Cymbalta, 30mg capsules, 14pcs

Composition

1 capsule contains duloxetine (in the form of hydrochloride) 30 mg

Pharmacological action

An antidepressant, a serotonin and norepinephrine reuptake inhibitor that weakly suppresses dopamine uptake, has no significant affinity for histamine, dopamine, choline, 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.

Indications

depression; painful form of diabetic neuropathy; generalized anxiety disorder; chronic pain syndrome of the musculoskeletal system (including caused by fibromyalgia, chronic pain syndrome in the lower back and in osteoarthritis of the knee joint).

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 the drug.
• Concomitant use with monoamine oxidase inhibitors (MAOIs).
• Uncompensated angle-closure glaucoma

With caution

If the manic / hypomanic state is aggravated, epileptic seizures, mydriasis, liver or kidney dysfunction, and suicide attempts are likely.

Side effects

Most common (10%): dizziness (except vertigo), dry mouth, nausea, constipation, sleep disorders (drowsiness or insomnia), headache (less often than with placebo).

Less common (1-10%): diarrhea, vomiting, tremor, decreased appetite, weight loss, weakness, increased sweating, hot flashes, blurred vision, anorgasmia, decreased libido, delayed and impaired ejaculation, and erectile dysfunction.

Slight increase in fasting blood glucose concentration in patients with painful diabetic neuropathy.

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

Interaction

Monoamine oxidase inhibitors (MAOIs). Due to the risk of serotonin syndrome, duloxetine should not be used in combination with MAOIs, and for at least 14 days after discontinuation of MAOIs treatment. 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 MAOI. For selective reversible MAOIs, such as moclobemide, the risk of serotonin syndrome is lower. However, the combined use of reversible MAOIs and duloxetine is not recommended. Inhibitors of the CYP1A2 isoenzyme. Due to the fact that the CYP1A2 isoenzyme is involved in the metabolism of duloxetine, simultaneous use 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 / day), reduced the mean plasma clearance of duloxetine by approximately 77%. Caution should be exercised when prescribing duloxetine with inhibitors of the CYP1A2 isoenzyme (for example, some quinolone antibiotics) and lower doses of duloxetine should be used. 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, especially those that have a similar mechanism of action, including alcohol. Concomitant use with other drugs that have serotonergic effects (for example, SSRIs, SSRIs, triptans and tramadol) may lead to the development of serotonin syndrome. Serotonin syndrome. In rare cases, serotonin syndrome has been observed with the combined use of SSRIs (for example, paroxetine, fluoxetine) and serotonergic drugs. Caution should be exercised when using duloxetine in combination with serotonergic antidepressants such as SSRIs, tricyclic antidepressants (clomipramine or amitriptyline), St. John’s wort, venlofaxine or triptans, tramadol, finidine and tryptophan. Drugs that are metabolized by the CYP1A2 isoenzyme. Concomitant use of duloxetine (60 mg twice daily) did not significantly affect the pharmacokinetics of theophylline, which is metabolized by the CYP1A2 isoenzyme. Duloxetine is unlikely to have a clinically significant effect on the metabolism of substrates of the CYP1A2 isoenzyme. Drugs that are metabolized by the CYP2D6 isoenzyme. Duloxetine is a moderate inhibitor of the CYP2D6 isoenzyme. When taking duloxetine at a dose of 60 mg 2 times / day together with a single dose of desipramine, a substrate of the CYP2D6 isoenzyme, the AUC of desipramine increases by 3 times. Concomitant use of duloxetine (40 mg twice daily) increased the steady – state 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 the CYP2D6 isoenzyme system and have a narrow therapeutic index. Inhibitors of the CYP2D6 isoenzyme. Since the CYP2D6 isoenzyme is involved in the metabolism of duloxetine, concomitant use of duloxetine with potential inhibitors of the CYP2D6 isoenzyme 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 inhibitors of the CYP2D6 isoenzyme (for example, SSRIs). Oral contraceptives and other steroid medications. The results of in vitro studies indicate that duloxetine does not induce the catalytic activity of the CYP3A isoenzyme. Specific in vivo drug interaction studies have not been performed. Anticoagulants and antithrombotic drugs. Due to the potential increased risk of bleeding associated with pharmacodynamic interactions, caution should be exercised when using duloxetine together with anticoagulants or antithrombotic drugs. In addition, the combined use of duloxetine and warfarin increased the MHO value. However, the concomitant use of duloxetine and warfarin under stable conditions in healthy volunteers in a clinical pharmacology study did not reveal a clinically significant change in the MHO indicator from the average or a change in the pharmacokinetics of the right – or left-rotating isomer of warfarin. Antacids and antagonists of H2-histamine receptors. The combined use of duloxetine and aluminum-and magnesium-containing antacids, or duloxetine and famotidine, did not significantly affect the degree of absorption of duloxetine at a dose of 40 mg. Inducers of the CYP1A2 isoenzyme. Population pharmacokinetic analysis showed that compared with non-smokers, the plasma concentration of duloxetine was almost 50% lower in smoking patients. Drugs that are highly bound to blood proteins. Duloxetine is highly bound to plasma proteins (> 90%). Therefore, use 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 use 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 use 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 for overdose. The specific antidote is not known. It is recommended to monitor cardiac activity and monitor the main indicators of vital activity, along with symptomatic and supportive treatment.

Special instructions

Monoamine oxidase inhibitors (MAOIs). In patients receiving a serotonin reuptake inhibitor in combination with MAOI, 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 who were discontinued a serotonin reuptake inhibitor shortly before the use of MAOI. In some cases, patients experienced symptoms characteristic of neuroleptic malignant syndrome.The effects of combined use of duloxetine and MAOI have not been evaluated in either humans or animals.

Therefore, given the fact that duloxetine is an inhibitor of both serotonin and norepinephrine, it is not recommended to take duloxetine in combination with MAOI or for at least 14 days after discontinuation of MAOI treatment. 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 MAOI.

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

Mydriaz: Cases of mydriasis have been reported with duloxetine, so caution should be exercised when prescribing duloxetine to patients with increased intraocular pressure or those at risk of developing acute angle-closure glaucoma.

Impaired liver or kidney function: in patients with severe renal impairment (creatinine clearance If the use of duloxetine is clinically justified in such patients, lower initial doses of the drug should be used.

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

Form of production

Capsules.

Storage conditions

At a temperature of 15-30 °C

Shelf life

3 years

Active ingredient

Duloxetine

Conditions of release from pharmacies

By prescription

Dosage form

Capsules