Azafen: instructions for use, indications, reviews, price, side effects and analogues

Pharmacodynamics and pharmacokinetics

Azafen is a tricyclic antidepressant and belongs to a group of drugs that indiscriminately inhibit (suppress) the neuronal uptake of monoamines . The antidepressant effectiveness of the active ingredient of the drug, pipofezin, is manifested due to its ability to non-selectively inhibit the neuronal reuptake of norepinephrine and serotonin , which leads to an increase in their levels in the central nervous system. In the drug Azafen, thymoleptic (improving mental state and mood) activity is combined with sedative (calming) effects and anxiolytic (anti-anxiety) effect.

Pipofezin has virtually no m-anticholinergic effects and does not affect the activity of the enzyme monoamine oxidase (MAO). Also, this drug is not characterized by cardiotoxic effects.

Oral administration of pipofezin leads to rapid and complete absorption from the gastrointestinal tract. The bioavailability of the drug is approximately 80%. Binding to plasma proteins occurs by 90%. With a single oral dose of 25 mg, the Cmax of pipofezin after 60-120 minutes is 24.5 ng/ml.

Metabolic transformations take place in the liver with the help of the CYP1A2 isoenzyme and the release of inactive metabolic products.

Pipofezin from the bloodstream quite quickly, T1/2 of the drug is 4.3 hours. Excretion is carried out primarily by the kidneys.

Azafen (pipofesin) - return to clinical practice

Shinaev N.N., Akzhigitov R.G., Galkina I.V., Rudneva N.I., Volkova N.P.

To obtain data on the safety and effectiveness of Azafen (pipofezin) in the treatment of mental pathology of the neurotic range, an open non-comparative study was conducted. 50 patients with affective pathology falling within the framework of borderline mental disorders who were undergoing inpatient treatment were examined. Azafen was prescribed in doses from 75 to 150 mg/day. The duration of the therapy period was 42 days. In the range of doses used, Azafen demonstrated good efficacy with no significant side effects.

Over the past years, the number of antidepressants presented on the Russian pharmaceutical market has increased significantly, as well as the frequency of their prescription by both psychiatrists and doctors of other specialties. Indications for the use of thymoleptics are very wide - in addition to depression itself, they also include a number of disorders in the structure of which affective symptoms are not dominant. This is primarily a group of anxiety and panic disorders, obsessive-compulsive disorders and phobias, neurasthenia, anorexia nervosa and bulimia, post-traumatic stress disorders and adaptation disorders, a wide range of personality and somatoform disorders.

On the threshold of the 21st century, there is a more and more clearly visible tendency for the scope of antidepressants to go beyond the boundaries of affective pathology, but also beyond the psychiatric field. A characteristic feature of the modern pathomorphosis of various painful manifestations is the high proportion of neurotic and somatoform disorders and the appearance of “mental masks” of internal diseases. As a consequence of this, there is an overlap between the areas of activity of psychiatrists and specialists in other medical disciplines. Large-scale multicenter studies conducted by psychiatrists together with doctors of other specialties reveal the presence of mental disorders requiring medical correction with antidepressants in up to 57% of general practitioners. Moreover, in 75% of cases, treatment of concomitant mental disorders in somatic hospitals can be carried out by a general practitioner, in 20% - by him, but with the close participation of a psychiatrist, and in 5% there is a need for transfer to a psychosomatic department [5]. Research data indicate the need to include antidepressants in therapeutic regimens for the treatment of chronic tension headaches, abuse headaches, autonomic dystonia syndrome, fibromyalgia, diseases of the cardiovascular and respiratory systems, and the gastrointestinal tract [3].

An indispensable guarantee of successful treatment of the listed disorders is the principle of an integrated approach, which includes, along with full-fledged pharmacotherapy, a wide range of psychotherapeutic, physiotherapeutic and social rehabilitation measures. However, a key role in achieving and stabilizing high effectiveness of treatment is played by adequate prescription of antidepressant therapy, the use of which would provide stable compensation for painful manifestations without causing significant side effects.

The current stage of development of psychopharmacotherapy is characterized by the active introduction of a large number of new antidepressants - both original and generics, produced mainly by Western pharmaceutical companies. The selectivity of psychopharmacological effects, or “precision of the site of application” and, as a consequence of this, a good tolerability profile with a sufficient level of effectiveness have allowed the latest generations of psychopharmaceuticals to steadily occupy a fairly wide niche in the structure of the total consumption of antidepressants by patients. However, the high cost of imported medicines makes them inaccessible to most patients, many of whom have low incomes. Alas, despite the high selectivity of action, almost all modern antidepressants are also not without side effects. Nausea, dizziness, decreased potency - this is not a complete list of adverse effects of therapy, for example, selective serotonin reuptake inhibitors. In this regard, the “rebirth” of the original domestic antidepressant Azafen (pipofezin) seems very timely and in demand. Its production was resumed by the Russian one, the production of which was designed and built in accordance with Russian and international GMP standards.

Azafen was synthesized as a “small” antidepressant, combining moderate thymoanaleptic and sedative effects, in the 60s of the 20th century by the Center for the Chemistry of Medicines under the direction of M.D. Mashkovsky. Being tricyclic in structure, it had virtually no anticholinergic activity, which predetermined its good tolerability and a minimum of side effects (Fig. 1). Its pharmacological properties included weakening the depressing effect of reserpine, enhancing the action of phenamine and 5-hydroxytryptophan, the absence of an inhibitory effect on MAO, and a combination of thymoleptic action with sedative activity [2]. This spectrum of its psychotropic action predetermined the widespread use of the drug in the treatment of mainly neurotic and neurosis-like disorders. These were mainly affective disorders with irritability, emotional lability, anxiety and asthenia, somatogenic and reactive depression, dysthymia and cyclothymia, minor alcoholic depression, occurring with both anxiety and lethargy. Azafen combined well in combination therapy with neuroleptics, anxiolytics and hypnotics. In the 70-80s of the 20th century, the overwhelming number of patients at the Moscow Neurosis Clinic who had indications for antidepressant therapy were prescribed Azafen [6]. Subsequently, due to the crisis in the domestic pharmaceutical industry, its production was discontinued and it disappeared from clinical practice. Nevertheless, over the years, at symposiums and conferences devoted to the treatment of borderline mental disorders, many speakers nostalgically remembered the drug with kind words and regretted its absence. And even when its release was discontinued, Azafen remained on the pages of reference books and monographs as the drug of choice for the treatment of affective pathology [1, 4].

Currently, the production of Azafen has been established, it has passed the necessary registration procedures and is available for purchase in the pharmacy chain. To determine the effectiveness, safety and tolerability of Azafen in patients with borderline forms of mental disorders, as well as to determine the possibilities of its use as monotherapy or in combination with psychopharmaceuticals of other groups in SKB No. 8 named after. Z.P. Solovyova - “Clinic of Neuroses” conducted an open non-comparative study. 50 patients were examined, 40 of whom received inpatient treatment, and 10 were treated as a day hospital.

The criteria for inclusion of patients in the study were:

presence of borderline mental pathology without psychotic symptoms;
informed consent;
cancellation of previous therapy at least 48 hours in advance;
age from 18 to 65 years;
a score of at least 11 on the Hamilton Rating Scale and a score of at least 3 on the CGI-S.

The exclusion criteria were as follows:

individual intolerance to the drug or a history of an allergic reaction to Azafen;
significant decrease in quality of life due to the action of the drug;
the presence of chronic somatic diseases in patients, including residual organic symptoms due to vascular diseases, traumatic brain injuries, involution, alcoholism, etc.;
high probability of non-compliance.

Among the patients studied, there were 10 men and 40 women, the average duration of the disease was 1.5 years. Before treatment, the condition of all patients was assessed as moderate. The duration of active therapy was 42 days, the “Wash out” period was 48 hours. All patients completely completed treatment. The effectiveness of therapy was assessed using the Hamilton Depression Scale (HAMD) and Clinical Global Assessment (CGI) on days 0, 7, 14, 21 and 42 of treatment. Azafen was prescribed at a dose of 75 mg/day, followed by an increase in the absence of a positive effect by day 7 to 150 mg/day. In cases of severe insomnia, the study protocol allowed the administration of one of the short-lived hypnotics (zolpidem, zopiclone), and in the event of maladaptive anxiety, the use of alprazolam. Tolerability was assessed using the UKU Adverse Event Scale, which includes a description of the adverse event, date of onset, duration, severity (mild, moderate, severe) and relationship to the study drug (possible, probable, clear). Throughout the study, vital functions were monitored - blood pressure and pulse control, general blood and urine tests.

During the study, not a single patient dropped out of the study. In all patients, the reduction of symptoms on the Hamilton scale exceeded 50%, i.e. all of them responded to Azafen therapy. The effect was observed already in the first weeks of treatment and then progressively increased. The distinct thymoanaleptic effect of the drug is emphasized by the fact that almost all patients experienced a complete reduction of depressive symptoms (the total score on the Hamilton scale at the end of the study was less than 10) (Fig. 2, 3). These data characterize the speed and completeness of the thymoanaleptic effect of the drug. However, given the open and non-comparative nature of the study, the role of the placebo effect in achieving such high efficacy rates of Azafen cannot be ruled out. It is known that the placebo effect in depression varies from 30 to 50% [7]. Nevertheless, it can be stated with a reasonable degree of confidence that the dynamics of reducing the degree of depression and anxiety during Azafen therapy is quite pronounced and indisputable. Azafen was very effective in eliminating sleep disorders associated with depression. Clinically, this was manifested by a gradual increase in the duration and then an increase in the quality of sleep in the absence of a truly hypnotic effect, symptoms of consequences and daytime sleepiness.

The antidepressant effect of Azafen was manifested not only by an anxiolytic and some activating components, but also by a harmonious reduction of the entire depressive syndrome, including the somatic symptom complex. Similar dynamics were noted in relation to other symptoms of depression - performance, activity, insomnia, lethargy, hypochondriacal manifestations. At the same time, the drug did not affect somatic characteristics - blood pressure, heart rate, body weight.

Of the adverse events, only isolated cases of dry mouth, nausea, and drowsiness were recorded. Moreover, these side effects were quickly reduced by reducing the dosage and in no case led to patients refusing to continue therapy. The drug did not increase anxiety, and also did not exhibit cardiotoxic and anticholinergic effects. During treatment with Azafen, the quality of life of patients significantly improved. At the end of the course of treatment, almost everyone characterized it as “good” or “excellent.”

It should be noted that such impressive results of the study were to a certain extent predetermined by the selection of patients with an average level of depression. We deliberately avoided prescribing Azafen to patients with severe and treatment-resistant depression. The issue of clarifying the effectiveness of Azafen in such groups of patients is a complex methodological task and requires randomized comparative studies. The main result of this work is the statement of the possibility of effective use of azafen in the treatment of various syndromic forms of depression of moderate severity. Good tolerability of the drug, the transient nature of side effects, the insignificant severity of the latter and the almost complete absence of influence on the condition and functioning of internal organs and systems are important advantages in the treatment of a wide range of patients with depression. Moreover, the above characteristics make it possible to recommend the prescription of azafen both in hospitals and in the community network by both psychiatrists and general practitioners.

Based on the results of the study, the following conclusions can be drawn:

Azafen, when used for 6 weeks, provides a significant reduction in affective pathology in patients with neurotic disorders, without causing significant side effects and without affecting the cognitive functions of patients.
The optimal daily dose was 75-150 mg/day.
If there are indications for antidepressant therapy, Azafen can be recommended for widespread use in both inpatient and outpatient settings.

Literature

1. Aleksandrovsky Yu.A., Bardenshtein L.M., Avedisova A.S.. Psychopharmacotherapy of borderline mental disorders. // M.: “Geotar-medicine”, 2000.

2. Mashkovsky M.D. Medicines. // M. “Medicine”, 1996, p. 121.

3. Mosolov S.N. Clinical use of modern antidepressants. // St. Petersburg: Medical Information Agency, 1995, p. 133.

4. Psychopharmacological and antiepileptic drugs approved for use in Russia. Ed. Mosolova S.N. 2nd ed.. M, 2004, p. 133.

5. Smulevich A.B. Depression in general medical practice. M., 2000.

6. Shinaev N.N., Dachevskaya I.I., Akzhigitov R.G. Experience in the treatment of borderline mental disorders in the “Clinic of Neuroses”. // Russian Psychiatric Journal. 2000, No. 1, p. 54-58.

7.down WA. Predictors of placebo-response in depression. Psychopharmacol Bull 1988; 24: 14-7.

Contraindications

Therapy with Azafen is absolutely contraindicated in the following cases:

severe liver and/or kidney pathologies;
breastfeeding;
concurrent use of MAO inhibitors ;
personal hypersensitivity to pipofezin or other auxiliary ingredients of tablets;
pregnancy.

Patients suffering from:

chronic heart failure;
infectious diseases;
myocardial infarction;
diabetes mellitus;
coronary heart disease;
cerebrovascular accidents (including post-stroke conditions).

Also, pediatric patients require a particularly careful approach to prescribing Azafen.

Side effects of Azafen

Some patients experienced side effects while using Azafen, such as headaches , nausea , dizziness and vomiting . Also, if the patient is sensitive to the active or auxiliary ingredients of the tablets, allergic reactions .

Release form and composition

Azafen belongs to the group of tricyclic antidepressants. Has sedative properties.

Available in the form of tablets containing 25 mg of the active substance - pipofezin dihydrochloride monohydrate, located in a carrier matrix.

Excipients:

Potato starch;
Colloidal silicon dioxide (aerosil);
Microcrystalline cellulose;
Lactose monohydrate;
Povidone (low molecular weight medical polyvinylpyrrolidone);
Magnesium stearate.

Azafen, instructions for use (Method and dosage)

Instructions for use of Azafen involve a course of prescription of the drug tablets for up to 1 year (the minimum therapeutic course is 1-1.5 months).

As a rule, Azafen is initially prescribed in a daily dose of 25-50 mg (1-2 tablets) taken twice a day (morning and afternoon). In case of good tolerability of the drug and adequate response of the patient to the treatment, a gradual increase in the daily dosage is practiced to 150-200 mg (6-8 tablets), sometimes up to 400 mg (16 tablets), with its 3-4-fold dose in 24 hours (last dose taken before bedtime). The optimal therapeutic dosage is considered to be a daily dose of 150-200 mg (6-8 tablets). It is permissible to take 500 mg (20 tablets) of the drug within a maximum of 24 hours. After achieving the desired positive effect of therapy, the patient is transferred to maintenance dosages varying in the range of 25-75 mg (1-3 tablets) per day.

Azafen® (Azaphen)

Manufacturer: NIZHFARM OJSC (Russia)

tab. 25 mg: 14, 28, 30, 40, 42, 50, 56, 100, 200, 250 or 300 pcs. Reg. No.: LS-000325

Clinical and pharmacological group:

Antidepressant

Release form, composition and packaging

Pills

yellowish-greenish color, flat-cylindrical, chamfered; Marbling is allowed.

1 tab.
pipofezin	25 mg

Excipients:

potato starch - 4 mg, colloidal silicon dioxide (aerosil) - 1.75 mg, microcrystalline cellulose - 45 mg, lactose monohydrate - 22 mg, povidone (low molecular weight medical polyvinylpyrrolidone) - 1.25 mg, magnesium stearate - 1 mg.

10 pieces. — cellular contour packages (3) — cardboard packs. 10 pieces. — contour cell packaging (4) — cardboard packs. 10 pieces. — contour cell packaging (5) — cardboard packs. 14 pcs. — cellular contour packages (1) — cardboard packs. 14 pcs. — contour cell packaging (2) — cardboard packs. 14 pcs. — cellular contour packages (3) — cardboard packs. 14 pcs. — contour cell packaging (4) — cardboard packs. 100 pieces. — polymer jars (1) — cardboard packs. 200 pcs. — polymer jars (1) — cardboard packs. 250 pcs. — polymer jars (1) — cardboard packs. 300 pcs. — polymer jars (1) — cardboard packs.

Description of the active components of the drug "Azafen®"

pharmachologic effect

Tricyclic antidepressant. By blocking the reverse neuronal uptake of monoamines by presynaptic membranes, it increases their content in the synaptic cleft, which leads to relief of symptoms of depression. The thymoleptic effect of the drug is combined with sedative activity and anxiolytic effect. Unlike tricyclic antidepressants, it does not have anticholinergic properties, does not affect the activity of MAO, and does not have a cardiotoxic effect.

Indications

- depressive disorders of mild and moderate severity (including depressive states in chronic somatic diseases).

Dosage regimen

Initial dose for adults

is 25-50 mg in 2 doses (morning and lunch). If well tolerated, the dose is gradually increased to 150-200 mg/day (in 3-4 doses, the last dose before bedtime), in some cases - up to 400 mg/day. The optimal daily dose is 150-200 mg, the maximum daily dose is 400-500 mg. When the desired effect is achieved, switch to maintenance doses - 25-75 mg/day. The course of treatment is up to 1 year (at least 1-1.5 months).

After establishing the optimal daily dose using Azafen® 25 mg tablets, Azafen® MB (modified-release tablets) 150 mg is prescribed 1 time (morning) or 2 times (morning and evening), taking into account effectiveness and tolerability.

Side effect

From the side of the central nervous system:

headache, dizziness.

From the digestive system:

nausea, vomiting.

Other:

allergic reactions.

Contraindications

- severe liver and/or kidney failure;

- simultaneous use of MAO inhibitors;

- pregnancy;

- lactation period (breastfeeding);

- hypersensitivity to the drug.

Carefully _

the drug should be prescribed for chronic heart failure, myocardial infarction, ischemic heart disease, a condition after an acute cerebrovascular accident, infectious diseases, diabetes mellitus, in childhood (there is insufficient data on the safety of use).

Pregnancy and lactation

The drug is contraindicated for use during pregnancy and lactation.

Use for liver dysfunction

The drug is contraindicated in severe renal failure.

Use for renal impairment

The drug is contraindicated in severe renal failure.

Application for children

Carefully _

the drug should be prescribed in childhood (there is insufficient data on the safety of use).

special instructions

After transferring from therapy with MAO inhibitors to Azafen®, an interval of 2 weeks is required.

Periodic monitoring of liver and kidney functions is necessary.

During the treatment period, alcohol consumption is prohibited.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, patients should refrain from engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions, for example, driving.

Overdose

There is no information about overdose.

Drug interactions

When used simultaneously, Azafen® potentiates the effects of ethanol and other central nervous system depressants, antihistamines and anticoagulants.

Reduces the effectiveness of anticonvulsant therapy.

An in vitro study showed that pipofezin is not an inhibitor or inducer of the isoenzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, therefore it is unlikely that Azafen® will interact with drugs that are substrates of these isoenzymes. Fluvoxamine, propafenone, mexiletine, ciprofloxacin, being inhibitors of CYP1A2, can increase the concentration of pipofezine in the blood plasma.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Storage conditions and periods

List B. The drug should be stored in a dry place, protected from light, out of reach of children, at a temperature not exceeding 25°C. The shelf life of tablets is 5 years, modified-release tablets are 3 years.

Drug interactions

When used simultaneously, Azafen® potentiates the effects of ethanol and other central nervous system depressants, antihistamines and anticoagulants.

Reduces the effectiveness of anticonvulsant therapy.

Interaction

While taking Azafen, there is a decrease in the effectiveness of concurrent anticonvulsant therapy .

The combined use of pipofezin with anticoagulants , antihistamines , ethanol-containing and other central nervous system depressants potentiates their effectiveness and, as a result, toxicity .

Co-administration of ciprofloxacin , fluvoxamine , mexiletine , propafenone and other drugs that inhibit the CYP1A2 isoenzyme may cause an increase in the plasma concentration of pipofezin .

Indications for use

The effectiveness of pipofezin is based on the relief of symptoms of depression, therefore indications for the use of Azafen are depression of various origins, including:

Endogenous;
Exogenous;
Alcohol;
Senile.

In addition, the drug is used to treat the following conditions:

Depression due to chronic somatic diseases;
Anxiety and depressive syndromes;
Depressive phase in manic-depressive syndrome;
Astheno-neurotic syndromes.

First of all, after the start of treatment, an improvement in mood occurs, followed by the disappearance of anxiety and lethargy.

special instructions

depressive state itself is associated with a risk of suicidal tendencies , and therefore, during the treatment of such mental disorders patients should be monitored for early detection of changes in their behavioral sphere and the prevention of possible suicide attempts .

between courses of therapy using MAO inhibitors and Azafen.

At all stages of the therapeutic course, it is necessary to periodically check the functionality of the liver / kidneys .

While taking Azafen tablets, it is better for the patient to refrain from performing potentially life-threatening activities, including driving.

Analogs

Level 4 ATC code matches:
Pipofezin

Bethol

Incazan

Melitor

Miaser

Velafax

Mirtazonal

Venlaxor

Remeron

Venlafaxine

Lerivon

Mirtazapine

Cymbalta

Velaxin

Coaxil

Pyrazidol

Deprim

Gelarium Hypericum

Negrustin

Trittico

Analogues of Azafen are represented by medicinal drugs with a similar main effect:

Alventa;
Velaxin;
Bethol;
Venlaxor;
Mirzaten;
Deprim;
Mirtazonal;
Coaxil;
Pyrazidol;
Noxibel;
Remeron;
Trittico;
Neuroplant;
Ephevelon;
Tetrindole , etc.

Reviews about Azafen

In the process of discussing the effectiveness and relative safety of using this antidepressant , positive reviews about Azafen are much more common than negative statements about it. Most patients who took this drug at one time managed to overcome their own depression , cope with feelings of anxiety and apathy , and significantly improve their mood and general mental state. Mentions of Azafen's side effects are quite rare and are mainly related to personal sensitivity to its ingredients.

However, it is worth recalling that the personal prescription and use of any antidepressant medications is unacceptable and can lead to serious negative consequences. Treatment of a person’s mental sphere, with individual selection of a medicinal drug and its dosage regimen, should be carried out exclusively by a psychotherapist with experience in conducting such therapy.

Azafen

Azafen (pipofezin) is a drug from the group of tricyclic antidepressants. Prescribed for mild to moderate depression. This is an original drug developed in the USSR in the 60s of the last century. Introduced into medical practice in 1970. In 1996, the drug was discontinued due to the lack of pharmaceutical raw materials for its production, but in 2005 Azafen reappeared on pharmacy shelves. The effect of the drug is based on its ability to increase the level of serotonin and norepinephrine in the central nervous system. Among other tricyclic antidepressants, the drug stands out due to its lack of toxic effect on the heart and anticholinergic activity. Azafen also has a moderate sedative effect. The effectiveness of the drug has been confirmed in several clinical trials. In patients with mild to moderate depression, Azafen showed a uniform reduction in the severity of symptoms of affective disorders. In half of the study participants, the symptoms were completely relieved; in the rest, the clinical picture was noticeably smoothed out. Experience with Azafen shows that when using the drug, mood improvement is observed most quickly, then anxiety symptoms (anxiolytic component) are eliminated, and lethargy is eliminated a little more slowly. Thus, the sedative and anxiolytic effects of the drug are somewhat ahead of its antidepressant effect. Complete elimination of inhibition of thinking and speech, as well as restoration of previous motor activity, is observed after a month of drug therapy. Azafen has demonstrated its effectiveness in depression of alcohol origin, both after abstinence and at the stage of remission.

The drug eliminates the craving for alcohol, reduces the risk of developing behavioral disorders, and improves mood. Azafen is also used for depression caused by somatic pathologies, incl. cardiovascular and gastrointestinal diseases, menopausal syndrome. Azafen has a favorable safety profile. Undesirable side reactions (weakness, drowsiness, absent-mindedness, slight increase in heart rate, hyposalivation, headache) are, as a rule, mild in severity and, when taking the drug in a daily dose of 100–200 mg, develop only in every fifth case. Pipofezin is quickly and completely absorbed from the gastrointestinal tract. Peak concentration in the blood is reached 2 hours after administration. Half-life is 16 hours. Excreted from the body mainly with urine. Azafen is contraindicated in persons with individual intolerance to pipofezin, severe liver and kidney diseases, during pregnancy and breastfeeding. The frequency of use of the drug is 2 times a day (after waking up in the morning and at lunchtime). If the drug is well tolerated, it is taken 3-4 times a day, with the last dose before going to bed. When control of the symptoms of the disease is achieved, the dose is reduced (so-called maintenance therapy). The duration of the medication course is at least one month. The maximum duration is up to one year. Taking Azafen is incompatible with drinking alcohol. During the medication course, you should refrain from engaging in potentially hazardous activities that require attention and concentration, incl. driving a car.