Clinical and pharmacological group: & nbsp

Antidepressants

Included in the formulation
  • Duloxent®
    capsules inwards 
  • Duloxetine Canon
    capsules inwards 
  • Simbalta®
    capsules inwards 
    Eli Lilly East SA     Switzerland
  • АТХ:

    N.06.A.X.21   Duloxetine

    Pharmacodynamics:

    Antidepressant, a reuptake inhibitor of serotonin and norepinephrine (norepinephrine). Slightly inhibits the capture of dopamine, does not have a significant affinity for histamine, dopamine, cholinergic and adrenergic receptors.

    The mechanism of action of duloxetine is to inhibit the reuptake of serotonin and norepinephrine (norepinephrine). Duloxetine has a central mechanism for suppressing the pain syndrome, which is primarily manifested by an increase in the threshold of pain sensitivity in the pain syndrome of neuropathic etiology.

    Pharmacokinetics:

    Absorption is complete, after 2 hours after intake, food intake reduces absorption by 11%. The connection with plasma proteins is 90% (albumin and acid alpha-1-glycoprotein). Biotransformation in the liver (CYP2D6, 1A2), with the formation of inactive metabolites: glucuron conjugate 4-hydroxyduloxetine, sulfate conjugate 5-hydroxy, 6-methoxyduloxetine. Half-life - 12 hours Cmax - 6 h. Clearance - 101 l / h (women have clearance below).

    Renal and hepatic insufficiency do not affect the degree of binding to proteins, slow down metabolism and elimination.

    After taking 20 mg of duloxetine in 6 patients with liver cirrhosis with moderate impaired hepatic function (Child-Pugh class B), the clearance of duloxetine increased by 15%, AUC by 5-fold, half-life - 3 times, the value of Cmax did not change.

    Indications:

    Depression, a painful form of diabetic neuropathy.

    V.F40-F48.F41.2   Mixed anxiety and depressive disorder

    V.F30-F39.F33   Recurrent depressive disorder

    V.F30-F39.F31   Bipolar affective disorder

    V.F30-F39.F32   Depressive episode

    VI.G60-G64.G63.2 *   Diabetic polyneuropathy (E10-E14 + with common fourth sign .4)

    Contraindications:

    Uncompensated closed-angle glaucoma, concomitant use with MAO inhibitors, hypersensitivity to duloxetine, breast-feeding, age to 18 years.

    For dosage forms containing sucrose (optional): congenital intolerance to fructose, glucose-galactose malabsorption, sucrose-isomaltase deficiency.

    Carefully:

    Mania and bipolar disorder (including history), convulsions (including a history), intraocular hypertension or the risk of developing an acute angle-closure glaucoma, suicidal thoughts and attempts in history, increased risk of hyponatremia (elderly patients, cirrhosis, dehydration, reception of diuretics), pregnancy.

    Use with caution in patients with manic episodes in an anamnesis, as well as with epileptic seizures in the anamnesis.

    In patients with impaired liver function, the initial dose of the drug should be reduced or the frequency of administration reduced. In patients with severe renal impairment (creatinine clearance <30 mL / min), the initial dose should be 30 mg once daily.

    Pregnancy and lactation:

    The category of FDA recommendations is not defined. Adequate and well-controlled studies on humans and animals have not been conducted. The use of the drug in pregnancy is possible only in cases where the intended use for the mother exceeds the potential risk for the fetus, since the clinical experience of duloxetine in pregnancy is not enough.

    If you need to use the drug during lactation, you should decide whether to stop breastfeeding (due to lack of experience).

    Patients should be warned that in the event of the onset or planning of pregnancy during the period of duloxetine, they must inform their doctor.

    Dosing and Administration:

    Inside, regardless of food intake.Capsules should be swallowed whole, not chewing and crushing. Do not add the drug to food or mix it with liquids, as this can damage the enteric coating of pellets.

    The recommended initial dose is 60 mg once a day. If necessary, you can increase the daily dose from 60 mg to a maximum dose of 120 mg per day in 2 divided doses.

    In patients with severe renal impairment (creatinine clearance <30 mL / min), the initial dose should be 30 mg once daily. In patients with impaired liver function, the initial dose of the drug should be reduced or the frequency of administration reduced.

    Side effects:

    From the side of the central nervous system: often - dizziness (except vertigo), sleep disturbances (drowsiness or insomnia), headache (headache was less common than with placebo); sometimes - tremor, weakness, blurred vision, lethargy, anxiety, yawning; very rarely - glaucoma, mydriasis, visual impairment, agitation, disorientation.

    From the digestive system: often - dry mouth, nausea, constipation; sometimes - diarrhea, vomiting, decreased appetite, change in taste, impaired liver function; very rarely - hepatitis, jaundice, increased activity of hepatic transaminases, alkaline phosphatase and bilirubin level; belching, gastroenteritis, stomatitis.

    From the musculoskeletal system: sometimes - muscle tension and / or twitching; very rarely - bruxism.

    From the cardiovascular system: sometimes - palpitations; very rarely - orthostatic hypotension, syncope (especially at the beginning of therapy), tachycardia, increased blood pressure, cold extremities.

    On the part of the reproductive system: sometimes - anorgasmia, decreased libido, delay and violation of ejaculation, erectile dysfunction.

    From the urinary system: sometimes - difficulty urinating; very rarely - nocturia.

    Other: sometimes - weight loss, increased sweating, hot flashes, night sweats; very rarely anaphylactic reactions, thirst, hyponatremia, chills, angioedema, rash, Stevens-Johnson syndrome, urticaria, poor health, feeling hot and / or cold, weight gain, dehydration, photosensitivity. With cancellation, dizziness, nausea, and headache were often noted. In patients with a painful form of diabetic neuropathy, there may be a slight increase in fasting blood glucose.

    Overdose:

    Symptoms: vomiting and decreased appetite, tremor, clonic convulsions, ataxia.

    Treatment: symptomatic and supportive. Control cardiovascular system and other indicators of life. The specific antidote is not known.

    Several cases of overdose were reported with a single-dose oral intake up to 1400 mg of the drug that did not have fatal consequences.

    Interaction:

    Desipramine (inhibitor of CYP2D6), a joint treatment with duloxetine (60 mg twice a day) - an increase in the AUC of desipramine by a factor of 3.

    Inhibitors of CYP1A2, fluvoxamine (100 mg once a day) - a decrease in the clearance of duloxetine by 77%.

    MAO inhibitors - hyperthermia, muscle rigidity, myoclonus, peripheral disorders with possible sharp fluctuations in vital signs and changes in mental status, including a marked excitement with the transition to delirium and to whom, sometimes fatal. Assign no earlier than 14 days after the abolition of MAO inhibitors.

    Paroxetine (20 mg once a day) (CYP2D6) - reduced clearance of duloxetine by 37%.

    Means metabolized in the CYP2D6 system, alcohol, other CNS depressant agents and having a narrow therapeutic index - use caution when using duloxetine.The simultaneous use of duloxetine with agents highly binding to plasma proteins leads to an increase in the concentration of free fractions of both drugs.

    Tolterodin (2 mg 2 times a day), combined with duloxetine (40 mg twice daily) - increase in tolterodine AUC by 71%, but does not affect the pharmacokinetics of the 5-hydroxyl metabolite.

    Quinolones (some) - increasing the concentration of duloxetine.

    Special instructions:

    In the appointment of serotonin reuptake inhibitors in combination with MAO inhibitors, severe reactions, sometimes with a fatal outcome (hyperthermia, rigidity, myoclonus, various disorders with possible sharp fluctuations in vital signs of the body and changes in mental status, including pronounced agitation with the transition to delirium and to whom). Such reactions are also possible in cases where the serotonin reuptake inhibitor was abolished shortly before administration of MAO inhibitors (possibly the development of symptoms, including those characteristic of malignant neuroleptic syndrome).

    Depressive conditions are accompanied by a high risk of suicidal behavior.As a consequence, patients with a diagnosis of depression receiving duloxetine, should inform the doctor of any disturbing thoughts and feelings.

    Against the background of the use of the drug, the development of mydriasis is possible, caution should be exercised in prescribing duloxetine to patients with increased intraocular pressure or in persons at risk of developing acute, closed-angle glaucoma.

    In patients with hypertension and / or other diseases of the cardiovascular system, it is recommended to control blood pressure.

    Patients receiving duloxetine, should be careful when dealing with potentially hazardous activities (due to the possible occurrence of drowsiness).

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