Serestill

PACKAGE LEAFLET: INFORMATION FOR THE USER

SERESTILL 10 mg/ml oral drops solution

paroxetine
Read this entire leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor. See section 4.

Contents of this leaflet:

1. What SERESTILL is and what it is used for
2. What you need to know before taking SERESTILL
3. How to take SERESTILL
4. Possible side effects
5. How to store SERESTILL
6. Contents of the pack and other information

1. WHAT SERESTILL IS AND WHAT IT IS USED FOR

SERESTILL is a treatment for adults with depression and/or anxiety disorders. The anxiety disorders for which treatment with SERESTILL is indicated are as follows: obsessive-compulsive disorder (repetitive, obsessive thoughts with uncontrollable behaviour), panic disorder (panic attacks, including those caused by agoraphobia, i.e. fear of open spaces), social anxiety disorder (fear of or avoidance of social situations), post-traumatic stress disorder (anxiety caused by a traumatic event), and generalized anxiety disorder (feeling excessively anxious or nervous in general).
SERESTILL belongs to a group of medicines called SSRIs (selective serotonin reuptake inhibitors).
Every person has a substance in the brain called serotonin. People who are depressed or anxious have lower levels of serotonin than others. It is not fully understood how SERESTILL and other SSRIs work, but they may be helpful by increasing the level of serotonin in the brain.
Proper treatment of depression and anxiety disorders is important to help you feel better.

2. WHAT YOU SHOULD KNOW BEFORE TAKING SERESTILL

Do not take SERESTILL:

• If you are allergic to paroxetine or any of the ingredients of this medicine (listed in section 6).
• If you are taking medicines called monoamine oxidase inhibitors (MAOIs, including moclobemide and methylthioninium chloride (methylene blue)), or have taken them within the last two weeks. Your doctor will advise you on how to start taking SERESTILL after stopping the MAOI.
• If you are taking an antipsychotic medicine called thioridazine or an antipsychotic called pimozide.
• If any of these cases apply to you, speak with your doctor before taking SERESTILL.

Warnings and precautions
Talk to your doctor or pharmacist before taking SERESTILL

• If you are taking other medicines (read “Other medicines and SERESTILL”).
• If you have kidney, liver, or heart problems.
• If you have epilepsy or have had seizures or convulsions.
• If you have episodes of mania (manic behaviours or thoughts).
• If you are undergoing electroconvulsive therapy (ECT).
• If you have previously experienced bleeding or are taking other medicines that may increase the risk of bleeding (these include medicines used to thin the blood, such as warfarin, antipsychotics such as perphenazine or clozapine, tricyclic antidepressants, medicines used for pain and inflammation called non-steroidal anti-inflammatory drugs or NSAIDs, such as acetylsalicylic acid, ibuprofen, celecoxib, etodolac, diclofenac, meloxicam) or if you are pregnant (see "Pregnancy, breastfeeding and fertility").
• If you are taking tamoxifen for the treatment of breast cancer or fertility problems, SERESTILL may make tamoxifen less effective; therefore, your doctor may recommend you take another antidepressant.
• If you have diabetes.
• If you are on a low-sodium diet.
• If you have glaucoma (increased eye pressure).
• If you are pregnant or planning to become pregnant (see Pregnancy, breastfeeding and fertility within this leaflet).
• If you are under 18 years of age (see Children and adolescents under 18 years, within this leaflet).

In these cases, and if you have not already discussed them with your doctor, consult your doctor and ask what you should do regarding taking SERESTILL.
Children and adolescents under 18 years
SERESTILL must not be used in children and adolescents under 18 years of age.
Furthermore, patients under 18 years of age have an increased risk of adverse effects such as suicide attempts, suicidal thoughts, and hostility (mainly aggression, oppositional behaviour, and anger) when taking SERESTILL. If your doctor has prescribed SERESTILL for you (or for your child) and you wish to discuss this, consult your doctor. You must inform your doctor if any of the symptoms listed above appear or worsen while you (or your child) are taking SERESTILL.
In addition, in this age group, the long-term effects of SERESTILL on growth, maturation, and cognitive and behavioural development have not yet been established.
In clinical studies with SERESTILL in patients under 18 years of age, the common adverse effects occurring in fewer than 1 in 10 children/adolescents were: increased suicidal thoughts and suicide attempts, deliberate self-harm, hostile attitude, aggressive or unfriendly behaviour, loss of appetite, tremors, abnormal sweating, hyperactivity (excess energy), agitation, emotional changes (including crying and mood changes), and unusual bruising or bleeding (such as nosebleeds). These studies also showed that similar symptoms occurred in children and adolescents taking sugar pills (placebo) instead of SERESTILL, although less frequently.
In these studies conducted in patients under 18 years of age, some patients experienced withdrawal symptoms after stopping SERESTILL. These symptoms were mostly similar to those observed in adults after discontinuation of SERESTILL (see section 3, How to take SERESTILL, within this leaflet). In addition, patients under 18 years of age commonly (in fewer than 1 in 10 cases) also experienced stomach pain, feeling nervous, and emotional changes (including crying, mood changes, self-harm attempts, suicidal thoughts, and suicide attempts).
Suicidal thoughts and worsening of depression or anxiety disorder
If you are depressed and/or have anxiety disorders, you may sometimes have self-harming or suicidal thoughts. These may increase when you first start taking antidepressants, as these medicines take time to work, usually about two weeks but sometimes longer. You may be more prone to these thoughts:

• If you have previously had suicidal or self-harming thoughts.
• If you are a young adult. Clinical studies have shown an increased risk of suicidal behaviour in adults under 25 years of age with psychiatric disorders treated with an antidepressant. If at any time you experience suicidal or self-harming thoughts, contact your doctor or go immediately to hospital. You may find it helpful to talk to a friend or relative about your 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 worsening or if they are concerned about changes in your behaviour.

Important adverse effects observed with SERESTILL
Some patients taking SERESTILL experience a condition called akathisia, meaning they feel restless and unable to sit or stand still. Other patients may develop serotonin syndrome or neuroleptic malignant syndrome, which may include some or all of the following symptoms: intense restlessness or irritability, confusion, agitation, feeling hot, sweating, tremors, chills, hallucinations (strange visions or sounds), muscle rigidity, sudden muscle contractions, or rapid heartbeat. Severity may increase, leading to loss of consciousness. If you experience any of these symptoms, contact your doctor. For more information on these or other side effects of SERESTILL, see section 4, Possible side effects, within this leaflet.
Medicines such as SERESTILL (so-called selective serotonin reuptake inhibitors (SSRIs)) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms may persist after discontinuation of treatment.
Other medicines and SERESTILL
Some medicines may affect the action of SERESTILL or increase the risk of adverse effects. SERESTILL may also affect the action of other medicines. These include:

• Medicines called monoamine oxidase inhibitors (MAOIs, including moclobemide and methylthioninium chloride (methylene blue)). See “Do not take SERESTILL” within this leaflet.
• Thioridazine or pimozide, antipsychotic medicines. See “Do not take SERESTILL” within this leaflet.
• Acetylsalicylic acid, ibuprofen, and other medicines called NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) such as celecoxib, etodolac, diclofenac, meloxicam, and rofecoxib, used for pain and inflammation.
• Tramadol, buprenorphine, or pethidine, painkillers.
• Medicines called triptans such as sumatriptan, used to treat migraine.
• Other antidepressants, including other SSRIs and tricyclic antidepressants such as clomipramine, nortriptyline, and desipramine.
• A dietary supplement called tryptophan.
• Mivacurium and succinylcholine (used in anaesthesia).
• Medicines such as lithium, risperidone, perphenazine, clozapine (called antipsychotics or neuroleptics) used to treat certain psychiatric disorders.
• St. John’s wort, an herbal remedy for depression.
• Atomoxetine used to treat attention deficit hyperactivity disorder (ADHD).
• Phenobarbital, phenytoin, or carbamazepine used to treat seizures or epilepsy.
• Procyclidine, used to relieve tremors, especially in Parkinson’s disease.
• Warfarin or other medicines (called anticoagulants) used to thin the blood.
• Propafenone, flecainide, and medicines used for arrhythmias (irregular heartbeat).
• Metoprolol, a beta-blocker used to treat high blood pressure and heart conditions.
• Pravastatin, used to treat high cholesterol levels.
• Rifampicin, used to treat tuberculosis (TB) and leprosy.
• Linezolid, an antibiotic.
• Fentanyl, used in anaesthesia or for treating chronic pain.
• A combination of fosamprenavir and ritonavir, used to treat Human Immunodeficiency Virus (HIV) infection.
• Tamoxifen, used for the treatment of breast cancer or fertility problems.

If you are taking a medicine from this list, and have not yet discussed it with your doctor, consult your doctor and ask what to do. It may be necessary to adjust the dosage or change the medicine.
If you are taking any other medicine, even those without a prescription, ask your doctor or pharmacist before taking SERESTILL. They will be able to advise you whether taking SERESTILL is safe in these circumstances.
Taking SERESTILL with alcohol
Do not drink alcohol while taking SERESTILL. Alcohol may worsen your symptoms or side effects.
Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine. In newborns whose mothers took SERESTILL during the first months of pregnancy, there has been evidence of an increased risk of birth defects, particularly heart defects. In the general population, about 1 in 100 babies is born with a heart defect. This risk increases to 2 in 100 babies in mothers who took SERESTILL.
You and your doctor will decide whether it is better for you to switch to another treatment or gradually discontinue SERESTILL during pregnancy. However, based on your clinical condition, your doctor may advise that it is better to continue taking SERESTILL.
If you take SERESTILL close to the end of pregnancy, there may be an increased risk of heavy vaginal bleeding shortly after delivery, especially if you have bleeding disorders. Inform your doctor or midwife that you are taking SERESTILL so they can advise you on what to do.
Make sure your midwife or doctor knows that you are taking SERESTILL.
When medicines such as SERESTILL are taken during pregnancy, particularly during the last three months, they may increase the risk in the baby of a serious condition called persistent pulmonary hypertension of the newborn (PPHN). In PPHN, the blood pressure in the blood vessels between the newborn’s heart and lungs is too high. If you take SERESTILL during the last three months of pregnancy, your baby may also experience other symptoms, usually appearing within the first 24 hours after birth.
These symptoms include:

• Breathing difficulties.
• Bluish, too hot, or too cold skin.
• Blue lips.
• Vomiting or feeding difficulties.
• Lethargy, inability to sleep, or excessive crying.
• Stiff or floppy muscles.
• Tremors, nervousness, or seizures.
• Exaggerated reflexes.

If your baby shows any of these symptoms at birth or you are concerned about your baby’s health, contact your doctor or midwife for assistance.
SERESTILL may pass into breast milk in very small amounts. If you are taking SERESTILL, consult your doctor before starting breastfeeding. You and your doctor may decide that you can breastfeed while taking SERESTILL.
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
SERESTILL may cause dizziness, confusion, drowsiness, and vision disturbances. If you experience these side effects, do not drive and do not operate machinery.
SERESTILL contains

• This product contains sucrose. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine. It may be harmful to teeth.
• This medicine contains 26.4 mg/ml of alcohol (ethanol) in each ml, equivalent to 3.3% v/v. Each 2 ml dose (20 mg paroxetine) contains 52.8 mg of ethanol, and each 6 ml dose (60 mg paroxetine) contains 158.4 mg of ethanol. The amount in a 1 ml dose of this medicine is equivalent to less than 1 ml of beer or 0.3 ml of wine (6 ml equivalent to 4 ml of beer or 1.6 ml of wine). The small amount of alcohol in this medicine will not produce significant effects.
• This medicine contains 0.001 g of benzoate salt per ml, equivalent to 0.002 g/2 ml (20 mg paroxetine) or 0.006 g/6 ml (60 mg paroxetine). Benzoate salt may increase jaundice (yellowing of the skin and eyes) in newborns up to 4 weeks of age.
• This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially 'sodium-free'.
• This product does not contain gluten and can be taken by people with coeliac disease.

3. HOW TO TAKE SERESTILL

Take SERESTILL drops, diluted in water, in the morning with breakfast.
It is important to take the medicine as prescribed by your doctor, who will advise you on the appropriate dose
to take when you first start using SERESTILL. Most people begin to feel better after a couple of weeks. If you do not start to feel better after this time,
inform your doctor, who may decide to gradually increase the dose, up to the maximum allowed daily dose.
The usual doses for the different indications are shown in the table below.

Your doctor will inform you about the daily dose and how long you should take the medicine. This may be for several months or longer.

Elderly patients
The maximum allowed dose for people over 65 years of age is 4 ml per day.

Patients with hepatic or renal impairment
If you have severe liver or kidney problems, your doctor may decide that you might need a lower than normal dose.

If you take more SERESTILL than you should
Do not take more medicine than your doctor has recommended. If you or someone else takes too many drops of SERESTILL, in addition to the symptoms listed in Section 4 “POSSIBLE UNDESIRABLE EFFECTS”, you may experience vomiting, dilated pupils, fever, changes in blood pressure, headache, involuntary muscle contractions, agitation, anxiety, and faster than normal heartbeat.

In any case, inform your doctor or go immediately to hospital, taking the medicine bottle with you.

If you forget to take SERESTILL
Take the medicine at the same time every day. If you forget to take a dose and remember before going to sleep, take it immediately and continue your treatment as usual the next day. If you remember only during the night or the following day, do not take the missed dose. You may experience withdrawal symptoms, but these will disappear once you have taken your usual dose at the regular time. Do not take a double dose to make up for the forgotten dose.

What you should do if you are not improving
STILIDEN will not improve your symptoms immediately; all antidepressants require time to take effect. Some people start to feel better within a couple of weeks, while others may need more time. If you have not started to improve after a couple of weeks, see your doctor, who will advise you on what to do. Some people taking antidepressants feel worse before they begin to improve. Your doctor should review you a couple of weeks after you have started treatment. Inform your doctor if you have not started to improve.

If you stop treatment with SERESTILL
Do not stop treatment with SERESTILL until your doctor advises you to do so. When you discontinue treatment, your doctor will help you gradually reduce the dose over several weeks or months to reduce the risk of withdrawal effects. One way to do this is to gradually reduce your SERESTILL dose by 10 mg per week. Most people find that withdrawal symptoms are mild and disappear spontaneously within two weeks. For some people, these symptoms may be more severe or last longer.

If you experience withdrawal effects when stopping the drops, your doctor may decide to discontinue the medicine more slowly. If you experience severe withdrawal effects when stopping SERESTILL, contact your doctor. Your doctor may ask you to restart taking the drops and discontinue treatment more gradually. Despite withdrawal effects, you will still be able to stop taking SERESTILL.

Possible withdrawal effects when stopping treatment
Studies show that 3 out of 10 patients report one or more symptoms when stopping treatment with SERESTILL. Some withdrawal symptoms occur more frequently than others.

Common undesirable effects which may affect up to 1 in 10 people:

• Dizziness, unsteadiness, or loss of balance.
• Tingling sensation, burning sensation, and (less commonly) electric shock-like sensations, even in the head, and ringing, buzzing, hissing, or other persistent noises in the ears (tinnitus).
• Sleep disturbances (disturbing dreams, nightmares, difficulty falling asleep).
• Anxiety.
• Headache.

Uncommon undesirable effects which may affect up to 1 in 100 people:

• Malaise (nausea).
• Sweating (including night sweats).
• Restlessness or agitation.
• Tremors (shaking).
• Confusion or disorientation.
• Diarrhea (loose stools).
• Increased emotional sensitivity or irritability.
• Vision disturbances.
• Changes in heartbeat (palpitations).

Inform your doctor if you are concerned about these withdrawal effects when stopping treatment with SERESTILL.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them. Adverse reactions are more likely to occur during the first weeks of treatment with SERESTILL.
If you experience any of the following adverse reactions during treatment, contact your doctor or go
immediately to hospital.
Uncommon – may affect up to 1 in 100 people

• If you develop bruises without a specific cause or bleeding, including blood in vomit or stools. Contact your doctor or go immediately to the nearest hospital.
• If you experience difficulty urinating. Contact your doctor or go immediately to the nearest hospital.

Rare – may affect up to 1 in 1,000 people

• If you have seizures. Contact your doctor or go immediately to the nearest hospital.
• If you feel restless or unable to sit still, you may be experiencing a condition called akathisia. Increasing your dose of SERESTILL could worsen these symptoms. Contact your doctor.
• If you feel tired, weak, or confused and have pain, stiffness, or lack of coordination in your muscles, this could be due to a rare effect of SERESTILL that may lead to low sodium levels in your blood. Contact your doctor.

Very rare – may affect up to 1 in 10,000 people

• Allergic reactions to SERESTILL, which can be severe. If you develop redness and skin rashes, swelling of the eyelids, face, lips, mouth, or tongue, itching, or difficulty breathing (shortness of breath) or swallowing, or if you feel weak or dizzy and collapse or lose consciousness, contact your doctor or go immediately to the nearest hospital.
• If you experience some or all of the following symptoms, you may have what is called serotonin syndrome or neuroleptic malignant syndrome. Symptoms include: intense restlessness or irritability, confusion, agitation, feeling hot, sweating, tremors, chills, hallucinations (strange visions or sounds), muscle rigidity, sudden muscle contractions, or rapid heartbeat. Severity may increase, leading to loss of consciousness. If you have these symptoms, contact your doctor.
• Acute glaucoma. If your eyes become painful and you experience blurred vision, contact your doctor.

Not known (frequency cannot be estimated from available data)

• Some people have had thoughts of harming themselves or of suicide while taking SERESTILL or immediately after stopping treatment (see section 2, "What you should know before taking SERESTILL").
• Some people have shown aggression during treatment with SERESTILL.
• Heavy vaginal bleeding shortly after childbirth (postpartum haemorrhage). See section 2, "Pregnancy, breastfeeding and fertility" for further information. If these side effects occur, contact your doctor.

If any of these adverse reactions occur, contact your doctor.
Other possible less serious adverse reactions that may occur during treatment
Very common – may affect more than 1 in 10 people

• Feeling unwell (nausea). Taking the medicine in the morning with breakfast will reduce the likelihood of these symptoms occurring.
• Changes in sexual habits or sexual function. For example, absence of orgasm, and in men, abnormal erection and ejaculation.

Common – may affect up to 1 in 10 people

• Increased cholesterol levels in the blood.
• Loss of appetite.
• Sleep disturbances (insomnia) or drowsiness.
• Abnormal dreams (including nightmares).
• Dizziness or shaking (tremors).
• Difficulty concentrating.
• Headache.
• Feeling restless.
• Blurred vision.
• Yawning, dry mouth.
• Diarrhoea or constipation.
• Vomiting.
• Weight gain.
• Feeling unusually weak.
• Sweating.

Uncommon – may affect up to 1 in 100 people

• Transient increase in blood pressure or transient drop in blood pressure upon moving from a lying or sitting position to a standing position, with dizziness, feeling faint, and possible visual disturbances.
• Faster than normal heartbeat.
• Inability to move, stiffness, shaking, or abnormal movements of the mouth and tongue.
• Pupil dilation.
• Skin rashes.
• Itching.
• Confusion.
• Hallucinations (strange visions and sounds).
• Inability to urinate (urinary retention) or uncontrolled and involuntary loss of urine (urinary incontinence).
• If you are a diabetic patient, you may notice changes in your blood glucose levels during treatment with SERESTILL. In such cases, consult your doctor, who will advise you on how to adjust your insulin dosage or other medications used to treat diabetes.

Rare – may affect up to 1 in 1,000 people

• Abnormal milk production in the mammary glands of men and women.
• Slowed heartbeat.
• Liver abnormalities detected by specific blood tests for liver function.
• Panic attacks.
• Manic behaviour or thoughts.
• Feeling detached from your body (depersonalisation).
• Anxiety.
• Irresistible urge to move the legs (Restless Legs Syndrome).
• Joint or muscle pain.
• Increased levels of a hormone called prolactin in the blood.
• Menstrual cycle disturbances (including heavy or irregular periods, bleeding between periods, or absence or delay of periods).

Very rare – may affect up to 1 in 10,000 people

• Liver problems causing yellowing of the skin or whites of the eyes.
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH), a condition in which the body retains excess water and sodium (salt) levels decrease, due to improper chemical signals. Patients with SIADH may become seriously ill or may have no symptoms at all.
• Water and fluid retention, which may cause swelling of the arms or legs.
• Sensitivity to sunlight.
• Skin rash, which may present with blisters and resemble small targets (dark central spots surrounded by a lighter area, with a dark ring around the edge), known as erythema multiforme.
• A widespread skin rash with blisters and peeling of the skin, particularly around the mouth, nose, eyes, and genitals (Stevens-Johnson syndrome).
• A widespread skin rash with blisters and peeling of the skin over a large part of the body (toxic epidermal necrolysis).
• Prolonged and painful erection of the penis.
• Unexpected bleeding, for example, bleeding gums, blood in urine or vomit, or appearance of unexpected bruises or broken blood vessels (rupture of veins).
• Some patients have reported persistent ringing, buzzing, whistling, or other noises in the ear (tinnitus) while taking SERESTILL.
• An increased risk of bone fractures has been observed in patients taking this type of medicine.

Frequency not known (frequency cannot be estimated from available data)
Teeth grinding
Inflammation of the colon (causing diarrhoea)

If you have any concerns while taking SERESTILL, speak with your doctor and/or pharmacist, who can provide advice.
Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor. You can also report adverse reactions directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE SERESTILL

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton after "exp". The expiry date refers to the last day of the month.
• After first opening the bottle, the oral solution is valid for 30 days for the 30 ml bottle and 60 days for the 60 ml bottle.
• Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. PACKAGING CONTENTS AND OTHER INFORMATION

What SERESTILL contains

• The active substance is paroxetine as paroxetine hydrochloride.
• The other excipients are: hydroxypropylbetadex, sucrose, anise flavour (anethole, water, ethanol), sodium benzoate E211, purified water, hydrochloric acid 1N.

Description of the appearance of SERESTILL and packaging contents
Each carton contains a 30 ml or 60 ml bottle and a graduated pipette. Each ml of liquid (20 drops) contains 10 mg of paroxetine.

Marketing Authorisation Holder and Manufacturer
Chemi S.p.A. - Via dei Lavoratori 54 - 20092 Cinisello Balsamo (MI)
Tel: +39.02.64431
Fax: +39.02.6128960
e-mail: [email protected]

Selling Agent
Farmaceutici CABER S.r.l.
Via del Mare n. 36
00071 Pomezia (RM)

Manufacturer and Final Control Authority
Italfarmaco S.A.
28108 Alcobendas (Madrid) (E), San Rafael, 3 – Polig. Industrial de Alcobendas
Tel: +39.02.64431
Fax: +39.02.644346

This medicinal product is authorised in the Member States of the European Community under the following names:
Italy Serestill