Actaparoxetine (Tablets) Instructions for Use

Marketing Authorization Holder

Actavis Group hf. (Iceland)

Manufactured By

Actavis, Ltd. (Malta)

ATC Code

N06AB05 (Paroxetine)

Active Substance

Paroxetine (Rec.INN registered by WHO)

Dosage Forms

	Actaparoxetine	Film-coated tablets, 20 mg: 30 pcs.
		Film-coated tablets, 30 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex, with a score on one side and the inscription “P20” on the other.

Excipients: magnesium stearate 2255 – 4.5 mg, sodium carboxymethyl starch – 6 mg, mannitol DC – 133.64 mg, microcrystalline cellulose – 133.64 mg, copolymer of methyl methacrylate, dimethylaminoethyl methacrylate and butyl methacrylate (eudragit E100) – 1.8 mg, opadry AMB white (aqueous solution): partially hydrolyzed polyvinyl alcohol – 5.46 mg, titanium dioxide (E171) – 3.84 mg, talc – 2.4 mg, soy lecithin (E322) – 0.24 mg, xanthan gum (E415) – 0.06 mg.

10 pcs. – blisters (3) – cardboard packs.

Film-coated tablets blue, round, biconvex, with a score on one side and the inscription “P30” on the other.

Excipients: magnesium stearate 2255 – 6.75 mg, sodium carboxymethyl starch – 9 mg, mannitol DC – 200.46 mg, microcrystalline cellulose – 200.46 mg, copolymer of methyl methacrylate, dimethylaminoethyl methacrylate and butyl methacrylate (eudragit E100) – 2.7 mg, opadry AMB blue (aqueous solution): partially hydrolyzed polyvinyl alcohol – 8.19 mg, titanium dioxide (E171) – 4.93 mg, talc – 3.6 mg, indigo carmine (E132) – 0.83 mg, soy lecithin (E322) – 0.36 mg, xanthan gum (E415) – 0.086 mg, sunset yellow FCF (E110) – 0.002 mg, quinoline yellow (E104) – 0.002 mg.

10 pcs. – blisters (3) – cardboard packs.

Film-coated tablets white or almost white, round, biconvex, with a score on one side and the inscription “P20” on the other.

Excipients: magnesium stearate 2255 – 4.5 mg, sodium carboxymethyl starch – 6 mg, mannitol DC – 133.64 mg, microcrystalline cellulose – 133.64 mg, copolymer of methyl methacrylate, dimethylaminoethyl methacrylate and butyl methacrylate (eudragit E100) – 1.8 mg, opadry AMB white (aqueous solution): partially hydrolyzed polyvinyl alcohol – 5.46 mg, titanium dioxide (E171) – 3.84 mg, talc – 2.4 mg, soy lecithin (E322) – 0.24 mg, xanthan gum (E415) – 0.06 mg.

10 pcs. – blisters (3) – cardboard packs.

Film-coated tablets blue, round, biconvex, with a score on one side and the inscription “P30” on the other.

Excipients: magnesium stearate 2255 – 6.75 mg, sodium carboxymethyl starch – 9 mg, mannitol DC – 200.46 mg, microcrystalline cellulose – 200.46 mg, copolymer of methyl methacrylate, dimethylaminoethyl methacrylate and butyl methacrylate (eudragit E100) – 2.7 mg, opadry AMB blue (aqueous solution): partially hydrolyzed polyvinyl alcohol – 8.19 mg, titanium dioxide (E171) – 4.93 mg, talc – 3.6 mg, indigo carmine (E132) – 0.83 mg, soy lecithin (E322) – 0.36 mg, xanthan gum (E415) – 0.086 mg, sunset yellow FCF (E110) – 0.002 mg, quinoline yellow (E104) – 0.002 mg.

10 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Antidepressant

Pharmacotherapeutic Group

Antidepressant

Pharmacological Action

Antidepressant. Paroxetine is a potent and selective inhibitor of serotonin (5-hydroxytryptamine, 5-HT) reuptake by neurons in the brain, which determines its antidepressant effect and efficacy in the treatment of obsessive-compulsive and panic disorder.

The main metabolites of paroxetine are polar and conjugated products of oxidation and methylation, which are rapidly eliminated from the body, have weak pharmacological activity and do not affect the therapeutic action. The metabolism of paroxetine does not impair its induced selective 5-HT neuronal reuptake.

Paroxetine has low affinity for m-cholinergic receptors. Being selective, unlike tricyclic antidepressants, Paroxetine is characterized by low affinity for α₁-, α₂-, β-adrenergic receptors, as well as for dopamine, 5-HT₁-like, 5-HT₂-like and histamine H₁ receptors.

Paroxetine does not impair psychomotor functions and does not potentiate the depressant effect of ethanol on them.

According to behavioral and EEG studies in patients taking Paroxetine, it has been proven that when prescribed in doses higher than those necessary to inhibit 5-HT reuptake, paroxetine exhibits weak activating properties. In healthy volunteers, it does not cause significant changes in blood pressure, heart rate and EEG.

Unlike antidepressants that inhibit norepinephrine reuptake, Paroxetine is much weaker in suppressing the antihypertensive effects of guanethidine.

Pharmacokinetics

Absorption

After oral administration, Paroxetine is well absorbed from the gastrointestinal tract. It undergoes first-pass metabolism in the liver.

The clinical effects of paroxetine (side effects and efficacy) do not correlate with its plasma concentration.

Distribution

Steady-state concentration (C_ss) is reached by 7-14 days after the start of treatment, and pharmacokinetics do not change during long-term treatment.

At therapeutic concentrations, the binding of paroxetine to plasma proteins is 95%.

Paroxetine is extensively distributed in tissues, and pharmacokinetic calculations show that only 1% of it is present in plasma.

Metabolism

Since the metabolism of paroxetine involves the first-pass effect through the liver, the amount determined in the systemic circulation is less than that absorbed from the gastrointestinal tract. When the dose of paroxetine is increased or with repeated dosing, when the load on the body increases, there is a partial saturation of the first-pass effect through the liver and a decrease in the plasma clearance of paroxetine. As a result, an increase in the plasma concentration of paroxetine and fluctuations in pharmacokinetic parameters are possible, which can be observed only in those patients in whom low doses of the drug achieve low plasma concentrations of paroxetine.

Elimination

The half-life (T_1/2) varies but is usually about 1 day. The elimination of paroxetine metabolites from the body is biphasic, first as a result of first-pass metabolism in the liver, and then it is controlled by systemic elimination.

Paroxetine is excreted mainly in the form of metabolites: 64% of metabolites are excreted in the urine and 36% in the bile through the intestine. 2% is excreted unchanged in the urine and 1% in the bile.

Pharmacokinetics in special clinical cases

In elderly patients, as well as in patients with severe renal and hepatic insufficiency, the plasma concentration of paroxetine is increased, and the range of plasma concentrations in them almost coincides with the range in healthy adult volunteers.

Indications

• Depression of all types (including reactive, severe endogenous depression and depression accompanied by anxiety);
• Obsessive-compulsive disorder;
• Panic disorder, including with agoraphobia;
• Social anxiety disorder/social phobia;
• Generalized anxiety disorder;
• Treatment of post-traumatic stress disorder.

ICD codes

Dosage Regimen

The drug is taken orally once a day, in the morning, with meals. The tablet should be swallowed whole with water.

The dose is selected individually during the first 2-3 weeks after the start of therapy and subsequently adjusted if necessary.

For treatment of depression, the drug is prescribed at a dose of 20 mg once a day. If necessary, the dose is gradually increased by 10 mg per day, the maximum daily dose is 50 mg.

For obsessive-compulsive disorders, the initial therapeutic dose is 20 mg/day, with a subsequent weekly increase of 10 mg. The recommended average therapeutic dose is 40 mg/day, if necessary, the dose can be increased to 60 mg/day.

For panic disorders, Actaparoxetine is prescribed at an initial dose of 10 mg/day (to reduce the possible risk of exacerbation of panic symptoms), with a subsequent weekly increase of 10 mg. The average therapeutic dose is 40 mg/day. The maximum dose is 50 mg/day.

For social anxiety disorders/social phobia, the initial dose is 20 mg/day, if there is no effect for at least 2 weeks, it is possible to increase the dose to a maximum of 50 mg/day. The dose should be increased by 10 mg at intervals of at least 1 week according to the clinical effect.

For post-traumatic mental disorders, for most patients, the initial and therapeutic doses are 20 mg/day. In some cases, an increase in the dose to a maximum of 50 mg/day is recommended. The dose should be increased by 10 mg each week according to the clinical effect.

For generalized anxiety disorders, the initial and recommended doses are 20 mg/day.

In renal and/or hepatic impairment, the recommended daily dose is 20 mg.

For elderly patients, the daily dose should not exceed 40 mg. To prevent the development of withdrawal syndrome, discontinuation of the drug should be gradual.

Adverse Reactions

From the central nervous system drowsiness, tremor, asthenia, insomnia, dizziness, fatigue, convulsions, extrapyramidal disorders, serotonin syndrome, hallucinations, mania, confusion, agitation, anxiety, depersonalization, panic attacks, increased nervous excitability, paresthesia, decreased ability to concentrate.

From the musculoskeletal system arthralgia, myalgia, myasthenia, myoclonus, myopathic syndrome.

From the senses visual disturbances, taste changes.

From the reproductive system sexual dysfunction (including impotence and ejaculation disorders), hyperprolactinemia/galactorrhea, anorgasmia.

From the urinary system urinary retention, increased urination.

From the digestive system decreased appetite, nausea, vomiting, dry mouth, constipation or diarrhea; very rarely – hepatitis.

From the cardiovascular system orthostatic hypotension.

Allergic reactions rash, urticaria, ecchymosis, itching, angioedema.

Other increased sweating, hyponatremia, impaired ADH secretion, withdrawal syndrome upon abrupt discontinuation of the drug, rhinitis.

Contraindications

• Concomitant use of MAO inhibitors and the period up to 14 days after their discontinuation;
• Concomitant use of thioridazine;
• Unstable epilepsy;
• Pregnancy;
• Lactation (breastfeeding);
• Childhood and adolescence under 18 years;
• Hypersensitivity to the components of the drug.

With caution, the drug should be prescribed for hepatic and renal insufficiency, closed-angle glaucoma, prostatic hyperplasia, mania, cardiac pathology, epilepsy, convulsive conditions, during electroconvulsive therapy, when taking drugs that increase the risk of bleeding, in the presence of risk factors for increased bleeding and diseases that increase the risk of bleeding, in elderly patients.

Use in Pregnancy and Lactation

Actaparoxetine is contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

In hepatic impairment, Actaparoxetine should be prescribed with caution. The recommended daily dose is 20 mg.

Use in Renal Impairment

In renal impairment, the drug Actaparoxetine should be prescribed with caution. The recommended daily dose is 20 mg.

Pediatric Use

Contraindicated: children and adolescents under 18 years of age.

Geriatric Use

With caution, the drug should be prescribed to elderly patients.

Special Precautions

To avoid the development of neuroleptic malignant syndrome (NMS), the drug should be prescribed with caution to patients taking antipsychotics.

Treatment with paroxetine should be started 2 weeks after discontinuation of MAO inhibitors.

In elderly patients, hyponatremia is possible during the drug administration.

In some cases, when Actaparoxetine is used concomitantly with insulin and/or oral hypoglycemic drugs, dose adjustment of the latter may be required.

If seizures develop, treatment with paroxetine should be discontinued.

At the first signs of mania, paroxetine therapy should be discontinued.

During the first few weeks, the patient’s condition should be carefully monitored due to possible suicide attempts.

The patient should be informed that during treatment it is necessary to refrain from drinking alcohol.

Effect on ability to drive vehicles and operate machinery

Paroxetine does not impair cognitive and psychomotor functions. Nevertheless, as with treatment with other psychotropic drugs, patients should exercise caution when driving a car and moving mechanisms. During the treatment period, the patient should refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms nausea, dilated pupils, fever, increased blood pressure, headache, involuntary muscle contractions, agitation, anxiety, sinus tachycardia, bradycardia, nodal rhythm; very rarely – depression of consciousness up to coma (with simultaneous use of other psychotropic drugs and/or alcohol).

Treatment gastric lavage, activated charcoal, symptomatic therapy. There is no specific antidote.

Drug Interactions

Food and antacids do not affect the absorption and pharmacokinetic parameters of the drug.

Paroxetine is incompatible with MAO inhibitors.

When co-administered with paroxetine, the concentration of procyclidine increases.

During therapy with paroxetine, alcohol consumption should be avoided due to the enhancement of the toxic effect of alcohol.

Due to the inhibition of cytochrome P450 isoenzymes by paroxetine, it is possible to enhance the effects of barbiturates, phenytoin, indirect anticoagulants, tricyclic antidepressants, phenothiazine antipsychotics, class I C antiarrhythmics, metoprolol and increase the risk of side effects when these drugs are co-administered.

When co-administered with drugs that inhibit liver enzymes, a reduction in the dose of paroxetine may be required.

Paroxetine increases bleeding time while taking warfarin, with unchanged prothrombin time.

When paroxetine is co-administered with atypical antipsychotics, phenothiazines, tricyclic antidepressants, acetylsalicylic acid, NSAIDs, caution is recommended due to possible bleeding disorders.

Concomitant use with serotonergic drugs (tramadol, sumatriptan) may lead to an increase in the serotonergic effect.

Mutual enhancement of the action of tryptophan, lithium preparations and paroxetine has been noted.

When paroxetine is co-administered with phenytoin and other anticonvulsants, a decrease in plasma concentration of paroxetine and an increase in the frequency of side effects are possible.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

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.