Ixel, 50 mg capsules, 56 pcs.

Ixel is an antidepressant, a selective inhibitor of monoamine reuptake (noradrenaline and serotonin). Ixel does not bind to m-cholinoreceptors, α1-adrenoreceptors, histamine H1-receptors, as well as to dopamine D1- and D2-receptors, benzodiazepine and opioid receptors.

Ixel has no sedative effect, while physiologically improving sleep and having no negative effect on cognitive function. Ixel also has no effect on the cardiac conduction system and BP, which is especially important for elderly patients who are constantly taking cardiotropic medications.

Pharmacokinetics

Ix absorption

After oral administration, milnacipran is well absorbed from the GI tract. Bioavailability is about 85% and does not depend on the nature and diet. Cmax in plasma is reached approximately 2 hours after intake.

Distribution

The equilibrium state is reached after 2-3 days of regular use. Binding to plasma proteins is about 13% and is not accompanied by saturation.

Metabolism

Biotransformed mainly by conjugation with glucuronic acid. Metabolites have no pharmacological activity.

The T1/2 is 8 hours. It is eliminated mainly by the kidneys – about 90%. It is completely eliminated from the body within 2-3 days.

Indications

Depressive disorders of varying severity.

Active ingredient

Milnacipran

Composition

Active substance:

Milnacipran hydrochloride 50 mg;

Ancillary substances:

calcium hydrophosphate dihydrate 101.85 mg;

calcium carmellose 44.3 mg;

povidone K30 4.2 mg;

colloidal silicon dioxide 1.25 mg;

magnesium stearate 4.2 mg;

talc 4.2 mg

How to take, the dosage

Ixel is intended to be taken orally.

The average daily dose is 100 mg; the drug should be taken in 2 doses in the morning. Depending on the severity of symptoms, the dose may be increased to 250 mg/day.

The drug should preferably be taken with food.

The duration of therapy is determined individually.

In patients with renal insufficiency (CKD 50-10 ml/min), reduction of the daily dose is recommended depending on CKD values.

Interaction

Simultaneous use of Ixel with non-selective MAO inhibitors (iproniazid), with selective MAO type B inhibitors (selegiline), with sumatriptan is contraindicated due to the risk of serotonin syndrome, arterial hypertension, coronary artery spasm (minimum interval after treatment with these drugs and administration of Ixel is 2 weeks).

The concomitant use of Ixel with adrenaline and noradrenaline is not recommended because of the risk of arterial hypertension and arrhythmias; with clonidine and related compounds because of a decrease in their hypotensive effect; with digoxin (especially when administered parenterally) due to the risk of tachycardia and arterial hypertension; with selective MAO type A inhibitors (moclobemide, toloxaton) due to the risk of serotonin syndrome.

With caution, Ixel should be used in combination with epinephrine (adrenaline) and norepinephrine (noradrenaline) (in case of local anesthesia, doses should not exceed 100 mcg per 10 min or 300 mcg per 1 h), with lithium preparations because of the risk of serotonin syndrome.

Special Instructions

Patients with a history of seizures, arterial hypertension, cardiomyopathy are prescribed with caution.
Ixel may not be administered earlier than 14 days after withdrawal of MAO inhibitors. In addition, at least 7 days should pass from the moment of withdrawal of Ixel drug to the beginning of therapy with MAO inhibitors.

In order to reduce the severity of side effects, a gradual increase in the dose of the drug is recommended.

In case of local anesthesia with preparations containing adrenaline or noradrenaline during therapy with Ixel, the anesthetic dose should not exceed 0.1 mg in 10 min and 0.3 mg in 1 hour.

Alcohol should not be consumed during treatment with Ixel.

Influence on driving and operating machinery

When using the drug, one should refrain from engaging in potentially hazardous activities requiring increased attention and quick psychomotor reactions.

Contraindications

• children and adolescents under 15 years of age (for lack of clinical data);
• current use of non-selective and selective MAO type B inhibitors, sumatriptan;
• high sensitivity to the drug components.
• obstruction of the urinary tract (mainly in prostatic hyperplasia);
• pregnancy;
• lactation (breastfeeding);
• concurrent use with adrenaline, noradrenaline, clonidine and its derivatives;
• concurrent use of selective MAO type A inhibitors, digoxin.

With caution, use the drug in closed-angle glaucoma and epilepsy.

Side effects

CNS disorders: possibly – anxiety, dizziness; rarely – tremor, headache.

The digestive system: rarely – dry mouth, nausea, vomiting, constipation; in some cases – moderate increase in transaminase activity without clinical manifestations.

Others: possible – increased sweating, hot flashes, difficulty in urination; rarely – palpitation, rash; in some cases – serotonin syndrome.

Overdose

Symptoms: nausea, vomiting, sweating, constipation have been reported with accidental increase in dose. When taking the drug in a dose greater than 800-1000 mg, vomiting, difficulty in breathing, tachycardia are possible. After overdose (1900-2800 mg of milnacipran) in combination with other psychotropic drugs (mostly benzodiazepines), drowsiness, hypercapnia, impaired consciousness are added to the symptoms described above. Manifestations of cardiotoxicity and lethal outcome in Ixel overdose have not been noted.

Treatment: gastric lavage followed by symptomatic therapy. Medical observation of the patient’s condition for at least 24 hours is recommended. A specific antidote is not known.