Active ingredients: Escitalopram
Entact 5 mg film-coated tablets
Entact 10 mg film-coated tablets
Entact 15 mg film-coated tablets
Entact 20 mg film-coated tablets
Entact package inserts are available for pack sizes: - Entact 5 mg film-coated tablets, Entact 10 mg film-coated tablets, Entact 15 mg film-coated tablets, Entact 20 mg film-coated tablets
- Entact 10 mg / ml oral drops, solution
- Entact 20 mg / ml oral drops, solution
Indications Why is Entact used? What is it for?
Entact contains the active substance escitalopram. Entact belongs to the group of antidepressant medicines called Selective Serotonin Reuptake Inhibitors (SSRIs). These medicines help increase serotonin levels in the brain. Alterations in the brain's serotonin system are considered important factors in the development of depression and related disorders.
The active substance in Entact is escitalopram and is used to treat depression (major depressive episodes) and anxiety (such as panic disorder with or without agoraphobia, social anxiety disorder and generalized anxiety disorder).
It may take a couple of weeks for you to start feeling better. Continue to take Entact even if it may take some time for you to feel an improvement in your condition.
Talk to your doctor if you don't feel better or if you feel worse.
Contraindications When Entact should not be used
Do not take Entact
- if you are allergic to escitalopram or any of the other ingredients of this medicine (listed in section 6).
- if you are taking other medicines that belong to a group known as MAO inhibitors, including selegiline (used to treat Parkinson's disease), moclobemide (used to treat depression) and linezolid (an antibiotic).
- if you have since birth or have had an episode of abnormal heart rhythm (identified with an ECG; a test conducted to assess how the heart is working).
- if you take medicines for heart rhythm problems or which can affect the heart's rhythm (see section 2 "Other medicines and Entact").
Precautions for use What you need to know before taking Entact
Talk to your doctor or pharmacist before taking Entact. Tell your doctor if you have any other conditions or illnesses, as your doctor may need to take them into consideration. In particular, tell your doctor:
- if you suffer from epilepsy. Treatment with Entact should be stopped if seizures occur for the first time or if there is an increase in the frequency of attacks (see also section 4 "Possible side effects").
- if you suffer from impaired liver or kidney function. Your doctor may need to adjust your dosage.
- if you have diabetes. Entact treatment can affect glycemic control. The insulin and / or oral hypoglycemic dose may need to be adjusted.
- if you have a low level of sodium in your blood.
- if you have a tendency to bleed and bruise.
- if you are receiving electroconvulsive treatment.
- if you suffer from coronary heart disease (coronary heart disease).
- if you have or have suffered from heart problems or have recently had a heart attack.
- if you have a low resting heart rate and / or if you know you have saline deficiencies as a result of prolonged severe diarrhea and vomiting (having felt sick) or use diuretics (medicines to urinate).
- if on standing up you have a rapid or irregular heart rhythm, faint, collapse or feel dizzy, which may indicate an abnormal heart rhythm.
- if you have or have ever had eye problems, such as certain types of glaucoma (increased pressure in the eye).
Keep in mind
Some patients with manic-depressive illness may enter a manic phase. This is characterized by unusual ideas that change rapidly, inappropriate happiness and excessive physical activity. If you experience these sensations, contact your doctor.
Symptoms such as restlessness or difficulty sitting or standing still may occur during the first few weeks of treatment. If these symptoms occur, tell your doctor immediately.
Thoughts of suicide and worsening of your depression or anxiety disorder
If you have depression and / or anxiety disorders you can sometimes have thoughts of harming or killing yourself. These thoughts may be more frequent when starting antidepressant treatment, as these medicines generally take about two weeks or more to show. their effect.
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. Clinical trial data showed an increased risk of suicide-related behavior in adults under the age of 25 with psychiatric disorders treated with an antidepressant.
If at any time you have thoughts of harming or killing yourself, contact your doctor or go to a hospital immediately.It may be helpful to tell a relative or good friend that you have depression or an anxiety disorder, and ask them to read this leaflet. You can ask them to tell you if they think your depression or anxiety is getting worse, or if they are worried about some change in your behavior.
Children and adolescents
Entact should normally not be taken by children and adolescents under 18 years of age. Furthermore, you should be aware that patients under 18 years of age have an increased risk of side effects such as suicide attempts, suicidal thoughts and hostility (essentially aggression, oppositional behavior and anger) when taking this class of medicines. ). Notwithstanding the above, your doctor may prescribe Entact to patients under the age of 18 if they think this is the best solution for them.
If your doctor has prescribed Entact for a patient under the age of 18 and you would like more information, please contact your doctor again. You should inform your doctor if any of the above symptoms appear or worsen while taking Entact by a patient under the age of 18.
Furthermore, Entact's long-term safety effects related to growth, maturation and cognitive and behavioral development have not yet been demonstrated in this age group.
Interactions Which drugs or foods can modify the effect of Entact
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Tell your doctor if you are taking any of the following medicines:
- "Non-selective monoamine oxidase inhibitors (MAOIs)" containing phenelzine, iproniazid, isocarboxazid, nialamide and tranylcypromine as the active ingredient. If you have taken any of these medicines you must wait 14 days before starting treatment with Entact. After stopping treatment with Entact, 7 days should elapse before taking any of these medicines.
- "Selective reversible MAO-A inhibitors" containing moclobemide (used in the treatment of depression).
- "Irreversible MAO-B inhibitors", containing selegiline (used in the treatment of Parkinson's disease). These increase the risk of side effects.
- Linezolid antibiotic.
- Lithium (used in the treatment of manic-depressive disorder) and tryptophan.
- Imipramine and desipramine (both used to treat depression).
- Sumatriptan and similar medicines (used to treat migraines) and tramadol (used to relieve severe pain). These increase the risk of side effects.
- Cimetidine, lansoprazole and omeprazole (used to treat stomach ulcer), fluvoxamine (antidepressant) and ticlopidine (used to reduce the risk of stroke). These can cause increased levels of escitalopram in the blood.
- St. John's Wort (hypericum perforatum) a herbal medicine used against depression.
- Acetylsalicylic acid and non-steroidal anti-inflammatory drugs (medicines used for pain relief or to reduce blood density, also called anti-aggregants). These can increase the tendency to bleed.
- Warfarin, dipyridamole and phenprocoumon (medicines used to reduce blood density, also called anti-coagulants). The doctor can probably check the clotting time at the beginning and at the end of treatment with Entact to verify the doses of anticoagulant however appropriate.
- Mefloquine (used to treat malaria), bupropion (used to treat depression) and tramadol (used to treat severe pain) due to the possible risk of a reduced seizure threshold.
- Neuroleptics (medicines used to treat schizophrenia, psychosis) and antidepressants (tricyclic antidepressants and SSRIs) due to the possible risk of a reduced seizure threshold.
- Flecainide, propafenone and metoprolol (used in cardiovascular diseases), clomipramine and nortriptyline (antidepressants) and risperidone, thioridazine and haloperidol (antipsychotics). Entact dosage may need to be adjusted.
- Medicines that reduce the levels of potassium or magnesium in the blood as these conditions increase the risk of life-threatening heart rhythm disturbances.
Do not take Entact if you are taking medicines for heart rhythm problems or which can affect the rhythm of the heart, such as class IA and III antiarrhythmics, antipsychotics (such as phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobial agents (such as sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, antimalarial treatments, especially halofantrine), some antihistamines (astemizole, mizolastine). If you have any further questions, please contact your doctor.
Entact with food, drink and alcohol
Entact can be taken on an empty or full stomach (see section 3 "How to take Entact").
Entact is not expected to interact with alcohol. However, as with many medicines, the combination of Entact and alcohol is not recommended.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
Tell your doctor if you are pregnant or planning to become pregnant. Do not take Entact if you are pregnant or breastfeeding unless your doctor has discussed the risks and benefits of treatment with you.
If you take Entact in the third trimester of pregnancy, you should be aware that the following effects may be observed in the newborn: difficulty breathing, blue skin, seizures, body temperature instability, difficulty feeding, vomiting, hypoglycaemia (low glucose levels). in the blood), hypertonia or hypotonia, hyperflexia, tremor, nervousness, irritability, lethargy, continuous crying, drowsiness and difficulty sleeping. If your baby has any of these symptoms, contact your doctor immediately.
Make sure your midwife and / or doctor know you are taking Entact. When taken during pregnancy, particularly in the last 3 months of pregnancy, medicines like Entact may increase the risk of a serious condition in babies, called hypertension. persistent pulmonary lung disease (PPHN), which causes the baby to breathe faster and appear bluish. These symptoms usually occur during the first 24 hours after the baby is born. If this happens to your baby, you should contact your midwife immediately. and / or the doctor.
Sudden interruption of Entact treatment should be avoided during pregnancy.
Entact is expected to be excreted in breast milk.
Citalopram, a medicine similar to escitalopram, has been shown in animal studies to reduce sperm quality. In theory, this could affect fertility but, the impact on human fertility has not yet been observed.
Driving and using machines
We advise you not to drive or use machines until you know what influence Entact has on you.
Dose, Method and Time of Administration How to use Entact: Posology
Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
Adults
Depression
The usual recommended dose of Entact is 10 mg per day, as a single dose. This dose can be increased by your doctor up to a maximum of 20 mg per day.
Panic Disorder
The starting dose of Entact for the first week of treatment is 5 mg per day and then increased to 10 mg per day. Your doctor may increase this dose to a maximum of 20 mg per day.
Social anxiety disorder
The normally recommended dose of Entact is 10 mg per day, as a single dose. Your doctor may decrease the dose to 5 mg per day or increase it to a maximum of 20 mg per day, based on your individual response to treatment.
Generalized anxiety disorder
The normally recommended dose of Entact is 10 mg per day, as a single dose. This dose can be increased by your doctor up to a maximum of 20 mg per day.
Elderly patients (over 65 years of age)
The recommended starting dose of Entact is 5 mg per day, as a single dose. This dose can be increased by your doctor up to 10 mg per day.
Children and adolescents
Entact should not normally be taken by children and adolescents. For more information see section 2 "What you need to know before you take Entact".
Entact can be taken regardless of food intake. Swallow the tablets with a glass of water. Do not chew them, as the taste is bitter.
If necessary the tablets can be broken by placing them on a flat surface with the score line facing up. The tablets can be broken by pressing down on each edge of the tablet, using both index fingers as seen in the drawing.
Duration of treatment
It may take a couple of weeks for you to feel any improvement. Continue to take Entact even if your disease does not improve immediately.
The dosage should never be changed without first consulting your doctor.
Continue to take Entact for as long as your doctor recommends. If treatment is stopped too soon, symptoms may reappear. It is recommended that treatment be continued for at least six months after symptoms resolve.
Overdose What to do if you have taken too much Entact
If you take more Entact than you should
If you have taken more Entact than prescribed, you should contact your doctor or go to the nearest hospital emergency department immediately, do so even if you do not feel unwell. Some of the symptoms of overdose may be dizziness, tremor , agitation, convulsions, coma, nausea, vomiting, altered heart rhythm, decreased blood pressure and altered electrolyte balance. Take the Entact bottle with you when you go to a doctor or hospital.
If you forget to take Entact
If you forget to take a dose of Entact, do not take a double dose. If you forget to take a dose of Entact, and remember it before bedtime, take it straight away. Continue taking it as usual the next day. If you remember it overnight or the next day, skip the missed dose and continue with your normal dosage.
If you stop taking Entact
Do not stop taking Entact until your doctor tells you to. When you have completed your treatment with Entact, it is generally recommended that the dose of Entact be gradually reduced over a couple of weeks.
When you stop taking Entact, especially if you stop suddenly, you may experience withdrawal symptoms. These are common when you stop taking Entact. The risk is greater if you have been taking Entact for a long time or in high doses or if the dose it is reduced too quickly. Most patients have found these symptoms to be mild and usually disappear spontaneously within a couple of weeks. However, in some patients, withdrawal symptoms may be severe in intensity or may be prolonged over time (2-3 months or more). If you experience severe withdrawal symptoms when you stop taking Entact, please tell your doctor. He may ask you to resume the treatment and continue reducing the doses more gradually.
Withdrawal symptoms include: dizziness (feeling unbalanced or unbalanced), pins and needles feeling, burning sensation and (less common) electric shock sensation, including in the head, sleep disturbances (vivid dreams, nightmares, difficulty sleep), anxiety, headache, malaise (nausea), sweating (including night sweats), restlessness or agitation, tremor (shaking), confusion or disorientation, excessive emotionality or irritability, diarrhea (loose stools), visual disturbances, disturbed heartbeat heart (palpitations).
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 Entact
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The side effects usually disappear after a few weeks of treatment. Keep in mind that many of the side effects can also be symptoms of your disease and therefore lessen as you start to feel better.
If any of the following symptoms occur, you should contact your doctor or go to a hospital immediately:
Uncommon (may affect up to 1 in 100 people):
- Abnormal bleeding, including gastrointestinal haemorrhage
Rare (may affect up to 1 in 1,000 people):
- Swelling of the skin, tongue, lips or face, or have difficulty breathing or choking (allergic reaction)
- High fever, agitation, confusion, tremor and sudden muscle twitching can be symptoms of a rare condition called serotonin syndrome
Not known (frequency cannot be estimated from the available data):
- Urinary difficulties
- Convulsions (fits), see also section "Warnings and precautions"
- Yellow discoloration of the skin and whites of the eyes are signs of impaired liver function / hepatitis
- Rapid, irregular heartbeat, feeling faint, which may be symptoms of a life-threatening condition known as Torsade de Pointes
- Thoughts of self harm or suicide, see also section "Warnings and precautions"
In addition to the side effects mentioned above, the following have also been reported:
Very common (may affect more than 1 in 10 people):
- Malaise (nausea)
- Headache
Common (may affect up to 1 in 10 people):
- Blocked nose or nasal discharge (sinusitis)
- Decreased or increased appetite
- Anxiety, restlessness, abnormal dreams, difficulty falling asleep, sleepiness, dizziness, yawning, tremors, skin changes
- Diarrhea, constipation, vomiting, dry mouth
- Increased sweating
- Muscle and joint pains (arthralgia and myalgia)
- Sexual disorders (delayed ejaculation, erection problems, decreased sexual urges and women may have difficulty reaching orgasm)
- Tiredness, fever
- Weight gain
Uncommon (may affect up to 1 in 100 people):
- Hives, rashes, itching
- Grinding of teeth, agitation, nervousness, panic attacks, confusion
- Disturbed sleep, changes in taste, fainting (syncope)
- Dilation of the pupils (mydriasis), visual disturbances, ringing in the ears (tinnitus)
- Hair loss
- Excessive menstrual bleeding
- Irregular menstrual period
- Weight loss
- Increased heart rate
- Swelling of arms or legs
- Nasal bleeding
Rare (may affect up to 1 in 1,000 people):
- Aggression, depersonalization, hallucinations
- Slowing of the heartbeat
Not known (frequency cannot be estimated from the available data):
- Decrease in the level of sodium in the blood (symptoms are feeling unwell with muscle weakness or confusion)
- Dizziness when standing up due to a drop in blood pressure (orthostatic hypotension)
- Changes in liver function values (increase in the amount of liver enzymes in the blood)
- Movement disorders (involuntary muscle movements)
- Painful erections (priapism)
- Signs of increased bleeding e.g. from the skin and mucous membranes (bruising)
- Sudden swelling of the skin or mucous membranes (angioedema)
- Increased urine volume (inappropriate ADH secretion)
- Milk secretion in men and women who are not breastfeeding
- Mania
- An increased risk of bone fractures has been observed in patients taking this type of medicine
- Alteration of heart rhythm (called "prolongation of the" QT interval ", as assessed by an ECG that records the" electrical activity of the heart)
In addition, a number of side effects are known for drugs that act like escitalopram (the active ingredient of Entact). And I'm:
- Motor restlessness (akathisia)
- Loss of appetite
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 the website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help 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 carton and blister after EXP (the expiry date). The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Entact
The active ingredient is escitalopram. Each Entact tablet contains 5 mg, 10 mg, 15 mg or 20 mg of escitalopram (as oxalate).
The other excipients are:
Tablet core: microcrystalline cellulose, anhydrous colloidal silica, talc, croscarmellose sodium and magnesium stearate.
Coating: hypromellose, macrogol 400, titanium dioxide (E 171).
Description of the appearance of Entact and contents of the package
Entact is available as 5 mg, 10 mg, 15 mg and 20 mg film-coated tablets.The tablets are described below.
Entact 5 mg: Round, white, film-coated tablet with "EK" on one side of the tablet.
Entact 10 mg: White, scored, film-coated oval tablet with "E" and "L" on each side of the tablet.
Entact 15 mg: White, scored, film-coated oval tablet with "E" and "M" on each side of the tablet.
Entact 20 mg: White, scored, film-coated oval tablet with "E" and "N" on each side of the tablet.
Entact is available in the following packs:
Blister (transparent) with outer carton box
5 mg, 10 mg, 15 mg and 20 mg: 14, 28, 56 and 98 tablets
Blister (white / opaque) with outer carton box
5 mg, 10 mg, 15 mg and 20 mg: 14, 20, 28, 50, 100 and 200 tablets
Polypropylene container
15 mg and 20 mg: 100 tablets
5 mg and 10 mg: 100 and 200 tablets
Single dose
5 mg, 10 mg, 15 mg, 20 mg: 49x1, 100x1 and 500x1 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
ENTACT TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Entact 5 mg: each tablet contains 5 mg of escitalopram (as oxalate)
Entact 10 mg: each tablet contains 10 mg of escitalopram (as oxalate)
Entact 15 mg: each tablet contains 15 mg of escitalopram (as oxalate)
Entact 20 mg: each tablet contains 20 mg of escitalopram (as oxalate)
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablets.
Entact 5 mg: Round, white, film-coated tablet with "EK" on one side of the tablet.
Entact 10 mg: White, scored, film-coated oval tablet with "E" and "L" on each side of the tablet.
Entact 15 mg: White, scored, film-coated oval tablet with "E" and "M" on each side of the tablet.
Entact 20 mg: White, scored, film-coated oval tablet with "E" and "N" on each side of the tablet.
The 10, 15 and 20 mg tablets can be divided into two equal doses.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Treatment of major depressive episodes.
Treatment of panic disorder with or without agoraphobia.
Treatment of social anxiety disorder (social phobia).
Treatment of generalized anxiety disorder.
04.2 Posology and method of administration
The safety of a daily dose greater than 20 mg has not been demonstrated.
Entact is administered in a single daily dose and can be taken regardless of food intake.
Major depressive episodes
The usual dose is 10 mg once a day. Based on the patient's individual response, the dose may be increased to a maximum of 20 mg per day.
It usually takes 2-4 weeks to get the antidepressant response. After the symptoms resolve, at least 6 months of treatment is required for response consolidation.
Panic disorder with or without agoraphobia
For the first week of treatment the recommended starting dose is 5 mg per day and then increased to 10 mg per day. The dose may be further increased up to a maximum of 20 mg per day, based on the individual patient response.
Maximum effectiveness is reached after about 3 months. The treatment lasts several months.
Social anxiety disorder
The usual dose is 10 mg once a day. It usually takes 2-4 weeks for symptoms to improve. Thereafter, based on the patient's individual response, the dose may be reduced to 5 mg or increased to a maximum of 20 mg per day.
Social anxiety disorder is a chronic disease, treatment for 12 weeks is recommended in order to consolidate the response. The long-term treatment of patients who responded to treatment has been studied for 6 months and can be considered on individual basis for relapse prevention; the benefits of treatment should be reassessed at regular intervals.
Social anxiety disorder is a well-defined diagnostic terminology for a specific disorder, which should not be confused with excessive shyness. Pharmacotherapy is indicated only if the disorder significantly interferes with professional and social activities.
The use of this treatment in comparison with cognitive behavioral therapy has not been evaluated. Pharmacotherapy is part of an overall therapeutic strategy.
Generalized anxiety disorder
The starting dose is 10 mg once a day. The dose may be increased to a maximum of 20 mg per day based on the individual patient response.
Long-term treatment of patients who responded to treatment was evaluated for at least 6 months in patients taking 20 mg per day. Benefits of treatment and dosage should be reassessed at regular intervals (see section 5.1).
Elderly (> 65 years)
The starting dose is 5 mg once a day. The dose can be increased to 10 mg per day based on individual patient response (see section 5.2).
The efficacy of Entact in social anxiety disorder has not been studied in this population.
Children and adolescents (
Entact should not be used for the treatment of children and adolescents under 18 years of age (see section 4.4).
Reduced kidney function
No dosage adjustment is necessary in patients with mild or moderate renal impairment. Caution is recommended in patients with severely decreased renal function (CLcr less than 30 ml / min.) (See section 5.2).
Reduced liver function
The recommended starting dose for the first two weeks of treatment is 5 mg per day in patients with mild or moderate hepatic impairment. Based on the individual patient response the dose can be increased up to 10 mg per day. Caution and increased attention in dose titration is advised in patients with severely reduced hepatic function (see section 5.2).
Poor metabolisers of CYP2C19
For patients known to be CYP2C19 poor metabolisers, a starting dose of 5 mg per day is recommended during the first two weeks of treatment. Depending on the individual patient response, the dose can be increased to 10 mg per day (see section 5.2).
Withdrawal symptoms seen when treatment is stopped
Abrupt discontinuation of treatment should be avoided. When discontinuing treatment with escitalopram, doses should be gradually reduced over at least one to two weeks to reduce the risk of withdrawal symptoms (see sections 4.4 and 4.8). If intolerable symptoms appear after dose reduction or during discontinuation of treatment, consider resuming the previous dose. Thereafter, the doctor may continue to reduce the dose, but more gradually.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Concomitant treatment with irreversible non-selective monoamine oxidase inhibitors (MAO-inhibitors) is contraindicated due to the risk of onset of serotonin syndrome manifested by agitation, tremor, hyperthermia, etc. (see section 4.5).
The combination of escitalopram with reversible monoamine oxidase inhibitors (e.g. moclobemide) or with linezolid, a reversible non-selective monoamine oxidase inhibitor, is contraindicated due to the risk of developing serotonin syndrome (see section 4.5).
Escitalopram is contraindicated in patients with known QT interval prolongation or congenital long QT syndrome.
Escitalopram is contraindicated in co-administration with medicinal products known to cause prolongation of the QT interval (see section 4.5).
04.4 Special warnings and appropriate precautions for use
The following special warnings and precautions are applicable to the entire therapeutic class of SSRIs (Selective Serotonin Reuptake Inhibitors).
For use by children and adolescents under the age of 18
Entact should not be used for the treatment of children and adolescents under 18 years of age. Suicidal behaviors (suicide attempts and suicidal ideation) and hostility (essentially aggression, oppositional behavior and anger) were observed more frequently in clinical trials in children and adolescents treated with antidepressants than in those treated with placebo. If, based on medical needs, a decision to treat is made, the patient should be closely monitored for the appearance of suicidal symptoms. Furthermore, long-term safety data for children and adolescents are not available with regard to growth, maturation and cognitive and behavioral development.
Paradoxical anxiety
Some patients with panic disorder may experience an "accentuation of anxiety symptoms at" initiation of antidepressant therapy. This paradoxical reaction usually tends to subside over two weeks of continued treatment. A low starting dose is recommended in order to reduce the likelihood of an anxiogenic effect (see section 4.2).
Convulsions
Escitalopram should be discontinued if the patient experiences seizures for the first time or if there is an increase in seizure frequency (in patients with a previous diagnosis of epilepsy). SSRIs should be avoided in patients with unstable epilepsy and patients with controlled epilepsy must be carefully monitored.
Mania
SSRIs should be used with caution in patients with a "history of mania / hypomania. SSRIs should be discontinued in patients about to enter a manic phase."
Diabetes
In diabetic patients, treatment with an SSRI can alter glycemic control (hypoglycemia or hyperglycemia). The insulin and / or oral hypoglycemic dose may need to be adjusted.
Suicide / suicidal thoughts or clinical worsening
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide increases in the early stages of disease improvement.
Other psychiatric conditions for which Entact has been prescribed may also be associated with an increased risk of suicide-related events. Additionally, these conditions may be comorbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder must therefore also be observed when treating patients with other psychiatric conditions.
Patients with a previous history of suicide-related events, or who exhibit a significant degree of suicidal ideation prior to initiation of treatment, are known to be at increased risk of suicidal thoughts or suicide attempts, and should therefore be closely monitored. controlled during treatment. A meta-analysis of clinical trials conducted with antidepressant drugs compared with placebo in adult patients with psychiatric disorders showed an increased risk of suicidal behavior in patients under 25 years of age treated with antidepressants compared to those treated with placebo Antidepressant therapy should always be associated with close surveillance of patients, particularly those at high risk, especially in the initial stages of treatment and after dose modifications.
Patients (and those involved in patient care) should be advised of the need to monitor for any clinical worsening, suicidal behaviors or thoughts, or changes in behavior, and to seek immediate medical attention if these symptoms appear.
Akathisia / psychomotor restlessness
The use of SSRIs / SNRIs has been associated with the development of akathisia, characterized by an unpleasant and stressful feeling of restlessness with the need to move often and accompanied by an inability to sit or stand still. This is more likely to appear within first weeks of treatment In patients who develop such symptoms, increasing the dose may be harmful.
Hyponatremia
Hyponatremia, possibly due to inappropriate antidiuretic hormone secretion (SIADH), has been reported rarely with the use of SSRIs and generally resolves upon discontinuation of therapy. Caution is needed in at-risk patients, such as the elderly, patients with cirrhosis or when used concomitantly with other medicines that can cause hyponatremia.
Hemorrhage
There have been reports of abnormal skin bleeding manifestations such as ecchymosis and purpura during SSRI treatment. Particular caution is advised in patients taking SSRIs concomitantly with oral anticoagulants, with medicinal products known to affect platelet function (e.g., atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory drugs (NSAIDs), ticlopidine and dipyridamole) as well as in patients with a tendency to bleed.
ECT (electroconvulsive therapy)
Data on the clinical experience of concomitant administration of SSRIs and ECTs are limited, therefore caution is advised.
Serotonin syndrome
Caution is advised when using escitalopram concomitantly with medicinal products with serotonergic effect such as sumatriptan or other triptans, tramadol and tryptophan.
In rare cases, serotonin syndrome has been reported in patients taking SSRIs concomitantly with serotonergic medicinal products. A combination of symptoms, such as agitation, tremor, myoclonus, and hyperthermia, may indicate the development of this condition. In this case, treatment with SSRIs and serotonergic medicinal products should be stopped immediately and symptomatic treatment instituted.
Hypericum
The concomitant use of SSRIs and herbal remedies containing St. John's wort (Hypericum perforatum) may result in an "increased incidence of adverse reactions (see section 4.5).
Withdrawal symptoms seen when treatment is stopped
Discontinuation symptoms on discontinuation of treatment are frequent, particularly if discontinuation occurs abruptly (see section 4.8). In clinical trials, adverse events during discontinuation of treatment were observed in approximately 25% of patients treated with escitalopram. and in 15% of patients treated with placebo.
The risk of withdrawal symptoms may be dependent on several factors, including the duration and dose of therapy and the rate of dose reduction. The most frequently reported reactions are dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, tremor, confusion, sweating, headache, diarrhea, palpitations, emotional instability, irritability and visual disturbances. Generally these symptoms are mild or moderate in severity; however, in some patients, they can be severe in severity. Generally these symptoms appear within the first few days of stopping treatment; however, there have also been rare reports of these symptoms in patients who inadvertently missed a dose. Generally these symptoms are self-limiting and usually resolve spontaneously within two weeks, although in some people they may be more prolonged (2-3 months or more).It is therefore recommended that, when discontinuing treatment with escitalopram, the dose of the drug be gradually reduced over several weeks or months, according to the patient's needs (see "Withdrawal symptoms observed when treatment is stopped", section 4.2. ).
Coronary heart disease
Due to limited clinical experience, caution is recommended in patients with coronary heart disease (see section 5.3).
Prolongation of the QT interval
Escitalopram was found to cause dose-dependent prolongation of the QT interval. Cases of QT interval prolongation and ventricular arrhythmias, including Torsade de Pointes, have been reported in post-marketing experience, predominantly in female patients with hypokalaemia. or with pre-existing QT interval prolongation or other cardiac disorders (see sections 4.3, 4.5, 4.8, 4.9 and 5.1).
Caution is advised in patients with significant bradycardia, or in patients with recent acute myocardial infarction or uncompensated heart failure.
Electrolyte imbalances such as hypokalaemia and hypomagnesaemia increase the risk of malignant arrhythmias and should be corrected before starting treatment with escitalopram.
If treating patients with stable cardiac disease, an ECG check should be considered before starting treatment.
If signs of cardiac arrhythmia occur during treatment with escitalopram, the treatment should be discontinued and an ECG performed.
Closed-angle glaucoma
SSRIs including escitalopram may have an effect on pupil size resulting in mydriasis. This mydriatic effect has the potential to reduce the angle of the eye resulting in increased intraocular pressure and closed angle glaucoma, especially in predisposed patients. Escitalopram should therefore be used with caution in patients with narrow-angle glaucoma or a history of glaucoma.
04.5 Interactions with other medicinal products and other forms of interaction
Pharmacodynamic interactions
Contraindicated associations:
Irreversible non-selective MAOIs
Cases of serious reactions have been reported in patients being treated with SSRIs in co-administration with non-selective, irreversible monoamine oxidase inhibitors (MAOIs) and in patients who had recently discontinued treatment with an SSRI and initiated one with such MAOIs. (see section 4.3). In some cases the patient developed a serotonin syndrome (see section 4.8).
Concomitant administration of escitalopram with irreversible non-selective MAOIs is contraindicated. Treatment with escitalopram can be started 14 days after stopping treatment with an irreversible MAOI. At least 7 days after stopping treatment with escitalopram should elapse before starting treatment with irreversible non-selective MAOIs.
Reversible selective MAO-A inhibitor (moclobemide)
Due to the risk of serotonin syndrome, the combination of escitalopram and MAO-A inhibitors such as moclobemide is contraindicated (see section 4.3). If the combination proves necessary, the minimum recommended dosage should be started and clinical monitoring should be strengthened. .
Reversible non-selective MAO inhibitor (linezolid)
The antibiotic linezolid is a reversible non-selective inhibitor of MAOs and should not be administered to patients treated with escitalopram. If the combination proves necessary, it should be initiated with minimal dosage and under close clinical monitoring (see section 4.3).
Irreversible selective MAO-B inhibitor (selegiline)
In concomitant administration with selegiline (irreversible MAO-B inhibitor) caution is required due to the risk of developing serotonin syndrome. Doses of selegiline up to 10 mg per day have been safely co-administered with the racemic compound citalopram.
Prolongation of the QT interval
Pharmacokinetic and pharmacodynamic studies on the combination of escitalopram and other medicinal products that prolong the QT interval have not been conducted. An additive effect of escitalopram with such medicinal products cannot be excluded. Consequently, co-administration of escitalopram with medicinal products that prolong the QT interval, such as class IA and III antiarrhythmics, antipsychotics (such as phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobial agents (such as sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, antimalarial treatments, in particular halofantrine), some antihistamines (astemizole, mizolastine).
Associations requiring caution for use:
Serotonergic medicines
Concomitant administration with serotonergic medicinal products (e.g. tramadol, sumatriptan and other triptans) can cause serotonin syndrome.
Medicines that lower the seizure threshold
SSRIs can lower the seizure threshold. Therefore, caution is required in co-administration with drugs that also lower this threshold (for example antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes and butyrophenones), mefloquine, bupropion and tramadol).
Lithium, tryptophan
There have been reports of potentiation of effects when SSRIs are administered together with lithium or tryptophan, therefore the concomitant use of SSRIs and these medicinal products requires caution.
Hypericum
The concomitant use of SSRIs and herbal remedies containing St. John's wort (Hypericum perforatum) may result in an "increased incidence of adverse reactions (see section 4.4).
Hemorrhage
Alterations of the anticoagulant effect may occur when escitalopram is administered with oral anticoagulants. Patients receiving oral anticoagulants should receive close monitoring of coagulation parameters upon initiation or discontinuation of escitalopram therapy (see section 4.4).
Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the tendency to bleed (see section 4.4).
Alcohol
No pharmacodynamic or pharmacokinetic interactions are expected between escitalopram and alcohol. However, as with other psychotropic medicinal products, such a combination is not recommended.
Medicinal products inducing hypokalaemia / hypomagnesaemia
Caution is advised in concomitant use of hypokalaemia / hypomagnesaemia inducing medicinal products as these conditions increase the risk of malignant arrhythmias (see section 4.4).
Pharmacokinetic interactions
Effects of other medicinal products on the pharmacokinetics of escitalopram
The metabolism of escitalopram is mainly mediated by CYP2C19. CYP3A4 and CYP2D6 may contribute to metabolism although to a lesser extent. The major metabolite S-DCT (demethylated escitalopram) appears to be partially catalyzed by CYP2D6.
Co-administration of escitalopram with omeprazole 30 mg once daily (CYP2C19 inhibitor) results in a moderate increase in plasma concentrations of escitalopram (approximately 50%).
Co-administration of escitalopram and cimetidine 400 mg twice daily (general enzyme inhibitor of moderate potency) resulted in a moderate increase in plasma concentrations of escitalopram (approximately 70%). Caution is advised when administering escitalopram in combination with cimetidine. Dose adjustments may be needed.
Therefore, caution is recommended when using it concomitantly with CYP2C19 inhibitors (eg omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. A reduction of the escitalopram dose may be necessary based on monitoring for undesirable effects during concomitant treatment.
Effects of escitalopram on the pharmacokinetics of other medicinal products
Escitalopram is an inhibitor of the CYP2D6 enzyme. Caution is advised when co-administering escitalopram with medicinal products that are metabolised predominantly by this enzyme and with a narrow therapeutic index, for example, flecainide, propafenone and metoprolol (when used in heart failure). o some medicinal products that act in the central nervous system and are mainly metabolised by CYP2D6 such as antidepressants such as desipramine, clomipramine, and nortriptyline or antipsychotics such as risperidone, thioridazine and haloperidol. A dose adjustment may be necessary.
Co-administration with desipramine or metoprolol resulted in both cases in a two-fold increase in the plasma levels of these two CYP2D6 substrates.
Education in vitro have shown that escitalopram can also cause weak inhibition of CYP2C19. Caution is advised in concomitant use of medicinal products metabolised by CYP2C19.
04.6 Pregnancy and lactation
Pregnancy
For escitalopram only limited clinical data are available with respect to exposure in pregnancy.
Animal studies have shown reproductive toxicity (see section 5.3). Entact should not be used during pregnancy unless strictly necessary and only after a "careful risk / benefit assessment".
Newborns of mothers who have continued taking Entact into late pregnancy, especially in the third trimester, should be observed. Abrupt discontinuation of treatment should be avoided during pregnancy.
The following symptoms may appear in the newborn after maternal use of SSRIs / SNRIs during late pregnancy: breathing difficulties, cyanosis, apnea, convulsions, body temperature instability, feeding difficulties, vomiting, hypoglycemia, hypertonia, hypotonia, hyperflexia , tremor, nervousness, irritability, lethargy, continuous crying, drowsiness and difficulty sleeping. These symptoms can be interpreted as either serotonergic effects or discontinuation symptoms. In most cases, complications begin immediately or soon after delivery (within 24 hours).
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 cases per 1000 pregnancies. In the general population, 1-2 cases of PPHN occur per 1000 pregnancies.
Feeding time
Escitalopram is expected to be excreted in milk.
Therefore, it is not recommended to breastfeed during treatment.
Fertility
Animal data have shown that citalopram may affect sperm quality (see section 5.3).
In humans, reports from patients treated with SSRIs have shown that the effect on sperm quality is reversible. No impact on fertility has been observed so far.
04.7 Effects on ability to drive and use machines
Although escitalopram has been shown not to affect intellectual function or psychomotor performance, psychoactive medicinal products may affect judgment or action. Patients should be warned of the potential risk that their ability to drive or use machines may be affected. .
04.8 Undesirable effects
Adverse reactions occur more frequently during the first or second week of treatment, and then decrease in intensity and frequency with continued treatment.
Table of undesirable effects
Adverse reactions known for SSRIs and also reported with escitalopram, both in placebo-controlled studies and as spontaneous post-marketing reports, are listed below by system organ class and frequency.
Frequencies reported are those observed in the studies and are not corrected to placebo. The frequency is defined as: very common (≥1 / 10), common (≥1 / 100 to
1 These events were reported for the therapeutic class of SSRIs.
2 Cases of suicidal ideation and suicidal behaviors have been reported during escitalopram therapy or early after treatment discontinuation (see section 4.4).
Prolongation of the QT interval
Cases of QT interval prolongation and ventricular arrhythmias, including Torsade de Pointes, have been reported during post-marketing experience, predominantly in female patients, with hypokalaemia or with pre-existing QT interval prolongation or other cardiac conditions ( see sections 4.3, 4.4, 4.5, 4.9 and 5.1).
Class effects
Epidemiological studies, mainly conducted in patients aged 50 or older, show an increased risk of bone fractures in patients treated with SSRIs and TCAs. The mechanism leading to this risk is not known.
Withdrawal symptoms seen when treatment is stopped
Discontinuation of SSRI / SNRI treatment (especially if it occurs abruptly) commonly results in withdrawal symptoms. The most frequently reported reactions are: dizziness, sensory disturbances (including paraesthesia and electric shock sensation), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, tremor, confusion, sweating, headache, diarrhea, palpitations, emotional instability, irritability and visual disturbances. These events are usually mild or moderate and self-limiting; however, in some patients may be severe and / or prolonged in duration, therefore it is recommended that treatment with escitalopram is no longer necessary to gradually discontinue treatment by progressively reducing the dose (see sections 4.2 and 4.4).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions that occur after authorization of the medicine is important, as it allows continuous monitoring of the benefit / risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via the website: http://www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
Toxicity
Clinical data on escitalopram overdose are limited and in many cases are associated with overdose of other concomitant drugs. In most cases, the symptoms were absent or mild. Fatal cases of escitalopram overdose have rarely been reported with escitalopram alone; in most cases it was an overdose with multiple concomitant medications. The intake of doses between 400 and 800 mg of escitalopram alone did not lead to the onset of severe symptoms.
Symptoms
Symptoms observed in cases of overdose with escitalopram were mainly related to the central nervous system (from dizziness, tremor, and agitation to rare cases of serotonin syndrome, seizures and coma), the gastrointestinal system (nausea / vomiting), the cardiovascular system ( hypotension, tachycardia, prolongation of the QT interval, and arrhythmias) and the condition of hydroelectrolytic balance (hypokalemia, hyponatremia).
Management
There is no specific antidote. Establish and maintain a patent airway, ensure adequate oxygenation and respiratory function. Consider gastric lavage and the use of activated charcoal. Gastric lavage should be performed as soon as possible after oral ingestion. Cardiac and vital sign monitoring is recommended in addition to normal symptomatic supportive measures.
In the event of overdose, ECG monitoring is advisable in patients with congestive heart failure / bradyarrhythmias, in patients using concomitant medications that prolong the QT interval, or in patients with impaired metabolism, eg hepatic impairment.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antidepressants, selective serotonin re-uptake inhibitors.
ATC code: N 06 AB 10
Mechanism of action
Escitalopram is a selective serotonin (5-HT) re-uptake inhibitor with high affinity for the primary binding site. It also binds to an allosteric site of the serotonin transporter, with a 1000-fold lower affinity.
Escitalopram has no or minimal affinity on a number of receptors including 5-HT1A, 5-HT2, DA D1 and D2, α1-, α2-, β- adrenoceptors, histamine H1 receptors, muscarinic cholinergics, benzodiazepine receptors, and opioids .
Inhibition of 5-HT re-uptake is the only probable mechanism of action explaining the pharmacological and clinical effects of escitalopram.
Pharmacodynamic effects
In a double-blind, placebo-controlled ECG study in healthy volunteers, the change from baseline in QTc (Fridericia's correction) was 4.3 msec (90% CI: 2.2, 6.4) at a dose of 10 mg / day and 10.7 msec (90% CI: 8.6, 12.8) at the supratherapeutic dose of 30 mg / day (see sections 4.3, 4.4, 4.5, 4.8 and 4.9).
Clinical Effectiveness
Major Depressive Episodes
Escitalopram was effective in the acute treatment of major depressive episodes in 3 of 4 short-term (8-week) double-blind, placebo-controlled studies. In a long-term relapse prevention study, 274 patients who responded to 8-week treatment with escitalopram 10 or 20 mg / day during the initial open-label phase were randomized to continue escitalopram treatment at the same dose or with placebo for 36 weeks. In this study, patients who continued to receive escitalopram experienced significantly longer relapse-free time than placebo during 36 weeks.
Social anxiety disorder
In the treatment of social anxiety disorder, escitalopram was effective in both 3 short-term studies (12 weeks) and in a 6-month study on relapse prevention in patients who responded to treatment. The efficacy of escitalopram 5, 10, 20 mg was demonstrated in a 24-week dose-finding study.
Generalized anxiety disorder
Escitalopram in doses of 10-20 mg per day was effective in 4 out of 4 of the placebo-controlled studies.
The pool of data obtained from three similarly designed studies comprising 421 patients treated with escitalopram and 419 treated with placebo show that 47.5% and 28.9% of patients respectively responded to treatment and that 37.1% respectively. % and 20.8% of patients were in symptomatic remission A sustained effect was observed after one week of treatment.
In a randomized maintenance efficacy study of 24 to 76 weeks duration in 373 patients who had responded to an initial open label treatment for 12 weeks, maintenance of efficacy by escitalopram at a dose of 20 was demonstrated. mg per day.
05.2 Pharmacokinetic properties
Absorption
Absorption is almost total and independent of food intake (the mean time to maximum concentration (mean Tmax) is 4 hours after multiple doses). The absolute bioavailability of escitalopram is expected to be approximately 80%, as for the racemic compound citalopram.
Distribution
The apparent volume of distribution (Vd, β / F) after oral administration is approximately 12 - 26 L / kg. Plasma protein binding is less than 80% for escitalopram and its major metabolites.
Biotransformation
Escitalopram is metabolised in the liver to demethylated and didemethylated metabolites. Both are pharmacologically active. Alternatively, nitrogen can be oxidized to form the N-oxide metabolite. Both parent drug and metabolites are partly excreted as glucuronides. Following multiple doses, mean concentrations of demethyl and didemethyl metabolites are usually 28 -31% and CYP3A4 and CYP2D6 enzymes.
Elimination
The elimination half-life (t½ β) after multiple doses is approximately 30 hours and the oral plasma clearance (Cloral) approximately 0.6 l / min. The major metabolites have a significantly longer half-life.
Escitalopram and its major metabolites are expected to be eliminated by both the hepatic (metabolic) and renal routes, with the majority of the dose excreted as metabolites in the urine.
Linearity
Pharmacokinetics are linear. Steady state plasma levels are achieved in approximately 1 week. Mean concentrations of 50 nmol / l (range 20 to 125 nmol / l) at steady state are achieved with a daily dose of 10 mg.
Elderly (> 65 years)
Escitalopram appears to be eliminated more slowly in the elderly than in younger patients. Systemic exposure (AUC) in the elderly is approximately 50% higher than in young healthy volunteers (see section 4.2).
Reduced liver function
In patients with mild or moderate hepatic dysfunction (Child-Pugh Criteria A and B), the half-life of escitalopram was approximately twice as long and the exposure approximately 60% higher than in patients with normal liver function (see paragraph 4.2).
Reduced renal function
A longer half-life and a smaller increase in exposure have been observed with the racemic compound citalopram in patients with reduced renal function (CLcr 10-53 ml / min). Plasma concentrations of metabolites have not been studied, but may be elevated ( see section 4.2).
Polymorphism
Poor metabolisers have been observed to have a twice as high plasma concentration of escitalopram compared to CYP2C19 compared to extensive metabolisers. No significant change in exposure was observed in poor metabolisers compared to CYP2D6 (see section 4.2).
05.3 Preclinical safety data
A full program of preclinical studies was not performed, as toxicokinetic and toxicological studies conducted in rats with citalopram and escitalopram showed a similar profile. Therefore all information on citalopram can be extrapolated to escitalopram.
In comparative toxicology studies in rats, escitalopram and citalopram caused cardiac toxicity, including congestive heart failure, after a few weeks of treatment using dosages that caused general toxicity. Cardiotoxicity appears to be related to peak plasma concentrations rather than systemic exposure (AUC). Peak plasma concentrations at no-effect levels were in excess (8-fold) of those achieved in clinical use, while the AUC of escitalopram it was only 3/4 times higher than the exposure achieved during clinical use. For citalopram, the AUC values of the S-enantiomer were 6/7 times higher than the exposure achieved in clinical use. The data are probably related to the exaggerated influence on biogenic amines, secondary to the primary pharmacological effects, which result in haemodynamic effects (reduction of coronary flow) and ischemia. However, the exact mechanism of cardiotoxicity in rats is unclear. Clinical experience with citalopram and clinical studies with escitalopram do not indicate that the data mentioned may have a clinical correlation.
An increase in phospholipid content was observed in some tissues after long-term treatment with escitalopram and citalopram, e.g. lung, liver and epididymis in rats. These findings in the liver and epididymis were found following exposures similar to those used in humans. The effect is reversible after discontinuation of treatment. Accumulation of phospholipids (phospholipidosis) in animals has been observed in combination with many cationic amphiphilic drugs. It is not known whether this phenomenon has any relevance in man.
In the developmental toxicity study in rats, embryotoxic effects (decreased fetal weight and reversible delay in ossification) were observed for exposures in terms of AUC in excess of the exposure achieved in clinical use.
There was no increase in the frequency of malformations. A pre- and postnatal study showed reduced survival during the lactation period due to exposures in terms of AUC in excess of the exposure achieved in clinical use.
Animal data have shown that citalopram induces a reduction in the fertility index and pregnancy index, a reduction in the number of implants, abnormal spermatozoa at exposure levels well above human exposure.
No animal data on this aspect are available for escitalopram.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Tablet core:
Microcrystalline cellulose
Anhydrous colloidal silica
Talc
Croscarmellose sodium
Magnesium stearate
Coating:
Hypromellose
Macrogol 400
Titanium dioxide (E 171)
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
PVC / PE / PVdC / Aluminum blister (transparent), with outer carton box: 14, 28, 56, 98 tablets; single dose: 49x1, 100x1, 500x1 tablets (5, 10, 15, 20 mg).
PVC / PE / PVdC / Aluminum blisters (white), with outer carton box: 14, 20, 28, 50, 100, 200 tablets (5, 10, 15, 20 mg).
Polypropylene container: 100 tablets (5, 10, 15, 20 mg) and 200 tablets (5 and 10 mg).
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
RECORDATI Chemical and Pharmaceutical Industries S.p.A. - via Civitali, 1 - 20148 MILAN
Exclusive dealer for sale: INNOVA PHARMA S.p.A. - Milan
08.0 MARKETING AUTHORIZATION NUMBER
5 MG TABLETS COATED WITH FILM
TRISTAR TRANSPARENT BLISTER)
14 TABLETS A.I.C. No. 035768011
28 TABLETS A.I.C. No. 035768023
56 TABLETS A.I.C. No. 035768035
98 TABLETS A.I.C. No. 035768047
100 TABLETS A.I.C. No. 035768213
49 TABLETS A.I.C. N. (UNIT DOSE) 035768492
100 TABLETS A.I.C. N. (UNIT DOSE) 035768504
500 TABLETS A.I.C. N (UNIT DOSE) 035768516
(WHITE TRISTAR BLISTER)
14 TABLETS A.I.C. No. 035768175
20 TABLETS A.I.C. No. 035768187
28 TABLETS A.I.C. No. 035768199
50 TABLETS A.I.C. No. 035768201
200 TABLETS A.I.C. No. 035768225
(POLYPROPYLENE CONTAINER)
100 TABLETS A.I.C. No. 035768415
200 TABLETS A.I.C. No. 035768427
10 MG TABLETS COATED WITH FILM
(TRISTAR TRANSPARENT BLISTER)
14 TABLETS A.I.C. No. 035768050
28 TABLETS A.I.C. No. 035768062
56 TABLETS A.I.C. No. 035768074
98 TABLETS A.I.C. No. 035768086
49 TABLETS A.I.C. N. (UNIT DOSE) 035768528
100 TABLETS A.I.C. N. (UNIT DOSE) 035768530
500 TABLETS A.I.C. N (UNIT DOSE) 035768542
(WHITE TRISTAR BLISTER)
14 TABLETS A.I.C. No. 035768237
20 TABLETS A.I.C. No. 035768249
28 TABLETS A.I.C.N.035768252
50 TABLETS A.I.C. No. 035768264
100 TABLETS A.I.C. No. 035768276
200 TABLETS A.I.C. No. 035768288
(POLYPROPYLENE CONTAINER)
100 TABLETS A.I.C. No. 035768439
200 TABLETS A.I.C. No. 035768441
15 MG TABLETS COATED WITH FILM
TRISTAR TRANSPARENT BLISTER)
14 TABLETS A.I.C. No. 035768098
28 TABLETS A.I.C. No. 035768100
56 TABLETS A.I.C. No. 035768112
98 TABLETS A.I.C. No. 035768124
49 TABLETS A.I.C. N. (UNIT DOSE) 035768555
100 TABLETS A.I.C. N. (UNIT DOSE) 035768567
500 TABLETS A.I.C. N (UNIT DOSE) 035768579
(WHITE TRISTAR BLISTER)
14 TABLETS A.I.C. No. 035768290
20 TABLETS A.I.C. No. 035768302
28 TABLETS A.I.C. No. 035768314
50 TABLETS A.I.C. No. 035768326
100 TABLETS A.I.C. No. 035768338
200 TABLETS A.I.C. No. 035768340
(POLYPROPYLENE CONTAINER)
100 TABLETS A.I.C. No. 035768454
20 MG TABLETS COATED WITH FILM
(TRISTAR TRANSPARENT BLISTER)
14 TABLETS A.I.C. No. 035768136
28 TABLETS A.I.C. No. 035768148
56 TABLETS A.I.C. No. 035768151
98 TABLETS A.I.C. No. 035768163
49 TABLETS A.I.C. N. (UNIT DOSE) 035768581
100 TABLETS A.I.C. N. (UNIT DOSE) 035768593
500 TABLETS A.I.C. N (UNIT DOSE) 035768605
(WHITE TRISTAR BLISTER)
14 TABLETS A.I.C. No. 035768353
20 TABLETS A.I.C. No. 035768365
28 TABLETS A.I.C.N. 035768377
50 TABLETS A.I.C. No. 035768389
100 TABLETS A.I.C. No. 035768391
200 TABLETS A.I.C. No. 035768403
(POLYPROPYLENE CONTAINER)
100 TABLETS A.I.C. No. 035768478
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 30 September 2003
Date of most recent renewal: 07 December 2006
10.0 DATE OF REVISION OF THE TEXT
December 2013
