Venlaxor, pills 75mg, 30pcs

Composition

1 tablet contains

the Active ingredient:

75 mg of venlafaxine (in the form of hydrochloride).

auxiliary substances:

anhydrous calcium hydrophosphate

, anhydrous lactose,

sodium carboxy-methyl starch,

magnesium stearate,

colloidal anhydrous silicon dioxide

, red iron oxide dye (E 172).

Pharmacological action

Pharmacodynamics

Venlafaxine, an antidepressant that is not chemically related to any class of antidepressants (tricyclic, tetracyclic or other), is a racemate of two active enantomers.

The mechanism of antidepressant action of the drug is associated with its ability to potentiate the transmission of nerve impulses in the central nervous system (CNS). Venlafaxine and its major metabolite O-desmethylvenlafaxine (EFA) are strong serotonin and norepinephrine reuptake inhibitors and weak dopamine reuptake inhibitors. In addition, venlafaxine and O-desmethylvenlafaxine reduce beta-adrenergic reactivity both after a single use and with continuous use. Venlafaxine and EFA are equally effective at uptake of neurotransmitters.

Venlafaxine has no affinity for muscarinic, cholinergic, histamine (H1) and α1-adrenergic receptors in the brain. Venlafaxine does not inhibit monoamine oxidase (MAO) activity. It has no affinity for opiate, benzodiazepine, phencyclidine or M-methyl-d-aspartate (NMDA) receptors.

Pharmacokinetics

Venlafaxine is well absorbed from the gastrointestinal tract. After a single dose of 25-150 mg, the maximum plasma concentration reaches 33-172 ng / ml for approximately 2.4 hours. It undergoes intensive metabolism during its first passage through the liver. Its main metabolite is O-desmethylvenlafaxine (EFA). The elimination half-lives of venlafaxine and EFA are 5 and 11 hours, respectively. The maximum concentration of EFA in blood plasma of 61-325 ng / ml is reached approximately 4.3 hours after use.

The binding of venlafaxine and EFA to plasma proteins is 27% and 30%, respectively. EFA and other metabolites, as well as unmetabolized venlafaxine, are excreted by the kidneys. With repeated use, the equilibrium concentrations of venlafaxine and EFA are reached within 3 days. In the daily dose range of 75-450 mg, venlafaxine and EFA have linear kinetics. After taking the drug with a meal, the time to reach the maximum concentration in blood plasma increases by 20-30 minutes, but the values of the maximum concentration and absorption do not change.

In patients with cirrhosis of the liver, plasma concentrations of venlafaxine and EFA are increased, and the rate of their elimination is reduced. In moderate or severe renal insufficiency, the total clearance of venlafaxine and EFA decreases, and the elimination half-life is prolonged. The decrease in total clearance is mainly observed in patients with creatinine clearance below 30 ml/min. The patient’s age and gender do not affect the pharmacokinetics of the drug.

Indications

Depression of various etiologies, treatment and prevention.

Use during pregnancy and lactation

The safety of using Venlaxor during pregnancy has not been proven, so the use of the drug during pregnancy (or prospective pregnancy) is contraindicated.

Women of childbearing age should be warned about this before starting treatment and should immediately consult a doctor in case of pregnancy or pregnancy planning during treatment with the drug.

If the mother’s treatment was completed shortly before delivery, the newborn may experience withdrawal symptoms.

Venlafaxine and its metabolite (EFA) are excreted in breast milk. The safety of these substances for newborns has not been proven, so taking venlafaxine during breastfeeding is not recommended. If it is necessary to take the drug during lactation, the question of stopping breastfeeding should be decided.

Contraindications

• Hypersensitivity.
• Simultaneous use of MAO inhibitors (see also the section “Interaction”).
• Severe renal and/or hepatic impairment (glomerular filtration rate less than 10 ml/min).
• Age up to 18 years (safety and efficacy for this age group have not been proven).
• An established or suspected pregnancy.
• Lactation period.

With caution: recent myocardial infarction, unstable angina, arterial hypertension, tachycardia, convulsive syndrome in the anamnesis, increased intraocular pressure, angle-closure glaucoma, manic conditions in the anamnesis, predisposition to bleeding from the skin and mucous membranes, initially reduced body weight, hyponatremia, hypovolemia, simultaneous use of diuretics, suicidal tendencies, renal/liver failure.

Side effects

Most of the side effects listed below are dose-dependent. With long-term treatment, the severity and frequency of most of these effects are reduced, and there is no need to cancel therapy.

Depending on the frequency of occurrence, the following groups of side effects are distinguished: frequent-more than 1%, infrequent-0.1-1%, rare-0.01-0.1%, very rare-less than 0.01%.

From the nervous system: often – dizziness, asthenia, insomnia, “nightmare” dreams, increased nervous excitability, paresthesia, muscle hypertonus, tremor, sedation; infrequently-apathy, hallucinations, myoclonus, fainting; rarely-convulsions, manic disorders, neuroleptic malignant syndrome.

From the cardiovascular system: often-increased blood pressure, hyperemia of the skin; infrequently-decreased blood pressure, postural hypotension, tachycardia; very rarely-changes in the Q-T interval, ventricular fibrillation, ventricular tachycardia (including ventricular fibrillation).

From the digestive system: often-decreased appetite, nausea, vomiting; infrequently-bruxism (involuntary gnashing of teeth), increased activity of “liver” transaminases; rarely-hepatitis.

From the genitourinary system: often-decreased libido, erectile dysfunction and/or ejaculation, anorgasmia, menorrhagia, urination disorders; infrequently – urinary retention, violation of orgasm in women.

From the sensory organs: often-a violation of accommodation, mydriasis, visual impairment; infrequently-a violation of taste perception.

Hematopoietic disorders: frequency unknown-agranulocytosis, aplastic anemia, neutropenia, pancytopenia.

Allergic reactions: infrequently-rash, photosensitization; very rarely-erythema multiforme (including Stevens – Johnson syndrome), anaphylaxis.

Laboratory parameters: infrequently-thrombocytopenia; rarely-increased bleeding time, hyponatremia; with prolonged use and use of high doses – hypercholesterolemia.

Other: often-weight loss, sweating (including night sweats); infrequently-ecchymosis, weight gain; rarely-syndrome of inadequate secretion of antidiuretic hormone, serotonin syndrome (nausea, vomiting, abdominal pain, diarrhea, flatulence, psychomotor agitation, tachycardia, hyperthermia, muscle rigidity, convulsions, myoclonus, sweating, depression of consciousness of varying severity).

If withdrawal symptoms occur: dizziness, headache, asthenia, increased fatigue, sleep disorders (changes in the nature of dreams, drowsiness or insomnia, difficulty falling asleep), hypomania, anxiety, increased nervous excitability, confusion, paresthesia, increased sweating, dry mouth, decreased appetite, nausea, vomiting, diarrhea (most of these reactions are expressed slightly and do not require treatment).

Interaction

Concomitant use of monoamine oxidase (MAO) inhibitors and venlafaxine is contraindicated. Venlaxor should be started at least 14 days after the end of MAO inhibitor therapy. If a reversible MAO inhibitor (moclobemide) was used, this interval may be shorter (24 hours). Therapy with MAO inhibitors can be started at least 7 days after discontinuation of Venlaxor. Venlafaxine does not affect the pharmacokinetics of lithium.

When co-administered with imipramine, the pharmacokinetics of venlafaxine and its EFA metabolite do not change.

Haloperidol: the effect of the latter may be enhanced due to an increase in the level of the drug in the blood when used together.

The pharmacokinetics of drugs and their main metabolites do not change significantly when used concomitantly with diazepam. There was also no effect on the psychomotor and psychometric effects of diazepam.

When used concomitantly with clozapine, an increase in its plasma level and the development of side effects (for example, epileptic seizures) may occur.

When used concomitantly with risperidone (despite an increase in the AUC of risperidone), the pharmacokinetics of the sum of the active components (risperidone and its active metabolite) did not change significantly.

Increases the effect of alcohol on psychomotor reactions.

When taking venlafaxine, special care should be taken with electroconvulsive therapy, since there is no experience of using venlafaxine in these conditions.

Medicinal products metabolized by cytochrome P 450 isoenzymes:

The cytochrome P450 CYP2D6 enzyme converts venlafaxine to the active metabolite of EFA. Unlike many other antidepressants, the dose of venlafaxine may not be reduced when administered concomitantly with drugs that inhibit CYP2D6 activity, or in patients with a genetically determined decrease in CYP2D6 activity, since the total concentration of the Active ingredient and metabolite (venlafaxine and EFA) will not change.

The main route of elimination of venlafaxine involves metabolism involving CYP2D6 and CYP3A4; therefore, special care should be taken when prescribing venlafaxine in combination with drugs that inhibit both of these enzymes. Such drug interactions have not yet been investigated.

Venlafaxine is a relatively weak inhibitor of CYP2D6 and does not inhibit the activity of the CYP1A2, CYP2C9, and CYP3A4 isoenzymes; therefore, it should not be expected to interact with other drugs that are metabolized by these liver enzymes.

Cimetidine inhibits the first-pass metabolism of venlafaxine and has no effect on the pharmacokinetics of EFA. In most patients, only a slight increase in the overall pharmacological activity of venlafaxine and EFA is expected (more pronounced in elderly patients and in patients with impaired liver function).

Clinically significant interactions of venlafaxine with antihypertensive (including beta-blockers, ACE inhibitors and diuretics) and hypoglycemic drugs were not detected.

Plasma protein-bound medicinal products: Plasma protein binding is 27% for venlafaxine and 30% for EFA. Therefore, it does not affect the concentration of drugs in the blood plasma that have a high degree of protein binding.

When taken concomitantly with warfarin, the anticoagulant effect of the latter may increase.

When co-administered with indinavir, the pharmacokinetics of indinavir changed (with a 28% decrease in the area under the AUC curve and a 36% decrease in the maximum concentration of Cmax), and the pharmacokinetics of venlafaxine and EFA did not change. However, the clinical significance of this effect is unknown.

How to take, course of use and dosage

Venlaxor tablets are recommended to be taken with meals.

The recommended starting dose is 75 mg in two doses (37.5 mg each) daily. If there is no significant improvement after several weeks of treatment, the daily dose can be increased to 150 mg (2 x 75 mg per day). If, in the opinion of the doctor, a higher dose is needed (severe depressive disorder or other conditions requiring hospital treatment), you can immediately prescribe 150 mg in two doses (2 x 75 mg per day). After that, the daily dose can be increased by 75 mg every 2-3 days until the desired therapeutic effect is achieved. The maximum daily dose of Venlaxor is 375 mg. After achieving the necessary therapeutic effect, the daily dose can be gradually reduced to the minimum effective level.

Maintenance therapy and relapse prevention:

Maintenance treatment may last for 6 months or more. The minimum effective doses used in the treatment of a depressive episode are prescribed.

Renal insufficiency: in mild renal insufficiency (glomerular filtration rate (GFR) greater than 30 ml / min), no dosage adjustment is required. In moderate renal insufficiency (GFR 10-30 ml / min), the dose should be reduced by 25-50%. Due to the prolongation of the half-life of venlafaxine and its active metabolite (EFA), such patients should take the entire dose once a day. It is not recommended to use venlafaxine in patients with severe renal insufficiency (GFR less than 10 ml / min), since reliable data on such therapy are not available. Patients on hemodialysis can receive 50% of the usual daily dose of venlafaxine after completing hemodialysis.

Hepatic insufficiency: in patients with mild hepatic insufficiency (prothrombin time (PV) less than 14 seconds), no dosage adjustment is required. In patients with moderate hepatic insufficiency (PV from 14 to 18 seconds), the dose should be reduced by 50%. It is not recommended to use venlafaxine in patients with severe hepatic insufficiency, as reliable data on such therapy are not available.

Elderly patients: the patient’s advanced age alone does not require a dose adjustment, but (as with other medications) caution is required in the treatment of elderly patients, for example, due to the possibility of impaired renal function. The lowest effective dose should be used. If the dose is increased, the patient should be under close medical supervision.

Discontinuation of Venlaxor:

After taking Venlaxor, it is recommended to gradually reduce the dosage of the drug for at least a week and monitor the patient’s condition in order to minimize the risk associated with drug withdrawal.

The period required for complete discontinuation of the drug depends on its dosage, the duration of treatment, and the individual characteristics of the patient.

Overdose

Symptoms: ECG changes (QT interval prolongation, bundle branch block, QRS complex expansion), sinus or ventricular tachycardia, bradycardia, hypotension, convulsive states, changes in consciousness (decreased level of wakefulness). Venlafaxine overdose with concomitant use of alcohol and / or other psychotropic drugs has been reported as fatal. Treatment: symptomatic. Specific antidotes are unknown. Continuous monitoring of vital functions (respiration and blood circulation) is recommended. use of activated charcoal to reduce the absorption of the drug. It is not recommended to induce vomiting due to the risk of aspiration. Venlafaxine and EFA are not eliminated by dialysis.

Special instructions

Venlaxor withdrawal: as with other antidepressant medications, abrupt discontinuation of venlafaxine therapy – especially after high doses of the drug – may cause withdrawal symptoms, and it is recommended to gradually reduce the dose before discontinuing the drug. The length of time required to reduce the dose depends on the size of the dose, the duration of therapy, and the individual sensitivity of the patient.

When prescribing Venlaxor tablets to patients with lactose intolerance, the lactose content should be taken into account (30 mg in each tablet 37.5 mg; 60 mg in each tablet 75 mg).

In patients with depressive disorders, the likelihood of suicide attempts should be considered before starting any drug 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 close medical supervision.

Patients with affective disorders may experience hypomanic or manic states when treated with antidepressants, including venlafaxine. Like other antidepressants, venlafaxine should be used with caution in patients with a history of mania. Such patients need medical supervision.

Like other antidepressants, venlafaxine should be used with caution in patients with a history of epileptic seizures. Treatment with venlafaxine should be discontinued if epileptic seizures occur.

Patients should be warned to seek immediate medical attention if they experience a rash, urticaria, or other allergic reaction.

In some patients, a dose-dependent increase in blood pressure was observed while taking venlafaxine, and therefore regular monitoring of blood pressure is recommended, especially during the period of dose selection or increase.

An increase in your heart rate may occur, especially when taking high doses. Caution is recommended for tachyarrhythmia. Patients, especially the elderly, should be warned about the possibility of dizziness and impaired sense of balance.

Like other serotonin reuptake inhibitors, venlafaxine may increase the risk of hemorrhage in the skin and mucous membranes. Caution should be exercised when treating patients predisposed to these conditions. Hyponatremia and/or a syndrome of insufficient antidiuretic hormone secretion may occur while taking venlafaxine, especially in conditions of dehydration or reduced blood volume (including in elderly patients and patients taking diuretics). While taking the drug, mydriasis may occur, and therefore it is recommended to monitor intraocular pressure in patients who are prone to its increase or suffer from angle-closure glaucoma.

Venlafaxine has not been studied in patients with recent myocardial infarction and decompensated heart failure. Such patients should be treated with caution.

Patients should be monitored for signs of drug abuse, especially for patients with a history of such symptoms.

Women of childbearing age should use appropriate methods of contraception while taking venlafaxine. Despite the fact that venlafaxine does not affect psychomotor and cognitive functions, it should be borne in mind that any drug therapy with psychoactive drugs can reduce the ability to make judgments, think or perform motor functions. The patient should be warned about this before starting treatment. If such effects occur, the extent and duration of restrictions should be determined by the doctor. It is also not recommended to take alcohol.

Form of production

Tablets

Storage conditions

In a dark place, at a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Venlafaxine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Depression