Elifor® [Desvenlafaxine]

Pharmacological properties

the exact mechanism of the antidepressant action of desvenlafaxine is unknown, but it is believed that it is associated with the potentiation of serotonin and norepinephrine in the central nervous system by inhibiting their reuptake. preclinical studies have shown that desvenlafaxine is a potent and selective serotonin and norepinephrine reuptake inhibitor.

Desvenlafaxine did not show a pronounced affinity for many receptors, including muscarino-cholinergic, N₁histaminergic or α₁-adrenoreceptors in vitro. Desvenlafaxine also did not show a pronounced activity as an MAO inhibitor.

Pharmacokinetics The pharmacokinetics of a single dose of desvenlafaxine is linear and dose-dependent in the dose range of 50-600 mg / day. When applied once a day, the equilibrium concentration in the blood plasma is reached within about 4-5 days. At equilibrium concentration, the accumulation of multiple doses of desvenlafaxine is linear and predictable, based on the pharmacokinetic profile of a single dose.

Suction and distribution. The bioavailability of Elifor after oral administration is about 80%.

Studies of the effects of food intake during the use of Elifor in healthy subjects on an empty stomach and after meals (foods with a high fat content of 800–1000 calories) have shown that C_max desvenlafaxine increased by about 16% after a meal, while AUC were similar. This difference has no clinical significance, therefore Elifor can be used regardless of food intake (see APPLICATION).

The binding of desvenlafaxine to plasma proteins is low (30%) and does not depend on the concentration of the drug. The volume of distribution of desvenlafaxine in equilibrium concentration after iv administration is 3.4 l / kg, which indicates the distribution in non-vascular parts of the body.

Metabolism and excretion. Desvenlafaxine is primarily metabolized by conjugation (mediated by isoforms of uridine-5-diphosphate (UDP)) and to a lesser extent through oxidative metabolism. CYP 3A4 is an isoenzyme of cytochrome P450 involved in the oxidative metabolism (N-demethylation) of desvenlafaxine. The metabolic pathway of CYP 2D6 is not busy, and after administration of a dose of 100 mg, the pharmacokinetics of desvenlafaxine is similar in patients with a slow and fast metabolism of CYP 2D6. About 45% of desvenlafaxine is excreted unchanged in the urine within 72 hours after oral administration. About 19% of the administered dose is excreted as a glucuronide metabolite and 5% as an oxidative metabolite (N, O-didemethylvenlafaxine) in the urine.

Age. A study of healthy subjects receiving doses of up to 300 mg showed an increase in C_max approximately 32% and an increase in AUC by 55% in individuals over 75 years of age (n = 17) compared with subjects aged 18–45 years (n = 16). Patients aged 65–75 years (n = 15) showed no change in C_max, but the AUC value in this age group increased by about 32% compared with that in subjects aged 18–45 years (see Dosage and Administration).

Floor. Dose adjustment based on gender is not required.

Race. Dose adjustment based on race is not required.

Renal failure. In patients with impaired renal function, the clearance of Elifor was reduced. In patients with severe renal failure (24-hour creatinine clearance 30 ml / min, Cockcroft-Gault formula) and end-stage renal failure T_½ significantly elongated, which increases the effect of the drug Elifor, therefore, dose adjustment is recommended for such patients.

Liver failure. T_½ varied from about 10 hours in healthy patients and patients with mild impairment of liver function to 13 and 14 hours with moderate and severe liver failure, respectively.The recommended dose for patients with liver failure is 50 mg / day. An increase in dose of 100 mg / day is not recommended (see APPLICATION, Use in special groups).

Indications

Treatment for major depressive disorder (BDD).

Application

The recommended dose of elifor is 50 mg 1 time per day, regardless of food intake.

Elifor should be used at approximately the same time each day. The tablets should be swallowed whole, washed down with liquid, not crushed, crushed, chewed or dissolved.

In clinical trials, doses of 50-400 mg / day were effective, no additional effect from the use of the drug at doses of 50 mg / day was noted, and adverse reactions and the risk of withdrawal were frequent at higher doses. If the doctor, based on the results of a clinical assessment of the patient’s condition, decides that a dose increase of 50 mg / day for a particular patient is appropriate, the maximum recommended dose should not exceed 100 mg / day.

During treatment discontinuation, a gradual dose reduction is recommended, if possible, in order to minimize withdrawal symptoms.

Application in special groups

Patients with impaired renal function. The maximum recommended dose for patients with moderate renal failure (creatinine clearance - 30-50 ml / min) is 50 mg / day. The maximum recommended dose for patients with severe renal failure (creatinine clearance of 30 ml / min) or end-stage renal failure is 50 mg every other day. Do not increase the dose to patients after dialysis.

Patients with impaired liver function. The recommended dose for patients with moderate and severe liver failure is 50 mg / day. An increase in dose of 100 mg / day is not recommended.

Maintenance therapy There is a general consensus that acute episodes of HDI require continuous drug therapy for several months or longer. The effectiveness of long-term use of the drug Elifor (50-400 mg) was established in two studies of maintenance therapy. A periodic assessment of the patients condition should be carried out to determine the need for continued therapy.

Cancel the drug Elifor. Symptoms related to withdrawal of Elifor, other selective serotonin and noradrenaline reuptake inhibitors (SSRIs) and selective serotonin reuptake inhibitors (SSRIs) have been reported. Patients who stop treatment should be monitored to identify withdrawal symptoms. A gradual dose reduction is recommended instead of abruptly discontinuing when possible. If symptoms of the disease occur after a dose reduction or discontinuation of treatment, renewal of the previously prescribed dose may be necessary. Later, the doctor may continue to reduce the dose, but more gradually.

Transfer patients from other antidepressants to Elifor. Withdrawal symptoms were reported when patients were transferred from other antidepressants, including venlafaxine, to Elifor. Initial antidepressant dose reductions may be required to minimize withdrawal symptoms.

MAO inhibitor therapy for the treatment of mental disorders. At least 14 days must elapse between the cessation of the use of an MAO inhibitor intended for the treatment of mental disorders and the initiation of therapy with Elifor, and at least 7 days must elapse after discontinuation of the drug Elifor before treatment with the MAO inhibitor, which is prescribed for the treatment of mental disorders.

The use of Elifor with other MAO inhibitors, such as linezolid or methylene blue. The drug should not be started with Elifor for a patient who is being treated with linezolid or methylene blue for iv use, because of the increased risk of serotonin syndrome.For a patient who needs emergency treatment of a mental condition, other methods should be considered, including hospitalization.

In some cases, a patient who is already receiving Elifor may need urgent treatment with linezolid or methylene blue for iv use. If there is no acceptable alternative to linezolid or methylene blue and the potential benefits of using these drugs exceed the risks of serotonin syndrome in a particular patient, Elifor should be withdrawn immediately and treatment with linezolid or methylene blue should be started for iv use. The patients condition must be monitored for symptoms of serotonin syndrome within 7 days or up to 24 hours after taking the last dose of linezolid or methylene blue for iv use, whichever comes first. Elifor therapy can be restored 24 hours after the last dose of linezolid or methylene blue for iv administration.

The risk of the simultaneous use of methylene blue for administration or in other forms (for example, in the form of oral tablets or by local injection) at doses well below 1 mg / kg body weight is unknown. The physician should consider the possibility of symptoms of serotonin syndrome with this use.

Contraindications

Hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or any excipients in the drug elifor;

simultaneous use of MAO inhibitors or their use within 7 days after discontinuation of treatment with Elifor. The use of the drug Elifor within 14 days after the withdrawal of MAO inhibitors;

simultaneous treatment with MAO inhibitors such as linezolid or iv methylene blue therapy.

Side effects

The safety of desvenlafaxine was established in clinical trials involving 7785 patients with bdr who used at least one dose of desvenlafaxine in the dose range of 10-400 mg / day. safety of long-term use was evaluated in more than 2000 subjects with bdr, in which desvenlafaxine was used for at least 6 months, and in 400 patients who took desvenlafaxine for 1 year.

In most cases, adverse reactions were most often noted during the 1st week of treatment; they were mild to moderate. The incidence of adverse reactions was generally dose-dependent.

The following are adverse reactions that were reported during pre-registration clinical studies of the use of desvenlafaxine in doses of 10-400 mg for the treatment of MDD. The frequency of adverse reactions is classified according to this scale: very often (≥1 / 10); often (≥1 / 100 and 1/10); infrequently (≥1 / 1000 and 1/100); rarely (≥1 / 10,000 and ≤1 / 1000); very rarely (1/10 000); unknown (it is not possible to set the frequency based on available data). Adverse reactions with a frequency of 1% were calculated manually; reactions with a frequency of ≥1% were classified as follows.

In each frequency group, adverse reactions are presented in decreasing order of severity.

From the immune system: infrequently - hypersensitivity.

From the side of metabolism and nutrition: often - loss of appetite, rarely - hyponatremia.

From the psyche: very often - insomnia; often - anxiety, nervousness, anorgasmia, decreased sex drive, unusual dreams; infrequently - depersonalization, unusual orgasm, withdrawal syndrome; rarely - hallucinations, hypomania, mania.

From the nervous system: very often - dizziness, headache; often - drowsiness, tremor, impaired attention, paresthesia, dysgeusia; infrequently - fainting; rarely - convulsions, dystonia; unknown - serotonin syndrome **.

From the side of the organ of vision: infrequently - mydriasis, blurred vision.

From the side of the organ of hearing and the vestibular apparatus: often - ringing in the ears, vertigo.

From the side of the heart: often - tachycardia, palpitations.

From the vessels: often - hot flashes; infrequently - cold in the limbs, orthostatic hypotension.

From the respiratory system, chest and mediastinal organs: often - yawning; infrequently - nosebleeds.

From the digestive system: very often - nausea, dry mouth, constipation; often - vomiting, diarrhea.

On the part of the skin and subcutaneous tissues: very often - hyperhidrosis; often a rash; infrequently - alopecia; rarely - angioedema **, photosensitivity reaction; unknown - Stevens-Johnson syndrome **.

From the side of musculoskeletal and connective tissue: infrequently - musculoskeletal rigidity.

From the kidneys and urinary tract: infrequently - proteinuria, urinary retention, difficulty starting urination.

From the genitals and mammary gland: often - erectile dysfunction *, delayed ejaculation *, lack of ejaculation *; infrequently - sexual dysfunction, violation of ejaculation *.

General disorders: often - fatigue, asthenia, chills, anxiety, irritability.

Laboratory studies: often - increase in blood pressure, increase in body weight, decrease in body weight; infrequently - a deviation from the norm of indicators of a functional liver test, an increase in the amount of TG in the blood, an increase in the level of prolactin in the blood, an increase in the level of cholesterol in the blood.

* Frequency is calculated only on the basis of data obtained from men.

** Adverse reactions identified during the use of the drug after registration.

Ischemic adverse reactions from the heart. Clinical studies have sometimes reported ischemic adverse reactions from the heart, including myocardial ischemia, myocardial infarction, and coronary vascular thrombosis, which required revascularization in patients with multiple concomitant risk factors for heart disease. Such phenomena were observed in a larger number of patients treated with desvenlafaxine compared with placebo.

Reactions when you stop taking the drug. Discontinuation (especially abrupt) of SSRIs / SSRIs, including desvenlafaxine, usually leads to withdrawal. Adverse reactions reported in connection with a sharp discontinuation of the drug, a dose reduction or a gradual dose reduction in clinical trials of BJD with a frequency of ≥2% included dizziness, withdrawal syndrome, nausea and headache. In general, withdrawal symptoms occurred more frequently with higher doses and a longer course of treatment. These reactions were mild or moderate in severity and went away on their own, but in some patients they could be severe and / or prolonged. Thus, when treatment with desvenlafaxine is no longer required, it is recommended to gradually stop taking the drug with a lower dose.

Adverse reactions reported as causes of discontinuation of the drug. In a combined 8–12-week, placebo-controlled study of BDD, 8% of 3,335 patients receiving desvenlafaxine (10–400 mg) and 4% of 1,873 patients receiving placebo discontinued treatment due to adverse reactions.

The most common adverse reaction that led to discontinuation of the drug in 2% of patients treated with desvenlafaxine was nausea (2%) in short-term studies (up to 12 weeks). In a long-term study (up to 11 months), in the double-blind phase, in patients receiving desvenlafaxine treatment, adverse reactions occurred more frequently than in patients receiving placebo, however, in 2% of patients, no phenomenon led to discontinuation of the drug .

When used at a dose of 50 mg of desvenlafaxine, the frequency of drug withdrawal due to adverse reactions (4%) was similar to that with placebo (4%).At doses of 100 and 200 mg of desvenlafaxine, the frequency of drug withdrawal due to adverse reactions was 8 and 15%, respectively.

Use in the elderly. In clinical trials of BDR, of 7785 patients treated with desvenlafaxine, 5% were over the age of 65. There was no overall difference in safety and efficacy between these patients and young patients. However, in short, placebo-controlled studies, more cases of systolic orthostatic hypotension were noted, and in short-term, placebo-controlled studies, increased systolic blood pressure in patients aged 65 years compared with patients aged ≤65 years who took desvenlafaxine.

Adverse reactions reported with other SSRIs. Although gastrointestinal bleeding is not considered an adverse reaction of desvenlafaxine, it is an adverse reaction of other SSRIs and can also occur with desvenlafaxine.

Reporting suspected adverse reactions. Reporting suspected adverse reactions in the post-registration period is an important event. This allows you to continue monitoring the benefit / risk ratio when using the drug. Doctors are encouraged to report any suspected adverse reactions in accordance with the current reporting system requirements.

special instructions

Suicidal thoughts and behavior in children, adolescents and young people. BDD patients, both adults and children, whether or not they are using antidepressants, may experience increased depression, the emergence of suicidal ideation and behavior (suicidality), or unusual changes in behavior, and this risk may persist until sustained remission . depression and some other mental disorders are known to be risk factors for suicide; these disorders themselves are considered its clear harbingers. however, antidepressants may play a role in enhancing depression and the emergence of suicidality in some patients in the early stages of treatment. generalized analyzes of short-term placebo-controlled studies of antidepressants (syoses and others) showed that these drugs increase the risk of suicidal thoughts and behavior (suicidality) in children, adolescents and young people (aged 18-24 years) with bds and other mental disorders. short-term studies do not show an increased risk of suicidality while taking antidepressants compared with placebo in adults over the age of 24 years; noted a reduction in the risk of suicide during antidepressant use compared with placebo in adults over 65 years of age.

A pooled analysis of placebo-controlled studies in children and adolescents with MDI, obsessive-compulsive disorder (OCD), or other mental disorders included 24 short-term studies of 9 antidepressants in more than 4,400 patients. A pooled analysis of placebo-controlled studies in adults with MDI or other mental disorders included a total of 295 short-term studies (mean duration 2 months) of 11 antidepressants in more than 77,000 patients. Significant differences were observed in the risk of suicidality between the drugs, however, with a tendency to increase with the participation of younger patients for almost all of the studied drugs. Differences in the absolute risk of suicide among various indications were revealed; a high level was noted with BDR. However, the differences in risk (drugs versus placebo) were relatively stable in age groups and for various indications. In one of the pediatric studies, suicides were not recorded.There were cases of suicide in studies among adults, but the number was insufficient for any conclusion about the effect of drugs on the risk of suicide.

It is unknown whether the risk of suicide extends to prolonged use, that is, longer than several months. However, according to placebo-controlled studies involving adult patients with depression, there is substantial evidence that antidepressants may delay the recurrence of depression.

The condition of all patients who receive antidepressant treatment for any indication should be adequately monitored and observed for clinical deterioration, suicidality and unusual changes in behavior, especially during the first few months of treatment or when the dose changes (increase or decrease).

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor anxiety), hypomania and mania have been reported in adults and children who received antidepressants for the treatment of MDD, as well as for other indications, psychiatric and non-psychiatric. Although a causal relationship between the onset of such symptoms and the intensification of depression and / or the occurrence of suicidal impulses has not been established, there are concerns that such symptoms may be the cause of suicidal behavior.

A change in the therapeutic regimen should be considered, including the possible discontinuation of the drug for patients whose depression is constantly increasing or who have suicidal ideation or symptoms - signs of increased depression or suicidal ideation, especially if these symptoms are severe, with a sharp onset or were not observed in the patient before treatment.

If it was decided to discontinue treatment, the drug should be discontinued, gradually reducing the dose, as quickly as possible, but given that a sudden cessation may be associated with certain symptoms (see APPLICATION).

Families and caregivers of patients who take antidepressants and receive treatment for MDD or other psychiatric and non-psychiatric illnesses should be warned about the need to observe patients regarding the appearance of arousal, irritability, unusual behavioral changes and other symptoms described above, as well as suicidality, and report such symptoms immediately to healthcare providers.

Examination of patients to detect bipolar disorder. An episode of BDD may be the initial symptom of bipolar disorder. It is believed (although this has not been established in controlled studies) that treating such an episode with antidepressants alone may increase the likelihood of an accelerated mixed / manic episode in patients at risk of developing bipolar disorder. It is not known whether the symptoms described above demonstrate the likelihood of this acceleration. However, prior to initiating antidepressant treatment, patients with symptoms of depression should be properly examined to determine if they are at risk of bipolar disorder; such an examination should include a detailed psychiatric history, including a history of family suicides, bipolar disorder and depression. It should be noted that Elifor is not used in the treatment of bipolar depression.

Serotonin syndrome. The development of serotonin syndrome, potentially life-threatening, has been reported with the use of SSRIs and SSRIs, including Elifor, separately, but especially when used simultaneously with other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone and St. Johns wort), as well as with drugs that reduce the metabolism of serotonin (in particular, MAO inhibitors, which are intended to treat mental disorders, and others, such as linezolid and methylene for blue / in use).

Symptoms of serotonin syndrome may include changes in mental state (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, fluctuations in blood pressure, dizziness, increased sweating, hot flashes, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, mi, hyperreflexia, impaired coordination), cramps and / or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhea). Patients should be monitored regarding the occurrence of serotonin syndrome.

The simultaneous use of Elifor with MAO inhibitors intended for the treatment of mental disorders is contraindicated. Elifor should also not be prescribed to patients who are being treated with MAO inhibitors, such as linezolid or methylene blue for iv use. Messages about methylene blue, containing information about the route of administration, related to the introduction in the dose range of 1-8 mg / kg of body weight. There are no reports of the use of methylene blue by other methods (for example, oral tablets or local injections) or in lower doses. If there is a need for the use of MAO inhibitors, such as linezolid or iv methylene blue, the patient who uses Elifor should discontinue its use before starting treatment with MAO inhibitors (see CONTRAINDICATIONS, APPLICATION).

If the simultaneous use of Elifor with other serotonergic agents, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan and St. Johns wort, is clinically justified, patients should be informed of a possible increase in the risk of serotonin syndrome, in particular at the beginning of treatment and doses.

Treatment with Elifor with the simultaneous use of serotonergic drugs should be stopped immediately if the above symptoms occur and appropriate symptomatic treatment should be started.

Increased blood pressure. Patients receiving Elifor should regularly monitor blood pressure, as its increase was noted in clinical trials (see ADVERSE EFFECTS). Prior to treatment with Elifor, control over blood pressure in patients with a history of hypertension should be established. Caution should be exercised in the treatment of patients with pre-existing hypertension, cardiovascular and cerebrovascular disorders, which may increase with an increase in blood pressure. Cases of elevated blood pressure have been reported that required immediate treatment with Elifor.

A sustained increase in blood pressure can have adverse effects. For patients who experience a steady increase in blood pressure while taking Elifor, the feasibility of lowering the dose or discontinuing therapy should be considered (see ADVERSE EFFECTS).

Abnormal bleeding. SSRIs and SSRIs, including Elifor, can increase the risk of bleeding. The simultaneous use of acetylsalicylic acid, NSAIDs, warfarin and other anticoagulants may increase this risk. The described clinical cases and epidemiological studies (case-control and group studies) demonstrated the relationship between the use of drugs that affect the reuptake of serotonin and the occurrence of gastrointestinal bleeding. Cases of bleeding associated with SSRIs and SSRIs ranged from ecchymosis, hematoma, epistaxis and petechiae to life-threatening bleeding. Patients should be aware of the risk of bleeding associated with the concomitant use of Elifor and NSAIDs, acetylsalicylic acid or other drugs that affect coagulation or bleeding.

Angle-closure glaucoma. Mydriasis associated with the use of Elifor has been reported, therefore, patients with increased intraocular pressure or with the risk of angle-closure glaucoma (narrow-angle glaucoma) should be monitored.

Activation of mania / hypomania.In all Phase 2 and Phase 3 studies, MDIs were observed in approximately 0.02% of patients receiving Elifor. Activation of mania / hypomania was also observed in a small number of patients with large affective disorder who received other registered antidepressants. Like all other antidepressants, Elifor should be used with caution in patients with mania or hypomania in a personal or family history.

Withdrawal syndrome. Withdrawal symptoms were evaluated in systematic and prospective studies among patients who received Elifor during clinical trials of BDR. A sudden cessation or dose reduction was associated with the appearance of new symptoms, which include dizziness, nausea, headache, irritability, insomnia, diarrhea, anxiety, fatigue, abnormal dreams and increased sweating. In general, withdrawal symptoms were frequent with longer therapy.

When using SSRIs and SSRIs, spontaneous reports were received about adverse reactions that occurred after discontinuation of these drugs, especially severe, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g. paresthesia, such as a sensation of electric current), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus and cramps. Although these reactions usually went away on their own, there were reports of severe withdrawal symptoms.

These symptoms should be controlled in patients who discontinue treatment with Elifor. A gradual dose reduction is recommended instead of abruptly discontinuing, if possible. If severe symptoms occur after a dose reduction or discontinuation of treatment, updating the previously prescribed dose should be considered. Subsequently, the doctor may continue to reduce the dose, but more gradually (see APPLICATION, ADVERSE EFFECTS).

Convulsive seizures. Cases of seizures have been reported in the pre-registration clinical studies of Elifor. A systemic analysis of the effect of Elifor was not performed among patients with epilepsy. Patients with a history of seizures were excluded from pre-registration clinical studies. Elifor should be prescribed with caution to patients with epilepsy.

Hyponatremia. Hyponatremia can occur as a result of treatment with SSRIs and SSRIs, including Elifor. In many cases, hyponatremia is the result of an inappropriate secretion of antidiuretic hormone. Cases where the level of sodium in the blood plasma would be 110 mmol / L have not been reported. Elderly patients are at greater risk of developing hyponatremia in the treatment of SSRIs and SSRIs. In addition, in patients using diuretics or for dehydration for other reasons, the risk of hyponatremia is also increased (see APPLICATION, Use in Special Groups and PHARMACOLOGICAL PROPERTIES). For patients with hyponatremia symptoms, Elifor® withdrawal and appropriate medical interventions may be required.

Symptoms of hyponatremia include headache, difficulty concentrating, memory loss, confusion, weakness, and loss of balance, which can lead to falls. Symptoms associated with more severe and / or acute cases included hallucinations, fainting, cramps, coma, respiratory arrest, and death.

Interstitial lung disease and eosinophilic pneumonia. Rarely reported the occurrence of interstitial lung disease and eosinophilic pneumonia, which were associated with the use of venlafaxine (the starting material of the drug Elifor). The possibility of these adverse reactions should be considered in patients taking Elifor and treating progressive shortness of breath, coughing, or chest discomfort.Such patients should undergo an immediate medical examination, and discontinuation of treatment with Elifor should also be considered.

Use in elderly patients. Of the 4158 patients participating in the pre-registration clinical studies of Elifor, 6% were over the age of 65. In general, there were no differences in safety and efficacy between these patients and younger patients, however, short-term placebo-controlled studies revealed a high level of systolic orthostatic hypotension in patients aged ≥65 years compared with patients aged 65 years who received Elifor . For elderly patients, the possible limitation of Elifors renal clearance should be considered when determining the dose.

SSRIs and SSRIs, including Elifor, have been associated with cases of clinically significant hyponatremia in elderly patients who may have an increased risk of these adverse reactions.

Use during pregnancy and lactation

Pregnancy (category C). Adequate and well-controlled studies of the effects of Elifor in pregnant women have not been conducted. In reproductive experimental studies of the effects of desvenlafaxine succinate in animals, evidence of teratogenicity was not observed at doses 30 times the dose of 100 mg / day for humans (in terms of mg / m²) An increase in mortality of young animals was noted during the first 4 days of lactation, provided that desvenlafaxine succinate was used during pregnancy and lactation in doses 10 times higher than the dose of 100 mg / day for humans (in terms of mg / m²) Elifor should not be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus.

Clinical findings. A prospective, long-term study of 201 women with a history of BDR, eutim