SEROXAT - PACKAGE LEAFLET - LEAFLETS

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Seroxat - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf life and Storage Composition and pharmaceutical form

Active ingredients: Paroxetine (Paroxetine hydrochloride hemihydrate)

SEROXAT 20 mg film-coated tablets

Seroxat package inserts are available for pack sizes:

SEROXAT 20 mg film-coated tablets
SEROXAT 2 mg / ml oral suspension

Why is Seroxat used? What is it for?

SEROXAT is a treatment for adults with depression and / or anxiety disorders. The anxiety disorders for which treatment with SEROXAT is indicated are: obsessive compulsive disorder (repetitive, obsessive thoughts with uncontrollable behaviors), panic (panic attacks, including those caused by agoraphobia, or fear of open spaces), social anxiety disorders (being afraid of or avoiding social situations), post-traumatic stress disorder (anxiety caused by a traumatic event), and anxiety disorder "generalized anxiety (generally feeling very anxious or nervous). SEROXAT belongs to a group of medicines called SSRIs (selective serotonin reuptake inhibitors). A substance called serotonin is commonly found in the brain. People who are depressed or anxious have lower serotonin levels than others. It is not fully known how SEROXAT and other SSRIs work, but they can help increase the level of serotonin in the brain.

Treating depression or anxiety disorders properly is important to help you feel better.

Contraindications When Seroxat should not be used

Do not take SEROXAT

If you are taking other medicines called monoamine oxidase inhibitors (MAOIs, including moclobemide and methylthioninium chloride (methylene blue)), or if you have taken them at any time in the last two weeks. Your doctor will advise you on how you should start taking SEROXAT once you have stopped taking the MAOIs.
If you are taking an anti-psychotic called thioridazine or an antipsychotic called pimozide.
If you are allergic to paroxetine or any of the other ingredients of this medicine (listed in section 6).

If any of the cases apply to you, talk to your doctor without taking SEROXAT.

Precautions for use What you need to know before taking Seroxat

Talk to your doctor or pharmacist before taking SEROXAT

Are you taking any other medicines (see inside this leaflet, Other medicines and SEROXAT)?
Are you taking tamoxifen to treat breast cancer or fertility problems? SEROXAT can make tamoxifen less effective, so your doctor may recommend that you take another antidepressant.
Do you have kidney, liver or heart problems?
Do you suffer from epilepsy or have you suffered from seizures in the past?
Have you ever suffered from episodes of mania (hyperactive behavior or thoughts)?
Have you received electroconvulsive therapy?
You have had bleeding in the past, or are taking other medicines that may increase the risk of bleeding (these include medicines that thin the blood, such as warfarin, antipsychotics such as perphenazine or clozapine, tricyclic antidepressants, medicines used for pain and inflammation called nonsteroidal anti-inflammatory drugs (NSAIDs), such as acetylsalicylic acid, ibuprofen, celecoxib, etodolac, diclofenac, meloxicam)?
Do you have diabetes?
Are you on a low sodium diet?
Do you have glaucoma (high eye pressure)?
Are you pregnant or planning to become pregnant (see Pregnancy, Breastfeeding and Fertility inside this leaflet)?
Are you under the age of 18 (see Children and adolescents under 18 in this leaflet)?

If you answered YES to any of these questions, and you have not already discussed them with your doctor, go back to your doctor and ask what to do about taking SEROXAT.

Children and adolescents under the age of 18

SEROXAT should not be used in children and adolescents under 18 years of age. In addition, patients under the age of 18 have an increased risk of side effects such as suicide attempts, suicidal thoughts and hostility (predominantly aggression, oppositional behavior and anger) when taking SEROXAT. If your doctor has prescribed SEROXAT for you (or your child) and if you want to talk about it, please go back to your doctor. You should tell your doctor if any of the symptoms listed above develop or worsen when you (or your child) is taking SEROXAT. Furthermore, the effects on long-term tolerability of SEROXAT related to growth, maturation and cognitive and behavioral development have not yet been demonstrated in this age group.

In studies with SEROXAT in patients under 18, common side effects affecting less than 1 in 10 children / adolescents were: increased thoughts of suicide and suicide attempts, deliberate harming of oneself, hostile attitude , aggressive or unfriendly, loss of appetite, tremors, abnormal sweating, hyperactivity (having too much energy), agitation, change in emotions (including crying and mood swings) and unusual bruising or bleeding (such as nosebleeds). These studies also showed that the same symptoms affected children and adolescents who took sugar pills (placebo) instead of SEROXAT, although they were observed less often.

In these studies in patients under 18 years, some patients experienced withdrawal effects after stopping SEROXAT. These effects were mostly similar to those seen in adults after stopping SEROXAT (see all " section 3, How to take SEROXAT) In addition, patients under the age of 18 also commonly (in less than 1 in 10 cases) also experienced stomach pain, feeling jittery and changes in emotions (including crying, mood, attempts to harm yourself, thoughts of suicide and suicide attempts).

Thoughts of suicide and worsening of depression or anxiety disorders

If you are depressed and / or have anxiety disorders you may sometimes have thoughts of harming or killing yourself. These thoughts may be more frequent the first time you start taking antidepressants, as all these medicines use some time to act, usually about two weeks, but sometimes more.

You may be more likely to have these kinds of thoughts:

If you have previously had thoughts about killing yourself or harming yourself.
If you are a young adult. Data from clinical trials have shown an increased risk of suicidal behavior in adults under the age of 25 with psychiatric disorders who were treated with an antidepressant.

Anytime you have thoughts of harming or killing yourself, contact your doctor or go to a hospital straight away. You may find it helpful to tell a relative or friend that you have depression or anxiety disorders, and ask them to read this leaflet. You may ask them to tell you if they think your depression or anxiety is getting worse, or if they are be concerned about changes in his behavior.

Important side effects seen with SEROXAT

Some patients who take SEROXAT have what is called akathisia, meaning they feel agitated and feel as if they cannot sit or stand still. Other patients have what is called serotonin syndrome or neuroleptic malignant syndrome, which means they may have some or all of the following symptoms: feeling very agitated or irritable, feeling confused, feeling restless, feeling hot, sweating, tremors, shivering, hallucinations (visions or sounds strange), muscle stiffness, sudden twitching of muscles or a fast heartbeat. Severity can increase, leading to loss of consciousness. If you notice any of these symptoms, please contact your doctor. For more information on these or other side effects of SEROXAT, please see Section 4, Possible Side Effects, inside this leaflet.

Interactions Which drugs or foods may change the effect of Seroxat

Other medicines and SEROXAT

Some medicines can interfere with the work of SEROXAT, or may make it more likely that you will have side effects. SEROXAT can also affect the work of other medicines. These include:

Medicines called monoamine oxidase inhibitors (MAOIs, including moclobemide and methylthioninium chloride (methylene blue)) - see inside this leaflet Do not take SEROXAT.
Thioridazine or pimozide, which are antipsychotics - see inside this leaflet Do not take SEROXAT.
Acetylsalicylic acid, ibuprofen or other medicines called NSAIDs (non-steroidal anti-inflammatory drugs) such as celecoxib, etodolac, diclofenac and meloxicam, used for pain and inflammation
Tramadol and pethidine, pain relievers
Medicines called triptans, such as sumatriptan, used to treat migraines
Other antidepressants, including other SSRIs, tricyclic antidepressants such as clomipramine, nortriptyline and desipramine
A dietary supplement called tryptophan
Mivacurium and succinylcholine (used in anesthesia)
Medicines such as lithium, risperidone, perphenazine, clozapine (called antipsychotics) used to treat some psychiatric conditions
Fentanyl, used in anesthesia or to treat chronic pain
A combination of fosamprenavir and ritonavir, used to treat Human Immunodeficiency Virus (HIV) infection
John's wort (Hypericum perforatum), St. John's wort, a herbal remedy for depression
Phenobarbital, phenytoin, sodium valproate or carbamazepine, used to treat seizures or epilepsy
Atomoxetine used to treat attention deficit hyperactivity disorder (ADHD)
Procyclidine, used to treat tremor, especially in Parkinson's disease
Warfarin or other medicines (called anticoagulants) used to thin the blood
Propafenone, flecainide and medicines used to treat irregular heartbeat
Metoprolol, a beta blocker used to treat high blood pressure and heart problems
Pravastatin, used to treat high cholesterol
Rifampicin, used to treat tuberculosis and leprosy
Linezolid, an antibiotic
Tamoxifen, used to treat breast cancer or fertility problems.

If you are taking or have recently taken any of the medicines on this list, and have not yet discussed them with your doctor, go back to your doctor and ask what to do. Your dose may need to be changed or you may need to take another medicine. Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription.

SEROXAT with food, drink and alcohol

Do not drink alcohol while you are taking SEROXAT. Alcohol can worsen your symptoms and side effects. Taking SEROXAT in the morning with food will reduce the likelihood of feeling sick (nausea).

Warnings It is important to know that:

Pregnancy, breastfeeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. In babies of mothers taking SEROXAT during the first months of pregnancy, there have been some reports showing an increased risk of birth defects, particularly of the heart. In the general population, about 1 in 100 babies are born with a heart defect. This ratio increases to 2 in 100 babies in mothers taking SEROXAT. Your doctor and you can decide whether it is better for you to switch to another treatment or to gradually stop taking SEROXAT during pregnancy. However, depending on your circumstances, your doctor may advise you that it is better for you to continue taking SEROXAT.

Make sure your midwife or doctor knows you are taking SEROXAT. When medicines such as SEROXAT are taken during pregnancy, particularly late pregnancy, they may increase the baby's risk of a serious condition, called persistent pulmonary hypertension of the newborn (PPHN). In PPHN, the pressure in the blood vessels between the baby's heart and the lungs is too high. If you take SEROXAT during the last three months of pregnancy, your baby may also have other conditions, which usually start during the first 24 hours after birth. Symptoms include:

trouble breathing
bluish skin or being too hot or too cold
lips of blue color
vomiting or feeding improperly
being very tired, unable to sleep or crying a lot
stiff or limp muscles
tremors, shaking, or seizures
exaggerated reflexes.

If your baby has any of these symptoms at birth, or you are concerned about your baby's health, contact your doctor or midwife who will be able to advise you.

SEROXAT can pass into breast milk in very small quantities. If you are taking SEROXAT, go back to your doctor and discuss this with him before you start breastfeeding. You and your doctor can decide whether you can breastfeed while you are taking SEROXAT.

Paroxetine has been shown to reduce sperm quality in animal studies. Theoretically, this could affect fertility, but no impact on human fertility has been observed so far.

Driving and using machines

Possible side effects of SEROXAT include dizziness, confusion, feeling sleepy or blurred vision. If you get these side effects, do not drive or use machines.

Dose, Method and Time of Administration How to use Seroxat: Posology

Always take this medicine exactly as your doctor or pharmacist has told you. If you are unsure, consult your doctor or pharmacist.

Sometimes it may be necessary to take more than one tablet or half a tablet. This table will show you how many tablets to take.

Dose Number of tablets to take 10 mg One white-pink tablet or Half a white tablet 20 mg One white tablet or Two white-pink tablets 30 mg One blue tablet or One and a half white tablets or One white tablet + one white-pink tablet or Three white-pink tablets 40 mg Two white tablets or One blue tablet + one white-pink tablet or Four white-pink tablets 50 mg One blue tablet + one white tablet or Two and a half white tablets or Two white tablets + one white-pink tablet or Five white-pink tablets 60 mg Two blue tablets or Three white tablets or Six white-pink tablets

The usual doses for the different conditions are shown in the table below.

Initial dose Recommended daily dose Maximum daily dose Depression 20 mg 20 mg 50 mg Obsessive Compulsive Disorder 20 mg 40 mg 60 mg Panic Disorder 10 mg 40 mg 60 mg Social anxiety disorder 20 mg 20 mg 50 mg Post-traumatic stress disorder 20 mg 20 mg 50 mg Generalized anxiety disorder 20 mg 20 mg 50 mg

Your doctor will tell you what dose to take when you start taking SEROXAT. Most people feel better after a couple of weeks. If you do not start to feel better after this time, talk to your doctor, who will advise you. You may decide to gradually increase the dose, 10 mg at a time, up to the maximum daily dose.

Take the tablets in the morning with food.

Swallow them while drinking water.

Don't chew them.

Your doctor will tell you how long it will be necessary for you to take your tablets. It can be for many months or even for a longer time.

Elderly patients

The maximum dose for patients over the age of 65 is 40 mg per day.

Patients with liver or kidney disease

If you have liver problems or severe kidney disease, your doctor may decide to reduce the dose of SEROXAT from the usual dose.

Overdose What to do if you have taken too much Seroxat

If you take more SEROXAT than you should

Do not take more tablets than your doctor recommends. If you take more SEROXAT tablets than you should (or if someone else is taking it), tell your doctor or hospital straight away. Show them the pack of tablets. Anyone who has taken an overdose of SEROXAT may have one of the symptoms listed in Section 4, Possible Side Effects, or one of the following symptoms: fever, uncontrollable tightening of the muscles.

If you forget to take SEROXAT

Take your medicine at the same time each day. If you forget to take a dose, and remember it before going to bed, take it immediately. Continue as usual the next day. In case you only remember it during the night, or the next day, do not take the missed dose. It may possibly have withdrawal effects, but these should go away after you take your next dose at the usual time. Do not take a double dose to make up for a forgotten dose.

What to do if you are not feeling better

SEROXAT does not improve your symptoms immediately - all antidepressants need time to work. Some people will start to feel better within a couple of weeks, but for others it may take a little longer. Some people taking antidepressants feel worse before they get better. If she doesn't start feeling better after a couple of weeks, go back to your doctor who will advise you on this. Your doctor should ask you to see you again a couple of weeks after starting treatment. Tell your doctor that you have not started to feel better.

If you stop taking SEROXAT

Do not stop taking SEROXAT unless your doctor tells you to. When you stop SEROXAT, your doctor will help you reduce your dose slowly over a number of weeks or months - this should help reduce the possibility of withdrawal effects. One way to do this is to gradually reduce your SEROXAT dose. you are taking 10 mg per week. Most people find that any symptoms of stopping SEROXAT are mild and go away on their own within two weeks. For some people, these symptoms may be more severe, or last longer.

If you get withdrawal effects when you are stopping the tablets, your doctor may decide to stop them more slowly. If you have severe withdrawal effects when you stop taking SEROXAT, contact your doctor. He or she may ask you to start taking the tablets again and stop taking them more slowly.

If you experience withdrawal effects, you will still be able to stop SEROXAT.

Possible withdrawal effects if treatment is stopped

Studies show that 3 out of 10 patients notice one or more symptoms upon discontinuation of SEROXAT. Some withdrawal effects occur more frequently than others upon discontinuation.

Common side effects, which are likely to affect up to 1 in 10 patients:

Feeling dizzy, feeling unstable or having a lack of balance
Pinprick sensations, burning sensations and (less commonly) electric shock sensations, including in the head, and buzzing, hissing, whistling, ringing or other persistent noises in the ear (tinnitus)
Sleep disturbances (vivid dreams, nightmares, inability to sleep)
Feeling anxious
Headache

Uncommon side effects, which are likely to affect up to 1 in 100 patients:

Feeling sick (nausea)
Sweating (including night sweats)
Feeling restless or agitated
Tremors
Feeling confused or disoriented
Diarrhea (loose stools)
Feeling emotional or irritable
Visual disturbances
Rapid or strengthened heartbeat (palpitations).

Talk to your doctor if you are concerned about withdrawal effects when you stop SEROXAT. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Side Effects What are the side effects of Seroxat

Like all medicines, this medicine can cause side effects, although not everybody gets them. Side effects are more likely to appear in the first few weeks of treatment with SEROXAT.

See your doctor if you get any of the following side effects during treatment. You may need to contact your doctor or go straight to a hospital.

Uncommon side effects, which are likely to affect up to 1 in 100 patients:

If you have unusual bruising and bleeding, including blood in your vomit or stool, contact your doctor or go to a hospital straight away.
If you are unable to urinate, contact your doctor or go straight to a hospital.

Rare side effects, which are likely to affect up to 1 in 1,000 patients:

If you have convulsions (fits), contact your doctor or go to a hospital straight away.
If you are feeling agitated and feel like you cannot sit or stand still, you may have what is called akathisia. Increasing the dose of SEROXAT may make these sensations worse. If you feel like this, contact your doctor.
If you feel tired, weak, or confused and have painful, stiff or uncoordinated muscles, this may be due to low blood sodium levels. If you get these symptoms, contact your doctor.

Very rare side effects, likely to affect up to 1 in 10,000 patients:

Allergic reactions, which can be serious, to SEROXAT. If you develop a rash with raised red skin, swollen eyelids, face, lips, mouth and tongue, start itchy and have difficulty breathing (shortness of breath) or swallowing and feel faint or dizzy resulting in collapse or loss of conscience, contact your doctor or go straight to a hospital.
If you have some or all of the following symptoms, you may have what is called serotonin syndrome or neuroleptic malignant syndrome. Symptoms include: feeling very agitated or irritable, feeling confused, feeling restless, feeling hot, sweating, tremors, chills, hallucinations (strange visions or sounds), muscle stiffness, sudden twitching of muscles or a rapid heart rate. Severity can increase, leading to loss of consciousness. If you feel like this, contact your doctor.
Acute glaucoma. If you start to feel pain in your eyes and your vision is blurred, contact your doctor.

Frequency not known

Some people have had thoughts of harming or killing themselves while taking SEROXAT or immediately after stopping treatment (see Section 2, What you need to know before taking SEROXAT). Some people have experienced aggression while taking SEROXAT. If you experience these side effects, please contact your doctor.

Other possible side effects during treatment

Very common side effects, likely to affect more than 1 in 10 patients:

Feeling sick (nausea). Taking the medicine in the morning with food will reduce the chance of this happening.
Changes in sexual conduct or sexual function. For example, lack of orgasm and, in men, abnormalities of erection and ejaculation.

Common side effects, which are likely to affect up to 1 in 10 patients:

Increase in the level of cholesterol in the blood
Lack of appetite
Not sleeping well (insomnia) or feeling sleepy
Abnormal dreams (including nightmares)
Feeling dizzy or shaking
Headache
Difficulty concentrating
Feeling agitated
Feeling unusually weak
Blurred vision
Yawns, dry mouth
Diarrhea or constipation
He retched
Weight gain
Sweating.

Uncommon side effects, which are likely to affect up to 1 in 100 patients:

Short-lived rise or fall in blood pressure, which can cause dizziness or fainting when standing up suddenly
Heart rate faster than normal
Lack of movement, stiffness, tremor or abnormal movements of the mouth and tongue
Dilation of the pupils
Skin rash
Itching
Feeling confused
Hallucinations (strange visions or sounds)
Inability to pass urine (urinary retention) or uncontrolled and involuntary loss of urine (urinary incontinence).
If you are a diabetic patient you may notice a loss of blood sugar control while taking SEROXAT. Consult your doctor for dosage adjustment of insulin or diabetes medicines.

Rare side effects, which are likely to affect up to 1 in 1,000 patients:

Abnormal breast milk production in men and women
Slow heartbeat
Effects on the liver visible in liver function blood tests
Panic attacks
Overactive behavior and thoughts (mania)
Feeling detached from yourself (depersonalization)
Feeling anxious
Irresistible urge to move the legs (Restless Legs Syndrome)
Pain in the joints or muscles
Increased levels of a hormone called prolactin in the blood.
Disorders of the menstrual cycle (including heavy or irregular periods, bleeding between cycles and no or delayed periods)

Very rare side effects, likely to affect up to 1 in 10,000 patients:

A rash, which may appear as blisters, and resemble small targets (central dark spots surrounded by a "paler" area, with a dark ring around the edge), called erythema multiforme
A widespread rash with blisters and peeling of the skin, particularly around the mouth, nose, eyes, and genitals (Stevens-Johnson syndrome)
A widespread rash with blisters and peeling of the skin over most of the body surface (toxic epidermal necrolysis)
Liver problems that cause the skin and whites of the eyes to turn yellow
Syndrome of Inappropriate Antidiuretic Hormone Production (SIADH) which is a condition in which the body develops an excess of water and a decrease in the concentration of sodium (a salt), as a result of improper chemical signals. Patients with SIADH may become seriously ill, or may not experience any symptoms.
Fluid or water retention which can cause swelling of the arms or legs
Sensitivity to sunlight
Painful erection of the penis that does not stop
Low platelet count.

Some patients have experienced buzzing, hissing, whistling, ringing or other persistent noises in the ear (tinnitus) when taking SEROXAT.

An increased risk of bone fractures has been observed in patients taking this type of medicine.

Reporting of side effects

If you get any side effects, including any possible side effects not listed in this leaflet, contact your doctor or pharmacist. Undesirable effects can also be reported directly via the national reporting system at http://www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicinal.

Expiry and Retention

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the blister or bottle and carton. The expiry date refers to the last day of that month. Do not store above 30 ° C. Store in the original package in order to protect from light. If you use the tablets divided in half, keep them carefully in the package .

Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

Composition and pharmaceutical form

What SEROXAT contains

20 mg film-coated tablets

The active substance is paroxetine (20 mg), as hydrochloride hemihydrate.

The excipients are:

Tablet core: dibasic calcium phosphate dihydrate (E341), magnesium stearate (E470b), sodium starch glycolate (Type A)

Film-coating: hypromellose (E464), titanium dioxide (E171), macrogol 400, polysorbate 80 (E433)

Description of what SEROXAT looks like and contents of the pack

SEROXAT 20 mg film-coated tablets are white, oval shaped, debossed with "20" on one side, and with a break line on the other side. Each pack of SEROXAT contains child resistant blisters of 50x1, 4, 10, 14, 20, 28, 30, 50, 56, 60, 98, 100, 250 or 500 tablets. Not all pack sizes may be marketed.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

More information about Seroxat can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction 04.6 Pregnancy and lactation 04.7 Effects on the ability to drive and use machines 04.8 Undesirable effects 04.9 Overdose 05.0 PHARMACOLOGICAL PROPERTIES 05.1 Pharmacodynamic properties 05.2 Pharmacokinetic properties 05.3 Preclinical safety data 06.0 PHARMACEUTICAL PARTICULARS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER 08.0 MARKETING AUTHORIZATION NUMBER 09 .0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS AND QUALITY CONTROLS

01.0 NAME OF THE MEDICINAL PRODUCT

SEROXAT

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 20 mg paroxetine (as paroxetine hydrochloride hemihydrate).

Each 10 ml of oral suspension contains 20 mg of paroxetine (as paroxetine hydrochloride hemihydrate).

Excipients with known effect - each 10 ml of oral suspension contains:

- 20 mg of methyl parahydroxybenzoate

- 6 mg of propyl parahydroxybenzoate

- 0.9 mg of the yellow-orange color FCF (E110)

- 4 g of sorbitol (E420).

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Film-coated tablet.

Oral suspension.

20 mg Tablet

White, film-coated, biconvex oval shaped tablets debossed with "20" on one side and with a score line on the other side.

The 20 mg tablet can be divided into two equal doses if necessary.

Oral suspension.

Slightly viscous, bright orange suspension with an orange odor, free from foreign bodies.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Treatment of

• Major depressive episode

• Obsessive Compulsive Disorder

• Panic disorder with or without agoraphobia

• Social anxiety disorder / social phobia

• Generalized anxiety disorder

• Post-traumatic stress disorder

04.2 Posology and method of administration

Dosage

EPISODES OF MAJOR DEPRESSION

The recommended dose is 20 mg once a day.In general, improvement in patients begins after one week but may only become evident from the second week of therapy.

As with all antidepressant drugs, the dosage should be reviewed and adjusted as necessary within the first three to four weeks after initiation of therapy and thereafter as deemed clinically appropriate.

In some patients, who have an insufficient response to the 20 mg dose, the dose may be gradually increased up to a maximum of 50 mg per day, in 10 mg increments, based on the patient's response.

Patients with depression should be treated for a sufficient period of at least six months to ensure they are symptom-free.

OBSESSIVE COMPULSIVE DISORDER

The recommended dose is 40 mg per day. Patients should be started on a dose of 20 mg per day and the dose can be gradually increased in 10 mg increments up to the recommended dose. If after a few weeks there is insufficient response to the recommended dose, some patients may benefit from gradually increasing the dose up to a maximum of 60 mg per day.

Patients with OCD should be treated for a sufficient period to ensure they are symptom-free. This period can be several months or even longer (see section 5.1 Pharmacodynamic properties).

PANIC DISORDER

The recommended dose is 40 mg per day. Patients should start on a dose of 10 mg per day and the dose gradually increased, with 10 mg increases to the recommended dose, based on the patient's response.

A low starting dose is recommended to minimize the potential for worsening of panic symptoms, as has generally been observed in the initial treatment of this disorder.

If after a few weeks there is insufficient response to the recommended dose, some patients may benefit from gradually increasing the dose up to a maximum of 60 mg per day.

Patients with panic disorder should be treated for a sufficient period to ensure they are symptom-free. This period can be several months or even longer (see section 5.1 Pharmacodynamic properties).

SOCIAL ANXIETY / SOCIAL PHOBIA DISORDER

The recommended dose is 20 mg per day. If insufficient response to the recommended dose is observed after a few weeks, some patients may benefit from gradually increasing their dose in 10 mg increments up to a maximum of 50 mg per day. Long-term use should be considered. periodically (see section 5.1 Pharmacodynamic properties).

GENERALIZED ANXIETY DISORDER

The recommended dose is 20 mg per day. If after a few weeks there is insufficient response to the recommended dose, some patients may benefit from gradually increasing the dose in 10 mg increments up to a maximum of 50 mg per day.

Long-term use should be evaluated periodically (see section 5.1 Pharmacodynamic properties).

POST-TRAUMATIC STRESS DISORDER

GENERAL INFORMATIONS

WITHDRAWAL SYMPTOMS OBSERVED AFTER WITHDRAWAL OF PAROXETINE TREATMENT

Abrupt discontinuation of treatment should be avoided (see section 4.4 Special warnings and precautions for use and section 4.8 Undesirable effects).

The tapering regimen used in clinical trials used a tapering daily dose of 10 mg at weekly intervals.

If intolerable symptoms occur following dose reduction or upon discontinuation of treatment, resuming the previously prescribed dose may be considered. Thereafter, the doctor may continue to reduce the dose, but more gradually.

Special populations:

• Senior citizens

Increased plasma concentrations of paroxetine have been observed in elderly subjects, however the range of plasma concentrations is similar to that seen in younger subjects.

Treatment should begin at the same doses as in adults. In some patients, increasing the dose may be useful, but the maximum dose should not exceed 40 mg per day.

• Children and adolescents (7-17 years)

Paroxetine should not be used for the treatment of children and adolescents as it has been found in controlled clinical trials that paroxetine is associated with an increased risk of suicidal behavior and hostile behavior. Furthermore, efficacy was not adequately demonstrated in these studies (see section 4.4 Special warnings and precautions for use and section 4.8 Undesirable effects).

• Children under the age of 7

The use of paroxetine in children less than 7 years of age has not been studied. Paroxetine should not be used until safety and efficacy in this age group have been established.

• Renal / hepatic impairment

In patients with severe renal impairment (clearance less than 30 ml / min) or in patients with hepatic impairment, increased plasma concentrations of paroxetine have been reported. Therefore, the dosage should be limited to the lowest doses of the dosage range.

Method of administration

It is recommended that paroxetine be administered once daily in the morning with food.

The tablets should be swallowed rather than chewed.

Shake the bottle before use.

04.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Paroxetine is contraindicated in combination with monoamine oxidase inhibitors (MAO inhibitors). In exceptional cases, linezolid (an antibiotic that is a reversible non-selective MAO inhibitor) can be administered in combination with paroxetine provided that careful observation of serotonin syndrome symptoms and blood pressure monitoring is possible (see section 4.5).

Paroxetine treatment can be initiated:

- two weeks after stopping treatment with an irreversible MAO inhibitor or

- at least 24 hours after stopping treatment with a reversible MAO inhibitor (eg moclobemide, linezolid, methylthioninium chloride (methylene blue, a preoperative visualization agent that is a reversible non-selective MAO inhibitor)).

Initiation of therapy with any MAO inhibitor should occur at least one week after stopping treatment with paroxetine.

Paroxetine should not be used in combination with thioridazine since, as with other CYP450 2D6 hepatic enzyme inhibitors, paroxetine may elevate plasma levels of thioridazine (see section 4.5 Interactions with other medicinal products and other forms of interaction).

Administration of thioridazine alone can induce QTc interval prolongation associated with severe ventricular arrhythmias such as torsades de pointes and sudden death.

Paroxetine should not be used in combination with pimozide (see section 4.5 Interactions with other medicinal products and other forms of interaction).

04.4 Special warnings and appropriate precautions for use

Treatment with paroxetine should be initiated with caution two weeks after cessation of irreversible MAO inhibitor treatment or 24 hours after cessation of reversible MAO inhibitor treatment. Paroxetine dosage should be gradually increased until an optimal response is achieved (see section 4.3 Contraindications and section 4.5 Interactions with other medicinal products and other forms of interaction).

Pediatric population

Paroxetine should not be used to treat children and adolescents under 18 years of age. Suicidal behaviors (suicide attempts and suicidal ideation) and hostility (predominantly aggression, oppositional behavior and anger) were observed more frequently in clinical trials in children and adolescents treated with antidepressants than in those treated with placebo. If, based on medical needs, a decision is made to carry out the treatment anyway, the patient should be carefully monitored for the appearance of suicidal symptoms. Furthermore, long-term safety data in children and adolescents relating to growth, maturation and cognitive and behavioral development are not available.

Suicide / suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide / related events). This risk persists until significant remission occurs. As improvement may not occur during the first or immediate weeks of treatment, patients should be monitored closely until improvement occurs. It is generally clinical experience that the risk of suicide may increase in the early stages of improvement.

Other psychiatric conditions for which paroxetine is prescribed may also be associated with an increased risk of suicidal behavior. Furthermore, these conditions can be associated with major depressive disorder. The same precautions followed when treating patients with other psychiatric disorders should therefore be observed when treating patients with major depressive disorders.

Patients with a history of suicidal behavior or thoughts, or who exhibit a significant degree of suicidal ideation prior to initiation of treatment, are at increased risk of suicidal thoughts or suicidal thoughts, and should be closely monitored during treatment. - Analysis of clinical trials conducted with antidepressant drugs in comparison with placebo in the therapy of psychiatric disorders, showed an increased risk of suicidal behavior in the age group below 25 years of patients treated with antidepressants compared to placebo (see also section 5.1).

Drug therapy with antidepressants should always be associated with close surveillance of patients, particularly those at high risk, especially in the initial stages of treatment and after dose changes. Patients (or caregivers) should be advised of the need to monitor and report immediately to their physician any worsening clinical picture, the onset of suicidal behavior or thoughts, or changes in behavior.

Akathisia / psychomotor agitation

The use of paroxetine has been associated with the development of akathisia, characterized by an internal feeling of restlessness and psychomotor agitation such as an inability to sit or stand still, usually associated with subjective malaise. This is most likely to happen within the first few weeks of treatment. In patients with these symptoms, increasing the dosage can be harmful.

Serotonin syndrome / neuroleptic malignant syndrome

On rare occasions, there have been reports of serotonin syndrome or neuroleptic malignant syndrome in association with paroxetine treatment, particularly when administered concomitantly with other serotonergic and / or neuroleptic drugs. Since these syndromes can lead to potentially life-threatening conditions, treatment with paroxetine should be discontinued in the event of such events (characterized by symptom pictures such as hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuation of signs mental status changes including confusion, irritability, extreme agitation leading to delirium and coma) and symptomatic supportive treatment should be initiated. Paroxetine should not be used in combination with serotonin precursors (such as L-tryptophan, oxitriptan) due to the risk of serotonin syndrome (see sections 4.3 Contraindications and 4.5 Interactions with other medicinal products and other forms of interaction).

Mania

As with all antidepressants, paroxetine should be used with caution in patients with a history of mania.

Paroxetine should be discontinued in all patients entering a manic phase.

Renal / hepatic insufficiency

Caution is recommended in patients with severe renal insufficiency or in patients with hepatic insufficiency (see section 4.2 Posology and method of administration).

Diabetes

In diabetic patients, treatment with SSRIs can impair glycemic control. The dosage of insulin and / or oral hypoglycaemics may need to be adjusted.

In addition, there have been studies suggesting that an increase in blood glucose may occur when paroxetine and pravastatin are co-administered (see section 4.5).

Epilepsy

As with other antidepressants, paroxetine should be used with caution in patients with epilepsy.

Seizures

The overall incidence of seizures in patients treated with paroxetine is less than 0.1%. The drug should be discontinued in all patients who present with seizures.

Electroconvulsive Therapy (ECT)

There is limited clinical experience in the concomitant administration of paroxetine with electroconvulsive therapy (ECT).

Glaucoma

As with other SSRIs, paroxetine can cause mydriasis and should be used with caution in patients with narrow-angle glaucoma or a history of glaucoma.

Cardiovascular pathologies

In patients with cardiovascular diseases the usual precautions should be observed.

Hyponatremia

Hyponatremia has been reported rarely, predominantly in the elderly. Caution should also be exercised in those patients at risk of hyponatremia, for example from concomitant medications and cirrhosis. Hyponatremia is usually reversible after discontinuation of paroxetine.

Hemorrhages

Cases of cutaneous bleeding disorders such as ecchymosis and purpura have been reported with SSRIs. Other haemorrhagic manifestations have been reported, for example gastrointestinal and gynecological haemorrhages. Elderly patients may be at increased risk for non-menstruation-related bleeding.

Caution is advised in patients taking SSRIs concomitantly with oral anticoagulants, drugs known to affect platelet function, or other drugs that may increase the risk of bleeding (e.g. atypical antipsychotics such as clozapine, phenothiazine, most tricyclic antidepressants, acid acetylsalicylic, non-steroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors) and in patients with a history of bleeding disorders or conditions that may predispose to bleeding (see section 4.8).

Interaction with tamoxifen

Paroxetine, a potent inhibitor of CYP2D6, may lead to decreased concentrations of endoxifen, one of the most important active metabolites of tamoxifen. Therefore, paroxetine should be avoided whenever possible during treatment with tamoxifen (see section 4.5).

Drugs that affect gastric pH

In patients taking the oral suspension, the plasma concentration of paroxetine may be affected by gastric pH. Data in vitro showed that an acidic environment is required for the release of the active drug from the suspension, so the absorption can be reduced in patients with an elevated gastric pH or with achlorhydria, as after the use of some drugs (antacids, receptor antagonists histaminergic H2, proton pump inhibitors), in some diseases (for example atrophic gastritis, pernicious anemia, chronic Helicobacter pylori), and after surgery (vagotomy, gastrectomy). Dependence on pH should be taken into account when using a different pharmaceutical form of paroxetine (eg plasma concentration of paroxetine may decrease in patients with elevated gastric pH switching from tablets to oral suspension). Therefore, caution is recommended in patients starting or ending treatment with drugs that increase gastric pH. In such situations a dose adjustment may be necessary.

Withdrawal symptoms observed on discontinuation of paroxetine treatment

Discontinuation symptoms observed when treatment is stopped are common, particularly in the event of abrupt discontinuation (see section 4.8 Undesirable effects).

In clinical trials, adverse events observed with treatment discontinuation occurred in 30% of patients taking paroxetine, compared with 20% of patients taking placebo:

the onset of withdrawal symptoms is not the same in cases where a drug is addictive or addictive.

The risk of withdrawal symptoms may be dependent on several factors, including the duration of therapy, the dose and the rate of dose reduction.

Dizziness, sensory disturbances (including paraesthesia, electric shock sensation and tinnitus), sleep disturbances (including intense dreams), agitation or anxiety, nausea, tremor, confusion, sweating, headache, diarrhea, palpitations, emotional instability, have been reported. irritability and visual disturbances. Generally these symptoms are mild to moderate, however in some patients they may be severe in intensity.They generally appear within the first few days of stopping treatment, but there have been very rare cases where they have occurred in patients who inadvertently missed a dose.

Generally these symptoms are self-limiting, and usually resolve within two weeks, although in some individuals they may last longer (two to three months or more). It is recommended that the dose of paroxetine should be gradually reduced when treatment is discontinued, over a period of several weeks or months, depending on the patient's needs (see "Withdrawal Symptoms Observed After Discontinuation of Treatment with paroxetine ", section 4.2 Posology and method of administration).

Warnings relating to excipients

Parabens

Paroxetine oral suspension contains methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216) (parabens), which are known to cause urticaria; these are generally delayed-type reactions, such as contact dermatitis, but immediate reactions with bronchospasm may rarely occur.

Orange yellow dye

Paroxetine oral suspension contains yellow-orange dye FCF (E110), which may cause allergic reactions.

Sorbitol E420

Paroxetine oral suspension contains sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take this medicine.

04.5 Interactions with other medicinal products and other forms of interaction

Serotonergic drugs

As with other SSRIs, co-administration with serotonergic drugs may lead to serotonin-associated effects (serotonin syndrome: see section 4.4 Special warnings and precautions for use). Caution should be advised and closer clinical monitoring is required when serotonergic drugs (such as L-tryptophan, triptans, tramadol, linezolid, methylthioninium chloride (methylene blue) SSRI, lithium, pethidine and St. John's wort preparations - Hypericum perforatum) are administered concomitantly with paroxetine. Caution is also advised with fentanyl, used in general anesthesia or in the treatment of chronic pain. The concomitant use of paroxetine and MAO inhibitors is contraindicated due to the risk of serotonin syndrome (see section 4.3 Contraindications).

Pimozide

A mean 2.5-fold increase in pimozide levels occurred in a low single dose study of pimozide (2 mg) when it was co-administered with paroxetine (at a dose of 60 mg). This can be explained on the basis of the inhibitory effect that paroxetine has on CYP2D6. Due to the reduced therapeutic index of pimozide and its known ability to prolong the QT interval, concomitant use of pimozide and paroxetine is contraindicated (see section 4.3 Contraindications).

Enzymes responsible for drug metabolism

The metabolism and pharmacokinetics of paroxetine may be affected by the induction or inhibition of drug metabolizing enzymes.

When paroxetine is administered concomitantly with a drug known to inhibit enzyme metabolism, the use of the lowest doses in the dosage range should be considered.

No starting dose adjustment is required when co-administered with drugs known to induce enzyme metabolism (e.g. carbamazepine, rifampicin, phenobarbital, phenytoin), or with fosamprenavir / ritonavir. Any modification of the paroxetine dosage (either after initiation or following discontinuation of a metabolic inducing drug) should be based on clinical response (tolerability and efficacy).

Neuromuscular blockers

SSRIs may reduce plasma cholinesterase activity resulting in prolongation of the neuromuscular blocking action of mivacurium and succinylcholine.

Fosamprenavir / ritonavir: Co-administration of fosamprenavir / ritonavir 700/100 mg twice daily with paroxetine 20 mg daily in healthy volunteers for 10 days significantly reduces the plasma levels of paroxetine by approximately 55%. Plasma levels of fosamprenavir / ritonavir during co-administration with paroxetine were similar to reference values from other studies, indicating that paroxetine has no significant effect on the metabolism of fosamprenavir / ritonavir. There are no data on the long-term effect of co-administration of paroxetine and fosamprenavir / ritonavir for longer than 10 days.

Procyclidine: Daily administration of paroxetine significantly increases plasma levels of procyclidine. If anticholinergic effects are observed, the dose of procyclidine should be reduced.

Anticonvulsants: carbamazepine, phenytoin, sodium valproate. Concomitant administration does not appear to show any effect on the pharmacokinetic and pharmacodynamic profile in epileptic patients.

Inhibitory potency of paroxetine on CYP2D6

Like other antidepressants, including other SSRIs, paroxetine inhibits the hepatic cytochrome P450 enzyme CYP2D6. Inhibition of CYP2D6 may lead to increased plasma concentrations of co-administered drugs metabolised by this enzyme. They include these drugs. some tricyclic antidepressants (e.g. clomipramine, nortriptyline and desipramine), phenothiazine neuroleptics (e.g. perphenazine and thioridazine, see section 4.3 Contraindications), risperidone, atomoxetine, some Type 1 C antiarrhythmics (e.g. propafenone and flecolainide).

The use of paroxetine in combination with metoprolol administered in heart failure is not recommended due to the reduced therapeutic index of metoprolol in this indication.

Pharmacokinetic interaction between CYP2D6 inhibitors and tamoxifen has been reported in the literature, showing a 65-75% reduction in plasma levels of endoxifen, one of the most active forms of tamoxifen. In some studies, reduced efficacy of tamoxifen has been reported with the concomitant use of some SSRI antidepressants. Since a reduced effect of tamoxifen cannot be excluded, concomitant administration with potent CYP2D6 inhibitors (including paroxetine) should be avoided whenever. possible (see section 4.4).

Alcohol

As with other psychotropic drugs, patients should be advised to avoid alcohol use while taking paroxetine.

Oral anticoagulants

There may be a pharmacodynamic interaction between paroxetine and oral anticoagulants. The concomitant use of paroxetine and oral anticoagulants can lead to an increase in anticoagulant activity and the risk of bleeding. Therefore paroxetine should be used with caution in patients being treated with oral anticoagulants (see section 4.4 Special warnings and precautions for use).

Non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid and other antiplatelet agents

A pharmacodynamic interaction between paroxetine and NSAID / acetylsalicylic acid may occur. Concomitant use of paroxetine and NSAIDs / acetylsalicylic acid may lead to an increased risk of bleeding (see section 4.4 Special warnings and precautions for use).

Caution is advised in patients taking SSRIs concomitantly with oral anticoagulants, drugs known to affect platelet function or other drugs that may increase the risk of bleeding (e.g. atypical antipsychotics such as clozapine, phenothiazine, most tricyclic antidepressants, acetylsalicylic acid , non-steroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors) and in patients with a history of bleeding disorders or conditions that may predispose to bleeding.

Pravastatin

Interaction between paroxetine and pravastatin has been observed in studies suggesting that co-administration of paroxetine and pravastatin may lead to an increase in the blood glucose level. Patients with diabetes mellitus receiving both paroxetine and pravastatin may require dose adjustments of the hypoglycaemic agents and / or insulin (see section 4.4).

Drugs that affect gastric pH

Data in vitro showed that the release of paroxetine from the oral suspension is pH-dependent. Therefore, drugs that alter gastric pH (such as antacid drugs, proton pump inhibitors or histamine H2 receptor antagonists) may affect the plasma concentrations of paroxetine in patients taking the oral suspension (see section 4.4. and precautions for use).

04.6 Pregnancy and lactation

Pregnancy

Some epidemiological studies have indicated an increased risk of congenital malformations, particularly cardiovascular (eg ventricular and atrial septal defects) associated with paroxetine use during the first trimester of pregnancy. The mechanism is unknown. The data indicate that the risk of giving birth to a newborn with a cardiovascular defect following maternal exposure to paroxetine is less than 2/100 compared to the risk of approximately 1/100 expected for such defects in the general population.

Paroxetine should only be administered during pregnancy when strictly indicated. The physician, at the time of the prescription, will have to evaluate the option of alternative treatments in women who are pregnant or who are planning to become pregnant. Abrupt termination during pregnancy should be avoided (see "Withdrawal symptoms observed following discontinuation of paroxetine treatment", section 4.2 Posology and method of administration).

Newborns should be observed if maternal use of paroxetine continues into the later stages of pregnancy, particularly in the third trimester.

The following symptoms may occur in newborns following maternal use of paroxetine in the later stages of pregnancy: respiratory distress, cyanosis, apnea, seizures, unstable temperature, difficulty in feeding, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia , tremor, agitation, irritability, lethargy, constant crying, drowsiness and difficulty falling asleep. These symptoms could be due to either serotonergic effects or withdrawal symptoms. In most cases, complications begin immediately upon delivery or immediately after (less than 24 hours).

Epidemiological data have suggested that the use of SSRIs during pregnancy, particularly during late pregnancy, may cause an increased risk of persistent pulmonary hypertension of the newborn (PPHN). The observed risk was approximately five in 1000 pregnancies. general population one to two cases of PPHN occur in 1000 pregnancies.

Studies in animals have shown reproductive toxicity but did not indicate direct harmful effects with respect to pregnancy, embryo-fetal development, parturition or postnatal development (see section 5.3 Preclinical safety data).

Feeding time

Small amounts of paroxetine are excreted in breast milk. In published studies, serum concentrations in breastfed infants were not detectable (sign of drug effect. Since no effects are expected, breastfeeding may be considered.

Fertility

Animal data showed that paroxetine can affect sperm quality (see section 5.3) in vitro with human material may suggest some effect on sperm quality, however, human cases with some SSRIs (including paroxetine) have shown an effect on sperm quality that appears to be reversible. No effects on human fertility have been observed to date.

04.7 Effects on ability to drive and use machines

Clinical experience has shown that paroxetine therapy is not associated with impaired cognitive or psychomotor functions. However, as with all psychoactive drugs, patients should be advised to exercise caution when driving and operating machinery.

Although paroxetine does not increase the psychic and motor damaging effects induced by alcohol intake, concomitant use of paroxetine and alcohol is not recommended.

04.8 Undesirable effects

Some of the adverse drug reactions listed below may decrease in intensity and frequency with continued treatment and do not generally lead to discontinuation of therapy. Adverse reactions are listed below by system organ and by frequency. Frequencies are defined as: very common (≥1 / 10), common (≥1 / 100,

Disorders of the blood and lymphatic system

Uncommon: bleeding disorders, particularly affecting the skin and mucous membranes (including ecchymosis and gynecological bleeding).

Very rare: thrombocytopenia.

Disorders of the immune system

Very rare: severe and life-threatening allergic reactions (including anaphylactoid reactions and angioedema).

Endocrine pathologies

Very rare: syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Metabolism and nutrition disorders

Common: increased cholesterol levels, decreased appetite.

Uncommon: impaired glycemic control has been reported in diabetic patients (see section 4.4)

Rare: hyponatremia.

Hyponatremia has been reported mainly in elderly patients and is sometimes due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Psychiatric disorders

Common: sleepiness, insomnia, agitation, abnormal dreams (including nightmares).

Uncommon: confusion, hallucinations.

Rare: manic reactions, anxiety, depersonalization, panic attacks, akathisia (see section 4.4).

Frequency not known: suicidal ideation, suicidal behavior, aggression.

Cases of suicidal ideation and suicidal behavior have been reported during paroxetine therapy or soon after treatment discontinuation (see section 4.4).

Cases of aggression have been observed in post-marketing experience.

These symptoms may also be due to the underlying disease.

Nervous system disorders

Common: dizziness, tremors, headache, impaired concentration.

Uncommon: extrapyramidal disorders.

Rare: convulsions, restless legs syndrome (RLS).

Very rare: serotonin syndrome (symptoms may include agitation, confusion, diaphoresis, hallucinations, hyperreflexia, myoclonus, chills, tachycardia and tremor).

There have been reports of extrapyramidal disorders, including orofacial dystonia, sometimes in patients already suffering from movement disorders or in patients receiving neuroleptics.

Eye disorders

Common: blurred vision.

Uncommon: mydriasis (see section 4.4 Special warnings and precautions for use).

Very rare: acute glaucoma.

Ear and labyrinth disorders

Frequency not known: tinnitus.

Cardiac pathologies

Uncommon: sinus tachycardia.

Rare: bradycardia.

Vascular pathologies

Uncommon: transient rise or fall in blood pressure, postural hypotension.

Transient increases or decreases in blood pressure have been reported following treatment with paroxetine, usually in patients with pre-existing hypertension or anxiety.

Respiratory, thoracic and mediastinal disorders

Common: yawn.

Gastrointestinal disorders

Very common: nausea.

Common: constipation, diarrhea, vomiting, dry mouth.

Very rare: gastrointestinal bleeding.

Hepatobiliary disorders

Rare: increase in liver enzymes.

Very rare: hepatic events (such as hepatitis, sometimes associated with jaundice and / or liver failure).

Elevations of liver enzymes have been reported. In the post-marketing period, hepatic events (such as hepatitis, sometimes associated with jaundice and / or liver failure) have also been reported very rarely. prolonged increase in liver function test values.

Skin and subcutaneous tissue disorders

Common: sweating.

Uncommon: skin rash, pruritus.

Very rare: severe skin adverse reactions (including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis), urticaria, photosensitivity reactions.

Renal and urinary disorders

Uncommon: urinary retention, urinary incontinence.

Diseases of the reproductive system and breast

Very common: sexual dysfunction.

Rare: hyperprolactinaemia / galactorrhoea, menstrual disturbances (including menorrhagia, metroraggia, amenorrhoea, delayed menstruation and irregular menstruation).

Very rare: priapism.

Musculoskeletal and connective tissue disorders

Rare: arthralgia, myalgia.

Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients given SSRIs and tricyclic antidepressants. The mechanism leading to this risk is unknown.

General disorders and administration site conditions

Common: asthenia, weight gain.

Very rare: peripheral edema.

WITHDRAWAL SYMPTOMS OBSERVED AFTER WITHDRAWAL OF PAROXETINE TREATMENT

Common: dizziness, sensory disturbances, sleep disturbances, anxiety, headache.

Uncommon: agitation, nausea, tremor, confusion, sweating, emotional instability, visual disturbances, palpitations, diarrhea, irritability.

Discontinuation of paroxetine treatment (especially if abrupt) usually leads to withdrawal symptoms.

Generally these events are mild to moderate and self-limiting, however in some patients they may be severe and / or prolonged. It is therefore recommended that, if treatment with paroxetine is no longer required, there is a gradual discontinuation, conducted by a gradual decrease of the dose (see section 4.2 Posology and method of administration and section 4.4 Special warnings and precautions for use).

ADVERSE EVENTS OBSERVED DURING CLINICAL STUDIES IN AGED PATIENTS PEDIATRIC

The following adverse events were observed:

Increased suicide-related behaviors (including suicide attempts and suicidal thoughts), self-harming behavior and increased hostile attitude. Suicidal thoughts and suicide attempts were mainly observed in clinical trials with adolescents with Major Depressive Disorder. "hostile attitude has particularly occurred in children with OCD, and especially in children under the age of 12.

Additional events observed were: decreased appetite, tremor, sweating, hyperkinesia, agitation, emotional lability (including crying and mood fluctuations), bleeding-related adverse events, especially of the skin and mucous membranes.

Events observed after stopping / tapering off of paroxetine are: emotional lability (including crying, mood fluctuations, self harm, suicidal thoughts and suicide attempts), nervousness, dizziness, nausea and abdominal pain (see section 4.4 Special warnings and precautions for use) ).

See section 5.1 for more information on pediatric clinical studies.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.

04.9 Overdose

Symptoms and signs

Based on the available information regarding overdose with paroxetine, a large margin of safety appears evident.

Experience with paroxetine overdose has indicated that, in addition to the symptoms described in section 4.8 Undesirable effects, fever and involuntary muscle contractions have been reported.

Patients generally recovered without serious sequelae even in cases where paroxetine was taken alone up to doses of 2000 mg. Events such as coma or ECG changes have occasionally been reported, very rarely with a fatal outcome, but generally when paroxetine was taken in combination with other psychotropic drugs, with or without alcohol.

Treatment

No specific antidote is known.

Treatment should be based on the general measures used in the treatment of overdose with antidepressants. To reduce the absorption of paroxetine, administration of 20-30 g of activated charcoal may be considered, if possible within hours of taking the overdose. Supportive therapy with careful observation and frequent monitoring of vital signs is indicated. Patient management should follow clinical indications.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: antidepressants - selective serotonin reuptake inhibitors.

ATC code: N06AB05.

Mechanism of action

Paroxetine is a potent and selective 5-hydroxytryptamine (5-HT; serotonin) reuptake inhibitor; its antidepressant action and its efficacy in the treatment of obsessive compulsive disorder, social anxiety disorder / social phobia, generalized anxiety disorder, post-traumatic stress disorder and panic disorder are believed to be related to this specific inhibition of reuptake of 5-HT in brain neurons.

Paroxetine is not chemically related to tricyclics, tetracyclics and other available antidepressants.

Paroxetine has low affinity for muscarinic-type cholinergic receptors and studies in animals have shown only weak anticholinergic properties.

In accordance with this selectivity of action, studies in vitro showed that, unlike tricyclic antidepressants, paroxetine has low affinity for alpha 1, alpha 2 and beta-adrenoceptors, for dopaminergic receptors (D2), for 5-HT1 like and 5-HT2 receptors, and for those of "histamine (H1). This lack of interaction with postsynaptic receptors in vitro has been confirmed by studies in vivo, which demonstrated the absence of depressive properties on the central nervous system and of hypotensive properties.

Pharmacodynamic effects

Paroxetine does not alter psychomotor functions and does not potentiate the depressive effects of ethanol.

Similar to other selective serotonin reuptake inhibitors, paroxetine causes symptoms related to excessive stimulation of the serotonin receptor when administered to animals previously treated with monoamine oxidase (MAO) inhibitors or tryptophan.

Behavioral and EEG studies indicate that paroxetine is weakly activating at doses generally higher than those required to inhibit serotonin reuptake. The activating properties are not by nature "amphetamine-like". Animal studies indicate that paroxetine is well tolerated by the cardiovascular system. Paroxetine does not cause significant changes in blood pressure, heart rate and ECG after administration to healthy subjects.

Studies indicate that paroxetine, unlike antidepressants which inhibit noradrenaline reuptake, has a more reduced propensity to inhibit the antihypertensive effects of guanethidine.

Paroxetine, in the treatment of depressive disorders, demonstrates efficacy comparable to that of standard antidepressants.

There is also some evidence that paroxetine may have therapeutic value in patients who are unresponsive to standard therapy.

Administration of the dose in the morning has no adverse effect on the quality or duration of sleep.

Additionally, patients may report improved sleep when they respond to paroxetine therapy.

Analysis of suicidality in adults

A paroxetine-specific analysis of clinical trials conducted in comparison with placebo in adult patients with psychiatric disorders showed a higher frequency of suicidal behavior in young adults (aged 18 to 24 years) treated with paroxetine compared to placebo ( 2.19% compared to 0.92%). In the older age group, no such increase was observed. In adults (of all ages) with major depressive disorder, there was an increased frequency of suicidal behavior in patients treated with paroxetine compared to placebo (0.32% compared to 0.05%); all events were suicide attempts. However, the majority of such attempts for paroxetine (8 of 11) occurred in young adults (see also section 4.4).

Dose response

In fixed dose studies, the dose response curve is flat, indicating no efficacy advantage in using higher than recommended doses. However, there are some clinical data that suggest that subsequent dose increases may be of benefit to some. patients.

Long-term efficacy

The long-term efficacy of paroxetine in depression was demonstrated in a 52-week maintenance study designed to evaluate relapse prevention: relapses in patients treated with paroxetine (20-40 mg per day) occurred in the 12% of cases, compared to 28% of cases in patients taking placebo.

The long-term efficacy of paroxetine in the treatment of OCD was examined in three 24-week maintenance studies, designed to evaluate relapse prevention. In one of the three studies, a significant difference was achieved in the proportion of patients with relapses between paroxetine (38%) and placebo (59%).

The long-term efficacy of paroxetine in the treatment of panic disorder was demonstrated in a 24-week maintenance study designed to evaluate relapse prevention: relapses in patients treated with paroxetine (10-40 mg per day) occurred in 5% of cases, compared to 30% of patients taking placebo.This was supported by a 36-week maintenance study.

The long-term efficacy of paroxetine in the treatment of social and generalized anxiety disorders and post-traumatic stress disorder has not been sufficiently demonstrated.

Adverse events observed in clinical trials in pediatric patients

During short-term clinical trials (up to 10-12 weeks) in children and adolescents, the following adverse events have been observed in patients treated with paroxetine with a frequency of at least 2% of patients and these events occurred with an incidence at least twice as high as placebo: increased suicide-related behaviors (including suicide attempts and suicidal thoughts), self-harming behavior and increased hostile attitude. Suicidal thoughts and suicide attempts were mainly observed in clinical trials with adolescents with Major Depressive Disorder. The increased hostile attitude occurred particularly in children with OCD, especially in children under the age of 12. Additional events that were observed more frequently in the paroxetine group than in the paroxetine group. that treated with placebo were: decrease in appetite, tremor, sweating, hyperkinesis, agitation, emotional lability (including crying and mood swings).

In studies where the tapering regimen was used, symptoms reported during the tapering phase or upon discontinuation of paroxetine, observed with a frequency of at least 2% of patients and occurring occurred with at least two times the incidence of placebo, were: emotional lability (including crying, mood fluctuations, self-harm, suicidal thoughts and suicide attempts), nervousness, dizziness, nausea and abdominal pain (see section 4.4. special and precautions for use).

In five parallel group studies of treatment duration from eight weeks to eight months, bleeding-related adverse events, mainly of the skin and mucous membranes, were observed at a frequency of 1.74% in patients treated with paroxetine compared to a frequency of 0.74% observed in patients treated with placebo.

05.2 "Pharmacokinetic properties

Absorption

Paroxetine is well absorbed after oral administration and undergoes first pass metabolism.

Due to first pass metabolism, the amount of paroxetine available in the systemic circulation is less than that absorbed from the gastrointestinal tract. In case of increased body burden following higher single doses or multiple doses, partial saturation of the first pass effect and a reduction in plasma clearance occur. Pharmacokinetic parameters are not constant, resulting in non-linear kinetics, however non-linearity is generally modest and is limited to those subjects who achieve low plasma levels at low doses.

Systemic steady-state levels are achieved within 7-14 days of initiation of treatment with the immediate or controlled release formulations and pharmacokinetics do not appear to change during long-term treatment.

Distribution

Paroxetine is widely distributed in tissues and pharmacokinetic calculations indicate that only 1% of the paroxetine present in the body is found in the plasma. About 95% of the paroxetine present in plasma is bound to proteins at therapeutic concentrations.

No correlation has been demonstrated between paroxetine plasma concentrations and clinical effects (adverse events and efficacy).

Biotransformation

The major metabolites of paroxetine are polar and conjugated products of oxidation and methylation, which are readily cleared. In view of their relative lack of pharmacological activity, they are extremely unlikely to contribute to the therapeutic effects of paroxetine.

Metabolism does not compromise the selectivity of action of paroxetine on neuronal reuptake of serotonin.

Elimination

Urinary excretion of unchanged paroxetine is generally less than 2%, while that of metabolites is about 64% of the dose. Approximately 36% of the dose is excreted in the faeces, probably via bile, of which unchanged paroxetine represents less than "1% of the dose. Thus paroxetine is almost completely eliminated by metabolism.

Excretion of metabolites is biphasic, being initially the result of first pass metabolism and subsequently controlled by the systemic elimination of paroxetine.

The elimination half-life is variable but is generally about one day.

Special patient populations

Elderly and renal / hepatic insufficiency

An increase in plasma concentrations of paroxetine has been observed in elderly subjects and in subjects with severe renal insufficiency and in subjects with hepatic insufficiency, but the range of plasma concentrations is similar to that of healthy adult subjects.

05.3 Preclinical safety data

Toxicological studies were conducted in the rhesus monkey and in the albino rat; in both species the metabolic profile is similar to that described in humans. As expected with lipophilic amines, including tricyclic antidepressants, phospholipidosis was detected in rats. Phospholipidosis was not observed in primate studies, lasting up to a year, at doses six times higher than the recommended clinical dose range.

Carcinogenicity: In two-year studies in mice and rats, paroxetine did not show carcinogenic effects.

Genotoxicity: Genotoxicity was not observed in a series of tests in vitro And in vivo.

Reproductive toxicity studies in rats showed that paroxetine affects male and female fertility by reducing the fertility index and the pregnancy rate. In rats, an increase in offspring mortality and a delay in ossification were observed. they are likely related to maternal toxicity and are not considered to have a direct effect on the fetus / neonate.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Tablets

Core of the tablet: dibasic calcium phosphate dihydrate (E341), sodium carboxymethyl starch (Type A), magnesium stearate (E470b).

Tablet coating: hypromellose (E464), macrogol 400, polysorbate 80 (E433), titanium dioxide (E171).

Oral suspension

Polacrilin potassium, dispersible cellulose (E460), propylene glycol, glycerol (E422), sorbitol (E420), methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216), sodium citrate dihydrate (E331), anhydrous citric acid (E330), saccharin (E954), natural orange flavor, natural lemon flavor, FCF yellow orange dye (E110), simethicone emulsion, purified water.

06.2 Incompatibility

Not relevant.

06.3 Period of validity

Tablets

3 years.

Oral suspension

2 years (1 month after first opening).

06.4 Special precautions for storage

Tablets

Do not store above 30 ° C.

Store in the original package to keep it away from light.

Oral suspension

Do not store above 25 ° C.

06.5 Nature of the immediate packaging and contents of the package

Tablets

Child resistant blister made of opaque polyvinyl chloride (PVC), with aluminum-paper bottom. Plastic containers (bottles) made of polypropylene, with a polyethylene closure, can also be used.

Pack sizes: 50x1, 4, 10, 14, 20, 28, 30, 50, 56, 60, 98, 100, 250 and 500 tablets.

Not all pack sizes may be marketed.

Oral suspension

Amber glass bottle with child resistant polypropylene closure and polyethylene safety seal.

A polypropylene measuring cup is included.

Packaging: 150 ml