Velaxin, 150 mg 28 pcs.

Pharmacodynamics

The mechanism of antidepressant effects of Velaksin is related to its ability to potentiate the transmission of nerve impulse in the central nervous system. Venlafaxine and its main metabolite O-desmethylvenlafaxine (ODV) are strong serotonin and noradrenaline reuptake inhibitors and weak dopamine reuptake inhibitors. Venlafaxine has no vehicle to muscarinic, cholinergic, histamine (H1) and 1-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

After taking Velaxin sustained release capsules, C_max of venlafaxine and EFA (the main metabolite) in plasma are reached within (6.0±1.5) and (8.8±2.2) h, respectively. The absorption rate of venlafaxine from long-acting capsules is lower than its elimination rate. Therefore, the T_1/2 of venlafaxine after administration of Velaxin as long-acting capsules, (15±6) h, is actually T_1/2 absorption than the T_1/2 distribution – (5±2) h – that occurs after administration of Velaxin as tablets.

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. C_ss venlafaxine and EFA are reached within 3 days when administered repeatedly. In the daily dose range of 75-450 mg, venlafaxine and EFA have linear kinetics. After taking the drug with meals, T_max in plasma is increased by 20-30 min, but the C_max and absorption values are unchanged.

In patients with cirrhosis, plasma concentrations of venlafaxine and EFAs are elevated and their elimination rate is reduced. In moderate to severe renal failure, total clearance of venlafaxine and EFA is decreased and T_1/2 is increased. Decreased total clearance is mainly seen in patients with a creatinine Cl below 30 ml/min.

Patient age and gender do not affect the pharmacokinetics of the drug.

Indications

Depression of various etiologies, treatment and prevention

Active ingredient

Composition

1 long-acting capsule contains:

the active ingredient:

venlafaxine hydrochloride 169.68 mg (equivalent to 150 mg of venlafaxine, respectively)

auxiliary substances:

MCC;

sodium chloride;

ethylcellulose;

How to take, the dosage

Ingestion, with meals. Each capsule should be swallowed whole and washed down with liquids. The capsules should not be divided, crushed, chewed or put in water. The daily dose should be taken in one sitting (morning or evening), at approximately the same time each time.

Depression. The recommended starting dose is 75 mg once daily.

If in the opinion of the physician a higher dose is necessary (severe depressive disorder or other conditions requiring hospital treatment), 150 mg once daily can be prescribed immediately. Subsequently, the daily dose may be increased by 75 mg at intervals of 2 weeks or more (but not more often than every 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 may be gradually reduced to the minimum effective level.

Supportive therapy and relapse prevention. Treatment of depression should continue for at least 6 months. In stabilizing therapy, as well as therapy to prevent relapses or new episodes of depression, doses that have been shown to be effective are usually used. The physician should regularly (at least once every 3 months) monitor the effectiveness of long-term therapy with Velaxin.

Transfer patients from Velaxin tablets. Patients taking Velaxin tablets may be switched to long-acting capsules with an equivalent dose once daily. However, individual dose adjustments may be necessary.

Renal insufficiency. In mild renal failure (FFR greater than 30 ml/min) dosage regimen adjustment is not required. In moderate renal failure (FFR 10-30 ml/min) the dose should be reduced by 50%. Due to the prolongation of T1/2 venlafaxine and EFA, such patients should take the entire dose once daily. It is not recommended to use venlafaxine in severe renal insufficiency (GFR less than 10 ml/min), since there are no reliable data on such therapy. Patients on hemodialysis may receive 50% of the usual daily dose of venlafaxine after completion of hemodialysis.

Hepatic failure. In mild hepatic insufficiency (PV less than 14 s) no dosage adjustment is required. In moderate hepatic insufficiency (PV of 14 to 18 s) the dose should be reduced by 50%. It is not recommended to use venlafaxine in severe hepatic impairment, since there are no reliable data on this therapy.

Elderly patients. Elderly patients do not require dose modification per se, but (as with other medications) caution is required when treating elderly patients, e.g., due to the possibility of impaired renal function. The lowest effective dose should be used. Patients should be under close medical supervision if the dose is increased.

Children and adolescents (under 18 years of age). The safety and effectiveness of venlafaxine in children and adolescents under 18 years of age have not been established.

Cancellation of the drug Velaxin. As with treatment with other antidepressants, abrupt withdrawal of venlafaxine (especially high doses) may cause withdrawal symptoms. Therefore, a gradual reduction in the dose is recommended before completely cancelling the drug. If high doses have been used for more than 6 weeks, it is recommended that doses be reduced for at least 2 weeks. The length of time required for dose reduction depends on the magnitude of the dose, the duration of therapy, and the patient’s reactions.

Interaction

The concomitant use of MAO inhibitors and venlafaxine is contraindicated. Valuxin may be started at least 14 days after the end of therapy with MAO inhibitors. If a reversible MAO inhibitor (moclobemide) was used, this interval may be shorter (24 hours). Therapy with MAO inhibitors may be started at least 7 days after withdrawal of Velaksin.

The concomitant use of venlafaxine with lithium may increase the level of the latter.

The pharmacokinetics of venlafaxine and EFA are not altered when used concomitantly with imipramine. However, their concomitant use enhances the effects of desipramine, the main metabolite of imipramine, and its other metabolite, 2-ON- imipramine, although the clinical significance of this phenomenon is unknown.

Haloperidol: co-administration increases blood levels of haloperidol and enhances its effects.

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

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

In concomitant use with risperidone (despite increased 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 was not increased after taking venlafaxine. Despite this, as with other CNS-affecting drugs, consumption of alcoholic beverages is not recommended during therapy with venlafaxine.

Particular caution should be exercised during venlafaxine administration during electroconvulsive therapy, as there is no experience with venlafaxine in this setting.

Drugs metabolized by cytochrome P450 isoenzymes: The enzyme CYP2D6 of the cytochrome P450 system converts venlafaxine to the active metabolite EFA. Unlike many other antidepressants, the dose of venlafaxine may not be decreased when concomitantly administered with drugs that inhibit CYP2D6 activity or in patients with genetically determined CYP2D6 activity decrease, because the total concentration of venlafaxine and EFA will not change.

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 investigated.

Venlafaxine is a relatively mild CYP2D6 inhibitor and does not inhibit the activity of CYP1A2, CYP2C9 and CYP3A4 isoenzymes; therefore, no interaction with other drugs whose metabolism involves these liver enzymes should be expected.

Cimetidine inhibits the first pass metabolism of venlafaxine and has no effect on EFA pharmacokinetics. 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 impaired hepatic function).

Clinical studies have found no clinically significant interactions of venlafaxine with antihypertensive drugs (including beta-adrenoblockers, ACE inhibitors and diuretics) and antidiabetic drugs.

Drugs bound to plasma proteins: binding to plasma proteins is 27% for venlafaxine and 30% for EFA, so no drug interactions due to protein binding should be expected.

Concomitant use with warfarin may increase anticoagulant effect of the latter, with prolongation of PV and increase in MHO.

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

Special Instructions

The risk of suicidal thoughts and suicide attempts increases with depression. This risk persists until the onset of a stable remission. Therefore, patients should be kept under constant medical supervision and should be given only small amounts of the drug capsules to reduce the risk of possible abuse and/or overdose.

Velaxin should not be used when treating children and adolescents under 18 years of age. Increased likelihood of suicidal behavior (suicide attempt and suicidal ideation) and hostility in clinical trials have been observed more frequently among children and adolescents receiving antidepressants compared to groups receiving placebo.

Harmful behavior has been reported while taking venlafaxine (especially at the beginning of treatment and after discontinuation of the drug).

The use of venlafaxine can cause psychomotor agitation, which clinically resembles akathisia, characterized by restlessness with a need to move, often combined with an inability to sit or stand still. This is most commonly seen during the first few weeks of treatment. If these symptoms occur, increasing the dose may have an adverse effect, and consideration should be given to whether to continue the drug.

As with all antidepressants, venlafaxine should be prescribed with caution in patients with a history of mania and/or hypomania, as the drug may aggravate their symptoms. In these cases, medical observation is necessary.

Caution should be exercised when treating patients with a history of convulsive seizures. Treatment with venlafaxine should be discontinued if seizures occur or increase in frequency.

Like selective serotonin reuptake inhibitors, venlafaxine should be used with caution when used concomitantly with antipsychotic medications because symptoms resembling neuroleptic malignant syndrome may develop.

Patients should be warned to consult a physician immediately if rash, urticaria, or other allergic reactions occur.

In some patients, a dose-dependent increase in BP has been noted while taking venlafaxine, so regular BP monitoring is recommended, especially at the beginning of treatment or when increasing the dose.

In some cases of orthostatic hypotension have been described while taking venlafaxine. Patients, especially the elderly, should be warned about the possibility of dizziness and impaired sense of balance.

Venlafaxine may cause increased heart rate, especially during high doses. Particular caution should be exercised when prescribing the drug in patients with conditions that may be exacerbated by increased heart rate.

There have been insufficient studies of venlafaxine use in patients who have recently had a myocardial infarction or who have decompensated heart failure, so caution should be exercised when using this medication in these patients.

As with other serotonin reuptake inhibitors, venlafaxine may increase the risk of bleeding in the skin and mucous membranes, so caution is necessary when treating patients who are prone to bleeding.

Hyponatremia and/or insufficient ADH secretion syndrome may occur during administration of venlafaxine, especially in conditions of dehydration or decreased blood volume (including elderly patients and patients taking diuretics).

In cases of mydriasis have been noted while taking venlafaxine, so patients with a predisposition to increased intraocular pressure or with a risk of closed-angle glaucoma require close medical monitoring.

In cases of renal and hepatic impairment, special caution is necessary. Dose reduction is required in some cases.

The safety and effectiveness of venlafaxine with weight-lowering agents, including phentermine, have not been established, so their simultaneous use (as well as use of venlafaxine as monotherapy for weight loss) is not recommended. A clinically significant increase in serum cholesterol levels was observed in some patients receiving venlafaxine for at least 4 months. Therefore, it is advisable to monitor serum cholesterol levels when taking the drug for a long time.

After discontinuation of the drug, especially abruptly, withdrawal symptoms often occur. The risk of withdrawal symptoms may depend on several factors, including the length of course and dose, and the rate of dose reduction. Withdrawal symptoms such as dizziness, sensory disturbances (including paresthesias and electrical currents), sleep disturbances (including insomnia and unusual dreams), agitation or anxiety, nausea and/or vomiting, tremor, sweating, headache, diarrhea, rapid and increased heart rate and emotional instability are usually mild to moderate in severity, but may be severe in some patients. They are usually observed in the first days after drug withdrawal, although there have been isolated reports of such symptoms occurring in patients who have accidentally missed a single dose. Usually these phenomena go away on their own within 2 weeks; however, in some patients they may be longer (2-3 months or more). Therefore, it is recommended that the dose of venlafaxine be reduced gradually over several weeks or months, depending on the patient’s condition, before withdrawing it.

The effect on the ability to drive a car or perform work requiring increased speed of physical and mental reactions. Note that any drug therapy with psychoactive medications may impair judgment, thinking or motor performance. The patient should be warned about this before starting treatment. If such effects occur, the degree and duration of restrictions should be determined by the physician.

Contraindications

With caution: recent myocardial infarction, unstable angina pectoris, heart failure, coronary artery disease, ECG changes including QT interval prolongation, electrolyte balance disorders, arterial hypertension, tachycardia, history of seizures, intraocular hypertension, closed-angle glaucoma, history of manic states, predisposition to bleeding of the skin and mucous membranes, initially low body weight.

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 discontinue therapy.

General symptoms: weakness, fatigue.

Gastrointestinal tract: decreased appetite, constipation, nausea, vomiting, dry mouth.

Metabolic side: increase in serum cholesterol levels, decrease in body weight.

Cardiovascular system: arterial hypertension. skin hyperemia.

Nervous system disorders: unusual dreams, dizziness, insomnia, increased excitability, paresthesias, stupor, increased muscle tone, tremor, yawning.

Urogenital system disorders: ejaculation disorders, erections, anorgasmia, dysuric disorders.

Senses: accommodation disorders, mydriasis, visual impairment.

Skin disorders: sweating.

After abrupt withdrawal of venlafaxine or reduction of its dose, fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, restlessness, increased irritability, sweating may occur. These symptoms are usually mild and go away without treatment. Because of the likelihood of these symptoms, it is important to gradually decrease the dose of the drug.

Overdose

Symptoms: ECG changes (QT interval prolongation, Gis bundle leg block, QRS complex extension), sinus or ventricular tachycardia, bradycardia, arterial hypotension, seizures, depression of consciousness (reduced level of wakefulness). In overdose of venlafaxine concomitantly taken with alcohol and/or other psychotropic drugs, lethal outcome has been reported.

Treatment: symptomatic. Specific antidotes are not known. Continuous control of vital functions (respiration and circulation) is recommended. Administration of activated charcoal to reduce absorption of the drug. Inducing vomiting is not recommended due to the risk of aspiration. Venlafaxine and EFA are not excreted by dialysis.

Pregnancy use

The safety of venlafaxine in pregnancy has not been proven, so use during pregnancy (or anticipated 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 before starting treatment and should immediately consult a physician if they become pregnant or plan to become pregnant during treatment with the drug.

Venlafaxine and EFA are excreted into 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, discontinuation of breastfeeding should be decided. If the mother’s treatment was completed shortly before delivery, the newborn may experience withdrawal symptoms from the drug.

Similarities