Active ingredients: Methylphenidate (methylphenidate hydrochloride)
Ritalin 10 mg tablets
Important things you need to know about your medicine
This medicine is used to treat ADHD
- The full name of ADHD is "Attention Deficit Hyperactivity Disorder".
- This medicine helps your brain activity. It can help you improve attention, concentration and be less impulsive.
- He needs other treatments for ADHD besides this medicine.
Before taking this medicine tell your doctor if:
- You have heart, circulation or mental disorders - you may not be able to take this medicine.
- You are taking other medicines of any kind - this is because methylphenidate can affect the way other medicines work.
While taking this medicine:
- See your doctor regularly. This is because your doctor will want to check how the medicine is working.
- Do not stop taking this medicine without first checking with your doctor.
- If you have been taking the medicine for more than a year, your doctor may stop treatment to see if it is still needed.
- The most common side effects are nervousness, insomnia or headache.
Tell your doctor right away if any of the following occur:
- The mood and the way he feels change.
- He feels he has heart trouble.
The remainder of this leaflet provides further details and other important information on the safe and effective use of this medicine.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, please ask your doctor.
- This medicine has been prescribed for you personally. Never give it to others. In fact, for others this medicine could be dangerous, even if their symptoms are the same as yours.
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.
This leaflet has been divided into sections:
- Paragraphs 1 to 6 are for parents and caregivers.
- The last is a special paragraph to be read by a child or teenager.
However, all paragraphs are written so that they can be read and understood by the child or adolescent who takes this medicine.
Why is Ritalin used? What is it for?
What is Ritalin used for
Ritalin is used to treat "Attention Deficit Hyperactivity Disorder" (ADHD).
- It is used in children and adolescents between the ages of 6 and 18.
- It is used only after trying other treatments that do not require the use of drugs, such as supportive care and behavioral therapy.
Ritalin should not be used to treat ADHD in children under the age of 6 or in adults. It is not known whether Ritalin is safe or effective in these patient populations.
How Ritalin works
Ritalin improves the activity of certain areas of the brain that are less active. The medicine can help improve attention, concentration and reduce impulsive behavior.
The medicine is given as part of a comprehensive treatment program which generally includes:
- psychological therapy
- educational therapy e
- social therapy.
It is only prescribed by doctors who have experience with the behavioral disorders of children or adolescents. Although there is no cure for ADHD, it can be managed using comprehensive treatment programs.
Information on ADHD
For children and adolescents with ADHD:
- it is difficult to sit still and
- it is difficult to concentrate.
It's not their fault that they can't do these things.
Many children and adolescents work hard to do these things. However, having ADHD, they can have problems in everyday life. Children and adolescents with ADHD can have difficulty learning and doing homework. It is difficult for them to perform well at home, at school or elsewhere.
ADHD has no influence on the intelligence of a child or adolescent.
Contraindications When Ritalin should not be used
Do not take methylphenidate if:
- you are allergic (hypersensitive) to methylphenidate or to any of the other ingredients of Ritalin (listed in section 6)
- have a thyroid problem
- have high blood pressure in the eye (glaucoma)
- have cancer of the adrenal gland (pheochromocytoma)
- has a problem with eating when not hungry or when she wants to eat, such as anorexia nervosà
- have very high blood pressure or narrow blood vessels, which can cause pain in the arms and legs
- have had heart problems in the past - such as heart attack, irregular heartbeat, chest pain and discomfort, heart failure, heart disease, or were already born with a heart problem
- have ever had problems with blood vessels in the brain - such as stroke, swelling and weakening of part of a blood vessel (aneurysm), narrowing or closing of blood vessels, or inflammation of blood vessels (vasculitis)
- have mental disorders such as: - a "psychopathic" or "borderline" personality problem - abnormal thoughts or visions or a disease called "schizophrenia" - signs of severe mood disorders such as: o wanting to commit suicide or severe depression, when you feel very sad, useless and desperate or mania, when you feel unusually excitable, hyper-active and uninhibited.
If any of these apply to you, do not take methylphenidate. If you are not sure, talk to your doctor before taking methylphenidate. This is because methylphenidate can make these conditions worse.
Check with your doctor before starting treatment if:
- have liver or kidney problems
- have suffered from seizures (epilepsy) or if any electroencephalographic tests have been abnormal (electroencephalogram, EEG)
- have ever had episodes of abuse or been addicted to alcohol, prescription drugs, or common drugs
- you are a girl and have already started menstruating (see below under "Pregnancy, breastfeeding and contraception")
- has difficulty controlling himself, has repeated contractions of any part of the body or repeats sounds and words
- Do you have high blood pressure
- have heart problems which are not described above in the section "Do not take methylphenidate if"
- you have a mental health problem which is not described above in the section "Do not take methylphenidate if". Other mental health problems include: - mood swings (from manic to depressed - this is called "bipolar disorder") - starting to be aggressive or hostile, or getting worse in your aggression - seeing, hearing or feeling things that are not there (hallucinations) - believing things that are not true (delusions) - feeling unusually suspicious (paranoia) - feeling agitated, anxious or tense - feeling depressed or guilty.
If any of these apply to you, talk to your doctor before starting treatment. This is because methylphenidate can make these conditions worse. Your doctor will want to check how the medicine works on you.
Check that your doctor will carry out before you start treatment with methylphenidate
These checks are used to decide if methylphenidate is the right medicine for you. Your doctor will ask you about:
- any other medicines you are taking
- any sudden death with no apparent explanation, any episode of ventricular arrhythmia and psychiatric disorder that occurred in your family
- any other medical problems (such as heart problems) that affect you or your family
- how you feel, such as feeling up or down, having strange thoughts or having any of these feelings in the past
- family history of "tics" (repeated contractions of any part of the body or repetition of sounds and words that are difficult to control)
- any mental health or behavior problems that you or your family have had. Your doctor will tell you if you are likely to have mood swings (from manic to depressed - it's called "bipolar disorder"). Your doctor will check your mental health history, and check if anyone in your family has a history of suicide, bipolar disorder or depression.
It is important that you provide as much information as possible. These will help your doctor decide if methylphenidate is the right medicine for you. Your doctor may think that other tests are needed before you start taking this medicine.
Precautions for use What you need to know before taking Ritalin
Pregnancy, breastfeeding and contraception
Ask your doctor for advice before taking any medicine. It is not known whether methylphenidate has any influence on the unborn child. Tell your doctor before taking your medicine if:
- has sexual activity. Your doctor will talk to you about contraceptive methods.
- you are pregnant or think you are pregnant. Your doctor will consider whether you should take methylphenidate.
- are breastfeeding or plan to breastfeed. It is possible for methylphenidate to pass into breast milk. Therefore, your doctor will consider whether you should breastfeed while taking methylphenidate.
Driving and using machines
It may happen that when you take methylphenidate you turn your head, have difficulty focusing or have blurred vision. If this happens, it can be dangerous to engage in activities such as driving, operating machinery, cycling or horseback riding, or climbing trees.
Important information about some of the ingredients of Ritalin
This medicine contains lactose (a type of sugar). If you have been told by your doctor that you cannot tolerate or digest some sugars, contact your doctor before taking this medicine. This medicine contains wheat starch. If you have chronic greasy diarrhea (but not celiac disease), you should not take Ritalin.
Interactions Which drugs or foods can modify the effect of Ritalin
Tell your doctor if you are taking or have recently taken any other medicines, including those not prescribed.
Do not take methylphenidate if:
- you are taking a medicine called a 'monoamine oxidase inhibitor' (MAOI) used for depression, or if you have taken a MAOI in the past 14 days. Taking a MAOI with methylphenidate can cause a sudden rise in blood pressure.
If you are taking other medicines, methylphenidate may affect their activity or may cause side effects. If you are taking any of the following medicines, ask your doctor for advice before taking methylphenidate:
- other medicines for depression
- medicines for severe mental health problems
- medicines for epilepsy
- medicines used to decrease or increase blood pressure
- some cough and cold remedies that contain substances that can affect blood pressure. It is important to check with your pharmacist when purchasing any of these products
- medicines that thin the blood to prevent clots.
If you are unsure whether any of the medicines you are taking are included in the list above, ask your doctor for advice before taking methylphenidate.
In case of surgery
Tell your doctor if you are about to have surgery. You should not take methylphenidate on the day of surgery if a certain type of anesthetic is used. This is because there is a possibility of a sudden rise in blood pressure during surgery.
Test for the research of narcotic substances
This medicine can give a positive result in tests for the detection of drugs, including tests carried out at a sports level.
Taking methylphenidate with food and drink
Taking methylphenidate with food can help stop stomach pain, nausea or vomiting.
Taking methylphenidate with alcohol
Do not drink alcohol while taking this medicine. Alcohol can make the side effects of this medicine worse. Remember that some foods and medicines contain alcohol.
Warnings It is important to know that:
What your doctor will do during Ritalin treatment
Your doctor will do some checkups
- before starting treatment - to make sure that Ritalin is safe for you and will benefit you.
- after starting treatment - checks should be done at least every 6 months, but if possible even more frequently. They will also be done when the dosage is changed.
- these checks will include: - control of appetite - measurement of height and weight - measurement of blood pressure, heart rate and possible electrocardiogram - verification of the onset or worsening, during treatment with Ritalin, of any problem concerning mood, mood or any other unusual sensation.
Long-term treatment
It is not necessary to take Ritalin forever. If you have been taking Ritalin for more than a year, your doctor must stop treatment for a short time, which may coincide with a school vacation. This will show if you still need to take the medicine.
If you have any further questions on the use of Ritalin, ask your doctor.
Dose, Method and Time of Administration How to use Ritalin: Posology
How much Ritalin to take
Always take Ritalin exactly as your doctor has told you. If in doubt, consult your doctor.
- Your doctor will usually start treatment with a low dose and gradually increase it as required.
- The maximum daily dose is 60 mg.
- Take Ritalin once or twice a day (eg at breakfast and / or at lunchtime).
- Do not take Ritalin in the evening: at least 4 hours should elapse from the last administration to bedtime. If you feel disturbed doing so in the evening, contact your doctor.
- The tablets should be swallowed with a drink of water.
- You can break the tablet to facilitate ingestion.
If you feel unwell after 1 month of treatment
If you feel unwell, tell your doctor. Your doctor may think you need different treatment.
Misuse of Ritalin
If Ritalin is not used correctly, abnormal behavior can occur. It can also mean that you are starting to depend on this medicine. Tell your doctor if you have ever been abused or been addicted to alcohol, prescription drugs, or common drugs.
This medicine is for you only. Do not pass it on to others, even if their symptoms seem similar.
Overdose What to do if you have taken too much Ritalin
If you take more Ritalin than you should
If you take too much medicine, contact a doctor or call an ambulance immediately. Tell them how much medicine you have taken.
Signs of overdose may include: vomiting, agitation, tremors, increased uncontrolled movement, muscle twitching, seizures (sometimes followed by coma), feeling euphoric, confusion, seeing, hearing or feeling things that are not real ( hallucinations), sweating, flushing, headache, high fever, changes in heartbeat (slow, fast or irregular), high blood pressure, dilated pupils and dryness of the nose and mouth.
If you forget to take Ritalin
Do not take a double dose to make up for a forgotten dose. If you miss a dose, wait until it is time for your next dose.
If you stop taking Ritalin
If you have any further questions on the use of Ritalin, ask your doctor. If you suddenly stop taking Ritalin, ADHD symptoms may come back or side effects such as depression may occur. The doctor may consider it appropriate to gradually reduce the amount of medicine taken each day, before stopping treatment permanently. Tell your doctor before stopping Ritalin treatment.
Side Effects What are the side effects of Ritalin
Like all medicines, Ritalin can cause side effects, although not everybody gets them. Although some people experience side effects, most believe that methylphenidate helps them.
Your doctor will inform you about these side effects.
Some side effects could be serious. If any of the side effects listed below occur, contact a doctor immediately:
Common (affects less than 1 in 10 people)
- irregular heartbeat (palpitations)
- mood swings or changes or personality changes
Uncommon (affects less than 1 in 100 people)
- thinking or feeling like committing suicide
- perceiving or feeling things that are not real - these are symptoms of psychosis
- uncontrolled language and body movements (Tourette's syndrome)
- signs of allergy such as rash, itching or hives of the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or difficulty in breathing
Rare (affects less than 1 in 1,000 people)
- feeling unusually excited, hyperactive and uninhibited (mania)
Very rare (affects less than 1 in 10,000 people)
- heart attack
- seizures (epilepsy)
- peeling of the skin or the appearance of red-purple spots
- uncontrollable muscle contractions of the eyes, head, neck, body and nervous system - this is due to a temporary lack of blood supply to the brain
- paralysis or problems with movement and vision, difficulty with speech (these may be signs of problems with the blood vessels in the brain)
- decrease in the number of blood cells (red blood cells, white blood cells and platelets) which can make infections more likely and facilitate bleeding and bruising
- sudden rise in body temperature, very high blood pressure and severe convulsions ("Neuroleptic Malignant Syndrome"). It is unclear whether these side effects are caused by methylphenidate or by other drugs that can be taken in combination with methylphenidate.
Other side effects (it is not known how often they occur)
- unwanted thoughts that come back all the time
- fainting for no reason, chest pain, shortness of breath (these may be signs of heart problems)
If any of the side effects described above occur, contact a doctor immediately.
Other side effects: if these become severe, tell your doctor:
Very common (affects more than 1 in 10 people)
- headache
- nervousness
- inability to fall asleep.
Common (affects less than 1 in 10 people)
- joint pain
- dry mouth
- high temperature (fever)
- unusual hair loss or thinning
- feeling unusually sleepy or drowsy
- loss or decreased appetite
- itchy, red, itchy rash or raised rash (hives)
- cough, sore throat or irritation of the nose and throat
- high blood pressure, fast heart beat (tachycardia)
- dizziness, uncontrollable movements, being unusually active
- feeling of aggression, agitation, anxiety, depression, irritability and abnormal behavior
- stomach pain, diarrhea, nausea, gastric discomfort and vomiting. These usually occur at the start of treatment and can be reduced by taking the medicine with food.
Uncommon (affects less than 1 in 100 people)
- constipation
- chest discomfort
- blood in the urine
- jolts or tremors
- double or blurred vision
- muscle pain, muscle twitching
- shortness of breath or chest pain
- elevated liver test values (found in a blood test)
- anger, feeling restless or sad, excessive awareness of your surroundings, sleep disturbances.
Rare (affects less than 1 in 1,000 people)
- changes in sex drive
- feeling of disorientation
- dilated pupils, disturbances in vision
- breast swelling in men
- excessive sweating, redness of the skin, red raised rashes
Very rare (affects less than 1 in 10,000 people)
- heart attack
- unexpected death
- muscle cramps
- small red marks on the skin
- inflammation or occlusion of the cerebral arteries
- abnormalities in liver function including hepatic failure and coma
- changes in test results - including liver and blood tests
- suicide attempt, abnormal thinking, lack of feeling or emotion, doing things repeatedly, being obsessed with something
- feeling of numbness in the fingers and toes, tingling and color change (from white to blue, then red) in cold weather ("Raynaud's phenomenon")
Other side effects (it is not known how often they occur)
- migraine
- very high fever
- slow, fast or extra-beats heartbeat
- a major convulsion ("grand mal")
- believing things that are not true, confusion
- severe stomach pain, often with nausea and vomiting
- brain blood vessel disorders (stroke, cerebral arteritis or cerebral occlusion)
- difficulty in erection.
Effects on growth
When used for more than a year, methylphenidate can cause stunted growth in some children. This occurs in less than 1 in 10 children.
- It can happen that your weight and height do not increase.
- Your doctor will closely monitor your weight and height, as well as assess your appetite.
- If it is not growing as expected, methylphenidate treatment can be stopped for a short time.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.
Expiry and Retention
Keep Ritalin out of the reach and sight of children. Make sure you keep the medicine in a safe place so that no one else can take it, especially younger brothers or sisters.
Do not use Ritalin after the expiry date which is stated on the label. The expiry date refers to the last day of the month.
Do not store above 25 ° C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Ritalin contains
The active ingredient is methylphenidate hydrochloride.
Ritalin tablets contain 10 mg of methylphenidate hydrochloride.
The other ingredients are: calcium phosphate, lactose monohydrate, wheat starch, gelatin, magnesium stearate, talc.
What Ritalin looks like and contents of the pack
Ritalin tablets are available in one dosage: 10 mg.
The medicine is available in blisters contained in packs of 20, 30, or 50 tablets. Not all pack sizes may be marketed.
Information for children and adolescents with ADHD
This information has been prepared for you to learn the main features of your medicine called Ritalin.
If you don't like reading, someone like your mom, dad or your carer can read them to you and answer any questions.
It can help you read small pieces at a time.
Why was I given this medicine?
This medicine can help children and adolescents with ADHD.
- ADHD can:
- make you run too much
- make you unable to pay attention
- make you act quickly without thinking about what will happen next (i.e. make you impulsive)
- ADHD affects your ability to learn, make friends and how you view yourself. It's not your fault.
While you are taking this medicine
- In addition to taking this medicine, you will also get help on coping with ADHD, such as talking to ADHD specialists.
- This medicine is supposed to help you, but it doesn't cure ADHD.
- You will need to go to the doctor several times a year for checkups. This is to make sure that the medicine is working and that your growth and development are OK.
- If you have been taking the medicine for more than a year, your doctor may stop treatment to see if it is still needed. This will likely happen during a school vacation.
- If you take this medicine more than once a day, you may need to remember to take it at school. Your mom, dad or your carer will need to check what the school rules are on this.
- Don't drink alcohol. Alcohol can make the side effects of this medicine worse.
- Girls should tell their doctor right away if they think they are pregnant. We do not know how this medicine affects unborn babies. If you are having sexual activity, talk to your doctor about contraceptive methods.
Some people cannot take this medicine
You cannot take this medicine if:
- you have a heart disorder
- you feel very unhappy, depressed or have a mental disorder.
Some people need to talk to their doctor before starting to take this medicine
You need to speak to your doctor if:
- suffer from epilepsy (seizures)
- you are pregnant or breastfeeding
- i taking other medicines - your doctor needs to know all the medicines you are taking.
How do I take my medicine (tablets)?
- Swallow your medicine with water.
- Your doctor will tell you how many times a day you need to take your medicine.
- Do not stop taking the medicine without first talking to your doctor.
Possible side effects
Side effects are unwanted things that can happen when you take a medicine. If any of these occur, speak to a trusted adult immediately, who can then report to your doctor. The main things that can happen to you are:
- Feeling nauseous, vomiting, or stomach ache. This can only happen when you start taking the medicine. It is best to take the medicine with food
- Feeling worried or nervous
- Feeling dizzy, or having a headache
- Being very depressed and unhappy or wanting to harm yourself
- Being in a different mood than usual, not being able to fall asleep
- Skin rashes, bruises that appear easily, run out of breath
- The medicine can also make you feel sleepy. If you feel sleepy, it is important that you do not engage in outdoor sports such as horseback riding or biking, swimming or climbing trees. You could harm yourself and others.
- Your heart beats faster than usual.
If you feel unwell at any time while you are taking the medicine, immediately talk to a trusted adult.
Other things to remember
- Make sure you keep the medicine in a safe place so that no one else can take it, especially younger brothers or sisters
- This medicine is specific to you - don't let anyone else take it. This medicine can help you, but it could hurt someone else.
- If you forget to take your medicine, the next time you do not take two tablets but just take one as usual.
- If you take too much medicine, tell your mom, dad, or your carer immediately.
- It is important not to take too much medicine, otherwise you will be sick.
- Don't stop taking your medicine until your doctor tells you you can.
Who should I ask if there is something I don't understand?
Your mom, dad, your carer, doctor or nurse can help you.
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
RITALIN 10 MG TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 10 mg of methylphenidate hydrochloride.
Excipient with known effects: lactose.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Attention Deficit Hyperactivity Disorder (ADHD)
Methylphenidate is indicated as part of a comprehensive treatment program for attention deficit hyperactivity disorder (ADHD) in children from 6 years of age and adolescents in cases where psycho-social or psycho-behavioral interventions alone prove insufficient. Treatment should be carried out under the supervision of a child and adolescent neuropsychiatrist or related specialist in charge of the territorial centers. Diagnosis should be made according to the criteria of the current version of the DSM or ICD-10 and it should be based on a complete "medical history and evaluation of the child and not just the presence of one or more symptoms."
The proper etiology of this syndrome is unknown and there is no single diagnostic test. An adequate diagnosis requires a medical, neuropsychological, educational and social investigation.
A comprehensive treatment program usually includes psychological, educational and social therapeutic measures as well as pharmacological and aims to stabilize children who have a behavioral syndrome characterized by symptoms that may include a chronic history of limited attention, a tendency to distraction, emotional lability, impulsivity, moderate to severe hyperactivity, secondary neurological signs and abnormal EEG. There may or may not be learning disabilities.
Methylphenidate treatment is not indicated in all children with ADHD and the decision to use the medicine must be based on a very thorough assessment of the severity and persistence of symptoms in relation to the child's overall picture.
A suitable educational program is essential, and psychosocial intervention is usually required. In cases where psycho-social or psycho-behavioral interventions alone prove insufficient, the decision to prescribe a stimulant must be based on a rigorous assessment of the severity of the child's symptoms. The use of methylphenidate must always be implemented in these ways, according to the authorized indications and according to the guidelines relating to prescribing and diagnosis.
The prescription of the methylphenidate-based medicine "Ritalin" must be carried out: on the diagnosis and treatment plan of the specialist centers, identified by the Regions and Autonomous Provinces of Trento and Bolzano (Reference Centers), in coordination with the territorial services of Child Neuropsychiatry, pediatricians of free choice or the general practitioner who has the patient among his clients.
04.2 Posology and method of administration
Therapy must be initiated under the supervision of a childhood and adolescent neuropsychiatrist or similar specialist in charge of the territorial centers.
Pre-treatment screening
Before prescribing, an initial assessment of the patient's cardiovascular status, including blood pressure and heart rate, and possibly ECG in the presence of a positive family and individual history of cardiovascular disease, should be performed. A "complete medical history should indicate concomitant medications, co-morbid medical and psychiatric symptoms or disorders, both past and present, family history of sudden / unexplained cardiac death, ventricular arrhythmias and psychiatric disorders, as well as an" accurate record, on a graph of the patient's growth, height and weight before treatment (see sections 4.3 and 4.4).
Continuous control
The patient's growth and psychiatric and cardiovascular status should be monitored (see also section 4.4).
• Blood pressure and heart rate should be recorded on a centile graph at each dose change and at least once every six months thereafter. A periodic check of the ECG is suggested in case of alterations detected at the pre-treatment screening and / or clinical indications arising during the treatment.
• You should check your height, weight and appetite at least every six months and keep a growth chart.
• Onset must be controlled from scratch o worsening of pre-existing psychiatric disorders at each dose change and at least once every six months and at each visit thereafter.
Patients should be monitored for the risk of diversion, misuse and abuse of methylphenidate.
Dose titration
Careful dose titration is required at the start of methylphenidate treatment. Dose titration should be started with the lowest possible dose.
Other strengths of this medicine and other methylphenidate medicines may be available.
The maximum daily dose of methylphenidate is 60 mg.
Start with 5 mg once or twice a day (for example at breakfast and lunch) in weekly increments of 5-10 mg. The total daily dose should be divided into several administrations.
The last administration should generally not be performed within 4 hours prior to bedtime to avoid disturbances in falling asleep.
However, if the effect of the medicine wears off too early in the evening, behavioral disturbances and / or inability to fall asleep may occur. A small dose in the evening may be helpful to avoid this.
The advantages and disadvantages of administering a small dose in the evening compared to the possibility of disturbances in falling asleep should be considered.
Prolonged use (over 12 months) in children and adolescents
The safety and efficacy of long-term use of methylphenidate has not been systematically evaluated in controlled studies. Treatment with methylphenidate must not and does not need to be continued indefinitely. Usually, methylphenidate treatment is stopped during or after puberty. The physician who decides to use methylphenidate for a prolonged period (over 12 months) in children and adolescents with ADHD should periodically re-evaluate the usefulness of prolonged use of the drug for the individual patient with periods of temporary withdrawal of the product to evaluate the patient behavior in the absence of drug therapy. It is recommended that the administration of methylphenidate be suspended at least once a year to assess the child's condition (preferably during school holidays). The improvement may persist even when the administration of the drug is temporarily suspended or permanently discontinued.
Dose reduction and treatment discontinuation
If symptoms do not improve within one month after dose titration, drug administration should be discontinued. In case of paradoxical aggravation of symptoms or if other serious adverse events occur, the dosage should be reduced or discontinued.
Adults
Methylphenidate is not licensed for use in adults with ADHD. The safety and efficacy of the product have not been established for patients in this age group.
Senior citizens
Methylphenidate is not recommended for use in elderly patients. The safety and efficacy of the product have not been established for patients in this age group.
Children under the age of 6
Methylphenidate is not recommended for use in children under 6 years of age. The safety and efficacy of the product have not been established for patients in this age group.
Hepatic impairment
Ritalin has not been studied in patients with hepatic impairment. Caution is recommended in these patients.
Renal impairment
Ritalin has not been studied in patients with renal impairment. Caution is recommended in these patients.
04.3 Contraindications
• Hypersensitivity to the active substance or to any of the excipients.
• Glaucoma.
• Pheochromocytoma.
• During treatment with monoamine oxidase inhibitors (iMAOs), and for at least 14 days following discontinuation of these drugs due to the risk of hypertensive crisis (see section 4.5).
• Hyperthyroidism or thyrotoxicosis.
• Diagnosis or history of severe depression, anorexia nervosa / anorexic disorders, suicidal tendency, psychotic symptoms, severe mood disorders, mania, schizophrenia or psychopathic / borderline personality disorder.
• Diagnosis or a history of severe and episodic (type I) bipolar (affective) disorder that is not well controlled.
• Pre-existing cardiovascular disorders, including severe hypertension, heart failure, arterial occlusive disease, angina, haemodynamically significant congenital heart disease, cardiomyopathy, myocardial infarction, potentially life-threatening arrhythmias and channelopathies (disorders caused by ion channel dysfunction).
• Pre-existing cerebrovascular disorders, brain aneurysm, vascular abnormalities including vasculitis or stroke.
04.4 Special warnings and appropriate precautions for use
Treatment with methylphenidate is not indicated in all children with ADHD and the decision to prescribe the medicine must be based on a very thorough assessment of the severity and persistence of symptoms in relation to the child's age.
Prolonged use (over 12 months) in children and adolescents
The safety and efficacy of long-term use of methylphenidate has not been systematically evaluated in controlled studies. Treatment with methylphenidate must not and does not need to be continued indefinitely. Usually, methylphenidate treatment is stopped during or after puberty.Patients requiring long-term therapy, i.e. for more than 12 months, should be carefully and continuously monitored according to the directions in sections 4.2 and 4.4 for cardiovascular status, growth, appetite, onset from scratch or worsening of pre-existing psychiatric disorders. Psychiatric disorders to control are listed below and include (but are not limited to) motor or verbal tics, aggressive or hostile behavior, agitation, anxiety, depression, psychosis, mania, delusions, irritability, lack of spontaneity, withdrawn and excessive obstinacy.
The physician who decides to use methylphenidate for a prolonged period (over 12 months) in children and adolescents with ADHD should periodically re-evaluate the usefulness of prolonged use of the drug for the individual patient with periods of temporary withdrawal of the product to evaluate the patient behavior in the absence of drug therapy. It is recommended that the administration of methylphenidate be suspended at least once a year to assess the child's condition (preferably during school holidays). The improvement may persist even when the administration of the drug is temporarily suspended or permanently discontinued.
Use in adults
Methylphenidate is not licensed for use in adults with ADHD. The safety and efficacy of the product have not been established for patients in this age group.
Use in the elderly
Methylphenidate is not recommended for use in elderly patients. The safety and efficacy of the product have not been established for patients in this age group.
Use in children under 6 years of age
Methylphenidate is not recommended for use in children under 6 years of age. The safety and efficacy of the product have not been established for patients in this age group.
Cardiovascular status
Patients for whom CNS stimulant therapy is being considered should undergo a "careful medical history (including family history of sudden death or unexplained death or malignant arrhythmia) as well as a medical examination target physician for the presence of heart disease and, in case of indications of heart disease, they should undergo additional cardiological examinations including ECG recommended. Patients who develop symptoms such as palpitations, chest pain after exertion, unexplained syncope, dyspnoea or other symptoms suggesting heart disease during treatment with methylphenidate should undergo immediate specialist cardiac evaluation.
The analysis of data from clinical studies on children and adolescents with ADHD and treated with methylphenidate has shown that, compared to controls, patients treated with methylphenidate may commonly have changes in systolic and diastolic blood pressure of more than 10 mmHg. The consequences Short- and long-term clinical findings of these cardiovascular effects in children and adolescents are unknown, but the possibility of clinical complications as a consequence of the effects of clinical trial data cannot be completely excluded. treatment of patients with clinical conditions that may be compromised by an increase in blood pressure or heart rate For conditions in which treatment with methylphenidate is contraindicated, see section 4.3.
Cardiovascular status must be carefully monitored. Blood pressure and heart rate should be recorded on a centile graph with each dosage adjustment, and at least every 6 months thereafter.
The use of methylphenidate is contraindicated in the presence of certain pre-existing cardiovascular disorders, except on the advice of a cardiology specialist with developmental experience (see section 4.3).
Sudden death and pre-existing structural cardiac abnormalities or other serious heart conditions
Sudden death has been reported in association with the use of central nervous system stimulants at the normal doses used in children, some of whom have structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone may lead to an increased risk of sudden death, stimulant products are not recommended in children and adolescents with known structural heart abnormalities, cardiomyopathy, severe heart rhythm abnormalities or other serious heart problems that may expose them to an "increased vulnerability to sympathomimetic effects caused by a central nervous system stimulant drug. Before starting treatment with Ritalin, patients should be monitored for the existence of cardiovascular disorders and the presence, in family history, of episodes of sudden / unexplained cardiac death and ventricular arrhythmia (see section 4.2).
Inappropriate use and cardiovascular effects
Inappropriate use of central nervous system stimulants may be associated with sudden death and other serious cardiovascular adverse events.
Cerebrovascular conditions
See section 4.3 for cerebrovascular conditions for which methylphenidate treatment is contraindicated. Patients with additional risk factors (history of cardiovascular disease, concomitant use of medicinal products that cause an increase in blood pressure) should be monitored regularly at each visit after starting methylphenidate treatment for the onset of neurological signs and symptoms.
Cerebral vasculitis is a very rare idiosyncratic reaction to methylphenidate exposure. There is little evidence that it is possible to identify patients at increased risk and that the initial onset of symptoms may be the first indication of an underlying clinical problem. An early diagnosis, based on a high index of suspicion, can allow prompt withdrawal of methylphenidate and prompt treatment. Therefore, this diagnosis should be considered for any patient who develops new neurological symptoms consistent with a diagnosis of cerebral ischaemia during methylphenidate therapy. These symptoms can include severe headache, numbness, weakness, paralysis, and impaired coordination, vision, speech or memory.
Treatment with methylphenidate is not contraindicated in patients with hemiplegic cerebral palsy.
Psychiatric disorders
Psychiatric co-morbidities in ADHD are common and should be considered when prescribing stimulant products. In the event of psychiatric symptoms or worsening of pre-existing psychiatric symptoms, methylphenidate should not be administered unless the treatment benefits do not outweigh the risks to the patient Before starting treatment with Ritalin, patients should be monitored for the presence, in personal and family history, of psychiatric disorders (see section 4.2).
The onset or worsening of psychiatric disorders should be monitored at each change in dosage, and thereafter at least every 6 months and at each visit; treatment discontinuation may be appropriate.
Worsening of pre-existing psychotic or manic symptoms
Administration of methylphenidate to patients with psychosis may worsen the symptoms of behavioral and thinking disorders.
Onset of new psychotic or manic symptoms
The onset, during treatment, of psychotic symptoms (visual, tactile and auditory hallucinations and delusions) or manias in children and adolescents in the absence of a history of psychosis or mania can be caused by methylphenidate at the usual doses. If manic or psychotic symptoms occur, the possibility of a causal role of methylphenidate should be considered, and discontinuation of therapy may be appropriate.
Aggressive or hostile behavior
The onset or worsening of aggressive or hostile behavior may be determined by treatment with stimulants. Patients treated with methylphenidate should be monitored closely for the onset or worsening of aggressive or hostile behavior at the onset of treatment. treatment, at each dose change and at least every 6 months thereafter and at each visit. Physicians should evaluate the need for dose adjustment in patients who exhibit changes in behavior, bearing in mind that both an increase in or a decrease in dose. Treatment interruption may also be considered.
Suicidal ideation and behavior
Patients who exhibit suicidal tendency and behavior during treatment for ADHD should be evaluated immediately by their physician. Both the worsening of a pre-existing psychiatric disorder and a possible causal role of methylphenidate treatment should be considered. It may be necessary to initiate adequate treatment of the existing psychiatric condition and to consider a possible discontinuation of methylphenidate treatment.
Tic
Methylphenidate is associated with the onset or worsening of motor and verbal tics. Worsening of Tourette's syndrome has also been reported. Family history should be reviewed and a clinical evaluation of tics or Tourette's syndrome in children should be made prior to "." use of methylphenidate. Patients should be monitored regularly for the onset or worsening of tics during methylphenidate therapy. Monitoring should be performed at each dose change and thereafter at least every 6 months or at each visit.
Anxiety, agitation or tension
Methylphenidate may be associated with the worsening of pre-existing anxiety, agitation or tension. Clinical evaluation of anxiety, agitation or tension should be performed prior to use of methylphenidate and patients should be monitored regularly for the onset or worsening of these symptoms during treatment, at any dose changes. and thereafter at least every 6 months or at each visit.
Bipolar disorder
Particular caution should be exercised in the use of methylphenidate for the treatment of ADHD in patients with concomitant bipolar disorder (including untreated bipolar I disorder or other forms of bipolar disorder) for fear of possible precipitation of a manic episode / mixed in these patients. Before initiating methylphenidate therapy, patients with concomitant depressive symptoms should be carefully monitored to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric medical history, including family history of suicide, bipolar disorder and depression. Careful and continuous monitoring is essential in these patients (see above "Psychiatric Disorders" and section 4.2). Patients should be monitored for symptoms at each dose change and at least every 6 months and at each visit thereafter.
Growth
With prolonged use of methylphenidate in children, moderate weight gain retardation and growth retardation have been reported.
To date, the effects of methylphenidate on final height and weight are unknown and are the subject of ongoing studies.
Growth should be monitored during methylphenidate treatment: the child's height, body weight and appetite should be recorded at least every 6 months and a growth chart kept. Treatment may need to be stopped in patients who do not grow or gain in height and weight as expected.
Convulsions
Methylphenidate should be used with caution in epileptic patients. Methylphenidate may lower the seizure threshold in patients with a history of seizures, in patients with electroencephalographic abnormalities in the absence of seizures, and rarely in patients who have neither a history of seizures nor electroencephalographic abnormalities. In case of increased frequency of attacks or new onset attacks, administration of methylphenidate should be discontinued.
Abuse, misuse and diversion
Patients should be carefully monitored for the risk of diversion, misuse and abuse of methylphenidate.
Methylphenidate should be used with caution in patients with known substance or alcohol dependence due to a possible risk of substance abuse, misuse or diversion.
Chronic methylphenidate abuse can lead to marked tolerance and psychological dependence with abnormal behaviors of varying severity. Overt psychotic episodes may occur, particularly in cases of injecting abuse.
The age of the patient, the presence of risk factors for substance use disorders (such as concomitant oppositional or conduct disorder and bipolar disorder) must be taken into account when deciding on the therapy to choose for ADHD. previous or current substance abuse. Caution is advised for emotionally unstable patients, such as those with a history of substance or alcohol dependence, as such patients may increase the dosage of the medicine on their own initiative.
For some patients at high risk of substance abuse, methylphenidate or other stimulants may not be suitable and non-stimulant drug therapy should be considered.
Discontinuation of the drug
Careful monitoring is required when treatment is discontinued, as states of depression and chronic hyperactivity may occur. Some patients may require extended follow-up.
Careful monitoring is required when treatment is stopped after drug abuse, as severe depression can occur.
Fatigue
Methylphenidate should not be used for the prevention or treatment of normal fatigue states.
Choice of methylphenidate formulation
The choice of the formulation of the drug based on methylphenidate will have to be made by the specialist on the basis of the individual patient and depends on the desired duration of effect.
Research of substances
Methylphenidate can induce false positives in laboratory tests for amphetamines, particularly with "immunoassay screen test.
Renal or hepatic insufficiency
There is no experience on the use of methylphenidate in patients with renal or hepatic insufficiency.
Hematological effects
The long-term safety of methylphenidate treatment is not fully understood. In the event of leukopenia, thrombocytopenia, anemia or other blood disorders, including those indicative of severe renal or hepatic disorders, treatment discontinuation should be considered.
Potential for gastrointestinal obstruction
As the Ritalin tablet is hard and does not change significantly in shape as it passes into the gastrointestinal (GI) tract, the medicine should not be given to patients with pre-existing severe gastrointestinal stenosis (pathological or iatrogenic) or in patients who suffer from dysphagia or have significant difficulties. when swallowing tablets. Rare cases of obstructive symptoms related to the ingestion of drugs in prolonged-release hard tablet formulations have been reported in patients with known strictures.
Important information about some of the ingredients
This medicine contains lactose: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose / galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Pharmacokinetic interactions
It is not known how methylphenidate can affect the plasma concentrations of other concomitantly administered medicinal products. Therefore, caution is recommended in combining methylphenidate with other medicinal products, especially those with a narrow therapeutic window.
Methylphenidate is not metabolised by cytochrome P450 to a clinically relevant extent.
No relevant effect on the pharmacokinetics of methylphenidate is expected from inducers or inhibitors of cytochrome P450. Conversely, the d- and l- enantiomers of methylphenidate in Ritalin do not significantly inhibit cytochrome P450 1A2, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A.
However, there are reports that methylphenidate may inhibit the metabolism of coumarin anticoagulants, anticonvulsants such as phenobarbital, phenytoin, primodone, and some antidepressants (tricyclics and selective serotonin reuptake inhibitors). At the beginning of methylphenidate therapy, and at the time of its discontinuation, it may be necessary to adjust the dosage of the above medicines when taken concomitantly and to establish their plasma concentrations (or, in the case of coumarin, the clotting time) .
Pharmacodynamic interactions
Antihypertensive drugs
Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Use with drugs that raise blood pressure
Methylphenidate should be used with caution in patients treated with drugs that may also increase blood pressure (see also section on Cardiovascular and Cerebrovascular Conditions in section 4.4).
Due to possible hypertensive crises, the use of methylphenidate is contraindicated in patients treated (concurrently or within the last 2 weeks) with monoamine oxidase inhibitors (MAOIs) (see section 4.3).
Use with alcohol
Alcohol can exacerbate central nervous system adverse events caused by psychoactive drugs, including methylphenidate. It is therefore recommended that patients refrain from drinking alcohol during treatment.
Use with anesthetics
There is a risk of a sudden increase in blood pressure, in some cases associated with an increase in heart rate, during surgical procedures. If surgery is planned, methylphenidate treatment should not be given on the day of the operation.
Use with centrally acting alpha-2 agonists (e.g. clonidine)
The long-term safety of methylphenidate in combination with clonidine or other centrally acting alpha-2 agonists has not been systematically established.
Use with dopaminergic drugs
Caution is advised when administering methylphenidate concomitantly with dopaminergic drugs, including antipsychotics. Since a predominant action of methylphenidate is to raise extracellular dopamine levels, methylphenidate may be associated with pharmacodynamic interactions when administered in combination with direct and indirect dopamine agonists (including DOPA and tricyclic antidepressants) or with the included dopamine antagonists. antipsychotics.
04.6 Pregnancy and lactation
Pregnancy
There are limited data on the use of methylphenidate in pregnant women.
There have been spontaneous case reports of cardiorespiratory toxicity in neonates, and specifically tachycardia and respiratory distress in the fetus.
Studies in animals have shown reproductive toxicity only at maternally toxic dosages (see section 5.3).
Methylphenidate is not recommended for use during pregnancy unless it has been clinically established that postponement of treatment poses an increased risk to the pregnancy itself. Methylphenidate is potentially teratogenic in rabbits (see section 5.3).
Feeding time
Methylphenidate was detected in the milk of a woman treated with methylphenidate.
There was a case report of a neonate who experienced an unspecified decrease in body weight during treatment of the mother but regained and resumed weight gain after the mother discontinued treatment with methylphenidate. It cannot be excluded. a risk to the breastfed infant.
A decision must be made whether to discontinue breast-feeding or to discontinue / abstain from methylphenidate therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility
There are no data to support special recommendations for women of childbearing age.
There are no data on the effect of methylphenidate on human fertility. Methylphenidate did not impair fertility in male or female mice (see 5.3).
04.7 Effects on ability to drive and use machines
Methylphenidate can cause dizziness, numbness and visual disturbances, including difficulty focusing, diplopia and blurred vision. It may have a moderate effect on the ability to drive and use machines. Patients should be warned of such possible effects and, if present, to avoid engaging in potentially hazardous activities such as driving or using machines.
04.8 Undesirable effects
The table below lists all adverse drug reactions (ADRs - Adverse Drug Reactions) observed during clinical trials and those reported from spontaneous post-marketing reports of Ritalin as well as adverse reactions observed with other methylphenidate hydrochloride formulations. In cases where the frequencies of adverse reactions observed with Ritalin and the other methylphenidate formulation were different, the higher frequency of the two databases was used.
Frequency classification:
very common (≥ 1/10)
common (≥ 1/100,
uncommon (≥ 1/1000,
rare (≥ 1 / 10,000,
very rare (
not known (frequency cannot be estimated from the available data).
* See section 4.4 Special warnings and precautions for use
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
04.9 Overdose
Signs and symptoms
Acute overdose, mainly due to hyperstimulation of the central and sympathetic nervous systems, can result in: vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (sometimes followed by coma), euphoric states, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias, hypertension, mydriasis and dry mucous membranes.
Treatment
There is no specific antidote for methylphenidate overdose.
Treatment consists of providing appropriate supportive measures.
Supportive measures include actions that prevent self-harm and protect the patient from external stimuli that would lead to exacerbating the already present overstimulation. If the signs and symptoms are not too severe and the patient is conscious, the stomach can be emptied by inducing vomiting or gastric lavage. Before performing gastric lavage, agitation and seizures, if present, should be controlled and the airways protected. Other means of detoxifying the intestine include the administration of activated charcoal and a cathartic. In the presence of severe intoxication, administer a carefully titrated dose of a benzodiazepine before performing gastric lavage.
Intensive treatments must be adopted to maintain adequate circulation and respiration; External cooling procedures may be required to reduce hyperpyrexia.
The efficacy of peritoneal dialysis or extracorporal hemodialysis in methylphenidate overdose has not been demonstrated.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: psychostimulant.
ATC code: N06B A04.
Ritalin is a weak central nervous system stimulant with more pronounced effects on mental rather than motor activities. Its mechanism of action in humans is not yet fully understood, but it is believed that its stimulating effects are due to an inhibition of dopamine reuptake in the striatum, without causing the release of dopamine.
The mechanism by which Ritalin exerts its effects on mental and behavioral activities in children has not yet been clearly demonstrated, nor is there clear evidence of how these effects relate to central nervous system conditions.
Ritalin is a racemate which consists of a 1: 1 mixture of d-methylphenidate (d-MPH) and l-methylphenidate (l-MPH).
The d- enantiomer is pharmacologically more active than the l- enantiomer.
The effect of treatment with 40 mg of desmethylphenidate hydrochloride, the pharmacologically active dextrorotatory enantiomer of Ritalin, on the QT / QTc interval was evaluated in a study conducted in 75 healthy volunteers. The mean value of the maximum prolongation of the QTcF interval is result
05.2 Pharmacokinetic properties
Absorption
After oral administration the active ingredient (methylphenidate hydrochloride) is rapidly and almost completely absorbed. Due to the remarkable first pass metabolism its absolute availability is 22 ± 8% for the d- enantiomer and 5 ± 3% for the l- enantiomer.
Intake with food has no significant effect on absorption. Maximum plasma concentrations of approximately 40 nmol / l (11 ng / ml) are achieved on average 1-2 hours after administration. Maximum plasma concentrations vary greatly between patients. The area under the curve (AUC) and the maximum plasma concentration (Cmax) are proportional to the dose.
Distribution
In the blood, methylphenidate and its metabolites are distributed between plasma (57%) and erythrocytes (43%). Plasma protein binding is low (10-33%). The volume of distribution is 2.65 ± 1.11 L / kg for d-MPH and 1.80 ± 0.91 L / kg for 1-MPH.
Biotransformation
Methylphenidate is rapidly and completely biotransformed by the CES1A1 carboxylesterase. Maximum plasma concentrations of the major non-esterified metabolite - α-phenyl-2-piperidin acetic acid (ritalinic acid) - are reached approximately 2 hours after administration and are 30-50 times higher than those of the parent substance. The half-life of α-phenyl-2-piperidine acetic acid is approximately double that of methylphenidate and its mean systemic clearance is 0.17 l / h / kg. Only small amounts of hydroxylated metabolites (e.g. hydroxymethylphenidate and hydroxyritalinic acid) are detectable. Therapeutic activity appears to be mainly due to the unchanged substance.
Elimination
Methylphenidate is eliminated from plasma with a mean half-life of 2 hours. The systemic clearance value is 0.40 ± 0.12 l / h / kg for d-MPH and 0.73 ± 0.28 l / h / kg for l-MPH. After oral administration, 78-97% of the dose is excreted in the urine and 1-3% in the faeces as metabolites within 48-96 hours. Only minimal amounts (
Characteristics in patients
There are no apparent differences in the pharmacokinetic characteristics of methylphenidate between hyperactive children and healthy adult volunteers. Elimination data in patients with normal renal function suggest that renal excretion of unchanged methylphenidate may be minimally decreased in the event of renal impairment. However, renal excretion of α-phenyl-2-piperidin acetic acid may be reduced.
05.3 Preclinical safety data
Carcinogenicity
In lifetime carcinogenicity studies in rats and mice, an increase in the number of malignant liver tumors was observed in male mice only. The significance of this observation for humans is unknown.
Fertility
Methylphenidate had no effect on reproductive function or fertility in mice and rats when administered in low multiples of the clinical dose.
Reproductive toxicity
Methylphenidate is not thought to be teratogenic in rats. In rats, fetal (total loss of offspring) and maternal toxicity were observed with maternal toxic dosages. Methylphenidate is potentially teratogenic in rabbits; the racemic mixture produced a low incidence of spina bifida at a maternal dose level of 200 mg / kg / day.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Calcium phosphate, gelatin, lactose monohydrate, magnesium stearate, talc, wheat starch.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
2 years.
06.4 Special precautions for storage
Do not store above 25 ° C. Store the tablets in the original package.
06.5 Nature of the immediate packaging and contents of the package
Pack of 30 tablets.
PA / AL / PVC blisters with aluminum foil bottom.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Novartis Farma S.p.A.
Largo Umberto Boccioni, 1
21040 Origgio (VA)
08.0 MARKETING AUTHORIZATION NUMBER
AIC n. 035040017
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 19.04.2007
Date of last renewal: 25.04.2012
10.0 DATE OF REVISION OF THE TEXT
04/2015
