EFEVELON®
Active material: Venlafaxine
When ATH: N06AA
CCF: Antidepressant
ICD-10 codes (testimony): F31, F32, F33, F41.2
When CSF: 02.02.06
Manufacturer: Actavis hf. (Iceland)
DOSAGE FORM, STRUCTURE AND PACKAGING
Pills, coated orange, round, lenticular, labeled “V2” one side.
| 1 tab. | |
| venlafaxine (the hydrochloride) | 37.5 mg |
Excipients: lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, povidone K30, magnesium stearate, Purified water.
The composition of the shell: Opadry 03В23319 orange, gipromelloza, Titanium dioxide, polyethylene glycol 400 (PEG 400) (macrogol), dye “sunset yellow” FCF.
10 PC. – blisters (3) – packs cardboard.
Pills, coated orange, round, lenticular, with the risks on both sides, side risk and marking “V” on the one hand, risks and “4” on the other hand there are risks.
| 1 tab. | |
| venlafaxine (the hydrochloride) | 75 mg |
Excipients: lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, povidone K30, magnesium stearate, Purified water.
The composition of the shell: Opadry 03В23319 orange, gipromelloza, Titanium dioxide, polyethylene glycol 400 (PEG 400) (macrogol), dye “sunset yellow” FCF.
10 PC. – blisters (3) – packs cardboard.
Pharmacological action
Antidepressant, chemically not related to any class of antidepressants (tricyclic, tetracyclic or other), is a mixture of two active enantiomers.
The mechanism of the antidepressant effect of the drug is associated with its ability to potentiate the transmission of nerve impulses to the central nervous system. Venlafaxine and its main metabolite O-desmetilvenlafaksin (EFA) are strong serotonin and norepinephrine reuptake inhibitors and weak dopamine reuptake inhibitors. Besides, venlafaxine and EDV reduce beta-adrenergic reactivity as after a single dose, as well as with constant use. Venlafaxine and EFA equally effective influence on the reuptake of neurotransmitters.
Venlafaxine has no affinity for m-cholinergic receptors, 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 taking the drug orally, venlafaxine is well absorbed from the gastrointestinal tract.. After receiving a single dose of the drug 25-150 mg Cmax achieved in approximately 2.4 h and is 33-172 ng / ml. 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 absorptions do not change. Cmax EDV in blood plasma 61-325 ng/ml is reached in approximately 4.3 hours after injection.
The daily doses range 75-450 mg pharmacokinetics of venlafaxine and EDV are linear.
Distribution
With repeated administration Css venlafaxine and EFA reached within 3 days.
The binding of venlafaxine and EFA to plasma proteins is respectively 27% and 30%.
Metabolism
Subjected to intensive metabolism in the “first pass” through the liver. The major metabolite – O-desmethylvenlafaxine (EFA).
Deduction
T1/2 venlafaxine and EDV are respectively 5 and 11 no. EFA and other metabolites, as well as unchanged venlafaxine, excreted in the urine.
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 patients with moderate or severe renal impairment, the total clearance of venlafaxine and EDV is reduced.; a T1/2 increases. 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
- treatment of depression;
- prevention of relapse of depression.
Dosage regimen
The drug is taken orally, preferably at the same time of day, mealtime. Tablets cannot be chewed, washed down with liquid.
The recommended starting dose is 75 mg (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).
At moderate depression The recommended daily dose is 225 mg po 75 mg 3 times / day. If necessary, the dose can be increased at intervals of at least 4 days for 75 mg / day.
If necessary, use the drug in a higher dose – major depression or other conditions, requiring hospital treatment, – you can immediately prescribe the drug in a daily dose 150 mg (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.
Maximum daily dose of Efevelon® is 375 mg. After achieving the desired therapeutic effect, the daily dose can be gradually reduced to the minimum effective level.
Supportive therapy and relapse prevention continues for 6 months or more. The drug is prescribed in the minimum effective dose, used in the treatment of depressive episodes.
At renal failure mild (glomerular filtration rate is more than 30 ml / min) correction dosing regime is not required. At renal failure moderate (glomerular filtration rate 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. At severe renal insufficiency (glomerular filtration rate of less than 10 ml / min) the use of venlafaxine is not recommended, since experience with such therapy is limited. Patients, on hemodialysis, can receive 50% usual daily dose of venlafaxine after completion of hemodialysis.
At mild hepatic insufficiency (prothrombin time /PT/ less 14 sec) correction dosing regime is not required. At moderate hepatic insufficiency (PV from 14 to 18 sec) the dose should be reduced by 50%. At severe hepatic insufficiency use of Efevelon® not recommended, since experience with such therapy is limited.
Elderly patients dose adjustment is required, However (as with the prescription of other medications) Caution is required during treatment, eg, due to the possibility of renal dysfunction. In elderly patients, the drug should be prescribed at the lowest effective dose. By increasing the dose the patient should be under close medical supervision.
After finishing taking Efevelon® It is recommended to reduce the dose gradually, at least, for a week and monitor the patient’s condition in order to, to minimize the risk, coupled with the abolition of the drug. Period, required to completely stop taking the drug, depends on its dose, duration of treatment and individual characteristics of the patient.
Side effect
Most of the side effects listed below are dose dependent. With long-term treatment of the severity and frequency of these effects is reduced majority, and there is no need for discontinuation.
The frequency of side effects: often (≥1%), sometimes (≥0.1%, but <1%), rarely (≥0.01%, but <0.1%), rarely (<0.01%).
From the digestive system: decreased appetite, constipation, nausea, vomiting, dry mouth; sometimes – changes in liver function laboratory tests; rarely – hepatitis.
Metabolism: increase in serum cholesterol, weight loss; sometimes – giponatriemiya, syndrome of inadequate secretion of ADH.
Cardio-vascular system: often – arterial hypertension, flushing of the skin; sometimes – postural hypotension, tachycardia.
From the central and peripheral nervous system: unusual dreams, dizziness, insomnia, hypererethism, paresthesia, stupor, increased muscle tone, tremor; sometimes – apathy, hallucinations, muscle spasms, serotonin syndrome; rarely – seizures, manic reactions, as well as the symptoms, resembling neuroleptic malignant syndrome.
From the senses: often – accommodation disturbances, midriaz, blurred vision; sometimes – dysgeusia.
From the urinary system: dizurija (primarily – difficulty initiating urination); sometimes – urinary retention.
On the part of the reproductive system: abnormal ejaculation, erection, anorgazmija; sometimes – decreased libido, menorragija.
Dermatological reactions: Sweating; sometimes – photosensitivity reaction; rarely – erythema multiforme, Stevens-Johnson syndrome.
From the hematopoietic system: sometimes – bleeding into the skin (ecchymosis) and mucous membranes, thrombocytopenia; rarely – prolonged bleeding.
Allergic reactions: sometimes – skin rash; rarely – anaphylactic reactions.
Other: weakness, fatigue.
After abrupt withdrawal of Efevelon® or reducing its dose possible fatigue, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, alarm, 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.
Contraindications
- Simultaneous MAO inhibitors;
- Severe renal dysfunction (SKF<10 ml / min);
- Severe liver;
- Childhood and adolescence up 18 years;
- established or suspected pregnancy;
- Lactation;
- Hypersensitivity to the drug.
FROM caution the drug should be used in cases of recent myocardial infarction, unstable angina, hypertension, tachycardia, history of convulsive syndrome, increased intraocular pressure, angle-closure glaucoma, history of manic state, predisposition to bleeding of the skin and mucous membranes, with initially reduced body weight.
Pregnancy and lactation
The safety of venlafaxine during pregnancy has not been proven., therefore use during pregnancy (or suspected pregnancy) possibly only, if the potential benefit to the mother outweighs the potential risk to the fetus.
Women of childbearing age should be warned about this before starting treatment and should immediately consult a doctor if they become pregnant or plan to become pregnant during treatment with the drug.
Venlafaxine and its metabolite are excreted in breast milk. The safety of these substances for newborn children is not proven, Therefore, taking venlafaxine during breastfeeding is not recommended. If it is necessary to take the drug during lactation, the issue of stopping breastfeeding should be decided..
If maternal treatment was completed shortly before the birth, a newborn may have symptoms of drug withdrawal.
Cautions
For depressive disorders, the possibility of suicide attempts should be considered before starting any drug therapy..
To reduce the risk of overdose, the initial dose of the drug should be as low as possible, 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.
Ephevelon® (as well as other antidepressants) It should be used with caution in patients with a history of seizures. Treatment should be interrupted if epileptic seizures occur.
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 cases, while taking Efevelon® a dose-dependent increase in blood pressure was noted, In this regard, we recommend regular monitoring of blood pressure, especially during dose escalation or clarification.
While taking Efevelon® possible increase in heart rate, especially when used in high doses. Caution is recommended for tachyarrhythmia.
Patients, particularly the elderly, should be warned about the possibility of dizziness and loss of balance.
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.
While taking Efevelon®, particularly under conditions of dehydration or reduction bcc (incl. in elderly patients and 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, Therefore, it is recommended to monitor intraocular pressure in patients, inclined to increase his suffering, or angle-closure glaucoma.
There is insufficient data on the use of venlafaxine in patients, recently suffered myocardial infarction and suffering from decompensated heart failure. The drug should be prescribed with caution in such patients..
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 observation is necessary for patients, with a history of such symptoms.
Despite, venlafaxine no effect on cognitive function and psychomotor, should be considered, that any drug therapy with psychoactive drugs may impair judgment, thinking or performing motor functions. This should warn the patient before treatment. If such effects occur, the degree and duration of restrictions should be determined by a physician..
While taking Efevelon® special care should be taken during electroconvulsive therapy, tk. experience with venlafaxine in these circumstances, there is no.
Taking Efevelon® 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 discontinuation of the drug Efevelon®.
During treatment with Efevelon® Alcohol consumption is not recommended.
When prescribing Efevelon® Patients with lactose intolerance should take into account, what in 1 tab. 25 mg contains 56.62 Lactose mg; in 1 tab. 37.5 mg – 84.93 Lactose mg; in 1 tab. 50 mg – 113.24 Lactose mg, in 1 tab. 75 mg – 169.86 Lactose mg.
Use in Pediatrics
Safety and effectiveness of the drug Efevelon® in children and adolescents under the age of 18 years not proven.
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 use of activated carbon is indicated to reduce drug absorption. Do not induce vomiting due to aspiration hazard. Venlafaxine and EFA are not displayed during dialysis.
Drug Interactions
Concomitant use of MAO inhibitors and venlafaxine is contraindicated.
When taking Efevelon simultaneously® with warfarin, the anticoagulant effect of the latter may be enhanced.
When used simultaneously with haloperidol, the effect of the latter may be enhanced due to an increase in its concentration in the blood plasma.
Venlafaxine does not affect the pharmacokinetics of lithium.
When used simultaneously with imipramine, the pharmacokinetics of venlafaxine and its metabolite EDV do not change..
With simultaneous use of Efevelon® with diazepam, pharmacokinetics of both active substances and their main metabolites, It 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.
Ephevelon® enhances the effect of alcohol on psychomotor reactions.
Medications, whose metabolism occurs with the participation of cytochrome P450 isoenzymes: CYP2D6 converts venlafaxine to the active metabolite EDV. Unlike many other antidepressants, the dose of venlafaxine may not be reduced when administered simultaneously with inhibitors of the CYP2D6 isoenzyme, or in patients with a genetically determined decrease in the activity of the CYP2D6 isoenzyme, Since the total concentration of the active substance and metabolites (venlafaxine and EFA) it won't change. The main route of elimination of venlafaxine involves metabolism involving the isoenzymes CYP2D6 and CYP3A4, Therefore, special care should be taken when prescribing Efevelon® in combination with inhibitors of these isoenzymes. This drug interaction has not yet been studied. Venlafaxine – a relatively weak inhibitor of the CYP2D6 isoenzyme and does not suppress the activity of the CYP1A2 isoenzymes, SYP2C9 and SYP3A4; so we should not expect its interaction with other drugs, in the metabolism of which these isoenzymes are involved.
Cimetidine inhibits the metabolism of venlafaxine for “first pass” through the liver and does not affect the pharmacokinetics of EDV. 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).
When taken simultaneously with indinavir, the pharmacokinetics of the latter changes (decrease in AUC by 28% and Cmakh – on 36%), and the pharmacokinetics of venlafaxine and EDV do not change. The clinical significance of these changes is unknown.
Clinically significant interaction of venlafaxine with antihypertensive drugs (incl. beta-blockers, ACE inhibitors and diuretics) and hypoglycemic drugs were not detected.
Ephevelon® does not affect the concentration of drugs in blood plasma, having a high degree of protein binding.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored in a dry, inaccessible to children at temperature not exceeding 30 ° C. Shelf life – 3 year.
