Duloxetine 60mg capsules №28

Tradename:

Duloxetine Canon

International non-proprietary name:

duloxetine

Dosage Form:

enteric capsules

Composition

Dosage 60 mg

One enteric capsule contains:

active substance: duloxetine, pellets 353 mg, including: duloxetine hydrochloride 67.36 mg, in terms of duloxetine 60 mg, hypromellose E5 (hydroxypropylmethylcellulose) 21.08 mg, hypromellose HP55 (hydroxypropylmethylcellulose) 31.02 mg, starchal, 88.18 mg mannitol 94.6 mg, sodium lauryl sulfate 10.44 mg, sucrose 34.92 mg, titanium dioxide 2.3 mg, cetyl alcohol 3.1 mg;

hard gelatin capsule number 1: case - dye blue patented V, titanium dioxide, gelatin; cap - dye blue patented V, titanium dioxide, gelatin.

Description

Hard gelatin capsules No. 3 (dosage 30 mg) or No. 1 (dosage 60 mg), body and cap blue. The contents of the capsules are spherical microgranules from almost white to yellowish white.

Pharmacotherapeutic group: antidepressant

Pharmacological properties

Pharmacodynamics

Duloxetine is an antidepressant, an inhibitor of serotonin and norepinephrine reuptake, weakly inhibits 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 noradrenaline, resulting in increased serotonergic and noradrenergic neurotransmission in the central nervous system.

Duloxetine has a central mechanism for the suppression of pain, which is primarily manifested by an increase in the pain sensitivity threshold in pain syndrome of neuropathic etiology.

Pharmacokinetics

Suction

Duloxetine is well absorbed when taken orally. Absorption begins 2 hours after taking the drug. Maximum concentration (C_max) is achieved after 6 hours after taking the drug.

Eating does not affect the maximum concentration of the drug, but increases the time to reach the maximum concentration (TC_max) from 6 to 10 hours, which indirectly reduces the degree of absorption (approximately 11%).

Distribution

Duloxetine binds well to plasma proteins (> 90%), mainly albumin and α_l-acid glycoprotein, but disorders of the liver or kidneys do not affect the degree of binding to proteins.

Metabolism

Duloxetine is extensively metabolized and its metabolites are mainly excreted in the urine.

Both the CYP2D6 isoenzyme and the CYP1A2 isoenzyme catalyze the formation of two major metabolites (glucuronic conjugate 4-hydroxiduloxetine, sulfate conjugate 5 ‑ hydroxy, 6-methoxydioxetine).

Circulating metabolites do not possess pharmacological activity.

Removal

The duration of the half-life (T_1/2) duloxetine is 12 hours. The average clearance of duloxetine is 101 l / h.

Selected patient groups

Floor: Although there were differences in pharmacokinetics between men and women (the average clearance of duloxetine is lower in women), these differences are not so great that there is a need for dose adjustment depending on gender.

Age: in spite of the fact that differences in pharmacokinetics between middle-aged and elderly patients were revealed (the area under the concentration / time curve (AUC) is longer and the duration of T_1/2 drug more in the elderly), these differences are not enough to change the dose depending only on the age of the patients.

Renal impairment: in patients with severely impaired renal function (end-stage CRF - chronic renal failure) on hemodialysis, C values_max and AUC of duloxetine increased by 2 times. In this regard, it is necessary to consider the feasibility of reducing the dose of the drug in patients with clinically significant renal dysfunction.

Liver dysfunction: in patients with clinical signs of liver failure, a slowdown in metabolism and elimination of duloxetine may be observed. After a single dose of 20 mg of duloxetine in 6 patients with cirrhosis of the liver with moderately impaired liver function (Class B on the Child-Pugh scale) duration T_1/2 duloxetine was approximately 15% higher than that of healthy people of the corresponding sex and age with a fivefold increase in the average exposure. Despite the fact that_max in patients with cirrhosis was the same as in healthy people, T_1/2 was about 3 times longer.

Indications for use

- Depression;

- A painful form of peripheral diabetic neuropathy;

- Generalized anxiety disorder;

- Chronic musculoskeletal pain syndrome (including due to fibromyalgia, chronic byuoli syndrome in the lower back and with osteoarthritis of the knee joint).

Contraindications

- Hypersensitivity to any of the components of the drug;

- Simultaneous use with monoamine oxidase inhibitors (IMAO);

- Uncompensated angle-closure glaucoma;

- Age up to 18 years (there is no clinical experience with the use of duloxetine in patients of this age group);

- Deficiency of sucrase / isomaltase, fructose intolerance, glucose-galactose malabsorption;

- Diseases of the liver, accompanied by liver failure;

- Simultaneous intake of powerful inhibitors of the isoenzyme CYP1A2 (fluvoxamine, Ciprofloxacin, enoxacin);

- Heavy CKD (creatinine clearance (CC) less than 30 ml / min);

- Uncontrolled arterial hypertension.

Carefully

Mania and bipolar disorder (including history), convulsions (including history), intraocular hypertension or the risk of developing an acute attack of angle-closure glaucoma, suicidal thoughts and attempts in history, increased risk of hyponatremia (elderly patients, cirrhosis, dehydration, edema, increased history of hyponatremia (elderly patients, cirrhosis, dehydration, dehydration), an increased history of hyponatremia (elderly patients, cirrhosis, dehydration, dehydration, dehydration), increased risk of hyponatremia (elderly patients, cirrhosis, dehydration, dehydration, dehydration) diuretic use), abnormal liver function and renal failure (CC 30-60 ml / min).

Use during pregnancy and lactation

Due to the lack of experience with the use of duloxetine during pregnancy, the drug should be prescribed only if the potential benefit to the mother greatly exceeds the potential risk to the fetus. Patients should be warned that in the event of the onset or planning of pregnancy during the period of treatment with duloxetine, they should be informed of this by their doctor.

Epidemiological data suggest that the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, especially in late periods, may increase the risk of persistent pulmonary hypertension in the newborn. Despite the lack of research on the relationship between persistent pulmonary hypertension in newborns and the use of SSRIs, the potential risk cannot be excluded, given the mechanism of duloxetine (inhibition of serotonin reuptake).

As with the appointment of other serotonergic drugs, the syndrome of "cancellation" can be observed in newborns in the case of the use of duloxetine by the mother in the late period of pregnancy. The "withdrawal" syndrome includes the following symptoms: low blood pressure, tremor, syndrome of increased neuro-reflex excitability, difficulty feeding, respiratory distress syndrome, convulsions. Most of the symptoms were observed during labor or during the first few days after birth.

Due to the fact that duloxetine penetrates into breast milk (concentration in the fetus is based on mg / kg body weight approximately 0.14% of the concentration in the mother), breastfeeding during duloxetine therapy is not recommended.

Dosage and administration

Inside Capsules should be swallowed whole without chewing or crushing. Do not add the drug to food or mix it with liquids, as this may damage the enteric shell of the pellets.

The recommended initial dose of the drug is 60 mg 1 time per day, regardless of the meal.

In some patients, to achieve a good result, it is necessary to increase the dose from 60 mg once a day to a maximum dose of 120 mg per day in two doses. A systematic assessment of the drug intake in a dose of more than 120 mg was not carried out.

In patients with renal failure: the initial dose should be 30 mg 1 time per day in patients with severe impaired renal function (end-stage CRF, creatinine clearance <30 ml / min).

In patients with impaired liver function: It should reduce the initial dose of the drug or reduce the frequency of intake in patients with cirrhosis.

Abrupt withdrawal of therapy should be avoided. When discontinuing treatment with duloxetine, the dose should be gradually reduced over one to two weeks in order to reduce the risk of developing “withdrawal” syndrome. If, after a dose reduction or after cessation of treatment, severe symptoms of “withdrawal” syndrome occur, the continuation of the previously prescribed dose may be considered.Subsequently, the doctor may continue to reduce the dose, but even more gradually.

Side effect

The most common side effects in patients taking duloxetine were nausea, headache, dry mouth, drowsiness, and dizziness. However, the majority of these side effects were mild and moderate, occurred at the beginning of therapy, and further their severity decreased.

WHO classification of the incidence of side effects:

very often - 1/10 of appointments (> 10%)

often 1/100 appointments (> 1% and <10%)

infrequently - 1/1000 of appointments (> 0.1% and <1%)

rarely - 1 / 10,000 appointments (> 0.01% and <0.1%)

very rarely - less than 1/10000 appointments (<0.01%)

Infectious and parasitic diseases

Infrequently: laryngitis.

Immune system disorders

Seldom: anaphylactic reaction, hypersensitivity.

Endocrine Disorders

Rarely: hypothyroidism.

Metabolic and nutritional disorders

Very often: decreased appetite¹⁵.

Infrequently: hyperglycemia (especially often observed in patients with diabetes).

Seldom: dehydration, hyponatremia, syndrome of inadequate secretion of antidiuretic hormone⁶.

Mental disorders

Very often: insomnia¹¹.

Often: agitation¹⁰, anxiety, unusual dreams²⁰, decreased libido (including loss of libido), impaired orgasm (including anorgasmia).

Infrequently: suicidal thoughts^5,22, sleep disorders, bruxism, disorientation¹⁹apathy.

Seldom: suicidal behavior^5,22, mania, hallucinations, aggression and hostility⁴.

Nervous system disorders

Very often: dizziness, headache, drowsiness¹².

Often: tremor, paresthesias¹⁸.

Infrequently: myoclonus, akathisia²², increased excitability, impaired concentration, lethargy, dysgeusia, dyskinesia, restless legs syndrome, reduced quality of sleep.

Seldom: serotonin syndrome⁶cramps¹psychomotor agitation⁶extrapyramidal disorders⁶.

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