Alventa

Alventa is an antidepressant that has a chemical structure that is not similar to the structure of antidepressant drugs from other categories (tricyclics, tetracyclics, etc.). The drug contains 2 racemic enantiomeric forms with therapeutic activity.

The antidepressant effect of the active drug element - venlafaxine - develops with the potentiation of neurotransmitter effects on the central nervous system. The component does not show affinity for the endings of benzodiazepines, opiates, phencyclidines (CCP), as well as for the element NMDA, histamine H1 and cholinergic endings of muscarinic and α-adrenergic receptors.

Indications Alventa

It is used for the treatment of episodes of severe depression, GAD, and also for anxiety that has a social variety (social phobia). In addition, it is prescribed to prevent the development of episodes of severe depression.

[1], [2]

Release form

The release of the drug substance is implemented in capsules with an extended effect - 14 pieces inside the package. In the box - 1, 2 or 4 packs.

[3]

Pharmacodynamics

Venlafaxine with its main metabolic element (EFA) are powerful SSRIs, as well as IOPs, but at the same time slightly slow down the reverse dopamine seizure. In addition, the drug has an effective effect on the processes of reverse neurotransmitter seizure and reduces the reactivity of β-adrenergic receptors of the CNS. In addition, venlafaxine does not suppress the activity of MAOIs. 

[4]

Pharmacokinetics

Venlafaxine is almost completely (about 92%) absorbed by oral administration, but undergoes extensive general metabolic processes (an EFA that has an active metabolic component is formed), due to which the bioavailability of drugs is approximately 42 ± 15%.

When medications are consumed, plasma Cmax values of venlafaxine and EFA are determined after the expiration of, respectively, 6.0 ± 1.5, as well as 8.8 ± 2.2 hours.

The rate of absorption of the drug in capsules with a prolonged effect is lower compared with the rate of excretion. Because of this, the explicit component half-life term (15 ± 6 hours) is truly the half-life of absorption instead of the standard half-life term (5 ± 2 hours), noted in the case of tablets with a fast release type.

The drug is widely distributed inside the body. Indicators of intraplasma synthesis of drugs with proteins are 27 ± 2% with values of 2.5-2215 ng / ml. The level of the analogous synthesis of the EFA element is 30 ± 12% with the indices of 100-500 ng / ml.

When absorbed, venlafaxine undergoes extensive general intrahepatic metabolism. The main metabolic component of the substance is EFA, but in addition it is transformed into N-desmethylvenlafaxine with N-, as well as O-didezmetilvenlafaksin with other non-essential decomposition products.

About 87% of the dose of the medicament is excreted with the urine for 48 hours after the application of 1 single dose - in the form of venlafaxine (by 5%), and also unbound EFA (by 29%), bound EFA (by 26%) and other metabolic elements (by 27%).

With long-term administration of drugs, there is no accumulation of venlafaxine inside the body.

[5], [6]

Dosing and administration

The capsule is required to be used in combination with food, swallowed whole and washed down with ordinary water. It is forbidden to put the capsule in water, crush, open or chew it. Use the drug 1-fold per day, at the same time - in the morning or in the evening.

With depression.

In the case of depression, it is prescribed to administer 75 mg of the drug one time a day. After 14 days, the dose can be doubled (0.15 g), with a 1-fold dose per day, in order to obtain a further improvement in the clinical condition. If required, the dosage can be increased to 225 mg per day with mild stages of the disease, as well as up to 375 mg per day with its heavy varieties.

Each increase in servings should occur at 37.5-75 mg with 2-week or more intervals (in general, the interval should reach at least 4-day).

In case of using 75 mg of Alventa, antidepressant activity develops after 14 days of therapy.

Sociophobia and GAD.

During the day, with special forms of anxiety (among which is social phobia), it is required to apply 75 mg of the substance 1-fold. To get clinical improvement, after 14 days, you can increase the portion to 0.15 g 1-fold per day. Also, if needed, the daily dosage can be increased to a single dose of 225 mg. It is allowed to increase the portion by 75 mg per day with 14-day or more intervals (the minimum period is 4 days).

In the case of the introduction of 75 mg of the drug anxiolytic activity is observed after 7 days of treatment.

Relapse prevention and supportive measures.

Doctors recommend to introduce drugs for depressive episodes for at least 0.5 years. Supporting activities and the prevention of relapses or new processes of violation are carried out with the use of portions that turned out to be effective before. The doctor must constantly, at least 1-fold for 3 months, monitor the effectiveness of long-term treatment.

Lack of kidney or liver function.

In case of problems with kidney function (GFR values <30 ml per minute), the daily dose of venlafaxine is required to be reduced by half. Persons undergoing hemodialysis also need to reduce the dosage of drugs by half. It is necessary to complete a hemodialysis session before taking the substance.

In the case of a moderate degree of insufficiency of the liver function, a portion of the drug is also reduced by 50%. Sometimes the dosage may be reduced by more than 50%.

Continuous, supportive or long-term treatment.

The acute stage of severe depression should be treated for at least a few months or longer. In the case of specific forms of anxiety (also in social phobia), a long treatment cycle is also required.

Due to the high probability of the appearance of negative signs depending on the size of the portion, the dosage can be increased only after performing a clinical assessment. It is necessary to maintain the minimum effective portion.

Removal of venlafaxine.

With the abolition of therapy you need a gradual reduction in dosage. If Alventa was used for more than 1.5 months, you should reduce the portion for at least 14 days.

Use Alventa during pregnancy

Use of Alventa in case of suspicion of conception, pregnancy or breastfeeding is prohibited.

[7], [8], [9], [10]

Contraindications

The main contraindications:

• strong personal sensitivity regarding venlafaxine or other elements of the medication;
• combination with any MAOI, and at the same time for 2 weeks from the moment of their introduction (it is necessary to cancel the therapy with venlafaxine at least 7 days before the introduction of any MAOI);
• increased blood pressure in the severe phase (before the course starts, they are 180/115 mm Hg or more);
• glaucoma;
• urinary disorders due to weak urinary outflow (for example, due to diseases affecting the prostate);
• failure of renal or hepatic function in severe.

Side effects Alventa

The development of adverse events is dose-dependent. The frequency and severity of disorders may increase during therapy.

Among the most frequent negative manifestations are insomnia, nervousness, dryness that affects the oral mucous membranes, hyperhidrosis, nausea, constipation, asthenia, dizziness, drowsiness, and also disorder of orgasm and ejaculation.

Other violations:

• systemic disorders: chills, anaphylaxis, asthenia, angioedema, and photosensitivity;
• damage to the CVS function: a decrease or increase in blood pressure values, tachycardia, and in addition orthostatic collapse, vasodilation (often reddening of the skin on the face or the appearance of heat), ventricular blinking, prolongation of the QT-interval values, and with it ventricular tachycardia (a kind of "pirouette is included ") Or loss of consciousness;
• disorders of the gastrointestinal tract: constipation, nausea, loss of appetite, gnash and vomiting;
• problems associated with the blood system and lymph: thrombocytopenia, ecchymosis, bleeding in the gastrointestinal tract or from mucous membranes, as well as prolongation of bleeding and blood dyscrasias (among them aplastic anemia, neutrocytes or pancytopenia and agranulocytosis);
• disorders of metabolic processes: an increase in prolactin levels, a decrease or increase in weight, an increase in cholesterol serum levels, abnormal liver function levels, diarrhea, hyponatremia, pancreatitis, bruxism, hepatitis, and Parhon's syndrome;
• Lesions associated with NA: problems with sleep, insomnia, dryness in the area of oral mucous membranes, nervousness, weakening of libido, paresthesia and dizziness, and with it increased muscle tone, sedation, apathy, convulsions and tremor. In addition, myoclonus, ZNS, coordination disorders, manic symptoms, hallucinations, serotonin intoxication, extrapyramidal disorders (among them dyskinesias and dystonia), ear noise, late dyskinesia, epileptic seizures, rhabdomyolysis and symptoms similar to ZNS are noted. Also encountered are thoughts of suicide and corresponding behavior, delirium or agitation, which has a psychomotor nature, aggression and depersonalization;
• impaired respiratory function: pulmonary eosinophilia, yawning, and flu-like syndrome;
• epidermal lesions: rash, SJS, erythema multiforme, hyperhidrosis (also at night), PET, and alopecia;
• disorders of the function of the sense organs: change in taste, accommodation disturbances and tinnitus;
• problems with the work of the urinary organs and kidneys: urinary retention or dysuria (mainly difficulties with the beginning of the urinary process);
• disorders of the breasts and reproductive organs: anorgasmia, urinary disorders (often problems with the onset of urination), orgasm disorders (men) or ejaculation and impotence, and in addition to this menstruation cycle disorder (their strengthening or irregularity - metrorrhagia or menorrhagia), orgasm disorders ( women) and pollakiuria;
• lesions of the visual organs: increased pupil size, glaucoma, accommodative disorder, and vision problems.

Signs of cancellation were observed in people who suffered from depression or particular forms of anxiety. With the abrupt cancellation of drugs or a strong or gradual decrease in its portion (at different dosages), the appearance of new signs is possible. The increase in the frequency of development of new manifestations is associated with an increase in the size of portions and the duration of therapy.

Observed such withdrawal symptoms were: diarrhea, dry oral mucous membranes, anxiety, aimless walking, anxiety with loss of appetite, mental disturbance and weakness, and in addition paresthesia, hypomania, nervousness with headaches, hyperhidrosis, dizziness, drowsiness, vomiting with insomnia, tremor, nausea, flu-like syndrome and vivid dreams. These manifestations were light and passed on their own.

In case of cancellation of antidepressants, it is required to monitor the patient's condition, proportionally reducing the portion of venlafaxine. The duration of the dosage reduction period is determined by the portion itself, the patient’s personal sensitivity and the duration of therapy.

Overdose

In post-marketing testing, poisoning was noted mainly when using the drug with alcohol or other medicines.

Often, intoxication develops tachycardia, mydriasis, vomiting, changes in consciousness (from drowsiness to coma) and seizures. Among other symptoms: changes in ECG indications (increase in QRS complex, prolongation of QT-interval marks or bundle of His), bradycardia, dizziness, ventricular tachycardia, decrease in blood pressure and death.

In the case of overdose, because of the toxic properties of venlafaxine, patients have an increased chance of suicide, due to which it is necessary to use the minimum amount of the drug that provides the desired result - to reduce the possibility of poisoning. Fatal outcome is possible with venlafaxine intoxication in combination with other drugs or alcohol.

It is necessary to clean the respiratory ducts, ensuring the passage of oxygen and, if necessary, carry out mechanical ventilation. You also need to perform symptomatic and supportive treatment procedures and closely monitor the heart rate and the work of other organs important for life.

With a high likelihood of aspiration, one cannot induce vomiting. Gastric lavage is possible if it is carried out shortly after taking the drug or when the corresponding symptoms appear. Acceptance of activated carbon is also able to reduce the absorption of drugs. Dialysis, forced diuresis, hemoperfusion, and also exchange hemotransfusion are ineffective. There are no antidotes for venlafaxine.

Interactions with other drugs

Application with IMAO.

Combining medication and MAOI is prohibited.

People who canceled the introduction of an MAO shortly before taking the drug, or who completed treatment with Alventa shortly before treatment with the MAO, experienced side effects of a severe nature. Among these are vomiting, dizziness, convulsions, tremor, seizures, nausea, profuse sweating and fever combined with NNS and convulsions (can lead to death).

It is allowed to start the administration of venlafaxine after at least 2 weeks from the end of IMAO-therapy.

The term between the abolition of the use of reversible MAOIs, the use of moclobemide and the start of taking Alventa should last at least 2 weeks. With the introduction of an MAOI at the stage of transferring a person from moklobemid to Alvent, the term for drug replacement should last at least 1-week.

Medications that affect the function of the central nervous system.

In connection with the principle of medical effect of venlafaxine and a high probability of serotonin intoxication, it is necessary to be extremely careful to combine medication and substances with a possible effect on the process of serotonergic transmission of neural impulses (for example, SSRIs, triptans or lithium).

Indinavir.

The combination of the drug and indinavira leads to a decrease in the AUC and Cmax values of the latter - by 28%, as well as 36%, respectively. Indinavir does not change the pharmacokinetic parameters of venlafaxine and EFA.

Warfarin.

In persons who used warfarin, at the start of treatment with Alventa, anticoagulant activity may increase, as well as PTV levels may increase.

Cimetidine.

In the elderly and people with liver problems who use the drug with cimetidine, the therapeutic interaction has not been investigated, therefore, such patients should be monitored for clinical control.

Ethanol.

When using venlafaxine you can not drink alcohol.

Substances that slow down the activity of CYP2D6.

CYP2D6 isoenzyme, which is involved in genetic polymorphism in relation to metabolic processes of many antidepressants, turns the element venlafaxine into the main metabolic component of EFA, which has medicinal activity. Therefore, we can expect the development of interaction with the sharing of drugs and agents that slow down the effect of CYP2D6.

Combinations that cause a weakening of the transformation processes of venlafaxine into EFA, theoretically, are able to increase serum indicators of venlafaxine and reduce EFA values.

Hypoglycemic and antihypertensive drugs.

Upon completion of drug therapy, there is an increase in the values of clozapine, which entails the temporary appearance of adverse symptoms, including seizures seizures.

Metoprolol.

The combination of the drug with metoprolol causes an increase in the plasma level of the latter, while not leading to a change in the indices of its active metabolic component, α-hydroxymetoprolol. The clinical consequences of such an effect for individuals with elevated BP values are not defined, therefore, it is necessary to very carefully combine these drugs.

Haloperidol

It should be borne in mind that the combined use of drugs and haloperidol reduces clearance and increases the Cmax and AUC, while leaving unchanged the term half-life of haloperidol. There is no information regarding the clinical significance of this interaction.

[11], [12],

Storage conditions

Alventa can be stored in a closed place for small children. Temperature values - not higher than 30 ° C.

Shelf life

Alventa can be used within the 5-year term since the sale of the drug substance.

[13]

Application for children

It is impossible to appoint in pediatrics (before the 18th anniversary).

[14]

Analogs

Analogues of drugs are the means Velaksin, Dapfiks, Venlafaksin with Velafax, Voksemel, Efevelon with Venlaksor, Newevelong and Venlift OD.

[15], [16]