Venlafaxine - instructions for use, doses, side effects, contraindications

Antidepressant. By chemical structure venlafaxine can not be attributed to any known class of antidepressants (tricyclic, tetracyclic or other). It has two active enantiomeric racemic forms.

The antidepressant effect of venlafaxine is associated with an increase in neurotransmitter activity in the CNS. Venlafaxine and its main metabolite, O-desmethylvenlafaxine, are potent inhibitors of the reuptake of serotonin and norepinephrine and weakly inhibit the reuptake of dopamine by neurons. Venlafaxine and O-desmethylvenlafaxine equally effective effect on the reverse capture of neurotransmitters. Venlafaxine and O-desmethylvenlafaxine reduce beta-adrenergic reactions.

Venlafaxine does not have an affinity for m- and n-cholinergic receptors, histamine H₁receptors and α₁-adrenoceptors of the brain. Venlafaxine does not suppress activity monoamine oxidase. Has no affinity for opioid, benzodiazepine, phencyclidine or NMDA receptors.

Pharmacokinetics:

After oral administration venlafaxine well absorbed from the digestive tract. After a single dose in doses of 25-150 mg C_max in blood plasma is achieved within approximately 2.4 hours and is 33-172 ng / ml. Venlafaxine is subjected to intensive metabolism at the "first passage" through the liver. C_max O-desmethylvenlafaxine in blood plasma is achieved approximately 4.3 hours after administration and is 61-325 ng / ml. In the range of daily doses of 75-450 mg venlafaxine and O-desmethylvenlafaxine have linear kinetics. After eating with meals, the time to reach C_max in blood plasma increases by 20-30 minutes, but the C_max and the absorption does not change.

Binding of venlafaxine and O-desmethylvenlafaxine with plasma proteins is 27% and 30%, respectively. With multiple reception of C_ss venlafaxine and O-desmethylvenlafaxine are achieved within 3 days.

The main metabolite - O-desmethylvenlafaxine. The half-life of venlafaxine and O-desmethylvenlafaxine is 5 and 11 hours, respectively. O-desmethylvenlafaxine and other metabolites, as well as unchanged venlafaxine are excreted by the kidneys.

In patients with cirrhosis, plasma concentrations of venlafaxine and O-desmethylvenlafaxine Increased, and the speed of their removal is reduced. With moderate or severe renal failure, the total clearance of venlafaxine and O-desmethylvenlafaxine decreases, and the half-life is prolonged. The decrease in overall clearance is mainly observed in patients with creatinine clearance less than 30 ml per minute. Age and sex of the patient do not affect the pharmacokinetics of venlafaxine.

Indications:

Depression of various etiologies (treatment and prevention).

ICD-10

V.F30-F39.F31 Bipolar affective disorder

V.F30-F39.F32 Depressive episode

V.F30-F39.F33 Recurrent depressive disorder

V.F40-F48.F41.2 Mixed anxiety and depressive disorder

Contraindications:

Severe renal insufficiency (creatinine clearance <10 mL / min); severe violations of liver function; simultaneous administration of inhibitors monoamine oxidase; children and adolescents under 18; established or suspected pregnancy; lactation period (breastfeeding); increased sensitivity to venlafaxine.

Carefully:

In elderly patients venlafaxine should be used at the lowest effective dose. When the dose is raised, the patient must be under careful medical supervision

Elderly patients should be warned about the possibility of dizziness and discomfort. When receiving venlafaxine, especially in conditions of dehydration or a decrease in the volume of circulating blood, in elderly patients there may be hyponatremia and / or an inadequate secretion syndrome antidiuretic hormone.

Caution should be applied venlafaxine After a recent myocardial infarction,with heart failure in the stage of decompensation, with unstable angina, arterial hypertension, tachycardia, tachyarrhythmia, history of convulsions, intraocular hypertension, angle-closure glaucoma, manic conditions in the anamnesis, predisposition to bleeding from the skin and mucous membranes, initially reduced body weight.

Pregnancy and lactation:

FDA Action Category - C.

Contraindicated in pregnancy and lactation (breastfeeding).

Women of childbearing age should apply reliable methods of contraception during the treatment period and immediately consult a doctor in case of pregnancy or pregnancy planning.

Venlafaxine and metabolite O-desmethylvenlafaxine excreted in breast milk. The safety of these substances for newborn babies is not proven, therefore, if necessary, taking venlafaxine during lactation should resolve the issue of stopping breastfeeding. If the mother's treatment was completed shortly before the birth, the newborn can experience withdrawal symptoms.

Dosing and Administration:

Inside, at the same time as eating.Dosing regimen is selected individually, it is desirable to assign the minimum effective dose. The recommended initial dose is 75 mg in day (pills - the daily dose is divided into 2-3 doses, capsules - 1 time at day, at about the same time of day - in the morning or in the evening). For some patients, a starting dose of 37.5 mg at day (within 4-7 days). If necessary, it is possible to increase the dose (gradually, by 75 mg at day, Once every 4 days or more) to 225 mg at day (the recommended dose for depression of moderate severity), in hospital (with severe depression), it is possible to increase the dose to a maximum of 375 mg at day.

In patients with impaired liver function from mild to moderate severity, a daily dose reduction of 50% is required, with a cirrhosis of the liver - and more than 50%. Against the background of impaired renal function (glomerular filtration rate - 10-70 ml / min), a dose reduction of 25-50% is necessary, with hemodialysis - by 50%, the drug should be taken after hemodialysis. In elderly patients, no special dose adjustments are required, but caution should be exercised in treating this category of patients, especially with increasing doses.

Side effects:

Most side effects depend on the dose.With long-term treatment, the severity and frequency of most of these effects is reduced, and there is no need to cancel therapy.

From the digestive system: loss of appetite, constipation, nausea, vomiting, dry mouth; rarely - hepatitis.

From the side of metabolism: increased serum cholesterol levels, weight loss; sometimes - a violation of functional liver tests, hyponatremia, an inadequate secretion syndrome antidiuretic hormone.

From the cardiovascular system: arterial hypertension, hyperemia of the skin; sometimes - postural hypotension, tachycardia.

From the side of the central nervous system and the peripheral nervous system: unusual dreams, dizziness, insomnia, nervous excitement, paresthesia, stupor, increased micetonus, tremor, yawning; sometimes - apathy, hallucinations, muscle spasms, serotonergic syndrome; rarely epileptic seizures, manic reactions, as well as symptoms reminiscent of malignant neuroleptic syndrome.

From the urinary system: dysuria (mainly - difficulty in the beginning of urination); sometimes - retention of urine.

On the part of the reproductive system: violations of ejaculation, erections, anorgasmia; sometimes - a decrease in libido, menorrhagia.

From the sense organs: disorders of accommodation, mydriasis, visual impairment; sometimes - a violation of taste sensations.

Dermatological reactions: sweating; sometimes - photosensitivity.

On the part of the hematopoiesis system: sometimes - hemorrhages in the skin (ecchymosis) and mucous membranes, thrombocytopenia; rarely - prolonged bleeding time.

Allergic reactions: sometimes - a skin rash; rarely - erythema multiforme, Stevens-Johnson syndrome; very rarely - anaphylactic reactions.

Other: weakness, fatigue.

After a sharp cancellation or dose reduction fatigability, drowsiness, headache, nausea, vomiting, anorexia, dry mouth, dizziness, diarrhea, insomnia, anxiety, anxiety, nervous irritability, disorientation, hypomania, paresthesia, sweating. These symptoms are usually mild and go untreated.

Overdose:

Symptoms: change ECG (lengthening interval QT, bundle branch blockade, expansion of the complex QRS and other), sinus and ventricular tachycardia, bradycardia, hypotension, dizziness, impaired consciousness of varying severity (from drowsiness to coma), convulsions, even to death.

Treatment: application of activated carbon, induction of vomiting, gastric lavage (to reduce absorption). Maintenance of airway patency for adequate ventilation and oxygenation. It is recommended to closely monitor and monitor the rhythm of the heart and other vital functions, symptomatic and supportive therapy. The effectiveness of such activities as forced diuresis, dialysis, hemoperfusion and exchange blood transfusion is unlikely. There is no specific antidote.

In post-marketing studies, cases of venlafaxine overdose have been noted predominantly with simultaneous use of alcohol and / or other medications.

Interaction:

Venlafaxine can be taken at least 14 days after the end of therapy with inhibitors monoamine oxidase. If a reversible inhibitor monoamine oxidase (moclobemide), this interval may be shorter (24 h). Therapy with inhibitors monoamine oxidase can be started no less than 7 days after the withdrawal of venlafaxine.

The simultaneous use of venlafaxine with lithium can increase the concentration of the latter in blood plasma.

It is possible to enhance the effects of haloperidol due to an increase in its concentration in the blood when combined with venlafaxine.

With simultaneous use with clozapine, there may be an increase in its level in the blood plasma and the development of side effects (eg, epileptic seizures).

The main way to eliminate venlafaxine involves metabolism involving CYP2D6 and CYP3A4, therefore, special care should be taken when administering venlafaxine in combination with drugs that are inhibitors of these two enzymes. The nature of this interaction has not yet been studied.

Cimetidine suppresses the metabolism of venlafaxine in the "first pass" through the liver and does not affect the pharmacokinetics O-desmethylvenlafaxine. Most patients expect only a slight increase in the total pharmacological activity of venlafaxine and O-desmethylvenlafaxine (more pronounced in elderly patients and in violation of liver function).

With simultaneous administration with warfarin, the anticoagulant effect of the latter may be enhanced.

Special instructions:

In patients with depressive disorders, the likelihood of suicidal attempts should be considered before initiating any drug therapy.Therefore, in order to reduce the risk of overdose at the beginning of treatment, venlafaxine in the minimum effective dose, and the patient should be under careful medical supervision.

In patients with affective disorders in the treatment of antidepressants (including venlafaxine), hypomanic or manic conditions may occur. Like other antidepressants, venlafaxine should be administered with caution to patients with a history of mania. Such patients need medical supervision.

If epileptic seizures occur, treatment should be discontinued.

The risk of tachycardia increases with venlafaxine in high doses.

During treatment, regular monitoring of blood pressure is recommended, especially during the period of refining or increasing the dose.

Patients, especially the elderly, should be warned about the possibility of dizziness and discomfort.

During the administration of venlafaxine, especially in conditions of dehydration or a decrease in the volume of circulating blood (including elderly patients and patients taking diuretics), hyponatremia and / or insufficient secretion syndrome antidiuretic hormone.

During the administration of the drug may be observed mydriasis, in connection with which it is recommended to control intraocular pressure in patients prone to its increase or suffering from an angle-closure glaucoma.

As with other drugs acting on the central nervous system, the physician should establish careful monitoring of patients to identify signs of abuse of venlafaxine. Careful monitoring and follow-up are necessary for patients who have a history of such symptoms.

On the background of taking venlafaxine, special care should be taken when conducting electroconvulsive therapy, since there is no experience with venlafaxine in these conditions.

During the treatment should avoid drinking alcohol.

Impact on the ability to drive vehicles and manage mechanisms

Although venlafaxine does not affect psychomotor and cognitive functions, it should be taken into account that any drug therapy with psychoactive drugs can worsen thinking processes and reduce the ability to perform motor functions. This should be warned by the patient before starting treatment.If such violations occur, the extent and duration of the restrictions should be determined by the physician.

Instructions

Venlafaxine (Venlafaxinum)