Venlaxor, pills 37.5mg, 30pcs

Composition

1 tablet contains venlafaxine (in the form of hydrochloride) 37.5 mg

Pharmacological action

An antidepressant. According to its chemical structure, venlafaxine does not belong to any class of antidepressants (tricyclic, tetracyclic or other), it 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 a nerve impulse to the central nervous system. Venlafaxine and its major metabolite O-desmethylvenlafaxine (EFA) are strong serotonin and norepinephrine reuptake inhibitors and weak dopamine reuptake inhibitors. In addition, venlafaxine and EFA 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 m-cholinergic receptors, histamine H1-receptors and α1-adrenergic receptors of the brain. Venlafaxine does not inhibit MAO activity. It has no affinity for opioid, benzodiazepine, phencyclidine or NMDA receptors.

Pharmacokinetics

Suction

Venlafaxine is well absorbed from the gastrointestinal tract. After a single oral dose of 25-150 mg, Cmax in blood plasma is 33-172 ng / ml and is reached within approximately 2.4 hours. After taking the drug with a meal, the time to reach Cmax in blood plasma increases by 20-30 minutes, but the values of Cmax and absorption do not change.

Distribution and metabolism

It undergoes intensive metabolism during the” first pass ” through the liver. Its main metabolite is O-desmethylvenlafaxine (EFA). Cmax 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.

With repeated use of Css in venlafaxine plasma, EFA is achieved within 3 days. In the daily dose range of 75-450 mg, venlafaxine and EFA have linear kinetics.

T1 / 2 elimination of venlafaxine and EFA is 5 and 11 hours, respectively. EFA and other metabolites, as well as unchanged venlafaxine, are eliminated by the kidneys.

Pharmacokinetics in special clinical cases

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 T1 / 2 increases. 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 venlafaxine 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.

Women of childbearing age should use appropriate methods of contraception while taking venlafaxine.

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

Venlafaxine and its EFA metabolite 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;
• concomitant use of MAO inhibitors;
• severe renal and / or hepatic impairment (glomerular filtration rate (GFR)
• under 18 years of age (safety and efficacy for this age group have not been proven);
• established or suspected pregnancy;
• breast-feeding period.

Side effects

Common symptoms: weakness, fatigue.

From the gastrointestinal tract: decreased appetite, constipation, nausea, vomiting, dry mouth; rarely-hepatitis.

From the side of metabolism: increased serum cholesterol, weight loss; sometimes-changes in laboratory tests of liver function, hyponatremia, syndrome of insufficient secretion of antidiuretic hormone.

From the cardiovascular system: arterial hypertension; sometimes-postural hypotension, tachycardia.

From the nervous system: unusual dreams, dizziness, insomnia, increased excitability, paresthesia, stupor, increased muscle tone, tremor, yawning; sometimes-apathy, hallucinations, muscle spasms, serotonin syndrome; rarely-epileptic seizures, manic reactions, as well as symptoms resembling neuroleptic malignant syndrome.

From the genitourinary system: ejaculation disorders, erections, anorgasmia, dysuric disorders (mainly difficulties at the beginning of urination); sometimes-decreased libido, menorrhagia, urinary retention.

From the sensory organs: accommodation disorders, mydriasis, visual impairment; sometimes-a violation of taste sensations.

From the skin: hyperemia of the skin; sweating; sometimes-photosensitivity reactions; rarely-erythema multiforme, Stevens-Johnson syndrome.

From the blood and hematopoietic system: sometimes-hemorrhages in the skin (ecchymosis) and mucous membranes, thrombocytopenia; rarely-prolongation of bleeding time.

Interaction

Concomitant use of 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.

When used concomitantly with haloperidol, the effect of the latter may be enhanced due to an increase in its concentration in the blood.

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 concentration in blood plasma 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.

Venlaxor enhances the effect of ethanol on psychomotor reactions.

The CYP2D6 isoenzyme 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 venlafaxine and its EFA metabolite 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 suppresses the metabolism during the “first pass” of venlafaxine through the liver and does not affect the pharmacokinetics of EFA. In most patients, only a slight increase in the overall pharmacological activity of venlafaxine and its EFA metabolite is expected (more pronounced in elderly patients and in patients with impaired liver function).

No clinically significant interaction of venlafaxine with antihypertensive (including beta-blockers, ACE inhibitors and diuretics) and hypoglycemic drugs was found.

Plasma protein binding is 27% for venlafaxine and 30% for EFA. Therefore, there was no effect on the concentration of drugs in the blood plasma that have a high degree of binding to proteins.

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

When co-administered with indinavir, the pharmacokinetics of indinavir change (AUC decreases by 28%, Cmax-by 36%), and the pharmacokinetics of venlafaxine and its EFA metabolite do not change. However, the clinical significance of this effect is unknown.

How to take it, course of use and dosage

Tablets are recommended to be taken during meals.

The recommended starting dose is 75 mg in 2 divided doses (37.5 mg twice daily). If there is no significant improvement after several weeks of treatment, the daily dose can be increased to 150 mg (75 mg 2 times / day).

If a higher dose is needed (severe depressive disorder or other conditions requiring hospital treatment), you can immediately prescribe 150 mg in 2 doses (75 mg 2 times a day). After that, the daily dose can be increased by 75 mg every 2-3 days until the desired therapeutic effect is achieved.

Maximum daily dose of the drug Venlaxor is 375 mg.After achieving the necessary therapeutic effect, the daily dose can be gradually reduced to the minimum effective level.

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

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: activated charcoal is prescribed to reduce the absorption of the drug. It is not recommended to induce vomiting due to the risk of aspiration. Conduct symptomatic therapy. Specific antidotes are unknown. Continuous monitoring of vital functions (respiration and blood circulation) is recommended. Venlafaxine and its EFA metabolite 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.

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