VELAKSIN (capsules)
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
Capsules of the prolonged action hard gelatin, self-closing, with colourless transparent body and orange-brown cap; contents of capsules – a mixture of white and yellow pellet, with little or no odor.
| 1 caps. | |
| venlafaxine (the hydrochloride) | 75 mg |
| -“- | 150 mg |
Excipients: microcrystalline cellulose, sodium chloride, ethyl cellulose, talc, Dimethicone, potassium chloride, kopovydon, Colloidal anhydrous silica, Xanthan Gum, iron oxide yellow.
Composition of gelatin capsules: Titanium dioxide, iron oxide yellow, gelatin.
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, Cmax venlafaxine and EFA (the major metabolite) in plasma achieved within 6.0 ± 1.5 and 8.5 ± 2.2 h, respectively. The rate of absorption of venlafaxine capsules prolonged action below its rate of elimination. Therefore T1/2 After the appointment of venlafaxine capsules prolonged action (15± 6 h) represents the actual T1/2 suction, than T1/2 distribution (5± 2 h), celebrated after the appointment of the drug in pill form.
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.
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 (incl. If there is anxiety), treatment and relapse prevention.
Dosage regimen
Capsule prolonged action should be taken with food. Each capsule should be swallowed whole and zapiwati liquid. The capsules cannot be divided, grind, chewed or placed in water. Daily dose should be taken in one go (in the morning or evening) each time at approximately the same time.
At depression The recommended starting dose is 75 mg 1 time / 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 1 time / day. Thereafter, the daily dose may be increased to 75 mg every 2 a week or more (but not more than 4 day) to achieve the desired therapeutic effect. The maximum daily dose Velaksin® is 350 mg. After achieving the desired therapeutic effect, the daily dose can be gradually reduced to the minimum effective level.
Supportive therapy and relapse prevention. Depression treatment should continue for at least 6 Months. When stabilizing therapy and therapy to prevent recurrence or new episodes of depression, the drug is prescribed in doses, proven. The doctor should regularly, no less 1 times a 3 Months, monitor the effectiveness of long-term therapy Velaksinom®.
Patients, host Velaksin® in pill form can be translated into taking the drug in capsules prolonged action with the appointment of equivalent dose 1 time / day. However, the individual may require dose adjustment.
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.
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. If the drug in high doses applied over 6 weeks, the lower dose for at least 2 weeks. 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 (<1/10 and >1/100), infrequently (<1/100 and >1/1000), rarely (<1/1000), rarely (<1/10 000).
From the body as a whole: weakness, fatiguability, chills, fever.
From the digestive system: decreased appetite, constipation, nausea, vomiting, dry mouth, abdominal pain; infrequently – bruxism, reversible increases in liver enzymes; rarely – gastrointestinal bleeding; rarely – hepatitis.
From the central and peripheral nervous system: headache, dizziness, insomnia, excitation, drowsiness; often – unusual dreams, anxiety, confusion, paresthesia, increased muscle tone, tremor; infrequently – apathy, hallucinations, myoclonus; rarely – ataxia, speech disorders, mania or gipomaniya, symptoms, resembling neuroleptic malignant syndrome, serotonergic syndrome, seizures; rarely – delirium, extrapyramidal disorder (including dyskinesia, dystonia, pozdnyaya dyskinesia), agitation/akathisia.
Cardio-vascular system: arterial hypertension, dilation of blood vessels (hot flushes), cardiopalmus; infrequently – orthostatic hypotension, fainting, tachycardia; rarely – the type of arrhythmia “pirouette”, QT prolongation, ventricular tachycardia, ventricular fibrillation.
From the senses: accommodation disturbances, midriaz, visual impairment, noise in ears; infrequently – dysgeusia.
From the hematopoietic system: infrequently – bleeding into the skin (ecchymosis) and mucous membranes; rarely – thrombocytopenia, prolonged bleeding; rarely – agranulocytosis, aplasticheskaya anemia, neutropenia, pancytopenia.
Dermatological reactions: increased perspiration; infrequently – photosensitivity; rarely – alopecia.
Metabolism: increase in serum cholesterol, weight loss; infrequently – giponatriemiya, syndrome of inadequate secretion of ADH, violation of the liver samples; rarely – elevated prolactin levels.
From the urinary system: infrequently – urinary retention.
On the part of the reproductive system: abnormal ejaculation, erection, anorgazmija; infrequently – decreased libido, menstrual irregularities, menorragija; rarely – galactorrhea.
On the part of the musculoskeletal system: arthralgia, myalgia; infrequently – muscle spasm; rarely – raʙdomioliz.
Allergic reactions: itching, rash; infrequently – angioedema, maculo-papular rash, hives; rarely – erythema multiforme, Stevens-Johnson syndrome.
Children have experienced the following side effects: abdominal pain, chest pain, tachycardia, refraining from eating, weight loss, constipation, nausea, ecchymosis, nose bleed, midriaz, myalgia, dizziness, emotional lability, tremor, hostility, suicidal thoughts.
After the abrupt cancellation Velaksina® or dose reduction is 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 less than 10 ml / min);
- Severe liver;
- Simultaneous MAO inhibitors;
- Up to 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, Heart Failure, diseases of the coronary arteries, ECG changes (incl. QT prolongation), violations elektrolitnogo balance, 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
Patients with depressive disorders before any drug therapy should consider the likelihood of suicide attempts. Therefore, to reduce the risk of abuse and/or overdose at the beginning of treatment should be issued only a small number of capsules, and the patient should be under close medical supervision.
Aggressive behaviour was reported while taking venlafaxine (especially at the beginning of treatment and after withdrawal of the drug).
Use venlafaxine may cause agitation, that clinically resembles akatiziû, characterized by a concern with the need to move, often combined with the inability to sit or stand on the spot. This is most commonly observed during the first few weeks of treatment. If you experience these symptoms increasing doses can have an adverse effect and should consider whether to continue taking the drug.
In patients with affective disorders with antidepressant (incl. venlafaxine), may experience hypomanic or manic state. As with other antidepressants, venlafaxine should be administered with caution to patients with delusions and/or gipomaniej in history. Such patients need medical supervision.
Velaksin® (as well as other antidepressants) It should be used with caution in patients with a history of seizures. Venlafaxine treatment should be interrupted when an epileptic seizures or raising their frequency.
The caution should appoint drug simultaneously with the antipsychotic drug, tk. may develop symptoms, reminiscent neirolepticeski Malignant Syndrome.
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.
The caution should be appointed patients taking venlafaxine, 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.
Against the backdrop of the admission preparation possible development orthostatic hypotension.
As with other antidepressants, influencing the exchange of serotonin, 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.
In patients receiving venlafaxine should be particularly careful during electroconvulsive therapy, tk. experience with venlafaxine in these circumstances, there is no.
Be wary appoint drug in kidney and liver failure.
Safety and efficacy of venlafaxine with tools, reducing body weight, incl. phentermine, not set, Therefore, their simultaneous use (as the use of venlafaxine as monotherapy to lower body mass index) not recommended.
Clinically significant increase in the level of serum cholesterol observed in some patients, receiving venlafaxine for at least 4 Months. Therefore, in the long admission preparation should be the control of serum cholesterol.
After discontinuation of the drug, especially sudden, You may experience withdrawal symptoms. The risk of withdrawal symptoms may depend on several factors, incl. course durations and doses, as well as reducing dose speed. Withdrawal symptoms (dizziness, sensory damage/etc.. paresthesia/, sleep disorders/etc.. insomnia and unusual dreams/, agitation or anxiety, nausea and / or vomiting, tremor, Sweating, headache, diarrhea, heart palpitations and and increased emotional lability) usually have a small or moderate intensity, However, some patients they may be severe. Usually seen in the first days after the drug, Although there have been sporadic reports of the occurrence of such symptoms in patients, accidentally have missed one dose. Typically, these phenomena are alone during 2 weeks. However, some patients they may be longer (2-3 month or more). So before canceling the venlafaxine recommended gradually reducing the dose over several weeks or months depending on the patient's condition
Use in Pediatrics
The safety and efficacy of the drug in children and adolescents under the age of 18 years not investigated. Increase the likelihood of suicidal behavior, and hostility, in clinical trials is more common among children and adolescents, receiving antidepressants, and compared with groups, receiving placebo.
Effects on ability to drive vehicles and management mechanisms
It should be taken into account, 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. In the same time, their simultaneous application enhances the effects dezipramina – the primary metabolite of imipramine – and its another metabolite 2-imipramine, Although the clinical significance of this phenomenon is unknown.
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, When this elongates and increases protrombinovoe time MHO.
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 – 2 year.
