Apo-Paroxetine (Tablets) Instructions for Use

Marketing Authorization Holder

Apotex, Inc. (Canada)

Manufactured By

Apotex, Inc. (Canada)

Packaging and Quality Control Release

APOTEX, Inc. (Canada)

Or

VEKTOR-MEDIKA, JSC (Russia)

ATC Code

N06AB05 (Paroxetine)

Active Substance

Paroxetine (Rec.INN registered by WHO)

Dosage Form

Apo-Paroxetine

Film-coated tablets, 20 mg: 10, 30, or 100 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets pink, oval, biconvex, with a score and engraving “20” on one side and engraving “APO” on the other side.

Excipients: anhydrous lactose, sodium carboxymethyl starch, magnesium stearate, hypromellose LF, hypromellose 2910 E5, macrogol 8000, titanium dioxide, dye D&C red No. 30 (carmine).

10 pcs. – blister packs (1) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (10) – cardboard packs.
10 pcs. – polyethylene bottles (1) – cardboard packs.
30 pcs. – polyethylene bottles (1) – cardboard packs.
100 pcs. – polyethylene bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antidepressant

Pharmacotherapeutic Group

Antidepressant

Pharmacological Action

Antidepressant, selective serotonin reuptake inhibitor. It has a bicyclic structure that differs from the structure of other known antidepressants.

It has antidepressant and anxiolytic effects with a sufficiently pronounced stimulating (activating) effect.

The antidepressant (thymoanaleptic) effect is associated with the ability of paroxetine to selectively block the reuptake of serotonin by the presynaptic membrane, which causes an increase in the free content of this neurotransmitter in the synaptic cleft and enhances its activity in the CNS.

The effect on m-cholinergic receptors, α- and β-adrenergic receptors is insignificant, which determines the extremely weak severity of the corresponding side effects.

Pharmacokinetics

After oral administration, Paroxetine is well absorbed from the gastrointestinal tract. Food intake does not affect absorption. Steady-state concentration is reached by day 7-14 from the start of therapy.

It is metabolized mainly in the liver. The main metabolites of paroxetine are polar and conjugated products of oxidation and methylation. Due to the low pharmacological activity of the metabolites, their influence on therapeutic efficacy is unlikely.

The average half-life is 16-24 hours. Less than 2% is excreted unchanged in the urine, the rest – in the form of metabolites either with urine (64%) or with bile.

The elimination of paroxetine is biphasic.

With long-term continuous use, the pharmacokinetic parameters do not change.

Indications

Depression of various etiologies, including conditions accompanied by anxiety, obsessive-compulsive disorders, panic disorders, including with agoraphobia, social phobia, generalized anxiety disorder, post-traumatic stress disorders.

ICD codes

Dosage Regimen

Take orally, once daily in the morning with food.

For depression, the recommended adult dose is 20 mg per day. Initiate therapy at this dose.

If clinically justified, increase the dose in 10 mg increments to a maximum of 50 mg per day. Make dose adjustments at intervals of at least one week.

For obsessive-compulsive disorder, start with 20 mg daily. Increase to a maximum of 60 mg per day if necessary.

For panic disorder, start with 10 mg daily. Increase to a maximum of 60 mg per day. The target dose is 40 mg daily.

For social anxiety disorder, the recommended dose is 20 mg daily.

For generalized anxiety disorder, the recommended dose is 20 mg daily.

For post-traumatic stress disorder, the recommended dose is 20 mg daily.

In elderly patients or those with severe renal/hepatic impairment, start with 10 mg daily. Do not exceed a maximum dose of 40 mg per day.

The tablet is scored and can be broken for dose titration. Do not chew.

The antidepressant effect may not be apparent for several weeks. Continue therapy as prescribed.

Do not stop taking this medicine abruptly due to the risk of withdrawal syndrome.

When discontinuing treatment, gradually reduce the dose over several weeks or months.

Adverse Reactions

From the blood coagulation system: uncommon – abnormal bleeding, predominantly hemorrhage into the skin and mucous membranes; very rare – thrombocytopenia.

From the nervous system: common – drowsiness, tremor, paresthesia, insomnia, dizziness, unusual dreams (including nightmares); uncommon – confusion, hallucinations, extrapyramidal symptoms; rare – mania, anxiety, depersonalization, panic attacks, restless legs syndrome, seizures, akathisia; very rare – serotonin syndrome; frequency unknown – suicidal thoughts, suicidal behavior (during therapy or in the early period after treatment discontinuation).

From the organ of vision: common – blurred vision; uncommon – mydriasis; very rare – closed-angle glaucoma.

From the organ of hearing: frequency unknown – tinnitus.

From the cardiovascular system: uncommon – transient increase or decrease in blood pressure, sinus tachycardia, orthostatic hypotension; very rare – peripheral edema.

From the digestive system: very common – nausea, decreased appetite; common – dry mouth, vomiting, constipation, diarrhea; rare – increased activity of liver transaminases; very rare – gastrointestinal bleeding, hepatitis (sometimes with jaundice), liver failure.

From the urinary system: rare – urinary retention, urinary incontinence.

From the reproductive system: very common – sexual dysfunction; rare – priapism.

From the endocrine system: rare – hyperprolactinemia/galactorrhea and hyponatremia, which is caused by the syndrome of inappropriate antidiuretic hormone secretion.

From the musculoskeletal system: rare – arthralgia, myalgia.

Allergic reactions: rare – skin rash; photosensitivity reactions; very rare – angioedema, urticaria/

Other: very common – asthenia, cholesterolemia, decreased appetite, increased sweating, yawning, weight gain; very rare – peripheral edema.

Paroxetine withdrawal syndrome: common – dizziness, sensory disturbances, sleep disorders, anxiety, headache; uncommon – agitation, nausea, tremor, confusion, increased sweating, diarrhea.

Contraindications

Hypersensitivity to paroxetine; concurrent use of MAO inhibitors and the period up to 14 days after their discontinuation; concurrent use with thioridazine and pimozide; pregnancy; age under 18 years.

With caution: hepatic insufficiency, renal insufficiency, closed-angle glaucoma, prostatic hyperplasia, mania, heart pathology, epilepsy, convulsive conditions, use of electroconvulsive therapy; use of drugs and presence of diseases that increase the risk of bleeding; presence of risk factors for increased bleeding; elderly age.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy. Contraindicated for use during breastfeeding. If use during lactation is necessary, the issue of discontinuing breastfeeding should be considered.

Use in Hepatic Impairment

Should be used with caution in patients with impaired liver function.

Use in Renal Impairment

Should be used with caution in patients with impaired renal function.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Should be used with caution in elderly patients.

Special Precautions

During treatment with paroxetine, special attention should be paid to patients with a history of suicidal behavior or suicidal thoughts, patients under 25 years of age, as well as patients who had suicidal thoughts before starting treatment. This category of patients requires careful monitoring during treatment.

It should be borne in mind that symptoms such as agitation, akathisia, or mania may be associated with the underlying disease or be a consequence of the therapy used. The likelihood of akathisia is highest in the first few weeks of treatment.

If symptoms of clinical worsening (including new symptoms) and/or suicidal thoughts/behavior occur, especially if they appear suddenly, if the severity of manifestations increases, or if they were not part of the previous symptom complex in this patient, it is necessary to review the treatment regimen, up to the withdrawal of paroxetine.

A major depressive episode may be the initial manifestation of bipolar disorder.

When treating patients with heart disease, precautions should be observed, and monitoring of the functional state of the cardiovascular system is necessary.

Paroxetine should be discontinued with caution to avoid withdrawal syndrome. It is recommended to gradually reduce the dose of paroxetine (over several weeks or months before its complete withdrawal, depending on the patient’s condition).

During treatment with paroxetine, alcohol consumption is contraindicated.

After discontinuation of MAO inhibitors, paroxetine can be started no earlier than after 14 days. The dose should be increased gradually. MAO inhibitors should not be prescribed within 2 weeks after complete withdrawal of paroxetine.

When used concomitantly with drugs that inhibit the metabolism of liver enzymes, Paroxetine should be used in the lowest recommended doses. When used concomitantly with drugs that induce metabolism, no change in the initial doses of paroxetine is required.

Paroxetine should be used with caution concomitantly with lithium preparations (it is recommended to monitor plasma lithium concentrations), oral anticoagulants.

Effect on ability to drive vehicles and mechanisms

During the use of paroxetine, patients should exercise caution when driving vehicles and mechanisms, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use with paroxetine, an increase in the plasma concentration of drugs metabolized with the participation of the CYP2D6 isoenzyme of the cytochrome P450 system (antidepressants, antipsychotic phenothiazine derivatives, class IC antiarrhythmic drugs) is possible.

With simultaneous use of agents that induce or inhibit protein metabolism, changes in the metabolism and pharmacokinetic parameters of paroxetine are possible.

With simultaneous use, the effect of alprazolam is enhanced due to a decrease in its metabolism due to inhibition of CYP3A isoenzymes of the cytochrome P450 system under the influence of paroxetine.

With simultaneous use with warfarin, oral anticoagulants, an increase in bleeding time with unchanged prothrombin time is possible.

Cases of serotonin syndrome have been described with simultaneous use with dextromethorphan, dihydroergotamine.

With simultaneous use with interferon, a change in the antidepressant effect of paroxetine is possible.

Concomitant use of tryptophan may cause the development of serotonin syndrome, manifested by agitation, anxiety, gastrointestinal disorders, including diarrhea.

With simultaneous use with perphenazine, Paroxetine enhances the side effects from the CNS due to inhibition of perphenazine metabolism under the influence of paroxetine.

With simultaneous use, the plasma concentration of tricyclic antidepressants increases, and there is a risk of developing serotonin syndrome.

Concomitant use of cimetidine increases the plasma concentration of paroxetine.

Storage Conditions

Store at 15°C (59°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.