Cymbalta, 60 mg capsules, 14 pcs.

Composition

1 capsule contains:

Active ingredient:

duloxetine (as hydrochloride) 60 mg

excipients:

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 (60 mg capsules only)

Pharmacological action

Simbalta has an antidepressant effect.

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, which is primarily 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. _{Cmax is} reached 6 hours after administration.

Food intake does not affect the maximum concentration of the drug, but increases the time to reach cmax 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 α>₁-globulin; 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 (glucuronic conjugate of 4-hydroxyduloxetine, sulfate conjugate of 5-hydroxy-6-methoxyduloxetine).

Circulating metabolites have no pharmacological activity.

Output. Duration of T_1/2 duloxetine — 12 hours. The average Cl of duloxetine is 101 l / h.

Individual patient groups

Gender: although there were differences in pharmacokinetics between men and women (the average clearance of duloxetine is lower in women), these differences are not so large that there is a need to adjust the dose depending on gender.

Age: although there were differences in pharmacokinetics in middle-aged and elderly patients (AUC is higher and the duration of T_1/2 of the drug is longer in the elderly), these differences are not sufficient to change the dose depending on the age of patients only.

Impaired renal function: in patients with severe renal impairment (end-stage chronic renal failure) who are on hemodialysis, the values of_cmax and AUC of duloxetine increased 2-fold. In this regard, it is necessary to consider the feasibility of reducing the dose of the drug in patients with clinically expressed renal impairment.

Impaired liver function: patients with clinical signs of hepatic insufficiency may experience a slowdown in the metabolism and elimination of duloxetine. After a single dose of 20 mg of duloxetine in 6 patients with cirrhosis of the liver and moderate hepatic impairment (Child-Pugh class B), the duration of T_1/2 of duloxetine was approximately 15% longer than in healthy people of the corresponding gender and age with a five-fold increase in average exposure to AUC. Despite the fact that the_cmax in patients with cirrhosis was the same as in healthy people, T_1/2 was about 3 times longer.

Indications

Depression; painful form of diabetic neuropathy.

Use during pregnancy and lactation

Due to insufficient experience of using Simbalta during pregnancy, the drug should be prescribed during pregnancy only if the potential benefit to the patient significantly exceeds the potential risk to the fetus. Patients should be warned that if pregnancy occurs or is planned during treatment with duloxetine, they should inform their doctor about this.

Due to the lack of experience with the use of duloxetine in women during breastfeeding, breast-feeding during therapy with duloxetine is not recommended.

Contraindications

• hypersensitivity to Simbalta;
• concomitant use with MAO inhibitors;
• uncompensated angle-closure glaucoma.

With caution:

• exacerbation of manic/hypomanic states;
• epileptic seizures;
• mydriasis;
• impaired liver or kidney function;
• the likelihood of suicide attempts.

Side effects

The most common symptoms (10%) in clinical trials were: dizziness (except vertigo), dry mouth, nausea, constipation, sleep disturbance (drowsiness or insomnia), and headache. Headache was observed less frequently than with placebo.

Less often (from 1 to

Dizziness, nausea, and headache were reported as frequent adverse effects when duloxetine was discontinued.

There may be a slight increase in fasting blood glucose when taking duloxetine in patients with a painful form of diabetic neuropathy.

Interaction

Drugs that are metabolized by CYP1A2. Concomitant administration of duloxetine (60 mg twice daily) did not significantly affect the pharmacokinetics of theophylline metabolized by CYP1A2. Duloxetine is unlikely to have a clinically significant effect on the metabolism of CYP1A2 substrates.

CYP1A2 inhibitors. Due to the fact that CYP1A2 is involved in the metabolism of duloxetine, concomitant administration of duloxetine with potential CYP1A2 inhibitors is likely to lead to an increase in the concentration of duloxetine. A 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 antibacterial agents) and use smaller doses of duloxetine.

Drugs that are metabolized by CYP2D6. Duloxetine is a moderate inhibitor of CYP2D6. When taking duloxetine 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 by 3 times. Concomitant administration of duloxetine (40 mg twice daily) increased the stable portion of tolterodine AUC (2 mg twice daily) by 71%, but did not affect the pharmacokinetics of 5-hydroxylmetabolite. Therefore, caution should be exercised when using duloxetine with drugs that are mainly metabolized by the CYP2D6 system and have a low therapeutic index.

CYP2D6 inhibitors. Since CYP2D6 is involved in the metabolism of duloxetine, concomitant use of duloxetine with potential CYP2D6 inhibitors may lead to an increase in the concentration of duloxetine.

Paroxetine (20 mg once a day) reduced the average clearance of duloxetine by approximately 37%. Caution should be exercised when using duloxetine with CYP2D6 inhibitors (e. g. SSRIs).

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

Drugs that are highly bound to blood proteins. Duloxetine is highly bound to plasma proteins (>90%). Therefore, administration of duloxetine to a patient who is taking another drug that is highly bound to plasma proteins may lead to an increase in the concentration of free fractions of both drugs.

How to take, course of administration and dosage

Simbalta is prescribed orally, regardless of food intake.

Capsules should be swallowed whole, without chewing or crushing. Do not add Simbalta to food or mix it with liquids, as this may damage the intestinal-soluble capsule shell.

The recommended starting dose of Simbalta is 60 mg once a day. If necessary, it is possible to increase the dose to a maximum dose of 120 mg per day in 2 divided doses. A systematic evaluation of Simbalta intake at a dose of more than 120 mg was not performed.

In end-stage chronic renal failure (creatinine clearance less than 30 ml/min), the initial dose of Simbalta is 30 mg once a day.

Overdose

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

Treatment: No specific antidote is known. It is recommended to monitor cardiac activity and monitor the main indicators of vital activity along with symptomatic and supportive treatment.

Special instructions

MAO inhibitors. In patients receiving a serotonin reuptake inhibitor in combination with MAO inhibitors, there were cases of serious reactions, sometimes fatal, including hyperthermia, rigidity, myoclonus, peripheral disorders with possible sharp fluctuations in vital signs, and changes in mental status, including severe agitation with the transition to delirium and coma.

These reactions were also observed in patients whose serotonin reuptake inhibitor was discontinued shortly before the appointment of MAO inhibitors.In some cases, patients experienced symptoms characteristic of neuroleptic malignant syndrome. The effects of combined use of duloxetine and MAO inhibitors have not been evaluated in either humans or animals. Therefore, given the fact that duloxetine is a reuptake inhibitor of both serotonin and norepinephrine, it is not recommended to take duloxetine in combination with MAO inhibitors or for at least 14 days after discontinuation of treatment with MAO inhibitors. Based on the duration of the half-life of duloxetine, you should take a break for at least 5 days after the end of duloxetine before taking MAO inhibitors.

Exacerbation of manic/hypomanic state: As with similar medications 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 medications 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, so caution should be exercised when prescribing duloxetine to patients with increased intraocular pressure or at risk of developing acute angle-closure glaucoma.

Impaired liver or kidney function: in patients with severe renal impairment (creatinine clearance

Suicidal attempts: with depression, there is a possibility of suicidal attempts, which may persist until the onset of persistent remission. Patients at risk should be carefully monitored.

Driving a car and performing work that requires increased attention

In the course of studies of duloxetine, no violations of psychomotor reactions, cognitive functions and memory were detected. However, taking the drug may be accompanied by drowsiness. In this regard, patients taking duloxetine should exercise caution when driving mechanical vehicles, including a car.

Form of production

Capsules

Storage conditions

At a temperature of 15-30 °C

Shelf life

2 years

Active ingredient

Duloxetine

Conditions of release from pharmacies

By prescription

Dosage form

of capsule

Weight

Weight: 25 gr.