Voksemel - instructions for use, dose, side effects, contraindications

Name component	Amount (mg)
	37.5 mg	75 mg	150 mg
Composition of the core of pellets: Active substance:
Venlafaxine hydrochloride	42.429 mg	84.858 mg	169.715 mg
(corresponding to vlaflaxin)	(37.50 mg)	(75.00 mg)	(150.00 mg)
Excipients:
Cellulose microcrystalline	48.313 mg	96.626 mg	193.252 mg
Hypromellose	0.462 mg	0.924 mg	1.848 mg
Pellet shell composition:
Cetostearyl alcohol [cetyl alcohol 60%,
stearyl alcohol 40%]	2.508 mg	5,016 mg	10.032 mg
Methyl methacrylate and ethyl acrylate copolymer [2: 1]
(Eudragit NE 30D) *	14.896 mg	29.792 mg	59.584 mg
Macrogol	1,490 mg	2,980 mg	5,960 mg
Talc	8,048 mg	16,096 mg	32,192 mg

* 30% polyacrylic ether suspension, contains 1.5% nonoxynol-100 as an emulsifier

The composition of capsules No. 3 (for a dosage of 37.5 mg): ferric oxide black oxide 0.07 mg (0.1429% by weight), titanium dioxide 0.96 mg (2.0000% by weight), gelatin 46.97 mg (up to 100% by weight).

Capsule composition No. 1 (for a dosage of 75 mg): iron dye oxide red 0.03 mg (0.0366% by weight), titanium dioxide 2.60 mg (3.4246% by weight), iron dye oxide yellow 0.02 mg (0.0270% by weight), gelatin 73.35 mg (up to 100% by weight).

Capsule composition No. 0 (for a dosage of 150 mg): iron dye oxide red 1.21 mg (1.2604% by weight), iron dye oxide yellow 0.91 mg (0.9453% by weight), titanium dioxide 0.11 mg (0.1103% by weight), gelatin 93.78 mg (up to 100% by weight).

Description:

Dosage 37,5 mg: hard gelatin capsules No. 3, with a body and a lid of light gray color. Contents of capsules: white or almost white pellets.

Dosage of 75 mg: Hard gelatin capsules No. 1, with a body and lid of light brown color. Contents of capsules: white or almost white pellets.

Dosage of 150 mg: hard gelatin capsules No. 0, with a body and an orange lid. Contents of capsules: white or almost white pellets.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.X.16 Venlafaxine

N.06.A.X Other antidepressants

Pharmacodynamics:

It is believed that the mechanism of antidepressant action of venlafaxine in humans is associated with an increase in neurotransmitter activity in the central nervous system. According to its chemical structure, it can not be assigned to any class of antidepressants (tricyclic, tetracyclic or other), is a racemate of two active enantomers. Venlafaxine and its main metabolite, O-desmethylvenlafaxine (EFA), are potent inhibitors of serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Besides, venlafaxine and O-desmethylvenlafaxine reduce β-adrenergic reactivity both after a single administration and at a constant intake. Venlafaxine and EFA are equally effective in reversing the capture of neurotransmitters. Venlafaxine practically does not have an affinity for muscarinic, cholinergic, histamine (H₁) and α₁-adrenergic receptors of the brain. Pharmacological activity against these receptors can be associated with various side effects that are characteristic of other antidepressants, for example, anticholinergic, sedative, and side effects from the cardiovascular system.

Venlafaxine does not suppress monoamine oxidase (MAO) activity. Research in vitro revealed that venlafaxine does not have an affinity for opiate, benzodiazepine, phencyclidine or N-methyl-D-acpartate (NMDA) receptors.

Large depressive episode

The efficacy of venlafaxine in a rapid release dosage form for the treatment of major depressive episodes was demonstrated in five short-term, randomized, double-blind, placebo-controlled studies of 4-6 weeks duration in which doses up to 375 mg / day were studied. The efficacy of venlafaxine in a sustained-release dosage form for the treatment of major depressive episodes was demonstrated in two short-term placebo-controlled studies of duration 8-12 weeks, in which doses from 75 to 225 mg / day were studied.

In one longer study, adult outpatients who had a therapeutic effect in a 8-week open trial of venlafaxine in a sustained-release dosage form (doses of 75, 150, or 225 mg) were randomized to continue receiving the prescribed dose of venlafaxine or placebo. For 26 weeks, patients were observed for relapse.

In a second, more prolonged study, the efficacy of venlafaxine for the prevention of recurrence of a depressive episode for 12 months was established in a placebo-controlled, double-blind clinical trial in adult outpatients with relapses of a major depressive episode who had the effect of treating the last episode of depression with venlafaxine (at a dose of 100 -200 mg / day, according to the scheme two times at day).

Pharmacokinetics:

Venlafaxine is extensively metabolized, primarily to the active metabolite O-desmethylvenlafaxine (EFA). Average (Mean ± SD) half-life (T_1/2) of venlafaxine and EFA from plasma is 5 ± 2 hours and 11 ± 2 hours, respectively.

The equilibrium concentrations of venlafaxine and EFA achieved within 3 days of oral treatment with multiple doses. In the range of daily doses from 75 to 450 mg venlafaxine and EFA have linear kinetics.

Suction

After a single oral intake of 25-150 mg of venlafaxine, the maximum concentration (C_mOh) In the blood plasma reaches 33-172 ng / ml for about 2.4 hours. The absolute bioavailability of 40-45%, due to presystemic metabolism. After taking the drug in the form of capsules with a modified release of C_mOh venlafaxine and EFA in plasma is achieved after 5.5 and 9 hours, respectively. When receiving identical daily doses of venlafaxine in a tablet form, the immediate release and prolonged action form of capsules latter provide slower absorption, but to the same degree as that of the rapid release tablet. Food does not affect the bioavailability of venlafaxine and EFA.

Distribution

Venlafaxine and EFA have minimal therapeutic concentrations, protein binding human plasma (27% and 30% respectively). The volume of venlafaxine distribution at an equilibrium concentration is 4.4 ± 1.6 l / kg after intravenous administration.

Metabolism

Venlafaxine is extensively metabolized in the liver. Research invitro and in vivo testify to the biotransformation of venlafaxine in its main active metabolite of EFA using an enzyme CYP2D6. Studies in vitro and in vivo indicate the metabolism of venlafaxine to a less significant and less active metabolite N-desmethylvenlafaxine by enzyme CYP3A4. Research invitro and in vivo evidence that venlafaxine is a weak inhibitor CYP2D6. Venlafaxine does not inhibit enzymes CYP1A2,CYP2C9 and CYP3A4.

Elimination

Venlafaxine and its metabolites are excreted mainly (87%) by the kidneys for 48 hours unchanged (5%), unconjugated EFA (29%), conjugated EFA (26%) and other less active metabolites (27%). The half-life of venlafaxine and EFA is, respectively, 5 and 11 hours. Average (Mean ± SD), the venlafaxine and EFA plasma clearance in the equilibrium state is 1.3 ± 0.6 l / h / kg and 0.4 ± 0.2 l / h / kg, respectively.

Special patient groups

Age and gender

The pharmacokinetics of venlafaxine and EFA are significante depends on the age and sex of the patients.

Fast / slow metabolizers CYP2D6

Concentrations of venlafaxine in blood plasma are higher in slower than in fast metabolizers CYP2D6.Since the total exposure (AUC) venlafaxine and EFA does not differ in slow and rapid metabolizers, different regimes of dosing of venlafaxine in these two groups are not required.

Patients with hepatic insufficiency

In patients with the severity class of liver cirrhosis in Child-Pugh A (mild liver failure) and Child-Pugh B-grade severity (moderate hepatic insufficiency), the half-life of venlafaxine and EFA increased in comparison with healthy participants. The oral clearance of venlafaxine and EFA was reduced. There was a greater degree of variability in the participants' indices. Data on the use of the drug in patients with severe hepatic insufficiency are limited.

Patients with renal insufficiency

In patients on hemodialysis, the half-life of venlafaxine increased by about 180%, and the clearance decreased by about 57% compared with healthy participants, while the half-life of EFA increased by about 142%, and the clearance decreased by about 56%. In patients with severe renal failure, as well as in patients on hemodialysis, dose adjustment is necessary.

Indications:

Depression of various etiologies, treatment and prevention of relapses.

Contraindications:

- Hypersensitivity to venlafaxine or any of the components of the drug;

- simultaneous administration with monoamine oxidase (MAO) inhibitors in connection with the risk of developing serotonin syndrome, accompanied by symptoms such as excitation, tremor and hyperthermia. Taking venlafaxine should not be started earlier than 14 days after discontinuation of treatment with MAO inhibitors. Taking venlafaxine should be stopped at least 7 days before treatment with MAO inhibitors;

- age to 18 years (safety of use of the drug in children of young and middle age is not established).

Pregnancy and lactation:

Pregnancy

Data on the use of venlafaxine in pregnant women is not enough. Studies in animals have shown reproductive toxicity. The potential risk to humans is unknown. The appointment of venlafaxine to a pregnant woman is allowed only if the expected benefit exceeds the possible risk.

As with other serotonin and norepinephrine reuptake inhibitors (SSRIs / SSRIs), newborns may experience withdrawal symptoms if the pregnant woman took venlafaxine until the very birth or shortly before the birth.Some newborns exposed to venlafaxine at the end of the third trimester developed complications requiring parenteral nutrition, respiratory support, or a prolonged stay in the hospital. Such complications can occur immediately after childbirth. Epidemiological evidence suggests that the use of SSRIs during pregnancy, especially at the end of pregnancy, may increase the risk of persistent pulmonary hypertension in newborns (PGHN). Although no studies have been conducted to study the relationship between PGHN and the treatment of SSRIs, given the similar mechanism of action (oppression of serotonin reuptake), this potential risk for the newborn should be taken into account when prescribing venlafaxine to pregnant women.

If the mother took SSRIs / SSRIs at the end of pregnancy, the following symptoms may occur in infants: irritability, tremor, hypotension, constant crying, and problems with sucking or sleeping. The cause of these symptoms may be serotonergic effects or symptoms of exposure. In most cases, these complications are observed immediately after birth or within 24hours after birth.

Lactation

Venlafaxine and its active metabolite EFA are excreted in breast milk. In the reports on the use of the drug in the postgistrict period, the occurrence of crying, irritability and sleep disturbances in infants was reported. It was also reported about the occurrence of the syndrome of cancellation of venlafaxine after the termination of breastfeeding. The risk for a child who is breastfed can not be ruled out.

Therefore, the decision to continue / stop breastfeeding or continue / stop treatment with the drug should be made taking into account the benefits of breastfeeding for the baby and the benefits of treating venlafaxine for a woman.

Dosing and Administration:

A drug Vokssel capsules of prolonged action should be taken with food. Each capsule should be swallowed whole and washed down with liquid. Capsules can not be divided, chopped, chewed or placed in water. The daily dose should be taken at one time (in the morning or in the evening) each time at approximately 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 required (severe depressive disorder or other conditions requiring in-patient treatment),you can immediately appoint 150 mg once a day. Subsequently, the daily dose can be increased by 75 mg with an interval of 2 weeks or more (but no more often than after 4 days), until the desired therapeutic effect is achieved.

The maximum daily dose is 350 mg. After achieving the necessary therapeutic effect, the daily dose can be gradually reduced to a minimum effective level.

Supportive therapy and prevention of relapses

Treatment of depression should last at least 6 months. With stabilizing therapy, as well as therapy for the prevention of recurrence or new episodes of depression, doses that have demonstrated their effectiveness are usually used. The physician should regularly (at least once every 3 months) monitor the effectiveness of prolonged therapy with Voxemel.

Transfer of patients from Voxel tablets

Patients taking the drug Vokssel in the dosage form of the tablet, can be converted to taking the drug Vokssel in the form of a capsule prolonged action with the appointment of an equivalent dose once a day. However, an individual dose adjustment may be required.

Use in patients with renal insufficiency

With mild renal failure (glomerular filtration rate (GFR) more than 30 ml / min), correction of the dosing regimen is not required. In patients on hemodialysis and in patients with severe renal failure (GFR <30 ml / min), the dose of the drug should be reduced by 50%. In such patients, due to the individual variability of the clearance, an individual approach to dose adjustment is necessary.

Use in patients with hepatic impairment

For mild (prothrombin time (PV) less than 14 s) and moderate hepatic insufficiency (MI from 14 to 18 s), the need to reduce the dose as a whole by 50% should be considered. Data on the use of venlafaxine in patients with severe hepatic insufficiency are limited. The drug is recommended to be used with caution, the need to reduce the dose by more than 50% should be considered. In treating patients with severe hepatic insufficiency, the possible benefits and risks should be compared.

Elderly patients

The old age of the patient does not require a dose change, however, as with the prescription of other medications, caution is needed in the treatment of elderly patients, for example,in connection with the possibility of impaired renal function and potential changes in neurotransmitter sensitivity and susceptibility that occur with age. The lowest effective dose should be used. When the dose is raised, the patient should be under careful medical supervision.

Cancellation of the drug Voksemel

As with the treatment with other antidepressants, abrupt withdrawal (especially high doses) of venlafaxine can cause withdrawal symptoms (see "Side effects" and "Special instructions" sections). Therefore, before the complete cancellation of the drug, a gradual dose reduction is recommended. If high doses have been used for more than 6 weeks, it is recommended to reduce doses for at least 2 weeks. The length of the period necessary to reduce the dose depends on the size of the dose, the duration of therapy, and the patient's response.

Capsules of prolonged action of venlafaxine contain spheroids, which slowly release the active substance into the digestive tract. The insoluble part of these spheroids is excreted from the body and can be found in feces.

Side effects:

According to the World Health Organization (WHO), undesirable effects are classified according to their frequency of development as follows: very often (≥1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, < 1/100), rarely (≥1 / 10000, <1/1000), very rarely (<1/10000), the frequency is unknown (the frequency can not be determined based on the available data).

System-organ class	Highly often	Often	Infrequently	Rarely	Frequency unknown
On the part of the hematopoiesis and lymphatic system					Elongation time bleeding, thrombocytopenia, pathologically with changes in blood (including agranulocytosis aplastic anemia, neutropenia and pancytopenia)
From the side immune system					Anaphylactic reaction
From the endocrine system and metabolism		Increase serum cholesterol levels	Weight gain, weight loss		Syndrome inadequate secretions antidiuretic hormone, hyponatremia level of prolactin
From the side nervous systems	Dizziness, headache *	Increase muscular tone, pathological dreams, decreased libido, anorgasmia, insomnia, increased excitability, paresthesia, drowsiness, tremor, confusion consciousness, depersonalization	Myoclonia, aparty, hallucinations, derealization, anxious agitation coordination and balance sheet, syncopal state, bruxism (involuntary rattle teeth), perversion taste (dysgeusia), hypomanic states, psychomotor agitation / akathisia	Convulsions, mania	Malignant neuroleptic syndrome, serotonin syndrome, delirium, extrapyramidal reactions (including dystonia and dyskinesia), late dyskinesia, suicidal thoughts and behavior, aggression*
From the side of the organ of vision		Visual impairment, including blurred vision, mydriasis, disruption of accommodation			Closed-angle glaucoma
From the side of the hearing organ and labyrinthine disorders		Noise in ears			Dizziness (vertigo)
From the side of the cardiovascular system		Hypertension, vasodilation (usually hot flushes, redness face), sensation palpitation	Orthostatic hypotension, tachycardia		hypotension, bleeding from the mucous membranes, prolongation of the QT interval, ventricular fibrillation, ventricular tachycardia (including pirouette type)
From the side respiratory system, bodies thoracic cells and the mediastinum		Yawn	Dyspnea		Pulmonary eosinophilia
From the gastro-intestinalmuscular tract	Nausea, dry mouth	Decreased appetite, constipation, vomiting, diarrhea	Gastrointestinal bleeding		Pancreatitis, hepatitis, pathologically with changes in liver function
From the skin and subcutaneous-fatty tissue	Sweating (including night sweats) sweating)		Skin rashes, alopecia, hemorrhages in the skin (ecchymosis), reactions photosensitivity, angioedema		Erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, pruritus, urticaria
From the side of the skeletal-muscular and connective tissue					Rhabdomyolysis
From the side urogenital systems		Violations ejaculation / orgasm (in men), erectile dysfunction, violations urination (usually, delay urination), violations menstrual cycle, Related reinforcing bleeding or lack of regularity bleeding (eg, menorrhagia, metrorrhagia), pollakiuria	Violations of orgasm (in women), retention of urination	Urinary incontinence
Are common disorders		Asthenia, fatigue, chills

* According to combined clinical studies, the incidence of headache with venlafaxine and placebo was not significantly different.

** Suicidal tendencies of thinking and suicidal behavior were reported during venlafaxine treatment or immediately after discontinuation of treatment.

*** See section "Special instructions".

A sharp discontinuation of the drug often leads to the emergence of the syndrome of "withdrawal": dizziness, headache or flu-like syndrome, asthenia, fatigue, sleep disturbances (change in the nature of dreams, drowsiness or insomnia), hypomania, anxiety, increased nervous excitability, confusion, impaired sensitivity (including paresthesia), tremor, vertigo, increased sweating, dryness of the oral mucosa, nausea, vomiting, diarrhea (most of these reactions are slightly expressed and do not require treatment). Therefore, when treatment with venlafaxine is no longer required, discontinuation of the drug is recommended with a gradual dose reduction.

Overdose:

Most cases of overdose of the drug are registered predominantly with venlafaxine in conjunction with alcohol and / or other medicines.

Symptoms: dizziness, vomiting, mydriasis, lowering of blood pressure (BP), changes in ECG (lengthening interval QT, bundle branch blockade, expansion of the complex QRS), sinus and ventricular tachycardia or bradycardia, depression of consciousness (from drowsiness to coma), convulsions and death. To reduce the risk of overdose, recipes for venlafaxine should be prescribed for a minimum amount of the drug, compatible with proper management of the patient.

Treatment: general, supporting, symptomatic; ECG monitoring and vital organs functions; at risk of aspiration, vomiting is not recommended. Gastric lavage is indicated if performed shortly after taking the drug, as well as in patients with the corresponding symptoms. The intake of activated carbon can also reduce the absorption of the active substance. Forced diuresis, dialysis, hemoperfusion and exchange blood transfusion, as a rule, are ineffective. The specific antidote for venlafaxine is unknown.

Interaction:

Inhibitors of monoamine oxidase (MAOI)

Irreversible non-selective MAOIs

Venlafaxine should not be used in combination with irreversible non-selective MAOIs.Venlafaxine should not be started earlier than 14 days after discontinuation of treatment by irreversible non-selective MAOIs. The use of venlafaxine should be stopped at least 7 days before the start of treatment by irreversible non-selective MAOIs.

The reversible selective MAO-A inhibitor (moclobemide)

In connection with the risk of developing serotonin syndrome, co-administration of venlafaxine and a reversible selective MAOI, such as moclobemide, Not recommended. The interruption between the onset of venlafaxine treatment and previous treatment with a reversible MAO inhibitor may be less than 14 days. It is recommended to stop taking venlafaxine at least 7 days before treatment with reversible MAOIs.

Reversible non-selective MAOI (linezolid)

Antibiotic linezolid is a weak reversible and nonselective MAOI. This drug should not be given to patients who take venlafaxine.

It has been reported of the development of severe adverse reactions in patients who have recently stopped taking MAOI and started taking venlafaxine, and also stopped the treatment with venlafaxine shortly before the start of MAOI treatment. These reactions include tremor, myoclonia, sweating, nausea,vomiting, redness of the face, dizziness and hyperthermia with signs similar to a malignant neuroleptic syndrome, as well as convulsions and death.

Serotonin syndrome

As with the use of other serotonergic drugs, with venlafaxine, serotonin syndrome, potentially life threatening, may occur, especially when combined with other drugs that have an effect on the serotonergic neurotransmitter system (including triptans, SSRIs, SSRIs, lithium, sibutramine, tramadol or St. John's Wort [Hypericum perforatum]), with drugs that interfere with the metabolism of serotonin (such as MAOI, for example, methylene blue), or with serotonin precursors (such as additives containing tryptophan).

If simultaneous treatment with venlafaxine and SSRIs, SSRIs or serotonin receptor agonists (tryptane) is clinically justified, careful monitoring of patients, especially at the beginning of treatment or during an increase in the dose of the drug, is necessary. The co-administration of venlafaxine and serotonin precursors (eg, additives containing tryptophan) is not recommended.

Substances acting on the central nervous system

The risk of joint use of venlafaxine and other drugs acting on the central nervous system has not been systematically evaluated. Therefore, when taking venlafaxine in combination with other substances acting on the central nervous system, caution should be exercised.

Ethanol

Shown, that venlafaxine Do not enhance the effects of mental and motor functions caused by ethanol. Nevertheless, as the use of other drugs acting on the CNS, patients should be advised to abstain from alcohol ingestion in the treatment of venlafaxine.

Effect of other drugs on venlafaxine

Ketoconazole (inhibitor of CUR3A4)

Pharmacokinetic study of ketoconazole in fast (BM) and poor metabolizers (MM) CYP2D6 showed an increase AUC venlafaxine (70% and 21% for MM and BM CYP2D6, respectively) and O-desmethylvenlafaxine (33% and 3% for MM and BM CYP2D6, respectively) after taking ketoconazole. Combined use of inhibitors CYP3A4 (e.g., atazanavir, clarithromycin, itraconazole, voriconazole, posaconazole, ketoconazole, nelfinavir, ritonavir, saquinavir, telithromycin) and venlafaxine can increase levels of venlafaxine and O-desmetilvenlafaksina. Therefore, if the patient's treatment involves the combined use of an inhibitor CYP3A4 and venlafaxine, caution is recommended.

Effect of venlafaxine on other drugs

Lithium

With the joint use of venlafaxine and lithium, the development of serotonin syndrome is possible (see "Serotonin syndrome").

Diazepam

Venlafaxine does not alter the pharmacokinetics and pharmacodynamics of diazepam and its active metabolite, desmethyldiazepam. Diazepam does not affect the pharmacokinetics of venlafaxine or O-desmethylvenlafaxine. There is no data on the pharmacokinetic and / or pharmacodynamic interaction of venlafaxine with other benzodiazepines.

Imipramine

Venlafaxine does not affect the pharmacokinetics of imipramine and 2-OH-imipramine. When taking venlafaxine in a dose of 75-150 mg per day, there was a dose-related increase AUC 2-OH-desipramine in 2.5-4.5 times. Imipramine does not affect the pharmacokinetics of venlafaxine or O-desmethylvenlafaxine. The clinical significance of this interaction is not known. Caution should be exercised while concomitant administration of venlafaxine and imipramine.

Haloperidol

A pharmacokinetic study of haloperidol showed a 42% reduction in total oral clearance, an increase AUC by 70%, the increase in C_mOh by 88%; the half-life of haloperidol was not observed. This should be taken into account in patients treated simultaneously with haloperidol and venlafaxine. The clinical significance of this interaction is not known.

Risperidone

Venlafaxine increased AUC risperidone by 50%, but did not significantly alter the pharmacokinetic profile of the total active components (risperidone plus 9-hydroxyrisperidone). The clinical significance of this interaction is not known.

Metoprolol

In a study of the pharmacokinetic interaction of venlafaxine and metoprolol in healthy volunteers, the concentration of metoprolol in plasma increased by about 30-40% as a result of the combined use of both drugs, while the plasma concentration of its active metabolite α-hydroxymethoprolol remained unchanged. The clinical significance of this data for patients suffering from hypertension is not known. Metoprolol does not change the pharmacokinetic profile of venlafaxine or its active metabolite O-desmethylvenlafaxine. Care should be taken when concomitant administration of venlafaxine and metoprolol is prescribed.

Indinavir

The pharmacokinetic study of indinavir showed a decrease AUC indinavir by 28% and a decrease in C_mOh by 36%. Indinavir does not affect the pharmacokinetics of venlafaxine and O-desmethyl venlafaxine. The clinical significance of this interaction is not known.

Special instructions:

Discontinuation of treatment

After cessation of treatment, especially severe, withdrawal syndrome is often observed. In clinical trials, adverse events observed after the withdrawal of treatment (with dose reduction and after reduction) occurred in approximately 31% of patients treated with venlafaxine and 17% of patients receiving placebo.

The risk of withdrawal may depend on several factors, including the duration of treatment and the doses used, as well as the rate of dose reduction. The most frequent reactions are dizziness, impaired sensory perception (including paresthesia), sleep disorders (including insomnia and vivid dreams), agitation or anxiety, nausea and / or vomiting, tremor and headache. Usually, these symptoms are mild or moderate, nevertheless, in some patients they can be severe.Typically, the symptoms appear within the first few days after cessation of treatment, but in very rare cases, the development of such symptoms has been reported in patients who accidentally missed the dose. Usually these are self-limiting symptoms that are usually resolved within 2 weeks, but in some patients they may persist for longer periods (2-3 months or more). Therefore, when discontinuing treatment, it is recommended to gradually reduce the dose of venlafaxine for several weeks or months in accordance with the patient's needs.

Serotonin syndrome

As with the use of other serotonergic drugs, the occurrence of serotonin syndrome, potentially life threatening state, or reactions similar to malignant neuroleptic syndrome (CNS), especially when combined with other serotonergic agents (including SSRIs, SSRIs and triptans), with preparations , which disrupt serotonin metabolism, such as MAO inhibitors (eg, methylene blue), with antipsychotics or other dopamine antagonists.

Symptoms of serotonin syndrome may include changes in mental status (eg, excitation, hallucinations, coma), autonomic instability (eg, tachycardia, unstable blood pressure, hyperthermia), neuromuscular abnormalities (eg, hyperreflexia, impaired coordination) and / or gastrointestinal symptoms (for example, nausea, vomiting, diarrhea). The most severe form of serotonin syndrome may resemble the NSH, which includes hyperthermia, muscle stiffness, autonomic instability with possible rapid fluctuations in vital functions, and a change in mental state.

The appointment of venlafaxine is possible not earlier than 14 days after discontinuation of therapy with MAO inhibitors and should be discontinued no less than 7 days prior to the commencement of taking any MAO inhibitor (dizziness, nausea, vomiting, increased sweating, hyperemia of the skin, tremor, myoclonus , hyperthermia, signs similar to malignant neuroleptic syndrome, seizures, until death).

If simultaneous treatment with venlafaxine and other drugs,which can affect serotonergic and / or dopaminergic neurotransmitter systems, is clinically justified, careful monitoring of patients, especially at the beginning of treatment or during a dose increase, is necessary.

The co-administration of venlafaxine and serotonin precursors (eg, additives containing tryptophan) is not recommended.

Suicidal thoughts and suicidal behavior

Depression is accompanied by an increased risk of suicidal thoughts, self-harm and suicide (events associated with suicide). This risk persists until a significant remission occurs. Because the improvement may not occur within the first few weeks of treatment or longer, careful monitoring of the patients should be noted until signs of improvement appear. Clinical experience indicates a possible increase in the risk of suicide in the early stages of treatment.

It is known that in patients with suicidal events in the anamnesis, as well as in patients who showed a significant degree of suicidal tendencies before starting treatment, there is a greater risk of suicidal thoughts and suicide attempts; during treatment they must be carefully monitored.A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behavior in patients under 25 years of age who took antidepressants compared to patients taking placebo.

During medical treatment, careful monitoring of patients, in particular, high-risk patients, is necessary, especially at the beginning of treatment and when changing the dose. Patients (and their caregivers) should be warned about the need for surveillance to detect clinical impairment, suicidal behavior or thoughts, unusual behavioral changes, and the need to seek medical help if these symptoms are present.

Arterial pressure

When taking venlafaxine, a dose-dependent increase in blood pressure is often recorded. During the period of post-marketing use of the drug, several cases of severe increase in arterial pressure requiring immediate treatment were reported. Before the start of venlafaxine treatment, all patients should undergo a thorough examination to detect high blood pressure, and pre-existing hypertension should be controlled.After the start of treatment, as well as after increasing the dose, periodic monitoring of blood pressure is necessary. Caution should be exercised in patients in whom the underlying disease may worsen with increased blood pressure, for example in patients with heart failure.

Heart rate

During the administration of the drug, an increase in the heart rate may be possible, especially if higher doses are prescribed. Caution should be exercised in the treatment of patients whose underlying illnesses may worsen with increased heart rate or increased blood pressure.

Heart Disease and Risk of Arrhythmias

The use of venlafaxine in patients who have recently undergone myocardial infarction or who suffer from decompensated heart failure has not been studied. Therefore, in such patients, the drug should be used with caution.

During the post-registration use of the drug, it was reported about the development of fatal cardiac arrhythmias, especially with an overdose. Before appointing venlafaxine patients at high risk of serious cardiac arrhythmias, it is necessary to assess the risk-benefit ratio.

Mania / Hypomania

Patients with affective disorders on the background of taking antidepressants, including venlafaxine, may develop hypomanic or manic conditions. Like other antidepressants, venlafaxine should be administered with caution to patients with a history of mania. Such patients need medical supervision.

Closed-angle glaucoma

During treatment, the emergence of mydriasis. It is recommended to control intraocular pressure in patients prone to its increase or with a closed-angle glaucoma.

Convulsions

On the background of treatment with venlafaxine, convulsions may occur. Like all other antidepressants, caution should be applied to the drug Voxel in patients with a history of seizures. When prescribing the drug, you need to carefully monitor the patient's condition; should stop treatment when the patient develops an epileptic fit.

Abnormal bleeding

Drugs that inhibit serotonin reuptake may help reduce platelet function. In patients receiving venlafaxine, there may be an increased risk of bleeding from the vessels of the skin and mucous membranes,including gastrointestinal bleeding. Like other serotonin reuptake inhibitors, venlafaxine should be administered with caution to patients prone to bleeding, including patients taking anticoagulants and platelet inhibitors.

Cholesterol in serum

A clinically significant increase in serum cholesterol was observed in 5.3% of patients receiving venlafaxine, and in 0.0% of patients receiving a placebo for at least 3 months in placebo-controlled clinical trials. Therefore, with prolonged use of the drug, it is advisable to monitor the serum cholesterol level.

Aggression

A small number of patients taking antidepressants, including venlafaxine, there may be aggression. Aggression was noted at the beginning of treatment, with a change in dose and discontinuation of treatment. Just like other antidepressants, venlafaxine It should be used with caution in patients with episodes of aggression in the anamnesis.

Joint use with drugs to reduce body weight

The safety and efficacy of venlafaxine in combination with drugs for weight loss, including phentermine, have not been established.Joint use of venlafaxine and drugs to reduce body weight is not recommended. The decrease in body weight is not an indication for the use of venlafaxine, either in the form of monotherapy or in combination with other drugs.

Hyponatremia

On the background of treatment in patients with hypovolemia or in dehydrated patients (including elderly patients or taking diuretics), hyponatremia and / or the syndrome of inadequate secretion of antidiuretic hormone may develop.

Akathisia / psychomotor anxiety

The use of venlafaxine is associated with the development of akathisia, characterized by subjectively unpleasant and distressing anxiety and the need to move, often in combination with the inability to sit or stand still. The development of akathisia is most likely during the first few weeks of treatment. In patients with similar symptoms, increasing the dose may have an adverse effect.

Dryness of the oral mucosa

Dryness of the oral mucosa is observed in 10% of patients receiving venlafaxine treatment. This can increase the risk of caries; patients should be informed about the importance of dental hygiene.

Diabetes

In patients with diabetes mellitus, treatment with SSRIs or venlafaxine may affect the glycemic profile. You may need to adjust the dose of insulin and / or antidiabetic drugs.

Effect on the results of laboratory tests on drugs

False positive results of immunological screening of urine for phencyclidine (FDC) and amphetamine in patients who took venlafaxine. This was due to the low specificity of the screening test. False positive results of the study can be recorded within a few days after the cessation of treatment with venlafaxine. Confirmatory tests, such as Gas chromatography / mass spectrometry, will distinguish venlafaxine from FCD and amphetamine.

To reduce the likelihood of an overdose at the beginning of therapy, the patient should be given a minimum amount of the drug.

During treatment it is recommended to refrain from taking ethanol.

Special precautions for the destruction of unused medicinal product

There is no need for special precautions when destroying an unused preparation.

Effect on the ability to drive transp. cf. and fur:

During the period of drug treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Capsules of prolonged action, 37.5 mg, 75 mg and 150 mg.

Packaging:

For 7 or 10 capsules in PVC / PVDC / Al-blisters.

For 3 blisters of 10 capsules or 4 or 8 blisters of 7 capsules are placed in a cardboard box along with instructions for medical use.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002868

Date of registration:19.02.2015 / 18.06.2015

Expiration Date:19.02.2020

Date of cancellation:2020-02-19

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

SANDOZ PRIVATE, Limited India

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp05.03.2017

Illustrated instructions

Instructions

Vokssel (VOXEMEL)