Expiration date: 05/2025
Release form and composition:
Tablets white or almost white, round, flat, bevelled on one side, engraved with E741, without or almost odorless.
1 tablet contains venlafaxine (hydrochloride) 37.5 mg
Excipients: lactose monohydrate (84.93 mg), microcrystalline cellulose, sodium starch glycolate (type A), silica colloidal anhydrous, magnesium stearate.
14 pcs. - Blisters (2) - packs cardboard.
Tablets white or almost white, round, flat, bevelled on one side, engraved with E743, without or almost odorless.
1 tablet contains venlafaxine (hydrochloride) 75 mg
Excipients: lactose monohydrate (169.86 mg), microcrystalline cellulose, sodium starch glycolate (type A), silica colloidal anhydrous, magnesium stearate.
14 pcs. - Blisters (2) - packs cardboard.
Pharmachologic effect:
Antidepressant. According to the chemical structure of venlafaxine can not be attributed to any known class of antidepressants (tricyclic, tetracyclic, or other). It has two enantiomeric active racemic forms.
Venlafaxine Antidepressant effect associated with increased activity in the CNS neurotransmitter. Venlafaxine and its main metabolite O-desmetilvenlafaksin (EFA) are potent inhibitors of the reuptake of serotonin and norepinephrine, and weakly inhibit the reuptake of dopamine neurons. Venlafaxine and EFA equally effective influence on the reuptake of neurotransmitters. Venlafaxine and EFA reduced beta adrenergic response.
Venlafaxine has no affinity for the m-and n-holinoretseptorami, histamine H1-receptors and brain apha1-adrenoceptors. Venlafaxine does not inhibit MAO activity. No affinity to opioid, benzodiazepine, or fentsiklidinovym NMDA-receptors.
Pharmacokinetics:
Suction
After oral administration of venlafaxine is well absorbed from the gastrointestinal tract. After single oral doses of 25-150 mg Cmax is reached within approximately 2.4 hours and the plasma is 33-172 ng / mL. Venlafaxine is extensively metabolized during the first passage through the liver.
EFA Cmax achieved after about 4.3 hours in the blood plasma after administration and is 61-325 ng / mL.
In the range of 75-450 mg daily doses of venlafaxine and EFA have linear kinetics. After taking the drug at meal time achieving increased Cmax for 20-30 minutes in the blood plasma, but Cmax values ??and removals are not changed.
Distribution
The binding of venlafaxine and EFA to plasma proteins is respectively 27% and 30%.
Repeated receiving venlafaxine and EFA Css attained within 3 days.
Metabolism and excretion
The main metabolite - EFA.
T1 / 2 and venlafaxine EFA is respectively 5 and 11 hours.
EFA and other metabolites, as well as unchanged venlafaxine excreted by the kidneys.
Pharmacokinetics in special clinical situations
In patients with liver cirrhosis the concentration of venlafaxine blood plasma and increased EFA and their reduced rate of excretion.
In moderate or severe renal insufficiency the overall clearance of venlafaxine and EFA reduced, and T1 / 2 longer. Reducing the total clearance is mainly observed in patients with CC less than 30 ml / min.
Age and sex of the patient did not affect the pharmacokinetics of the drug.
Testimony:
- Depression different etiology (treatment and prevention).
Dosage and administration:
Velaxin recommended to take tablets during meals.
The recommended starting dose is 75 mg in 2 hours (at 37.5 mg 2 times / day) daily. If after several weeks of treatment, no significant improvement is observed, the daily dose can be increased to 150 mg (75 mg of 2 times / day). If the opinion of the physician, a higher dose (major depression or other conditions that require hospital treatment), you can immediately assign 150 mg in 2 divided doses (75 mg 2 times / day). Thereafter, the daily dose may be increased to 75 mg every 2-3 days until the desired therapeutic effect. The maximum daily dose Velaxin® drug is 375 mg. After achieving the desired therapeutic effect, the daily dose can be gradually reduced to the minimum effective level. The length of time required to reduce the dose depends on the dose, duration of therapy, as well as individual patient sensitivity.
Supportive therapy and relapse prevention. Supportive therapy can continue for 6 months or more. The drug is prescribed at the lowest effective doses used in the treatment of depressive episodes.
In renal insufficiency, mild (creatinine clearance gt 30 ml / min) correction mode is not required. In renal failure of moderate severity (CC 10-30 ml / min), the dose should be reduced by 25-50%. In connection with the extension of T1 / 2 of venlafaxine and its active metabolite (EFA) in such patients should take the entire dose of 1 times / day. Not recommended for venlafaxine in renal failure severe (CC t 10 mL / min), since reliable data on the safety of this therapy are not available.
Patients on hemodialysis may receive 50% of the usual daily dose of venlafaxine after completion of the hemodialysis session.
For mild hepatic insufficiency (prothrombin time less than 14 seconds) correction mode is not required. In moderate hepatic insufficiency (prothrombin time of 14 to 18 seconds), the dose should be reduced by 50%. Not recommended for venlafaxine in severe hepatic insufficiency, since reliable data on the safety of this therapy are not available.
In elderly patients the drug should be used with caution due to the possibility of renal impairment. Use the smallest effective dose. When the dose the patient should be under close medical supervision.
After receiving Velaxin recommended to gradually reduce the dosage of the drug, at least for a week and observe the patient's condition, to minimize the risk associated with the abolition of the drug. The length of time required to reduce the dose depends on the dose, duration of therapy, as well as individual patient sensitivity.
Side effects:
Most of the side effects depends on the dose. With long-term treatment of the severity and frequency of most of these effects is reduced, and there is no need for treatment discontinuation.
In decreasing order of frequency: often (ge1%), rarely (ge0.1% and t1%), rarely (ge0.01% and t0.1%), very rare (t0.01%).
From the digestive system: loss of appetite, constipation, nausea, vomiting, dry mouth, rarely - hepatitis.
On the part of metabolism: increased levels of serum cholesterol, weight loss rarely - a violation of liver function tests, hyponatremia, syndrome of inadequate secretion of ADH.
Since the cardiovascular system: hypertension, flushing of the skin rarely - postural hypotension, tachycardia.
From the central and peripheral nervous system: abnormal dreams, dizziness, insomnia, nervous irritability, paresthesias, stupor, increased muscle tone, tremor, yawning infrequently - apathy, hallucinations, muscle spasms, serotonergic syndrome rarely - seizures, manic reaction, as well as symptoms resembling neuroleptic malignant syndrome.
From the urinary system: dysuria (mostly - the difficulties at the beginning of urination) Infrequent - urinary retention.
From the reproductive system: ejaculation disorders, erectile dysfunction, anorgasmia infrequently - decreased libido, menorrhagia.
From the senses: accommodation disturbances, mydriasis, visual disturbances rarely - a violation of taste sensations.
Dermatological reactions: sweating rarely - photosensitivity.
Hematopoietic system: rarely - bleeding in the skin (ecchymosis) and mucous membranes, thrombocytopenia, rarely - prolongation of bleeding time.
Allergic reactions: seldom - skin rash, rarely - erythema multiforme, Stevens-Johnson syndrome is very rare - anaphylactic reactions.
Other: weakness, fatigue.
After the abrupt cancellation Velaxin or dose reduction may be fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, restlessness, anxiety, nervous irritability, disorientation, hypomania, paraesthesia, sweating. These symptoms are usually mild and go away without treatment. Because of the likelihood of these symptoms it is important to gradually reduce the dose of the drug (or any other antidepressant), particularly after taking high doses.
Contraindications:
- Severe renal dysfunction (creatinine clearance 10 mL t / min)
- Severe hepatic dysfunction
- Simultaneous reception of MAO inhibitors
- Child and adolescence to 18 years (safety and efficacy for these patients has not been proven)
- Established or suspected pregnancy
- Lactation (breastfeeding)
- Hypersensitivity to the drug.
Precautions should be prescribed the drug at a recent myocardial infarction, unstable angina, hypertension, tachycardia, spasms in the history of ocular hypertension, angle-closure glaucoma, manic states in history, predisposition to bleeding from the skin and mucous membranes, initially reduced body weight.
Pregnancy and lactation:
Safety of Velaxin not proved during pregnancy. Therefore, the use during pregnancy (or suspected pregnancy) is possible only if the expected benefit to the mother outweighs the potential risk to the fetus.
Women of childbearing age should use reliable methods of contraception during treatment with the drug and consult a doctor immediately in case of pregnancy or pregnancy planning.
Venlafaxine and EFA metabolite are excreted in breast milk. The safety of these substances for newborn children is not proven, so if necessary, taking the drug during lactation should decide the issue of termination of breastfeeding. If maternal treatment was completed shortly before the birth, the newborn drug withdrawal symptoms may occur.
Special instructions:
Abrupt discontinuation of Velaxin therapy (as well as other antidepressants), especially after use in high doses, can cause withdrawal symptoms, and therefore it is recommended to repeal the drug gradually reduce the dose. The length of time required to reduce the dose depends on the dose, duration of therapy, as well as individual patient sensitivity.
Patients with depressive disorders before starting any drug therapy should consider the likelihood of suicide attempts. Therefore, to reduce the risk of overdose in the early treatment of the drug should be possible to apply the minimum effective dose, and the patient should be under close medical supervision.
In patients with affective disorders in the treatment with antidepressants (including venlafaxine) may experience hypomanic or manic state. As with other antidepressants, venlafaxine should be used with caution in patients with mania in history. Such patients need medical supervision.
Velaxin® (like other antidepressants) should be administered with caution to patients with a history of seizures. venlafaxine treatment should be interrupted in case of epileptic seizures.
Precautions should be prescribed Velaxin® patients with recent myocardial infarction, and suffering from decompensated heart failure, because the safety of the drug in these patients has not been studied.
The caution is recommended to use the drug in patients with tachyarrhythmia. Against the background of treatment with the possibility of increasing the heart rate, especially during the reception in high doses.
Patients should be warned of the need to consult a doctor immediately in case of rash, urticaria or other elements of allergic reactions.
In some patients, while receiving venlafaxine observed a dose-dependent increase in blood pressure, in this regard, we recommend regular monitoring of blood pressure, especially in the period specification or increasing the dose.
Patients, especially the elderly, should be warned about the potential for dizziness and impaired sense of balance.
As with other serotonin reuptake inhibitors, venlafaxine can increase the risk of hemorrhages in the skin and mucous membranes. When treating patients predisposed to these conditions, caution is required.
While receiving venlafaxine, especially in conditions of dehydration or reduction bcc (including elderly patients, and patients taking diuretics) can be observed hyponatremia and / or syndrome of inadequate secretion of ADH.
In mydriasis may occur while taking the drug, and therefore recommended that the control of intraocular pressure in patients who are prone to increase his suffering or narrow-angle glaucoma.
Conducted to date in clinical trials showed no tolerance to venlafaxine or depending on him. Despite this, as well as in the treatment of other drugs acting on the central nervous system, the physician should establish a careful monitoring of patients for signs of drug abuse. Careful monitoring and observation are needed for patients having in the anamnesis on symptoms.
In appointing Velaxin tablets to patients with lactose intolerance should take into account the content of lactose (84.93 mg in each tablet 37.5 mg 169.86 mg in each tablet 75 mg).
In patients receiving venlafaxine should be particularly careful during electroconvulsive therapy, as experience with venlafaxine in these conditions is missing.
During Velaxin treatment should avoid drinking alcohol.
Use in Pediatrics
The safety and efficacy of the drug in children and adolescents under the age of 18 years have not been studied.
Effects on ability to drive vehicles and management mechanisms
Despite the fact that venlafaxine does not affect the psychomotor and cognitive function, please note that any medication psychoactive drug may impair the mental processes and reduce the ability to perform motor functions. This should warn the patient before treatment. In the event of such violations degree and duration of the restrictions should be set by your doctor.
Overdose:
Symptoms: ECG changes (prolongation of the interval QT, bundle branch block, the expansion of the QRS complex), sinus and ventricular tachycardia, bradycardia, hypotension, apnea condition, the change of consciousness (decreased level of consciousness). With an overdose of venlafaxine while taking alcohol and / or other psychotropic drugs, it reported deaths.
Treatment: symptomatic therapy. Specific antidotes are not known. Recommended continuous monitoring of vital functions (respiration and circulation). Appointment of activated charcoal to reduce absorption of the drug. Do not induce vomiting due to aspiration hazard. Venlafaxine and EFA are not displayed during dialysis.
Drug Interactions:
Concomitant use Velaxin with MAO inhibitors is contraindicated. Admission Velaxin can begin at least 14 days after the end of therapy MAO inhibitors. If you used a reversible MAO inhibitor (moclobemide), this interval may be shorter (24 h). MAO inhibitor therapy can begin at least 7 days after the cancellation Velaxin® drug.
Concomitant use of venlafaxine with lithium may increase the level of the latter.
In an application with imipramine pharmacokinetics of venlafaxine and its metabolite EFA does not change.
Perhaps strengthening the effects of haloperidol due to the increase of its concentration in the blood when combined with Velaxin.
While the use of diazepam pharmacokinetics of drugs and their main metabolites does not change significantly. Also not revealed effects on psychomotor and psychometric effects of diazepam.
In an application with clozapine may experience an increase in its level in the blood plasma and the development of side effects (eg, seizures).
In an application with risperidone (despite the increase in AUC of risperidone), the pharmacokinetics of the amount of active ingredients (risperidone and its active metabolite) did not change significantly.
With simultaneous use of venlafaxine and ethanol were observed decrease of psychomotor reactions. However, during venlafaxine therapy is not recommended to drink alcohol.
The metabolism of venlafaxine with the formation of the active metabolite of EFA occur with the participation of isoenzyme CYP2D6. Unlike many other antidepressants, venlafaxine dose can not reduce while the use of CYP2D6 inhibitors, or in patients with a genetically determined reduction in CYP2D6 activity, as the total concentration of the active substance and metabolite (venlafaxine and EFA) is not changed.
The primary route of elimination of venlafaxine includes metabolism by CYP2D6 and of CYP3A4, so you should be very careful in the appointment of venlafaxine in combination with drugs that are inhibitors of these two enzymes. The nature of this interaction has not been studied.
Venlafaxine is a relatively weak inhibitor of CYP2D6 and does not inhibit the activity of isozymes CYP1A2, CYP2C9 and CYP3A4 so do not expect its interaction with other drugs in the metabolism of the liver enzymes which are involved.
Cimetidine inhibits the metabolism of venlafaxine in the first pass through the liver and has no effect on the pharmacokinetics of EFA. The majority of patients are expected only a slight increase in the overall pharmacological activity of venlafaxine and EFA (more pronounced in older patients and with abnormal liver function).
There were no clinically significant interaction between venlafaxine and antihypertensive (including beta-blockers, ACE inhibitors and diuretics) and hypoglycemic drugs.
As the plasma protein binding of venlafaxine and EFA is respectively 27% and 30%, are not expected to drug interaction, caused by violation of binding to plasma proteins.
When concomitantly with warfarin may increase the anticoagulant effect of the latter.
When concomitantly with indinavir AUC of indinavir, a decrease of 28% and a decrease in its Cmax by 36%, while the pharmacokinetic parameters of venlafaxine and EFA are not changed. The clinical significance of this is unknown effect.
Conditions and terms:
The drug should be stored in a dry place inaccessible to children at temperature not above 30 ° C. Shelf life - 5 years.
