Portal (Capsules) Instructions for Use

Marketing Authorization Holder

Lek d.d. (Slovenia)

ATC Code

N06AB03 (Fluoxetine)

Active Substance

Fluoxetine (Rec.INN registered by WHO)

Dosage Form

Portal

Capsules 20 mg: 7, 14, or 28 pcs.

Dosage Form, Packaging, and Composition

Capsules gelatin No. 3, opaque, with a white body and a green cap; the capsule contents are a white or almost white powder.

Excipients: dimethylpolysiloxane, pregelatinized starch.

7 pcs. – blister packs (1) – cardboard packs.
7 pcs. – blister packs (2) – cardboard packs.
7 pcs. – blister packs (4) – cardboard packs.

Clinical-Pharmacological Group

Antidepressant

Pharmacotherapeutic Group

Antidepressant

Pharmacological Action

Antidepressant, a propylamine derivative. The mechanism of action is associated with the selective blockade of the neuronal reuptake of serotonin in the CNS. Fluoxetine is a weak antagonist of cholinergic, adrenergic, and histamine receptors.

Unlike most antidepressants, Fluoxetine apparently does not cause a reduction in the functional activity of postsynaptic beta-adrenergic receptors. It helps improve mood, reduces feelings of fear and tension, and eliminates dysphoria. It does not cause a sedative effect.

When taken in average therapeutic doses, it has practically no effect on the functions of the cardiovascular and other systems.

Pharmacokinetics

Absorbed from the gastrointestinal tract. Weakly metabolized during the first-pass effect through the liver. Food intake does not affect the extent of absorption, although it may slow its rate. C_max in plasma is reached after 6-8 hours. C_ss in plasma is achieved only after continuous administration for several weeks. Protein binding is 94.5%.

Easily penetrates the blood-brain barrier. Metabolized in the liver by demethylation to form the main active metabolite, norfluoxetine.

T_1/2 of fluoxetine is 2-3 days, of norfluoxetine – 7-9 days. Excreted by the kidneys 80% and through the intestine – about 15%.

Indications

Depression of various origins, obsessive-compulsive disorders, bulimic neurosis.

ICD codes

Dosage Regimen

Initiate treatment at 20 mg once daily, administered in the morning.

If clinical response is insufficient after 3-4 weeks, consider a dose increase.

For bulimia nervosa, administer a dose of 60 mg once daily; this may also be the recommended dose for obsessive-compulsive disorder.

Divide daily doses exceeding 20 mg into twice-daily administrations (morning and noon).

Do not exceed the maximum daily dose of 80 mg.

Adjust the dosage regimen for elderly patients and those with concomitant diseases.

Use with particular caution and at lower doses in patients with hepatic impairment.

Reduce the dose or frequency of administration in patients with renal impairment; contraindicated in severe impairment.

Continue dosage for a sufficient period to achieve therapeutic effect, which may be several months.

Adverse Reactions

From the nervous system: anxiety, tremor, nervousness, drowsiness, headache, sleep disturbances are possible.

From the digestive system: diarrhea, nausea are possible.

From metabolism: increased sweating, hypoglycemia, hyponatremia (especially in elderly patients and with hypovolemia) are possible.

From the reproductive system: decreased libido.

Allergic reactions: skin rash, itching are possible.

Other: joint and muscle pain, difficulty breathing, increased body temperature.

Contraindications

Glaucoma, bladder atony, severe renal impairment, benign prostatic hyperplasia, concurrent use of MAO inhibitors, convulsive syndrome of various origins, epilepsy, pregnancy, lactation, hypersensitivity to fluoxetine.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation.

Use in Hepatic Impairment

Use with particular caution in patients with impaired liver function.

Use in Renal Impairment

Contraindicated in severe renal impairment. Use with particular caution in patients with moderate and mild renal impairment.

Pediatric Use

The safety of fluoxetine use in children has not been established.

Geriatric Use

Elderly patients require dose regimen adjustment.

Special Precautions

Use with particular caution in patients with impaired liver and kidney function, with a history of epileptic seizures, cardiovascular diseases.

In patients with diabetes mellitus, changes in blood glucose levels are possible, which requires adjustment of the dosage regimen of hypoglycemic drugs. When used in debilitated patients, the likelihood of developing epileptic seizures increases when taking fluoxetine.

With the simultaneous use of fluoxetine and electroconvulsive therapy, prolonged epileptic seizures may develop.

Fluoxetine can be used no earlier than 14 days after discontinuation of MAO inhibitors. The period after discontinuation of fluoxetine before starting therapy with MAO inhibitors should be at least 5 weeks.

Elderly patients require dose regimen adjustment.

The safety of fluoxetine use in children has not been established.

Do not consume alcohol during treatment.

Effect on ability to drive vehicles and operate machinery

During the treatment period, one should refrain from potentially hazardous activities requiring increased attention and rapid psychomotor reactions.

Drug Interactions

With simultaneous use with drugs that have a depressant effect on the central nervous system, with ethanol, a significant enhancement of the depressant effect on the central nervous system, as well as an increase in the likelihood of seizures, is possible.

With simultaneous use with MAO inhibitors, furazolidone, procarbazine, tryptophan, the development of serotonin syndrome (confusion, hypomanic state, motor restlessness, agitation, convulsions, dysarthria, hypertensive crisis, chills, tremor, nausea, vomiting, diarrhea) is possible.

With simultaneous use, Fluoxetine inhibits the metabolism of tricyclic and tetracyclic antidepressants, trazodone, carbamazepine, diazepam, metoprolol, terfenadine, phenytoin, which leads to an increase in their serum concentration and an enhancement of their therapeutic and side effects.

With simultaneous use, inhibition of the biotransformation of drugs metabolized with the participation of the CYP2D6 isoenzyme is possible.

With simultaneous use with hypoglycemic agents, an enhancement of their effect is possible.

There are reports of enhanced effects of warfarin when used concomitantly with fluoxetine.

With simultaneous use with haloperidol, fluphenazine, maprotiline, metoclopramide, perphenazine, periciazine, pimozide, risperidone, sulpiride, trifluoperazine, cases of extrapyramidal symptoms and dystonia have been described; with dextromethorphan – a case of hallucinations has been described; with digoxin – a case of increased digoxin concentration in blood plasma.

With simultaneous use with lithium salts, an increase or decrease in the plasma concentration of lithium is possible.

With simultaneous use, an increase in the plasma concentration of imipramine or desipramine by 2-10 times is possible (may persist for 3 weeks after discontinuation of fluoxetine).

With simultaneous use with propofol, a case was described in which spontaneous movements were observed; with phenylpropanolamine – a case was described in which dizziness, weight loss, hyperactivity were observed.

With simultaneous use, an enhancement of the effects of flecainide, mexiletine, propafenone, thioridazine, zuclopenthixol is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.