Zoloft - 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: Sertraline

Zoloft 25 mg film-coated tablets
Zoloft 50 mg film-coated tablets
Zoloft film-coated tablets 100 mg
Zoloft concentrate for oral solution 20 mg / l

Why is Zoloft used? What is it for?

Zoloft contains the active substance sertraline. Sertraline belongs to a group of medicines called Selective Serotonin Reuptake Inhibitors (SSRIs); these medicines are used to treat depression and or anxiety disorders.

Zoloft can be used to treat the following conditions:

  • Depression and prevention of recurrence of depression (in adults).
  • Social anxiety disorder (in adults).
  • Post-traumatic stress disorder (PTSD) (in adults).
  • Panic Disorder (in adults).
  • Obsessive Compulsive Disorder (OCD) (in adults and in children and adolescents aged 6-17 years).

Depression is a clinical disease with symptoms such as feeling sad, being unable to sleep properly or enjoying life the way you used to. OCD and panic disorder are anxiety-related diseases with symptoms such as being continually preoccupied with persistent thoughts (obsessions) that cause her to perform ritual actions (compulsions). PTSD is a condition that can occur after an emotionally strong traumatic experience and some symptoms of this condition are similar to depression and anxiety. Social anxiety disorder (social phobia) is an anxiety-related disease. It is characterized by feelings of intense anxiety or stress in social situations (e.g., talking to strangers, speaking in public, eating or drinking in the presence of other people, or the worry of behaving awkwardly).

Your doctor has determined that this medicine is suitable for treating your condition.

Ask your doctor if you are not sure why Zoloft has been prescribed for you.

Contraindications When Zoloft should not be used

Medicines are not always suitable for everyone. Tell your doctor before taking Zoloft if you suffer from or have suffered in the past from any of the following conditions:

  • Epilepsy or history of seizures. If you have a seizure (convulsions), contact your doctor immediately.
  • If you have suffered from manic depressive illness (bipolar disorder) or schizophrenia. If you have a manic episode, contact your doctor immediately.
  • If you have or have had thoughts about harming or killing yourself (see below - Thoughts of suicide and worsening of your depression or anxiety disorder).
  • Serotonin syndrome. In rare cases this syndrome can occur when certain medicines are taken together with sertraline (for symptoms, see section 4. Possible Side Effects). Your doctor will tell you if you have ever suffered from this condition.
  • If you have low levels of sodium in your blood, as this can occur as a result of treatment with Zoloft. You should also tell your doctor if you are taking certain medicines for hypertension, as these medicines can also affect blood sodium levels.
  • Be careful if you are elderly as you are at an increased risk of low blood sodium levels (see above).
  • Liver disease: your doctor may decide to prescribe a lower dose of Zoloft.
  • Diabetes: Blood glucose levels may be altered due to treatment with Zoloft and the dose of diabetes medicines may need to be adjusted.
  • If you have suffered from bleeding problems or if you have taken medicines that thin the blood (e.g. acetylsalicylic acid (aspirin) or warfarin) or which may increase the risk of bleeding.
  • Children or adolescents under the age of 18. Zoloft is only to be used to treat children and adolescents between the ages of 6 and 17 who suffer from obsessive-compulsive disorder (OCD). If your child or adolescent is being treated for this disorder, your doctor will want to monitor you closely (see Use in children and adolescents below).
  • If you are on electroconvulsive therapy (ECT). If you have eye problems, such as certain types of glaucoma (increased pressure in the eye).

Restlessness / Akathisia

If you are taking or have taken disulfiram within the past 2 weeks. Sertraline concentrate for oral solution should not be used in combination with disulfiram or for 2 weeks after stopping treatment with disulfiram. Use of sertraline has been linked to distressing restlessness and need to move, often associated with an inability to sit or stand still (akathisia). This condition is most likely to occur in the first few weeks of treatment. Increasing the dose may be harmful to patients who develop these symptoms so in this case, talk to your doctor.

Drug withdrawal reaction

Side effects related to stopping treatment (withdrawal reactions) are common, particularly if treatment is stopped suddenly (see section 3 If you stop taking Zoloft and section 4 Possible side effects). The risk of withdrawal reactions depends on the duration of treatment, the dosage and the extent of the dose reduction. Generally these symptoms are mild to moderate in intensity; however in some patients they can be severe. They usually occur in the first few days after stopping treatment. Generally these symptoms disappear on their own within 2 weeks. In some patients they may have a longer duration (2-3 months or more). When stopping treatment with sertraline it is recommended to reduce the dose gradually over a period of several weeks or months, always talk to your doctor to determine the best way to stop treatment.

Thoughts of suicide and worsening of your depression or anxiety disorder:

If you are depressed and / or have anxiety disorders you may sometimes have thoughts of harming or killing yourself. These thoughts may get worse when you first take antidepressants, as all these medicines take some time to work. usually about 2 weeks but sometimes longer. You are more likely to think like this if:

  • You have previously had thoughts about killing or harming yourself.
  • If you are a young adult. Available information from clinical trials has shown an increased risk of suicidal behavior in adults under the age of 25 with psychiatric conditions treated with an antidepressant.

If at any time you have thoughts of harming or killing yourself, contact your doctor or go to the nearest hospital straight away. You may find it helpful to tell a relative or close friend that you are depressed or have a disease anxiety and ask them to read this leaflet. You can ask them if they think your depression or anxiety disorder is getting worse, or if they are worried about changes in your behavior.

Use in children and adolescents:

Sertraline should not routinely be used in children and adolescents under the age of 18, with the exception of patients with Obsessive Compulsive Disorder (OCD). Patients under the age of 18 have an increased risk of side effects, such as suicide attempt, thoughts of harming or killing themselves (suicidal thoughts) and hostile behavior (mainly aggression, oppositional behavior and anger) when treated with this class of medicines. However, it is possible that your doctor may decide to prescribe Zoloft to a patient under the age of 18 if this is in the patient's best interest. If your doctor has prescribed Zoloft for you and you are under 18 and you wish to speak to your doctor about this In addition, if any of the symptoms listed above develop or worsen when a patient under the age of 18 is being treated with Zoloft, you should inform your doctor. Finally, the long-term safety of Zoloft on growth, maturation, learning ability (cognitive development) and behavioral development, in this age group, have not been demonstrated.

Precautions for use What you need to know before taking Zoloft

Do not take Zoloft:

  • If you are allergic (hypersensitive) to sertraline or any of the other ingredients of Zoloft (see Section 6 Other Information for a list of other ingredients).
  • If you are taking or have taken monoamine oxidase inhibitors (MAOIs) (e.g. selegiline, moclobemide) or medicines with a similar action to MAOIs (such as linezolid). If you stop taking sertraline, you must wait one week before resuming treatment with a MAOI. After stopping treatment with a MAOI, you must wait at least 2 weeks before starting treatment with sertraline.
  • If you are taking another medicine called Pimozide (a medicine for mental disorders such as psychosis).
  • If you are taking or have taken disulfiram within the past 2 weeks. Sertraline concentrate for oral solution should not be used in combination with disulfiram or for 2 weeks after stopping treatment with disulfiram.

Interactions What medications or foods can change the effect of Zoloft

Tell your doctor if you are taking or have recently taken any other medicines, even those without a prescription. Some medicines can affect the way Zoloft works, or Zoloft can reduce the effectiveness of other medicines taken at the same time.

Taking Zoloft with the following medicines can cause serious adverse events:

  • Medicines called monoamine oxidase inhibitors (MAOIs), such as moclobemide (to treat depression) and selegiline (to treat Parkinson's disease) and the antibiotic linezolid. Do not use Zoloft together with these medicines.
  • Medicines to treat mental disorders such as psychosis (pimozide). Do not use Zoloft together with pimozide.
  • Do not use Zoloft together with disulfiram.

Tell your doctor if you are taking any of the following medicines:

  • Herbal medicine containing St. John's wort (Hypericum perforatum). The effects of St. John's wort can last for 1-2 weeks.
  • Products containing the amino acid tryptophan.
  • Medicines to treat severe pain (e.g. tramadol).
  • Medicines used in anesthesia or to treat chronic pain (e.g. fentanyl).
  • Medicines to treat migraine (eg sumatriptan).
  • Medicines to thin the blood (warfarin).
  • Medicines to treat pain / arthritis (Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, acetylsalicylic acid (aspirin)).
  • Sedatives (diazepam).
  • Diuretics.
  • Medicines to treat epilepsy (phenytoin).
  • Medicines to treat diabetes (tolbutamide).
  • Medicines to treat excess stomach acid and ulcers (cimetidine).
  • Medicines to treat mania and depression (lithium).
  • Other medicines to treat depression (such as amitriptyline, nortriptyline).
  • Medicines to treat schizophrenia and other mental disorders (such as perphenazine, levomepromazine and olanzapine).
  • Medicines used to regulate heart rate and rhythm (such as flecainide and propafenone)

Taking Zoloft with food and drink:

Zoloft tablets can be taken with or without food. Zoloft concentrate for oral solution can be taken with or without food. The consumption of alcohol should be avoided during treatment with Zoloft. Sertraline should not be taken in combination with grapefruit juice, as this can increase the levels of sertraline in the body.

Warnings It is important to know that:

Pregnancy, breastfeeding and fertility:

Ask your doctor or pharmacist for advice before taking any medicine. The safety of sertraline has not been fully established in pregnant women. Sertraline should only be given to pregnant women if the doctor considers that the benefit to the mother outweighs any possible risk to the development of the fetus. If you are a woman of childbearing potential being treated with sertraline, you must use a reliable method of contraception (such as the contraceptive pill). Make sure your midwife and / or doctor are aware that you are being treated with Zoloft. When taken during pregnancy, particularly during the last three months, medicines like Zoloft may increase the risk of a serious condition in babies called Persistent pulmonary hypertension in the newborn (PPHN). This condition causes rapid breathing in the newborn and a bluish color. These symptoms usually begin within the first 24 hours after delivery. If this occurs to your baby, contact your midwife and / or immediately. the doctor. Can your child? have other conditions as well, which generally begin in the first 24 hours after giving birth. Symptoms include:

  • breathing difficulties,
  • bluish skin color or being too hot or too cold,
  • blue lips,
  • vomiting or difficulty in feeding,
  • being very tired, unable to sleep or crying a lot,
  • stiff or limp muscles,
  • tremors, nervousness, jerks,
  • increased reflex reactions,
  • irritability,
  • low sugar levels.

If your baby has any of the symptoms listed above at birth, or if you have any concerns about your baby's health, contact your doctor or midwife who will be able to advise you. There is evidence that sertraline is excreted in breast milk. Sertraline should only be used during breastfeeding if the doctor considers that the benefit to the mother outweighs any possible risk to the baby. In animal studies, some drugs such as sertraline can reduce sperm quality. In theory this could affect fertility, but the impact on human fertility has not yet been observed.

Driving and using machines:

Psychotropic medicines such as sertraline may affect the ability to drive and use machines. Therefore, you should not drive or operate machinery until you have ascertained whether this medicine affects your ability to perform these activities.

Important information about some of the ingredients of Zoloft concentrate for oral solution:

This medicinal product contains 12% ethanol (alcohol) and must be diluted before use. Each ml of oral liquid contains 150.7 mg of alcohol. May be harmful to alcoholics. To be taken into consideration in pregnant or pregnant women. breastfeeding, in children and in high-risk groups such as people with liver disease or epilepsy. This medicine contains butylhydroxytoluene which can cause irritation to the eyes, skin and mucous membranes. It also contains glycerol which in high doses, can cause sore head, pain

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

Always take Zoloft exactly as your doctor has told you. Zoloft tablets can be taken with or without food. Zoloft concentrate for oral solution can be taken with or without food. Take this medicine once a day, in the morning or in the evening. If in doubt, you should consult your doctor or pharmacist.

The usual dose is:

Adults: Depression and Obsessive Compulsive Disorder: For depression and OCD, the usual effective dose is (2.5 ml) 50 mg / day. The daily dose may be increased by (2.5 ml) 50 mg and at intervals of at least one week in the span of a few weeks. The maximum recommended dose is (10 ml) 200 mg / day. Panic Disorder, Social Anxiety Disorder, and PTSD: For panic disorder, social anxiety, and PTSD, treatment should begin at a dose of (1.25 ml) 25 mg / day, then increased to (2.5 ml) 50 mg / day after one week. The daily dose can then be increased by (2.5 ml) to 50 mg over a period of several weeks. The maximum recommended dose is 200 mg / day.

Children and adolescents: Zoloft is only to be used for the treatment of children and adolescents with Obsessive Compulsive Disorder (OCD) between the ages of 6 and 17. Obsessive Compulsive Disorder: Children aged 6-12 years: the recommended starting dose is 25 mg / day.After one week the doctor may increase the dose by 50 mg / day. The maximum dose is (10 ml) 200 mg / day. Adolescents aged 13-17 years: The recommended starting dose is (2.5 ml) 50 mg / day. The maximum dose is (10 ml) 200 mg / day.

If you have liver or kidney problems, please tell your doctor and follow the doctor's instructions. Your doctor will tell you how long to take this medicine. This will depend on the duration of the disease and the response to treatment. It can take several weeks for symptoms to start to improve. Treatment for depression should usually continue for 6 months after improvement is observed.

Instructions for a correct use of Zoloft:

The concentrate for oral solution must always be diluted before use. Never drink the concentrate without first diluting it.

When opening the bottle of oral concentrate for the first time, you must place the dispenser on the bottle as follows:

  1. Unscrew the cap on the bottle by pushing hard on the cap while turning it to the left (counterclockwise). Remove the cap.
  2. Place the dispenser on the bottle and close tightly. The dispenser is located inside the package.
  3. When you then open the bottle, push down firmly while turning the dispenser to the left (counterclockwise).
  4. Put the dispenser back on the bottle after use.

Dose measurement:

Use the dispenser to measure the dose as prescribed by your doctor. Mix the measured dose with 120ml (one glass) of liquid, which can be water, lemon soda, lemonade and orange juice. Do not mix Sertraline Concentrate for Oral Solution with other liquids than those listed. The solution should be taken immediately after dilution. The solution may be cloudy, but this is normal.

Overdose What to do if you have taken too much Zoloft

If you take more Zoloft than you should:

If you accidentally take too much Zoloft contact your doctor right away or go to the nearest emergency room. Always carry a pack of medicine with you, whether it contains medicine or not. Symptoms of overdose may include drowsiness, nausea and vomiting, rapid heartbeat, tremors, agitation, dizziness and in rare cases unconsciousness.

If you forget to take Zoloft:

If you forget to take a dose, do not take the missed dose. Take your next dose at the correct time. Do not take a double dose to make up for any forgotten doses.

If you stop taking Zoloft:

Do not stop taking Zoloft unless your doctor tells you to. Your doctor may wish to gradually reduce your dose of Zoloft over several weeks before you stop using this medicine completely. If you suddenly stop using this medicine, you may experience side effects such as dizziness, numbness, sleep disturbances, agitation or anxiety, headache, nausea, vomiting and tremors. If you experience any of these side effects, or any other side effects while taking Zoloft, please talk to your doctor. If you have any further questions on the use of Zoloft, ask your doctor or pharmacist.

Side Effects What are the side effects of Zoloft

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

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Nausea is the most common side effect. Side effects depend on the dose and often disappear or lessen with continued treatment.

Tell your doctor immediately:

If you get any of the following symptoms after taking this medicine, these symptoms can be serious.

  • If you develop a severe skin reaction which causes blistering (erythema multiforme) (may affect the mouth and tongue). These may be signs of a condition known as Stevens Johnson Syndrome or Toxic Epidermal Necrolysis. In these cases the doctor will stop the treatment.
  • Allergic reactions or allergies, which may include symptoms such as an itchy rash, trouble breathing, wheezing, swollen eyelids, face or lips.
  • If you experience agitation, confusion, diarrhea, high fever and high blood pressure, excessive sweating and a fast heartbeat. These are the symptoms of Serotonin Syndrome. In rare cases, this syndrome can occur when certain medicines are taken together with sertraline. The doctor may wish to stop the treatment.
  • If you develop a yellow color of the skin and eyes which may be indicative of liver damage.
  • If you develop depressive symptoms with thoughts of harming or killing yourself (suicidal thoughts).
  • If you start feeling restless and can no longer sit or stand still after starting treatment with Zoloft. You should tell your doctor if you start to feel restless.
  • If you have convulsions
  • If a manic episode occurs (see section 2 "Take special care with Zoloft")

The following side effects were observed in clinical studies in adult patients:

Very common side effects (affects more than 1 in 10 patients):

Insomnia, dizziness, somnolence, headache, diarrhea, nausea, dry mouth, absence of ejaculation, fatigue.

Common side effects (may affect up to 1 in 10 people)

  • Sore throat, anorexia, increased appetite,
  • depression, feeling strange, nightmares, anxiety, agitation, nervousness, reduced sexual interest, teeth grinding,
  • numbness and tingling, tremors, muscle tension, taste disturbance, lack of attention,
  • visual disturbances, ringing in the ears,
  • palpitations, hot flashes, yawns,
  • abdominal pain, vomiting, constipation, stomach upset, stomach air,
  • rash, increased sweating, muscle pain, sexual dysfunction, erectile dysfunction, chest pain.

Uncommon side effects (may affect up to 1 in 100 people):

  • Cold chest, runny nose,
  • hypersensitivity,
  • low thyroid hormone levels,
  • hallucinations, feelings of excessive happiness, lack of personal care, altered thoughts, aggression,
  • convulsions, involuntary muscle contractions, impaired coordination, excessive movement, amnesia, decreased sensation, speech disturbance, dizziness when standing up, fainting, migraine,
  • dilation of the pupils,
  • ear pain, rapid heartbeat, high blood pressure, flushing of the face,
  • difficulty in breathing, possible wheezing, shortness of breath, nosebleed,
  • inflammation of the esophagus, difficulty in swallowing, haemorrhoids, increased salivation, tongue discomfort, belching,
  • eye swelling, red spots on the skin, face edema, hair loss, cold sweats, dry skin, hives, itching,
  • osteoarthritis, muscle weakness, back pain, muscle twitching,
  • urination at night, inability to pass urine, increased amount of urine, increased urinary frequency, problems urinating, urinary incontinence,
  • vaginal bleeding, sexual dysfunction, female sexual dysfunction, menstrual irregularities, leg swelling, chills, fever, weakness, thirst, increased liver enzyme levels, weight reduction, weight gain.

Rare side effects (may affect up to 1 in 1,000 people):

  • bowel problems, ear infections, cancer, swollen glands, high cholesterol levels, low blood sugar levels,
  • physical symptoms due to stress or emotions, drug addiction, psychotic disorders, paranoia, suicidal thoughts, sleepwalking, premature ejaculation,
  • severe allergic reaction,
  • coma, abnormal movement, difficulty moving, increased sensation, sensory disturbance,
  • glaucoma, lacrimation problems, eye spots, double vision, light discomfort, blood in the eye,
  • problems controlling blood sugar levels (diabetes),
  • heart attack, slow heartbeat, heart problems, poor blood circulation in the arms and legs, closing of the throat, fast breathing, slow breathing, difficulty speaking, hiccups,
  • blood in stools, mouth pain, tongue ulceration, tooth disorder, tongue problems, mouth ulceration, liver function problems,
  • skin problems with blistering, inflammation of the hair follicles, changes in hair structure, changes in skin odor, bone disorders,
  • decreased urination, initial difficulty urinating, blood in urine,
  • excessive vaginal bleeding, dry vaginal area, red painful penis and foreskin, genital discharge, prolonged erection, breast discharge,
  • hernia, drug tolerance impaired, difficulty walking, seminal fluid change, increased blood cholesterol levels, wounds, blood vessel relaxation procedure,
  • Cases of suicidal thoughts and suicidal behaviors have been reported in patients receiving sertraline or soon after treatment discontinuation (see section 2).

The following undesirable effects have been reported in the post-marketing setting of sertraline:

  • Reduction in the number of white blood cells, reduction in the number of blood clotting cells, endocrine problems, low blood salt levels, increased blood sugar levels,
  • terrifying altered dreams, suicidal behavior,
  • problems with muscle movements (such as frequent movements, tense muscles, difficulty walking and stiffness, spasms and involuntary movements of the muscles), sudden severe headaches (which may be a sign of a serious condition known as reversible cerebral vasoconstriction syndrome (RCVS) )).
  • impaired vision, unequal pupils, bleeding problems (such as stomach bleeding), progressive scarring of lung tissue (Interstitial Pulmonary Disease), pancreatitis, severe liver function problems, yellowish skin and eyes (jaundice),
  • skin edema, skin reaction to sun exposure, muscle cramps, breast enlargement, bleeding problems, altered laboratory tests, enuresis.
  • light-headedness, fainting or chest pain, which could be signs of changes in the electrical activity of the heart (as shown by the electrocardiogram) or an abnormal rhythm of the heart.

Side effects in children and adolescents:

In clinical trials in children and adolescents, side effects were generally similar to those seen in adults (see above). The most common side effects in children and adolescents were headache, insomnia, diarrhea and nausea.

Symptoms that can occur when treatment is stopped:

If you suddenly stop taking this medicine, side effects such as dizziness, tingling, disturbed sleep, agitation or anxiety, headache, nausea, vomiting and tremor may occur (see section 3 "If you stop taking Zoloft"). An increased risk of bone fractures has been observed in patients taking this type of medicine. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Expiry and Retention

Keep out of the reach and sight of children. Do not use Zoloft after the expiry date which is stated on the label. The expiry date refers to the last day of the month. Do not store above 30 ° C Medicines should not be disposed of 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 ZOLOFT contains

Zoloft film-coated tablets: Each film-coated tablet contains sertraline hydrochloride equivalent to 25 mg of sertraline

Each film-coated tablet contains sertraline hydrochloride equivalent to 50 mg of sertraline.

Each film-coated tablet contains sertraline hydrochloride equivalent to 100 mg of sertraline.

The other ingredients are: Calcium hydrogen phosphate dihydrate (E341), microcrystalline cellulose (E460), Hydroxypropylcellulose (E463), Sodium starch glycolate, magnesium stearate (E572), Titanium dioxide (E171), Hypromellose (E464), Macrogol 80 (E433) ).

ZOLOFT concentrate for oral solution 20 mg / ml Each ml of the concentrate contains 20 mg of sertraline (as hydrochloride) The other ingredients are: Glycerol (E422), ethanol, levomentol and butylhydroxytoluene (E321).

What Zoloft looks like and contents of the pack

Zoloft film-coated tablets Zoloft (sertraline) 25 mg film-coated tablets are white, capsule-shaped film-coated tablets debossed with "ZLT25" on one side and "Pfizer" on the other. Zoloft film-coated tablets (sertraline) 50 mg are white, scored, capsule-shaped, film-coated tablets debossed with "ZLT50" on one side and "Pfizer" on the other.

The tablets can be divided into equal parts.

Zoloft (sertraline) 100 mg film-coated tablets are white, capsule-shaped, film-coated tablets debossed with "ZLT100" on one side and "Pfizer" on the other.

Zoloft film-coated tablets 25 mg The tablets are packed in blisters containing 7, 28 or 98 tablets.

Zoloft 50 mg film-coated tablets The tablets are packed in blisters containing 10, 14,15, 20, 28, 30, 50, 56, 60, 84, 98, 100, 200, 294, 300 or 500 tablets.

Zoloft film-coated tablets 100 mg The tablets are packed in blisters containing 10, 14,15, 20, 28, 30, 50, 56, 60, 84, 98, 100, 200, 294, 300 or 500 tablets.

Not all pack sizes may be marketed.

Zoloft concentrate for oral solution: Sertraline 20 mg / ml oral concentrate is a clear and colorless solution in a 60 ml dark glass bottle equipped with a graduated dispenser.

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

More information about Zoloft 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

ZOLOFT

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Zoloft 25 mg film-coated tablets

Each film-coated tablet contains sertraline hydrochloride equivalent to 25 mg of sertraline.

Zoloft 50 mg film-coated tablets

Each film-coated tablet contains sertraline hydrochloride equivalent to 50 mg of sertraline.

Zoloft film-coated tablets 100 mg

Each film-coated tablet contains sertraline hydrochloride equivalent to 100 mg of sertraline

Zoloft concentrate for oral solution 20 mg / ml

Each ml of the concentrate contains 20 mg of sertraline (as hydrochloride)

The other ingredients are: glycerol (E422), ethanol, levomentol and butylhydroxytoluene (E321).

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Zoloft film-coated tablets

Zoloft 25 mg film-coated tablets are white, capsule-shaped film-coated tablets debossed with "ZLT25" on one side and "Pfizer" on the other.

Zoloft 50 mg film-coated tablets are white, scored, capsule-shaped, film-coated tablets debossed with "ZLT50" on one side and "Pfizer" on the other.

The tablets can be divided into equal parts.

Zoloft 100 mg film-coated tablets are white, capsule-shaped film-coated tablets debossed with "ZLT100" on one side and "Pfizer" on the other.

Zoloft concentrate for oral solution

Clear and colorless solution in a dark glass bottle. The bottle is equipped with a screw cap with a dispenser incorporated in the cap.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Sertraline is indicated in the treatment of:

• major depressive episodes. Prevention of the recurrence of major depressive episodes.

• panic disorder, whether or not associated with agoraphobia.

• obsessive-compulsive disorder (OCD) in adult patients and in pediatric patients aged 6 to 17 years.

• social anxiety disorder.

• Post-Traumatic Stress Disorder (PTSD).

04.2 Posology and method of administration

Sertraline should be taken in a single daily administration, either in the morning or in the evening.

Sertraline tablets can be administered with or without food.

Sertraline concentrate for oral solution can be administered with or without food.

Sertraline concentrate for oral solution must be diluted before use (see section 6.6).

Initial treatment

Depression and OCD

Sertraline treatment should be initiated at a dose of 50 mg / day.

Panic Disorder, PTSD and Social Anxiety Disorder

Therapy should be initiated at a dose of 25 mg / day. After one week, the dose should be increased to 50 mg once a day. This dosing regimen has been shown to reduce the frequency of undesirable effects that characterize panic disorder early in treatment.

Titration

Depression, OCD, Panic Disorder, Social Anxiety Disorder, and PTSD

Patients unresponsive to the 50 mg dose may benefit from dose increases. Dose modifications should be made in increments of 50 mg at intervals of at least one week, up to a maximum of 200 mg / day. Taking into account that sertraline has an elimination half-life of 24 hours, no dose modifications should be made more frequently than once a week.

The onset of the therapeutic effect can be observed within 7 days. However, the therapeutic effect can manifest itself after longer periods of time, particularly in the treatment of OCD.

Maintenance

During prolonged treatment, the dosage should be maintained at the lowest therapeutic level, with subsequent dose adjustment depending on the therapeutic response.

Depression

Prolonged treatment may also be appropriate in preventing recurrence of major depressive episodes (MDE). In most cases, the recommended dose in preventing recurrence of major depressive episodes is the same as that used during the episodes themselves. Patients with depression should be treated for a sufficient period of at least 6 months to ensure they are symptom-free.

Panic Disorder and OCD

Continuation of treatment in panic disorder and OCD should be evaluated regularly, because efficacy in relapse prevention has not been demonstrated for these disorders.

Pediatric patients

Children and adolescents with Obsessive Compulsive Disorder

Age 13-17: start treatment at a dose of 50 mg once daily.

Age 6-12: start treatment at a dose of 25 mg once daily. The dose can be increased to 50 mg once daily after one week.

If there is no response, subsequent doses can be increased by 50 mg to 50 mg over a period of several weeks, as needed. The maximum daily dose is 200 mg per day.

However, the body weight of children generally lower than that of adults should be taken into account when increasing the dose beyond 50 mg. Dosage changes should not be made at intervals of less than one week.

Efficacy has not been demonstrated in pediatric patients with major depressive disorders.

No data are available in children below 6 years of age (see also section 4.4).

Use in the elderly

Administration to the elderly should be undertaken with caution as these patients may be at increased risk of hyponatraemia (see section 4.4).

Use in patients with hepatic insufficiency

Use of sertraline in patients with hepatic disorders should be undertaken with caution. Lower and less frequent doses should be used in patients with hepatic impairment (see section 4.4).

Sertraline should not be used in cases of severe hepatic impairment because no clinical data are available in these patients (see section 4.4).

Use in patients with renal insufficiency

No dosage adjustments are required in patients with renal insufficiency (see section 4.4).

Withdrawal symptoms observed following discontinuation of sertraline

Abrupt discontinuation of treatment should be avoided. When stopping treatment with sertraline the dose should be gradually reduced over a period of at least 1-2 weeks to reduce the risk of withdrawal reactions (see sections 4.4 and 4.8). If intolerable symptoms occur following dose reduction or upon discontinuation of treatment, resuming the previously prescribed dose may be considered. Thereafter, your doctor may continue to reduce the dose, but more gradually.

04.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

The concomitant use of irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of serotonin syndrome with symptoms such as agitation, tremor and hyperthermia. Treatment with sertraline should not be started for at least 14 days after stopping treatment with a Irreversible MAOI. Treatment with sertraline should be stopped at least 7 days before starting treatment with an irreversible MAOI (see section 4.5).

Concomitant use of pimozide is contraindicated (see section 4.5).

Concomitant use of sertraline and disulfiram concentrate for oral solution is contraindicated because the oral concentrate contains alcohol (see sections 4.4 and 4.5).

04.4 Special warnings and appropriate precautions for use

Serotonin Syndrome (SS) or Neuroleptic Malignant Syndrome (NMS)

The development of life-threatening syndromes such as serotonin syndrome (SS) or neuroleptic malignant syndrome (NMS) has been reported with the use of SSRIs, including treatment with sertraline. The risk of serotonin syndrome. o Neuroleptic malignant syndrome with SSRIs increases with concomitant use of serotonergic drugs (including triptans), with drugs that impair serotonin metabolism (including MAOIs), with antipsychotics and other dopamine antagonists. Patients should be monitored for signs or symptoms of SS or NMS (see section 4.3 - Contraindications).

Switching from Selective Serotonin Reuptake Inhibitor (SSRI) therapy, antidepressants, or drugs for obsessive-compulsive disorder

The clinical experience acquired so far does not allow us to establish the most appropriate time to switch from a therapy with other SSRIs, antidepressants or drugs indicated in the treatment of obsessive-compulsive disorders to one with sertraline. In this phase, particular caution is required and vigilance by the doctor, especially if substituting a long-acting drug such as fluoxetine.

Other serotonergic medicinal products (e.g. tryptophan, fenfluramine and 5-HT agonists)

Concomitant administration of sertraline and other medicinal products that enhance the effects of serotonergic neurotransmission such as tryptophan, fenfluramine or 5-HT agonists or St. John's Wort (Hypericum perforatum), a herbal medicinal product, should be carried out with caution and avoided whenever possible due to the potential pharmacodynamic interaction.

Activation of hypomania or mania

The onset of symptoms of mania / hypomania has been reported in a small number of patients treated with commercially available antidepressants and drugs for obsessive-compulsive disorders, including sertraline. Therefore, sertraline should be used with caution in patients with a history. positive of mania / hypomania. Careful medical supervision is required. Treatment with sertraline should be discontinued in patients entering a manic phase.

Schizophrenia

Psychotic symptoms can be aggravated in schizophrenic patients.

Seizures

Seizures may occur during treatment with sertraline; the use of sertraline should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be closely monitored. Sertraline should be discontinued in patients experiencing seizures.

Suicide / suicidal thoughts / suicide attempts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicidal behavior or thoughts). 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. AND AND; general clinical experience that the risk of suicide may increase in the early stages of improvement.

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

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

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

Children and adolescents under the age of 18

Sertraline should not be used for the treatment of children and adolescents under 18 years of age, except in patients with obsessive-compulsive disorder between the ages of 6 and 17. 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. In addition, long-term safety data in children and adolescents related to growth, maturation and cognitive and behavioral development are not available. Physicians should monitor pediatric patients undergoing long-term treatment for the possible development of abnormalities related to these processes.

Abnormal bleeding / haemorrhage

There have been reports of cutaneous bleeding disorders, such as ecchymosis and purpura, and other haemorrhagic events such as gastrointestinal or gynecological bleeding with the use of SSRIs. Caution is advised in patients taking SSRIs, particularly in case of concomitant use with medicines known to affect platelet function (e.g. anticoagulants, atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory drugs (NSAIDs)), as well as in patients with previous bleeding disorders (see section 4.5) .

Hyponatremia

Hyponatremia can occur following treatment with SSRIs or SNRIs, including sertraline. In many cases, hyponatraemia appears to be the result of a syndrome of inappropriate antidiuretic hormone secretion (SIADH). serum sodium below 110 mmol / L. Elderly patients may be at increased risk of hyponatremia when being treated with SSRIs and SNRIs. Patients taking diuretics or otherwise volume depleted may also be at increased risk (see also Use in elderly patients). Discontinuation of sertraline should be considered in patients with symptomatic hyponatremia and appropriate medical therapy instituted. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment. , confusion, weakness and physical instability which can cause falls. Signs and symptoms associated with more severe and / or acute cases have included hallucinations, syncope, seizures, coma, respiratory arrest and death.

Withdrawal symptoms observed following discontinuation of sertraline treatment

Discontinuation symptoms observed when treatment is stopped are common, particularly in the event of abrupt discontinuation (see section 4.8). In clinical studies, among patients treated with sertraline, the incidence of withdrawal reactions was 23% in patients who discontinued sertraline compared with 12% in patients who continued treatment with sertraline.

The risk of withdrawal symptoms may be dependent on several factors, including the duration and dose of therapy and the frequency of dose reduction. The most commonly reported reactions were dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, tremor and headache. 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 in very rare cases these symptoms have appeared in patients who had inadvertently missed a treatment. Generally these symptoms are self-limiting, and usually resolve within 2 weeks, although in some individuals they may last longer (2-3 months or more). It is therefore recommended to gradually reduce the dose of sertraline when discontinuing treatment, over a period of several weeks or months, according to the patient's needs (see section 4.2).

Akathisia / psychomotor restlessness

The use of sertraline has been associated with the development of akathisia, characterized by subjective malaise or psychomotor agitation and the need to keep moving, often associated with the inability to sit or stand still. This is most likely to happen within the first few weeks of treatment. In patients with these symptoms, increasing the dosage can be harmful.

Use in case of hepatic impairment

Sertraline is extensively metabolised in the liver. A multiple-dose pharmacokinetic study conducted in subjects with mild and non-progressive liver cirrhosis demonstrated an increase in the plasma half-life of the drug and an AUC and Cmax corresponding to approximately three times the values ​​found in normal subjects. They were not observed. Significant differences between the two groups in plasma protein binding. Sertraline should therefore be used with caution in subjects with liver disease. Lower and less frequent doses should be used if sertraline is administered to patients with hepatic impairment. it must not be used in patients with severe hepatic impairment (see section 4.2).

Use in case of renal impairment

Sertraline is extensively metabolised and the amount of drug excreted unchanged in the urine is negligible. In studies in patients with mild-moderate (creatinine clearance 30-60 ml / min) or moderate-severe (creatinine clearance 10-29 ml / min) renal impairment, the pharmacokinetic parameters (AUC0-24 or Cmax) after administration of multiple doses were not significantly dissimilar from controls. The dosage of sertraline should not be modified in relation to the degree of renal impairment.

Use in elderly patients

Over 700 elderly patients (aged> 65 years) have participated in clinical trials. The type and incidence of adverse reactions in elderly patients were similar to those seen in younger patients.

The use of SSRIs and SRNIs, including sertraline, has however been associated with cases of clinically significant hyponatraemia in elderly patients who may be at increased risk for this adverse event (see Hyponatraemia in section 4.4).

Use in case of diabetes

In patients with diabetes, treatment with an SSRI can impair glycemic control. Dosage adjustment of insulin and / or oral hypoglycaemics may be required.

Electroconvulsive therapy

There are no clinical studies that have established the risks or benefits of the combined use of ECT and sertraline.

Grapefruit juice

Administration of sertraline with grapefruit juice is not recommended (see section 4.5).

Interference with the urine screening test

False positive results for benzodiazepines have been reported in urine immunoassay laboratory tests in patients receiving sertraline. This is due to the lack of specificity of the tests. False positive results in laboratory tests can be expected for several days after stopping treatment with sertraline. Confirmatory tests such as gas chromatography / mass spectrometry will distinguish sertraline from benzodiazepines.

Closed-angle glaucoma

SSRIs, including sertraline, can affect pupil size resulting in mydriasis. This mydriatic effect has the ability to narrow the angle of the eye resulting in increased intraocular pressure and angle-closure glaucoma, especially in predisposed patients. Sertraline should be used with caution in patients with narrow-angle glaucoma or with history of glaucoma.

Sertraline concentrate for oral solution

Sertraline concentrate for oral solution contains 12% ethanol (see sections 4.3 and 4.5), glycerol and butylhydroxytoluene.

Ethanol: The alcohol content must be taken into account in patients with hepatic impairment, alcoholics, people with epilepsy, patients with brain trauma or brain disease, pregnant women and children.

Butylhydroxytoluene: can cause irritation to the eyes, skin and mucous membranes.

Glycerol: in high doses it can cause headache, abdominal pain and diarrhea.

04.5 Interactions with other medicinal products and other forms of interaction

Contraindicated

Monoamine oxidase inhibitors

Irreversible MAOIs (e.g. selegiline)

Sertraline should not be used in combination with irreversible MAOIs such as selegiline. Treatment with sertraline should not be started for at least 14 days after stopping treatment with an irreversible MAOI. Treatment with sertraline should be stopped for at least 7 days before starting treatment with an irreversible MAOI (see section 4.3). .

Reversible and selective inhibitor of MAOIs (moclobemide)

Due to the risk of serotonin syndrome, reversible and selective MAOIs, such as moclobemide, should not be administered in combination with sertraline. Following treatment with a reversible and selective MAOI inhibitor, a withdrawal period of less than 14 days is possible before starting treatment with sertraline. It is recommended that sertraline be discontinued for at least 7 days prior to initiation of treatment with a reversible MAOI (see section 4.3).

Reversible non-selective MAOI (linezolid)

The antibiotic linezolid is a weak reversible and non-selective MAOI and should not be given to patients being treated with sertraline (see section 4.3).

Serious adverse reactions have been reported in patients who have recently stopped treatment with a MAOI and started treatment with sertraline, or who recently stopped treatment with sertraline before starting treatment with a MAOI. These reactions included tremor, myoclonus, diaphoresis, nausea, vomiting, hot flashes, dizziness and hyperthermia with characteristics similar to those of neuroleptic malignant syndrome, convulsions and death.

Pimozide

An increase in pimozide levels of approximately 35% was observed in a study conducted with single-dose pimozide (2 mg). This increased levels have not been associated with ECG changes. While the mechanism of this interaction is unknown, due to the narrow therapeutic index of pimozide, concomitant administration of sertraline and pimozide is contraindicated (see section 4.3).

Concomitant administration with sertraline is not recommended

CNS depressants and alcohol

Concomitant administration of sertraline 200 mg / day did not potentiate the effects of alcohol, carbamazepine, haloperidol or phenytoin on cognitive and psychotomoric performance in healthy subjects; however, the concomitant use of sertraline and alcohol is not recommended.

Other serotonergic drugs

See section 4.4.

Caution is advised with fentanyl used in general anesthesia or in the treatment of chronic pain.

Special precautions

Lithium

In a placebo-controlled study in healthy volunteers, concomitant administration of sertraline and lithium did not result in significant alterations in the pharmacokinetics of lithium, but resulted in an increase in tremor episodes compared to the placebo group, highlighting a possible pharmacodynamic interaction. Patients should be monitored appropriately when sertraline is administered with lithium.

Phenytoin

From a placebo-controlled clinical study in healthy volunteers it was found that chronic administration of sertraline at a dose of 200 mg / day does not cause a clinically significant inhibition of phenytoin metabolism. Since exposure to high phenytoin levels has been reported in some cases in patients receiving sertraline, it is recommended that plasma phenytoin concentrations be monitored after initiation of sertraline therapy, making appropriate adjustments to the phenytoin dosage. Furthermore, concomitant administration of phenytoin may cause a reduction in plasma levels of sertraline.

Triptans

There have been rare reports of patients with weakness, hyperreflexia, incoordination, confusion, anxiety and agitation following the use of sertraline and sumatriptan in the post-marketing setting.

Symptoms of serotonin syndrome can also occur with other drugs of the same class (triptans).

If the concomitant use of sertraline and triptans is clinically justified, appropriate observation of the patient is advised (see section 4.4).

Warfarin

Concomitant administration of sertraline 200 mg / day and warfarin resulted in a small but statistically significant increase in prothrombin time, which in some rare cases may alter the INR value. Therefore, the prothrombin time should be closely monitored when starting or stopping treatment with sertraline.

Interactions with other medicines, digoxin, atenolol, cimetidine

Concomitant administration of cimetidine caused a substantial reduction in the clearance of sertraline. The clinical significance of these changes is unknown. Sertraline had no effect on the beta-adrenergic blocking ability of atenolol. No interactions were observed between sertraline 200 mg / day and digoxin.

Medicines that affect platelet function

The risk of bleeding may be increased when medicinal products that affect platelet function (e.g. NSAIDs, acetylsalicylic acid and ticlopidine) or other medicinal products that may increase the risk of bleeding are co-administered with SSRIs, including sertraline (see section 4.4).

Medicinal products metabolised by Cytochrome P450

Sertraline may exert a mild to moderate inhibitory action on CYP 2D6 activity. Chronic administration of sertraline 50 mg / day resulted in moderate (mean 23% -37%) steady-state increase in plasma levels of desipramine (a marker of CYP 2D6 isozyme activity). Clinically relevant interactions may occur with other CYP 2D6 substrates with a narrow therapeutic index including class 1C antiarrhythmics such as propafenone and flecainide, tricyclic antidepressants and typical antipsychotics, especially if sertraline is administered in high doses.

Sertraline does not act as an inhibitor of CYP 3A4, CYP 2C9, CYP 2C19 and CYP 1A2 to a clinically relevant extent. This was confirmed by the interaction studies in-vivo conducted with CYP 3A4 substrates (endogenous cortisol, carbamazepine, terfenadine, alprazolam), with the CYP 2C19 substrate diazepam and with CYP 2C9 substrates (tolbutamide, glibenclamide and phenytoin). Studies in vitro indicate that sertraline has negligible or no inhibitory potential for CYP 1A2.

Intake of three glasses of grapefruit juice per day increased sertraline plasma levels by approximately 100% in a cross-over study of eight Japanese healthy subjects.

Interaction with other CYP 3A4 inhibitors has not been established. Therefore the intake of grapefruit juice should be avoided during treatment with sertraline (see section 4.4).

Plasma levels of sertraline increased by approximately 50% in poor metabolisers of CYP 2C19 when compared to extensive metabolisers of CYP 2C19 (see section 5.2). Interactions with strong CYP 2C19 inhibitors cannot be excluded.

Concentrate for oral solution of sertraline and disulfiram

Sertraline concentrate for oral solution contains a small amount of alcohol. As long as the serum levels of disulfiram persist, or until the activity of acetaldehyde dehydrogenase is diminished, taking ethanol with disulfiram will result in an adverse reaction. Based on liver function, this effect may persist for two weeks following the last dose of disulfiram, although one week is the most often observed duration of action with standard doses. Therefore, sertraline concentrate for oral solution should not be used in combination with disulfiram or within 14 days of discontinuing treatment with disulfiram (see sections 4.3 and 4.4).

04.6 Pregnancy and breastfeeding

Pregnancy

There are no adequate studies in pregnant women. However, a substantial amount of available data has not revealed that sertraline induces congenital malformations. Reproductive effects have been observed in animal studies, possibly caused by toxicity resulting from the pharmacodynamic action of the compound towards the mother and / or the direct pharmacodynamic action of the compound towards the fetus (see section 5.3).

In some infants whose mothers had undergone sertraline therapy, the use of sertraline during pregnancy has been reported to cause symptoms consistent with drug deprivation syndrome. This has also been reported with other SSRI antidepressants. The use of sertraline is not recommended in pregnancy unless the clinical condition of the woman is such that the benefits of treatment outweigh the potential risks.

Newborns should be monitored if the mother's use of sertraline continues during the latter stages of pregnancy, particularly in the third trimester. following symptoms: breathing difficulties, cyanosis, apnea, seizures, temperature changes, difficulty in feeding, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia, tremors, nervousness, irritability, lethargy, continuous crying, drowsiness and sleep difficulties. Symptoms may result from serotonergic effects or withdrawal symptoms In most cases, complications occur immediately or soon (childbirth.

Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly during the later stages, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 in 1000 pregnancies. In the general population 1 to 2 cases of persistent pulmonary hypertension in the newborn (PPHN) per 1000 pregnancies may occur.

Feeding time

Published data on detectable sertraline levels in breast milk show that small amounts of sertraline and its metabolite N-desmethylsertaline are excreted in breast milk. Serum levels of sertraline in neonates were generally negligible or undetectable, with the exception of a neonate with serum levels corresponding to approximately 50% of the level found in the mother (but with no obvious clinical effects on the neonate). No reported clinical effects have been reported. to date adverse health events in nursing infants from mothers receiving sertraline, but the risk cannot be excluded. The use of sertraline in breastfeeding women is not recommended unless, in the physician's judgment, the benefits outweigh the risks.

Fertility

Animal data did not show an effect of sertraline on fertility parameters (see section 5.3).

In humans, reports from patients treated with some SSRIs have shown that the effect on sperm quality is reversible. No impact on human fertility has been observed so far.

04.7 Effects on ability to drive and use machines

Clinical pharmacology studies have shown that sertraline does not affect psychomotor skills. However, because psychotropic drugs can alter the mental or physical faculties required to cope with potentially dangerous tasks, such as driving a car or operating machinery, patients must be appropriately warned.

04.8 Undesirable effects

Nausea is the most common side effect. In the treatment of social anxiety disorder, sexual dysfunction (ejaculation failure) occurred in men in 14% of subjects taking sertraline compared with 0% with placebo. These undesirable effects are dose-dependent and are often transient in nature with continued treatment.

The undesirable effect profile commonly observed in double-blind placebo-controlled studies in patients with OCD, panic disorder, PTSD and social anxiety disorder was similar to that seen in clinical trials in patients with depression.

In Table 1 Adverse reactions observed from post-marketing experience (frequency not known) and from placebo-controlled clinical trials (involving a total of 2542 patients on sertraline and 2145 on placebo) in depression, OCD, seizure disorder of panic, PTSD and social anxiety disorder.

Some of the adverse drug reactions listed in Table 1 may decrease in intensity and frequency with continued treatment and generally do not lead to discontinuation of therapy.

Table 1: Adverse reactions


Very common (≥1 / 10) Common (≥1 / 100, Uncommon (≥1 / 1,000 to Rare (≥1 / 10,000, Very rare ( Frequency not known Infections and infestations Pharyngitis Upper respiratory tract infections, rhinitis Diverticulitis, gastroenteritis, otitis media Neoplasms benign, malignant (including cysts and polyps) Neoplasms † Disorders of the blood and lymphatic system Lymphadenopathy Leukopenia, thrombocytopenia Disorders of the immune system Anaphylactoid reaction, allergic reaction, allergy Endocrine pathologies Hyperprolactinemia, hypothyroidism and syndrome of inappropriate antidiuretic hormone secretion Metabolism and nutrition disorders Anorexia, increased appetite * Hypercholesterolemia, hypoglycemia Hyponatremia, diabetes mellitus, hyperglycemia Psychiatric disorders Insomnia (19%) Depression *, depersonalization, nightmares, anxiety *, agitation *, nervousness, decreased libido *, brussism Hallucination *, euphoric mood *, apathy, abnormal thoughts Conversion disorder, drug addiction, psychotic disorder *, aggression *, paranoia, suicidal ideation / behavior ***, sleepwalking, premature ejaculation Paroniria Nervous system disorders Dizziness (11%), Somnolence (13%), headache (21%) * Paresthesia *, tremors, hypertonia, dysgeusia, attention disturbance, Convulsions *, involuntary muscle contractions *, impaired coordination, hyperkinesia, amnesia, hypoesthesia *, speech disturbances, postural dizziness, migraine * Coma *, choreoathetosis, dyskinesia, hyperesthesia, sensory disturbances Movement disorders (including extrapyramidal symptoms such as hyperkinesis, hypertonia, dystonia, teeth grinding or gait changes), syncope. Signs and symptoms associated with Serotonin Syndrome or Neuroleptic Malignant Syndrome have also been reported; in some cases associated with concomitant use of serotonergic medicinal products which have included agitation, confusion, diaphoresis, diarrhea, fever, hypertension, rigidity and tachycardia. Akathisia and psychomotor restlessness (see section 4.4), Cerebrovascular spasm (including reversible cerebral vasoconstriction syndrome and Call-Fleming syndrome). Eye disorders Visual disturbances Glaucoma, lacrimation disorder, scotoma, diplopia, photophobia, hyphema, mydriasis * Vision alteration Ear and labyrinth disorders Tinnitus * Ear pain Cardiac pathologies Palpitations * Tachycardia Myocardial infarction, bradycardia, cardiac disorders Vascular pathologies Hot flashes * Hypertension *, flushing of the face Peripheral ischemia Bleeding abnormalities (such as epistaxis, gastrointestinal bleeding or hematuria) Respiratory, thoracic and mediastinal disorders Yawns * Bronchospasm *, dyspnoea, epistaxis Laryngospasm, hyperventilation, hypoventilation, stridor, dysphonia, hiccups Gastrointestinal disorders Diarrhea (18%), nausea (24%), dry mouth (14%) Abdominal pain, vomiting *, constipation * dyspepsia, flatulence Esophagitis, dysphagia, haemorrhoids, salivary hypersecretion, tongue disorder, belching Melaena, haematochezia, stomatitis, tongue ulceration, tooth disorder, glossitis, mouth ulceration Pancreatitis Hepatobiliary disorders Abnormal liver function Serious hepatic events (including hepatitis, jaundice and liver failure) Skin and subcutaneous tissue disorders Rash *, Hyperhidrosis Periorbital edema *, purpura *, alopecia *, cold sweat, dry skin, hives * Dermatitis, bullous dermatitis, follicular rash, hair structure alteration, skin odor alteration Rare reports of serious skin adverse reactions (SCARs), eg. Stevens-Johnson syndrome and epidermal necrolysis, angioedema, face edema, photosensitivity, skin reactions, pruritus Musculoskeletal and connective tissue disorders Myalgia Osteoarthritis, muscle weakness, back pain, muscle twitching Bone disorders Arthralgia, muscle cramps Renal and urinary disorders Nocturia, urinary retention *, polyuria, pollakiuria, micturition disturbances Oliguria, urinary incontinence *, initial difficulty in urination Reproductive system and breast disorders ** Failure to ejaculate (14%) Sexual dysfunction, erectile dysfunction Vaginal bleeding, female sexual dysfunction Menorrhagia, atrophic vulvovaginitis, balanoposthitis, genital discharge, priapism *, galactorrhea * Gynecomastia, menstrual irregularities General disorders and administration site conditions Fatigue (10%) * Chest pain * Malaise *, chills, pyrexia *, asthenia *, thirst Hernia, injection site fibrosis, drug tolerance impaired, gait disturbance, non-evaluable events Peripheral edema Diagnostic tests Weight reduction, * weight gain * Alanine aminotransferase increased, aspartate aminotransferase increased, seminal fluid changes Altered laboratory results, altered platelet function, increased serum cholesterol Injury and poisoning Wounds Medical and surgical procedures Vasodilation procedure If the adverse reactions occurred in patients being treated for depression, OCD, panic disorder, PTSD, and social anxiety disorder, the term for the classification was reclassified based on the system organ classification used in the depression studies. One case of malignancy was reported in one patient receiving sertraline versus no case reported in the placebo arm. * these adverse reactions also occurred in the post-marketing phase of the medicinal product ** the denominator uses the number of patients in that combined group based on gender: sertraline (1118 males, 1424 females), placebo (926 males, 1219 females). For OCD, only studies lasting 1-12 weeks are available for short-term treatment *** Cases of suicidal ideation and suicidal behaviors have been reported during treatment with sertraline or soon after treatment discontinuation (see section 4.4).

Withdrawal symptoms observed following discontinuation of sertraline

Discontinuation of sertraline (especially if abrupt) usually leads to withdrawal symptoms. The most commonly reported events were dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, tremor and headache. Generally these events are mild to moderate in intensity and are self-limiting; however, in some patients they may be severe and / or prolonged. Therefore, if treatment with sertraline is no longer If necessary, gradual discontinuation of treatment by gradual dose decrease is recommended (see sections 4.2 and 4.4).

Elderly subjects

The use of SSRIs or SRNIs, including sertraline, has been associated with clinically significant cases of hyponatraemia in elderly patients who may be at increased risk for this adverse event (see section 4.4).

Pediatric population

In the more than 600 pediatric patients treated with sertraline, the overall adverse reaction profile was generally comparable to that seen in adult studies. The following adverse reactions were reported in controlled clinical trials (n = 281 patients treated with sertraline):

Very common (≥1 / 10): headache (22%), insomnia (21%), diarrhea (11%), and nausea (15%).

Common (≥ 1/100,: chest pain, mania, pyrexia, vomiting, anorexia, affective instability, aggression, agitation, nervousness, disturbance in attention, dizziness, hyperkinesia, migraine, somnolence, tremors, visual disturbances, dryness of the mouth, dyspepsia, nightmares, fatigue, urinary incontinence, rash, acne, epistaxis, flatulence.

Uncommon (≥1 / 1000,: QT interval prolongation on ECG, suicide attempt, convulsions, extrapyramidal disorders, paraesthesia, depression, hallucinations, purpura, hyperventilation, anemia, liver function abnormalities, alanine aminotransferase increased, cystitis, herpes simplex, otitis externa, ear pain, eye pain, mydriasis, malaise, haematuria, pustular rash, rhinitis, wounds, weight reduction, muscle contractions, abnormal dreams, apathy, albuminuria, pollakiuria, polyuria, pain in the breast, menstrual disorders, alopecia, dermatitis, skin disorders, altered skin odor, hives, brussism, flushing of the face.

Frequency not known: enuresis.

Class effects

Epidemiological studies conducted mainly in patients 50 years of age and older have shown an increased risk of bone fractures in patients treated with SSRIs or tricyclic antidepressants. The mechanism underlying this risk is not known.

04.9 Overdose

Toxicity

Available data demonstrate that sertraline has a large safety margin in case of overdose. Cases of overdose have been reported due to taking sertraline alone at doses up to 13.5 grams. Deaths have been reported due to overdoses of sertraline mainly taken in combination with other medicines and / or alcohol. Therefore, any case of overdose should be treated clinically with determination.

Symptoms

Symptoms of overdose include serotonin-mediated side effects such as sleepiness, gastrointestinal disturbances (such as nausea and vomiting), tachycardia, tremor, agitation and dizziness. Coma episodes have been reported less frequently.

Treatment

There are no specific antidotes to sertraline. If necessary, a clear airway should be established and maintained and adequate oxygenation and ventilation ensured. Activated charcoal, which can be used with a cathartic, may be as effective or more effective than gastric lavage and should be considered. in the treatment of overdose. Induction of emesis is not recommended. Along with general symptomatic and supportive measures, monitoring of cardiac and other vital signs is recommended. Due to the large volume of distribution of sertraline, it is unlikely that forced diuresis, dialysis, haemoperfusion and exchange transfusion may be beneficial.

Overdose of sertraline may prolong the QT interval; ECG monitoring is recommended in all cases of ingestion of excessive doses of sertraline.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: Selective serotonin reuptake inhibitors (SSRIs). ATC code: N06AB06.

Sertraline is a potent specific inhibitor of neuronal uptake of serotonin (5-HT) in vitro, with a resultant enhancement of the effects of 5-HT in animals. It has only a very weak effect on the neuronal re-uptake of norepinephrine and dopamine. When administered at therapeutic doses, sertraline blocks the uptake of serotonin into human platelets. In animals, it lacks stimulating, sedative or anticholinergic activity as well as cardiotoxicity. In controlled clinical trials in healthy volunteers, sertraline did not cause sedation and did not interfere with psychomotor performance. According to its selective inhibition of 5-HT re-uptake, sertraline does not potentiate catecholaminergic activity. Sertraline has no affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA or GABA receptors. Chronic administration of sertraline in animals has been associated with down-regulation of brain norepinephrine receptors, as observed with other clinically effective antidepressants and drugs for obsessive-compulsive disorder.

Sertraline has not been shown to be addictive. In a randomized, double-blind, placebo-controlled clinical trial conducted to compare addiction induced in humans by sertraline, alprazolam and amphetamine-D, sertraline produced no obvious subjective effects indicative of potential abuse. , the magnitude of drug dependence, euphoria and abuse potential related to alprazolam and amphetamine-D was judged by study subjects to be significantly higher than placebo. Administration of sertraline produced neither the stimulation and anxiety associated with amphetamine-D nor the sedative effects and psychomotor impairment associated with alprazolam. Sertraline does not act as a positive reinforcer in rhesus monkeys trained to self-administer cocaine. nor does it replace the discriminative stimulus induced by D-amphetamine or pentobarbital in these animals.

Clinical Studies

Major depression

A study was conducted involving outpatients with depression who responded to an initial 8-week open-label treatment phase with sertraline 50-200 mg / day. These patients (n = 295) were randomized to continue a 44-week double-blind treatment with sertraline 50-200 mg / day or placebo. A statistically lower relapse rate was observed in patients taking sertraline compared to those in the placebo group. The mean dose for subjects who completed treatment was 70 mg / day. The% of patients responder (defined as those patients who did not relapse) in the sertraline and placebo groups was 83.4% and 60.8%, respectively.

Post-Traumatic Stress Disorder (PTSD)

The pooled data from the 3 PTSD studies conducted in the general population showed a lower response rate in men than in women. In the two positive studies on the general population, the percentage of responder for men and women taking sertraline versus placebo was similar (women: 57.2% vs 34.5%; men: 53.9% vs 38.2%). The number of men and women in the pooled general population studies was 184 and 430, respectively, and therefore the results obtained in women are more robust and other variables at baseline were associated in men (higher substance abuse, longer duration of treatment, origin of the trauma) related to a reduction of the effect.

Pediatric OCD

The safety and efficacy of sertraline (50-200 mg / day) has been evaluated in the treatment of non-depressed, outpatient children (6-12 years) and adolescents (13-17 years) with obsessive-compulsive disorder (OCD). . After one week of single-blind placebo treatment, patients were randomized and assigned to twelve weeks of flexible dosing of sertraline or placebo. Children (ages 6-12 years) were initially treated with the dose from 25 mg Patients treated with sertraline reported significantly greater improvement than patients in the placebo group on the scales Children "s Yale-Brown Obsessive Compulsive Scale CY-BOCS (p = 0.005), NIMH Global Obsessive Compulsive Scale (p = 0.019), and CGI Improvement (p = 0.002). In addition, a trend for greater improvement in patients taking sertraline compared to those taking placebo was also observed at the scale CGI Severity (p = 0.089). The mean baseline score and changes from baseline on the CY-BOC scale for the placebo group were 22.25 ± 6.15 and -3.4 ± 0.82, respectively, while the mean score for the sertraline group was at baseline and score changes from baseline were 23.36 ± 4.56 and -6.8 ± 0.87, respectively. As part of a post-hoc analysis, patients responder, defined as patients with a 25% or greater reduction in CY-BOC scale (main efficacy measure) from baseline to endpoint, were 53% of patients treated with sertraline compared to 37% of those treated with placebo ( p = 0.03).

No long-term safety and efficacy data are available in this pediatric population.

No data are available in children below 6 years of age.

05.2 Pharmacokinetic properties

Absorption

Sertraline exhibits dose proportional pharmacokinetics over the dose range of 50 mg to 200 mg. In humans, following a daily oral dose of 50 mg-200 mg for 14 days, peak plasma concentrations of sertraline are they reach between 4.5 and 8.4 hours after daily administration of the drug.

Food does not significantly alter the bioavailability of sertraline tablets.

Food does not significantly alter the bioavailability of sertraline concentrate for oral solution.

Distribution

About 98% of the circulating drug is bound to plasma proteins.

Biotransformation

Sertraline exhibits extensive hepatic first pass metabolism.

Based on clinical data e in-vitro, it can be concluded that sertraline follows multiple metabolic pathways including CYP3A4, CYP2C19 (see section 4.5) and CYP2B6. Sertraline and its major metabolite desmethylsertraline are also substrates for P-glycoprotein. in-vitro.

Elimination

The mean plasma half-life of sertraline is approximately 26 hours (dose range 22-36 hours). Consistent with the terminal elimination half-life, there is approximately two-fold accumulation until steady-state concentrations are reached. after one week with once-a-day administration of the medicine. The half-life of N-desmethylsertraline is in the range of 62-104 hours. Sertraline and N-desmethylsertraline are both extensively metabolised in humans and the resulting metabolites are excreted in the faeces and urine in equal amounts. Only a small amount (

Pharmacokinetics in particular groups of patients

Pediatric patients with OCD

The pharmacokinetics of sertraline were studied in 29 pediatric patients, aged 6-12 years, and in 32 adolescent patients aged 13-17 years. The dose of sertraline in these patients was gradually increased to a dose of 200 mg / day over 32 days, starting with a starting dose of 25 mg or 50 mg, followed by gradual increases. The 25 mg and 50 mg dosing regimens were equally tolerated. At steady-state for the 200 mg dose, plasma levels of sertraline in the 6 to 12 year old group were approximately 35% higher than in the 13 to 17 year old group, and 21% higher than in the 13 to 17 year old group. reference of adults. No significant differences in clearance were observed between males and females. Therefore, in children, particularly those with low body weight, the use of a low starting dose and gradual increases of 25 mg is recommended. The same dosage as in adults can be used in adolescents.

Teenagers and the elderly

The pharmacokinetic profile in adolescents or the elderly does not differ significantly from that found in adults aged 18 to 65 years.

Hepatic impairment

In patients with hepatic impairment, the half-life of sertraline is prolonged and the AUC increases three-fold (see sections 4.2 and 4.4).

Renal impairment

There was no significant accumulation of sertraline in patients with moderate to severe renal impairment.

Pharmacogenomics

Plasma levels of sertraline were 50% higher in CYP2C19 poor metabolisers than in extensive metabolisers. The clinical significance is unclear and patients need to be titrated based on their clinical response.

05.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. Reproductive toxicity studies in animals revealed no teratogenic or adverse effects on fertility. The observed fetotoxicity was probably attributable to maternal toxicity. Postnatal survival and body weight of the offspring decreased only in the first day after birth. Early postnatal mortality was shown to be caused by postnatal exposure in utero. 15th day of pregnancy. The postnatal developmental delays observed in the offspring of treated females were probably due to effects on the mother and therefore not relevant in the assessment of risks to humans.

Data from rodent and non-rodent animals revealed no effects on fertility.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Zoloft film-coated tablets

Tablet core:

Calcium hydrogen phosphate (E341)

Microcrystalline cellulose (E460)

Hydroxypropylcellulose (E463)

Sodium starch glycolate

Magnesium stearate (E572)

Tablet coating:

White Opadry containing:

Titanium dioxide (E171)

Hypromellose (E464)

Macrogol

Polysorbate 80 (E433)

Opadry Clear containing:

Hypromellose (E464)

Macrogol

Zoloft concentrate for oral solution

Glycerol (E422)

Ethanol

Levomenthol

Butylated hydroxytoluene (E321)

06.2 Incompatibility

Film-coated tablets

Not relevant

Concentrate for oral solution

Zoloft (sertraline) concentrate for oral solution must not be diluted with other liquids except those specified in section 6.6.

06.3 Period of validity

Film-coated tablets: 5 years.

Concentrate for oral solution: 3 years.

After first opening the bottle: 28 days.

06.4 Special precautions for storage

Do not store above 30 ° C.

06.5 Nature of the immediate packaging and contents of the package

Zoloft 25 mg film-coated tablets

The tablets are packed in aluminum / PVC blister packs of 7, 28 or 98 tablets.

Zoloft 50 mg film-coated tablets

The tablets are packed in aluminum / PVC blister packs of 10, 14,15, 20, 28, 30, 50, 56, 60, 84, 98, 100, 200, 294, 300 or 500 tablets.

Zoloft film-coated tablets 100 mg

The tablets are packed in aluminum / PVC blister packs of 10, 14,15, 20, 28, 30, 50, 56, 60, 84, 98, 100, 200, 294, 300 or 500 tablets.

Zoloft concentrate for oral solution

Zoloft oncentrate for oral solution 20 mg / ml is available in 60 ml dark glass bottles. The bottle is equipped with a screw cap with a dispenser incorporated in the cap.

Not all pack sizes may be marketed.

06.6 Instructions for use and handling

Film-coated tablets

No special instructions.

Concentrate for oral solution

Sertraline concentrate for oral solution contains 20 mg / ml of sertraline. It must be diluted before use. Use the dispenser to remove the required amount of concentrate for oral solution and dilute in approximately 120 ml (a glass) of water, lemon soda, lemonade or orange juice. Do not dilute sertraline concentrate for oral solution with other liquids than those listed. The dose should be taken immediately after dilution. It does not need to be prepared in advance. Sometimes, after dilution, the solution may be cloudy, but this is normal.

07.0 MARKETING AUTHORIZATION HOLDER

Pfizer Italia S.r.l. - Via Isonzo, 71 - 04100 Latina

08.0 MARKETING AUTHORIZATION NUMBER

Zoloft film-coated tablets 25 mg - 7 tablets - AIC n. 027753122

Zoloft film-coated tablets 25 mg - 28 tablets - AIC n. 027753134

Zoloft film-coated tablets 50 mg - 15 divisible tablets - AIC n. 027753033

Zoloft film-coated tablets 50 mg - 30 divisible tablets - AIC n. 027753108

Zoloft film-coated tablets 100 mg - 15 tablets - AIC n. 027753045

Zoloft film-coated tablets 100 mg - 30 tablets - AIC n. 027753110

Zoloft concentrate for oral solution 20 mg / ml - 60 ml bottle with dispenser - AIC n. 027753096

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

7 May 2002/23 June 2009

10.0 DATE OF REVISION OF THE TEXT

AIFA determines of 17/12/2012

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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