Alventa

Alventa is an antidepressant with 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 that have therapeutic activity.

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

Indications Alventa

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

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Release form

The medicinal substance is released in capsules with an extended effect - 14 pieces per package. In a box - 1, 2 or 4 packages.

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Pharmacodynamics

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

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Pharmacokinetics

Venlafaxine is almost completely (about 92%) absorbed when taken orally, but undergoes extensive general metabolic processes (an active metabolic component is formed - AMC), due to which the bioavailability values of the drug are approximately 42±15%.

When using the drug, plasma values of Cmax of venlafaxine and ODV are determined after 6.0±1.5 and 8.8±2.2 hours, respectively.

The rate of drug absorption in extended-release capsules is lower than the rate of excretion. Because of this, the apparent half-life of the component (15±6 hours) is truly the half-life of absorption instead of the standard half-life (5±2 hours) observed in the case of immediate-release tablets.

The drug is widely distributed within the body. The indicators of intraplasmic synthesis of the drug with proteins are 27±2% with values of 2.5-2215 ng/ml. The level of similar synthesis of the element ODV is 30±12% with values of 100-500 ng/ml.

When absorbed, venlafaxine undergoes extensive general intrahepatic metabolism processes. The main metabolic component of the substance is ODV, but in addition, it is transformed into N-desmethylvenlafaxine with N-, as well as O-didesmethylvenlafaxine with other minor decay products.

Approximately 87% of the drug dose is excreted in the urine within 48 hours of taking a single dose - in the form of venlafaxine (5%), as well as unbound venlafaxine (29%), bound venlafaxine (26%) and other metabolic components (27%).

With prolonged administration of the drug, accumulation of venlafaxine in the body does not occur.

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Dosing and administration

The capsule must be taken with food, swallowed whole and washed down with plain water. It is forbidden to put the capsule in water, crush, open or chew it. The medicine is taken once a day, at the same time - in the morning or in the evening.

For depression.

In case of depression, it is prescribed to administer 75 mg of the medication once a day. After 14 days, the dose can be doubled (0.15 g), with 1 dose per day - to achieve further improvement of the clinical condition. If necessary, the dosage can be increased to 225 mg per day in mild stages of the disease, and up to 375 mg per day in its severe varieties.

Each increase in dosage should be by 37.5-75 mg at intervals of 2 weeks or more (in general, the interval should be at least 4 days).

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

Social phobia and GAD.

For special forms of anxiety (including social phobia), it is necessary to use 75 mg of the substance once a day. To achieve clinical improvement, after 14 days, the dose can be increased to 0.15 g once a day. Also, if necessary, the daily dosage can be increased to 225 mg once a day. The dose can be increased by 75 mg per day at 14-day or more intervals (minimum interval is 4 days).

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

Relapse prevention and supportive measures.

Doctors recommend administering drugs for depressive episodes for at least 0.5 years. Supportive measures and prevention of relapses or new processes of the disorder are carried out using doses that have proven effective previously. The doctor must constantly, at least once every 3 months, monitor the effectiveness of long-term treatment.

Insufficiency of kidney or liver function.

In case of problems with kidney function (SCF values are <30 ml per minute), it is necessary to reduce the daily dose of venlafaxine by half. People undergoing hemodialysis sessions also need to reduce the dosage of the drug by half. It is necessary to finish the hemodialysis session before taking the substance.

In case of moderate liver failure, the dose of the medication is also reduced by 50%. Sometimes the dosage can be reduced by more than 50%.

Continuous, maintenance or long-term treatment.

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

Due to the high potential for dose-related adverse effects, dosage increases should only be made after clinical evaluation. The minimum effective dose should be maintained.

Discontinuation of venlafaxine.

When discontinuing therapy, the dosage should be gradually reduced. If Alventa has been used for more than 1.5 months, the dose should be reduced for at least 14 days.

Use Alventa during pregnancy

It is prohibited to use Alventa if you suspect you are pregnant, are pregnant or are breastfeeding.

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Contraindications

Main contraindications:

• strong personal sensitivity to venlafaxine or other components of the drug;
• combination with any MAOI, and at the same time for 2 weeks from the moment of their administration (therapy with venlafaxine must be discontinued at least 7 days before the administration of any MAOI);
• increased blood pressure values in the severe phase (before the start of the course they are 180/115 mm Hg or more);
• glaucoma;
• urinary disorders due to weak urinary outflow (for example, due to diseases affecting the prostate);
• severe renal or hepatic insufficiency.

Side effects Alventa

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

Among the most common adverse effects are: insomnia, nervousness, dryness affecting the oral mucosa, hyperhidrosis, nausea, constipation, asthenia, dizziness, drowsiness, as well as orgasmic and ejaculatory disorders.

Other violations:

• systemic disorders: chills, anaphylaxis, asthenia, angioedema and photosensitivity;
• damage to the function of the cardiovascular system: a decrease or increase in blood pressure, tachycardia, and also orthostatic collapse, vasodilation (often reddening of the skin on the face or the appearance of fever), ventricular fibrillation, prolongation of the QT interval, and along with this ventricular tachycardia (including the “pirouette” variety) or loss of consciousness;
• gastrointestinal disorders: constipation, nausea, loss of appetite, teeth grinding and vomiting;
• problems associated with the blood system and lymph: thrombocytopenia, ecchymosis, bleeding in the gastrointestinal tract or from the mucous membranes, as well as prolongation of the bleeding period and blood dyscrasias (including aplastic anemia, neutro- or pancytopenia and agranulocytosis);
• metabolic disorders: increased prolactin levels, decreased or increased weight, increased serum cholesterol levels, abnormal liver function tests, diarrhea, hyponatremia, pancreatitis, bruxism, hepatitis, and Parhon syndrome;
• Lesions associated with the nervous system: sleep problems, insomnia, dry mouth, nervousness, decreased libido, paresthesia and dizziness, along with increased muscle tone, sedation, apathy, seizures and tremor. In addition, myoclonus, NMS, coordination disorders, manic symptoms, hallucinations, serotonin intoxication, extrapyramidal disorders (including dyskinesia and dystonia), tinnitus, late-phase dyskinesia, epileptic seizures, rhabdomyolysis and signs similar to NMS are observed. Suicidal thoughts and behavior, delirium or agitation of a psychomotor nature, aggression and depersonalization are also observed;
• respiratory dysfunction: pulmonary eosinophilia, yawning, and flu-like syndrome;
• epidermal lesions: rashes, SJS, erythema multiforme, hyperhidrosis (also at night), TEN and alopecia;
• disorders of sensory function: changes in taste sensations, accommodation disorders and tinnitus;
• problems with the functioning of the urinary organs and kidneys: urinary retention or dysuria (mainly difficulties with the beginning of the urinary process);
• disorders of the mammary glands and reproductive organs: anorgasmia, urinary disorders (often problems with the onset of urination), orgasmic disorders (men) or ejaculation and impotence, as well as menstrual cycle disorders (increased or irregular menstruation – metrorrhagia or menorrhagia), orgasmic disorders (women) and pollakiuria;
• damage to the visual organs: enlarged pupils, glaucoma, accommodation disorder and vision problems.

Withdrawal symptoms have been observed in people who suffered from depression or specific forms of anxiety. With abrupt withdrawal of the drug or a strong or gradual reduction in its dose (at different dosages), new symptoms may appear. An increase in the frequency of new manifestations is associated with an increase in the dose size and duration of therapy.

Withdrawal symptoms included diarrhea, dry mouth, anxiety, aimless walking, restlessness with loss of appetite, mental disturbance and weakness, as well as paresthesia, hypomania, nervousness with headaches, hyperhidrosis, dizziness, drowsiness, vomiting with insomnia, tremor, nausea, flu-like syndrome and vivid dreams. These manifestations were mild and resolved spontaneously.

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

Overdose

In post-marketing testing, poisoning was observed mainly when the drug was used together with alcohol or other medications.

Tachycardia, mydriasis, vomiting, changes in consciousness (from drowsiness to coma) and seizures often develop during intoxication. Other symptoms include changes in ECG readings (increased QRS complex, prolongation of QT interval marks or bundle branch of His), bradycardia, dizziness, ventricular tachycardia, decreased blood pressure and death.

In case of overdose, due to the toxic properties of venlafaxine, the risk of suicide increases in patients, which is why it is necessary to use the minimum amount of the drug that provides the required result - to reduce the possibility of poisoning. A fatal outcome is possible with intoxication with venlafaxine in combination with other drugs or alcoholic beverages.

It is necessary to clear the respiratory tract, ensure the passage of oxygen and, if necessary, carry out artificial ventilation. Symptomatic and supportive treatment procedures should also be carried out and the heart rate and the function of other vital organs should be closely monitored.

If there is a high probability of aspiration, vomiting should not be induced. Gastric lavage is possible if it is carried out shortly after taking the drug or when the corresponding signs appear. Taking activated carbon can also reduce the absorption of the drug. Dialysis, forced diuresis, hemoperfusion, and exchange blood transfusion are ineffective. There are no antidotes for venlafaxine.

Interactions with other drugs

Use with MAOIs.

Combining the drug with MAOIs is prohibited.

In people who stopped taking MAOIs shortly before taking the drug, or who stopped Alventa therapy shortly before taking MAOIs, severe side effects have been reported. These include vomiting, dizziness, seizures, tremors, attacks, nausea, profuse sweating, and feverish state, combined with NMS and seizures (may lead to death).

Venlafaxine administration may be started after at least 2 weeks have passed since the end of MAOI therapy.

The period between stopping the use of reversible MAOIs, starting moclobemide and starting Alventa should last at least 2 weeks. When introducing an MAOI at the stage of transferring a person from moclobemide to Alventa, the period of drug change should last at least 1 week.

Medicines that affect the function of the central nervous system.

Due to the principle of the medicinal effect of venlafaxine and the high probability of serotonin intoxication, it is necessary to combine the drug and substances with a possible effect on the process of serotonergic transmission of neural impulses (for example, SSRIs, triptans or lithium agents) with extreme caution.

Indinavir.

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

Warfarin.

In individuals who have used warfarin, anticoagulant activity and PT levels may increase when initiating therapy with Alventa.

Cimetidine.

In elderly people and people with liver problems using the drug together with cimetidine, the therapeutic interaction has not been studied, therefore, such patients should be clinically monitored.

Ethanol.

Do not drink alcohol while using venlafaxine.

Substances that inhibit CYP2D6 activity.

The CYP2D6 isoenzyme, which is involved in genetic polymorphism in the metabolic processes of many antidepressants, converts the venlafaxine element into the main metabolic component of ODV, which has medicinal activity. Therefore, interactions can be expected when the drug is used together with agents that slow down the action of CYP2D6.

Combinations that cause a weakening of the processes of transformation of venlafaxine into ODV are theoretically capable of increasing serum venlafaxine levels and decreasing ODV values.

Hypoglycemic and antihypertensive medications.

Upon completion of drug therapy, clozapine levels increase, which leads to the temporary appearance of side effects, including seizures.

Metoprolol.

Combination of the drug with metoprolol causes an increase in the plasma level of the latter, without changing the indicators of its active metabolic component - α-hydroxymetoprolol. The clinical consequences of such an effect for people with elevated blood pressure values have not been determined, so it is necessary to combine these drugs very carefully.

Haloperidol.

It is necessary to take into account that the combined use of drugs and haloperidol reduces clearance and increases Cmax and AUC, while leaving the half-life of haloperidol unchanged. There is no information regarding the clinical significance of such interaction.

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Storage conditions

Alventa can be stored in a place closed to small children. Temperature values - no higher than 30°C.

Shelf life

Alventa can be used within a 5-year period from the date of sale of the medicinal substance.

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Application for children

Cannot be prescribed in pediatrics (under 18 years of age).

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Analogues

Analogues of the drug are Velaxin, Dapfix, Venlafaxine with Velafax, Voxemmel, Efevelon with Venlaxor, Newelong and Venlift OD.

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