Duloxetine Canon, 60 mg 28 pcs

Pharmgroup:

antidepressant.

Pharmic action:

Inhibits serotonin and noadrenaline reuptake, resulting in increased serotonergic and noradrenergic neurotransmission in the CNS.

It weakly inhibits dopamine uptake without significant affinity for histaminergic, dopaminergic, cholinergic and adrenergic receptors.

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

Indications

Depression, diabetic peripheral neuropathy (painful form).

Active ingredient

Composition

Enco-soluble capsules solid gelatin № 1, body and cap blue; the contents of the capsules – spherical microgranules from almost white to yellowish-white.

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

Supplementary substances:

Hypromellose E5 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,

Patent blue dye V.

How to take, the dosage

To be taken by mouth, regardless of meals.

The 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 capsule contents (pellets).

The recommended initial 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 doses.

Interaction

The concomitant use of duloxetine (60 mg twice daily) had no significant effect on the pharmacokinetics of CYP1A2 metabolized theophylline.

Concomitant administration of duloxetine with potential CYP1A2 inhibitors may result in increased concentrations of duloxetine. The 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 CYP2D6 inhibitor. When duloxetine is taken at a dose of 60 mg twice daily along with a single dose of desipramine (a CYP2D6 substrate), the AUC of desipramine is increased 3-fold. Concomitant administration of duloxetine (40 mg 2 times daily) increases the AUC of tolterodine (2 mg 2 times daily) by 71%, but has no effect on the pharmacokinetics of the 5-hydroxyl metabolite. Caution should be exercised when using duloxetine with drugs metabolized mainly by CYP2D6 system and having a narrow therapeutic index.

Concomitant use of duloxetine with potential CYP2D6 inhibitors may result in increased concentrations of duloxetine.
Paroxetine (20 mg once daily) reduces duloxetine clearance by approximately 37%. Caution should be exercised when using duloxetine with CYP2D6 inhibitors.

Caution should be exercised when using duloxetine concomitantly with other CNS-acting drugs (including benzodiazepines, antipsychotic drugs, phenobarbital, antihistamine drugs with sedative effect, ethanol), especially with a similar mechanism of action.
Concomitant use of duloxetine with drugs that are highly bound to plasma proteins may increase the concentration of free fractions of both drugs.

. In patients receiving serotonin reuptake inhibitor in combination with non-selective non-reversible MAOI inhibitors, there have been cases of severe adverse reactions (hyperthermia, muscle rigidity, myoclonus, peripheral disorders with possible dramatic fluctuations of vital functions and mental status changes, including severe agitation with transition to delirium and coma) sometimes with fatal outcome. These reactions have also been observed in patients who had a serotonin reuptake inhibitor discontinued shortly before the MAO inhibitor prescription. In some cases, patients exhibited symptoms characteristic of malignant neuroleptic syndrome. The effects of the combined use of duloxetine and MAO inhibitors have not been evaluated in either humans or animals. Therefore, given that duloxetine is an inhibitor of both serotonin and norepinephrine, it is not recommended that duloxetine be taken in combination with non-selective non-reversible MAOI inhibitors or for at least 14 days after their withdrawal. Based on the T1/2 duration of duloxetine, a break of at least 5 days should be taken after duloxetine is discontinued before taking MAO inhibitors. For 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 – risk of bleeding. There have been reported cases of increased INR when concomitant use with warfarin.

In rare cases, the development of serotonin syndrome has been reported when using 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.

Special Instructions

Systematic evaluation of doses above 120 mg has not been performed.

There have been cases of mydriasis with duloxetine; therefore, caution should be exercised when prescribing duloxetine in patients with intraocular hypertension or in those at risk of acute closed-angle glaucoma.

In patients with severe CKD (KC less than 30 ml/min) or severe hepatic impairment, increased plasma concentrations of duloxetine have been observed. If duloxetine administration is clinically reasonable in such patients, lower initial doses of the drug should be used.
In depression, there is a possibility of suicide attempts, which may persist until sustained remission occurs. Close monitoring of patients at risk is necessary.

The drug should be withdrawn gradually to avoid withdrawal.

Because of insufficient experience with duloxetine use during pregnancy, the drug should only be prescribed during pregnancy if the potential benefit to the mother significantly exceeds the potential risk to the fetus. Patients should be advised that if they become pregnant or plan to become pregnant while on duloxetine treatment, they should inform their physician.

In view of the lack of experience with duloxetine in women during lactation, breastfeeding during duloxetine therapy is not recommended.

Duloxetine studies have not shown impairment of psychomotor reactions, cognitive function, or memory. However, taking the drug may be accompanied by somnolence. Patients taking duloxetine should therefore be cautious when engaged in potentially hazardous activities requiring increased concentration and quick psychomotor reactions, including driving.

Contraindications

Hypersensitivity, liver diseases accompanied by hepatic insufficiency, simultaneous use of non-selective irreversible MAO inhibitors, potent CYP1A2 inhibitors (fluvoxamine, ciprofloxacin, enoxacin), severe CPH (CK less than 30 ml/min), uncontrolled arterial hypertension, lactation period, age under 18 years (no experience of use).

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

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

Side effects

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

Nervous system disorders: very common – headache, somnolence; common – dizziness, tremor, lethargy, paresthesia, insomnia, unusual dreams, anxiety, agitation; infrequent – dyskinesia, poor sleep quality, nervousness, myoclonus, impaired concentration, sleep disturbance, apathy, disorientation, bruxism; rare – mania, aggression, anger; frequency unknown – serotonin syndrome, seizures, akathisia, psychomotor anxiety, extrapyramidal syndrome, suicide attempts, suicidal ideation, hallucinations.

Digestive system disorders: very often – nausea, dry mouth 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 – unpleasant odor when breathing, unchanged blood in feces; frequency is unknown – gastrointestinal bleeding, jaundice, liver failure.

Genitourinary system: often – erectile dysfunction, decreased libido, altered ability to experience orgasm; infrequent – urinary retention, intermittent urination, dysuria, nycturia, polyuria, decreased urine flow, impaired sexual function, ejaculation disorders, including slow ejaculation.including delayed ejaculation, gynecologic bleeding; rarely – menopausal symptoms; frequency unknown – change of urine odor.
Cardiovascular system: frequently – palpitations, “hot flashes” of blood; infrequently – tachycardia, fainting and orthostatic hypotension (which were reported only at the beginning of treatment), increased BP, cold extremities; rarely – supraventricular arrhythmia, mainly atrial fibrillation; frequency is unknown – hypertensive crisis.

Sensory system disorders: often – blurred vision, tinnitus; infrequent – visual disturbances, mydriasis, vertigo, tinnitus pain; rarely – glaucoma.

Respiratory system: frequently – yawning; infrequently – nasal bleeding, feeling of tightness of the throat.

Skin: frequently – rash, increased sweating, night sweats, infrequent – photosensitization, increased tendency to subcutaneous bleeding, contact dermatitis, urticaria, cold sweats; frequency unknown – angioedema, Stevens-Johnson syndrome.

Musculoskeletal system: often – muscle spasm, skeletal-muscular pain, muscle stiffness; infrequent – muscle twitching; rarely – trismus.

Endocrine system: rarely – hypothyroidism.

Metabolism: often – decreased appetite; infrequent – hyperglycemia (reported mainly in patients with diabetes); rarely – dehydration, syndrome of inadequate secretion of antidiuretic hormone, hyponatremia.

Infections: infrequent – laryngitis.

Other: frequent – fatigue, decreased body weight; infrequent – weight gain, malaise, gait disturbance, impaired sensitivity, feeling cold, feeling warm, thirst, chills, increased CPK; rarely – hypercholesterolemia; frequency unknown – pain in the chest.
Allergic reactions: infrequent – hypersensitivity reactions; rare – anaphylactoid reactions.

In acute 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.

Overdose

Symptoms: vomiting and decreased appetite, tremor, clonic convulsions, ataxia. Treatment: symptomatic and supportive. Control of cardiovascular system and other vital signs. Specific antidote is not known.

Several cases of overdose have been reported with up to 1400 mg of the drug administered at one time with no fatal consequences.

Similarities