VELAKSIN (tablets)
Active material: Venlafaxine
When ATH: N06AX16
CCF: Antidepressant
ICD-10 codes (testimony): F31, F32, F33, F41.2
When CSF: 02.02.06
Manufacturer: EGIS PHARMACEUTICALS Plc (Hungary)
PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING
Pills white or nearly white, round, flat, bevelled on one side, Engraved “E741”, with little or no odor.
| 1 tab. | |
| venlafaxine (the hydrochloride) | 37.5 mg |
Excipients: lactose monohydrate (84.93 mg), microcrystalline cellulose, sodium starch glycolate (Type A), Colloidal anhydrous silica, magnesium stearate.
14 PC. – blisters (2) – packs cardboard.
Pills white or nearly white, round, flat, bevelled on one side, Engraved “E743”, with little or no odor.
| 1 tab. | |
| venlafaxine (the hydrochloride) | 75 mg |
Excipients: lactose monohydrate (169.86 mg), microcrystalline cellulose, sodium starch glycolate (Type A), Colloidal anhydrous silica, magnesium stearate.
14 PC. – blisters (2) – packs cardboard.
Pharmacological action
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 active enantiomeric form of racemic.
Antidepressant effect of venlafaxine is associated with increased activity of the neurotransmitter in the central nervous system. Venlafaxine and its main metabolite O-desmetilvenlafaksin (EFA) are potent serotonin reuptake inhibitors and noradrenaline and weakly inhibit the reuptake of dopamine neurons. Venlafaxine and EFA equally effective influence on the reuptake of neurotransmitters. Venlafaxine and EFA reduce beta-adrenergic reactions.
Venlafaxine has no affinity for the m- and n-holinoretseptorami, histamine H1-рецепторам и a1-adrenoceptors brain. Venlafaxine does not inhibit MAO activity. No affinity for the opioid, benzodiazepine, phencyclidine or NMDA receptors.
Pharmacokinetics
Absorption
After oral administration of venlafaxine is well absorbed from the gastrointestinal tract. After receiving a single dose 25-150 mg Cmax plasma levels achieved for about 2.4 h and is 33-172 ng / ml. Venlafaxine is extensively metabolized in the “first pass” through the liver.
Cmax EFA in plasma is approximately 4.3 hours after administration and was 61-325 ng / ml.
The daily doses range 75-450 mg of venlafaxine and EFA have linear kinetics. After taking the drug during meal time to reach Cmax in the blood plasma is increased by 20-30 m, However, the value of Cmax and removals are not changed.
Distribution
The binding of venlafaxine and EFA to plasma proteins is respectively 27% and 30%.
With repeated intake of Css venlafaxine and EFA reached within 3 days.
Metabolism and excretion
The major metabolite – EFA.
T1/2 venlafaxine and EFA is respectively 5 and 11 no.
EFA and other metabolites, as well as the kidneys unchanged venlafaxine.
Pharmacokinetics in special clinical situations
Patients with cirrhosis of the liver blood plasma concentration of venlafaxine and EFA increased, and the rate of elimination is reduced.
In moderate or severe renal insufficiency total clearance of venlafaxine and EFA reduced, a T1/2 lengthens. Reduced total clearance is mainly observed in patients with CC less 30 ml / min.
Age and sex of the patient did not affect the pharmacokinetics.
Testimony
- Depression of various etiologies (Treatment and Prevention).
Dosage regimen
Tablets Velaksina® It recommended to be taken with food.
The recommended starting dose is 75 mg 2 admission (by 37.5 mg 2 times / day) daily. If after several weeks of treatment, no significant improvement, the daily dose can be increased to 150 mg (by 75 mg 2 times / day). If the opinion of a doctor, a higher dose of (major depression or other conditions, requiring hospital treatment), you can immediately assign 150 mg 2 admission (by 75 mg 2 times / day). Thereafter, the daily dose may be increased to 75 mg every 2-3 day to achieve the desired therapeutic effect. The maximum daily dose Velaksin® is 375 mg. After achieving the desired therapeutic effect, the daily dose can be gradually reduced to the minimum effective level. Length of the period, necessary to reduce the dose, It depends on the dose of, duration of therapy, as well as the individual sensitivity of the patient.
Supportive therapy and relapse prevention. Supportive therapy may continue 6 months or more. The drug is prescribed at the lowest effective doses, used in the treatment of depressive episodes.
At renal failure mild (CC > 30 ml / min) correction mode is not required. At renal failure moderate (CC 10-30 ml / min) the dose should be reduced by 25-50%. In connection with the elongation T1/2 venlafaxine and ego aktivnogo metabolite (EFA) such patients should take the entire dose 1 time / day. Not recommended if venlafaxine severe renal insufficiency (CC < 10 ml / min), since reliable data about the safety of such therapy are absent.
Patients, located at gemodialize, can receive 50% usual dose of venlafaxine after hemodialysis.
At mild hepatic insufficiency (prothrombin time less 14 sec) correction mode is not required. At moderate hepatic insufficiency (prothrombin time from 14 to 18 sec) the dose should be reduced by 50%. Not recommended if venlafaxine severe hepatic insufficiency, since reliable data about the safety of such therapy are absent.
In patients Seniors the drug should be used with caution due to the possibility of renal impairment. Use the smallest effective dose. By increasing the dose the patient should be under close medical supervision.
After receiving Velaksina® it is recommended to gradually reduce the dosage of the drug, at least, during the week and monitor the patient's condition, to minimize the risk, coupled with the abolition of the drug. Length of the period, necessary to reduce the dose, It depends on the dose of, duration of therapy, as well as the individual sensitivity of the patient.
Side effect
Most side effects are dose-. With long-term treatment of the severity and frequency of these effects is reduced majority, and there is no need for discontinuation.
In decreasing order of frequency: often ( ≥1%), infrequently (And ≥0.1% <1%), rarely (≥0.01% and <0.1% ), rarely (<0.01%).
From the digestive system: decreased appetite, constipation, nausea, vomiting, dry mouth; rarely – hepatitis.
Metabolism: increase in serum cholesterol, weight loss; infrequently – violation of liver function tests, giponatriemiya, syndrome of inadequate secretion of ADH.
Cardio-vascular system: arterial hypertension, flushing of the skin; infrequently – postural hypotension, tachycardia.
From the central and peripheral nervous system: unusual dreams, dizziness, insomnia, nervous anxiety, paresthesia, stupor, increased muscle tone, tremor, zevota; infrequently – apathy, hallucinations, muscle spasms, serotonergic syndrome; rarely – seizures, manic reactions, as well as the symptoms, resembling neuroleptic malignant syndrome.
From the urinary system: dizurija (primarily – difficulty initiating urination); infrequently – urinary retention.
On the part of the reproductive system: abnormal ejaculation, erection, anorgazmija; infrequently – decreased libido, menorragija.
From the senses: accommodation disturbances, midriaz, visual impairment; infrequently – dysgeusia.
Dermatological reactions: Sweating; infrequently – photosensitivity.
From the hematopoietic system: infrequently – bleeding into the skin (ecchymosis) and mucous membranes, thrombocytopenia; rarely – prolonged bleeding.
Allergic reactions: infrequently – skin rash; rarely – erythema multiforme, Stevens-Johnson syndrome; rarely – anaphylactic reactions.
Other: weakness, fatiguability.
After the abrupt cancellation Velaksina® or dose reduction possible fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, anxiety, alarm, nervous irritability, disorientation, hypomania, paresthesia, 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 (as well as any other antidepressant), especially after receiving high doses.
Contraindications
- Severe renal dysfunction (CC < 10 ml / min);
- Severe liver;
- Simultaneous MAO inhibitors;
- Childhood and adolescence up 18 years (safety and efficacy for these patients has not been proven);
- Or suspected pregnancy;
- Lactation (breast-feeding);
- Hypersensitivity to the drug.
FROM caution should be prescribed at the recent myocardial infarction, unstable angina, hypertension, tachycardia, a history of convulsions, ocular hypertension, angle-closure glaucoma, manic states history, predisposition to bleeding from the skin and mucous membranes, initial weight loss.
Pregnancy and lactation
Safety of Velaksina® during pregnancy has not been proven. Therefore, the use during pregnancy (or suspected pregnancy) possibly only, if the expected benefit to the mother outweighs the potential risk to the fetus.
Women of childbearing age We should use reliable methods of contraception during treatment with the drug and seek immediate medical attention in case of pregnancy or planning a pregnancy.
Venlafaxine and EFA metabolite are excreted in breast milk. The safety of these substances for newborn children is not proven, therefore, if necessary, taking the drug during lactation should decide the issue of termination of breastfeeding. If maternal treatment was completed shortly before the birth, a newborn may have symptoms of drug withdrawal.
Cautions
Abrupt cessation of therapy Velaksinom® (Like other antidepressants), especially when used in high doses, can cause withdrawal symptoms, and therefore it is recommended to remove the drug gradually reduce the dose. Length of the period, necessary to reduce the dose, It depends on the dose of, duration of therapy, as well as the individual sensitivity of the patient.
Patients with depressive disorders before any drug therapy should consider the likelihood of suicide attempts. Therefore, to reduce the risk of an overdose of the drug at the beginning of the treatment should be possible to apply a minimum effective dose, and the patient should be under close medical supervision.
In patients with affective disorders with antidepressant (incl. venlafaxine), may experience hypomanic or manic state. As with other antidepressants, venlafaxine should be used with caution in patients with a history of mania. Such patients need medical supervision.
Velaksin® (as well as other antidepressants) It should be used with caution in patients with a history of seizures. Treatment with venlafaxine should be interrupted in the event of seizures.
Precautions should be prescribed Velaksin® patients, recent myocardial infarction, 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. The treatment drug may increase heart rate, especially during the administration of high doses.
Patients should be warned of the need to consult a doctor immediately in the event of an eruption, urticaria elements or other 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 during dose escalation or clarification.
Patients, particularly the elderly, should be warned about the potential for dizziness and balance disorders feeling.
As with other serotonin reuptake inhibitors, venlafaxine may increase the risk of bleeding into the skin and mucous membranes. When treating patients, predisposed to such states, caution.
During the reception, venlafaxine, particularly under conditions of dehydration or reduction bcc (incl. in elderly patients and in patients, taking diuretics), Hyponatremia may occur and / or the syndrome of inadequate secretion of ADH.
During the administration of the drug can be observed mydriasis, and therefore recommended that the control of intraocular pressure in patients with, inclined to increase his suffering, or angle-closure glaucoma.
Conducted to date in clinical trials showed no tolerance to venlafaxine or dependence. Despite this, as well as other drugs in the treatment of, acting on the central nervous system, the physician should establish a close monitoring of patients for signs of drug abuse. Careful monitoring and surveillance are needed for patients, with a history of these symptoms indicate.
When assigning tablets Velaksina® patients with lactose intolerance should be considered lactose (84.93 mg per tablet 37.5 mg; 169.86 mg per tablet 75 mg).
In patients receiving venlafaxine should be particularly careful during electroconvulsive therapy, tk. experience with venlafaxine in these circumstances, there is no.
During treatment Velaksinom® Avoid drinking alcohol.
Use in Pediatrics
The safety and efficacy of the drug in children and adolescents under the age of 18 years not investigated.
Effects on ability to drive vehicles and management mechanisms
Despite, venlafaxine no effect on cognitive function and psychomotor, should be considered, that any drug therapy psychoactive drugs 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 of the extent and duration of the restrictions should be established physician.
Overdose
Symptoms: ECG changes (QT prolongation, bundle branch block, extension of the QRS complex), sinus or ventricular tachycardia, bradycardia, gipotenziya, convulsive status, change of consciousness (reduction of wakefulness). With an overdose of venlafaxine when taken with alcohol and / or other psychotropic drugs, reported fatal outcome.
Treatment: symptomatic therapy. Specific antidotes are not known. Recommended continuous monitoring of vital functions (respiratory and circulatory). The 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 Velaksina® MAO inhibitors is contraindicated. Admission Velaksina® You can not start less than 14 days after the end of therapy MAO inhibitors. If you are using a reversible inhibitor of MAO (moclobemide), This interval may be shorter (24 no). MAO inhibitor therapy can begin in no less than 7 days after the drug Velaksin® .
The simultaneous use of venlafaxine with lithium may improve the latter.
In an application with the pharmacokinetics of imipramine and its metabolite of venlafaxine is not changed EFA.
Intensifying the effects of haloperidol due to an increase in its concentration in the blood when combined with Velaksinom® .
While the use of diazepam pharmacokinetics of drugs and their main metabolites does not change significantly. Also, no effect on the psychomotor and psychometric effects of diazepam.
While the use of clozapine may be an increase in its level in the blood plasma and the development of side effects (eg, seizures).
While the use of risperidone (despite the increase in AUC of risperidone) Pharmacokinetics of total active ingredients (risperidone and ego aktivnogo metabolite) It did not change significantly.
With simultaneous use of venlafaxine and ethanol were noted decrease psychomotor reactions. However, during treatment with venlafaxine is not recommended to drink alcohol.
The metabolism of venlafaxine to form the active metabolite of EFA occur with the participation of CYP2D6 isoenzyme. Unlike many other antidepressants, dose of venlafaxine can not reduce while the use of CYP2D6 inhibitors, or in patients with a genetically determined reduction of CYP2D6, Since the total concentration of the active substance and metabolites (venlafaxine and EFA) It is not changed.
The main route of excretion of venlafaxine include metabolism by CYP2D6 and CYP3A4, so you should be very careful in the appointment of venlafaxine in combination with medicines, which are inhibitors of these two enzymes. The nature of this interaction has not been studied.
Venlafaxine is a relatively weak inhibitor of CYP2D6 and CYP1A2 isozyme suppresses activity, CYP2C9 и CYP3A4; so we should not expect its interaction with other drugs, metabolism involving the liver enzymes.
Cimetidine inhibits the metabolism of venlafaxine for “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 abnormal liver function).
There were no clinically significant interaction between venlafaxine and antihypertensive (incl. with beta-blockers, ACE inhibitors and diuretics) and hypoglycemic drugs.
As the plasma protein binding of venlafaxine and EFA is respectively 27% and 30%, not expected drug interactions, due to the violation of binding to plasma proteins.
When concomitantly with warfarin may increase the anticoagulant effect of the latter.
At simultaneous reception with indinavir, a decrease in the AUC of indinavir 28% and reducing its Cmax on 36%, wherein venlafaxine pharmacokinetic parameters are not changed and EFA. The clinical significance of this effect is unknown.
Conditions of supply of pharmacies
The drug is released under the prescription.
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.
