Active ingredients: Sertraline
Sertraline Actavis 50 mg film-coated tablets
Sertraline Actavis 100 mg film-coated tablets
Why is Sertraline used - Generic Drug? What is it for?
Sertraline Actavis 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.
Sertraline Actavis 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 syndrome (SSPT) (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).
SSPT 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 (eg, 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 Sertraline Actavis has been prescribed for you.
Contraindications When Sertraline - Generic Drug should not be used
Do not take Sertraline Actavis:
- If you are allergic to sertraline or any of the other ingredients of this medicine (listed in section 6.1);
- 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 (antipsychotic medicine).
Precautions for use What you need to know before taking Sertraline - Generic Drug
Medicines are not always suitable for everyone. Tell your doctor before taking Sertraline if you suffer from or have suffered in the past from any of the following conditions:
- Serotonin Syndrome or Neuroleptic Malignant Syndrome. In rare cases, these syndromes 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 Sertraline Actavis. You will also need to 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 bump of Sertraline Actavis.
- Diabetes: Blood glucose levels may be altered due to treatment with Sertraline Actavis and the dose of diabetes medicines may need to be adjusted.
- 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 previously had suicidal thoughts (see below - suicidal thoughts and worsening of your depression or anxiety disorder). - If you have suffered from bleeding problems or if you have taken medicines that thin the blood (eg acetylsalicylic acid (aspirin) or warfarin) or which may increase the risk of bleeding.
- Children or adolescents under the age of 18. Sertraline Actavis is only to be used to treat children and adolescents between the ages of 6 and 17 who suffer from obsessive-compulsive disorder. If your child or adolescent is being treated for this disorder, the doctor will want to monitor them carefully (see Use in children and adolescents below).
- If you are undergoing electroconvulsive therapy (ECT).
- If you have eye problems, such as certain types of glaucoma (increased pressure in the eye).
Urinalysis for benzodiazepines can give false positives when taking sertraline.
By carrying out more specific analyzes, sertraline can be distinguished from bezodiazepines.
Restlessness / Akathisia
The use of sertraline has been related to akathisia (distressing restlessness and need to move, often associated with the inability to sit or stand still). This condition is more likely to occur in the first few weeks of treatment. An increase in dose may be harmful to patients who develop these symptoms.
Drug withdrawal reaction
Withdrawal reactions that develop when medication is stopped are common, particularly if treatment is stopped suddenly (see section 4 Possible side effects). The risk of withdrawal reactions depends on the duration of treatment, the dose and the extent of the dose reduction. Generally these symptoms are mild to moderate in intensity; however, in some patients they may be severe. They usually occur in the first few days after discontinuation. of treatment. These symptoms generally 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, depending on the individual patient's needs.
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 can get worse when you first take antidepressants, because all these medicines take some time to work. usually about 2 weeks but sometimes even 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.
It may be helpful to tell a relative or close friend that you are depressed or have an anxiety disorder and ask them to read this leaflet. You may want to ask them if they think your depression or anxiety disorder is getting worse, or if they are concerned about changes in their behavior.
Use in children and adolescents:
Sertraline should not normally be used in children and adolescents under the age of 18, with the exception of patients with Obsessive Compulsive Disorder. Patients under the age of 18 have an increased risk of side effects, such as suicide attempt, suicidal thoughts and hostile behavior (mainly aggression, oppositional behavior and anger) when treated with this class of medicines. However, it is possible that the doctor may decide to prescribe Sertraline Actavis to a patient under the age of 18 if this is in the patient's best interest. If the doctor has prescribed Sertraline Actavis to a patient under the age of 18 and you wish to speak to contact your doctor about this decision.In addition, if any of the symptoms listed above develop or worsen when a patient under the age of 18 is being treated with Sertraline Actavis, you should inform your doctor.
Finally, the long-term safety of Sertraline Actavis on growth, maturation and cognitive and behavioral development in this age group has not been demonstrated.
Interactions Which drugs or foods can modify the effect of Sertraline - Generic Drug
Tell your doctor if you are taking, have recently taken or might take any other medicines.
Some medicines can affect the way Sertraline Actavis works, or Sertraline Actavis can reduce the effectiveness of other medicines taken at the same time.
Taking Sertraline Actavis 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 Sertraline Actavis together with MAOIs.
- Medicines to treat mental disorders (pimozide). Do not use Sertraline Actavis together with pimozide.
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. Talk to your doctor.
- Products containing the amino acid tryptophan.
- Medicines to treat severe pain (e.g. tramadol).
- Medicines used in anesthesia or to treat chronic pain (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 for the treatment of epilepsy (phenytoin, phenobarbital, carbamazepine).
- 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, nefazodone, fluoxetine, fluoxamine).
- Medicines to treat schizophrenia and other mental disorders (such as perphenazine, levomepromazine and olanzapine).
- Medicines to treat fungal infections (e.g. ketoconazole, itraconazole, posaconazole, voriconazole, fluoconazole).
- Medicines to treat bacterial infections (e.g. erythromycin, clarithromycin, telithromycin).
- Medicines to treat tuberculosis (rifampicin). - Medicines to treat viral infections including HIV and hepatitis C (e.g. protease inhibitors).
- Medicines to treat high blood pressure or other heart conditions (e.g. verapamil, diltiazem).
- Medicines for the reduction of gastric acid secretion (e.g. omeprazole, lansoprazole, pantoprazole, rabeprazole).
- Medicines to prevent nausea and vomiting (aprepitant).
Sertraline Actavis with food, drink and alcohol:
Sertraline Actavis tablets can be taken with or without food.
Grapefruit juice should not be taken concomitantly with Sertraline Actavis as it may increase the level of sertraline in the body.
Alcohol consumption should be avoided during treatment with Sertraline Actavis
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility:
If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this 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 fetus. Women of childbearing potential should use an adequate method of contraception if they are being treated with sertraline.
Make sure your midwife and / or doctor know you are being treated with Sertraline Actavis. When taken during pregnancy, particularly in the last trimester, medicines such as Sertraline Actavis may increase the risk in newborns of a serious condition called Persistent Pulmonary Hypertension of the Newborn (PPHN), which causes rapid breathing and a bluish discoloration of the baby. These symptoms usually begin during the first 24 hours after the baby is born.If the baby experiences these symptoms, you should contact your midwife and / or doctor immediately.
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 your 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.
If you have been told by your doctor that you have an "intolerance to some sugars, contact your doctor before taking this medicinal product.
Dose, Method and Time of Administration How to use Sertraline - Generic Drug: Posology
Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
Sertraline Actavis tablets can be taken with or without food.
Take this medicine once a day, in the morning or in the evening.
The recommended dose is:
Adults:
Depression and Obsessive Compulsive Disorder:
For depression and OCD, the usual effective dose is 50 mg / day. The daily dose can be increased by 50 mg to 50 mg and at intervals of at least one week over a period of several weeks. The maximum recommended dose is 200 mg / day.
Panic Disorder, Social Anxiety Disorder and Post Traumatic Stress Syndrome:
For panic disorder, social anxiety and post-traumatic stress syndrome, treatment should be started at a dose of 25 mg / day, and then increased to 50 mg / day after one week.
The daily dose can then be increased by 50 mg to 50 mg over a period of several weeks. The maximum recommended dose is 200 mg / day.
Children and adolescents:
Sertraline Actavis is only to be used for the treatment of children and adolescents with Obsessive Compulsive Disorder (OCD) aged 6-17 years.
Obsessive Compulsive Disorder:
Children aged 6-12 years: the recommended starting dose is 25 mg / day.
After one week your doctor may increase the dose to 50 mg / day. The maximum dose is 200 mg / day.
Teenagers aged 13-17:
The recommended starting dose is 50 mg / day. The maximum dose is 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 may take several weeks for symptoms to start improving
Overdose What to do if you have taken an overdose of Sertraline - Generic Drug
If you take more Sertraline Actavis than you should:
If you accidentally take an overdose of Sertraline Actavis contact your doctor immediately or go to the nearest emergency department. 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 Sertraline Actavis:
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 Sertraline Actavis:
Do not stop taking Sertraline Actavis unless your doctor tells you to. Your doctor may wish to gradually reduce your dose of Sertraline Actavis 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 Sertraline Actavis, please talk to your doctor.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Sertraline - Generic Drug
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Nausea is the most common side effect. Side effects depend on the dose and are often transient 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, swelling of the eyelids, face or lips.
- If you experience agitation, confusion, diarrhea, high fever and high blood pressure, excessive sweating and rapid heartbeat. These are the symptoms of Serotonin Syndrome or Neuroleptic Malignant Syndrome. In rare cases, these syndromes can occur when certain medicines are taken together with sertraline. Your doctor may want 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 suicidal thoughts, contact your doctor or go to a hospital immediately (see section 2).
If you start feeling restless and can no longer sit or stand after starting treatment with Sertraline Actavis. You should tell your doctor if you start to feel restless.
The following side effects were observed in clinical studies in adult patients:
Very common side effects (affects more than 1 in 10 people):
Insomnia, dizziness, somnolence, headache, diarrhea, nausea, dry mouth, absence of ejaculation, fatigue.
Common side effects (affects 1 to 10 in 100 people): Sore throat, anorexia, increased appetite, depression, feeling strange, nightmares, anxiety, agitation, nervousness, decreased sexual interest, teeth grinding, numbness and tingling , tremors, muscle tension, taste disturbance, lack of attention, disturbed vision, ringing in the ears, palpitations, flushing, yawning, abdominal pain, vomiting, constipation, stomach upset, stomach air, rash, increased blood pressure sweating, muscle pain, sexual dysfunction, erectile dysfunction, chest pain.
Uncommon side effects (affects 1 to 10 users in 1,000):
Cold chest, runny nose, hallucinations, excessive feeling of happiness, lack of personal care, altered thoughts, seizures, involuntary muscle twitching, impaired coordination, excessive movement, amnesia, decreased sensation, slurred speech, dizziness when sitting stand up, migraine, ear pain, rapid heartbeat, high blood pressure, flushing of the face, difficulty in breathing, possible wheezing, shortness of breath, nosebleed, esophageal problems, difficulty swallowing, haemorrhoids, increased salivation , tongue disorders, belching, swollen eyes, red spots on the skin, hair loss, cold sweats, dry skin, hives, osteoarthritis, muscle weakness, back pain, muscle twitching, urination at night, inability to urinate, increased amount of urine, increased urinary frequency, problems urinating, vaginal bleeding, female sexual dysfunction, malaise, chills, fever, weakness, thirst, weight reduction, weight gain.
Rare side effects (affects 1 to 10 users in 10,000):
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, aggression, paranoia, thoughts and behaviors suicidal, sleepwalking, premature ejaculation, coma, abnormal movements, difficulty moving, increased sensations, sensory disturbances, glaucoma, lacrimation problems, eye spots, double vision, light discomfort, blood in the eye , dilation of the pupils, heart attack, slow heartbeat, heart problems, poor blood circulation in the arms and legs, closing of the throat, faster breathing, slowed breathing, difficulty speaking, hiccups, blood in stools, sore throat, tongue ulceration, dental disorder, tongue problems, mouth ulceration, liver function problems, blistered skin, inflammation of the hair follicles, altered hair structure, altered skin odor, bone disorders, decreased urination, urinary incontinence, urinary hesitation, excessive vaginal bleeding, dryness of the vaginal area, red painful penis and foreskin, genital discharge, prolonged erection, breast discharge, hernia, impaired drug tolerance, difficulty walking, abnormal laboratory test values, altered semen, wounds, relaxation of blood vessels.
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, low thyroid hormone levels, endocrine problems, diabetes, high blood sugar levels, low blood salt levels, terrifying altered dreams, severe pain sudden head (which could be a sign of a serious condition called Reversible Cerebral Vasoconstriction Syndrome (RCVS)), problems with muscle movements (such as frequent movements, tense muscles and difficulty walking), fainting, impaired vision, unequal pupil size, problems bleeding (such as nosebleed, stomach bleeding or blood in the urine), lung disease, pancreatitis, severe liver function problems, jaundice, skin edema, skin reaction to the sun, itching, joint pain, muscle cramps, enlargement breasts, menstrual irregularities, leg swelling, bleeding problems and severe reactions allergic ions.
An increased risk of bone fractures has been observed in patients taking this type of medicine.
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.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via AIFA, Website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
Reporting side effects can provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the blister and / or bottle and carton after "EXP". The expiry date refers to the last day of that month.
This medicinal product does not require any special storage conditions.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What Sertraline Actavis contains
- The active ingredient is: sertraline
- The other ingredients are: lactose monohydrate, microcrystalline cellulose, povidone K30, croscarmellose sodium, magnesium stearate. Coating (50 mg): hypromellose 6, talc, propylene glycol and titanium dioxide (E 171). Coating (100 mg): hypromellose 6, hypromellose 15, talc, propylene glycol and titanium dioxide (E 171).
What Sertraline Actavis looks like and contents of the pack
Sertraline Actavis 50 mg film-coated tablets:
White, oval, 10 mm x 5 mm, biconvex, film-coated tablets. On one side they have a fracture line and on the other they are marked with the letter "L".
Sertraline Actavis 100 mg film-coated tablets:
White, round, 10mm, biconvex, film-coated tablets. On one side they have a fracture line and on the other they are marked with the letter "C".
The tablets can be divided into equal halves.
Sertraline Actavis 50 mg and 100 mg are available in blisters of 7, 10, 14, 15, 20, 28, 28x1, 30, 30x1, 50, 50x1, 60, 98, 98x1, 100 and 100x1 tablets and in bottles of 100, 250 and 500 tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
SERTRALINA ACTAVIS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Sertraline Actavis 50 mg film-coated tablets
Each film-coated tablet contains 50 mg of sertraline (as hydrochloride).
Excipient: 79.65 mg lactose monohydrate / film-coated tablet.
Sertraline Actavis 100 mg film-coated tablets
Each film-coated tablet contains 100 mg of sertraline (as hydrochloride).
Excipient: 159.3 mg lactose monohydrate / film-coated tablet.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablet
Sertraline Actavis 50 mg film-coated tablets
White, oval, biconvex film-coated tablet, scored on one side and marked with "L" on the other side.
Sertraline Actavis 100 mg film-coated tablets
White, round, biconvex, film-coated tablets, scored on one side and marked with "C" on the other side.
The tablets can be divided into equal halves.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Sertraline is indicated in the treatment of:
• Major depressive episodes. Prevention of relapses of major depressive episodes.
• Panic Disorder, with or without agoraphobia.
• Obsessive Compulsive Disorder (OCD) in adult patients and in pediatric patients aged 6 to 17 years.
• Social anxiety disorder.
• Post-traumatic stress syndrome (SSPT)
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.
Initial treatment
Depression and OCD
Sertraline treatment should be initiated at a dose of 50 mg / day
Panic Disorder, SSPT 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 SSPT
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 adjustments depending on the clinical response.
Depression
Prolonged treatment may also be appropriate in preventing recurrence of major depressive episodes (EDM). In most cases, the recommended dose in preventing relapse 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
The use of sertraline in patients with hepatic disorders should be done with caution. Lower and less frequent doses should be used in patients with hepatic insufficiency (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).
04.4 Special warnings and appropriate precautions for use
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 drugs (e.g. tryptophan, fenfluramine, and 5-HT agonists)
Concomitant administration of sertraline and other drugs that potentiate 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 of 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.
Convulsions
Convulsions 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. It is 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 of 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 for 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 drugs 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 hyponatraemia and appropriate medical therapy instituted. The 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. epileptics, 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 insufficiency
Sertraline is extensively metabolised in the liver. A multiple dose pharmacokinetic study conducted in subjects with mild, 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 hepatic disorders. Lower and less frequent doses should be used if sertraline is administered to patients with hepatic insufficiency. it must not be used in patients with severe hepatic impairment (see section 4.2).
Use in case of renal insufficiency
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
Clinical trials were conducted on over 700 elderly patients (age> 65 years). 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 may alter glycemic control, possibly due to an improvement in depressive symptoms. Glycemic control should be closely monitored in patients concomitantly taking sertraline and dose adjustments 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.
Medicinal product containing lactose
As the tablets contain the excipient lactose (see section 6.1), patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.
04.5 Interactions with other medicinal products and other forms of interaction
Contraindicated
Monoamine oxidase inhibitors
Irreversible (non-selective) inhibitors of MAOIs (selegiline)
Sertraline should not be used in combination with irreversible (non-selective) MAOIs such as selegiline. Sertraline treatment should not be started for at least 14 days after stopping treatment with an irreversible (non-selective) MAOI.Treatment with sertraline should be stopped for at least 7 days prior to initiation of treatment with an irreversible (non-selective) MAOI (see section 4.3).
Reversible and selective inhibitor of MAOIs (moclobemide)
Due to the risk of serotonin syndrome, the combination of sertraline and a reversible and selective MAOI inhibitor, such as moclobemide, is not recommended. 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 recently stopped treatment with a MAOI and started 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 depressant drugs 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.
Special precautions
Lithium
In a placebo-controlled study in healthy volunteers, the co-administration of sertraline and lithium did not result in significant changes in the pharmacokinetics of lithium, but it did result in an increase in tremor episodes compared to the placebo group, showing a possible pharmacodynamic interaction. Patients should be monitored appropriately when sertraline is administered with lithium.
Phenytoin
From a placebo-controlled clinical study conducted 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 still advisable to monitor plasma phenytoin concentrations 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
Cases of patients with weakness, hyperreflexia, incoordination, confusion, anxiety and agitation following the use of sertraline and sumatriptan have been rarely reported in the marketing phase of the product.
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.
Drugs 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).
Drugs 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 a moderate (mean 23% -37%) increase in steady-state 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), CYP 2C19 substrate diazepam and CYP 2C9 substrates (tolbutamide, glibenclamide and phenytoin). Studies in vitro indicate that sertraline has negligible or no inhibitory potential for CYP 1A2.
04.6 Pregnancy and lactation
Pregnancy
There are no adequate studies in pregnant women. However, the extensive data available did not reveal 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).
Symptoms consistent with drug deprivation syndrome have been reported in some infants whose mothers were treated with sertraline. The same symptoms have 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 quickly (delivery.
Epidemiological data indicate that the use of SSRIs during pregnancy, particularly late pregnancy, 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 PPHN cases per 1000 pregnancies have occurred.
Feeding time
Published data on detectable sertraline levels in breast milk show that sertraline and its metabolite N-desmethyl sertraline 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 effects on the health of nursing infants from mothers being treated with sertraline, but possible risks cannot be excluded. The use of sertraline in breastfeeding women is not recommended unless, in the opinion of the physician, the benefits are greater than the risks.
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 properly 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 to 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, SSPT and social anxiety disorder was similar to that observed in clinical trials in patients with depression.
Table 1 shows adverse reactions observed from post-marketing experience (frequency not known) and from placebo-controlled clinical trials (including a total of 2542 patients on sertraline and 2145 on placebo) in depression, OCD, panic disorder, SSPT 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
Frequency of adverse reactions observed in placebo-controlled clinical trials in depression, OCD, panic disorder, SSPT and social anxiety disorder. Pooled analysis and experience related to drug marketing phase (frequency not known).
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 tapering the dose is advised (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, bruxism, facial flushing.
Effects of the class
Epidemiological studies, conducted predominantly in patients aged 50 years and older, show an increased risk of bone fractures in patients treated with SSRIs and TCAs. The mechanism leading to 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 due to the intake of sertraline have occurred with doses greater than 13.5 grams. The use of excessive doses of sertraline mainly associated with other drugs and / or alcohol has sometimes been fatal. Therefore, any case of overdose must be dealt with vigorously.
Symptoms
Symptoms of overdose include serotonin-mediated undesirable 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, cardiac and vital sign monitoring is recommended. Due to the large volume of distribution of sertraline, it is unlikely that forced diuresis, dialysis, hemoperfusion and exchange transfusion may be beneficial.
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 the animal 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 Syndrome (SSPT)
Pooled data from the 3 SSPT 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). one week of single-blind placebo treatment, patients were randomized and assigned to twelve weeks of treatment with flexible doses of sertraline or placebo. Children (ages 6-12 years) were initially treated with the 25 mg dose 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 the daily administration of the drug.
Food does not significantly alter the bioavailability of sertraline tablets.
Distribution
About 98% of the circulating drug is bound to plasma proteins.
Biotransformation
Sertraline exhibits extensive hepatic first pass metabolism.
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 a week with the administration of the drug once a day. 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, a low starting dose and gradual increases of 25 mg are recommended in children, particularly those with low body weight. 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 insufficiency
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).
Kidney failure
There was no significant accumulation of sertraline in patients with moderate to severe renal impairment.
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 in utero exposure. after the 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.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Sertraline Actavis 50 mg film-coated tablets
Tablet core:
Lactose monohydrate
Microcrystalline cellulose
Povidone K30
Croscarmellose sodium
Magnesium stearate
Tablet coating:
Hypromellose 6
Talc
Propylene glycol
Titanium dioxide (E 171)
Sertraline Actavis 100 mg film-coated tablets
Tablet core:
Lactose monohydrate
Microcrystalline cellulose
Povidone K30
Croscarmellose sodium
Magnesium stearate
Tablet coating:
Hypromellose 6
Hypromellose 15
Talc
Propylene glycol
Titanium dioxide (E 171)
06.2 Incompatibility
Not relevant.
06.3 Period of validity
4 years.
06.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Nature and contents of the container.
PVC / PVDC / aluminum blisters in one pack: 30 tablets.
06.6 Instructions for use and handling
No particular need.
07.0 MARKETING AUTHORIZATION HOLDER
ACTAVIS Group PTC ehf - Reykjavíkurvegi 76-78, 220 Hafnarfjörð (Iceland)
08.0 MARKETING AUTHORIZATION NUMBER
AIC n. 038309074 / M - 50 mg film-coated tablets - 30 tablets in PVC / PVDC / AL blister
AIC n. 038309264 / M - 100 mg film-coated tablets - 30 tablets in PVC / PVDC / AL blister
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Determination n. 869 of 30.05.2008 - Official Gazette no. 136 of 12.06.2008
10.0 DATE OF REVISION OF THE TEXT
November 2010
