Duloxenta, 60 mg 28 pcs

– Depression.

– Painful form of peripheral diabetic neuropathy.

– Generalized anxiety disorder.

– Chronic musculoskeletal pain syndrome (including those due to fibromyalgia, chronic pain syndrome in the lower back and in osteoarthritis of the knee).

Active ingredient

Composition

1 capsule enteric-soluble 30 mg/60 mg contains pellets:

Active substance:

Duloxetine hydrochloride 33.675 mg/67.350 mg, equivalent to duloxetine 30,000 mg/60,000 mg

Duloxetine hydrochloride 33.675 mg/67.350 mg, equivalent to duloxetine 30,000 mg/60,000 mg

Excipients:

Sugar cereal, hypromellose 6cP, sucrose, HP-50 hypromellose phthalate, talc, triethylcitrate

Solid gelatin capsules #3/#1

Corpus:

Titanium dioxide (E171), indigo carmine (E132) (for 60 mg capsules), iron oxide yellow dye (E172) (for 60.00 mg capsules), gelatin

Cap:

Indigo carmine (E132), titanium dioxide (E171), gelatin

Ink Composition:

Shellac (E904), ethanol (E1510), isopropanol, butanol, propylene glycol (E1520), aqueous ammonia (E527), black iron oxide dye (E172), potassium hydroxide (E525), purified water

How to take, the dosage

Ingestion. The capsules should be swallowed whole without chewing or crushing.

Do not add Duloxenta® to food or mix it with liquids, as this may damage the enteric shell of the pellets.

Depression

The starting and recommended maintenance dose is 60 mg once daily, regardless of meal times. Doses ranging from 60 mg to a maximum dose of 120 mg daily have been evaluated for safety in clinical trials. However, no clinical evidence has been obtained that patients who did not respond to the initial recommended dose showed any improvement with increasing doses.

Response to therapy is usually noted 2-4 weeks after treatment initiation.

To avoid a relapse after a response to antidepressant therapy is achieved, it is recommended to continue treatment for several months. In patients responding positively to duloxetine therapy with a history of recurrent depression, continued long-term therapy at doses ranging from 60 mg/day to 120 mg/day is possible.

Generalized anxiety disorder

The recommended starting dose in patients with generalized anxiety disorder is 30 mg daily, regardless of meal times. In patients with insufficient response to therapy, it is possible to increase the dose to 60 mg/day, the usual maintenance dose in most patients.

In patients with concomitant depression, the starting and maintenance dose is 60 mg/day (see also recommendations above). Doses up to 120 mg/day have been shown to be effective in clinical trials, and such doses have also been evaluated for safety. Therefore, in patients with insufficient response to 60 mg/day, it may be appropriate to increase the daily dose to 90 mg or 120 mg. Dose increases should be based on clinical response and tolerability.

In order to avoid a relapse after a response to therapy is achieved, it is recommended that treatment be continued for several months.

Painful form of peripheral diabetic neuropathy

The initial and recommended maintenance dose is 60 mg once daily, regardless of meal times. Doses ranging from 60 mg/day to a maximum dose of 120 mg/day, divided into equal doses, were also evaluated for safety during clinical trials. Duloxetine plasma concentrations are characterized by considerable individual variability. Therefore, some patients with inadequate response to the 60 mg/day dose may experience improvement with a higher dose.

The response to therapy should be evaluated after 2 months. Patients with insufficient initial response are unlikely to improve response after this time period.

Therapeutic effect should be evaluated regularly (at least once every 3 months).

Chronic musculoskeletal pain syndrome (including those due to fibromyalgia, chronic lower back pain and osteoarthritis of the knee)

: justify;”> Initial treatment: the recommended dose of Duloxant® is 60 mg once daily. Therapy may be started with a dose of 30 mg for 1 week to allow patients to adjust to the drug before increasing the dose to 60 mg once daily. Evidence that higher doses provide additional benefit is lacking, even in patients who do not respond to therapy with 60 mg/day. Higher doses are associated with a higher incidence of adverse reactions.

Continuation of treatment: the efficacy of duloxetine in the treatment of fibromyalgia has been demonstrated in placebo-controlled trials lasting up to 3 months. Efficacy has not been established in longer studies, but the decision to continue treatment should be based on individual patient response.

Kidney function impairment

Dose adjustment is not required for CK of 30-80 ml/min, Duloxant® is contraindicated for CK less than 30 ml/min.

Hepatic dysfunction

The drug Duloxenta® should not be administered to patients with liver disease accompanied by liver failure.

Age

In elderly patients for treatment of generalized anxiety disorder, an initial dose of 30 mg/day for 2 weeks is recommended before starting duloxetine at a target dose of 60 mg/day. Thereafter, use of the drug at a dose greater than 60 mg/day may be possible to achieve good results. There has been no systematic evaluation of dosing above 120 mg/day. When using duloxetine for other indications, dosage adjustment depending on the patient’s age is not required.

The use of the drug is recommended in patients ≥18 years of age. Duloxetine is not recommended for use in children < 18 years of age due to insufficient data on its safety and efficacy when used in this age group of patients.

Cancellation of therapy

Abrupt withdrawal of therapy should be avoided. When discontinuing duloxetine treatment, the dose should be gradually reduced over 1-2 weeks to reduce the risk of withdrawal. If significant withdrawal symptoms occur after reducing the dose or discontinuing treatment, continuation of the previously prescribed dose may be considered. Subsequently, the physician may continue the dose reduction, but even more gradually.

Interaction

Monoamine oxidase inhibitors (MAOIs)

Because of the risk of serotonin syndrome, duloxetine should not be used in combination with MAOIs and for at least 14 days after stopping MAOI treatment. Based on the duration of T1/2 duloxetine, a break of at least 5 days should be taken after stopping duloxetine before taking IMAOs.

For selective reversible IMAOs, such as moclobemide, the risk of serotonin syndrome is lower. However, concomitant use of reversible IMAOs and duloxetine is not recommended.

Inhibitors of CYP1A2 isoenzyme

Due to the fact that the CYP1A2 isoenzyme is involved in the metabolism of duloxetine, concomitant administration of duloxetine with potential CYP1A2 isoenzyme inhibitors will likely result in higher duloxetine concentrations. The potent CYP1A2 isoenzyme inhibitor fluvoxamine (100 mg once daily) reduced mean plasma clearance of duloxetine by approximately 77%. Caution should be exercised when using duloxetine with CYP1A2 isoenzyme inhibitors (e.g., some quinolone antibiotics) and lower doses of duloxetine should be used.

Drugs affecting the CNS

Caution should be exercised when using duloxetine concomitantly with other drugs and agents affecting the CNS, especially those with a similar mechanism of action, including ethanol. Concomitant use with other drugs with serotonergic effects (e.g., SSRIs, SSRIs, triptans, and tramadol) may lead to the development of serotonin syndrome.

Serotonin syndrome

In rare cases, serotonin syndrome has been observed when SSRIs (eg, paroxetine, fluoxetine) and serotonergic drugs are used simultaneously. Caution should be exercised when using duloxetine concomitantly with serotonergic antidepressants such as SSRIs, tricyclic antidepressants (clomipramine or amitriptyline), St. John’s Wort, venlafaxine or triptans, tramadol, pethidine and tryptophan.

Drugs metabolized by CYP1A2 isoenzyme

The concomitant use of duloxetine (60 mg 2 times daily) had no significant effect on the pharmacokinetics of theophylline, which is metabolized by the CYP1A2 isoenzyme. Duloxetine is unlikely to have a clinically significant effect on the metabolism of CYP1A2 isoenzyme substrates.

Drugs metabolized by the CYP2D6 isoenzyme

Duloxetine is a moderate inhibitor of the CYP2D6 isoenzyme. When duloxetine is taken at a dose of 60 mg twice daily concomitantly with a single dose of desipramine, a CYP2D6 isoenzyme substrate, the AUC of desipramine is increased 3-fold. Concomitant administration of duloxetine (40 mg 2 times daily) increased the equilibrium concentration of tolterodine (2 mg 2 times daily) by 71%, but had no effect on the pharmacokinetics of 5-hydroxymetabolite. Thus, caution should be exercised when using duloxetine with drugs that are primarily metabolized by the CYP2D6 isoenzyme and have a narrow therapeutic index.

CYP2D6 isoenzyme inhibitors

Since the CYP2D6 isoenzyme is involved in the metabolism of duloxetine, concomitant use of duloxetine with potential CYP2D6 isoenzyme inhibitors may result in increased concentrations of duloxetine. Paroxetine (20 mg once daily) decreased mean clearance of duloxetine by approximately 37%. Caution should be exercised when using duloxetine with CYP2D6 isoenzyme inhibitors (e.g., SSRIs).

Contraceptives for oral administration and other steroid drugs

The results ofin vitro, studies indicate that duloxetine does not induce the catalytic activity of the CYP3A isoenzyme. No specific studies on drug interactions under in vivo conditions have been conducted.

Anticoagulants and antithrombotic drugs

Due to the potential increased risk of bleeding associated with pharmacodynamic interactions, caution should be exercised when using duloxetine and anticoagulants or antithrombotic drugs concomitantly. In addition, concomitant use of duloxetine and warfarin increased the international normalized ratio (INR). However, concomitant use of duloxetine and warfarin under stable conditions in healthy volunteers in a clinical pharmacology study showed no clinically significant change in INR from the mean or change in the pharmacokinetics of the right- or left-handed warfarin isomer.

Antacids and H2-histamine receptor antagonists

The concomitant use of duloxetine and aluminum- and magnesium-containing antacids or duloxetine and famotidine had no significant effect on the degree of absorption of duloxetine when the 40-mg dose was used.

CYP1A2 isoenzyme inducers

Population pharmacokinetic analysis showed that compared to nonsmoking patients, smoking patients had nearly 50% lower plasma concentrations of duloxetine.

Drugs that bind highly to plasma proteins

Duloxetine binds highly to plasma proteins (> 90%). Therefore, the use of duloxetine in a patient who is taking another drug that binds to plasma proteins to a high degree may result in higher concentrations of free fractions of both drugs.

Special Instructions

Mania and bipolar disorder (including history), seizures (including history), intraocular hypertension or risk of acute attack of closed-angle glaucoma, suicidal thoughts and attempts in history, increased risk of hyponatremia (elderly patients, cirrhosis, dehydration, taking diuretics), hepatic dysfunction and renal failure (CK 30-60 ml/min).

Duloxetine is not recommended for use in children younger than 18 years of age due to insufficient data on its safety and effectiveness when used in this age group of patients.

Kidney function impairment

Dose adjustment is not required for CK of 30-80 ml/min; Duloxant® is contraindicated for CK less than 30 ml/min.

Hepatic dysfunction

The drug Duloxenta® should not be administered to patients with liver disease accompanied by liver failure.

Age

In elderly patients for treatment of generalized anxiety disorder, an initial dose of 30 mg/day for 2 weeks is recommended before starting duloxetine at a target dose of 60 mg/day. Thereafter, use of the drug at a dose greater than 60 mg/day may be possible to achieve good results. There has been no systematic evaluation of dosing above 120 mg/day. When using duloxetine for other indications, dosage adjustment depending on the patient’s age is not required.

Exacerbation of manic/hypomanic state

As with similar drugs that affect the CNS, duloxetine should be used with caution in patients with a history of manic episodes.

Epileptic seizures

As with similar drugs that affect the CNS, duloxetine should be used with caution in patients with a history of epileptic seizures.

Mydriasis

Mydriasis has been observed while taking duloxetine, so caution should be exercised when using duloxetine in patients with elevated intraocular pressure or in those at risk of developing acute closed-angle glaucoma.

Elevation of blood pressure

In single cases, elevation of blood pressure during duloxetine treatment has been observed. In patients with arterial hypertension and/or other cardiovascular diseases, it is recommended to measure blood pressure.

Disorders of renal function, liver

In patients with severe renal dysfunction (CK < 30 ml/min) or severe hepatic impairment, increased plasma concentrations of duloxetine have been observed. If duloxetine administration is clinically justified in such patients, lower initial doses of the drug should be used.

Suicidal behavior

The risk of suicide exists in all patients with depression and some other psychiatric disorders. This danger may persist until the onset of remission. As a consequence, patients who are at highest risk of suicide should be closely monitored by the pharmacologist during pharmacotherapy. As with other drugs with a pharmacological mechanism of action similar to duloxetine (SSRIs, SSRIs), duloxetine administration during treatment or upon discontinuation has in some cases been associated with the development of suicidal ideation and suicidal behavior. The use of duloxetine in patients under 18 years of age has not been studied, so duloxetine is not indicated for use in these patients. A causal relationship between duloxetine administration and the occurrence of suicidal ideation in patients in this age group has not been established. At the same time, some analytic reviews of several studies using antidepressants for the treatment of psychiatric disorders indicate an increased risk of suicidal ideation and/or suicidal behavior in children, adolescents and adults under the age of 25 compared to placebo. Physicians should encourage patients to report any disturbing thoughts and feelings at any time.

Sexual dysfunction

SSRIs/IOPSNs can cause symptoms of sexual dysfunction. There have been reports of long-term sexual dysfunction in which symptoms persisted despite discontinuation of SSRIs/IOZSNs.

Elevated risk of bleeding

SSRIs and SSRIs, including duloxetine, may increase the risk of bleeding, including gastrointestinal bleeding (see See section “Side effects”). Therefore, duloxetine should be used with caution in patients taking anticoagulants and/or drugs that affect platelet function (e.g., non-steroidal anti-inflammatory drugs, including aspirin) and in patients with a tendency to bleeding in the anamnesis.

Hyponatremia

Very rarely have cases of hyponatremia been reported (in some cases, serum sodium levels were lower than 110 mmol/L). Most of these cases occurred in elderly patients, especially when combined with an altered fluid balance in a recent history or when conditions predisposing to altered fluid balance are present.

Hyponatremia may manifest as nonspecific symptoms (such as dizziness, weakness, nausea, vomiting, confusion, drowsiness, lethargy). Signs and symptoms manifested in more severe cases included fainting, falls, and seizures.

IMAO

In patients taking a serotonin reuptake inhibitor concomitantly with IMAO, there have been cases of serious reactions, sometimes fatal, including hyperthermia, rigidity, myoclonus, peripheral disturbances with possible dramatic fluctuations of vital functions and mental status changes, including severe agitation with a transition to delirium and coma. These reactions were also observed in patients who, shortly before the use of IMAO, had had a serotonin reuptake inhibitor withdrawn. In some cases, patients exhibited symptoms characteristic of malignant neuroleptic syndrome. The effects of concomitant use of duloxetine and IMAO have not been evaluated in either humans or animals. Therefore, given the fact that duloxetine is an IOSS, it is not recommended to take duloxetine concomitantly with IMAO or for at least 14 days after stopping IMAO treatment. Based on the duration of T1/2 duloxetine, you should take a break for at least 5 days after stopping duloxetine before taking an IMAO.

Elevated plasma liver enzyme activity

Some patients who took duloxetine in clinical trials showed increased plasma liver enzyme activity. The observed abnormalities were usually transient and disappeared spontaneously or after cessation of duloxetine. Significant increase in plasma liver enzyme activity (10 times or more above the upper limit of normal), as well as liver damage of cholestatic or mixed genesis were observed rarely, and in some cases were associated with excessive alcohol intake, or previous liver disease. It is recommended with caution to use duloxetine in patients consuming significant amounts of alcohol and with existing liver disease.

Special information about excipients

Synopsis

Capsules 30 mg:Strong gelatin capsules № 3, the capsule body is white, the capsule cap is dark blue. On the body of the capsule in black ink marked 30. The content of the capsules – pellets of white or almost white color.

Capsules 60 mg: Strong gelatin capsules № 1, the capsule body is yellowish-green, the capsule cap is dark blue. On the body of the capsule in black ink marked 60. The contents of the capsules are pellets of white or almost white color.

Contraindications

Overdose

In clinical trials, overdoses have been known to occur with up to 3000 mg of duloxetine taken alone or in combination with other drugs at one time. One of these cases was fatal. However, spontaneous (post-marketing) reports contained descriptions of fatal acute overdoses, usually with combined intake of several drugs, in which the dose of duloxetine was no more than 1000 mg.

Symptoms

Duloxetine overdose (isolated or combined) may be accompanied by the following symptoms: Drowsiness, coma, clonic seizures, serotonin syndrome, vomiting, and tachycardia. In preclinical studies (in animals) the main signs of intoxication associated with overdose were CNS and digestive system disorders and included such manifestations as tremors, clonic convulsions, ataxia, vomiting and decreased appetite.

Treatment

A specific antidote is not known, but corrective treatment with cyproheptadine and body temperature normalization methods are possible if serotonin syndrome developed. Adequate fresh air should be provided. Cardiac monitoring and monitoring of basic vital signs are recommended, along with symptomatic and supportive treatment. Gastric lavage may be indicated if little time has elapsed since ingestion or as part of symptomatic treatment. Activated charcoal may be used to limit absorption. Duloxetine is characterized by a large volume of distribution, due to which the effectiveness of forced diuresis, hemoperfusion, exchange perfusion is questionable.

Pregnancy use

Pregnancy

Due to insufficient experience with duloxetine during pregnancy, Duloxenta® should be administered during pregnancy only if the potential benefit to the mother significantly exceeds the potential risk to the fetus. Patients should be warned that if they become pregnant or plan to become pregnant while on duloxetine treatment, they should inform their physician.

Epidemiologic evidence suggests that the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, particularly late in pregnancy, may increase the risk of persistent pulmonary hypertension in newborns (PHH). Although there are no studies on the relationship between PAHN and SSRI use, the potential risk cannot be excluded, given the mechanism of action of duloxetine (serotonin reuptake inhibition).

As with other serotonergic drugs, “withdrawal” syndrome may be observed in infants if the mother uses duloxetine late in pregnancy.

The “withdrawal” syndrome includes the following symptoms: decreased blood pressure, tremors, increased neuroreflexivity syndrome, feeding difficulties, respiratory distress syndrome, and seizures. Most of the symptoms were observed during labor or in the first few days after delivery.

Breastfeeding period

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

Fertility

In animal studies, duloxetine had no effect on male fertility, and effects in females were observed only when doses were administered that had toxic effects on the maternal body.

Similarities