Mantadan

Package leaflet: Information for the patient

Mantadan® 100 mg tablets
Amantadine
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 others, even if their symptoms are the same as yours, as it could be harmful.
• 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 Mantadan is and what it is used for
2. What you need to know before taking Mantadan
3. How to take Mantadan
4. Possible side effects
5. How to store Mantadan
6. Contents of the pack and other information

1. What Mantadan is and what it is used for

Mantadan contains the active substance amantadine, which belongs to a group of medicines called
dopaminergic agents.
Mantadan is indicated in adults and elderly patients for the treatment:

• of Parkinson's disease (a disease of the central nervous system that impairs movement control, manifesting, for example, with tremor, rigidity, slowness of movement, difficulty maintaining balance, due to reduced levels in the central nervous system of a substance called dopamine)
• of parkinsonism (conditions resembling Parkinson's disease and thus referred to as parkinsonism)
• of bradypsychism in involutional age (conditions causing slowing of mental functions), whether or not associated with arteriosclerosis, with or without signs of extrapyramidal involvement (involvement of the area of the nervous system that controls movement).

Consult your doctor if you do not feel better or if you feel worse.

2. What you should know before taking Mantadan

Do not take Mantadan

• if you are allergic to amantadine or to any of the other ingredients of this medicine (listed in section 6);
• during pregnancy;
• if you have previously experienced allergic reactions to this medicine;
• if you suffer from severe heart diseases such as severe decompensated heart failure, cardiomyopathies, or myocarditis (diseases of the heart muscle);
• if you have second- or third-degree atrioventricular block (severe disturbance of the heart's electrical conduction system);
• if you have bradycardia (reduced heart rate, i.e. number of heartbeats per minute) with a heart rate below 55 beats per minute;
• if you or someone in your family has been diagnosed with ECG (electrocardiogram, a test to assess heart function) abnormalities such as prolonged QT interval, visible U waves, or congenital long QT syndrome;
• if you have previously experienced severe ventricular arrhythmias (abnormal heart rhythms), including torsades de pointes (a specific type of arrhythmia);
• if you are being treated with budipine or other medicines that cause ECG abnormalities, such as QT interval prolongation (see section “Other medicines and Mantadan”);
• in case of low levels of potassium and magnesium in the blood.

Warnings and precautions
Talk to your doctor or pharmacist before taking Mantadan.
Before starting treatment and again after 1 and 3 weeks, your doctor will prescribe an examination called an electrocardiogram (ECG) to assess your heart function. If your doctor decides to increase the dose at a later time, they will prescribe another ECG before increasing the dose and again two weeks later. Subsequently, your doctor will prescribe periodic control ECGs at least annually. Based on ECG values before and during treatment with Mantadan, your doctor will evaluate whether you should discontinue treatment.
Contact your doctor if you, a family member, or your caregiver notice that you are developing an urge or craving to behave in an unusual way and are unable to resist the impulse, desire, or temptation to engage in activities that could harm you or others. These types of behaviors are known as impulse control disorders and may include gambling addiction, compulsive eating or spending, abnormally increased sexual desire, or increased sexual thoughts or sensations.
Your doctor may need to adjust the dose or discontinue treatment with Mantadan.
Electrolyte imbalances
If you are at risk of electrolyte imbalances (abnormal concentrations of salts normally dissolved in blood and body fluids), for example: if you are taking diuretics (medicines that increase urine production), if you have frequent vomiting and/or diarrhea, if you use insulin in emergency situations, if you have kidney disease or anorexia (loss of appetite), your doctor will prescribe the necessary monitoring tests and, if needed, will restore appropriate electrolyte levels, particularly potassium and magnesium.
Cardiovascular diseases (affecting the heart and blood circulation)
If you have heart or circulatory diseases, you should undergo regular medical check-ups during treatment with Mantadan. Peripheral edema (swelling in certain parts of the body) may occur during prolonged use of Mantadan.
At the first appearance of symptoms such as palpitations, dizziness, or syncope (sudden, temporary loss of consciousness), you must stop taking Mantadan and contact your doctor immediately. Your doctor will evaluate – within 24 hours – any possible ECG abnormalities. If no ECG abnormalities are present, your doctor will decide whether you can continue treatment with Mantadan, taking into account contraindications and interactions (see also section “Other medicines and Mantadan”).
If you have a pacemaker (i.e. you have undergone surgery to implant a device that electrically stimulates your heart's contractions), ECG values cannot be accurately determined. Therefore, the decision on treatment with Mantadan must be made on a case-by-case basis, in consultation with your cardiologist.
Treatment with neuroleptics
If you are receiving concomitant treatment with neuroleptics (a class of medicines used to treat certain mental illnesses) and Mantadan, do not abruptly stop treatment with Mantadan, as there is a risk of developing neuroleptic malignant syndrome (a serious nervous system disorder), which may be life-threatening (see also section “If you stop taking Mantadan”).
Kidney disorders
Mantadan should be taken with caution in the presence of impaired kidney function, as intoxication may occur.
Consult your doctor if you experience urinary disorders (problems with urination).
Nervous system disorders
Mantadan should be used with caution in the following cases:

• if you have previously suffered from organic brain syndrome or cerebral seizures (diseases of the nervous system), as symptoms may worsen and seizures may occur (see sections “Possible side effects” and “How to take Mantadan”);
• if you suffer from confusion, hallucinations, or underlying psychiatric disorders;
• if Mantadan has been prescribed together with other medicines acting on the central nervous system (see also section “Other medicines and Mantadan”).

Other precautions for use
In patients with Parkinson’s disease, symptoms such as hypotension (low blood pressure), sialorrhea (excessive saliva production), generalized sweating, hyperthermia (increased body temperature), heat stroke, fluid retention, and depressive mood disorders are often observed. These conditions should be managed considering the potential side effects and interactions of Mantadan (see sections “Possible side effects” and “Other medicines and Mantadan”).
If blurred vision or other visual disturbances occur, consult an ophthalmologist immediately.
Children
There is insufficient experience in children; therefore, the use of this product in children is not recommended.
Other medicines and Mantadan
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
During treatment with amantadine, you must not take other medicines that cause ECG alterations, including, for example:

• certain antiarrhythmics (medicines used to treat heart rhythm disorders), such as quinidine, disopyramide, procainamide, amiodarone, sotalol;
• certain antipsychotics (medicines used for certain mental illnesses), such as thioridazine, chlorpromazine, haloperidol, pimozide;
• certain tricyclic and tetracyclic antidepressants (medicines used to treat depression), such as amitriptyline;
• certain antihistamines (medicines used to treat allergies), such as astemizole, terfenadine;
• certain antibiotics (e.g. erythromycin, clarithromycin, sparfloxacin);
• azole antifungals (medicines used for fungal skin infections);
• other medicines such as budipine (a medicine for Parkinson’s disease), halofantrine (a medicine used to treat malaria), cotrimoxazole and pentamidine (antibacterial medicines used for infections), ziprasidone (a medicine used to treat certain mental illnesses), or bepridil (a medicine used to treat angina pectoris, chest pain). This list may not be complete. Before combining amantadine with any other medicine, consult your doctor or pharmacist.

Mantadan may be combined with other medicines for Parkinson’s disease.
There are no targeted studies on the effects of administering Mantadan together with other antiparkinsonian or antidementia medicines (e.g. bromocriptine, trihexyphenidyl, etc.) (see section “Possible side effects”).
Levodopa may be combined with Mantadan. The combination with levodopa enhances the therapeutic effect of both medicines.
Memantine may increase the activity and side effects of Mantadan (see section “Do not take Mantadan”).
To avoid side effects (e.g. psychotic reactions, i.e. mental disturbances), your doctor may consider it necessary to reduce the dosage of other medicines or their combination.
During treatment with Mantadan, if you are taking any of the following groups of medicines or active substances simultaneously, the following conditions may occur:
Anticholinergics (medicines that block the effects of acetylcholine, a substance involved in nerve impulse transmission)
When combined with anticholinergics such as trihexyphenidyl, benzatropine, hyoscine, biperiden, orphenadrine, etc., an increase in anticholinergic side effects (confusion and hallucinations) may occur.
Indirect-acting central sympathomimetics (a class of medicines acting on the central nervous system)
Increased action of amantadine on the central nervous system.
Diuretics
Concomitant administration of diuretics (medicines that increase urine production), such as triamterene/hydrochlorothiazide combination, may reduce the body's ability to eliminate the medicine from the blood, leading to toxic levels of amantadine in the blood. Therefore, you should avoid taking these medicines together.
Mantadan and alcohol
Mantadan reduces tolerance to alcohol. You should take this into account if consuming alcoholic beverages during treatment with Mantadan.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before using this medicine.
Pregnancy
Do not use Mantadan if you are pregnant.
Breastfeeding
Amantadine is excreted in breast milk. Consult your doctor before taking this medicine.
Driving and using machines
Mantadan may cause side effects such as dizziness or blurred vision. Consider the potential risks if you drive or operate machinery requiring attention and vigilance.
Mantadan contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, consult them before taking this medicine.

3. How to take Mantadan

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

Adults
The recommended dose is 1 tablet twice daily (in the morning and at midday).
Your doctor will adjust the dosage according to any concomitant therapies you are receiving (e.g. levodopa, anticholinergics, etc.) and your individual response.
Before starting treatment, and again after 1 and 3 weeks, your doctor will prescribe an examination called an electrocardiogram (ECG), based on which the function of your heart will be assessed.
If your doctor decides to increase your dose at a later stage, they will prescribe a new ECG before increasing the dose and again two weeks thereafter. Subsequently, your doctor will prescribe control ECGs at least once a year.
Based on the ECG values before and during treatment with Mantadan, your doctor will evaluate whether you should discontinue treatment. In this way, and considering also the contraindications listed in section "Do not take Mantadan", it is possible to avoid the very rare but dangerous adverse effect of torsade de pointes ventricular tachycardia (a specific type of arrhythmia, i.e. disturbance of heart rhythm) (see section "Possible side effects").
If you are receiving concomitant treatment with other antiparkinsonian medicines, your doctor will adjust the dosage on a case-by-case basis.

Elderly
In elderly patients, due to reduced renal clearance (reduced kidney capacity to filter and cleanse the blood), which leads to higher blood levels of amantadine, the recommended dose is 100 mg daily (1 tablet daily).

Patients with impaired kidney function
In general, if kidney function is impaired, your doctor will adjust the dosage based on assessment of your kidney function, particularly considering the reduction in renal clearance (the kidney's capacity to filter and cleanse the blood, measured by a parameter called glomerular filtration rate – GFR).

*) to be achieved by alternately administering one 100 mg tablet and then two 100 mg tablets of amantadine hydrochloride.
How to take the tablets
The tablets should be swallowed with some liquid, preferably in the morning and in the afternoon.
The last daily dose should be taken no later than 4 p.m.
Duration of treatment
The duration of treatment depends on the type and severity of the clinical condition and will be determined by your physician.
Do not stop taking the medicine on your own initiative.
Do not abruptly discontinue taking Mantadan, as this may lead to a severe worsening of symptoms, potentially resulting in akinetic crisis (collapse due to temporary loss of muscle strength and tone). There is also the possibility that withdrawal symptoms may occur, which could even progress to delirium (see also section “If you stop taking Mantadan”).
Use in children
There is insufficient experience in children; therefore, the use of this product in children is not recommended.
If you take more Mantadan than you should
In case of accidental ingestion/overdose of Mantadan, you must immediately contact your doctor or go to the nearest hospital.

• Symptoms Acute intoxication is characterized by nausea, vomiting, hyperexcitability, tremor, ataxia (progressive loss of muscular coordination), blurred vision, lethargy (deep sleep state with reduced response to normal stimuli), depression, dysarthria (difficulty articulating words), and cerebral seizures; in one case, a malignant cardiac arrhythmia (malignant alteration of heart rhythm, i.e., abnormal number of beats per minute) was reported.
• Therapeutic measures There is no specific pharmacological treatment or antidote available. In cases of intoxication due to excessive tablet ingestion, vomiting should be induced or gastric lavage performed (to be carried out in hospital by trained personnel). In life-threatening intoxications, additional measures will be required as determined by the physician.

If you forget to take Mantadan
Do not take a double dose to make up for the missed tablet.
If you stop taking Mantadan
If you have any doubts about using this medicine, consult your doctor or pharmacist.
Do not stop treatment with Mantadan on your own initiative.
If you are being treated simultaneously with neuroleptics (a class of medicines used in the treatment of certain mental illnesses) and Mantadan, do not abruptly discontinue treatment with Mantadan, as there is a risk of developing neuroleptic malignant syndrome (a serious disorder of the nervous system), which may be life-threatening.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The adverse reactions are listed below according to the following frequency:
Not known (frequency cannot be estimated from the available data):

• Urge to behave in an unusual way
• Strong urge to gamble, altered or increased interest in sex, excessive and uncontrollable spending or shopping, uncontrolled eating (consuming large amounts of food in a short time), or compulsive eating (consuming amounts of food greater than normal and greater than necessary to satisfy hunger)

Common (may affect up to 1 in 10 people):

• Motor and mental restlessness
• Paranoid psychosis (unfounded feelings of persecution or grandiosity), accompanied by visual hallucinations, particularly in predisposed elderly patients. These adverse effects may occur more frequently, especially when Mantadan is used in combination with other antiparkinsonian or antidementia medicines (e.g. levodopa, bromocriptine, memantine)
• Sleep disorders
• Dizziness
• Drop in blood pressure upon sudden standing, accompanied by symptoms such as dizziness/light-headedness (orthostatic hypotension)
• Dry mouth
• Nausea
• Urinary retention (inability of the urinary bladder to empty completely) in the presence of prostatic hypertrophy (enlargement of the prostate)
• Livedo reticularis (a skin condition characterized by a net-like pattern of skin discoloration), sometimes associated with swelling of the legs and ankles due to fluid accumulation

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

• Blurred vision

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

• Corneal lesion, corneal edema, reduced visual acuity

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

• Decrease in the number of white blood cells in the blood (leucopenia)
• Decrease in the number of platelets in the blood (thrombocytopenia)
• Anorexia (loss of appetite)
• Headache
• Brief and involuntary contraction of one or more muscles (myoclonus)
• Symptoms of peripheral neuropathy (disease of the peripheral nervous system)
• Seizures
• Temporary loss of vision
• Increased sensitivity to light (photophobia)
• Cardiac arrhythmias
• Ventricular tachycardia (increased heart rate of the ventricles)
• Ventricular fibrillation (disordered and very rapid contraction of the ventricles)
• Torsades de pointes (a specific type of arrhythmia)
• Changes in ECG (see sections “Do not take Mantadan” and “Other medicines and Mantadan”)
• Vomiting
• Diarrhea
• Stomach ache

Reporting of side effects
If you experience any side effect, 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.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Mantadan

This medicine does not require any special storage conditions.
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 packaging after EXP. The expiry
date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Mantadan contains

• the active substance is amantadine hydrochloride 100 mg
• the other components are: maize starch, lactose monohydrate (see section 2 “What you need to know before taking Mantadan”), talc, magnesium stearate.

Description of the appearance of Mantadan and contents of the pack
20 tablets packed in blisters.
Marketing Authorization Holder
Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó, 8, 8A and 8B - Fervença
2705-906 Terrugem SNT
Portugal
Tel.: +351 219 608 410
Fax: +351 219 615 102
e-mail: [email protected]
Marketing Authorization Holder in Italy
Hikma Italia SpA
Viale Certosa 10
27100 Pavia
Manufacturer
Istituto De Angeli S.r.l.
Loc. Prulli 103/c - Reggello (Florence)