Venlafaxine

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Venlafaxine: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. Drug interactions
12. Analogs
13. Terms and conditions of storage
14. Terms of dispensing from pharmacies
15. Reviews
16. Price in pharmacies

Latin name: Venlafaxine

ATX code: N06AX16

Active ingredient: venlafaxine (venlafaxine)

Manufacturer: ALSI Pharma (Russia)

Description and photo update: 2019-19-08

Prices in pharmacies: from 120 rubles.

Buy

Venlafaxine is an antidepressant drug.

Release form and composition

The dosage form of Venlafaxine is tablets: flat-cylindrical, white or white with a yellowish tinge of color (slight marbling is possible), with a score and a chamfer (10 pieces in blisters, in a cardboard box 1, 2, 3, 4 or 5 packages).

Active ingredient: venlafaxine (in the form of hydrochloride), 1 tablet - 37.5 or 75 mg.

Additional components: colloidal silicon dioxide (aerosil), pregelatinized starch, microcrystalline cellulose, magnesium stearate, talc.

Pharmacological properties

Pharmacodynamics

Venlafaxine is a specific antidepressant that does not chemically belong to any class of antidepressant drugs (tricyclic, tetracyclic, or others), and is a racemate of two pharmacologically active enantiomers.

Venlafaxine and its main metabolite, O-desmethylvenlafaxine (EFA), are potent inhibitors of norepinephrine and serotonin reuptake and weak dopamine reuptake inhibitors. The mechanism of the drug's antidepressant action lies in its ability to enhance the activity of neurotransmitters during the transport of nerve impulses to the central nervous system. Venlafaxine and EFA have an equally effective effect on the reuptake of the above neurotransmitters. At the same time, in vitro studies confirm the presence of an affinity of venlafaxine and EFA with benzodiazepine, cholinergic (muscarinic), opioid and alpha ₁-adrenergic receptors. Also, these substances do not inhibit the activity of monoamine oxidase (MAO). Based on the degree of inhibition of serotonin reuptake, the effect of the drug is less pronounced than with the use of selective serotonin reuptake inhibitors.

Pharmacokinetics

Venlafaxine is well absorbed from the gastrointestinal tract (with a single dose, up to 92% of the dose taken). The degree of absorption does not depend on food intake. The general bioavailability of the substance is 40–45% and is due to intensive first-pass metabolism in the liver. The degree of binding of venlafaxine and EFA to blood plasma proteins is 27% and 30%, respectively. Both venlafaxine and its major metabolite pass into breast milk. When venlafaxine is taken in a daily dose ranging from 75 to 450 mg, the drug itself and EFA differ in linear pharmacokinetics. The maximum concentration of venlafaxine and EFA in blood plasma is achieved in 2 and 3 hours, respectively, with oral administration of the drug. When taking prolonged forms of venlafaxine, the time to reach the maximum concentration increases to 5.5 and 9 hours, respectively.

The half-life is 5 ± 2 hours and 11 ± 2 hours for venlafaxine and its metabolite, respectively. The equilibrium concentration of these compounds in plasma is recorded after 3 days of repeated administration of the drug in therapeutic doses.

Venlafaxine is metabolized mainly in the liver with the participation of the isoenzyme CYP2D6 and with the formation of EFA, the only metabolite with pharmacological activity, as well as an inactive metabolite of N-desmethylvenlafaxine. The drug is a weak inhibitor of the CYP2D6 isoenzyme and does not inhibit the CYP3A4, CYP2C9 or CYP1A2 isoenzymes.

Venlafaxine is excreted mainly in the urine: approximately 87% of a single dose taken is excreted through the kidneys within 48 hours (29% as unconjugated EFA, 26% as conjugated EFA, 5% unchanged, 27% other pharmacologically inactive metabolites). After 72 hours, approximately 92% of the dose taken is excreted in the urine. On average, the plasma clearance of venlafaxine and EFA is 1.3 ± 0.6 l / h / kg and 0.4 ± 0.2 l / h / kg, respectively. The apparent half-life is 5 ± 2 hours and 11 ± 2 hours, respectively. The apparent volume of distribution, determined at equilibrium, is 7.5 ± 3.7 l / kg and 5.7 ± 1.8 l / kg, respectively.

The age and gender of patients do not significantly affect the pharmacokinetic parameters of venlafaxine and EFA. There is no need for a special dose adjustment in elderly patients.

For patients with diagnosed low activity of the isoenzyme CYP2D6, individual dose selection is not required. Despite the fact that the concentrations of venlafaxine and EFA, taken separately, change in different directions (the level of venlafaxine increases, while the EFA decreases), the sum of the areas under the pharmacokinetic curves of these compounds remains practically unchanged due to the reduced activity of the isoenzyme CYP2D6, therefore dose adjustment is not mandatory.

In patients with moderate and severe renal and hepatic insufficiency, the metabolism of venlafaxine and the excretion of EFA are reduced, and their maximum concentrations also increase, and the half-life is lengthened. In patients with CC less than 30 ml / min, the decrease in the total clearance of venlafaxine is most pronounced. In patients on renal hemodialysis, the elimination half-life increases by 180% for venlafaxine and 142% for EFA, and the clearance of both active components is reduced by approximately 57%. For such patients, especially those undergoing hemodialysis procedures, it is recommended to individually select the dose of the drug and control its pharmacokinetic parameters, taking into account the duration of the course of therapy.

Although the information concerning patients with severe hepatic impairment according to the Child-Pugh scale is limited, it is worth considering that the pharmacokinetics of the drug, in particular its clearance and half-life, individually vary in a variety of ways, which must be taken into account when prescribing a drug so sick.

In patients with hepatic insufficiency class A (mild liver dysfunction) and class B (moderate liver dysfunction) according to the Child-Pugh scale, the half-life of venlafaxine and EFA increases by about 2 times compared with healthy patients, and the clearance decreases by more than 2 times.

Indications for use

According to the instructions, Venlafaxine is used to treat depression and prevent relapse.

Contraindications

severe liver dysfunction;
severe renal dysfunction [glomerular filtration rate (GFR) less than 10 ml / minute];
pregnancy and lactation;
age up to 18 years;
simultaneous administration of MAO (monoamine oxidase) inhibitors;
hypersensitivity to any component of the drug.

Venlafaxine should be used with caution in the presence of the following diseases and conditions:

simultaneous use of diuretics;
combined use with drugs for the treatment of obesity;
dehydration;
hyponatremia;
initially reduced body weight;
suicidal tendencies;
a history of convulsive syndrome;
a history of manic conditions;
predisposition to bleeding from the skin and mucous membranes;
unstable angina;
recent myocardial infarction;
increased intraocular pressure;
arrhythmias (especially tachycardia);
arterial hypertension;
moderate hepatic impairment [prothrombin time (PT) 14-18 seconds];
angle-closure glaucoma.

Instructions for the use of Venlafaxine: method and dosage

Venlafaxine tablets should be taken orally with meals: swallow without chewing and drink plenty of water, preferably at the same time of day.

At the beginning of treatment, 37.5 mg is usually prescribed 2 times a day. If necessary, the dose is increased to 75 mg 2 times a day. If in this case the effect is not enough, it is possible to increase the daily dose to 225 mg. The dose should be increased by 75 mg at intervals of at least 2 weeks. With severe symptoms, a faster increase in dose is possible, but the interval should not be less than 4 days.

The highest daily dose is 375 mg (2-3 divided doses).

If it is necessary to prescribe a dose of more than 225 mg / day to the patient, inpatient observation is required.

After achieving a therapeutic effect, the dose can be gradually reduced to the minimum effective.

The duration of maintenance therapy, including for the prevention of relapse, can be 6 months or more. In this case, the minimum effective dose used in the treatment of depression is prescribed.

Recommendations for dose adjustment for renal failure:

mild degree (GFR more than 30 ml / minute) - no correction required;
moderate degree (GFR 10-30 ml / minute) - the dose is reduced by 25-50%;
severe (GFR less than 10 ml / minute) - the appointment of the drug is not recommended;
hemodialysis - the dose is reduced by 50% (the drug should be taken after the end of the session).

Recommendations for dose adjustment of Venlafaxine in liver failure:

mild degree (PV less than 14 seconds) - no correction required;
moderate degree (PV 14-18 seconds) - the dose is reduced by at least 50%;
severe - the appointment of the drug is not recommended.

Elderly patients in the absence of any acute and chronic diseases do not need to change the dosage regimen, but the lowest effective dose should be used.

The treatment should be discontinued gradually, reducing the dose for at least 2 weeks.

Side effects

from the nervous system: very often (≥ 1/10) - headache, dry mouth; often (≥ 1/100 to <1/10) - depersonalization, dizziness, decreased libido, confusion, increased excitability, insomnia, unusual dreams, tremor, paresthesia, increased muscle tone, stupor; infrequently (≥ 1/1000 to <1/100) - impaired coordination of movements and balance, hallucinations, agitation, apathy, myoclonus; rarely (≥ 1/10 000 to <1/1000) - psychomotor agitation, manic reactions, epileptic seizures, akathisia; frequency not established - extrapyramidal reactions (including dystonia and dyskinesia), aggression, tardive dyskinesia, delirium, dizziness, serotonin syndrome, suicidal thoughts and behavior, neuroleptic malignant syndrome;
from the side of metabolism: often - a decrease in body weight, an increase in serum cholesterol; infrequently - an increase in body weight; very rarely (<1/10 000) - an increase in prolactin content; the frequency is not established - hyponatremia, hepatitis, syndrome of insufficient secretion of antidiuretic hormone, changes in laboratory tests of liver function;
on the part of the cardiovascular system: often - hyperemia of the skin, arterial hypertension; infrequently - tachycardia, postural hypotension, syncope; frequency not established - ventricular tachycardia (including bidirectional tachycardia), lengthening of the QT interval, hypotension, ventricular fibrillation;
from the hematopoietic system: infrequently - ecchymosis (hemorrhage into the skin), gastrointestinal bleeding; frequency not established - lengthening of bleeding time, hemorrhage in the mucous membranes, thrombocytopenia, pathological changes in the blood (including aplastic anemia, pancytopenia, neutropenia, agranulocytosis);
from the respiratory system: often - yawning, shortness of breath, bronchitis; rarely - chest pain, eosinophilic pneumonia, interstitial lung disease;
from the gastrointestinal tract: very often - nausea; often - vomiting, constipation, loss of appetite (anorexia); infrequently - diarrhea, bruxism; rarely - hepatitis; frequency not established - pancreatitis;
on the part of the musculoskeletal system: frequency not established - rhabdomyolysis;
on the part of the genitourinary system: often - menstrual irregularities (menorrhagia, metrorrhagia), pollakiuria, dysuric disorders (mainly difficulties at the beginning of urination), anorgasmia, erectile dysfunction (impotence), ejaculation / orgasm disorders in men; infrequently - orgasm disorders in women, urinary retention; rarely - urinary incontinence;
on the part of the skin: very often - sweating; infrequently - a fast-passing rash, alopecia; frequency not established - urticaria, pruritus, toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome;
from the senses: often - visual impairment, mydriasis, accommodation disturbances; infrequently - ringing or tinnitus, impaired taste; frequency not established - angle-closure glaucoma;
general symptoms: often - chills, increased fatigue, weakness; infrequently - photosensitivity, Quincke's edema; frequency not established - anaphylactic reactions.

With a sharp decrease in the dose and a sudden withdrawal of the drug, the development of a withdrawal syndrome is possible: sleep disturbances (difficulty falling asleep, unusual dreams, insomnia or drowsiness), agitation (increased nervous irritability, irritability), anxiety, headache, hypomania, asthenia, confusion, dizziness, increased fatigue, increased sweating, paresthesia (a spontaneously arising unpleasant sensation of burning, tingling, creeping, numbness, etc.), loss of appetite, diarrhea, dry mouth, nausea, vomiting.

Overdose symptoms: dizziness, agitation, mydriasis, tremor, convulsive states, impaired consciousness (from drowsiness to coma), sinus or ventricular tachycardia or bradycardia, decrease or slight increase in blood pressure, diarrhea, vomiting, changes in the electrocardiogram (expansion of the QRS complex, blockade legs of the bundle of His, lengthening the QT interval).

Overdose

An overdose of Venlafaxine is manifested by such symptoms as changes in the ECG (expansion of the QRS complex, blockade of the bundle branch, prolongation of the QT interval), ventricular or sinus bradycardia or tachycardia, a decrease or slight increase in blood pressure, altered states of consciousness (from drowsiness to coma), dizziness, agitation, tremors, convulsive states, mydriasis, sometimes diarrhea and vomiting.

Post-marketing experience of taking the drug shows that most often an overdose of Venlafaxine is observed when it is combined with alcoholic beverages and / or other psychotropic drugs. There are numerous reports of deaths. Literary publications regarding retrospective studies of drug overdose suggest that an increased risk of death may be a specific feature of venlafaxine itself compared to other antidepressants used in medicine from the group of selective serotonin reuptake inhibitors (SSRIs), but this risk is slightly lower than in the case of tricyclic antidepressants. The results of epidemiological studies confirm that patients receiving venlafaxine have a higher burden in terms of the risk of suicide,compared with patients treated with other SSRIs. However, it is still not clear to what extent such a high percentage of deaths (due to overdose of venlafaxine) is due to the specific characteristics of the group of patients receiving venlafaxine, or the toxic properties of the drug itself. In accordance with clinical experience, it is recommended in prescriptions for venlafaxine to prescribe it in the lowest possible dose, sufficient only until the next patient visit, which reduces the risk of deliberate overdose.or the toxic properties of the drug itself. In accordance with clinical experience, it is recommended in prescriptions for venlafaxine to prescribe it in the lowest possible dose, sufficient only until the next patient visit, which reduces the risk of deliberate overdose.or the toxic properties of the drug itself. In accordance with clinical experience, it is recommended in prescriptions for venlafaxine to prescribe it in the lowest possible dose, sufficient only until the next patient visit, which reduces the risk of deliberate overdose.

In case of venlafaxine overdose, supportive and symptomatic therapy is prescribed. There are no specific antidotes. It is necessary to conduct regular monitoring of vital functions (heart rate, circulation, respiration). You should also immediately perform a gastric lavage and take activated charcoal to reduce the absorption of the drug. Induction of vomiting is not recommended, since there is a risk of aspiration of vomit. The effectiveness of dialysis, forced diuresis, blood transfusion is considered minimal.

special instructions

Depression is always associated with an increased risk of suicidal thoughts and behavior, which persists until severe remission of the disease occurs. Since improvement from therapy may not occur for several weeks of taking the drug or even more, careful monitoring of the patient's condition is required. According to clinical data, the risk of suicide may increase in the early stages of recovery and with dose adjustments. In this regard, the patients themselves and those caring for them should be warned about the need to immediately consult a doctor in case of deterioration, unusual changes in behavior, the appearance of suicidal thoughts or behavior.

To date, there has been no evidence of tolerance or dependence on venlafaxine. Nevertheless, the patient should be under close medical supervision for the timely detection of possible signs of drug abuse.

Venlafaxine is not recommended for the treatment of bipolar depression, therefore, before starting treatment, it is necessary to determine if the patient is at risk for bipolar disorder. This check includes a detailed study of the history, including family history.

The drug can change the level of glucose in blood plasma in patients with diabetes mellitus, as a result of which it may be necessary to adjust the dose of insulin or antidiabetic drug.

Women of childbearing age should use reliable methods of contraception during therapy.

During treatment, it is recommended to stop drinking any alcoholic beverages, care should be taken when doing activities that require quick psychophysical reactions and increased attention, including when driving.

Application during pregnancy and lactation

The use of Venlafaxine during pregnancy and lactation is contraindicated because its safety has not been sufficiently established due to the lack of adequately controlled clinical trials covering a large sample of such patients. This applies both to the state of health of the mother and, to a greater extent, to the fetus or child. Women of reproductive age should be warned about this before starting therapy. If you are planning a pregnancy or if it occurs during treatment with Venlafaxine, you should immediately consult a doctor.

Venlafaxine and EFA are determined in breast milk. If it is necessary to use the drug during lactation, breastfeeding should be canceled.

In practice, venlafaxine is sometimes prescribed to mothers during pregnancy and shortly before delivery if, in a particular situation, the potential benefit to the mother outweighs the potential risk to the fetus. In these cases, newborns often had complications that led to an increase in hospitalization time and maintenance of breathing and tube feeding, which developed immediately after childbirth. Symptoms of such complications may include respiratory disorders, insomnia or drowsiness, cyanosis, constant crying, apnea, lethargy, convulsions, irritability, temperature instability, tremors, tremors, difficulty feeding, vomiting, hyperreflexia, muscle hypotension or hypertension, hypoglycemia. Such disorders can be evidence of the serotonergic effects of the drug. If the mother took venlafaxine during pregnancy,and the course of treatment was completed shortly before delivery, the newborn may develop withdrawal syndrome. In such a child, it is necessary to exclude the presence of neuroleptic malignant syndrome or serotonin syndrome. Epidemiological evidence suggests that the use of venlafaxine in pregnant women may increase the risk of persistent pulmonary hypertension of the newborn.

Pediatric use

For patients under 18 years of age, the drug is not prescribed.

Drug interactions

Venlafaxine does not have an increased bond with blood plasma proteins, therefore, with simultaneous use, it practically does not increase the concentration of drugs, which are characterized by a high bond with plasma proteins.

The patient's condition should be carefully monitored with the concomitant administration of other drugs that affect the central nervous system, since their interaction with venlafaxine has not been studied.

The drug is contraindicated to be used in conjunction with MAO inhibitors and within 14 days after their withdrawal, since this combination can cause serious side effects, up to and including death. MAO inhibitors can be prescribed no earlier than 7 days after discontinuation of venlafaxine.

Other possible drug interactions when combined with venlafaxine:

serotonergic drugs (triptans, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, fentanyl and its analogues (tramadol, dextromethorphan, etc.), sibutramine, lithium: the risk of serotonin syndrome increases;
ethanol: increased impairment of psychomotor functions caused by venlafaxine;
haloperidol: its total clearance decreases by 42% (when a dose of 2 mg is taken orally), the total and maximum concentration increases by 70% and 88%, respectively;
metoprolol: its concentration in blood plasma increases by about 30-40%;
clozapine: its concentration in blood plasma increases, which is accompanied by an increase in side effects, especially the frequency of seizures;
indinavir: its pharmacokinetics changes (total and maximum concentrations decrease by 28% and 36%, respectively);
ketoconazole, ritonavir, itraconazole: the plasma concentration of venlafaxine increases;
drugs that affect blood clotting and platelet function (nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, warfarin and other anticoagulants): the risk of bleeding increases (prothrombin time must be controlled);
inhibitors of CYP2D6, such as paroxetine, quinidine, haloperidol, fluoxetine, levomepromazine, perphenazine: their plasma concentration may increase.

There is no experience with venlafaxine in combination with electroconvulsive therapy.

Analogs

Venlafaxine analogs are: Velaxin, Velafax, Venlaxor, Dapfix.

Terms and conditions of storage

Store at temperatures up to 25 ° C in a place protected from light and out of reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews of Venlafaxine

Due to the individual sensitivity to the drug, reviews of Venlafaxine are quite diverse. Patients often complain of adverse reactions, the severity of which is not determined by the dose taken. In some people, they manifested themselves when taking tablets with a dosage of 37.5 mg, others, on the contrary, tolerated the drug in a dose of 150 mg well. There are reports that Venlafaxine was ineffective for anxiety and insomnia, and taking the drug at a dosage of 37.5 mg 2 times a day led to such undesirable reactions as nausea, dilated pupils, cramped jaw, sleep disturbances, and dizziness. At the beginning of therapy, some patients complained of twitching during sleep, panic attacks, weakness, increased depression, which often disappeared during treatment. Also, treatment was often accompanied by a withdrawal syndrome,which could last from 2 weeks to 2-3 months. A gradual dose reduction over several months avoided this condition.

Price for Venlafaxine in pharmacies

The average price for Venlafaxine with a dosage of 37.5 mg is 225-268 rubles, and with a dosage of 75 mg - 270-362 rubles (the package contains 30 tablets).

Venlafaxine: prices in online pharmacies

Drug name

Price

Pharmacy

Venlafaxine Organic 37.5 mg film-coated tablets 30 pcs.

120 RUB

Buy

Reviews Venlafaxine Organics

120 RUB

Buy

Venlafaxine 37.5 mg tablets 30 pcs.

229 r

Buy

Venlafaxine Organics tablets p.o. 37.5mg 30 pcs.

251 RUB

Buy

Venlafaxine 37.5mg tablets 30 pcs.

280 RUB

Buy

Venlafaxine Organica 75 mg film-coated tablets 30 pcs.

289 r

Buy

Venlafaxine 75 mg tablets 30 pcs.

299 r

Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!