Simbalta capsules 60mg, No. 28

• Depression.

• Painful form of diabetic neuropathy.

• generalized anxiety disorder

Inside. The capsules should be swallowed whole without chewing or crushing. Do not add the drug to food or mix it with liquids, as this can damage the enteric pellet shell.

The recommended starting dose of duloxetine is 60 mg once a day with or without food. In some patients, in order to achieve a good result, it is necessary to increase the dose from 60 mg once a day to a maximum dose of 120 mg per day in two divided doses. A systematic assessment of taking the drug at a dose of more than 120 mg has not been carried out.

In patients with renal impairment: the initial dose should be 30 mg once a day in patients with severely impaired renal function (end-stage chronic renal failure) (creatinine clearance In patients with impaired liver function: the initial dose of the drug should be reduced or the frequency of administration should be reduced in patients with cirrhosis.

Age: is it recommended to use the drug in patients? 18 years.
There is no clinical experience with duloxetine in patients under 18 years of age.

Each capsule contains:
active substance: duloxetine hydrochloride, equivalent to 60 mg of duloxetine;
excipients:
capsule contents - sucrose, hypromellose, granulated sugar (no more than 91.5% sucrose, starch), talc, hypromellose acetate succinate, triethyl citrate, white dye (titanium dioxide, hypromellose);
capsule shell - indigo carmine, titanium dioxide, sodium lauryl sulfate, gelatin, iron oxide yellow dye (only for 60 mg capsules).

• Hypersensitivity to the drug.

• Simultaneous use with monoamine oxidase inhibitors (MAOIs) (see section 'Special instructions').

• Uncompensated angle-closure glaucoma

With caution
In case of exacerbation of a manic / hypomanic state, epileptic seizures, mydriasis, impaired liver or kidney function, with the likelihood of suicidal attempts (see section 'Special instructions').

Trade name of the drug:

Simbalta Ѓ (Cymbalta Ѓ)

International Non-Proprietary Name (INN):

Duloxetine

Dosage form

Capsules

Composition

Each capsule contains:
active ingredient: duloxetine hydrochloride, equivalent to 30 mg or 60 mg of duloxetine;
excipients:
capsule contents - sucrose, hypromellose, granulated sugar (no more than 91.5% sucrose, starch), talc, hypromellose acetate succinate, triethyl citrate, white dye (titanium dioxide, hypromellose);
capsule shell - indigo carmine, titanium dioxide, sodium lauryl sulfate, gelatin, iron oxide yellow dye (only for 60 mg capsules).

Description
30 mg capsules:
opaque, blue / white, hard gelatin capsules (size 3) coated with 30 mg green ink and identification code 9543.
60 mg capsules:
opaque, blue / green, hard gelatin capsules (size 1) coated with white ink 60 mg and with identification code 9542.
The contents of the capsules are white to grayish-white pellets.

Pharmacotherapeutic group

Antidepressant.

ATX code : N06AA

Pharmacological properties

Pharmacodynamics

Duloxetine is an antidepressant, serotonin and norepinephrine reuptake inhibitor, and weakly suppresses 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 norepinephrine, resulting in increased serotonergic and noradrenergic neurotransmission in the central nervous system.

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

Pharmacokinetics

Suction. Duloxetine is well absorbed when taken orally. Absorption begins 2 hours after taking the drug. The maximum concentration of the drug is reached 6 hours after administration.
Food intake does not affect the maximum concentration of the drug, but increases the time to reach the maximum concentration from 6 to 10 hours, which indirectly reduces the degree of absorption (by approximately 11%).
Distribution.
Duloxetine binds well to plasma proteins (> 90%), mainly albumin and ?1-globulin, but liver or kidney disorders do not affect the degree of protein binding.
Metabolism.
Duloxetine is extensively metabolized, and its metabolites are mainly excreted in the urine. Both CYP2D6 and CYP1A2 catalyze the formation of two major metabolites (4-hydroxyduloxetine glucuronic conjugate, 5-hydroxy sulfate conjugate, 6-methoxyduloxetine conjugate).
Circulating metabolites have no pharmacological activity.
Excretion.
The half-life of duloxetine is 12 hours. The average clearance of duloxetine is 101 l / h.

Separate groups of patients.
Gender:
Despite the fact that there were differences in pharmacokinetics between men and women (mean clearance of duloxetine is lower in women), these differences are not so great that there was a need for dose adjustment depending on gender. Age: despite the fact that there were differences in pharmacokinetics between middle-aged and elderly patients (AUC - the area under the concentration / time curve is higher and the half-life of the drug is longer in the elderly), these differences are not enough to change the dose depending only on the age of the patients.

Renal impairment:
in patients with severe renal impairment (end-stage chronic renal failure - chronic renal failure) on hemodialysis, the values ??of Cmax (maximum concentration) and AUC of duloxetine increased by 2 times. In this regard, the advisability of reducing the dose of the drug in patients with clinically expressed renal dysfunction should be considered.

Impaired liver function:
in patients with clinical signs of hepatic failure, a slowdown in metabolism and excretion of duloxetine may be observed. After a single dose of 20 mg of duloxetine in 6 patients with cirrhosis of the liver with moderate hepatic impairment (Child-Pugh Class B), the half-life of duloxetine was approximately 15% longer than in healthy people of the same sex and age with a fivefold increase in the average exposure ( AUC). Despite the fact that the Cmax in patients with cirrhosis was the same as in healthy people, the half-life was approximately 3 times longer.

Indications for use

• Depression.

• Painful form of diabetic neuropathy.

• generalized anxiety disorder

Contraindications

• Hypersensitivity to the drug.

• Simultaneous use with monoamine oxidase inhibitors (MAOIs) (see section 'Special instructions').

• Uncompensated angle-closure glaucoma

With caution
In case of exacerbation of a manic / hypomanic state, epileptic seizures, mydriasis, impaired liver or kidney function, with the likelihood of suicidal attempts (see section 'Special instructions').

Application during pregnancy and breastfeeding

Due to insufficient experience with duloxetine during pregnancy, the drug should be prescribed during pregnancy only if the potential benefit to the patient significantly outweighs the potential risk to the fetus. Patients should be warned that in the event of a pregnancy or planning a pregnancy during treatment with duloxetine, they should inform their doctor about it.
Due to the lack of experience with duloxetine in women during breastfeeding, breastfeeding is not recommended during duloxetine therapy.

Method of administration and dosage

Inside. The capsules should be swallowed whole without chewing or crushing. Do not add the drug to food or mix it with liquids, as this can damage the enteric pellet shell.

The recommended starting dose of duloxetine is 60 mg once a day with or without food. In some patients, in order to achieve a good result, it is necessary to increase the dose from 60 mg once a day to a maximum dose of 120 mg per day in two divided doses. A systematic assessment of taking the drug at a dose of more than 120 mg has not been carried out.

In patients with renal impairment: the initial dose should be 30 mg once a day in patients with severely impaired renal function (end-stage chronic renal failure) (creatinine clearance In patients with impaired liver function: the initial dose of the drug should be reduced or the frequency of administration should be reduced in patients with cirrhosis.

Age: is it recommended to use the drug in patients? 18 years.
There is no clinical experience with duloxetine in patients under 18 years of age.

Side effect

The most common (?10%) clinical studies reported:
dizziness (except for vertigo), dry mouth, nausea, constipation, sleep disturbances (drowsiness or insomnia) and headache. Headache was reported less frequently than with placebo.

Less frequently (from? 1 to dizziness, nausea, headache) were noted as frequent adverse effects when duloxetine was discontinued.

Effect on glucose concentration in patients with painful form of diabetic neuropathy: there may be a slight increase in fasting blood glucose while taking duloxetine.

Overdose

Several cases of overdose have been reported with simultaneous ingestion of up to 1400 mg of the drug, which did not have fatal consequences. Overdose may be accompanied by the following symptoms: tremors, clonic seizures, ataxia, vomiting, and decreased appetite.

Overdose treatment. No specific antidote is known. It is recommended to monitor cardiac activity and monitor vital signs, along with symptomatic and supportive treatment.

Interaction with other medicinal products

Drugs metabolized by CYP1A2.
Concomitant use of duloxetine (60 mg 2 times a day) did not significantly affect the pharmacokinetics of theophylline, which is metabolized by CYP1A2. Duloxetine is unlikely to have a clinically significant effect on the metabolism of CYP1A2 substrates.

Inhibitors of CYP1A2.
Due to the fact that CYP1A2 is involved in the metabolism of duloxetine, concomitant administration of duloxetine with potential inhibitors of CYP1A2 is likely to lead to an increase in duloxetine concentration. The potent CYP1A2 inhibitor fluvoxamine (100 mg once daily) reduced the mean plasma clearance of duloxetine by approximately 77%. Caution should be exercised when prescribing duloxetine with CYP1A2 inhibitors (for example, some quinolone antibiotics) and lower doses of duloxetine should be used.

Drugs metabolized by CYP2D6.
Duloxetine is a moderate CYP2D6 inhibitor. When duloxetine is taken at a dose of 60 mg 2 times a day, together with a single dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increases 3 times. Concomitant administration of duloxetine (40 mg 2 times a day) increased the stable part of the AUC of tolterodine (2 mg 2 times a day) by 71%, but did not affect the pharmacokinetics of the 5-hydroxyl metabolite. Thus, caution should be exercised when using duloxetine with drugs that are mainly metabolized by the CYP2D6 system and have a narrow therapeutic index.

Inhibitors of CYP2D6.
Since CYP2D6 is involved in the metabolism of duloxetine, concomitant use of duloxetine with potential inhibitors of CYP2D6 may lead to an increase in duloxetine concentrations. Paroxetine (20 mg once daily) reduced the mean clearance of duloxetine by approximately 37%. Caution should be exercised when using duloxetine with CYP2D6 inhibitors (eg SSRIs).

Drugs affecting the central nervous system.
Caution should be exercised when using duloxetine together with other drugs and agents that affect the central nervous system, especially with those that have a similar mechanism of action, including alcohol.

Drugs that bind to a high degree of blood proteins.
Duloxetine is highly associated with plasma proteins (> 90%). Therefore, the administration of duloxetine to a patient who is taking another drug that binds to plasma proteins to a high degree can lead to an increase in the concentration of free fractions of both drugs.

special instructions

Monoamine oxidase inhibitors (MAOIs). In patients receiving a serotonin reuptake inhibitor in combination with MAOIs, there were cases of serious reactions, sometimes fatal, among which there were hyperthermia, rigidity, myoclonus, peripheral disorders with possible sharp fluctuations in vital signs and changes in mental status, including pronounced excitement with the transition to delirium and coma. These reactions were also observed in patients who had a serotonin reuptake inhibitor canceled shortly before the appointment of an MAOI. In some cases, patients showed symptoms characteristic of neuroleptic malignant syndrome. The effects of the combined use of duloxetine and MAOIs have not been evaluated in either humans or animals. Therefore, given the fact that duloxetine is a serotonin inhibitor,and norepinephrine, it is not recommended to take duloxetine in combination with an MAOI or for at least 14 days after stopping treatment with an MAOI.

Based on the elimination half-life of duloxetine, you should take a break for at least 5 days after you stop taking duloxetine before taking an MAOI.

Exacerbation of a manic / hypomanic state: As with 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 similar drugs that affect the central nervous system, duloxetine should be used with caution in patients with a history of epileptic seizures.

Mydriasis: there have been cases of mydriasis when taking duloxetine, therefore, caution should be exercised when prescribing duloxetine to patients with increased intraocular pressure or in those at risk of developing acute angle-closure glaucoma.

Liver or renal impairment: in patients with severe renal impairment (creatinine clearance Suicidal attempts: in depression, there is a possibility of suicidal attempts, which may persist until a stable remission occurs. Careful monitoring of patients at risk is necessary.

Driving and performing work requiring increased attention
In the course of studies of duloxetine, there were no violations of psychomotor reactions, cognitive functions and memory. However, taking the drug may be accompanied by drowsiness. In this regard, patients taking duloxetine should exercise caution when driving dangerous mechanical means, including a car.

Release form

Capsules 30 mg or 60 mg.

Storage conditions

At a temperature of 15-30 ? C, out of the reach of children.
List B.

Shelf life

3 years.
Do not use after the date printed on the package.

Conditions of dispensing from pharmacies

On prescription.