Venlaksor, tablets 75 mg, 30 pcs.

PHARMACODINAMICS
Venlafaxine is an antidepressant chemically unrelated to any class of antidepressants (tricyclic, tetracyclic or other) and is a racemate of two active enantomers.
The mechanism of antidepressant effects of the drug is related to its ability to potentiate nerve impulse transmission in the central nervous system (CNS). Venlafaxine and its main metabolite O-desmethylvenlafaxine (ODV) are strong serotonin and noradrenaline reuptake inhibitors and weak dopamine reuptake inhibitors. In addition, venlafaxine and O-desmethylvenlafaxine reduce beta-adrenergic reactivity after both single administration and continuous administration. Venlafaxine and EFA are equally effective on neurotransmitter reuptake.
Venlafaxine has no affinity for muscarinic, cholinergic, histamine (H1), and a1-adrenergic brain receptors. Venlafaxine does not inhibit monoamine oxidase (MAO) activity. It has no affinity for opiate, benzodiazepine, phencyclidine or N-methyl-d-aspartate (NMDA) receptors.

PHARMACOKINETICS
Venlafaxine is well absorbed from the gastrointestinal tract. After a single dose of 25-150 mg, maximum plasma concentrations reach 33-172 ng/mL within approximately 2.4 hours. It is metabolized extensively during its first passage through the liver. Its main metabolite is O-desmethylvenlafaxine (ODV). The elimination half-life of venlafaxine and EFA is 5 and 11 hours, respectively. Maximum plasma concentrations of EFA of 61-325 ng/ml are reached approximately 4.3 hours after administration. 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. When administered repeatedly, 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 maximum plasma concentration is increased by 20-30 minutes, but the values of maximum concentration and absorption do not change.
In patients with cirrhosis, plasma concentrations of venlafaxine and EFA are elevated and their elimination rate is reduced. In moderate or severe renal failure, total clearance of venlafaxine and EFA is decreased and the elimination half-life is prolonged. A decrease in total clearance is mainly observed in patients with creatinine clearance below 30 ml/min.
Age and gender of the patient do not affect the pharmacokinetics of the drug.

Indications

Depression, Depressed Mood

Depression of various etiologies, treatment and prevention.

Active ingredient

Venlafaxine

Composition

1 tablet contains 37.5 mg or 75 mg of venlafaxine (as hydrochloride). Excipients: anhydrous calcium hydrophosphate, anhydrous lactose, sodium carboxy-methyl starch, magnesium stearate, colloidal anhydrous silica, red iron oxide dye (E 172).

How to take, the dosage

Tablets of Venlaxor are recommended to be taken with food.

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 may be increased to 150 mg (2 x 75 mg daily). If a higher dose is required, 150 mg can be prescribed at once in two doses (2 x 75 mg per day). Thereafter, the daily dose may be increased by 75 mg every 2-3 days until the desired therapeutic effect is achieved. The maximum daily dose of the drug Venlaksor is 375 mg. After achieving the desired therapeutic effect, the daily dose may be gradually reduced to the minimum effective level.

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

In mild renal (glomerular filtration rate (GFR) greater than 30 ml/min) and hepatic (prothrombin time (PV) less than 14 sec) dosing adjustments are not required. In moderate renal (FFR 10-30 ml/min) and hepatic insufficiency (PV of 14 to 18 sec) the dose should be reduced by 25-50 %. It is not recommended to use venlafaxine in severe renal and hepatic impairment. Patients on hemodialysis may receive 50% of the usual daily dose of venlafaxine after completion of hemodialysis.

Elderly age patients do not require dose changes, but caution is required when treating older patients, such as due to possible renal dysfunction. The lowest effective dose should be used. If the dose is increased, the patient should be under close medical supervision.

At the end of the drugVenlaxor it is recommended that the dose of the drug be gradually reduced for at least a week and the patient be monitored to minimize the risk associated with withdrawal of the drug (see below). The period required for complete discontinuation depends on the dosage of the drug, the duration of treatment, and the individual characteristics of the patient.

Interaction

The simultaneous use of monoamine oxidase inhibitors (MAOIs) and venlafaxine is contraindicated.

Haloperidol: the effects of the latter may be enhanced by increased blood levels of the drug when used together.

Concomitant use with clozapine may result in increased plasma levels and side effects (e.g., epileptic seizures).

Accelerates the effects of alcohol on psychomotor reactions.

Particular caution should be used with venlafaxine during electroconvulsive therapy because there is no experience with venlafaxine in this setting.

Drugs metabolized by cytochrome P 450 isoenzymes:

The major route of excretion of venlafaxine involves metabolism involving CYP2D6 and CYP3A4; therefore, special caution should be exercised when venlafaxine is prescribed in combination with drugs that inhibit both of these enzymes. These drug interactions have not yet been studied.

Concomitant use with warfarin may increase the anticoagulant effect of the latter.

The pharmacokinetics of indinavir is altered when taken concomitantly with indinavir (with a 28% decrease in the area under the AUC curve and a 36% decrease in maximum Cmax concentration), and the pharmacokinetics of venlafaxine and EFA are not altered. However, the clinical significance of this effect is unknown.

Special Instructions

Cancellation of Venlaxor:As with other antidepressants, abrupt discontinuation of venlafaxine therapy – especially after high doses of the drug – may cause withdrawal symptoms, so it is recommended that the dose be gradually reduced before withdrawing the drug.

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

In patients with depressive disorders, the possibility of suicide attempts should be considered before starting any drug therapy. Therefore, to reduce the risk of overdose, the starting dose of the drug should be as low as possible and the patient should be under close medical supervision.

In patients with mood disorders, treatment with antidepressants, including venlafaxine, may result in hypomanic or manic states. Like other antidepressants, venlafaxine should be prescribed with caution in patients with a history of mania. These patients need medical monitoring.

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

While venlafaxine has no effect on psychomotor or cognitive function, it should be considered that any drug therapy with psychoactive drugs may reduce judgment, thinking or motor performance. The patient should be warned about this before starting treatment. If such effects occur, the degree and duration of restriction should be determined by the physician. Alcohol intake is also not recommended.

Synopsis

Tablets 75 mg – light pink flattened cylindrical tablets with dark pink flecks, beveled and ribbed on one side.

Contraindications

Hypersensitivity. Concomitant use of MAO inhibitors (see also section “Interaction”). Severe renal and/or hepatic impairment (glomerular filtration rate less than (GFR) 10 ml/min). Age under 18 years (safety and efficacy for this age group is not proven). Established or suspected pregnancy. Period of lactation.

With caution:. Recent myocardial infarction, unstable angina pectoris, arterial hypertension, tachycardia, seizure syndrome in the history, increased intraocular pressure, closed-angle glaucoma, manic states in the history, predisposition to bleeding from the skin and mucous membranes, baseline weight loss, hyponatremia, hypovolemia, concomitant use of diuretics, suicidal tendencies, and 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 decrease, 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 %.

Nervous system disorders: frequently – dizziness, asthenia, insomnia, “nightmares” dreams, increased nervous excitability, paresthesias, muscle hypertonicity, tremor, sedative effect; infrequently – apathy, hallucinations, myoclonus, syncope; rarely – seizures, manic disorders, malignant neuroleptic syndrome.

Cardiovascular system: often – increase of arterial pressure, skin hyperemia; infrequent – decrease of arterial pressure, postural hypotension, tachycardia; very rarely – change of Q-T interval, ventricular fibrillation, ventricular tachycardia (including ventricular fibrillation).

Digestive system: often – decreased appetite, nausea, vomiting; infrequent – bruxism (involuntary grinding of teeth), increased activity of “liver” transaminases; rarely – hepatitis.

Urogenital system: often – decreased libido, impaired erection and/or ejaculation, anorgasmia, menorrhagia, urinary disorders; rarely – urinary retention, violation of orgasm in women.

Sensory system: often – accommodation disorders, mydriasis, visual disturbances; rarely – violation of sense of taste.

Hematopoietic organs: frequency unknown – agranulocytosis, aplastic anemia, neutropenia, pancytopenia.

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

Laboratory measures: infrequent thrombocytopenia; rarely – prolongation of bleeding time, hyponatremia; with long-term use and with high doses – hypercholesterolemia. Nocturnal); infrequent – ecchymosis, weight gain; rare – syndrome of inadequate secretion of antidiuretic hormone, serotonin syndrome (nausea, vomiting, abdominal pain, diarrhea, flatulence, psychomotor agitation, tachycardia, hyperthermia, muscle rigidity, seizures, myoclonus, sweating, depression of consciousness of varying severity).

When withdrawal syndrome occurs: Dizziness, headache, asthenia, increased fatigue, sleep disorders (change in the nature of dreams, drowsiness or insomnia, difficulty falling asleep), hypomania, anxiety, increased nervous excitability, confusion, paresthesias, increased sweating, dry mouth, decreased appetite, nausea, vomiting, diarrhea (most of these reactions are mild and do not require treatment)

Overdose

Symptoms: E ECG changes (QT interval prolongation, Gis bundle leg block, dilated QRS complex), sinus or ventricular tachycardia, bradycardia, hypotension, seizures, altered consciousness (reduced wakefulness level). If venlafaxine overdose is taken concomitantly with alcohol and/or other psychotropic drugs, a fatal outcome has been reported.

Treatment: symptomatic. Specific antidotes are not known. Inducing vomiting is not recommended due to the risk of aspiration. Venlafaxine and EFA are not excreted by dialysis.

Pregnancy use

Use of the drug during pregnancy (or anticipated pregnancy) is contraindicated. If treatment of the mother was completed shortly before delivery, the newborn may experience withdrawal symptoms. Venlafaxine and its metabolite (EFA) are excreted into breast milk. Administration of venlafaxine during breastfeeding is not recommended; if it is necessary to take the drug, discontinuation of breastfeeding should be considered.

Similarities

Velafax, Venlaxor, Venlafaxine