Duloxetine Canon enteric soluble capsules 60mg, 28pcs

Composition

Enteric-soluble solid gelatin capsules No. 1, body and lid are blue in color; the contents of the capsules are spherical microgranules from almost white to yellowish-white in color.

1 capsule of duloxetine (in the form of hydrochloride) 60 mg

Excipients:

hypromellose E 5 21.08 mg,

hypromellose HP55 31.02 mg,

starch 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.

Capsule shell composition:

gelatin,

titanium dioxide,

dye blue patent V.

Pharmacological action

Pharmaceutical group:

antidepressant.

Pharmaceutical action:  

Inhibits the reuptake of serotonin and noadrenaline, resulting in increased serotonergic and noradrenergic neurotransmission in the central nervous system.

Weakly suppresses the uptake of dopamine, without significant affinity for histaminergic, dopaminergic, cholinergic and adrenergic receptors.

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, diabetic peripheral neuropathy (pain form).

Contraindications

Hypersensitivity, liver diseases accompanied by hepatic insufficiency, concomitant use of non-selective irreversible MAO inhibitors, potent CYP1A2 inhibitors (fluvoxamine, ciprofloxacin, enoxacin), severe CRF (creatinine clearance less than 30 ml/min), uncontrolled arterial hypertension, lactation, age up to 18 years (no experience).

For medicinal products containing sucrose (optional): congenital fructose intolerance, glucose-galactose malabsorption, sucrose-isomaltase deficiency.

With caution. Mania and bipolar disorder (including in the anamnesis), seizures (including in the anamnesis), intraocular hypertension or risk of developing an acute attack of angle-closure glaucoma, suicidal thoughts and attempts in the anamnesis, increased risk of hyponatremia (elderly patients, cirrhosis of the liver, dehydration, taking diuretics), pregnancy.

Side effects

Frequency: very common (1/10 or more), common (more than 1/100 or less than 1/10), infrequent (1/1000 or less than 1/100), rare (1/10000 or less than 1/1000), very rare (less than 1/10000), frequency unknown (cannot be estimated from available data).

From the nervous system: very often – headache, drowsiness; often – dizziness, tremor, lethargy, paresthesia, insomnia, unusual dreams, anxiety, agitation; infrequently – dyskinesia, poor sleep quality, nervousness, myoclonus, impaired concentration, sleep disturbance, apathy, disorientation, bruxism; rarely – mania, aggressiveness, anger; frequency unknown – serotonin syndrome, convulsions, akathisia, psychomotor anxiety, extrapyramidal syndrome, suicidal attempts, suicidal thoughts, hallucinations.

From the digestive system: very often – nausea, dryness of the oral mucosa; often – diarrhea, constipation, vomiting, dyspepsia, flatulence, abdominal pain; infrequently – gastroenteritis, stomatitis, gastritis, belching, taste disorders, hepatitis, acute liver failure, increased activity of “liver” transaminases (ALT, AST, ALP); rarely – bad breath, unchanged blood in the stool; frequency unknown – gastrointestinal bleeding, jaundice, liver failure.

From the genitourinary system: often-erectile dysfunction, decreased libido, changes in the ability to experience the feeling of orgasm; infrequently-urinary retention, intermittent urination, dysuria, nocturia, polyuria, decreased urine flow, violation of sexual function, violation of ejaculation, including delayed ejaculation, gynecological bleeding; rarely – symptoms of menopause; frequency unknown-change in the smell of urine. From the cardiovascular system: often-palpitations, “hot flashes” of blood; infrequently – tachycardia, syncope and orthostatic hypotension (which were reported only at the beginning of treatment), increased blood pressure, cold extremities; rarely – supraventricular arrhythmia, mainly atrial fibrillation; frequency unknown – hypertensive crisis.

From the sensory organs: often-blurred vision, tinnitus; infrequently-visual impairment, mydriasis, vertigo, pain in the ears; rarely-glaucoma.

From the respiratory system: often-yawning; infrequently-nosebleeds, a feeling of compression of the pharynx.

From the skin: often-rash, increased sweating, night sweats, infrequently-photosensitization, increased tendency to subcutaneous hemorrhage, contact dermatitis, urticaria, cold sweat; frequency unknown-angioedema, Stevens-Johnson syndrome.

From the musculoskeletal system: often-muscle spasm, musculoskeletal pain, muscle stiffness; infrequently-muscle twitching; rarely-trismus.

From the endocrine system: rarely-hypothyroidism.

From the side of metabolism: often-decreased appetite; infrequently-hyperglycemia (reported mainly in patients with diabetes mellitus); rarely-dehydration, syndrome of inadequate secretion of antidiuretic hormone, hyponatremia.

Infections: infrequently-laryngitis.

Other: often-fatigue, weight loss; infrequently-weight gain, malaise, gait disorder, sensitivity disorder, cold sensation, heat sensation, thirst, chills, increased CPK; rarely-hypercholesterolemia; frequency unknown-chest pain. Allergic reactions: infrequently-hypersensitivity reactions; rarely-anaphylactoid reactions.

With abrupt withdrawal – withdrawal syndrome, the most common symptoms of which were dizziness, sensory disturbances (including paresthesia), sleep disorders (including insomnia, intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, headache, irritability, diarrhea, hyperhidrosis, vertigo.

Interaction

Concomitant use of duloxetine (60 mg twice daily) did not significantly affect the pharmacokinetics of theophylline metabolized by CYP1A2.

Concomitant use of duloxetine with potential CYP1A2 inhibitors may increase the concentration of duloxetine. CYP1A2 inhibitor fluvoxamine (100 mg once daily) reduces the plasma clearance of duloxetine by approximately 77% and increases the AUC by 6 times, so duloxetine should not be used in combination with potential CYP1A2 inhibitors, such as fluvoxamine. Duloxetine is a moderate inhibitor of CYP2D6. When taking duloxetine at a dose of 60 mg 2 times a day together with a single dose of desipramine (a CYP2D6 substrate), the AUC of desipramine increases by 3 times. Concomitant use of duloxetine (40 mg twice daily) increases the AUC of tolterodine (2 mg twice daily) by 71%, but does not affect the pharmacokinetics of the 5-hydroxyl metabolite. Caution should be exercised when using duloxetine with drugs that are mainly metabolized by the CYP2D6 system and have a narrow therapeutic index.

Concomitant use of duloxetine with potential CYP2D6 inhibitors may lead to increased duloxetine concentrations. Paroxetine (20 mg once a day) reduces the clearance of duloxetine by approximately 37%. Caution should be exercised when using duloxetine with CYP2D6 inhibitors.

Caution should be exercised when using duloxetine concomitantly with other drugs that affect the central nervous system (including benzodiazepines, antipsychotic drugs, phenobarbital, antihistamines with a sedative effect, ethanol), especially with a similar mechanism of action. Simultaneous use of duloxetine with drugs that are highly bound to plasma proteins may lead to an increase in the concentration of free fractions of both drugs.

In patients receiving a serotonin reuptake inhibitor in combination with non-selective irreversible MAO inhibitors, there were cases of severe adverse reactions (hyperthermia, muscle rigidity, myoclonus, peripheral disorders with possible sharp fluctuations in vital signs and changes in mental status, including severe agitation with a transition to delirium and coma), sometimes with a fatal outcome. These reactions were also observed in patients who had been discontinued a serotonin reuptake inhibitor shortly before being prescribed an MAO inhibitor. In some cases, patients experienced symptoms characteristic of neuroleptic malignant syndrome. The effects of combined use of duloxetine and MAO inhibitors 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 non-selective irreversible MAO inhibitors or for at least 14 days after their withdrawal. Based on the duration of T1/2 of duloxetine, you should take a break for at least 5 days after the end of duloxetine before taking MAO inhibitors. With regard to selective reversible MAO inhibitors, such as moclobemide, the risk of serotonin syndrome is low, however, concomitant use of the drug with selective reversible MAO inhibitors is not recommended. Anticoagulants and antiplatelet drugs increase the risk of bleeding. Cases of increased INR have been reported when co-administered with warfarin.

In rare cases, the development of serotonin syndrome has been reported with the use of SSRIs (including:paroxetine, fluoxetine) with serotonergic drugs. Caution should be exercised when using duloxetine concomitantly with serotonergic antidepressants such as SSRIs, tricyclic antidepressants such as clomipramine and amitriptyline, St. John’s wort, venlafaxine or triptans, tramadol, pethidine and tryptophan.

How to take, course of use and dosage

Inside, regardless of food intake.

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 coating of the contents of capsules (pellets).

The recommended starting dose 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.

Overdose

Symptoms: vomiting and loss of appetite, tremor, clonic seizures, ataxia. Treatment: symptomatic and supportive. CVS monitoring, etc. vital signs. The specific antidote is not known.

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.

Special instructions

Systematic evaluation of the drug intake at a dose of more than 120 mg was not carried out.

Mydriasis has been reported with duloxetine, so caution should be exercised when prescribing duloxetine to patients with intraocular hypertension or those at risk of developing acute angle-closure glaucoma.

In patients with severe CRF (creatinine clearance less than 30 ml/min) or severe hepatic insufficiency, an increase in the concentration of duloxetine in plasma is observed. If the use of duloxetine is clinically justified in such patients, lower initial doses of the drug should be used. 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.

Discontinuation of the drug should be carried out gradually to avoid the “withdrawal” syndrome.

Due to insufficient experience with the use of duloxetine during pregnancy, the drug should be prescribed during pregnancy only if the potential benefit to the mother 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 lactation, breast-feeding during duloxetine therapy is not recommended.

In the course of studies of duloxetine, no violations of psychomotor reactions, cognitive functions and memory were detected. However, taking the drug may be accompanied by drowsiness. In this regard, patients taking duloxetine should exercise caution when engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions, including driving a car.

Active ingredient

Duloxetine

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

For adults as directed by your doctor

Indications

Polyneuropathy, Depression