Velaxin

Velaxin is a drug from the antidepressant category.

Indications Velaxina

It is used in the treatment of episodes of severe depression (in addition to this, also for the prevention of their development). In addition, it is used for generalized anxiety disorders and social phobias.

[ 1 ]

Release form

Release in capsules. One blister contains 10 capsules, a separate package contains 3 blister plates. Also released with 14 capsules inside a blister package. In a separate pack there are 2 blisters.

[ 2 ], [ 3 ]

Pharmacodynamics

The antidepressant properties of the substance venlafaxine are associated with the potentiation of the activity of neurotransmitters in the central nervous system.

Venlafaxine with its main breakdown product (O-desmethylvenlafaxine – ODV) is a potent aspartate-type serotonin and norepinephrine reuptake inhibitor. In addition, these substances are capable of inhibiting the process of dopamine reuptake by neurons.

The active component of the drug together with ODV, in case of single or multiple use, reduces the manifestations of the β-adrenergic type. They also act with similar efficiency on the reverse neurotransmitter uptake. At the same time, venlafaxine does not have a suppressive effect on the activity of MAO agents.

In addition, venlafaxine has no affinity for phencyclidine, benzodiazepine, opiate or NMDA endings, and does not affect the processes of norepinephrine release through brain tissue.

Pharmacokinetics

About 92% of the substance is absorbed after a single oral administration of the capsule. When using capsules with a prolonged release type, peak values of the active component and its metabolite in the plasma are observed in the period of 6.0±1.5 and 8.8±2.2 hours, respectively.

The rate of absorption of the substance is slower than similar values of its elimination. Therefore, the real half-life when using capsules with a prolonged release type (15±6 hours) can generally be considered the half-absorption period, replacing it with the real half-life (5±2 hours), which develops in the case of using a drug with immediate release.

When equal daily doses of the drug were administered in the form of immediate-release tablets or prolonged-release capsules, the effects of both the active ingredient and the metabolite were similar for both forms of the drug. The variations in plasma drug values were slightly lower when using prolonged-release capsules. As a result, prolonged-release capsules have a reduced absorption rate, but the absorption volume remains the same as that of immediate-release tablets.

Excretion of venlafaxine and its breakdown products occurs primarily via the kidneys. About 87% of the component is excreted in the urine within 48 hours (unchanged components, conjugated and unconjugated ODV, or other minor breakdown products are excreted).

The half-life of venlafaxine with its active breakdown product (B-desmethylvenlafaxine) is prolonged in individuals with hepatic/renal impairment.

Taking extended-release capsules with food does not affect the absorption of the drug components.

[ 4 ], [ 5 ]

Dosing and administration

The capsule of the medicine should be taken with food, swallowed whole and washed down with water. Do not crush, open or chew the capsule, or put it in water. Take it once a day at approximately the same time - in the morning or in the evening.

In case of depression, it is required to take 75 mg of the medicine per day. If necessary, the dosage can be increased to 150 mg once per day after the end of a 2-week course of treatment. This is done to obtain subsequent clinical improvement. In case of a mild degree of the disease, the daily dose can be increased to 225 mg, and in case of a severe degree - to 375 mg. Any increase in dosage must be made after every 2 weeks or a longer period (in general after at least 4 days) - by 37.5-75 mg.

In the case of using Velaxin at a dosage of 75 mg, the antidepressant effect of the drug was noted after 2 weeks of therapy.

In the treatment of generalized anxiety disorders, as well as social phobias.

During the treatment of certain anxiety disorders (including social phobia), it is recommended to take 75 mg of the drug per day. If this is required to obtain a stronger medicinal effect, after 2 weeks of treatment, the daily dosage may be increased to 150 mg. It may also be increased to 225 mg per day. The dosage must be increased after each subsequent 2 weeks of therapy (or a longer period, but not less than 4 days) - by 75 mg.

In case of taking the drug in the amount of 75 mg, the anxiolytic effect develops after the first week of treatment.

To prevent the development of relapses or for maintenance treatment.

Doctors recommend treating depressive episodes for at least six months.

In the maintenance form of treatment, and also in the prevention of relapses or new depressive episodes, doses similar to those that were effective in the treatment of a regular depressive episode are often used. The doctor needs to constantly, at least once every 3 months, determine the degree of effectiveness of a long-term therapeutic course.

Stopping venlafaxine.

During the period of discontinuation of the drug, it is necessary to gradually reduce its dosage. When using Velaxin for a period longer than 6 weeks, the dosage should be reduced for at least 2 weeks.

The time period required for gradual reduction of the dosage depends on the size of the dose taken during therapy, as well as on the duration of the course and the individual tolerance of the patient.

In case of kidney or liver failure.

In patients with renal insufficiency, in which the SCF values are >30 ml/minute, there is no need to change the dose. In patients with SCF <30 ml/minute, the daily dose of the drug should be reduced by 50%. Patients on hemodialysis should also reduce the daily dose of the drug by 50%. In this case, Velaxin should be taken after the end of the treatment procedure.

For people with moderate liver failure, the daily dose is also reduced by 50%. Sometimes a reduction of more than 50% is required.

[ 9 ]

Use Velaxina during pregnancy

It is prohibited to use Velaxin capsules during pregnancy or lactation.

Contraindications

Among the main contraindications:

• intolerance to the components of the drug;
• combined use with MAO inhibitor drugs, and also during the 2-week period after completion of the latter use;
• it is necessary to discontinue the use of venlafaxine no later than 1 week before starting treatment with any drug from the MAOI category;
• severely elevated blood pressure (180/115 or more before starting treatment);
• presence of glaucoma;
• problems with urination due to insufficient urine flow (for example, in prostate diseases);
• severe renal/liver failure;
• There have been no studies conducted on the effectiveness and safety of using the drug in children, so they are prohibited from taking the drug.

[ 6 ]

Side effects Velaxina

Taking capsules may cause the following side effects:

• reactions from the cardiovascular system: vasodilation is often observed (mainly in the form of facial flushing or hot flashes), as well as an increase in blood pressure. Sometimes tachycardia, orthostatic collapse and a decrease in blood pressure develop. Ventricular fibrillation, increased heart rate, prolongation of the QT interval, loss of consciousness and ventricular tachycardia (including pirouette-type arrhythmia) are observed sporadically;
• Gastrointestinal dysfunction: constipation, vomiting, loss of appetite and nausea often occur. Sometimes teeth grinding may occur;
• manifestations from the lymph and blood flow: bleeding in the mucous membranes (for example, in the gastrointestinal tract) and ecchymosis are occasionally observed. In some cases, the bleeding period may be prolonged and thrombocytopenia may develop. Blood dyscrasia may occur (this includes neutro- and pancytopenia, agranulocytosis and aplastic anemia);
• nutritional and metabolic disorders: weight loss and increased serum cholesterol levels are common. Less common is hyponatremia, abnormal liver function tests and weight gain. Rarely, diarrhea, hepatitis, pancreatitis and ADH hypersecretion syndrome occur, and prolactin levels increase;
• Disorders of the nervous system: often observed is a decrease in libido, muscle hypertonia, dizziness, as well as sleep disorders, tremor and paresthesia, dry mouth, a feeling of nervousness, sedation and insomnia, as well as akathisia and problems with balance coordination. Less common are hallucinations, a feeling of apathy, myoclonus and serotonin intoxication. Rarely, manic manifestations, seizures, extrapyramidal syndromes (including dyskinesia and dystonia), NMS (including symptoms similar to NMS) occur, as well as rhabdomyolysis, late-stage dyskinesia, epileptic seizures and tinnitus. The development of delirium or psychomotor agitation is possible;
• Mental disorders: insomnia, a feeling of depersonalization and confusion, and strange dreams are often observed. Suicidal thoughts and suicidal behavior may develop;
• Respiratory system reactions: yawning mainly develops. Pulmonary eosinophilia may develop;
• Skin manifestations: hyperhidrosis is often observed (also at night). Less frequently, itching, alopecia and rashes occur. Lyell's or Stevens-Johnson syndromes and erythema multiforme are occasionally observed;
• reactions of the sense organs: mydriasis, accommodation or vision disorders and glaucoma are often observed. Less frequently, taste bud disorders appear;
• urinary and renal dysfunction: dysuria often appears (usually there is difficulty in starting to urinate). Urinary retention is occasionally observed;
• disorders in the mammary glands and reproductive organs: men often develop ejaculation disorders and impotence; women experience anorgasmia and menstrual cycle disorders, which develop due to an increase in the amount of irregular bleeding (for example, with metrorrhagia or menorrhagia);
• Systemic manifestations: mainly a feeling of fatigue or weakness is observed, as well as anaphylaxis, fever and photosensitivity.

[ 7 ], [ 8 ]

Overdose

Manifestations of drug overdose: changes in ECG parameters (prolongation of the QT interval, LBBB, and prolongation of the QRS complex), ST and ventricular tachycardia, decreased blood pressure, bradycardia, vertigo and mydriasis, as well as the occurrence of seizures, vomiting and the development of impaired consciousness (from a feeling of drowsiness to a state of coma). Often, such disorders and signs disappear on their own.

When treating intoxication, it is necessary to maintain patency in the respiratory system, ensuring adequate oxygen saturation and ventilation.

Long-term monitoring of heart rate and vital signs is required, as well as symptomatic and supportive treatment. Activated charcoal may also be used. Do not induce vomiting because of the risk of aspiration.

[ 10 ], [ 11 ]

Interactions with other drugs

MAOI drugs.

The combination of venlafaxine with MAOI drugs is prohibited.

Serious adverse reactions have been reported in individuals who have stopped taking MAOIs shortly before starting venlafaxine or who have taken venlafaxine shortly before using an MAOI. Reactions have included seizures, vomiting, tremors with nausea, as well as dizziness, profuse sweating, and a febrile state that has been associated with NMS and seizures, and sometimes death.

As a result, venlafaxine should be used at least 2 weeks after completion of MAOI therapy.

It is recommended that a minimum of 14 days be observed between the end of use of a reversible MAOI with moclobemide and the start of venlafaxine therapy. When using MAOIs, due to the adverse reactions described above, this period should be at least 1 week when switching a patient from moclobemide to venlafaxine.

Medicines that have an effect on the function of the nervous system.

Taking into account the mechanism of the medicinal action of Velaxin, as well as the risk of serotonin intoxication, in the case of a combination of this drug with agents capable of influencing the transmission of serotonergic nerve impulses (including selective serotonin reuptake inhibitors, Triplan or lithium drugs), therapy must be carried out with caution.

Indinavir.

Co-administration of the drug with indinavir resulted in a decrease in peak and AUC values of the latter by 36% and 28%, respectively. In addition, indinavir had no effect on the pharmacokinetic characteristics of venlafaxine with ODV.

Warfarin.

In patients taking warfarin, an increase in anticoagulant properties may be observed with the initiation of venlafaxine. In addition, prolongation of PT values is observed.

Haloperidol.

Because haloperidol can accumulate in the body, its effects may be enhanced.

Cimetidine.

Cimetidine in equilibrium values is capable of inhibiting the process of venlafaxine metabolism during the first pass, but at the same time does not have a significant effect on the formation and elimination of the substance B-desmethyl-venlafaxine, which is inside the circulatory system in much more significant quantities. This allows us to conclude that with a combination of the above-described drugs in a healthy person, a change in dosage will not be necessary. But in elderly people with liver disorders, such a combination should be used with caution, because there is no information on the interaction of drugs. In such a case, constant monitoring of the therapy process is required.

Medicines that inhibit the action of the CYP2D6 element.

The CYP2D6 isoenzyme, which is responsible for the processes of genetic polymorphism and affects the metabolism of a large number of antidepressants, converts the substance venlafaxine into its main breakdown product - ODV. This creates conditions for the development of interaction of Velaxin with drugs that inhibit the CYP2D6 element.

Interactions that reduce the amount of active component transformed into ODV could, in theory, increase serum levels of the substance and decrease levels of its active breakdown product.

Ketoconazole (a substance that inhibits the CYP3A4 element).

Tests of ketoconazole in rapid and slow metabolizers of the CYP2D6 component showed that when using this drug, the AUC of venlafaxine increases (by 21% and 70%, respectively). The level of O-desmethylvenlafaxine also increases (by 23% and 33%, respectively).

Combination of drugs with CYP3A4 inhibitors (including itraconazole, clarithromycin with atazanavir and voriconazole, as well as indinavir, saquinavir and posaconazole with nelfinavir and telithromycin, as well as ketoconazole with ritonavir) increases the levels of the active ingredient of the drug and ODV. Therefore, it is necessary to combine the above-described drugs and Velaxin with caution.

Hypoglycemic and hypotensive drugs.

An increase in clozapine levels has been observed, which is temporally associated with the development of side effects (including seizures), after discontinuation of venlafaxine.

While taking venlafaxine, you must refrain from drinking alcohol.

[ 12 ], [ 13 ], [ 14 ]

Storage conditions

Velaxin should be kept out of reach of children. Temperature values – maximum 30°C.

[ 15 ]

Shelf life

Velaxin is permitted to be used for a period of 5 years from the date of release of the drug.

[ 16 ]