Velaxin retard capsules 75mg №28

Composition

Description of the dosage form

Dosage 75 mg: hard gelatin capsules CONI-SNAPZ, with a colorless, transparent casing and lid of an orange-brown color, containing a mixture of white and yellow pellets, with little or no odor.

Dosage 150 mg: hard gelatin capsules CONI-SNAPOEL, with a colorless, transparent casing and lid of an orange-brown color, containing a mixture of white and yellow pellets, with little or no odor.

Mechanism of action

Pharmacological action - antidepressant.

Pharmacodynamics

Venlafaxine is an antidepressant. By chemical structure, it can not be attributed to any known class of antidepressants (tricyclic, tetracyclic, or others). It has two active enantiomeric racemic forms.

The antidepressant effect of venlafaxine is associated with increased neurotransmitter activity in the central nervous system. Venlafaxine and its main metabolite O-desmethylvenlafaxine (EFA) are potent inhibitors of serotonin reuptake and norepinephrine and weakly inhibit dopamine reuptake by neurons. Venlafaxine and EFA equally effectively affect the reuptake of neurotransmitters. Venlafaxine and EFA reduce beta-adrenergic reactions.

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

Pharmacokinetics

After taking Velaxin^® long acting capsules, C_max venlafaxine and EFA (major metabolite) in plasma are achieved within (6.0 ± 1.5) and (8.8 ± 2.2) h, respectively. The rate of absorption of venlafaxine from the capsules of prolonged action is lower than the rate of its elimination. Therefore t_1/2 venlafaxine after the appointment of Velaxin^® in the form of capsules of prolonged action - (15 ± 6) h - is actually T_1/2 suction than t_1/2 distribution - (5 ± 2) h, - which is observed after the appointment of the drug^® in the form of tablets.

The binding of venlafaxine and EFA to plasma proteins is respectively 27 and 30%. EFA and other metabolites, as well as non-metabolized venlafaxine, are excreted by the kidneys. With repeated administration of C_ss venlafaxine and EFA are achieved within 3 days. In the range of daily doses of 75-450 mg, venlafaxine and EFA have linear kinetics. After taking the drug while eating T_max in plasma increases by 20-30 minutes, but the values ​​of C_max and removals do not change.

In patients with liver cirrhosis, plasma concentrations of venlafaxine and EFA are elevated, and their elimination rate is reduced. In moderate to severe renal failure, the total clearance of venlafaxine and EFA decreases, and T_1/2 increases. A decrease in total clearance is mainly observed in patients with Cl creatinine below 30 ml / min.

The age and sex of the patient do not affect the pharmacokinetics of the drug.

Indications drug Velaxin

Depression (including anxiety), treatment and prevention of relapse.

Contraindications

hypersensitivity to any component of the drug;

simultaneous administration of MAO inhibitors (see also "Interaction");

severe impaired renal and / or liver function (glomerular filtration rate (GFR) less than 10 ml / min, PT more than 18 s);

age under 18 years (safety and efficacy for this age group have not been proven);

pregnancy or presumed pregnancy;

lactation period (not enough data from controlled studies).

Carefully: recent myocardial infarction, unstable stenocardia, heart failure, coronary artery disease, ECG changes, incl. prolongation of the QT interval, electrolyte imbalance, arterial hypertension,tachycardia, history of convulsions, intraocular hypertension, angle-closure glaucoma, history of manic states, susceptibility to bleeding from the skin and mucous membranes, initially reduced body weight.

Use during pregnancy and lactation

The safety of venlafaxine during pregnancy has not been proven, therefore, use during pregnancy (or presumptive pregnancy) is possible only if the potential benefit to the mother outweighs the possible risk to the fetus. Women of childbearing age should be warned about this before starting treatment and should immediately consult a doctor if pregnancy occurs or pregnancy planning during the period of drug treatment.

Venlafaxine and EFA are excreted into breast milk. The safety of these substances for newborns is not proven, therefore, taking venlafaxine during breastfeeding is not recommended. If necessary, taking the drug during lactation should decide on the termination of breastfeeding. If the mother’s treatment was completed shortly before delivery, the newborn may experience withdrawal symptoms.

Side effects

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

In order of decreasing frequency: often - <1/10 and> 1/100; infrequently - <1/100 and> 1/1000; rarely - <1/1000; very rarely - <1/10000.

Common symptoms: weakness, fatigue, headache, abdominal pain, chills, fever.

From the digestive tract: loss of appetite, constipation, nausea, vomiting, dry mouth; infrequently - bruxism, reversible increase in liver enzymes; rarely, Gastrointestinal bleeding; very rarely - pancreatitis.

Nervous system: dizziness, insomnia, agitation, drowsiness; often - unusual dreams, anxiety, confusion, increased muscle tone, paresthesia, tremor; infrequently - apathy, hallucinations, myoclonus; rarely - ataxia, speech disorders, incl. dysarthria, mania or hypomania (see "Special Instructions"), manifestations resembling neuroleptic malignant syndrome, seizures (see "Special Instructions"), serotonergic syndrome; very rarely - nonsense, extrapyramidal disorders, incl. dyskinesia and dystonia, tardive dyskinesia, psychomotor agitation / akathisia (see “Special Instructions”).

From the CCC: arterial hypertension, dilation of blood vessels (flushing), rapid heartbeat; infrequently - orthostatic hypotension, syncope, tachycardia; very rarely - arrhythmia of the "pirouette" type, prolongation of the QT interval, ventricular tachycardia, ventricular fibrillation.

Special senses: accommodation disturbances, mydriasis, blurred vision, tinnitus; infrequently - a violation of taste.

Hemic and lymphatic: infrequently - hemorrhages in the skin (ecchymosis) and mucous membranes; rarely, thrombocytopenia, prolonged bleeding time; very rarely - agranulocytosis, aplastic anemia, neutropenia, pancytopenia.

From the skin: sweating, itching and rash; infrequently - photosensitivity reactions, angioedema, maculo-papular rash, urticaria; rarely - alopecia, erythema multiforme, Stevens-Johnson syndrome.

From the genitourinary system: impaired ejaculation, erection, anorgasmia; infrequently - decreased libido, menstrual disorders, menorrhagia, urinary retention; rarely - galactorrhea.

Metabolism: increased serum cholesterol, weight loss; infrequently - hyponatremia, syndrome of insufficient secretion of ADH, impaired laboratory tests of liver function; rarely, hepatitis; very rarely - an increase in prolactin levels.

Musculoskeletal system: arthralgia, myalgia; infrequently - muscle spasm; very rarely - rhabdomyolysis.

Children had the following side effects: abdominal pain, chest pain, tachycardia, refusal of food, weight loss, constipation, nausea, ecchymosis, nosebleeds, mydriasis, myalgia, dizziness, emotional lability, tremor, hostility and suicidal thoughts.

After abrupt cancellation of venlafaxine or a reduction in its dose, the following can be observed: fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, anxiety, anxiety, disorientation, hypomania, paresthesia, sweating. These symptoms are usually mild and go away without treatment.Because of the likelihood of these symptoms, it is very important to gradually reduce the dose of the drug (as well as any other antidepressant), especially after taking high doses. The duration of the period required to reduce the dose depends on the dose, the duration of therapy, as well as the individual sensitivity of the patient.

Interaction

The simultaneous use of MAO inhibitors and venlafaxine contraindicated. Taking the drug Velaxin^® You can start at least 14 days after the end of therapy with MAO inhibitors. If a reversible MAO inhibitor (moccobemide) was used, this interval may be shorter (24 hours). Therapy with MAO inhibitors can be started no less than 7 days after discontinuation of the drug Velaxin^®.

The simultaneous use of venlafaxine with lithium can increase the level of the latter.

With simultaneous use with imipramine, the pharmacokinetics of venlafaxine and EFA do not change. At the same time, their simultaneous use enhances the effects of desipramine, the main metabolite of imipramine, and its other metabolite, 2-OH-imipramine, although the clinical significance of this phenomenon is unknown.

Haloperidol: combined use increases the level of Haloperidol in the blood and enhances its effects.

With simultaneous use with diazepam pharmacokinetics of drugs and their major metabolites are not significantly changed. The effect on the psychomotor and psychometric effects of diazepam was also not detected.

With simultaneous use with clozapine, an increase in its blood plasma level and the development of side effects (for example, seizures) can be observed.

With simultaneous use with Risperidone (despite an increase in the AUC of risperidone), the pharmacokinetics of the sum of the active components (risperidone and its active metabolite) do not change significantly.

The decrease in mental and motor activity under the influence of alcohol did not increase after taking venlafaxine. Despite this, as in the case of taking other drugs that affect the central nervous system, the use of alcoholic beverages is not recommended during venlafaxine therapy.

While taking venlafaxine, special care should be taken during electroconvulsive therapy, since experience with venlafaxine in these conditions is missing.

Drugs metabolized by cytochrome P450 isoenzymes: CYP2D6 enzyme of the cytochrome P450 system converts venlafaxine into the active metabolite of EFA. Unlike many other antidepressants, the dose of venlafaxine can not be reduced with simultaneous administration with drugs that suppress CYP2D6 activity, or in patients with a genetically determined reduction of CYP2D6 activity, since the total concentration of 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 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 CYP1A2, CYP2C9 and CYP3A4 isoenzymes; therefore, one should not expect its interaction with other drugs, in the metabolism of which these liver enzymes are involved.

Cimetidine inhibits first-pass venlafaxine metabolism and does not affect the EFA pharmacokinetics. In the majority of patients, only a slight increase in the total pharmacological activity of venlafaxine and EFA is expected (more pronounced in elderly patients and in violation of liver function).

Clinical studies have not found clinically significant interactions with venlafaxine with antihypertensives (including beta-blockers, ACE inhibitors and diuretics) and antidiabetic drugs.

Drugs associated with plasma proteins: Plasma protein binding is 27% for venlafaxine and 30% for EFA; therefore, drug interactions due to protein binding should not be expected.

When taken simultaneously with Warfarin, the anticoagulant effect of the latter can be enhanced, while the prolonged exposure and increased MHO.

When taken simultaneously with indinavir, the pharmacokinetics of indinavir changes (with a 28% decrease in AUC and a 36% decrease in C_max), and the pharmacokinetics of venlafaxine and EFA does not change. However, the clinical significance of this effect is unknown.

Dosage and administration

Inside while eating.Each capsule should be swallowed whole and washed down with liquid. Capsules must not be divided, crushed, chewed or placed in water. The daily dose should be taken at one time (in the morning or in the evening), each time at about the same time.

Depression. The recommended initial dose is 75 mg once a day.

If, in the opinion of the doctor, a higher dose is necessary (severe depressive disorder or other conditions requiring inpatient treatment), 150 mg can be prescribed immediately once a day. Subsequently, the daily dose can be increased by 75 mg with an interval of 2 weeks or more (but not more often than after 4 days), until the desired therapeutic effect is achieved. The maximum daily dose is 350 mg.

After achieving the desired therapeutic effect, the daily dose can be gradually reduced to the minimum effective level.

Supportive Therapy and Prevention of Relapse. Treatment of depression should last at least 6 months. With stabilizing therapy, as well as therapy for the prevention of relapses or new episodes of depression, doses that have been shown to be effective are commonly used. The physician should regularly (at least once every 3 months) monitor the effectiveness of long-term therapy with Velaxin.^®.

Transfer of patients from tablets Velaxin^®. Patients taking