Duloxent - instructions for use, dose, side effects, contraindications

Active substanceDuloxetineDuloxetine

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Duloxent®

capsules inwards

KRKA, dd, Novo mesto, AO

Duloxetine Canon

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CANONFARMA PRODUCTION, CJSC Russia

Simbalta®

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Eli Lilly East SA Switzerland

Dosage form: & nbspenteric-coated capsules

Composition:

1 capsule, enteric, 30 mg contains pellets:

Active substance: duloxegine hydrochloride 33.675 mg, equivalent to duloxetine 30,000 mg;

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

Hard gelatin capsules № 3

Housing: titanium dioxide (E171), gelatin;

Cap: indigo carmine (E132), titanium dioxide (E171), gelatin.

1 capsule, enteric 60 mg contains pellets:

Active substance: duloxetine hydrochloride 67.350 mg, equivalent to duloxetine 60,000 mg;

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

Hard gelatin capsules № 1

Housing: titanium dioxide (E171), indigocarmine (E132), iron dye oxide yellow (E172), gelatin

Cap: indigo carmine (E132), titanium dioxide (E171), gelatin.

Composition of ink: shellac (E904), ethanol (E1510), isopropanol, butanol, propylene glycol (E1520), aqueous ammonia (E527), iron dye black oxide (E172), potassium hydroxide (E525), purified water.

Description:

Capsules 30 mg:

Hard gelatin capsules No. 3, capsule body white, cap capsule dark blue. On the capsule body black ink is marked 30. The contents of the capsules are pellets of white or almost white color.

Capsules 60 mg:

Hard gelatin capsules number 1, the capsule body is yellowish green, the cap of the capsule is dark blue. On the shell of the capsule, black ink is marked 60. The contents of the capsules are pellets of white or almost white color.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.X.21 Duloxetine

Pharmacodynamics:

Duloxetine is an antidepressant, an inhibitor of reuptake of serotonin and norepinephrine, and weakly suppresses the capture of dopamine, without significant affinity for histaminergic. dopaminergic, cholinergic and adrenergic receptors.

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

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

Pharmacokinetics:

Suction

Duloxetine is well absorbed when ingested. Suction begins 2 hours after taking the drug. The maximum concentration (C_mOh) duloxetine is reached 6 hours after admission.

Eating does not affect C_mOh duloxetine, but increases the time to reach C_mOh from 6 to 10 hours, which slightly reduces the degree of absorption (by approximately 11%).

Distribution

The apparent volume of distribution is about 1640 liters. Duloxetine binds well to plasma proteins (> 90%), mainly with albumin and α1-acid glycoprotein, but violations 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. As isoenzyme CYP2D6, and isoenzyme CYP1A2 catalyze the formation of two major metabolites (4-hydroxyduloxetine glucuronide, 5-hydroxy, 6-methoxyduloxetine sulfate).

Circulating metabolites do not have pharmacological activity.

Excretion

The half-life of the half-life (T_1/2) of duloxetine is 12 hours.The average clearance of duloxetine is 101 l / h.

Special patient groups

Floor

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

Age

Despite the fact that the differences in the pharmacokinetics of duloxetine in patients of middle and old age (area under the concentration-time curve (AUC) above and duration T_1/2of the drug is greater in elderly patients), these differences are not sufficient to change the dose depending only on the age of the patient.

Impaired renal function

In patients with severe renal dysfunction (terminal stage of chronic renal failure) who are on hemodialysis, the values of C_mOh and medium exposure (AUC) of duloxetine increased 2-fold. In this connection, it should be considered the expediency of reducing the dose of duloxetine in patients with clinically pronounced renal dysfunction.

Impaired liver function

In patients with clinical signs of hepatic insufficiency, a slowdown in the metabolism and elimination of duloxetine can be observed.After a single dose of 20 mg of duloxetine in 6 patients with cirrhosis of the liver with moderate impairment of liver function (grade B on the Child-Pugh scale), the duration of T_1/2Duloxetine was approximately 15% higher than in healthy people of the corresponding sex and age with a fivefold increase in average exposure. Despite the fact that C_mOh in patients with cirrhosis was the same as in healthy people, T_1/2was about 3 times longer.

Indications:

- Depression;

- bolefic form of peripheral diabetic neuropathy;

- ggeneralized anxiety disorder;

- xthe chronic pain syndrome of the musculoskeletal system (including due to fibromyalgia, chronic pain syndrome in the lower back and osteoarthrosis of the knee joint).

Contraindications:

- Hypersensitivity to the drug;

- aboutsimultaneous use with monoamine oxidase inhibitors (see section "Special instructions");

- Mr.Compensated closed angle glaucoma;

- dEthnic age under 18;

- dsugar content / isomaltase, fructose intolerance, glucose-galactose malabsorption syndrome;

- zliver abnormalities accompanied by hepatic insufficiency;

- aboutsimultaneous intake of potent inhibitors of isoenzyme CYP1A2 (fluvoxamine, ciprofloxacin, enoxacin);

- tsevere chronic renal insufficiency (creatinine clearance (CK) less than 30 ml / min);

- Mr.controlled arterial hypertension.

Carefully:

Mania and bipolar disorder (including history), convulsions (including history), intraocular hypertension or the risk of developing an acute angle-closure glaucoma, suicidal thoughts and attempts in history, an increased risk of hyponatremia (elderly patients , liver cirrhosis, dehydration, diuretic administration), liver dysfunction and kidney failure (QC 30-60 ml / min).

Pregnancy and lactation:

Pregnancy

Due to the lack of experience with duloxetine during pregnancy, Duloxent® should be given during pregnancy only if the potential benefit to the mother is significantly greater than the potential risk to the fetus. Patients should be warned that in the event of the onset or planning of pregnancy during treatment with duloxetine, they need to inform their physician about it.

Epidemiological evidence suggests that the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, especially in later life, may increase the risk of persistent pulmonary hypertension in newborns. Despite the lack of research on the relationship between persistent pulmonary hypertension in newborns and the use of SSRIs, the potential risk can not be ruled out, given the mechanism of action of duloxetine (inhibition of serotonin reuptake).

As with the use of other serotonergic drugs, the "cancellation" syndrome can be observed in newborns if duloxetine is used by a mother at a late pregnancy.

The syndrome of "withdrawal" includes the following symptoms: lowering of blood pressure, tremor, a syndrome of increased nervous reflex excitability, feeding difficulties, respiratory distress syndrome, convulsions. Most of the symptoms were observed during childbirth or in the first few days after childbirth.

Breastfeeding period

Due to the fact that duloxetine penetrates into breast milk (concentration in the fetus is calculated as mg / kg body weightapproximately 0.14% of the concentration in the mother), breastfeeding is not recommended during therapy with Duloxent^®.

Dosing and Administration:

Inside. Capsules should be swallowed whole, not chewing and crushing.

Do not add Duloxent® to food or mix it with liquids, as this can damage the enteric coating of pellets.

Depression

The initial and recommended maintenance dose is 60 mg once a day, regardless of the time of ingestion. In clinical trials, a safety assessment of doses from 60 mg to a maximum dose of 120 mg per day was performed. However, there was no clinical evidence that no improvement was seen in patients not responding to the initial recommended dose, with an increase in dose.

The response to therapy is usually noted in 2-4 weeks after the start of treatment.

To avoid recurrence after reaching the answer to antidepressant therapy, it is recommended to continue treatment for several months. In patients who respond positively to duloxetine therapy, with repeated cases of depression in the history, further long-term treatment with a dose of 60 mg to 120 mg / day is possible.

Generalized anxiety disorder

The recommended initial dose in patients with generalized anxiety disorder is 30 mg per day, regardless of the time of ingestion. In patients with insufficient response to therapy, an increase in the dose to 60 mg, the usual maintenance dose in most patients, is possible.

In patients with concomitant depression, the initial and maintenance dose is 60 mg per day (see also the recommendations above). Clinical studies have shown the effectiveness of doses up to 120 mg / day, in addition, an assessment of these dosages in terms of safety. Therefore, in patients with an insufficient response to a dose of 60 mg, it may be advisable to increase the dose to 90 mg or 120 mg. The dose increase should be based on clinical response and tolerability.

To avoid relapse after reaching a response to therapy, it is recommended to continue treatment for several months.

Painful form of peripheral diabetic neuropathy

The initial and recommended maintenance dose is 60 mg once a day, regardless of the time of ingestion. During clinical trials, a safety assessment of doses from 60 mg to a maximum dose of 120 mg / day, divided into equal doses, was also performed.The concentration of duloxetine in blood plasma is characterized by significant individual variability. Therefore, in some patients with an insufficient response to a dose of 60 mg / day, improvements with a higher dose may be noted.

Evaluation of the response to therapy should be conducted after 2 months. In patients with an insufficient initial response, an improvement in response after a given period of time is unlikely.

It is necessary to regularly evaluate the therapeutic effect (at least once every 3 months).

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

Initial treatment: the recommended dose of Duloxent® is 60 mg once a day. Therapy can be started with a dose of 30 mg for 1 week to allow patients to adapt to the drug before increasing the dose to 60 mg once a day.

Evidence that higher doses provide an additional benefit are not available, even in patients who do not respond to drug therapy at a dose of 60 mg.Higher doses are associated with a high incidence of adverse reactions.

Continuation of treatment: the effectiveness of duloxetine in the treatment of fibromyalgia was demonstrated in placebo-controlled studies of up to 3 months. Efficacy has not been established in longer-term studies, but the decision to continue treatment should be based on the individual response of the patient.

Impaired renal function

With QC 30-80 ml / min dose adjustment is not required, with QC less than 30 ml / min, the use of Duloxent® is contraindicated.

Impaired liver function

The drug Duloxent® can not be administered to patients with liver disease leading to liver failure.

Age

Elderly patients for the treatment of generalized anxiety disorder are recommended an initial dose of 30 mg for 2 weeks before starting duloxetine at a target dose of 60 mg. In the future, the use of the drug in a dose of more than 60 mg per day to achieve a good result. A systematic evaluation of the drug intake in a dose exceeding 120 mg was not performed. When duloxetine is used for other indications, dose adjustment is not required depending on the age of the patient. Recommended use of the drug in patients ≥ 18 years. Duloxetine is not recommended for children <18 years of age, due to the lack of data on its safety and efficacy when used in this age group of patients.

Abolition of therapy

It should be avoided abrupt discontinuation of therapy. If treatment with duloxetine is discontinued, the dose should be gradually reduced within 1-2 weeks in order to reduce the risk of withdrawal syndrome. If after the dose reduction or after the cessation of treatment the expressed symptoms of "withdrawal" appear, then continuation of the administration of the previously prescribed dose may be considered. Subsequently, the doctor may continue to reduce the dose, but even more gradually.

Side effects:

The most common side effects in patients taking duloxetine, there was nausea, headache, dryness of the oral mucosa, drowsiness and dizziness. Nevertheless, most of these side effects were mild and moderate, occurred at the beginning of therapy, and subsequently their severity decreased.

Table 1 presents side effects and abnormalities in laboratory indicators noted in clinical trials and / or post-marketing periods.

Table 1.

Often (≥ 10%)	Often (<10% and ≥ 1%)	Infrequently (<1% and ≥ 0,1%)	Rarely (<0.1% and ≥ 0,01%)	Rarely (<0,01%)
Infectious and parasitic diseases
		Laryngitis
Immune system disorders
			Anaphylactic reaction Hypersensitivity
Disorders from the endocrine system
			Hypothyroidism
Disorders from the metabolism and nutrition
	Decreased appetite	Hyperglycemia (especially often observed in patients with diabetes mellitus)	Dehydration Hyponatremia Syndrome of inadequate secretion of antidiuretic hormone (ADH)⁶
Disorders of the psyche
	Insomnia Agitation Decreased libido Anxiety Violation of orgasm Unusual dreams	Suicidal thoughts^5,7 Sleep disturbance Bruxism Disorientation Apathy	Suicidal behavior^5,7 Mania Hallucinations Aggression and rage⁴
Disturbances from the nervous system
Headache Drowsiness	Dizziness Lethargy Tremor Paresthesia^4,8	Myoclonic cramps and akathisia⁷ Nervousness Violation of attention Dysgeusia Dyskinesia Restless legs syndrome Decreased sleep quality	Serotonin syndrome⁶ Convulsions¹ Psychomotor agitation⁶ Extrapyramidal disorders⁶
Disturbances on the part of the organ of sight
	Blurred vision	Mydriasis Visual impairment	Glaucoma
Hearing disorders and labyrinthine disorders
	Noise in ears¹	Vertigo Ear pain
Heart Disease
	Heart palpitations	Tachycardia Nadzheludochkovaya arrhythmia, mainly atrial fibrillation
Vascular disorders
	Increased blood pressure³ Hyperemia (including "hot flashes")	Fainting² Hypertension^3,7 Orthostatic hypotension² Coldness of the extremities	Hypertensive crisis^3,6
Disturbances from the respiratory system, chest and mediastinal organs
	Yawn	Feeling tight in the throat Nose bleed
Disorders from the gastrointestinal tract
Nausea Dryness of the oral mucosa	Constipation Diarrhea Abdominal pain Vomiting Dyspepsia Flatulence	Gastrointestinal bleeding⁷ Gastroenteritis Belching Gastritis Dysphagia	Stomatitis Smell from the mouth Hematocheia Microscopic colitis
Disturbances from the liver and bile ducts
		Hepatitis³ Increased activity of "hepatic" enzymes (alanine aminotransferase (ALT), Aspartate aminotransferase (ACT) Acute liver damage	Liver failure⁶ Jaundice⁶
Disturbances from the skin and subcutaneous tissues
	Increased sweating Rash	Night sweating Hives Contact dermatitis Cold sweat The photosensitization reaction Increased tendency to bruising	Stevens-Johnson Syndrome⁶ Angioedema	Cutaneous vasculitis
Disturbances from musculoskeletal and connective tissue
	Musculoskeletal pain Muscle spasm	Muscle Stress Muscle cramps	Trism (spasm of masticatory muscles)
Disorders from the kidneys and urinary tract
	Dysuria (urination disorder) Pollakiuria (frequent urination)	Retention of urine Difficult beginning of urination Nocturia Polyuria Reduction of the flow of urine	Abnormal odor of urine
Violations of the genitals and mammary gland
	erectile disfunction Ejaculation disorder Ejaculation delay	Gynecological bleeding Violation of the menstrual cycle Sexual dysfunction Pain in the testicles	Symptoms of menopause Galactorrhea Hyperprolactinemia
General disorders and disorders at the site of administration
	Falls Fatigability	Chest pain⁷ Abnormal sensations Feeling cold Thirst Chills Malaise Feeling of heat Violation of gait
Laboratory and instrumental data
	Weight loss	Weight gain Increase in activity of creatine phosphokinase in blood plasma Increase in the content of potassium in blood plasma	Increase in the concentration of cholesterol in the blood plasma

¹ Cases of seizures and noise in the ears were also noted after the abolition of therapy.

²Cases of orthostatic hypotension and syncope were noted more often at the beginning of therapy.

³See section "Special instructions".

⁴Cases of aggression and rage were noted especially at the beginning of treatment with duloxetine or after the completion of therapy.

⁵Cases of suicidal thoughts or suicidal behavior were noted during duloxetine therapy or immediately after the completion of therapy.

⁶ The estimated incidence of adverse reactions reported during post-marketing follow-up was not observed during placebo-controlled clinical trials.

⁷There are no statistically significant differences from placebo.

⁸Falls were more common in elderly patients (≥65 years of age).

⁹ Estimated frequency based on data from all clinical trials.

Description of some unwanted reactions

The abolition of duloxetine (especially severe) often leads to a withdrawal syndrome, which includes the following symptoms: dizziness, sensory disturbances (including paresthesia or an electric shock, especially in the head), sleep disturbances (including insomnia and unusual dreams), weakness, drowsiness, agitation or anxiety, nausea and / or vomiting, tremor, headache, myalgia, irritability, diarrhea, hyperhidrosis and vertigo.

Usually, when SSRIs and serotonin and noradrenaline reuptake inhibitors (SSRIs) are taken, these phenomena have a weak or moderate degree of severity and limited character. Nevertheless, in some patients, these phenomena can be more severe and / or prolonged. Therefore, in the absence of the need for further duloxetine therapy, a gradual dose reduction is recommended (see the section on "Dosage and administration" and "Special instructions").

At a short-term duloxetine intake (up to 12 weeks) in patients with painful form of peripheral diabetic neuropathy, there was a slight increase in fasting blood glucose concentration while maintaining a stable concentration of glycosylated hemoglobin, duloxetine, and in the placebo group.With prolonged therapy with duloxetine (up to 52 weeks), there was a slight increase in the concentration of glycosylated hemoglobin (HbAlc), which was 0.3% higher than the increase in the corresponding indicator in patients receiving other treatment. With regard to the fasting glucose and total cholesterol in the blood in patients taking duloxetine, there was a slight increase in these indicators compared with a slight decrease noted in the control group of patients.

Corrected (relative to the heart rate) value of the interval QT in patients taking duloxetine, did not differ from this indicator in the placebo group.

Clinically significant differences between the intervals QT, PR, QRS, or QTcB in the group of patients taking duloxetine, and in the placebo group it was not revealed.

Overdose:

It is known about cases of overdose in clinical studies with simultaneous ingestion of up to 3000 mg of duloxetine, either alone or in combination with other drugs. In this case, one of these cases ended in a fatal outcome. However, spontaneous (postmarketing) reports contained descriptions of lethal acute overdoses, usually with a combined intake of several drugs,in which the dose of duloxetine was not more than 1000 mg.

Symptoms

An overdose of duloxetine (isolated or combined) can be accompanied by the following symptoms: drowsiness, coma, clonic convulsions, serotonin syndrome, vomiting and tachycardia. In preclinical studies (in animals), the main signs of intoxication associated with overdose were disorders of the central nervous and digestive systems and included such manifestations as tremor, clonic convulsions, ataxia, vomiting and decreased appetite.

Treatment

A specific antidote is not known, but in the case of the development of serotonin syndrome, it is possible to correct treatment with cyproheptadine and apply methods of normalizing body temperature. A sufficient supply of fresh air should be ensured. It is recommended to monitor cardiac activity and monitor the main indicators of vital activity, along with the conduct of symptomatic and supportive treatment. Gastric lavage can be indicated if there is little time left from the time of taking the drug inside, or within the symptomatic treatment.In order to limit the absorption can be applied Activated carbon. Duloxetine characterized by a large volume of distribution, and therefore the effectiveness of forced diuresis, hemoperfusion, exchange perfusion is questionable.

Interaction:

Inhibitors of monoamine oxidase (MAOI)

Because of the risk of developing serotonin syndrome duloxetine should not be used in combination with MAOI, and for at least 14 days after discontinuation of MAOI treatment. Based on the duration T_1/2 duloxetine, you should take a break, at least 5 days after the end of duloxetine intake before taking MAOI.

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.

Inhibitor inhibitors CYP1A2

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

Drugs affecting the central nervous system

Caution should be exercised when duloxetine is used concurrently with other drugs and agents that affect the central nervous system, especially those that have a similar mechanism of action, including ethanol. Simultaneous use with other drugs that have a serotonergic effect (eg, SSRI, SSRIs, triptans and tramadol), can lead to the development of serotonin syndrome.

Serotonin syndrome

In rare cases with simultaneous use of SSRIs (for example, paroxetine, fluoxetine) and serotonergic drugs, serotonin syndrome was observed. Care should be taken when using duloxetine concomitantly with serotonergic antidepressants, such as SSRIs, tricyclic antidepressants (clomipramine or amitriptyline), St. John's Wort, venlafaxine or triptans, tramadol, pethidine and tryptophan.

Drugs metabolized by isoenzyme CYP1A2

The simultaneous use of duloxetine (60 mg twice daily) did not significantly affect the pharmacokinetics of the isophosphin metabolized geofillin CYP1A2. Duloxetine unlikely to have a clinically significant effect on the metabolism of isoenzyme substrates CYP1A2.

Drugs metabolized by the isoenzyme CYP2D6

Duloxetine is a mild isoenzyme inhibitor CYP2D6. When taking duloxetine in a dose of 60 mg 2 times a day, simultaneously with a single dose of desipramine, the substrate of the isoenzyme CYP2D6, AUC desipramine is increased 3 times. Simultaneous administration of duloxetine (40 mg twice daily) increased the equilibrium concentration of tolterodine (2 mg twice daily) by 71%, but did not affect the pharmacokinetics of 5-hydroxymetabolite. Therefore, caution should be exercised when using duloxetine with drugs that are mainly metabolized by isoenzyme CYP2D6 and have a narrow therapeutic index.

Inhibitor inhibitors CYP2D6

Since the isoenzyme CYP2D6 is involved in the metabolism of duloxetine, the simultaneous use of duloxetine with potential isoenzyme inhibitors CYP2D6 can lead to an increase in the concentration of duloxetine. Paroxetine (20 mg once a day) reduced the average clearance of duloxetine by about 37%. When duloxetine is used with isoenzyme inhibitors CYP2D6 (for example, SSRIs), care should be taken.

Contraceptives for oral administration and other steroid preparations

Research results in vitro evidence that duloxetine does not induce catalytic activity of the isoenzyme CYP3A. Specific studies of drug interactions in conditions in vivo not conducted.

Anticoagulants and antithrombotics

In connection with the potential increased risk of bleeding associated with pharmacodynamic interaction, caution should be exercised when duloxetine and anticoagulants or antithrombotic agents are used concomitantly. In addition, with the simultaneous use of duloxetine and warfarin, the importance of the international normalized relationship (INR) has increased. Nevertheless, the simultaneous use of duloxetine and warfarin in stable conditions in healthy volunteers within the framework of a clinical study of pharmacology did not reveal a clinically significant change in the INR from the mean or changepharmacokinetics of the right- or left-handed isomer of warfarin.

Antacids and antagonists H₂-gistaminovyh receptors

Simultaneous use of duloxetine and aluminum- and magnesium-containing antacids or duloxetine and famotidine did not significantly affect the degree of absorption of duloxetine when a dose of 40 mg was administered.

Inductors of isoenzyme CYP1A2

Population pharmacokinetic analysis showed that compared with non-smokers in smokers, the concentration of duloxetine in plasma is almost 50% lower.

Drugs that are highly binding to blood proteins

Duloxetine largely binds to plasma proteins (> 90%). Therefore, the use of duloxetine in a patient who takes another drug that binds highly to plasma proteins can lead to an increase in the concentration of free fractions of both drugs.

Special instructions:

Exacerbation of manicMr.th / hypomaniacal state

As with the use of similar drugs that affect the central nervous system, duloxetine should be used with caution in patients with manic episodes in the anamnesis.

Epileptic seizures

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

Mydriasis

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

Increased blood pressure

In isolated cases, there was an increase in blood pressure during the treatment with duloxetine. In patients with hypertension and / or other cardiovascular diseases, it is recommended to perform a blood pressure measurement.

Impaired renal function, liver

In patients with severe renal dysfunction (CK <30 ml / min) or severe hepatic insufficiency, an increase in the concentration of duloxetine in the blood plasma is observed. If duloxetine is clinically justified in such patients, lower initial doses of the drug should be used.

Suicidal behavior

The risk of suicide exists in all patients with depression and some other mental disorders.This danger can persist until the onset of remission. As a result, patients who have the highest risk of committing suicide should be under careful medical supervision in the process of pharmacotherapy.

Just as the reception of other drugs that have a pharmacological action mechanism similar to duloxetine (SSRIs, SSRIs), the duloxetine intake in the course of treatment, or when it ceased in some cases, was associated with the development of suicidal ideation and suicidal behavior.

The use of duloxetine in patients under 18 years of age has not been studied, duloxetine It is not intended for use in such patients. The causal relationship between duloxetine intake and the occurrence of suicidal phenomena in patients of this age group has not been established. At the same time, some analytical reviews of a number of studies using antidepressants for the treatment of mental disorders indicate an increased risk of suicidal ideation and / or suicidal behavior in children, adolescents and adults younger than 25 years compared with placebo.Doctors should convince patients at any time to report all their thoughts and feelings that concern them.

Increased risk of bleeding

SSRIs and SSRIs, including duloxetine, may increase the risk of bleeding, including gastrointestinal (see "Side effects"). therefore duloxetine should be used with caution in patients taking anticoagulants and / or drugs that affect platelet function (eg non-steroidal anti-inflammatory drugs, including aspirin) and in patients with a history of bleeding.

Hyponatremia

Very rarely reported cases of hyponatremia (in some cases, the sodium content in the blood serum was lower than 110 mmol / l). Most of these cases occurred in elderly patients, especially in combination with a changed fluid balance in a recent history or in the presence of conditions predisposing to a change in fluid balance.

Hyponatremia can manifest in the form of nonspecific symptoms (such as dizziness, weakness, nausea, vomiting, confusion, drowsiness, lethargy).Symptoms and symptoms manifested in more severe cases included fainting, falling and convulsions.

Inhibitors of monoamine oxidase

In patients taking a serotonin reuptake inhibitor simultaneously with MAOI, there have been cases of serious reactions, sometimes fatal, including hyperthermia, stiffness, myoclonus, peripheral disorders with possible abrupt fluctuations in vital signs and changes in mental status, including marked agitation transition to delirium and to whom. These reactions were also observed in patients who, shortly before the use of MAOI, the serotonin reuptake inhibitor was canceled.

In some cases, patients exhibited symptoms characteristic of malignant neuroleptic syndrome.

The effects of simultaneous use of duloxetine and MAOI were not evaluated in either humans or animals. Therefore, given the fact that duloxetine is a reuptake inhibitor and serotonin, and norepinephrine, it is not recommended to take duloxetine simultaneously with MAOI or for at least 14 days after discontinuation of MAOI treatment. Based on the duration T_1/2duloxetine, you should take a break for at least 5 days after the end of duloxetine before taking MAOI.

Increase in activity of liver enzymes

In some patients who took duloxetine in clinical studies, there was an increase in the activity of liver enzymes. The observed deviations were, as a rule, transient and disappeared spontaneously, or after the abolition of duloxetine.

A significant increase in the activity of liver enzymes (10 times or more exceeding the upper limit of the norm), as well as liver damage of cholestatic or mixed genesis, were rare, and in some cases were associated with excessive alcohol consumption or previous liver disease. It is recommended to use caution duloxetine in patients who consume alcohol in significant quantities, as well as with the existing liver disease.

Special information on excipients

The Duloxent® preparation contains sucrose, so it should not be used in the following conditions: sugarase / isomaltase deficiency, fructose intolerance, syndrome glucose-galactose malabsorption.

Effect on the ability to drive transp. cf. and fur:

Against the background of taking duloxetine, sedation, drowsiness and other side effects can occur. In this regard, patients taking the drug Duloxent^®, it follows that take care when driving or dangerous mechanical means.

Form release / dosage:

Capsules are enteric, 30 mg and 60 mg.

Packaging:

For 7 or 10 capsules in a blister of the combined material OPA / Al / PE + DES and aluminum foil.

For 1, 2, 4 or 12 blisters (a blister for 7 capsules) or 1, 2, 3 or 9 blisters (a blister of 10 capsules), together with instructions for use, put in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004065

Date of registration:10.01.2017

Expiration Date:10.01.2022

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp28.01.2017

Illustrated instructions

Instructions

Duloxent® (Duloxenta®)