SIMBALTA

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Active material: Duloxetine
When ATH: N06AX21
CCF: Antidepressant
ICD-10 codes (testimony): F31, F32, F33, F41.2, G63.2
When CSF: 02.02.06
Manufacturer: ELI LILLY VOSTOK S.A.. (Switzerland)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Capsules hard gelatin, size №3, opaque, blue/white, with green ink dosage “30 mg” and an identification code “9543”; contents of capsules – pellets made from white to grayish-white.

	1 caps.
Duloxetine (the hydrochloride)	30 mg

Excipients: sucrose, gipromelloza, sugar, granulated (no more 92% sucrose, starch), talc, gipromellozy acetate succinate, triэtiltsitrat, dye white (Titanium dioxide, gipromelloza).

The composition of the shell: indigokarmin, Titanium dioxide, sodium lauryl, gelatin.

7 PC. – blisters (1) – packs cardboard.
7 PC. – blisters (2) – packs cardboard.
7 PC. – blisters (4) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.
14 PC. – blisters (6) – packs cardboard.

Capsules hard gelatin, size №1, opaque, Blue/Green, with white ink dosage “60 mg” and an identification code “9542”; contents of capsules – pellets made from white to grayish-white.

	1 caps.
Duloxetine (the hydrochloride)	60 mg

Excipients: sucrose, gipromelloza, sugar, granulated (no more 92% sucrose, starch), talc, gipromellozy acetate succinate, triэtiltsitrat, dye white (Titanium dioxide, gipromelloza).

The composition of the shell: indigokarmin, Titanium dioxide, sodium lauryl, gelatin, dye iron oxide yellow.

Pharmacological action

Antidepressant, reuptake inhibitor and a norepinephrine (noradrenaline). Weakly inhibits dopamine uptake, has no significant affinity for gistaminovm, dopamine, holino- and adrenoreceptoram. The mechanism of action of duloxetine is to suppress reuptake of serotonin and norepinephrine (noradrenaline), as a result, increases serotoninergičeskaâ and noradrenergičeskaâ nejrotransmissiâ in the central nervous system.

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

Pharmacokinetics

Absorption

After oral duloxetine is well absorbed from the gastrointestinal tract, absorption begins 2 h after administration, C_max achieved through 6 h after administration. Admission at the same time with food increases the time to reach C_max to 10 no, which reduces the extent of absorption (approximately 11%), but no effect on the C_max.

Distribution

Plasma protein binding is high (more 90%), mainly to albumin and α₁-globulin. Disorders of the liver or kidneys no effect on protein binding.

Metabolism

Duloxetine actively biotransformiruetsya with uchastiem izofermentov CYP2D6 and CYP1A2, which catalyze the formation of two major metabolites (glucuronic conjugates 4 gidroksiduloksetina, sulphate conjugate of 5-hydroxy,6-metoksiduloksetina). Circulating metabolites do not possess pharmacological activity.

Deduction

T_1/2 is 12 no. The average clearance of duloxetine 101 l /. Excreted in the urine as metabolites.

Pharmacokinetics in special clinical situations

Some studies the differences between pharmacokinetics processes for men and women (the average clearance of Duloxetine is lower in women), but the need for dose adjustment depending on the floor no.

Some studies the differences between pharmacokinetics processes between middle-aged and older patients (AUC and T_1/2 more in seniors), but the need for dose adjustment depending only upon the age of the patients is not.

In patients with end-stage renal disease, hemodialysis, C values_max and AUC increased in duloxetine 2 times. In this connection, should consider reducing the dose in patients with clinically severe impaired renal function.

In patients with clinical signs of liver failure may slow metabolism and excretion of Duloxetine. After receiving a single dose of duloxetine 20 mg 6 patients with cirrhosis and mild hepatic impairment (Class B for Child-Pugh) the duration T_1/2 duloxetine was about 15% higher, than in healthy individuals of the corresponding age and gender with a five-fold increase in mean AUC values. Despite, that C_max patients with cirrhosis had a, as in healthy humans, T_1/2 about 3 times.

Testimony

- Depression;

-sensitive form of diabetic neuropathy.

Dosage regimen

The drug is taken orally with or without food.

The recommended starting dose is 60 mg 1 time / day. If necessary, the daily dose can be increased to 60 mg 1 Once/day up to a maximum dose of 120 mg / day 2 admission. Systematic assessment of the safety of drugs in dose 120 mg has not been.

In patients with chronic renal insufficiency in the terminal stage (CC<30 ml / min) the initial dose is 30 mg 1 time / day.

In patients with impaired liver function should reduce the initial dose of the drug or reduce the frequency of reception.

Clinical experience with the drug in patients under the age of 18 years no.

The capsules should be swallowed whole, not liquid and not razdavlivaâ. You cannot add the preparation in food or mix it with liquids, tk. This can damage the shell kišečnorastvorimuû pellets. The drug can be taken regardless of meals.

Side effect

CNS: ≥10% – dizziness (Additionally vertigo), sleep disorders (drowsiness or insomnia), headache (Headache was observed less frequently, than in patients receiving placebo); by ≥1% to <10% – tremor, weakness, lethargy, alarm, zevota; ≤1% – excitation, disorientation.

From the digestive system: ≥10% – dry mouth, nausea, constipation; by ≥1% to <10% – diarrhea, vomiting, decreased appetite, weight loss, violation of the liver laboratory tests, change in taste; ≤1% – hepatitis, jaundice, increased activity of alkaline phosphatase, GOLD, AST and bilirubin, belching, gastroenteritis, stomatitis.

On the part of the musculoskeletal system: by ≥1% to <10% – muscle tension and / or twitching; ≤1% – bruxism.

Cardio-vascular system: by ≥1% to <10% – heartbeat; ≤1% – orthostatic hypotension, syncope (especially early in treatment), tachycardia, increased blood pressure, cold extremities.

On the part of the reproductive system: by ≥1% to <10% – anorgazmija, decreased libido, delay, and abnormal ejaculation, erectile dysfunction.

From the urinary system: by ≥1% to <10% – shortness mocheispuskannie; ≤1% – nocturia.

Metabolism: by ≥1% to <10% – weight loss, increased perspiration, tides, night sweat; ≤1% – giponatriemiya, thirst, weight gain, degidratatsiya.

From the senses: by ≥1% to <10% – blurred vision, change in taste; ≤1% – glaucoma, glaucoma, midriaz, visual impairment.

Allergic reactions: ≤1% – anaphylactic reactions, chills, angioedema, rash, Stevens-Johnson syndrome, hives.

Other: ≤1% – chills, bad feeling, feeling hot and / or cold, photosensitivity. Denial of drug often experienced dizziness, nausea, headache. Patients with painful diabetic neuropathy, the form may be a slight increase in fasting blood glucose.

In clinical trials in patients with a painful form of diabetic neuropathy the following data were identified concerning the possible effects of Duloxetine on the concentration of glucose. With short-term admission (to 12 Sun.) Perhaps a slight increase in fasting blood glucose, while striving to maintain a stable level of glycosylated hemoglobin. Against the backdrop of long-term therapy (to 52 Sun.) There was a slight increase in the level of glycosylated hemoglobin, that on 0.3% the increase was higher than the corresponding figure in patients, receiving a different treatment; There was also a slight increase in the concentration of prandial glucose and total cholesterol in the blood.

Postmarketing reports

On the part of the endocrine system: < 0.01% – violation of secretion of ADH.

CNS: < 0.01% – extrapyramidal syndrome, serotonin syndrome; 0 .01%-0.1% – hallucinations.

From the urinary system: 0.01%-0.1% – urinary retention.

Contraindications

-the simultaneous use of MAO inhibitors;

-uncorrected zakratougolnaya glaucoma;

- Hypersensitivity to the drug.

FROM caution used in acute manic/gipomaniakalnogo status, seizures, midriaze, violations of the liver and kidney, When the likelihood of suicide attempts.

Pregnancy and lactation

Use of the drug during pregnancy is possible only in cases, when the intended benefits to the mother outweighs the potential risk to the fetus, tk. clinical experience with duloxetine during pregnancy is not enough.

Women of childbearing age should be warned that, that in the event of or planning pregnancy during the period of application of Simbalta^® they should inform their doctor.

If necessary, use during lactation should decide the issue of termination of breastfeeding (due to lack of experience with).

Cautions

In the appointment of serotonin reuptake inhibitors in combination with MAO inhibitors there have been cases of serious reactions, sometimes with fatal consequences (hyperthermia, rigidity, myoclonus, various violations with possible sharp fluctuations in vital signs of the body and changes in mental status, including expressed excitement with the transition to delirium and to whom). Such reactions are also possible in cases, When serotonin reuptake inhibitor was canceled shortly before the appointment of MAO inhibitors. In some cases, symptoms were observed, characteristic for CSN.

Effects of combined use of duloxetine and MAOIs have not been evaluated in humans or, nor in animals. Use Simbalty^® at the same time as MAO inhibitors, or in the period prior to the 14 days after their withdrawal is not recommended, tk. Duloxetine is a serotonin reuptake inhibitor, and norepinephrine (noradrenaline). Based on the length of T_1/2 Duloxetine MAO inhibitors should not be appointed for a period of at least 5 days after discontinuation of duloxetine.

Like other drugs, having similar effects on the central nervous system, Simbaltu^® should use caution in patients with Mania episodes in history, and with a history of seizures.

Depressive state are accompanied by high risk of suicidal thinking and behavior. Consequently, patients diagnosed with depression, prinimayushtie duloxetine, You must inform the doctor about any troubling thoughts and feelings.

Against the background of the drug may develop mydriasis, Therefore, caution should be exercised in the appointment of Duloxetine patients with increased vnutriglaznam pressure or persons at risk of acute angle closure glaucoma.

In patients with severe renal impairment (CC< 30 ml / min) or severe hepatic insufficiency, there has been an increased concentration of Duloxetine plasma. If such patients receiving Duloxetine clinically justified, You should use the drug in lower primary doses.

In patients with arterial hypertension and/or other cardiovascular diseases recommended that monitoring ad.

The drug should be used with caution in patients with chronic alcoholism.

Effects on ability to drive vehicles and management mechanisms

Against the backdrop of the admission Simbalty^® Perhaps the sedation and sleepiness, Therefore, during treatment, patients need to be careful when driving vehicles and other potentially hazardous activities.

Overdose

Cases of overdose with a single ingestion of up to 2000 mg Duloxetine as a, and in combination with other drugs.

Symptoms (mainly in cases of concomitant overdose): serotonin syndrome, drowsiness, vomiting, clonic seizures. Extremely rare and are also mainly in cases of concomitant dreadfully reported overdose.

Treatment: recommend that the monitoring of the cardiovascular system and other vital signs; When simptomaticescuu and supportive therapy. In the case of serotonin syndrome ciprogeptadinom treatment and application of methods for normalization of body temperature. No specific antidote.

Drug Interactions

Concomitant use of duloxetine (60 mg 2 times / day) It had no significant effect on the pharmacokinetics of theophylline, metabolized by CYP1A2. Clinically significant effect of Duloxetine on the metabolism of CYP1A2 substrates are unlikely.

While receiving the drug Simbalta^® with potential inhibitors of CYP1A2 (eg, some antibiotics derived quinolone) perhaps increasing the concentration of Duloxetine in plasma, tk. CYP1A2 is involved in duloxetine metabolism (such combinations should be used with caution, When this Duloxetine should appoint at low doses). Strong CYP1A2 inhibitor fluvoxamine (upon receiving a dose 100 mg 1 time / day) reduced mean plasma clearance of duloxetine by about 77%.

Duloxetine is a moderate inhibitor of CYP2D6, Therefore, together with the use of Duloxetine in the dose 60 mg 2 times / day AUC of desipramine (the CYP2D6 substrate) increases 3 times. Together with the use of Duloxetine (dose 40 mg 2 times / day) increasing stable part of the AUC tol′terodina (It is applied at a dose of 2 mg 2 times / day) on 71%, When the 5-hydroxyl metabolite pharmacokinetics has not changed. The drug should be used with caution Simbalta^® with drugs, metabolized by CYP2D6 and izofermentom which have a narrow therapeutic index.

The simultaneous use of duloxetine potential CYP2D6 inhibitors may lead to increased concentrations of duloxetine in plasma. Paroxetine (at an application rate 20 mg 1 time / day) reduced the average clearance of duloxetine by about 37%. When using duloxetine with inhibitors of CYP2D6 (eg, with selective serotonin reuptake inhibitors) Caution should be exercised.

With simultaneous use of duloxetine and other drugs, affecting the central nervous system and have a similar mechanism of action (including ethanol and drugs etanolsoderzhaschie), possible mutual reinforcement effects (this combination requires caution).

Duloxetine largely bound to plasma proteins, therefore concurrent use with other drugs, highly bound to plasma proteins, may lead to increased concentrations of free fractions of both drugs.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at temperature from 15 ° to 30 ° C. Shelf life - 3 year.

Vladimir Andreevich Didenko

582 8 minutes read