Tetrabenazine Aristo

Patient Information Leaflet

Tetrabenazina Aristo 25 mg tablets

tetrabenazine
Generic medicine
Please read this leaflet carefully before taking this medicine as it contains
important information for you.

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

Contents of this leaflet:

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

1. What Tetrabenazina Aristo is and what it is used for

Tetrabenazina Aristo are oral tablets. The active substance in Tetrabenazina Aristo is tetrabenazine.
Tetrabenazine inhibits the storage of certain neurotransmitters in the brain. This reduces the transmission of nerve impulses in nerve cells within specific brain regions involved in the regulation of sequences of individual movements. As a result, excessive and/or involuntary movements (hyperkinesia) can be better controlled. These excessive and/or involuntary movements may have an organic (physical) origin (such as in Huntington's disease). However, they may also be caused by medications, e.g., following prolonged use of neuroleptics (medications used to treat mental disorders). In the latter case, the condition is known as tardive dyskinesia (late-onset movement disorders).
Tetrabenazina Aristo is used to treat the following conditions:

• Excessive and/or involuntary movements (hyperkinesia) in Huntington's disease.
• Moderate to severe tardive dyskinesia (late-onset movement disorders); Tetrabenazina Aristo may be taken for this type of movement disorder only if other treatment options have failed.

2. What you should know before taking Tetrabenazine Aristo

Do not take Tetrabenazine Aristo

• if you are allergic to tetrabenazine or to any of the other ingredients of this medicine (listed in section 6);
• if you have thoughts of self-harm or suicide;
• if you suffer from depression or if symptoms persist despite antidepressant treatment;
• if you have a tumour dependent on the hormone prolactin, such as breast cancer or a pituitary gland tumour (pituitary prolactinoma);
• if you have a tumour of the adrenal medulla (phaeochromocytoma);
• if you are breastfeeding;
• if you are taking, or have taken within the last 14 days, a monoamine oxidase inhibitor (a medicine used to treat depression);
• if liver function is impaired;
• if you are taking medicines containing reserpine as the active ingredient;
• if you have Parkinson’s disease or symptoms of Parkinson’s disease.

Warnings and precautions
Talk to your doctor before taking tetrabenazine
if you know you are a poor or intermediate metabolizer of an enzyme called CYP2D6. In this
case, a different dose may be required for you;
if you have been diagnosed with depression or if you have had suicidal thoughts or attempted
suicide;
if you have ever suffered from depression.

Treatment of tardive dyskinesia (delayed movement disorders)
Ask your doctor whether treatment with Tetrabenazine Aristo may be considered for you.
Your doctor will advise you accordingly. However, tetrabenazine is a centrally acting substance that
depletes neurotransmitters, which in humans may also cause extrapyramidal symptoms and,
theoretically, tardive dyskinesia.

Development of depression (depressed mood) / suicide (suicidal thoughts or behaviour)
Tetrabenazine may cause depression or worsen pre-existing depression.
If depression occurs, it may be managed by reducing the dose. Isolated cases have been reported in
which patients treated with tetrabenazine have considered taking their own life (suicidal thoughts) or
have exhibited suicidal behaviour.
If severe depression or suicidal thoughts occur, tetrabenazine must be discontinued and antidepressant
therapy should be initiated.
If you develop depression during treatment with Tetrabenazine Aristo, inform your doctor.
Your doctor will take the necessary actions.

Irritability and aggressive behaviour
In patients with depression or a history of other psychiatric disorders taking tetrabenazine,
there is a potential risk of developing or worsening irritability and aggressive behaviour.

Onset of parkinsonism
Tetrabenazine Aristo may trigger symptoms of Parkinson’s disease and worsen pre-existing
Parkinson’s disease symptoms. If this happens to you, inform your doctor, who will take the
necessary actions.

Dysphagia
Dysphagia is a component of Huntington’s disease. However, medicines that reduce dopaminergic
transmission have been associated with esophageal dysmotility and dysphagia. Dysphagia may be
associated with aspiration pneumonia. If you notice difficulty swallowing, consult your doctor.

Development of neuroleptic malignant syndrome
During treatment with Tetrabenazine Aristo, the so-called neuroleptic malignant syndrome (NMS)
may rarely occur.
This is a potentially life-threatening condition in which high fever, sweating, blood pressure fluctuations,
irregular or rapid pulse, cardiac arrhythmias, muscle rigidity, and impaired consciousness may occur.
If one or more of these symptoms occur, you must contact your doctor or the nearest hospital
immediately.

Patients with a history of tumours
If Tetrabenazine Aristo is taken for a prolonged period, blood concentrations of prolactin (a hormone)
may increase. This higher concentration may, in rare cases, promote the growth of cells in breast tumours.
For this reason, inform your doctor before taking Tetrabenazine Aristo if you have previously had tumours.

Patients with prolonged QT interval
Tetrabenazine causes a slight prolongation of the QT interval on the ECG. Therefore, caution is
recommended in patients with congenital long QT syndrome, a history of cardiac arrhythmias, or in
patients taking other medicines that may prolong the QT interval.

Cardiac disease
Inform your doctor if you have recently had heart problems such as myocardial infarction or unstable
heart disease.

Restlessness and agitation
Inform your doctor if you notice difficulty remaining seated or standing still for prolonged periods
(inability to stay still), or if you experience restlessness or increased agitation. These side effects may
require a dose reduction.

Sedation and somnolence
Tetrabenazine may cause sedation or somnolence (drowsiness or unusual tiredness). In this case, you
should refrain from activities requiring particular attention (e.g. driving or operating dangerous machinery).

Orthostatic hypotension
A drop in blood pressure with symptoms such as dizziness upon standing and loss of consciousness
(syncope) may occur under certain conditions in patients treated with Tetrabenazine Aristo (e.g. when
rising from a lying position). Inform your doctor if you have been told you have low blood pressure
(associated with symptoms such as dizziness, headache, increased heart rate, or collapse).

Binding to melanin-containing tissues
Tetrabenazine and its metabolites may bind to melanin-containing tissues, where they accumulate over
time. Therefore, tetrabenazine may potentially cause damage to these tissues if used for long periods.
Although there are no specific recommendations for regular eye examinations, prescribers should be
aware of the possible long-term effects of tetrabenazine on the eyes.

Laboratory tests
Clinically significant changes in laboratory parameters have not been reported in clinical studies with
tetrabenazine. In controlled clinical trials, tetrabenazine caused a slight increase in ALT and AST
laboratory values compared to placebo.

Other medicines and Tetrabenazine Aristo
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicine, including those obtained without a prescription.
The following medicines may interact with Tetrabenazine Aristo when taken concurrently:

• Levodopa, a medicine for Parkinson’s disease
• Medicines with a sedative effect on the brain, such as neuroleptics, hypnotics, and opioids
• Medicines for high blood pressure (antihypertensives) and beta-blockers (medicines that reduce heart rate and blood pressure)
• Some medicines that slow down the breakdown of tetrabenazine, such as fluoxetine, paroxetine, quinidine, duloxetine, terbinafine, amiodarone, sertraline
• Medicines that prolong the QT interval on the ECG, such as neuroleptics, certain antibiotics (gatifloxacin, moxifloxacin), certain antiarrhythmics (quinidine, procainamide, amiodarone, sotalol)
• MAO inhibitors (certain antidepressants): to avoid the risk of a potentially serious interaction leading to hypertensive crisis, care must be taken to ensure a minimum interval of 14 days between discontinuation of Tetrabenazine Aristo and initiation of treatment with an MAO inhibitor, as well as between discontinuation of the MAO inhibitor and initiation of treatment with Tetrabenazine Aristo.
• Medicines metabolized by CYP2D6 (e.g. metoprolol, amitriptyline, imipramine, haloperidol, and risperidone): the effects of these medicines may be enhanced. Concomitant use of medicines that inhibit CYP2D6 (e.g. fluoxetine, paroxetine, quinidine, duloxetine, terbinafine, amiodarone, or sertraline) may further increase this effect.
• Reserpine: tetrabenazine must not be taken concurrently with reserpine. If switching from reserpine treatment to tetrabenazine, this should be done cautiously with a sufficient interval of several days.

Tetrabenazine Aristo and alcohol
The sedative effect of Tetrabenazine Aristo may be enhanced if alcohol is consumed at the same time.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding,
consult your doctor or pharmacist before taking this medicine.

Pregnancy
There are inadequate data on the safety of tetrabenazine in pregnant women. Therefore,
Tetrabenazine Aristo is not recommended for use during pregnancy unless your doctor considers it
strictly necessary.
The use of tetrabenazine is not recommended during pregnancy or in women of childbearing potential
who are not using adequate contraceptive measures.
It is therefore essential that you inform your doctor if you are pregnant, suspect you may be pregnant, or
wish to become pregnant. Your doctor will decide whether you may continue taking Tetrabenazine Aristo.

Breastfeeding
You must not breastfeed during treatment with Tetrabenazine Aristo.

Fertility
Animal studies with tetrabenazine have not shown any effect on pregnancy or intrauterine survival. An
increase in the length of menstrual cycles and a delay in the fertile phase have been observed.

Driving and using machines
Tetrabenazine Aristo may cause drowsiness. This could affect your ability to drive or use machinery.
You should discuss with your doctor the effects of Tetrabenazine Aristo on your ability to drive, as the
degree of impairment may vary significantly between individuals.

Tetrabenazine Aristo contains lactose
Each tablet of Tetrabenazine Aristo contains 63.4 mg of lactose (as lactose monohydrate).
If your doctor has told you that you have an intolerance to certain sugars, consult your doctor before
taking this medicine.

3. How to take Tetrabenazina Aristo

Take this medicine exactly as directed by your doctor. If you have
any doubts, consult your doctor or pharmacist.
During initial prescribing, your doctor will gradually increase the dose of tetrabenazine over
several weeks to find a chronic maintenance dose that reduces symptoms and is well tolerated.
Notes
The dosage depends on the clinical condition and the response to treatment. The required dose may
vary from patient to patient. The following dosage recommendations are therefore intended only
as a guide. Always follow your doctor’s instructions regarding dosage. Your doctor will review the dosage at
regular intervals.
If you have liver or kidney problems, your doctor may prescribe you a different dosage.

Dosage for excessive and/or involuntary movements (hyperkinesia) in Huntington’s disease
Unless otherwise prescribed by your doctor, the usual initial dose is one tablet of Tetrabenazina Aristo
three times daily.
This dose may be increased by one tablet per day every three or four days until optimal efficacy is achieved.
The maximum daily dose of 8 tablets of Tetrabenazina Aristo must not be exceeded.

Dosage for tardive dyskinesia (late-onset movement disorders)
Adults
Unless otherwise prescribed by your doctor, the usual initial dose is half a tablet per day.
If you respond favourably to treatment, your doctor will gradually increase the dose. Your
doctor may discontinue treatment with Tetrabenazina Aristo if:

• there is no clinical improvement after increasing the dose;
• severe adverse reactions occur.

Restarting treatment
If treatment has been interrupted for more than 5 days, or if treatment has been paused due to a medical condition or concomitant use of other medicines, tetrabenazine therapy must be re-titrated upon resumption. Depending on your doctor’s instructions, treatment should be restarted at 12.5 mg twice daily. This low dose should be maintained for 7 days, after which your dose will be increased in steps of 12.5 mg per day.
If you experience adverse reactions such as inability to stay still (akathisia), restlessness, parkinsonism such as impaired balance, tremors or increased salivation, depression, insomnia, anxiety or intolerable sedation, contact your doctor.
Your doctor will decide whether to stop titration and reduce the dose.

Special populations
Elderly patients and children
No specific studies have been conducted in either of these age groups. Your doctor will determine the
appropriate dose.
Elderly patients usually receive the recommended adult dose.
Children usually start with approximately half the adult daily dose. This dose may then be slowly and carefully adjusted according to individual tolerance and response.
Talk to your doctor or pharmacist if you feel that the effect of Tetrabenazina Aristo is too strong or too weak.

Patients with hepatic impairment, renal impairment
If you have liver or kidney problems, your doctor may prescribe a different dosing schedule and/or a
different dose.
Talk to your doctor before taking tetrabenazine if you know you are a slow or intermediate metabolizer
of an enzyme called CYP2D6. In this case, a different dose may be required.

Method of administration
Tetrabenazina Aristo is for oral use.
Take the tablets with sufficient liquid (water or other non-alcoholic beverages). Do not take the
tablets with alcohol, and do not chew them.
The tablets have a score line and can be divided into equal doses. This allows you to take half tablets.

If you take more Tetrabenazina Aristo than you should
If you take too many tablets or if someone else accidentally takes your medicine, contact
your doctor, pharmacist or nearest hospital immediately.
Symptoms of overdose include uncontrollable muscle spasms affecting the eyes, head, neck and body,
involuntary rolling of the eyes, excessive blinking, nausea, vomiting, diarrhoea, sweating, dizziness,
feeling cold, confusion, hallucinations, drowsiness, flushing/inflammation and tremor.

If you forget to take Tetrabenazina Aristo
Do not take a double dose to make up for the missed dose.
Continue treatment with the next dose as usual.

If you stop taking Tetrabenazina Aristo
Under no circumstances should you change the dosage of Tetrabenazina Aristo without first consulting your doctor.
If you no longer wish to take Tetrabenazina Aristo, you must discuss this first with your doctor.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Significant side effects or warning signs to watch for and actions to take if affected
If you experience muscle stiffness or fever and changes in consciousness (such as confusion or hallucinations), stop taking Tetrabenazina Aristo. Contact your doctor or the nearest hospital as soon as possible (see also section 2 "Warnings and precautions").

Seek immediate medical advice or go to the nearest hospital if you experience any of the following side effects:

• If you develop muscle rigidity, fever, or disturbances in consciousness (e.g. confusion or hallucinations), stop taking Tetrabenazina Aristo. Contact your doctor or the nearest hospital as soon as possible (see also section 2 "Warnings and precautions").
• Very common (may affect more than 1 in 10 people): Tetrabenazina Aristo may cause depression, which in some people may lead to suicidal thoughts. If you feel down or very sad, you may become depressed and you must inform your doctor of this change.
• Very rare (may affect up to 1 in 10,000 people): if you have attempted suicide, intentionally harmed yourself, or deliberately thought about harming yourself.

Other possible side effects
Very common: may affect more than 1 in 10 people:

• Tetrabenazina Aristo may cause depression, which may lead to suicidal thoughts in some people. If you feel low or very sad, you may begin to feel depressed and must inform your doctor of this change;
• drowsiness
• Parkinson-like symptoms such as impaired balance, tremors, or increased salivation

Common: may affect up to 1 in 10 people:

• restlessness
• confusion
• feeling anxious
• insomnia
• decreased appetite

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

• pneumonia
• reduced number of white blood cells (leucopenia)
• involuntary rotation of the eyes (oculogyric crisis)
• light sensitivity (photophobia)
• dehydration
• aggression, anger
• suicidal thoughts, deliberate self-harm, or deliberate thoughts of harming oneself
• neuroleptic malignant syndrome (a condition characterized by high fever, sweating, fluctuations in blood pressure, muscle rigidity, and impaired consciousness) – see section 2 "Warnings and precautions"
• skin rash, itching, urticaria
• weight loss
• increased risk of falls

Not known: frequency cannot be estimated from the available data:

• disorder of balance and movement coordination (ataxia)
• inability to stay still (akathisia)
• movement disorder with involuntary spasms and abnormal postures (dystonia)
• memory loss
• dizziness
• disorientation
• nervousness
• restlessness
• sleep disorders
• slow heart rate (bradycardia)
• drop in blood pressure with dizziness when standing up (orthostatic hypotension)
• hypertensive crisis
• difficulty swallowing
• nausea (feeling unwell)
• vomiting
• pain in the upper abdomen
• diarrhoea
• constipation
• dry mouth
• sweating
• irregular menstrual cycle
• fatigue
• weakness
• decreased body temperature (hypothermia)
• increased appetite
• weight gain

To avoid the risk of a potentially serious interaction that could lead to a hypertensive crisis, it is necessary to ensure that at least 14 days pass between stopping Tetrabenazina Aristo and starting treatment with a MAO inhibitor, as well as between stopping a MAO inhibitor and starting treatment with Tetrabenazina Aristo.

If Tetrabenazina Aristo is taken for prolonged periods, the blood concentration of prolactin (a hormone secreted by the pituitary gland) may increase. This returns to normal levels after stopping treatment. As a result, abnormal milk secretion (galactorrhoea), absent or irregular menstrual cycles, enlargement of the male breast (gynaecomastia), breast pain, breast enlargement, pituitary tumours (prolactinomas), orgasm disorders, and impotence may occur.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Tetrabenazina Aristo

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 label after "Exp.". The expiry date refers to the last day of that month.
Do not store above 30 °C. Keep in the original packaging to protect from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Tetrabenazina Aristo contains

• The active substance is tetrabenazine.
• The excipients are: monohydrate lactose (see section 2 "What you need to know before taking Tetrabenazina Aristo"), maize starch, microcrystalline cellulose, talc, magnesium stearate (Ph.Eur.), yellow iron oxide (E172).

Description of the appearance of Tetrabenazina Aristo and contents of the pack
Tetrabenazina Aristo 25 mg tablets are pale yellow, round, with a score line on one side and a diameter of approximately 7.00 mm ± 0.2 mm.
The tablet can be divided into equal doses.
Tetrabenazina Aristo is available in bottles containing 112 tablets.
Marketing Authorization Holder and Manufacturer
Aristo Pharma GmbH
Wallenroder Straße 8-10
13435 Berlin
Germany
Marketing Authorization Holder in Italy
Aristo Pharma Italy S.r.l.
[email protected]
This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Germany: Tetrabenazin Aristo 25 mg Tabletten
Austria: Tetrabenazin Aristo 25 mg Tabletten
Italy: Tetrabenazina Aristo
Portugal: Tetrabenazina Aristo
Spain: Tetrabenazina Aristo 25 mg comprimidos
United Kingdom: Tetrabenazine Aristo 25 mg tablets