Newvelong - instructions for use, doses, side effects, contraindications

auxiliary substances: Mannitol 10.0 mg / 20.0 mg / 30.0 mg, povidone-K90 7.0 mg / 14.0 mg / 21.0 mg, macrogol 400 5.0 mg / 10.0 mg / 15.0 mg, microcrystalline cellulose 70.34 mg / 140.68 mg / 211.02 mg, silicon dioxide colloid 1.0 mg / 2.0 mg / 3.0 mg,magnesium stearate 1.80 mg / 3.60 mg / 5.40 mg;

shell A (osmotic): cellulose acetate 320S NF 6.55 mg / 9.90 mg / 12.15 mg, cellulose acetate 398-10 NF 9.58 mg / 11.00 mg / 13.50 mg, macrogol-400 0.88 mg / 1.10 mg / 1.35 mg;

shell B (cosmetic): Opadrai® Y-30-18037 (hypromellose, lactose monohydrate of silicon dioxide, triacetin) 9.0 mg / 15.0 mg / 17.0 mg

Description:

Round biconvex tablets, coated with a white film membrane, having an opening on one side.

Pharmacotherapeutic group:antidepressant

ATX: & nbsp

N.06.A.X.16 Venlafaxine

N.06.A.X Other antidepressants

Pharmacodynamics:

Venlafaxine is a structurally new antidepressant, which is a racemate with two active enantiomers. The mechanism of antidepressant action of venlafaxine is associated with its potentiating effect on neurotransmitter activity in the central nervous system. Venlafaxine and its main metabolite, O-desmethylvenlafaxine (EFA) are potent inhibitors of the reuptake of serotonin and norepinephrine and weak inhibitors of dopamine reuptake. On the inhibition of serotonin reuptake venlafaxine is inferior to selective serotonin reuptake inhibitors.

Pharmacokinetics:

Absorption - at least 92% of the once-ingested dose of venlafaxine.The absolute bioavailability of venlafaxine is about 45%. After a single dose of venlafaxine tablets, the maximum concentration (C_mOh) venlafaxine and EFA in plasma is achieved in the range of 6.0 ± 1.5 and 8.8±2.2 hours respectively. The half-life of the long-acting drug is 15 ± 6 hours and is limited by the rate of absorption.

Distribution. Venlafaxine and EFA by 27% and 30% respectively bind to plasma proteins.

Metabolism. Venlafaxine undergoes a pronounced metabolism of the "first passage" in the liver with the participation of cytochrome P450 (isoenzyme CYP2D6) to form the active metabolite of O-desmethyl venlafaxine. Venlafaxine is also metabolized by isoenzymes CYP3A3/4 to N-desmethylvenlafaxine and other metabolites. In patients with reduced isoenzyme activity CYP2D6 there is 2-3 times greater venlafaxine exposure and 2-3 times less exposure to the active metabolite of EFA.

Excretion. The venlafaxine clearance in plasma is 1.3 l / h / kg, and for the active metabolite of EFA it is 0.4 l / h / kg. The half-life of venlafaxine is 15 hours and EFA - 11h.

Venlafaxine is excreted mostly by the kidneys about 87% within 48 hours, unchanged - 5%, in the form of unconjugated EFA - 29%,conjugated EFA - 26% and other inactive metabolites - 27%.

Special patient groups

Sex and age do not significantly affect the pharmacokinetics of venlafaxine.

There was no accumulation of venlafaxine or EFA during long-term admission in healthy subjects.

With hepatic and renal insufficiency from moderate to severe, there was a decrease in venlafaxine metabolism and elimination of EFA, which led to an increase in C_mOh, reduced clearance and an elongated half-life. The decrease in the total clearance of the drug is most pronounced in patients with creatinine clearance (CC) below 30 ml / min.

Taking venlafaxine with food does not affect the absorption of venlafaxine, nor the subsequent formation of EFA.

Indications:

Depression (treatment, prevention of relapse).

Contraindications:

- Hypersensitivity to venlafaxine or another component of the drug;

- simultaneous administration with MAO inhibitors;

- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

- pregnancy, lactation period;

- age to 18 years.

Carefully:

Recently suffered myocardial infarction, unstable angina, arterial hypertension, tachycardia,convulsions in history, intraocular hypertension, angle-closure glaucoma, manic conditions in the anamnesis, hyponatremia, hypovolemia, dehydration, simultaneous reception of diuretics, suicidal tendencies, predisposition to bleeding from the skin and mucous membranes, renal / hepatic insufficiency.

Dosing and Administration:

Venlafaxine should be taken internally with food, not chewing and washing with liquid once a day, it is desirable at the same time, in the morning or in the evening.

Attacks of severe depression

The effective dose for treating depression usually lies between 75 mg and 225 mg. Treatment should begin with 75 mg once a day. A noticeable effect will appear after 2-4 weeks of treatment with the standard adequate dose. If the clinical result is unsatisfactory, the dose may be increased to 150 mg, then to 225 mg. The maximum allowable daily dose is 375 mg, but it should be noted that the use of high doses has not been adequately studied. In all cases, high doses should be administered under close medical supervision. Doses can be increased at intervals of about 2 weeks or more, a minimum of 4 days between each increase.If after 2-4 weeks of positive dynamics is not observed, treatment should be discontinued.

Supportive treatment

It is generally accepted that acute attacks of deep depression require 4-6 months of therapy. Some patients may require longer treatment. The physician should periodically reassess the usefulness of prolonged treatment with venlafaxine for each patient individually.

Cancellation of the drug should be carried out gradually to avoid the syndrome of "withdrawal": in the course of treatment for 6 weeks or more, the period of gradual withdrawal of the drug should be at least 2 weeks and depends on the dose, duration of therapy and individual characteristics of the patient.

In case of impaired renal function (the rate of glomerular filtration is 10-70 ml / min), the daily dose should be reduced by 25-50%.

With hemodialysis The daily dose should be reduced by 50%, the drug should be taken after the end of the hemodialysis session.

In patients with hepatic insufficiency the average daily dose should be reduced by 50% or more.

Side effects:

It is often difficult to distinguish unwanted effects from symptoms of depression.

The degree of most side effects depends on the dose.

Frequency estimation:

Very often:> 1/10

Frequently:> 1/100 <1/10

Infrequently:> 1/1000 <1/100

Rarely:> 1/10000 <1/1000

Very rarely <1/10000 including individual messages

On the part of the organs of hematopoiesis

Rarely: thrombocytopenia.

Rarely: violation of hematopoiesis (including agranulocytosis, aplastic anemia, neutropenia and pancytopenia).

From the immune system

Infrequently: photosensitization.

Very rarely: anaphylaxis.

From the endocrine system

Very rarely: hyperprolactinaemia.

Metabolism and nutrition disorders

Often: hypercholesterolemia (especially associated with long-term treatment and, possibly, with the use of large doses), weight loss.

Infrequent: hyponatremia, weight gain.

Rarely: syndrome of inadequate secretion of antidiuretic hormone.

From the nervous system

Often: dizziness, headache, increased muscle tone, paresthesia, sedation, tremor; insomnia, drowsiness, nervousness, aggression, abnormal dreams, orgasm disorders (men); yawning, decreased appetite, anorexia, weakness, fatigue, asthenia.

Infrequently: myoclonia, apathy, hallucinations, agitation, disorders of orgasm (women).

Rarely: serotonergic syndrome, malignant neuroleptic syndrome, convulsions, akathisia, mania or hypomania.

Very rarely: extrapyramidal reactions (including dystonia and dyskinesia), tardive dyskinesia, delirium.

From the sense organs

Often: disorders of accommodation, mydriasis, anomalies of perception.

Infrequent: noise in the ears.

From the side of cardio-vascular system

Often: increased blood pressure, vasodilation (very often a feeling of "hot flushes"), ecchymosis, bleeding from the mucous membranes.

Infrequent: arrhythmias (including tachycardia), lowering blood pressure, postural hypotension, fainting.

Rarely: hemorrhage (including cerebral hemorrhage), gastrointestinal bleeding.

Very rarely: lengthening the interval QT and expansion of the complex QRS, ventricular fibrillation, ventricular tachycardia (including torsade des pointes), decompensation of heart failure, heart failure.

On the part of the respiratory system

Very rarely: pulmonary eosinophilia with respiratory failure, chest pain.

From the side of the digestive system

Often: constipation, decreased appetite, nausea, vomiting, dry mouth, indigestion.

Infrequently: bruxism, changes in taste, diarrhea; impaired hepatic functional tests.

Rarely: hepatitis.

Rarely: pancreatitis.

From the skin

Often: increased sweating (including nocturnal profuse sweating).

Infrequent: dermatitis, alopecia, photosensitivity, rash.

Very rarely: multi-form exudative erythema, Stevens-Johnson syndrome, itching, prurigo, urticaria.

From the side of the musculoskeletal system

Very rarely: rhabdomyolysis.

From the genitourinary system

Often: violation of urination (most often - intermittent urination), ejaculation disorders, erectile dysfunction, decreased libido.

Infrequent: retention of urine; menorrhagia, violation of orgasm in women.

Change in laboratory indicators

Rarely: increased bleeding time.

If there is a syndrome of "cancellation"dizziness, headache, asthenia, fatigue, sleep disturbances (change in the nature of dreams, drowsiness or insomnia, difficulty falling asleep), hypomania, anxiety, increased nervous excitability, confusion, paresthesia, increased sweating, dry mouth, decreased appetite, nausea , vomiting,diarrhea (most of these reactions are expressed slightly and do not require treatment).

Overdose:

Symptoms (often occur with simultaneous intake of ethanol): a disturbance of consciousness (from drowsiness to coma), as well as agitation, gastrointestinal disorders such as vomiting, diarrhea; tremor, change of electrocardiogram (ECG) (lengthening QT interval, block blocking the bundle of the bundle, expansion of the complex QRS), sinus and ventricular tachycardia or bradycardia, decrease or (weak) increase in arterial pressure, epileptic seizures, rhabdomyolysis, mydriasis.

Treatment: symptomatic; ECG monitoring and vital organs functions; at risk of aspiration, vomiting is not recommended; gastric lavage (if an overdose has occurred recently, or the symptoms of an overdose persist); Activated carbon. Forced diuresis, dialysis, hemoperfusion or metabolic transfusion are not effective. There is no specific antidote.

Interaction:

It is inadmissible simultaneous use of venlafaxine with monoamine oxidase (MAO) inhibitors. The use of venlafaxine is possible no earlier than 14 days after discontinuation of therapy with MAO inhibitors and should beterminated at least 7 days prior to the commencement of taking any MAO inhibitor because of the risk of side effects.

Increases the effect of ethanol on psychomotor reactions.

When administered orally reduces the total clearance of haloperidol by 42%, increases its area under the pharmacokinetic curve (AUC) by 70% and C_ma_x by 88%.

Venlafaxine does not affect the metabolism of imipramine and its metabolite 2-hydroxyimipramine, although the total renal clearance of 2-hydroxydesipramine decreases, and the area under the concentration-time curve and C_mа_x of desipramine are increased by about 35%.

Cimetidine inhibits the metabolism of the "first pass" of venlafaxine, but does not affect the pharmacokinetics of O-desmethylvenlafaxine (EFA). 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 liver failure).

With the simultaneous use of venlafaxine with antidepressants (selective serotonin reuptake inhibitors) (SSRIs), prolonged seizures are noted.

The risk of increasing side effects, including seizures, increases with simultaneous use of venlafaxine with clozapine, due to increased concentrations of clozapine in the blood.

Venlafaxine should be used with caution in patients taking concomitant medications that increase the risk of bleeding, such as anticoagulants, salicylic acid derivatives and nonsteroidal anti-inflammatory drugs (NSAIDs).

With simultaneous use with warfarin, there was an increase in prothrombin time, partial thromboplastin time, or an international normalized ratio

Caution is required when concomitantly using venlafaxine with isoenzyme inhibitors CYP2D6 (e.g., quinidine, paroxetine, fluoxetine, perphenazine, haloperidol, levomepromazine), because the venlafaxine can disrupt the action of other isoenzyme substrates CYP2D6, increasing their concentration in plasma.

A high concentration of venlafaxine can be observed in patients with low isoenzyme activity CYP2D6.

With the simultaneous use of drugs - inhibitors of isoenzyme CYP3A3/4 (ketoconazole, itraconazole, ritonavir) the concentration of venlafaxine in the blood plasma can be increased.

Does not interact with lithium preparations, as well as preparations metabolized by isoenzymes CYP3A4, CYP1A2 and CYP2C9 (incl.alprazolam, caffeine, carbamazepine, diazepam, tolbutamide).

Does not affect the concentration of drugs in the plasma, which have a high degree of binding to proteins.

Special instructions:

In patients (under 24 years) with depression or other mental disorders antidepressants compared to placebo, increased the risk of suicidal thoughts or suicidal behavior. Therefore, when appointing venlafaxine, patients younger than 24 years should be associated with the risk of suicide and the benefits of their use. In short-term studies in people over 24 years of age, the risk of suicide did not increase, but in people older than 65 years, it declined slightly. Any depressive disorder in itself increases the risk of suicide. Therefore, during treatment with antidepressants, all patients should be monitored for early detection of abnormalities or behavioral changes, as well as suicidal tendencies.

For patients with diabetes mellitus, treatment with SSRIs / SSRIs (selective norepinephrine reuptake inhibitors) may affect glucose levels. The dose of insulin and / or oral antidiabetic agents should be adjusted.

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

Careful dosing and regular monitoring are used in the following cases:

- narrow-angle glaucoma, increased intraocular pressure (since venlafaxine has a weak m-anticholinergic effect),

- diseases of the cardiovascular system (conduction disorders, angina, recently transferred myocardial infarction, ventricular arrhythmia, arterial hypertension or hypotension).

In the course of long-term treatment with venlafaxine, it is necessary to control the concentration of serum cholesterol. When hypercholesterolemia appears, consider switching to another antidepressant.

In patients receiving venlafaxine, the risk of cutaneous or mucosal bleeding may be increased.

During treatment with the drug it is recommended to refrain from drinking alcohol.

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

During treatment with venlafaxine, care must be taken when driving vehicles or performing work,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Tablets of prolonged action, film-coated, 75 mg, 150 mg and 225 mg.

Packaging:

For 10 tablets in blisters, consisting of an intact aluminum layer, welded to a film of PVC-ACLAR/ aluminum.

3 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

In a dry place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years

Do not use the drug with expired shelf life.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006938/10

Date of registration:21.07.2010

The owner of the registration certificate:Italfarmaco SpAItalfarmaco SpA Italy

Manufacturer: & nbsp

Laboratorios LICONSA, S.A. Spain

Representation: & nbspITALFARMAKO SpA ITALFARMAKO SpA Italy

Information update date: & nbsp14.12.2015

Illustrated instructions

Instructions

Newvelong (Newvelong)