Dyulok hard enteric-coated capsules 60 mg blister No. 30

Instructions for use: Dyulok hard enteric-coated capsules 60 mg, blister pack No. 30

Composition

active ingredient: duloxetine;

1 capsule contains duloxetine hydrochloride – 33.7 mg or 67.4 mg, which is equivalent to duloxetine – 30 mg or 60 mg;

excipients: spherical sugar, hydroxypropyl methylcellulose, polyethylene glycol 6000, talc, sucrose, hydroxypropyl methylcellulose acetate succinate, triethyl citrate;

Hard gelatin capsule No. 3 (for 30 mg capsules):

capsule shell composition: titanium dioxide (E 171), indigotine blue (E 132), gelatin;

Hard gelatin capsule No. 1 (for 60 mg capsules):

capsule shell composition: titanium dioxide (E 171), indigotine blue (E 132), quinoline yellow (E 104), erythrosine (E 127), gelatin.

Dosage form

Enteric-coated hard capsules.

Main physicochemical properties:

Capsules 30 mg: hard gelatin capsule No. 3, blue body, white cap. Capsule contents are white or almost white pellets.

Capsules 60 mg: hard gelatin capsule No. 1, blue body, ivory cap. Capsule contents are white or almost white pellets.

Pharmacotherapeutic group

Antidepressants. ATX code N06A X21.

Pharmacological properties

Pharmacodynamics

Duloxetine is a combined serotonin and norepinephrine reuptake inhibitor. It has little dopamine reuptake inhibition and has low affinity for histamine, dopamine, cholinergic, and adrenergic receptors. The mechanism of action of duloxetine in the treatment of depression is due to inhibition of serotonin and norepinephrine reuptake and, as a result, increased serotonergic and noradrenergic neurotransmission in the central nervous system. Duloxetine also has analgesic effects, which are likely to be the result of slowing the transmission of pain impulses in the central nervous system.

Pharmacokinetics

Duloxetine is well absorbed after oral administration. Peak concentrations are reached 6 hours after administration. Food intake delays absorption, increasing the time to peak concentration from 6 to 10 hours and decreasing absorption (by approximately 11%).

Distribution: Duloxetine is highly bound to serum proteins (>90%).

Metabolism: Duloxetine is metabolized by CYP2D6 and CYP1A2 isoenzymes. The metabolites formed are pharmacologically inactive.

Elimination: The elimination half-life of duloxetine is 12 hours. The mean plasma clearance of duloxetine is 101 L/h.

Renal impairment: Patients with end-stage renal disease undergoing dialysis have been shown to have a two-fold increase in duloxetine concentrations and exposure (AUC) compared to healthy subjects. Therefore, a lower starting dose should be used in patients with chronic renal failure.

Indication

Treatment of major depressive disorder.

Treatment of diabetic peripheral neuropathic pain.

Treatment of generalized anxiety disorder.

Contraindication

A contraindication for the use of the drug is hypersensitivity to duloxetine or to any of the drug's excipients.

Duloxetine should not be administered concomitantly with non-selective, irreversible monoamine oxidase (MAO) inhibitors or for at least 14 days after discontinuation of MAO inhibitors. Given the half-life of duloxetine, MAO inhibitors should not be administered for at least 5 days after discontinuation of duloxetine.

Duloc® should not be prescribed to patients with unstable hypertension, as it may trigger a hypertensive crisis.

Duloc® should not be prescribed to patients with end-stage renal failure (creatinine clearance up to 30 ml/min).

Duloc® should not be prescribed to patients with liver disease - it may cause liver failure.

Duloxetine is not recommended for use in children due to insufficient data on its safety and efficacy in this age group.

Duloxetine should not be administered in combination with fluvoxamine, ciprofloxacin or enoxacin (strong CYP1A2 inhibitors) due to increased plasma concentrations of duloxetine.

Interaction with other medicinal products and other types of interactions

Drugs metabolized by CYP1A2: In a clinical study, theophylline, a CYP1A2 substrate, was co-administered with duloxetine (60 mg twice daily) and their pharmacokinetics did not significantly affect each other.

Drugs metabolized by CYP2D6. Duloxetine is a moderate inhibitor of CYP2D6. When duloxetine 60 mg twice daily was administered with a single dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold. Co-administration of duloxetine (40 mg twice daily) increased the steady-state AUC of tolterodine (2 mg twice daily) by 71% but did not affect the pharmacokinetics of the 5-hydroxy metabolite. Therefore, caution should be exercised when administering duloxetine with CYP2D6 inhibitors that have a narrow therapeutic index.

Central nervous system drugs: Certain precautions should be taken when prescribing duloxetine in combination with other drugs and substances that act on the central nervous system, especially those with a similar mechanism of action, including alcohol and sedative drugs.

MAO inhibitors: Duloxetine should not be administered with non-selective, irreversible monoamine oxidase (MAO) inhibitors due to the risk of serotonin syndrome. Reversible, selective monoamine oxidase (MAO) inhibitors, such as moclobemide, have a lower risk of serotonin syndrome, but this combination is not recommended.

Serotonin syndrome. Caution should be exercised when prescribing Duloc® in combination with serotonergic and tricyclic antidepressants, St. John's wort preparations, tramadol, peptidine, and tryptophan.

Anticoagulants and antithrombotic agents: Duloxetine should be administered with caution with oral anticoagulants and antithrombotic agents due to an increased risk of bleeding due to pharmacodynamic interactions.

Medicines containing duloxetine.

Concomitant use with other medicinal products containing duloxetine should be avoided.

Preparations containing St. John's wort herb.

When used together with the drug Duloc®, adverse reactions often occur.

Application features

WARNING

Patients at high risk of suicide should be closely monitored during treatment, as the possibility of a suicide attempt cannot be ruled out until significant remission occurs.

Duloxetine hydrochloride has not been studied in patients under 18 years of age and is not indicated for use in this age group.

Seizures and mania: As with other drugs that act on the central nervous system, duloxetine should be prescribed with caution in patients with a history of seizures, mania, or bipolar disorder.

Mydriasis: Mydriasis has been reported in association with duloxetine, therefore duloxetine should be used with caution in patients with elevated intraocular pressure or at risk of acute narrow-angle glaucoma.

Blood pressure and palpitations. In some patients, duloxetine has been associated with an increase in blood pressure. Monitoring of blood pressure is recommended in patients with hypertension and/or other heart disease. Patients with persistently elevated blood pressure should have their dose reduced or the drug gradually discontinued. Treatment is not appropriate in patients with unstable hypertension.

Haemorrhage: Several cases of haemorrhage have been reported, including purpura, gastrointestinal haemorrhage and hemorrhage.

Hyponatremia. Caution should be exercised in prescribing to patients at increased risk of hyponatremia: the elderly, individuals with antidiuretic hormone deficiency, and individuals with cirrhosis of the liver.

Withdrawal syndrome: Withdrawal symptoms are quite common, especially when treatment is stopped abruptly. Treatment should be discontinued over a period of at least 2 weeks with a gradual reduction in dose.

Akathisia/psychomotor restlessness: These symptoms occur within the first few weeks of treatment.

Elevated liver enzymes. Severe elevations of liver enzymes (>10 times the upper limit of normal) or liver injury with cholestasis or severe elevations of enzymes together with liver injury have occurred rarely. These events have been reported most frequently during the first months of treatment. Liver injury is most often hepatocellular in nature. Caution should be exercised when prescribing duloxetine to patients taking medications that can cause liver injury.

Presence of sucrose. Enteric-coated capsules of Duloc® should not be prescribed to patients with hereditary fructose intolerance, malabsorption syndrome, or sucrase-isomaltase insufficiency.

Suicide.

Major depressive disorder and generalized anxiety disorder.

Other psychiatric conditions for which Duloxetine is prescribed are also associated with an increased risk of suicidal behaviour. In addition, these psychiatric conditions may be comorbid if they accompany major depressive disorder. Therefore, caution should be exercised when treating patients with both major depressive disorder and other psychiatric conditions. Patients with a history of suicidal behaviour or a significant level of suicidal ideation are at greater risk of suicidal behaviour and should be monitored closely during treatment. Suicidal ideation and behaviour have been reported during duloxetine therapy or early after discontinuation. Patients should be closely monitored during therapy, particularly those at risk, and the dosage should be adjusted accordingly.

Diabetic peripheral neuropathic pain.

Isolated cases of suicidal ideation and suicidal behaviour have been reported during or early after treatment with duloxetine, as with other medicinal products with similar pharmacological effects (antidepressants). Physicians should advise patients to report any feelings of distress.

Elderly people.

Data on the use of Duloc® 120 mg in elderly people with major depressive disorder and generalized anxiety disorder are limited.

Serious skin reactions.

The following skin reactions have been reported very rarely in post-marketing studies: angioedema, contusion, hemorrhage, Stevens-Johnson syndrome, bruising, urticaria.

Use during pregnancy or breastfeeding

There are no adequate and well-controlled studies in pregnant women, so the use of the drug during pregnancy is not recommended. As with other serotonergic drugs, withdrawal symptoms may occur in infants whose mothers have used duloxetine before delivery. Symptoms of withdrawal syndrome include orthostatic hypotension, tremor, hyperexcitability, difficulty swallowing, sucking, respiratory distress, and seizures. In most cases, these symptoms have occurred immediately after birth or within the first few days of life. Women should be advised to inform their doctor if they become pregnant or plan to become pregnant while taking duloxetine.

The use of the drug during pregnancy is recommended only if the expected effect outweighs the risk.

Duloxetine is excreted in breast milk to a small extent. The estimated dose to the infant (on a mg/kg basis) is 0.14% of the maternal dose. The safety of duloxetine in children is unknown, so breastfeeding is not recommended while taking duloxetine.

Ability to influence reaction speed when driving vehicles or other mechanisms

During treatment, patients should refrain from potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Method of administration and doses

For major depressive disorder: Duloxetine is prescribed at a dose of 60 mg once daily, regardless of meals.

A daily dose above 60 mg may be recommended for some patients, up to a maximum dose of 120 mg per day, divided into 2 doses. The feasibility of prescribing doses above 120 mg has not been systematically evaluated.

For diabetic peripheral neuropathic pain. The recommended starting dose is 60 mg once daily, with or without food. Some patients may be prescribed a daily dose higher than 60 mg - up to a maximum dose of 120 mg per day, divided into 2 doses.

The therapeutic effect of treatment is evident within 2 months.

For generalized anxiety disorder. The recommended initial dose is 30 mg once daily, regardless of meals. In case of insufficient treatment effect, the dose should be increased to 60 mg per day. In case of insufficient treatment effect at a dose of 60 mg, an increase in the dose to 90 or 120 mg per day may be considered.

The therapeutic effect of treatment is evident within 2–4 weeks.

Patients with renal insufficiency. No dose adjustment is required for patients with mild to moderate renal insufficiency. It is not used to treat patients with end-stage renal disease (creatinine clearance <100 mL/min).

Patients with hepatic insufficiency. Duloc® should not be prescribed to patients with liver disease.

Age. No dose adjustments are required for elderly patients.

Children.

Clinical studies on the use of duloxetine in children have not been conducted, therefore the drug is not used in pediatric practice.

Overdose

Treatment of overdose. Specific antidotes are not known, and specific treatment (cyproheptadine and/or temperature control) is necessary if serotonin syndrome occurs. Airway patency should be checked. Cardiac monitoring and vital signs should be monitored, along with appropriate symptomatic and supportive measures. Gastric lavage may be appropriate if administered immediately after ingestion or in patients with symptoms of overdose. Activated charcoal reduces absorption. Duloxetine has a large volume of distribution, so forced diuresis, hemoperfusion, and exchange perfusion are unlikely to be useful.

Adverse reactions

Dizziness, nausea and headache (> 5%) have been reported as adverse reactions on discontinuation of duloxetine. Sensory disturbances, sleep disturbances, agitation or anxiety, tremor, irritability, diarrhoea and hyperhidrosis have also been observed on discontinuation of the drug. The table below lists the adverse reactions with duloxetine based on data from spontaneous reports and placebo-controlled clinical trials.

Frequency estimate: very common (≥ 10%), common (≥ 1% and and (≥ 0.01% and.

1 Cases of seizures and tinnitus have been observed after discontinuation of treatment.

2 Cases of orthostatic hypotension and loss of consciousness were observed mainly at the beginning of treatment.

3 Patients who experience persistent elevations in blood pressure while taking duloxetine should have their dose reduced or therapy gradually discontinued.

4 Cases of aggression and anger have been reported at the start of treatment and after treatment discontinuation.

5 Cases of suicidal ideation and suicidal behaviour have been reported early in treatment and early after treatment discontinuation.

6 The frequency of adverse reactions identified from post-marketing studies that were not observed in placebo-controlled clinical trials.

7 Statistically not significantly different from placebo.

8 Falls were more common in older people (≥ 65 years).

Discontinuation of therapy (especially abrupt discontinuation) is often accompanied by a withdrawal syndrome. The most common adverse reactions in this case are: dizziness, drowsiness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and severe delusions), weakness, anxiety or aggression, nausea and/or vomiting, tremor, headache, irritability, diarrhoea, hyperhidrosis and vertigo. Gradual discontinuation of therapy is recommended.

Kidney failure.

In patients with severe renal impairment (creatinine clearance

Hepatitis/increased liver enzymes.

Cases of liver injury have been reported, including marked elevations of liver enzymes (up to 10 times the upper limit of normal), hepatitis and jaundice. Most of these events occurred within the first month of treatment. The most common type of liver injury is hepatocellular. Duloxetine should be used with caution in patients taking medications that can cause liver injury.

Minor increases in blood potassium levels have been reported. Transient abnormal values of potassium levels were uncommon in patients treated with duloxetine compared to placebo.

Expiration date

2 years.

Do not use the drug after the expiration date indicated on the package.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 ºС.

Keep out of reach of children.

Packaging

Enteric-coated hard capsules 30 mg or 60 mg. 10 capsules in blisters. 3 or 6 blisters in a pack (bulk packaging from the manufacturer Laboratorios Norman, S.A., Spain).

Vacation category

According to the recipe.

Producer

JSC "Farmak".

Location of the manufacturer and its business address

Ukraine, 04080, Kyiv, Kyrylivska St., 74.