patients with a history of aggression, venlafaxine should be used with caution. In patients with affective disorders, bipolar disorder when treated with antidepressants, incl. venlafaxine, hypomanic and manic states may occur. Like other antidepressants, venlafaxine should be used with caution in patients with a history of mania. Such patients require medical supervision. Convulsive disorders may occur during therapy with venlafaxine. As with all antidepressants, venlafaxine should be used with caution in patients with a history of seizure disorders and such patients should be closely monitored. Treatment should be discontinued if seizures develop. Akathisia The use of venlafaxine has been associated with the development of akathisia, which is characterized by an unpleasant feeling of internal motor restlessness for the patient and manifested in the patient’s inability to sit quietly in one position for a long time or remain motionless for a long time. This condition may occur at the beginning of treatment and during the first weeks of treatment. In patients who develop such symptoms, increasing the dose is not recommended. Bipolar disorder Before initiating treatment, it is necessary to identify those patients who are at risk for bipolar disorder. Such a check should include a detailed examination of the medical history, incl. family, to identify cases of suicide, bipolar disorder. It should be noted that venlafaxine is not recommended for use in the treatment of bipolar depression. Use in patients with concomitant diseases Clinical experience with the use of venlafaxine in patients with concomitant diseases is limited. It should be used with caution in patients with diseases in which the effect of venlafaxine on hemodynamic parameters and/or metabolism may be significant. Patients should be warned to immediately consult a doctor if a rash, urticaria or other allergic reactions occur. Some patients while taking venlafaxine experienced a dose-dependent increase in blood pressure and/or an increase in heart rate, so regular monitoring of blood pressure and ECG is recommended, especially during the period of adjusting or increasing the dosage of venlafaxine. In post-marketing experience with venlafaxine (overdose), fatal cardiac arrhythmias have been reported. Before prescribing venlafaxine to patients at high risk of developing serious cardiac arrhythmias, the ratio of the likely benefit to the possible risk of use should be assessed. Patients, especially the elderly, should be warned about the possibility of dizziness and impaired balance in order to prevent injury. While taking venlafaxine, especially in conditions of dehydration or decreased blood volume (including in elderly patients and patients taking diuretics), hyponatremia and/or syndrome of insufficient secretion of antidiuretic hormone may occur. Venlafaxine has not been studied in patients with recent myocardial infarction and decompensated heart failure. The drug should be prescribed to such patients with caution. Taking SSRIs or venlafaxine in patients with diabetes may cause changes in plasma glucose levels. Dosage adjustments of insulin and/or antidiabetic medications may be required. During treatment, it is recommended to refrain from drinking any alcohol-containing drinks. The safety and effectiveness of venlafaxine in combination with weight loss medications (including phentermine) have not been established. The simultaneous use of venlafaxine and drugs that reduce body weight is not recommended. Women of childbearing potential should use appropriate contraception while taking venlafaxine. Explanations of special symptoms and conditions that may occur during treatment with the drug Dry mouth is observed in 10% of patients receiving venlafaxine. This may increase your risk of developing tooth decay. Patients should practice good oral hygiene. The use of venlafaxine may cause the development of akathisia, characterized by subjective discomfort or restlessness and the need to move frequently, often accompanied by an inability to sit or stand still. This mostly occurs during the first few weeks of treatment. Increasing the dose in patients who develop these symptoms may cause undesirable effects. In placebo-controlled clinical trials, a clinically significant increase in serum cholesterol was reported in 5.3% of patients. Cholesterol level control is necessary during long-term treatment. Withdrawal syndrome When stopping treatment, withdrawal syndrome is common, especially if it is stopped abruptly. The risk of withdrawal syndrome may depend on several factors, including the duration of treatment, the size of therapeutic doses and the rate of dose reduction. These symptoms are very rarely reported in patients who accidentally missed taking the drug. Withdrawal symptoms usually occur within the first few days after stopping treatment. These symptoms usually go away within 2 weeks, although in some people they may last 2-3 months or more. It is recommended to gradually reduce the dose of venlafaxine when stopping the drug - over several weeks or months, depending on the severity of the clinical symptoms of the disease. Serotonin syndrome Venlafaxine, like other serotonergic drugs, can cause serotonin syndrome, a potentially life-threatening condition, especially when co-administered with other drugs that can affect serotonergic neurotransmitter systems such as MAO inhibitors. Symptoms of serotonin syndrome may include mental status changes (agitation, hallucinations, coma), autonomic instability (tachycardia, blood pressure lability, hyperthermia), neuromuscular disorders (hyperreflexia, incoordination), and/or gastrointestinal symptoms (nausea, vomiting). , diarrhea). Effect on the ability to drive vehicles and operate machinery During the treatment period, care should be taken when performing potentially hazardous types of work that require increased concentration and psychomotor reaction speed (including driving a car and operating machinery).
Dispensing conditions in pharmacies
On prescription
Special instructions for the use of the drug Velaxin
In patients with depression, the likelihood of suicide attempts should be considered before starting any therapy. Therefore, to reduce the risk of overdose, the initial dose of the drug should be as low as possible, and the patient should be under medical supervision. Aggressive behavior of the patient has been reported during the use of venlafaxine (especially at the beginning of the course of treatment and after discontinuation of the drug). The use of venlafaxine is associated with the development of psychomotor agitation, which is characterized by subjectively unpleasant restlessness with a need to move. Most often this occurs during the first weeks of treatment. If such symptoms occur, increasing the dose may not be appropriate, so the question of whether it is advisable to continue taking venlafaxine should be decided. In patients with mood disorders, hypomanic or manic states may occur when treated with antidepressants, including venlafaxine. Velaxin should be prescribed with caution to patients with a history of mania. These patients require medical supervision. Velaxin should be prescribed with caution to patients with a history of epileptic seizures. If epileptic seizures occur, treatment must be stopped. The patient should be warned about the need to immediately consult a doctor if a skin rash, elements of urticaria or other allergic reactions occur. In some patients, during the period of use of venlafaxine, a dose-dependent increase in blood pressure is possible, and therefore it is recommended to regularly monitor blood pressure, especially during the period of dose adjustment or increase. An increase in heart rate is possible, especially when taken in high doses. In this case, medical supervision of the patient's condition is necessary. Occasionally, orthostatic hypotension was observed during use of the drug. Patients, especially the elderly, should be warned about the possibility of dizziness. Velaxin may increase the risk of hemorrhages in the skin and mucous membranes in patients predisposed to these conditions. Patients should be warned about this and advised to exercise caution while using the drug. During the use of Velaxin, especially in conditions of dehydration or decrease in blood volume (including in elderly patients and in patients taking diuretics), hyponatremia and/or syndrome of insufficient secretion of antidiuretic hormone is possible. During the period of use of the drug, mydriasis may occur, and therefore it is recommended to monitor intraocular pressure in patients with a tendency to increase it, in patients with angle-closure glaucoma. When treating patients with impaired renal or hepatic function, caution and careful medical monitoring of the patient's condition is necessary (dose reduction is possible). In patients who have recently suffered a myocardial infarction and with signs of decompensated heart failure, the drug should be prescribed with caution under constant medical supervision. The safety and effectiveness of the combined use of venlafaxine and drugs used for weight loss, including phentermine, have not been established, so their simultaneous use is not recommended. With prolonged use of the drug, it is advisable to monitor the level of cholesterol in the blood serum. After stopping the use of Velaxin, especially suddenly, withdrawal syndrome often occurs. The risk of developing withdrawal syndrome depends on the duration of treatment, the dose used, and the rate of dose reduction. With withdrawal syndrome, dizziness, paresthesia, sleep disturbance, agitation, anxiety, nausea, vomiting, tremor, sweating, headache, diarrhea, tachycardia, and emotional disorders appear. These symptoms are usually observed in the first days after discontinuation of the drug and disappear on their own within 2 weeks. Therefore, the drug should be discontinued gradually, reducing the dose of venlafaxine gradually over several weeks or months, depending on the patient's condition. Velaxin does not cause the development of symptoms of tolerance or dependence. Despite this, as with other drugs that act on the central nervous system, patients need to be monitored for signs of drug abuse (especially patients with a history of similar problems). While using Velaxin, women of reproductive age should use adequate methods of contraception. The drug may negatively affect the ability to drive vehicles and operate potentially dangerous machinery. Therefore, doses at which driving vehicles and working with machinery are possible are determined for each patient individually.
Indications
Velaxin is a strong antidepressant, which is among the top 12 most effective drugs in this group. Its appointment is justified in the following cases:
- A single episode of severe depression;
- Recurrent depressive disorder is a current episode of severe depression;
- Recurrent depressive disorder remission - for the purpose of preventing attacks;
- Anxiety disorders;
- Social phobias.
In some cases, Velaxin is prescribed for other diseases. For example, it is used to prevent migraine attacks and treat some other neurological diseases.
Interactions of the drug Velaxin
The use of Velaxin in combination with MAO inhibitors is contraindicated: tremor, myoclonus, sweating, nausea, vomiting, flushing, dizziness, fever, convulsive seizures, and death are possible. The use of Velaxin can be started no earlier than 14 days after the end of MAO inhibitor therapy. If a reversible MAO inhibitor is used, this interval may be shorter (24 hours). After discontinuation of Velaxin, you should take a break of at least 7 days before starting therapy with MAO inhibitors. Particular caution is required when using Velaxin with drugs that affect the central nervous system. The mutual influence of Velaxin and the following drugs should be taken into account: Lithium: there are reports of interaction between lithium and venlafaxine, as a result of which the level of lithium in the blood increases. Imipramine: the pharmacokinetics of venlafaxine and its metabolite EDV do not change, so a dose reduction of venlafaxine is not required when these drugs are used in combination. Haloperidol: its effect may be enhanced. Diazepam: the pharmacokinetics of the drugs and their main metabolites do not change significantly. Clozapine: an increase in the level of clozapine in the blood and the development of its side effects (for example, epileptic seizures) were noted. Risperidone: with the simultaneous use of these drugs (despite the increase in the AUC of risperidone), the pharmacokinetics of the sum of the active components (risperidone and its active metabolite) does not change significantly. Alcohol: depression of psychomotor activity under the influence of alcohol after taking venlafaxine does not increase, however, during the period of use of the drug Velaxin, the consumption of alcoholic beverages is not recommended. Electroconvulsive therapy: when conducting electroconvulsive therapy while taking selective inhibitors of neuronal reuptake of serotonin, an increase in the duration of epileptic activity was noted. It is necessary to exercise caution and ensure careful medical monitoring of the patient's condition when combined with this type of therapy and the use of Velaxin. Drugs metabolized by cytochrome P450 isoenzymes : the CYP 2D6 enzyme of the cytochrome P450 system converts venlafaxine into the active metabolite EDV. Unlike many other antidepressants, the dose of Velaxin does not need to be reduced when used once with drugs that inhibit CYP 2D6 activity, or in patients with a genetically determined decrease in CYP 2D6 activity, since the total concentration of the active substance and metabolite (venlafaxine and ODV) does not change. The main route of elimination of venlafaxine involves metabolism with the participation of CYP 2D6 and CYP 3A4, so special caution should be exercised when prescribing venlafaxine in combination with drugs that inhibit both of these enzymes. Venlafaxine is a relatively weak inhibitor of CYP 2D6 and does not inhibit the activity of CYP 1A2, CYP 2C9 and CYP 3A4 isoenzymes; therefore, it should not be expected to interact with other drugs in which these liver enzymes are involved in the metabolism. Cimetidine: inhibits the metabolism of venlafaxine during its initial passage through the liver, but does not have a significant effect on its conversion to EDV or the rate of elimination of EDV, the concentration of which in the circulating blood is much higher. Therefore, there is no need to change the dose of Velaxin and cimetidine when used in combination. This interaction may be more pronounced in elderly patients or with impaired liver function, therefore, in such cases, the combined use of cimetidine and Velaxin requires medical supervision. Antihypertensive and antidiabetic agents: no clinically significant interactions of venlafaxine with antihypertensive (including beta-adrenergic receptor blockers, ACE inhibitors and diuretics) and hypoglycemic agents have been identified. Drugs that bind to plasma proteins: Plasma protein binding is 27% for venlafaxine and 30% for EDV. Therefore, interactions due to their binding to proteins should not be expected. Warfarin: the anticoagulant effect of the latter may be enhanced; at the same time, prothrombin time increases. Indinavir: When used concomitantly with this drug, the pharmacokinetics of indinavir changes (with a 28% decrease in AUC and a 36% decrease in maximum concentration).
Reviews
Pavel M .: “I started taking Velaxin due to a severe phobic disorder. I found it very difficult to interact with people, I was afraid of crowds and wary of strangers. I took the drug for about six months. The anxiety went away, I was able to calmly go out and communicate with other people. The effect of the product developed gradually. At the beginning of the treatment there was nausea, but it quickly passed. I’m still afraid to stop taking the drug.”
Christina N .: “I have recurrent depressive disorder. The last hospitalization was a year ago. Then I was prescribed Velaxin due to the severe course of the disease. I was treated for about a month and noticed a significant improvement. The rest of the time I took pills to prevent depression and so far they are helping. The only negative is that I have no appetite. I fight anorexia by eating on an alarm clock, I think it’s because of the medication.”
Review from a psychiatrist : “Velaxin is a new generation antidepressant that selectively affects the emotional-volitional sphere of the patients’ psyche. This is a strong remedy that we use in severe cases. Velaxin is highly effective and well tolerated by patients. We recommend starting treatment with this drug in a hospital setting due to the risk of adverse reactions.”
Content
Velaxin overdose, symptoms and treatment
Symptoms: ECG changes (increased QT , bundle branch block, expansion of the QRS ), sinus and ventricular tachycardia, bradycardia, hypotension, convulsions, impaired consciousness. In some cases, fatalities due to overdose have been reported when high doses of venlafaxine were taken concomitantly with alcohol and/or other psychotropic drugs. Treatment: there is no specific antidote. Gastric lavage and the use of activated carbon are indicated. Inducing vomiting is not recommended. It is necessary to ensure airway patency, adequate ventilation and oxygenation. Monitoring of ECG and vital body functions is recommended, as well as supportive and symptomatic therapy. In case of overdose, the possibility of the patient taking several psychotropic drugs simultaneously should be taken into account. Venlafaxine and EDV are not eliminated by dialysis.
