Duloxenta 30mg capsules №14

Composition

1 capsule enteric 30 mg contains pellets:

Active substance:

duloxetine hydrochloride 33.675 mg, equivalent to duloxetine 30,000 mg

Excipients: sugar grits, hypromellose 6cP, sucrose, hypromellose phthalate HP-50, talc, triethyl citrate

Hard gelatin capsules No. 3

Body: titanium dioxide (E171), gelatin

Lid: indigo carmine (E132), titanium dioxide (E171), gelatin

Ink composition: shellac (E904), ethanol (E1510), isopropanol, butanol, propylene glycol

(E1520), ammonia water (E527), iron dye black oxide (E172), potassium hydroxide (E525), purified water

Duloxetine is an antidepressant, serotonin and noradrenaline reuptake inhibitor, and weakly inhibits dopamine uptake, without significant affinity for histaminergic, dopaminergic, cholinergic and adrenergic

receptors. The mechanism of action of duloxetine in the treatment of depression is to suppress the reuptake of serotonin and noradrenaline, resulting in increased serotonergic and noradrenergic neurotransmission in the central nervous system.
system (CNS).

Duloxetine has a central mechanism for the suppression of pain, which is primarily manifested by an increase in the pain sensitivity threshold in pain syndrome of neuropathic etiology.

Suction

Duloxetine is well absorbed when taken orally. Absorption begins 2 hours after taking the drug. The maximum concentration (Stah) of duloxetine is reached 6 hours after administration.

Meal does not affect Stach duloxetine, but increases the time it takes to reach Stax from 6 to 10 hours, which slightly decreases the degree of absorption (approximately by 11%).

Distribution 2

The apparent volume of distribution is about 1640 liters. Duloxetine binds well to plasma proteins (> 90%), mainly with albumin and a 1-acid glycoprotein, but disorders of the liver or kidneys do not affect the degree of binding to plasma proteins.

Metabolism

Duloxetine is actively metabolized and its metabolites are mainly excreted by the kidneys. Both the CYP2D6 isoenzyme and the CYP1A2 isoenzyme catalyze the formation of two major metabolites (4-hydroxiduloxetine glucuronide, 5-hydroxy, 6-methoxydioxy-type sulfate).

Circulating metabolites do not possess pharmacological activity.

Removal

The duration of the half-life (T1 / 2) of duloxetine is 12 hours. The average clearance of duloxetine is 101 l / h.

Special patient groups

Floor

Although differences in the pharmacokinetics of duloxetine in men and women were found (the average clearance of duloxetine is lower in women), these differences are not so great that there is a need for dose adjustment depending on gender.

Age

Although differences were foundThe pharmacokinetics of duloxetine in middle-aged and elderly patients (the area under the concentration-time curve (AUC) is longer and the duration of T 1/2 of the drug is greater in elderly patients), these differences

not enough to change the dose depending only on the age of the patient.

Renal dysfunction

In patients with severe impaired renal function (end-stage chronic renal failure) on hemodialysis, the values ​​of Stax and the average exposure (AUC) of duloxetine were increased 2 times. In this connection follows

consider the feasibility of reducing the dose of duloxetine in patients with clinically significant renal dysfunction.

Liver dysfunction

Patients with clinical signs of liver failure may experience slower metabolism and duloxetine elimination. After a single dose of 20 mg of duloxetine in 6 patients with cirrhosis of the liver with moderate impairment

liver function (class B on the Child-Pugh scale), the duration of T1 / 2 duloxetine was approximately 15% higher than in healthy people of a corresponding sex and age with a fivefold increase in the average exposure. Despite the fact that Stach in patients with

cirrhosis was the same as in healthy people, T1 / 2 was about 3 times longer.

Exacerbation of manic / hypomania state. As with the use of similar drugs that affect the central nervous system, duloxetine should be used with caution in patients with a history of manic episodes.

Epileptic seizures

As with the use of similar drugs that affect the central nervous system, duloxetine should be used with caution in patients with history of epileptic seizures.

Midriaz

When taking duloxetine, cases of mydriasis were observed, so caution should be exercised when using duloxetine in patients with elevated intraocular pressure or in individuals at risk of developing acute angle-closure glaucoma.

Increased blood pressure In isolated cases, there was a rise in blood pressure during the treatment period. duloxetine. In patients with arterial hypertension and / or other cardiovascular diseases, it is recommended to measure blood pressure.

Impaired renal function, liver

In patients with severe impaired renal function (CK <3 0 ml / min) or severe hepatic insufficiency, an increase in plasma duloxetine concentration is observed. If these patients have clinically justified duloxetine, apply lower initial doses of the drug.

Suicidal behavior

The risk of suicide exists in all patients with depression and certain other mental disorders. This danger may persist until remission occurs. As a consequence, patients who have the danger of suicide is the highest, should be in the process of pharmacotherapy under careful medical supervision.As well as taking other medications that have a similar pharmacologic action mechanism (duo -settin) (SSRI), the use of duloxetine in the process of treatment, or when it was discontinued in some cases, was associated with the development of suicidal thoughts and suicidal behavior.

Application

duloxetine in patients under 18 years of age has not been studied, duloxetine is not intended for use in these patients. A causal relationship between taking duloxetine and the occurrence of suicidal events in patients of this age

group is not installed. At the same time, some analytical reviews of the results of a number of studies using antidepressants for the treatment of mental disorders indicate an increased risk of developing suicidal thoughts and / or suicidal behavior in children, adolescents and adults under 25 years of age compared with placebo. Doctors should convince patients at any time to report any thoughts or feelings that are disturbing them.

Increased risk of bleeding SIOZS and PPRI, including duloxetine, may increase the risk of bleeding, including gastrointestinal (see section "Side effects"). Therefore, duloxetine should be used with caution in patients taking anticoagulants and / or drugs that affect platelet function. (for example, nonsteroidal anti-inflammatory drugs, including aspirin) and in patients with a history of bleeding.

Hyponatremia

Cases of hyponatremia were reported very rarely (in some cases, the serum sodium content was lower than 110 mmol / l). Most of these cases occurred in elderly patients, especially in combination with altered fluid balance in recent history or in the presence of conditions that predispose to changes in fluid balance.

Hyponatremia may manifest as nonspecific symptoms (such as dizziness, weakness, nausea, vomiting, confusion, drowsiness, lethargy).

Signs and symptoms in more severe cases included fainting, falling, and seizures.

Monoamine oxidase inhibitors

In patients taking a serotonin reuptake inhibitor simultaneously with MAOI, there were cases of serious reactions, sometimes fatal, among which were hyperthermia, rigidity, myoclonus, peripheral disorders with possible sharp fluctuations in the indices of vital functions and changes in mental status, including pronounced agitation with the transition to delirium and coma. These reactions were also observed in patients who, shortly before use MAOI has been canceled serotonin reuptake inhibitor. In some cases, patients had symptoms characteristic of neuroleptic malignant syndrome. Effects of simultaneous use of duloxetine and MAOI were not evaluated. neither in humans nor in animals.Therefore, taking into account the fact that duloxetine is an inhibitor of reuptake of both serotonin and noradrenaline, it is not recommended to take duloxetine simultaneously with an MAOI or for at least 14 days after termination of treatment of MAOI. Based on the duration of the T-dose of duloxetine, a break should be taken for at least 5 days after the end of taking duloxetine before taking an MAOI.

Enhance the activity of liver enzymes

In some patients taking duloxetine in clinical studies, there was an increase in the activity of liver enzymes. The observed deviations were usually transient in nature and disappeared spontaneously or after the cancellation duloxetine. A significant increase in the activity of liver enzymes (10 times or more above the upper limit of the norm), as well as damage to the liver of cholestatic or mixed genesis, were rarely observed, and in some cases were associated with excessive use of alcohol or previous liver disease. It is recommended to use duloxetine with caution in patients who consume significant amounts of alcohol, as well as with existing liver disease.

Specific information on auxiliary substances Duloxent® contains sucrose, therefore it should not be used in the following conditions: sucrase / isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption syndrome.

Impact on the ability to perform potentially hazardous activities that require special attention and quick reactions (for example, driving, working with moving machinery)

While taking duloxetine, sedation, drowsiness, and other side effects may occur. In this regard, patients taking the drug Duloksenta®, should be careful when driving a car or dangerous mechanical means.

• Depression.

• Painful form of peripheral diabetic neuropathy.

• Generalized anxiety disorder.

• Chronic musculoskeletal pain (including due to fibromyalgia, chronic pain in the lower back and with osteoarthritis of the knee joint).

• Hypersensitivity to the drug.
  
  Simultaneous use with monoamine oxidase inhibitors (see section "Special instructions").

• Noncompensated angle-closure glaucoma.

• Children's age up to 18 years.

• Surase / isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption syndrome.

• Diseases of the liver, accompanied by liver failure.

• Concurrent use of potent inhibitors of the CYP1A2 isoenzyme (fluvoxamine, Ciprofloxacin , enoxacin).

• Severe chronic renal failure (creatinine clearance (CK) less than 30 ml / min).

• Uncontrolled arterial hypertension.

Carefully

Mania and bipolar disorder (including history), seizures (including history), intraocular hypertension or the risk of developing an acute attack of angle-closure glaucoma, suicidal thoughts and attempts at anamnesis, increased risk of developing hyponatremia (elderly patients , liver cirrhosis, dehydration, diuretic administration), impaired liver function and renal failure (CC 30-60 ml / min).

Use during pregnancy and during breastfeeding

Pregnancy

Due to the lack of experience with duloxetine during pregnancy, Duloxent® should be prescribed during pregnancy only if the potential benefit to the mother greatly exceeds the potential risk to the fetus.

Patients should be warned that in the event of the onset or planning of pregnancy during the period of treatment with duloxetine, they should be informed of this by their doctor.

Epidemiological data suggest that the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, especially in late periods, may increase the risk of persistent pulmonary hypertension in the newborn. Despite the lack of research on the relationship between persistent pulmonary hypertension in newborns and the use of SSRIs, the potential risk cannot be excluded, given the mechanism of duloxetine (inhibition of serotonin reuptake).

As with the use of other serotonergic drugs, the syndrome of "cancellation" can be observed in newborns in the case of the use of duloxetine by the mother in the late period of pregnancy. Syndrome "cancellation" includes the following symptoms: decreased blood pressure, tremor, syndrome of increased neuro-reflex excitability, difficulty feeding, respiratory distress syndrome, convulsions. Most of the symptoms were observed during labor or during the first few days after birth.

Breastfeeding period

Due to the fact that duloxetine penetrates into breast milk (the concentration in the fetus is based on mg / kg body weight approximately 0.14% of the concentration in the mother), breastfeeding is not recommended during therapy with Duloxenta

Monoamine oxidase inhibitors (MAOIs)

Due to the risk of serotonin syndrome, duloxetine should not be used in combination with an MAOI, and for at least 14 days after stopping the treatment of MAOI. Based on the duration of T | / 2 duloxetine, you should take a break, for at least 5 days after the end of douloxetine intake before receiving IMAO.

For selective reversible MAOIs such as moclobemide, the risk of developing serotonin syndrome is lower. However, the simultaneous use of reversible MAOI and duloxetine is not recommended.

Inhibitors of the isoenzyme CYP1A2

Due to the fact that the CYP1A2 isoenzyme is involved in the metabolism of duloxetine, simultaneous administration of duloxetine with potential inhibitors of the CYP1A2 isoenzyme is likely to lead to an increase in the concentration of duloxetine.A potent inhibitor of the CYP1A2 isoenzyme fluvoxamine (100 mg 1 time per day) reduced the average plasma clearance of duloxetine by about 77%. Caution should be exercised when using duloxetine with CYP1A2 isoenzyme inhibitors (for example, some quinolone antibiotics) and lower doses of duloxetine should be used.

Drugs affecting the central nervous system

Caution should be exercised when using duloxetine simultaneously with other drugs and agents that affect the central nervous system, especially with those that have a similar mechanism of action, including ethanol. Simultaneous use with other drugs possessing serotonergic action (for example, IOZSN, SIOZS, triptans and tramadol), can lead to development of a serotoninovy ​​syndrome.

Serotonin syndrome

In rare cases, serotonin syndrome was observed with simultaneous use of SSRIs (for example, paroxetine, fluoxetine) and serotonergic drugs.

Care must be taken when using duloxetine concurrently with serotonergic antidepressants such as SSRIs, tricyclic antidepressants (clomipramine or amitriptyline), St. John's wort, venlafaxine or tryptans, tramadol, petidine and tryptophan.