Daparox - 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 mesylate)

Daparox 20 mg film-coated tablets

Daparox package inserts are available for pack sizes:
  • Daparox 20 mg film-coated tablets
  • Daparox 33.1mg / ml, oral drops, solution

Why is Daparox used? What is it for?

Paroxetine belongs to the group of drugs known as selective serotonin reuptake inhibitors (SSRIs) which are antidepressant drugs.

Daparox is used in the treatment of:

  • Depression (major depressive episode)
  • Obsessive Compulsive Disorder (obsessive compulsive thoughts or actions)
  • Panic disorder with or without agoraphobia (eg severe fear of leaving the house, entering shops, or fear of public places)
  • Social anxiety disorder / social phobia (strong fear or desire to avoid everyday social interaction situations)
  • Generalized anxiety disorder (anxiety always present, with excessive tension and chronic worry)
  • Post-traumatic stress disorder (anxiety related to traumatic events)

Contraindications When Daparox should not be used

Do not take Daparox

  • if you are allergic to paroxetine or any of the other ingredients of Daparox (listed in section 6) (see section 2, "Daparox contains alcohol").
  • if you take certain medicines used to treat depression or Parkinson's disease (called monoamine oxidase inhibitors (MAOIs)). - You can start taking paroxetine only if at least 14 days have passed since you stopped using irreversible MAOIs (such as isocarboxazid and phenelzine). - If you take a reversible MAOI (such as moclobemide, linezolid, methylene blue (methylthioninium chloride)), you must wait at least 24 hours before starting paroxetine. - Instead, you must wait at least 7 days after stopping paroxetine before you start taking a MAOI.
  • if you are taking a certain medicine (thioridazine) used to treat severe mental illness, such as psychosis. Paroxetine may increase the blood levels of thioridazine, resulting in an increased risk of side effects from thioridazine. One of the possible side effects is irregular heartbeat (ventricular arrhythmia) and sudden death (see also section 2, "Other Medicines and Daparox").
  • if you are taking a certain antipsychotic medicine (pimozide). Paroxetine may increase the blood levels of pimozide, resulting in an increased risk of developing any of the related side effects (see section 2, "Other medicines and Daparox").

Precautions for use What you need to know before taking Daparox

Talk to your doctor or pharmacist before taking Daparox

  • if you are under the age of 18. Paroxetine should not be used to treat children and adolescents under 18 years of age. In fact, these patients, in case of taking drugs belonging to this group, present a greater risk of experiencing undesirable effects such as suicide attempts, suicidal thoughts and hostile attitudes (mainly aggression, hostile behavior and anger). Notwithstanding the foregoing, your doctor may decide to prescribe paroxetine to patients under the age of 18 anyway, if he deems it strictly necessary. If your doctor has prescribed paroxetine for a patient under the age of 18 and you would like more information, please do not hesitate to contact him again. You should tell your doctor if any of the above symptoms appear or worsen while a patient under the age of 18 is taking paroxetine. Furthermore, the long-term safety effects of paroxetine related to growth, maturation and cognitive and behavioral development in this age group have not yet been demonstrated.
  • Thoughts of suicide and worsening of your depression or anxiety disorder. If you are depressed and / or have anxiety disorders, you can 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 take some time to work, usually around two weeks but sometimes longer. You may be more likely to have these kinds of thoughts if: either you have previously had thoughts about killing yourself or harming yourself or you are a young adult. Information from clinical trials has shown an increased risk of suicidal behavior in adults under the age of 25 with psychiatric disorders and treated with antidepressants. 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 friend or relative that you have depression or anxiety disorder 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 worried. regarding changes in his behavior.
  • if you feel restless, hyperactive or unable to sit or stand still (akathisia). This is most likely to happen within the first few weeks of treatment. If you experience such symptoms, do not hesitate to contact your doctor. In fact, in such cases, increasing the dose could be harmful.
  • if you have a certain syndrome (serotonin syndrome). This syndrome is characterized by a combination of symptoms such as: (extreme) agitation, confusion, irritability, seeing things that do not exist in reality (hallucinations), sweating, tremors or chills, marked reflexes, sudden onset of muscle spasms (myoclonus) , increased body temperature or soreness (see section 2, "Other medicines and Daparox"). If any of these symptoms occur at the same time, contact your doctor immediately and stop taking paroxetine.
  • if you have experienced (periods of) extreme euphoria or overexcitation resulting in unusual behavior (mania). The use of paroxetine could cause the transformation of a depressive phase into a manic phase. If a manic phase occurs, treatment with paroxetine should be discontinued.
  • if you have or have previously had severe liver or kidney problems. Dosage adjustment by your doctor is required.
  • if you have diabetes. Treatment with paroxetine may alter your blood sugar (glycaemia) values, so close monitoring is required. The dose of insulin and / or other oral antidiabetic drugs may need to be adjusted.
  • if you have or have had in the past from epilepsy or fits. Paroxetine can cause seizures (convulsions), so you will need special attention from your doctor. If you experience fits (fits) you should contact your doctor immediately. Treatment with paroxetine may need to be stopped.
  • if you have undergone electroconvulsive therapy (ECT). Clinical experience of concomitant administration of paroxetine with ECT is limited, therefore special caution is required from your physician.
  • if you have or have suffered from elevated intraocular pressure (glaucoma). Paroxetine can cause excessive dilation of the pupils (mydriasis), possibly resulting in increased pressure inside the eyeball. Your doctor will need to take special care.
  • if you suffer from cardiovascular diseases. The safety of using paroxetine has not been studied in patients with these conditions, so special precautions are needed by your doctor.
  • if you are an elderly patient, use other medicines or have liver problems (cirrhosis), as a result of which you are at high risk of a decrease in blood sodium levels. Paroxetine may further lower blood sodium levels, resulting in a feeling of weakness and fatigue. If this happens, consult your doctor.
  • if you have an increased tendency to bleed or are taking medicines which may increase the risk of bleeding. Examples in this sense are some drugs that are used to thin the blood (anticoagulants), some drugs used in the treatment of severe mental illness or nausea and vomiting (phenothiazines), certain drugs used in the treatment of schizophrenia (clozapine), aspirin (acetylsalicylic acid) and some drugs that fight pain and inflammation (NSAIDs, such as ibuprofen or COX-2 inhibitors). Paroxetine may cause abnormal bleeding, so special caution is required from your doctor (see section 2 , "Other Medicines and Daparox").
  • if you want to stop taking paroxetine. You may experience withdrawal symptoms, especially if you stop abruptly (see section 3, "If you stop taking Daparox"). Consult your doctor before stopping paroxetine treatment.

Interactions Which drugs or foods can modify the effect of Daparox

Some drugs may affect the effects of paroxetine, or the latter may affect their effects. Paroxetine may interact with:

  • drugs which, like paroxetine, can change the amount of serotonin in the brain, such as some drugs used in the treatment of depression or Parkinson's disease (MAOI such as moclobemide or isocarboxazid), some dietary supplements (L-tryptophan), some drugs used in the treatment of migraine (triptans, such as sumatriptan, almotriptan), some analgesics (tramadol, pethidine), drugs used in the treatment of infections (linezolid), a preoperative highlighting agent (methylene blue), other selective serotonin reuptake inhibitors ( SSRIs, such as fluoxetine, sertraline), some drugs used in the treatment of certain psychiatric conditions (lithium, risperidone), a certain drug used in the treatment of chronic pain or in anesthesia (fentanyl) and St. John's Wort (Hypericum perforatum) , natural remedy for depression. Concomitant use of these drugs may lead to the development of a serotonin syndrome (see section 2, "Do not take Daparox" and "Warnings and precautions").
  • some drugs used in the treatment of psychosis (pimozide). Studies investigating the simultaneous use of paroxetine and pimozide have shown how, in cases of concomitant use, paroxetine can cause an increase in the blood levels of pimozide. Since pimozide can prolong the QT interval (a QT interval is detectable on an electrocardiogram and its prolongation may cause irregular heartbeat) you should not take paroxetine together with pimozide (see section 2, "Do not take Daparox").
  • enzyme inhibitors, such as some drugs used to treat depression (clomipramine). It is likely that your doctor will decide to prescribe a lower dose than usual. If you are going to take paroxetine together with enzyme inducers (such as carbamazepine, rifampicin, phenobarbital and phenytoin) a lower starting dose is usually not required and your doctor will adjust subsequent doses based on the effects of the drug.
  • the combination of certain drugs used in the treatment of Human Immunodeficiency Virus (HIV) infection (fosamprenavir and ritonavir).
  • a certain drug, used in the treatment of Parkinson's disease (procyclidine). Potentiation of the efficacy, as well as side effects, of procyclidine may occur. If you experience side effects such as dry mouth, blurred vision, constipation and bladder emptying problems (urinary retention), you may need to see your doctor for advice. "possible reduction of the dose of procyclidine.
  • some drugs used in the treatment of epilepsy (anticonvulsants such as sodium valproate). Although a direct effect has not been shown, your doctor should be especially careful when prescribing paroxetine to epileptic patients.
  • drugs that are subjected to destruction by the same liver enzymes that metabolize paroxetine. Examples in this sense are: some drugs used in the treatment of depression (tricyclic antidepressants, such as desipramine), some drugs used in the treatment of severe mental illnesses, such as psychoses (perphenazine, thioridazine and risperidone), a certain drug used to treat affected children from ADHD (atomoxetine), some drugs used in the treatment of irregular heartbeat (such as flecainide and propafenone), a certain drug used in the treatment of chest pain (angina pectoris) and high blood pressure (metoprolol), finally some useful drugs in the treatment severe mental illness, or nausea and vomiting (phenothiazines). Potentiation of the efficacy and side effects of these drugs may occur. Paroxetine and thioridazine should not be taken together, due to the risk of serious side effects, such as irregular heart rhythm (see section 2, "Do not take Daparox") .
  • some drugs that prevent blood clotting (anti-coagulants, such as acenocoumarol, phenprocoumon). Potentiation of the efficacy and side effects of these drugs and increased risk of bleeding may occur. In these cases, closer monitoring by your physician is required and the dosage of anticoagulants may need to be adjusted (see section 2, "Warnings and Precautions").
  • a certain drug used in the treatment of breast cancer or fertility problems (tamoxifen).
  • drugs that increase the risk of bleeding. Examples of this are: some drugs useful in the treatment of severe mental illness or nausea and vomiting (phenothiazines, such as chlorpromazine, perphenazine), a drug used in the treatment of schizophrenia (clozapine), some drugs used in the treatment of depression (tricyclic antidepressants ), aspirin (acetylsalicylic acid) and drugs that fight pain and inflammation (NSAIDs, such as ibuprofen or COX-2 inhibitors, such as rofecoxib, celecoxib) (see section 2, "Warnings and precautions").
  • Medicines used to reduce the amount of acid in the stomach (such as cimetidine, omeprazole).

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Daparox with food, drink and alcohol

The concomitant intake of alcohol and paroxetine should be avoided.

The tablets should be taken in the morning with food.

Warnings It is important to know that:

Pregnancy, breastfeeding and fertility

If you are already taking paroxetine and realize you are pregnant, you should contact your doctor immediately. Also contact your doctor if you are planning a maternity leave. There are insufficient data to determine the safety and efficacy of paroxetine use during pregnancy. Some studies have suggested an increased risk of heart defects (e.g. ventricular septal defects (VSD, mostly) and atrial septal defects (ASD), conditions in which the partition of the heart chambers is damaged) in children whose mothers had taken paroxetine in the first three months of pregnancy. In agreement with your doctor, you may decide that it would be best to gradually stop taking paroxetine during pregnancy. However, taking into account your condition, your doctor may suggest, as a more appropriate choice for you, to continue taking the paroxetine. paroxetine.

Be sure to tell your midwife or doctor that you are taking paroxetine. When drugs such as paroxetine are taken during pregnancy, especially in the last three months, infants may increase the risk of developing persistent pulmonary hypertension of the newborn (PPHN), leading to the baby to breathe heavily and appear cyanotic. This usually occurs within the first 24 hours of birth. If this happens to your baby, contact your midwife and / or doctor immediately.

If you have taken paroxetine in the last 3 months of pregnancy, your baby may have other symptoms, which usually occur in the first 24 hours after birth. Symptoms include difficulty falling asleep or feeding, difficulty breathing, cyanosis or unstable body temperature, feeling sick (vomiting), constant crying, muscle stiffness or weakness, lethargy, shaking, nervousness or fits. If your baby has any. of these symptoms at birth and are concerned, ask your doctor for advice.

Paroxetine is excreted in breast milk in small quantities. If you are taking paroxetine, consult your doctor before you start breastfeeding. In agreement with your doctor, you may decide to breastfeed while using paroxetine.

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.

Paroxetine, in animal studies, has been shown to reduce sperm quality. In theory, this could affect fertility, but the impact on human fertility has not yet been observed.

Driving and using machines

There is no evidence on the influence of paroxetine on the ability to drive or use machines.

However, this medicine can cause side effects (such as blurred vision, feeling dizzy, sleepy or confused). If you get any of these side effects, do not drive, use machines, or do any other activities that require attention and concentration.

Daparox contains lactose

This medicinal product contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this drug.

Dosage and method of use How to use Daparox: Dosage

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

Paroxetine should preferably be taken in the morning with food. The tablets should be swallowed whole, without chewing.

Avoid taking alcohol together with Daparox.

The tablet can be divided into equal parts

The recommended dose is:

  • major depressive episode The recommended starting dose is one tablet (20 mg of paroxetine) once daily. In general, improvement in patients begins after one week but may become noticeable later (for example in the second week). In the event of an inadequate response, your doctor may decide to increase the dose, with gradual increases of 1⁄2 tablet (10 mg of paroxetine), up to a maximum of 2 and 1⁄2 tablets (50 mg of paroxetine) per day. .Your doctor will decide on the duration of the therapy, which could last for more than 6 months.
  • obsessive-compulsive disorder The recommended dose is 2 tablets (40 mg of paroxetine) per day, with a starting dose of 1 tablet (20 mg of paroxetine) per day. In case of inadequate response, your doctor may decide to gradually increase the dose, with gradual increases of 1⁄2 tablet (10 mg, of paroxetine) up to a maximum of 3 tablets (60 mg of paroxetine) per day. Your doctor will decide on the duration of the therapy, which could extend for a few months or longer.
  • panic disorder with or without agoraphobia The recommended dose is 2 tablets (40 mg paroxetine) per day, with a starting dose of 1⁄2 tablet (10 mg paroxetine) per day. In the event of an inadequate response, your doctor may decide to gradually increase the dose, with gradual increases of 1⁄2 tablet (10 mg of paroxetine), up to a maximum of 3 tablets (60 mg of paroxetine) per day. A low starting dose is recommended to avoid the potential worsening of panic symptoms at the start of treatment. Your doctor will decide how long you need to continue taking the tablets. The duration of therapy may be extended for a few months or longer. .
  • social anxiety disorder / social phobia The recommended dose is 1 tablet (20 mg of paroxetine) per day. In case of inadequate response, your doctor may decide to gradually increase the dosage, with gradual increases of 1⁄2 tablet ( 10 mg paroxetine), up to a maximum of 2 1⁄2 tablets (50 mg paroxetine) per day. Your doctor will decide how long you need to continue taking the tablets. The duration of therapy may be prolonged for a long time. period, during which it will be evaluated periodically.
  • generalized anxiety disorder The recommended dose is 1 tablet (20 mg of paroxetine) per day. In case of inadequate response, your doctor may decide to gradually increase the dosage, with gradual increases of 1⁄2 tablet (10 mg of paroxetine), up to a maximum of 2 1⁄2 tablets (50 mg paroxetine) per day. Your doctor will decide how long you need to continue taking the tablets. The duration of therapy may be prolonged for a long time, during which will be evaluated periodically.
  • PTSD The recommended dose is 1 tablet (20 mg of paroxetine) per day. In the event of an inadequate response, your doctor may decide to gradually increase the dose, with gradual increases of 1⁄2 tablet (10 mg of paroxetine), up to a maximum of 2 and 1⁄2 tablets (50 mg of paroxetine). day. Your doctor will decide how long you need to continue taking the tablets. The duration of therapy could be prolonged for a long period, during which it will be evaluated periodically.

Use in the elderly

The recommended starting dose for elderly patients is the same as the starting dose used in adults, but the maximum dose should not exceed 2 tablets (40 mg of paroxetine) per day.

Use in children and adolescents under the age of 18

Paroxetine should not be taken by children and adolescents under the age of 18 (see section 2, "Warnings and precautions").

Patients with impaired liver or kidney function

In the event of impaired liver or kidney function, dosage adjustment is required.

Duration of treatment

Depending on your condition, you may need to take paroxetine for a long time.

You must continue to take paroxetine for some time, even after the symptoms have disappeared, to make sure it does not come back. Never stop taking paroxetine without consulting your doctor. Abrupt discontinuation of paroxetine treatment could lead to withdrawal symptoms, therefore the dosage should be gradually reduced (see section 3, "If you stop taking Daparox").

Overdose What to do if you have taken too much Daparox

If you take more Daparox than you should

In the event of an overdose, contact your doctor immediately or go to the nearest hospital immediately. Show this leaflet and the remaining solution to your doctor. In addition to the known side effects (see section 4, "Possible side effects") you may experience the following symptoms: vomiting, pupil dilation, headache, fever, changes in blood pressure, agitation, anxiety, increased heart rate (tachycardia ) and uncontrollable shaking of the limbs (tremor).

If you forget to take Daparox

Do not take a double dose of paroxetine to make up for a forgotten dose. Skip the missed dose and take the next one at the usual time. If in doubt, always consult your doctor.

If you stop taking Daparox

Never stop taking paroxetine without consulting your doctor and never stop treatment abruptly, as this may cause withdrawal symptoms.

Symptoms that may occur after stopping paroxetine treatment include: dizziness, sensory disturbances (tingling or burning sensation, electric shock sensation), anxiety, sleep disturbances (including vivid dreams or nightmares) and headache. Less common effects include: agitation, nausea, tremor, confusion, sweating, emotional instability, visual disturbances, strong and rapid perception of the pulse (palpitations), diarrhea and irritability (see also section 4, "Possible side effects").

These symptoms usually occur in the first few days after stopping treatment, but can also occur in patients who have forgotten to take a dose. Withdrawal symptoms usually disappear within two weeks, but in some patients they may be more severe or persist for longer. a longer period (2-3 months or longer). If, in agreement with your doctor, you have decided to stop taking paroxetine, the daily dose should be gradually reduced over a few weeks or months (starting with reductions 10 mg per week.) You should always consult your doctor before reducing your dose.

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 Daparox

Like all medicines, Daparox can cause side effects, although not everybody gets them

Side effects can be:

  • Very common (may affect more than 1 in 10 people);
  • common (may affect up to 1 in 10 people);
  • uncommon (may affect up to 1 in 100 people);
  • rare (may affect up to 1 in 1000 people);
  • very rare (may affect up to 1 in 10,000 people).
  • not known: frequency cannot be estimated from the available data.

Blood (blood and lymphatic system disorders)

Uncommon: abnormal bleeding, especially skin contusions (ecchymosis).

Very rare: decrease in blood platelets, increasing the risk of haemorrhage or contusion (thrombocytopenia)

Immune system (immune system disorders)

Very rare: allergic reactions, accompanied by increasing itching and a painful skin rash (urticaria) or a severe reaction resulting in swelling of the skin, throat or tongue, difficulty breathing and / or itching (angioedema)

Hormones (Endocrine Disorders)

Very rare: fluid retention and low blood sodium levels as a consequence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Food (metabolic and nutrition disorders)

Common: increased blood cholesterol levels, decreased appetite.

Rare: low blood levels of sodium (hyponatremia), predominantly in elderly patients

Mental (psychiatric disorders)

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

Uncommon: confusion, seeing things that don't exist in reality (hallucinations).

Rare: (periods of) extreme euphoria or overexcitation, resulting in unusual behavior (mania, manic periods), anxiety, panic attacks, depersonalization, restlessness and hyperactivity accompanied by inability to sit or stand still (akathisia).

Frequency not known: Cases of self-harming or suicidal thoughts / behaviors have been reported during therapy with paroxetine or as soon as treatment is stopped (see section 2, "Warnings and precautions").

This symptomatology, however, could be due to the pathology from which he is affected.

Nerves (Nervous system disorders)

Very common: inability to concentrate.

Common: dizziness, feelings of insecurity (tremors), headache.

Uncommon: involuntary movements of the body or face (extrapyramidal disorders)

Rare: seizures, seizures (convulsions), irresistible need to move the legs (restless legs syndrome).

Very rare: so-called serotonin syndrome (symptoms of which may include agitation, confusion, sweating, seeing things that do not exist in reality (hallucinations), hyperreflexia, sudden onset of muscle spasms (myoclonus), chills, tremor and increased frequency heart beats (tachycardia))

Eyes (Eye disorders)

Common: blurred vision

Uncommon: enlargement of the pupils (mydriasis)

Very rare: sudden increase in intraocular pressure (acute glaucoma)

Ear (Ear and labyrinth disorders)

Frequency not known: ringing in the ear (tinnitus).

Heart (Cardiac disorders)

Uncommon: accelerated heart rate (sinus tachycardia)

Rare: slow heart rate (bradycardia)

Blood vessels (Vascular disorders)

Uncommon: transient rise or fall in blood pressure, sudden fall in blood pressure after standing up (postural hypotension)

Airways (Respiratory, thoracic and mediastinal disorders)

Common: yawn

Stomach and intestine (Gastrointestinal disorders)

Very common: nausea

Common: constipation, diarrhea, vomiting, dry mouth

Very rare: gastrointestinal bleeding

Liver (Hepatobiliary disorders)

Rare: increase in liver enzymes

Very rare: liver disorders, such as inflammation (hepatitis), sometimes associated with jaundice and / or liver failure

Skin (Skin and subcutaneous tissue disorders)

Common: sweating

Uncommon: skin rash, pruritus

Very rare: severe skin side effects (including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis), sensitivity to sunlight (photosensitivity reactions)

Muscles (Musculoskeletal and connective tissue disorders)

Rare: muscle pain (myalgia), joint pain (arthralgia)

Kidneys (Renal and urinary disorders)

Uncommon: problems with emptying the bladder (urinary retention) and uncontrollable and involuntary passing of urine (urinary incontinence)

Genitals and mammaries (Reproductive system and breast disorders)

Very common: sexual dysfunction, such as ejaculation problems, decreased desire, male impotence and inability to reach orgasm

Rare: increased blood concentration of the hormone prolactin (hyperprolactinaemia), which can cause abnormal milk production (galactorrhea) in both men and women

Very rare: painful erection (priapism)

General (General Disorders and Administration Site Conditions)

Common: weight gain, general tired feeling with loss of muscle strength (asthenia)

Very rare: edema of arms and / or legs (peripheral edema)

Withdrawal symptoms observed following discontinuation of paroxetine treatment

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

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

Generally, such events are mild and self-limiting. Never stop taking paroxetine without first consulting your doctor and never stop treatment abruptly, as you may experience withdrawal symptoms (see section 3, "If you stop taking Daparox").

In cases of administration of paroxetine to children and adolescents under the age of 18, more than 1 in 100 but less than 1 in 10 children / adolescents experienced one of the following side effects: emotional lability (including crying and mood swings ), self-injurious behavior, suicide attempts and suicidal thoughts, hostile or acrimonious behavior, loss of appetite, tremor, abnormal sweating, hyperactivity, agitation, nausea, abdominal pain and nervousness.

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

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

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 and carton after "EXP". The first two digits indicate the month and the last four digits indicate the year. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

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 Daparox contains

  • The active ingredient is paroxetine (as mesylate). One tablet contains paroxetine mesylate, equivalent to 20 mg of paroxetine.
  • The other ingredients are: - Core: anhydrous dibasic calcium phosphate, sodium starch glycolate (type A), magnesium stearate. - Coating: lactose monohydrate, hypromellose, macrogol 4000, titanium dioxide (E171), yellow iron oxide (E172) and red iron oxide (E172). (see section 2, "Daparox contains lactose")

What Daparox looks like and contents of the pack

Daparox tablets are round, yellow, film-coated, embossed with "POT 20" on one side and a score line on both sides.

Daparox 20 mg is available in cartons of 10, 12, 14, 20, 28, 30, 50, 56, 60 or 100 tablets in blisters and in a container of 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.

Further information on Daparox 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 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 primary packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER 08.0 MARKETING AUTHORIZATION NUMBER CIO 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIO DRUGS, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON PREPARATION AND QUALITY CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

DAPAROX 20 MG TABLETS COATED WITH FILM

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains paroxetine mesylate equivalent to 20 mg of paroxetine base.

Excipients with known effects:

Each tablet contains 3.81 mg of lactose monohydrate

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Film-coated tablet.

Round, yellow, film-coated tablets embossed with the code "POT 20" on one side and scored on both sides.

The tablet can be divided into equal halves.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Treatment of:

• episode of major depression

• 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

It is recommended that paroxetine be given once daily in the morning with food. The tablets should be swallowed rather than chewed.

MAJOR DEPRESSION EPISODE

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 dose of 20 mg, 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 steps 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).

PANIC DISORDER

The recommended dose is 40 mg per day. Patients should be started on a dose of 10 mg per day and the dose may be gradually increased in 10 mg increments until the recommended dose is reached, 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).

SOCIAL ANXIETY / SOCIAL PHOBIA 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).

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).

POST-TRAUMATIC STRESS 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).

GENERAL INFORMATIONS

WITHDRAWAL SYMPTOMS OBSERVED AFTER WITHDRAWAL OF PAROXETINE TREATMENT

Abrupt discontinuation of treatment should be avoided (see sections 4.4 and 4.8).

In the tapering regimen used in clinical trials, a tapering of the daily dose of 10 mg, at weekly intervals, was used.

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 in a manner that more gradual.

Special populations

• Senior citizens

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

Treatment should begin at the same starting 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 under 18 years of age 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 sections 4.4 and 4.8).

• 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 of creatinine.

04.3 Contraindications

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

Paroxetine is contraindicated in combination with monoamine oxidase inhibitors (MAOIs). In exceptional circumstances, linezolid (an antibiotic that is a reversible, non-selective monoamine oxidase inhibitor) can be given in combination with paroxetine if the conditions exist for careful control of symptoms of the serotonin syndrome and for monitoring of serotonin syndrome. blood pressure (see section 4.5).

Paroxetine treatment can be initiated:

• two weeks after stopping treatment with a non-reversible MAOI or

• at least 24 hours after stopping treatment with a reversible MAOI (eg moclobemide, linezolid, methylthioninium chloride (methylene blue a non-selective reversible MAOI used as a preoperative highlighting agent)).

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

Paroxetine should not be used in combination with thioridazine as, as with other CYP450 2D6 hepatic enzyme inhibitors, paroxetine may elevate plasma thioridazine levels (see section 4.5).

Administration of thioridazine alone may 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).

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 sections 4.3 and 4.5).

For use by children and adolescents under the age of 18

Paroxetine should not be used to treat children and adolescents under 18 years of age. Suicidal behaviors (suicide attempts and suicidal ideation) and hostility (essentially 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 need, a decision to treat is made, the patient should be closely monitored for the appearance of suicidal symptoms. Furthermore, long-term safety data for children and adolescents are not available with regard to growth, maturation and cognitive and behavioral development.

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. Therefore, the same precautions followed when treating patients with major depressive disorder should be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events, or who exhibit a significant degree of suicidal ideation prior to initiation of treatment, are known to have an increased risk of suicidal thoughts or suicide attempts, and should be closely monitored during treatment. A meta-analysis of clinical trials, conducted in adult patients with psychiatric disorders treated with antidepressant drugs compared with placebo, showed an increased risk of suicidal behavior in the age group below 25 years of patients treated with antidepressants compared to placebo.

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 (and caregivers) should be advised of the need to monitor and report immediately to their physician any clinical worsening, the onset of suicidal behavior or thoughts, and unusual behavioral changes.

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 dose may be harmful.

Serotonin syndrome / neuroleptic malignant syndrome

On rare occasions, serotonin syndrome or neuroleptic malignant syndrome-like events have been reported in association with paroxetine treatment, particularly when administered concomitantly with other serotonergic and / or neuroleptic drugs. Since these syndromes can involve 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 nervous system imbalances with possible rapid fluctuation of vital 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 and 4.5).

Mania

Like 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 impairment

Caution is recommended in patients with severe renal impairment or in patients with hepatic impairment (see section 4.2).

Diabetes

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

Epilepsy

Like 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

Like other SSRIs, paroxetine rarely causes mydriasis and should be used with caution in patients with narrow-angle glaucoma or a history of glaucoma.

Cardiac pathologies

In patients with heart disease 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, for example gastrointestinal haemorrhages, have been reported.

Elderly patients may be at increased risk.

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, phenothiazines, 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.

Interaction with Tamoxifen

Some studies have shown that the efficacy of tamoxifen, as measured by the risk of breast cancer recurrence / mortality, may be reduced when prescribed with paroxetine as a result of irreversible inhibition of CYP2D6 by paroxetine (see section 4.5). . Whenever possible paroxetine should be avoided while using tamoxifen when it is used for the treatment or prevention of breast cancer.

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).

In clinical trials, adverse events observed with discontinuation of treatment occurred in 30% of patients taking paroxetine, compared with 20% of patients taking placebo. The onset of withdrawal symptoms is not the same as in the previous which 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, the intensity of these symptoms is mild to moderate, however in some patients they may be severe. They usually appear within the first few days of stopping treatment, but there have been very rare cases in which they have appeared in patients who inadvertently skipped. Usually these symptoms are self-limiting, and usually resolve within two weeks, although in some individuals they may last longer (2-3 months or more). It is therefore recommended that the dose of paroxetine be gradually reduced when treatment is discontinued, over a period of several weeks or months, as needed by the patient (see section 4.2).

Lactose

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

04.5 Interactions with other medicinal products and other forms of interaction

Serotonergic drugs

As with other selective serotonin reuptake inhibitors (SSRIs), co-administration of serotonergic drugs may lead to 5HT-associated effects (serotonin syndrome: see sections 4.3 and 4.4). Caution should be exercised, and closer clinical monitoring is also required, when serotonergic drugs (such as L-tryptophan, triptans, tramadol, linezolid, methylthioninium chloride (methylene blue), SSRIs, lithium, pethidine and hypericum preparations or St. John's wort - Hypericum perforatum) are administered concomitantly with paroxetine. Caution should also be exercised in cases of use of fentanyl, administered under general anesthesia or in the treatment of chronic pain.

The concomitant use of MAOIs is contraindicated due to the risk of serotonin syndrome (see section 4.3).

Pimozide

Increases in blood levels of pimozide on average 2.5-fold were demonstrated during a study in which a single low dose of pimozide (2mg) was co-administered with 60mg of paroxetine. This is due to the known inhibitory properties of paroxetine on the CYP2D6 enzyme. The concomitant use of pimozide and paroxetine is contraindicated, due to the narrow therapeutic index of pimozide and the known possibility of pimozide to prolong the QT interval (see section 4.3 ).

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 paroxetine doses lower than the dose range should be considered.

When concomitantly administered with drugs known to induce enzyme metabolism (e.g. carbamazepine, rifampicin, phenobarbital, phenytoin) or fosamprenavir / ritonavir, no starting dose adjustment is required. Any modification of the paroxetine posology (either after initiation of treatment with an enzyme inducer or following its discontinuation) should be based on clinical response (tolerability and efficacy).

Fosamprenavir / ritonavir

Co-administration of fosamprenavir / ritonavir 700/100 mg twice daily with 20 mg paroxetine once daily to healthy volunteers for 10 days demonstrated a significant decrease in plasma paroxetine levels of approximately 55%. Plasma levels of fosamprenavir / ritonavir during concomitant treatment with paroxetine were similar to the reference values ​​used in other studies, indicating that paroxetine has no significant effect on the metabolism of fosamprenavir / ritonavir. No data are available on the effects of long-term co-administration of paroxetine with fosamprenavir / ritonavir exceeding 10 days.

Procyclidine

Daily administration of paroxetine significantly increases the 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), risperidone, atomoxetine, some Type 1 C antiarrhythmics (e.g. propafenone and flecainide) and metoprolol is not recommended. the use of paroxetine in combination with metoprolol, administered in heart failure, due to the reduced therapeutic index of metoprolol in this indication.

Tamoxifen has an important active metabolite, endoxifen, which is produced by CYP2D6 and contributes significantly to the efficacy of tamoxifen. Irreversible inhibition of CYP2D6 by paroxetine may lead to decreased plasma concentrations of endoxifen (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. Concomitant use of paroxetine and oral anticoagulants may lead to increased anticoagulant activity and the risk of bleeding. Therefore paroxetine should be used with caution in patients receiving oral anticoagulants (see section 4.4).

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 haemorrhage (see section 4.4).

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, phenothiazines, 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.

04.6 Pregnancy and lactation

Fertility

Animal data have shown that paroxetine can affect sperm quality (see section 5.3). In vitro data on human material show some effect on sperm quality, however, in humans patients treated with SSRIs (including paroxetine) have shown that the effect on sperm quality is reversible. No impact on fertility has been observed so far.

Pregnancy

Some epidemiological studies have indicated an increased risk of congenital malformations, particularly cardiovascular (eg, ventricular and atrial septal defects) associated with the use of paroxetine 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 expected risk, equal to about 1/100, 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 "Discontinuation symptoms observed following discontinuation of paroxetine", section 4.2).

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: breathing difficulties, cyanosis, apnea, seizures, unstable temperature, difficulty in feeding, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia , tremor, agitation, irritability, lethargy, constant crying, sleepiness and difficulty falling asleep. These symptoms may 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 selective serotonin reuptake inhibitors (SSRIs) during pregnancy, particularly in late pregnancy, may cause an increased risk of persistent pulmonary hypertension of the newborn (PPHN). The observed risk it has been about 5 cases per 1000 pregnancies.In the general population, 1 to 2 cases of PPHN per 1000 pregnancies occur.

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).

Feeding time

Small amounts of paroxetine are excreted in breast milk. In published studies, serum concentrations in breastfed infants were undetectable (sign of drug effect. As no effect is expected, breastfeeding can be considered.

04.7 Effects on ability to drive and use machines

There is no evidence on the influence of paroxetine on the ability to drive and use machines. 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 class 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 (mostly ecchymosis).

Very rare: thrombocytopenia.

Disorders of the immune system

Very rare: allergic reactions (including urticaria and angioedema).

Endocrine pathologies

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

Metabolism and nutrition disorders

Common: increased cholesterol levels, decreased appetite.

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.

Frequency not known: Cases of suicidal ideation and suicidal behaviors have been reported during paroxetine therapy or as soon as treatment is discontinued (see section 4.4).

These symptoms may be due to the underlying disease.

Nervous system disorders

Very common: impaired concentration.

Common: dizziness, tremors, headache.

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).

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.

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, liver-related events (such as hepatitis, sometimes associated with jaundice and / or liver failure) have also been reported very rarely. Discontinuation of treatment should be considered in the event of a prolonged increase. of liver function test values.

Skin and subcutaneous tissue disorders

Common: sweating.

Uncommon: skin rash, pruritus.

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

Musculoskeletal and connective tissue disorders

Rare: arthralgia, myalgia.

Epidemiological studies, mainly conducted in patients aged 50 and over, show an increased risk of bone fractures in patients taking selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). The mechanism leading to this risk is not known.

Renal and urinary disorders

Uncommon: urinary retention, urinary incontinence.

Diseases of the reproductive system and breast

Very common: sexual dysfunction.

Rare: hyperprolactinaemia / galactorrhea.

Very rare: priapism.

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.

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 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 sections 4.2 and 4.4).

ADVERSE EVENTS OBSERVED DURING CLINICAL STUDIES IN PEDIATRIC AGE PATIENTS

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

Additional observed events are: decreased appetite, tremor, sweating, hyperkinesia, agitation, emotional lability (including crying and mood swings), bleeding, mostly of the skin and mucous membranes.

Symptoms observed after stopping / reducing 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. and precautions for use).

See section 5.1 for further information on pediatric clinical studies.

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", vomiting, mydriasis, fever, changes in blood pressure, headache, involuntary muscle contractions, agitation, anxiety and tachycardia have been reported. .

Patients generally recovered without serious consequences 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. Where appropriate, gastric emptying by induction of emesis or gastric lavage or both should be performed. After emptying, activated charcoal may be administered, 20 or 30 g every 4-6 hours during the first 24 hours after ingestion. Supportive therapy with careful observation and frequent monitoring of vital signs is indicated.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: antidepressants - selective serotonin reuptake inhibitors, ATC code: N06A B05

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 agreement with this selectivity of action, some studies in vitro showed that, unlike tricyclic antidepressants, paroxetine has low affinity for alpha1, alpha2 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 depressant effects of ethanol. Like other selective serotonin reuptake inhibitors, paroxetine causes symptoms related to excessive stimulation of the serotonin receptor when administered to animals previously treated with inhibitors. monoamine oxidase (MAO) or tryptophan.

Behavioral and EEG studies indicate that paroxetine is weakly activating at doses generally greater than those required to inhibit serotonin reuptake. Activating properties are not inherently "amphetamine-like". Animal studies indicate that. paroxetine is well tolerated by the cardiovascular system. Paroxetine does not cause clinically 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 the tendency to suicidal behavior in adults

An analysis, specific for paroxetine, performed in placebo-controlled clinical trials in adult patients with psychiatric disorders showed a higher frequency of suicidal behavior in young adults (18-24 years of age) treated with paroxetine compared to those treated with placebo (2.19% vs 0.92%). This increase was not observed in older age groups. In adults with major depressive disorder (belonging to all ages), an increase in frequency of behavior was observed. suicidal in paroxetine-treated versus placebo-treated patients (0.32% vs 0.05%); all of these events were suicide attempts. However, the majority of these cases of paroxetine suicide attempt (8 out of 11) affected young adults (see also section 4.4).

Dose-response relationship

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 reported in patients treated with paroxetine with a frequency of at least 2% of patients and these events have occurred with at least twice as high an incidence 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, which were observed more frequently in the group treated with paroxetine compared to that treated with placebo, were: decrease d appetite, tremor, sweating, hyperkinesis, agitation, emotional lability (including crying and mood fluctuations).

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 higher incidence than 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 warnings and precautions for use).

In 5 parallel group studies, whose treatment duration ranged from 8 weeks to 8 months, bleeding-related adverse events, mainly of the skin and mucous membranes, were observed with a frequency of 1.74% in patients treated with paroxetine. compared with 0.74% of 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).

The passage into human breast milk, and into the fetuses of laboratory animals, occurs in small quantities.

Biotransformation

The main metabolites of paroxetine are polar and conjugated products of oxidation and methylation, which are readily eliminated. 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% of the dose, 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. Therefore paroxetine is almost completely eliminated by metabolism.

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

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

Special patient populations

Elderly and subjects with renal / hepatic impairment

Increased plasma concentrations of paroxetine have been observed in elderly subjects and in subjects with severe renal impairment and in subjects with hepatic impairment, 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 for lipophilic amines, including tricyclic antidepressants, phospholipidosis was detected in rats. Phospholipidosis was not observed in primate studies, lasting up to one year, at doses six times higher than the recommended clinical dose range.

Carcinogenicity: In two-year studies conducted 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, higher infant mortality and delayed ossification were observed. The latter effects are likely related to maternal toxicity and are not considered to be a direct effect on the fetus / neonate.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Nucleus:

anhydrous dibasic calcium phosphate

sodium carboxymethyl starch (type A)

magnesium stearate

Coating:

lactose monohydrate

hypromellose

macrogol 4000

titanium dioxide (E171)

yellow iron oxide (E172)

red iron oxide (E172)

06.2 Incompatibility

Not relevant.

06.3 Period of validity

3 years.

06.4 Special precautions for storage

This medicine does not require any special storage conditions.

06.5 Nature of the immediate packaging and contents of the package

Cardboard boxes containing 10, 12, 14, 20, 28, 30, 50, 56, 60 or 100 tablets in:

blister of PVC / PE / PVDC / Al or

blister by Al / Al

HDPE container containing 500 tablets

Not all pack sizes may be marketed

06.6 Instructions for use and handling

Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.

07.0 MARKETING AUTHORIZATION HOLDER

Synthon BV - Microweg 22 - 6545 CM Nijmegen - The Netherlands

08.0 MARKETING AUTHORIZATION NUMBER

Blister of PVC / PE / PVDC / Al:

AIC 035444013 / M - Box of 10 tablets

AIC 035444025 / M - Box of 14 tablets

AIC 035444114 / M - Box of 20 tablets

AIC 035444037 / M - Box of 28 tablets

AIC 035444049 / M - Box of 30 tablets

AIC 035444126 / M - Box of 50 tablets

AIC 035444138 / M - Box of 56 tablets

AIC 035444052 / M - Box of 60 tablets

AIC 035444140 / M - Box of 100 tablets

Blister by Al / Al:

AIC 035444064 / M - Box of 10 tablets

AIC 035444076 / M - Box of 14 tablets

AIC 035444153 / M - Box of 20 tablets

AIC 035444088 / M - Box of 28 tablets

AIC 035444090 / M - Box of 30 tablets

AIC 035444165 / M - Box of 50 tablets

AIC 035444177 / M - Box of 56 tablets

AIC 035444102 / M - Box of 60 tablets

AIC 035444189 / M - Box of 100 tablets

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

Date of first authorization: 08/08/2002

Date of most recent renewal: 23/10/2010

10.0 DATE OF REVISION OF THE TEXT

December 2012

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL

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