Active ingredients: Amantadine
Mantadan 100 mg tablets
Why is Mantadan used? What is it for?
Mantadan contains the active substance amantadine, which belongs to a group of medicines called dopaminergic medicines.
Mantadan is indicated in adults and the elderly for the treatment:
- Parkinson's disease (central nervous system disease that prevents movement control, manifested for example by tremor, feeling of stiffness, slowing of movements, difficulty in maintaining balance, due to the reduction in the central nervous system of a substance called dopamine)
- of parkinsonisms (diseases which due to their similarity to Parkinson's disease are called parkinsonisms)
- bradypsychisms of the involutionary age (diseases that cause a slowing down of mental functions) also on an arteriosclerotic basis, with or without signs of extrapyramidal involvement (involvement of the area of the nervous system that controls movement).
Talk to your doctor if you don't feel better or if you feel worse.
Contraindications When Mantadan should not be used
Do not take Mantadan
- if you are allergic to amantadine or any of the other ingredients of this medicine (listed in section 6);
- pregnant;
- if you have ever had allergic reactions to this same medicine in the past;
- if you have severe heart diseases such as severe decompensated heart failure, cardiomyopathies and myocarditis (heart muscle diseases);
- if you have Grade II and III atrioventricular block (severe changes in the electrical conduction system of the heart);
- if you suffer from bradycardia (reduced heart rate, i.e. the number of heart beats per minute) with a rate of less than 55 beats / min;
- if you or someone in your family have been diagnosed with changes in the ECG (electrocardiogram, test to evaluate heart function) such as long QT interval or appreciable U waves or congenital long QT syndrome;
- if you have ever had severe ventricular arrhythmias (changes in heart rhythm) including torsades de pointes (a particular form of arrhythmia);
- if you are being treated with the medicine budipine or with other medicines that cause changes in the ECG, such as prolongation of the QT interval (see section "Other medicines and Mantadan");
- in case of low levels of potassium and magnesium in the blood.
Precautions for use What you need to know before taking Mantadan
Talk to your doctor or pharmacist before taking Mantadan.
Before the start of therapy and after 1 and 3 weeks, your doctor will prescribe an examination called an electrocardiogram (ECG) on the basis of which he will evaluate the function of your heart. Should the doctor increase the dosage at a later time, the Your doctor will prescribe the ECG again before increasing the dose and two weeks later. Subsequently, your doctor will prescribe a control ECG at least once a year. Based on the ECG values before and during treatment with Mantadan, your doctor will decide whether you should be excluded from treatment.
Electrolyte imbalances
If you are at risk of electrolyte imbalances (changes in the concentrations of salts normally dissolved in the blood and body fluids), for example: if you are taking diuretics (medicines that cause increased urine production), if you have vomiting and / or frequent diarrhea, if you use insulin in emergency situations, if you have kidney disease or states of anorexia (loss of appetite), your doctor will prescribe the necessary check-ups and, if necessary, will restore adequate electrolyte values , especially potassium and magnesium.
Cardio-circulatory diseases (affecting the heart and blood circulation)
If you have heart and circulation diseases, you should have regular medical checks during treatment with Mantadan. Peripheral edema (swelling in parts of the body) may occur during prolonged use of Mantadan.
At the first appearance of symptoms such as palpitations, dizziness (dizziness) or syncope (sudden and transient loss of consciousness), you should stop taking Mantadan and contact your doctor immediately. Your doctor will evaluate - within 24 hours - any changes in your electrocardiogram. (ECG). If there are no changes in the ECG, your doctor will decide whether you can continue therapy with Mantadan, taking into account the contraindications and interactions (see also section "Other medicines and Mantadan").
If you have a pacemaker (that is, if you have undergone a surgical operation in which a device capable of electrically stimulating the contraction of your heart has been applied to your heart), it is not possible to determine exactly the values of the ECG. Therefore, the decision on Mantadan therapy must be made on a case-by-case basis, in agreement with your treating cardiologist.
Neuroleptic therapy
If you are being treated simultaneously with neuroleptics (a class of medicines used to treat certain mental illnesses) and Mantadan, you should not abruptly stop treatment with Mantadan, as there is a risk of developing a neuroleptic malignant syndrome (severe nervous system disorder). which may be life-threatening (see also section "If you stop taking Mantadan").
Disorders of the kidney
In the presence of impaired renal function, Mantadan should be taken with caution as intoxication may occur. Consult your doctor if you have problems with urination (urinating problems).
Disorders of the nervous system
Mantadan should be used with caution in the following cases:
- if you have suffered in the past from organic brain syndrome and brain seizures (diseases of the nervous system), as individual symptoms of the disease may worsen and seizures may occur (see sections "Possible side effects" and "How to take Mantadan") ;
- if you suffer from confusion or underlying hallucinations or psychiatric illnesses;
- if you have been prescribed Mantadan together with other medicines that affect the central nervous system (see also section "Other medicines and Mantadan").
Other precautions for use
Often, symptoms of the disease such as hypotension (low blood pressure), drooling (excessive saliva production), widespread sweating, hyperthermia (increased body temperature), heat stroke, accumulation of water and depressive mood disorders, which must be treated taking into account the side effects and interactions of Mantadan (see sections "Possible side effects" and "Other medicines and Mantadan").
Children
There is insufficient experience in children, therefore the use of the product in children is not recommended.
Interactions Which drugs or foods can change the effect of Mantadan
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
During therapy with amantadine you should not take other medicines which cause an "alteration of the ECG" at the same time, including, for example:
- some antiarrhythmics (medicines used to treat heart rhythm disturbances) such as quinidine, disopyramide, procainamide, amiodarone, sotalol
- some antipsychotics (medicines used for some mental illnesses) such as thioridazine, chlorpromazine, haloperidol, pimozide
- some tricyclic and tetracyclic antidepressants (medicines used to treat depression) such as amitriptyline
- some antihistamines (medicines used in the treatment of allergies) such as astemizole, terfenadine
- some antibiotics (such as erythromycin, clarithromycin, sparfloxacin)
- azole antifungals (medicines used for fungal skin infections)
- other medicines such as budipine (medicine for Parkinson's disease), halofantrine (medicine used in the treatment of malaria), cotrimoxazole and pentamidine (antibacterial medicines used in infections), ziprasidone (medicine used in the treatment of some mental illnesses) or bepridil ( medicine used in the treatment of angina pectoris, chest pain).
This list may not be complete. Before combining amantadine with any other medicine, talk to your doctor or pharmacist.
Mantadan can 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 anti-dementia medicines (eg bromocriptine, trihexyphenidyl etc.) (see section "Possible side effects").
Levodopa can be combined with Mantadan. The combination with levodopa results in an increase in the therapeutic effect of both drugs. Memantine may increase the activity and side effects of Mantadan (see section "Do not take Mantadan").
To avoid undesirable effects (such as psychotic reactions, ie mental disorders), the doctor may find it necessary to reduce the dosage of the other medicines or the combination.
During therapy with Mantadan, if you are taking the following groups of medicines or active substances at the same time, the following conditions may occur:
- Anticholinergics (medicines that block the effects of acetylcholine, a substance involved in the transmission of nerve impulses)
In case of association with anticholinergics such as for example with trihexyphenidyl, benzatropine, hyoscine, biperidene, orphenadrine etc. there may be an increase in the side effects of anticholinergics (confusional states and hallucinations).
- Indirect centrally acting sympathomimetics (a class of medicines that affect the central nervous system)
Increased action of amantadine on the central nervous system.
- Diuretics
Co-administration of diuretics (medicines that lead to increased urine production) such as the combination triamterene / hydrochlorothiazide may reduce the body's ability to clear the medicine from the blood and thus lead to toxic concentrations of amantadine in the blood. Therefore, you should avoid taking such medicines at the same time.
Mantadan with alcohol
Mantadan reduces your tolerance to alcohol, this should be taken into account if you consume alcohol while taking Mantadan.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.
Pregnancy
Do not use Mantadan if you are pregnant.
Feeding time
Amantadine is excreted in breast milk.
Ask your doctor for advice before taking this medicine.
Driving and using machines
The use of Mantadan may cause side effects such as dizziness or blurred vision. Please take into account the potential risks if you drive or plan to operate machinery that require attention and vigilance.
Mantadan contains lactose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Dosage and method of use How to use Mantadan: Dosage
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
Adults
The recommended dose is 1 tablet 2 times a day (in the morning and at noon). Your doctor will adjust the dose taking into account any associated therapies you are using (levodopa, anticholinergics, etc.) and your response.
Before the start of therapy and after 1 and 3 weeks, your doctor will prescribe an examination called an electrocardiogram (ECG) on the basis of which he will evaluate the function of your heart. In case your doctor should increase your dosage at a later time, your doctor will prescribe the ECG again before increasing the dose and two weeks later.
Subsequently, your doctor will prescribe a control ECG at least once a year.
Based on the ECG values before and during the treatment with Mantadan, the doctor will decide whether he should be excluded from the treatment. In this way, and also taking into account the contraindications mentioned in the section "Do not take Mantadan", it is possible to avoid the effect. very rare, but dangerous, undesirable side effect of torsades de pointes ventricular tachycardia (a particular form of arrhythmia, abnormal heart rhythm) (see section "Possible side effects").
If you are taking combination therapy with other antiparkinsonian medicines, your doctor will adjust your dose on a case-by-case basis.
Senior citizens
In the elderly, due to reduced renal clearance (reduced ability of the kidney to filter and clean the blood) resulting in higher blood levels of amantadine, the recommended dose is 100 mg per day (1 tablet per day).
Patients with impaired kidney function
In principle, in case of renal impairment, your doctor will adjust the dosage by evaluating the function of your kidneys based on the reduction in renal clearance (ability of the kidney to filter and clean the blood, measured according to a parameter that called glomerular filtration rate - VFG).
*) to be obtained by administering alternatively once 1 tablet of 100 mg and once 2 tablets of 100 mg of amantadine hydrochloride.
How to take the tablets
The tablets should be swallowed with some liquid, preferably in the morning and afternoon.
The last daily dose should be taken no later than 4 pm.
Duration of treatment
The duration of treatment depends on the type and severity of the clinical picture and will be determined by the attending physician. You must not stop the medicine on your own initiative.
You should not abruptly stop taking Mantadan, as otherwise you may experience a sharp worsening of symptoms, which can lead to akinetic crisis (collapse of the body due to temporary loss of strength and muscle tone), and there is the possibility that withdrawal phenomena occur which can lead to delirium (see also section "If you stop taking Mantadan").
Use in children
There is insufficient experience in children, therefore the use of the product in children is not recommended.
If you forget to take Mantadan
Do not take a double dose to make up for a forgotten tablet.
If you stop taking Mantadan
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
You must not stop Mantadan treatment on your own initiative.
If you are being treated simultaneously with neuroleptics (a class of medicines used to treat certain mental illnesses) and Mantadan, you should not abruptly stop treatment with Mantadan, as there is a risk of developing a neuroleptic malignant syndrome (severe nervous system disorder). , which can pose a risk to his life.
Overdose What to do if you have taken too much Mantadan
In case of accidental ingestion / intake of an overdose of Mantadan you should notify your doctor immediately or go to the nearest hospital.
Symptoms
The state of acute intoxication is characterized by nausea, vomiting, hyperexcitability, tremor, ataxia (progressive loss of muscle coordination), blurred vision, lethargy (deep sleep with reduced response to normal stimuli), depression, dysarthria (difficulty in articulating words) and brain seizures; in one case a "malignant cardiac arrhythmia (malignant alteration of the heart rhythm, ie the number of beats per minute) was reported.
Therapeutic measures
There is no specific drug therapy, nor an antidote. In case of intoxication due to excessive ingestion of tablets, he must induce vomiting or resort to gastric lavage (to be carried out in hospital by specialized personnel).
In case of intoxications that pose a risk to his life, measures are also necessary that will be established by the doctor.
Side Effects What are the side effects of Mantadan
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Adverse reactions are listed below according to the following frequency:
Common (may affect up to 1 in 10 patients):
- motor and psychic restlessness
- paranoid psychosis (unjustified feeling of persecution or sense of grandiosity), accompanied by visual hallucinations, especially in predisposed elderly patients. These side effects may occur more commonly especially if Mantadan is combined with other antiparkinsonian or anti-dementia medicines (e.g. levodopa, bromocriptine, memantine)
- sleep disorders
- dizziness
- decrease in blood pressure following the sudden transition to 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 (skin disease characterized by mesh-like patches), sometimes associated with swelling of the legs and ankles due to fluid accumulation
Rare (may affect up to 1 in 1,000 patients):
- blurred vision
Very rare (may affect up to 1 in 10,000 patients):
- reduction in the number of white blood cells in the blood (leukopenia)
- reduction in the number of platelets in the blood (thrombocytopenia)
- anorexia (lack of appetite)
- headache (headache)
- short and involuntary contraction of one or more muscles (myoclonia)
- symptoms of peripheral neuropathy (peripheral nervous system disease)
- Seizures
- temporary loss of vision
- increased sensitivity to light (photophobia)
- cardiac arrhythmias
- ventricular tachycardia (increased rate of ventricular beats in the heart)
- ventricular fibrillation (disordered, ultra-high-rate contraction of the ventricles)
- torsades de pointes (a particular form of arrhythmia)
- ECG changes. (see sections "Do not take Mantadan" and "Other medicines and Mantadan")
- He retched
- diarrhea
- stomach ache
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at http://www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
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 carton after EXP. The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Deadline "> Other information
What Mantadan contains
- the active ingredient is 100 mg amantadine hydrochloride
- the other ingredients are: maize starch, lactose monohydrate (see section 2 "What you need to know before you take Mantadan"), talc, magnesium stearate.
What Mantadan looks like and contents of the pack
20 tablets packed in blisters.
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 -
MANTADAN 100 MG TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
One tablet contains:
active ingredient: amantadine hydrochloride 100 mg;
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Tablets.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Parkinson's disease, parkinsonisms, bradypsychisms of the involutionary age, also on an arteriosclerotic basis, with or without signs of extrapyramidal involvement.
04.2 Posology and method of administration -
Parkinson's disease, parkinsonisms, bradypsychisms of the involutionary age:
1 tablet twice a day (morning and noon) is adequate in most cases.
The posology must however be adjusted by the doctor taking into account the associated therapies (levodopa, anticholinergics, etc.) and the individual response.
Before starting therapy and 1 and 3 weeks later, an ECG (50 mm / s) should be taken and the Bazett-corrected QT interval for heart rate (QTc) determined manually.
If the dosage is increased at a later time, an ECG of this type should be taken before the increase and two weeks later. Subsequently, ECG checks should be carried out at least annually.
Patients with baseline QTc values greater than 420 ms or a QTc increase greater than 60 ms during treatment with Mantadan or with QTc intervals> 480 ms during treatment with Mantadan, as well as with appreciable U waves should be excluded from treatment.
In this way, while keeping in mind the contraindications listed in section 4.3, it is possible to avoid the very rare but dangerous side effect of torsades de pointes ventricular tachycardia.
In case of combination therapy with other antiparkinsonian drugs, the dosage should be adjusted on a case-by-case basis.
In elderly patients, due to reduced renal clearance resulting in higher plasma levels of amantadine, the recommended dose is 100 mg per day.
In principle, in patients with impaired renal function the dosage should be adjusted to the extent of the reduction in renal clearance (measured by glomerular filtration rate - GFR), as follows:
*) to be obtained by administering alternatively once 1 tablet of 100 mg and once 2 tablets of 100 mg of amantadine hydrochloride.
In order to evaluate the glomerular filtration rate (GFG), the following approximation can be used:
where ClCr = creatinine clearance in ml / min
and creatinine = serum creatinine in mg / 100 ml.
The creatinine clearance value calculated in this way is valid for men, for women it is approximately 85% and, for the purpose of determining the GFR, it can be considered equivalent to the clearance of inulin (120 mg / min in adults ).
Amantadine is available for dialysis only to a limited extent (approx. 5%).
The tablets should be swallowed with some liquid, preferably in the morning and afternoon.
The last daily dose should be taken no later than 4 pm.
The duration of treatment depends on the type and severity of the clinical picture and will be determined by the attending physician. The patient should not discontinue the drug on his own initiative.
You must avoid abruptly discontinuing the intake of Mantadan, since otherwise parkinsonian patients may experience a sharp worsening of extrapyramidal symptoms, which can go as far as akinetic crisis, and there is the possibility that withdrawal phenomena may occur which may occur. until delirium.
04.3 Contraindications -
Mantadan is contraindicated in:
- hypersensitivity to the active substance or to any of the excipients
- severe decompensated heart failure (NYHA stage IV)
- cardiomyopathies and myocarditis
- Grade II and III atrioventricular block
- pre-existing bradycardia less than 55 beats / min
- known long QT interval (Bazett QTc> 420 ms) or appreciable U waves or congenital long QT syndrome in family history
- history of severe ventricular arrhythmias, including torsades de pointes
- concomitant therapy with budipine or other drugs that cause QT prolongation (see section "Interactions with other medicinal products and other forms of interaction").
- reduction in blood levels of potassium and magnesium.
Mantadan should not be used concomitantly with other drugs that prolong the QT interval (see also section "Interactions with other medicinal products and other forms of interaction").
04.4 Special warnings and appropriate precautions for use -
Children:
There is insufficient experience in children.
Before starting therapy and 1 and 3 weeks later, an ECG (50 mm / s) should be taken and the Bazett-corrected QT interval for heart rate (QTc) determined manually. If the dosage is increased at a later time, an ECG of this type should be taken before the increase and two weeks later. Subsequently, ECG checks should be carried out at least annually. Patients with baseline QTc values greater than 420 ms or a QTc increase greater than 60 ms during treatment with Mantadan or with QTc intervals> 480 ms during treatment with Mantadan, as well as with appreciable U waves should be excluded from treatment.
In groups at risk of electrolyte imbalances (e.g. therapy with diuretics, frequent vomiting and / or diarrhea, use of insulin in emergency situations, kidney disease or states of anorexia) adequate laboratory checks and restoration of related electrolytes, especially potassium and magnesium.
At the first appearance of symptoms such as palpitations, dizziness or syncope, Mantadan should be stopped and the patient examined - within 24 hours - for QT prolongation. If QT prolongation is not present, Mantadan can be reintroduced. , taking into account contraindications and interactions.
In patients with pacemakers, it is not possible to determine exactly the QT intervals. Therefore, the decision on Mantadan therapy must be made on a case-by-case basis, in agreement with the treating cardiologist.
Special precautions for use :
In patients on concomitant treatment with neuroleptics and Mantadan, if Mantadan is stopped abruptly, there is a risk of developing a neuroleptic malignant syndrome, which can be life-threatening for the patient.
In the presence of impaired renal function, intoxication may occur.
In patients with a history of organic brain syndrome and cerebral seizures, the administration of Mantadan requires particular caution, as worsening of individual disease symptoms may occur and seizures may occur (see "Undesirable effects" and "Dose method and time of administration" ).
Patients with known cardiovascular disease should have regular medical checks during concomitant treatment with Mantadan.
At the first appearance of symptoms such as palpitations, dizziness or syncope, amantadine should be discontinued and the patient examined - within 24 hours - for QT prolongation. If QT prolongation is not present, the patient can be reintroduced. "amantadine, taking into account contraindications and interactions (see section" Undesirable effects ").
Disease symptoms such as hypotension, drooling, profuse sweating, hyperthermia, heatstroke, water accumulation and depressive mood disorders are often observed in parkinsonian patients, which must be treated taking into account the side effects and interactions of Mantadan.
Patients should be advised to consult the treating physician if urination disturbances occur.
Important information about some of the excipients
The medicine contains lactose, therefore, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glugose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction -
Concomitant administration of amantadine together with other drugs known to cause prolongation of the QT interval is contraindicated, including, for example:
- some antiarrhythmics of class IA (such as quinidine, disopyramide, procainamide) and class III (such as amiodarone, sotalol)
- some antipsychotics (e.g. thioridazine, chlorpromazine, haloperidol, pimozide)
- some tricyclic and tetracyclic antidepressants (e.g. amitriptyline)
- some antihistamines (e.g. astemizole, terfenadine)
- some macrolide antibiotics (e.g. erythromycin, clarithromycin)
- some DNA gyrase inhibitors (e.g. sparfloxacin)
- azole antifungals and other drugs such as budipine, halofantrine, cotrimoxazole, pentamidine, ziprasidone or bepridil.
This list may not be complete. Before associating amantadine with another drug, its technical data sheet should be checked to see if it is possible an "interaction between that drug and amantadine due to QT prolongation.
Mantadan can be combined with other antiparkinsonian drugs. To avoid undesirable effects (such as psychotic reactions), it may be necessary to reduce the dosage of the other drugs or the combination.
There are no targeted studies on the occurrence of interactions following administration of Mantadan together with other antiparkinsonian or anti-dementia drugs (e.g. levodopa, bromocriptine, memantine, trihexyphenidyl etc.) (see Undesirable effects).
In case of concomitant therapy with Mantadan together with the drug groups or active substances listed below, the interactions described below may occur:
Anticholinergics:
In case of association, for example with trihexyphenidyl, benzatropine, hyoscine, biperidene, orphenadrine etc .: enhancement of the side effects of anticholinergics (confusional states and hallucinations).
Indirect centrally acting sympathomimetics:
Enhancement of the central action of amantadine.
Alcohol:
Reduction of alcohol tolerance.
Levodopa (antiparkinsonian drug):
Enhancement of the therapeutic effect of both drugs. For this reason, levodopa can be combined with Mantadan.
Other antiparkinsonian or anti-dementia medications:
Memantine may increase the effect and side effects of Mantadan (see Contraindications).
Other drugs:
Concomitant administration of diuretics of the combination type triamterene / hydrochlorothiazide may reduce the plasma clearance of amantadine and lead to toxic plasma concentrations. Concomitant administration of these drugs should therefore be avoided.
04.6 Pregnancy and breastfeeding -
Pregnancy
No data are available regarding passage through the placenta. There is insufficient experience with the administration of amantadine to pregnant women. There are some reports of healthy babies, but also of pregnancy complications and five malformations (cardiovascular defects, limb reduction). In animal studies, amantadine was found to be embryotoxic and teratogenic (see section "Preclinical safety data"). The potential risk to humans is unknown. For this reason, amantadine should only be used during pregnancy in cases of extreme necessity. In case of therapy in the 1st trimester, an ultrasound should be done for diagnostic purposes.
If amantadine is prescribed to a patient of childbearing age, she should be urged to contact her physician immediately if she wishes to become pregnant or suspects that she is pregnant.
Feeding time
Amantadine is excreted in breast milk. If administration of the drug during lactation is absolutely necessary, the infant should be observed for possible effects of the drug (rash, urinary retention, vomiting). If necessary, lactation should be discontinued.
04.7 Effects on ability to drive and use machines -
Effects on alertness and visual accommodation - also in combination with other drugs for the treatment of parkinsonian syndromes - cannot be excluded. At the start of treatment, in addition to the limitations due to the disease, a reduction in the ability to drive and drive may therefore occur. to use machinery.
This is even more true in the case of concomitant alcohol consumption.
04.8 Undesirable effects -
Commonly sleep disturbances, motor and psychic restlessness, urinary retention in the presence of prostatic hypertrophy may occur.
In particular in predisposed elderly patients, the drug can cause exogenous psychosis with paranoid connotations, accompanied by optical hallucinations.These side effects may occur more commonly especially if Mantadan is combined with other antiparkinsonian or anti-dementia medicines (eg levodopa, bromocriptine, memantine).
It is observed commonly also the development of livedo reticularis (pattern of "skin marbling"), sometimes associated with edema affecting the legs and ankles.
Occur commonly nausea, dizziness, dry mouth, orthostatic regulation disturbances e rarely blurred vision.
Very rarely, haematological undesirable effects such as leukopenia and thrombocytopenia have been reported during treatment with amantadine.
Very rarely Cardiac arrhythmias such as ventricular tachycardia, ventricular fibrillation, torsades de pointes and QT prolongations have been reported. Most of these cases occurred in the presence of overdoses, certain associated therapies or risk factors for cardiac arrhythmias (see sections "Contraindications" and "Interactions with other medicinal products and other forms of interaction").
Very rarely Temporary loss of vision, increased sensitivity to light and heart rhythm disturbances with tachycardia have been reported. In isolated cases, seizures have also been observed, mostly associated with doses higher than those recommended.
Very rarely myoclonia and symptoms of peripheral neuropathy have been described.
In addition, nausea, vomiting, diarrhea, stomach pain, anorexia and headache have also been reported for the oral form containing amantadine hydrochloride.
04.9 Overdose -
First aid measures, symptoms and antidotes
In principle, one should always think about the possibility of "multiple intoxication, for example in the case of taking multiple drugs with suicidal intent."
a) Symptoms of overdose
The state of acute intoxication is characterized by nausea, vomiting, hyperexcitability, tremor, ataxia, blurred vision, lethargy, depression, dysarthria and cerebral convulsions; in one case a "malignant cardiac arrhythmia was reported.
In case of concomitant administration of amantadine together with other antiparkinsonian drugs, acute toxic psychoses in the form of confusional states with visual hallucinations up to coma, as well as myoclonus, have been observed.
b) Therapeutic measures in case of overdose
There is no specific drug therapy, nor an antidote. In case of intoxication due to ingestion of capsules / tablets, vomiting or gastric lavage should be induced.
In case of intoxications that pose a risk to the patient's life, intensive surveillance measures are also necessary.
From the therapeutic point of view, the administration of liquids, the acidification of the urine to accelerate the excretion of the substance, possibly sedation, the implementation of anticonvulsant measures and the administration of antiarrhythmics (lidocaine i.v.) can also be considered.
For the treatment of neurotoxic symptoms (described above), intravenous administration of physostigmine 1-2 mg every 2 hours in adults can be tried, in children 0.5 mg twice 5-10 minutes apart until a maximum dose of 2 mg.
Due to the limited availability of amantadine for dialysis (approx. 5%), hemodialysis is not advisable.
It is recommended that patients be closely monitored for possible QT prolongation and factors favoring the occurrence of torsade de pointes, eg electrolyte imbalances (particularly hypokalaemia and hypomagnesaemia) or bradycardia.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Antiviral and antiparkinsonian drug
ATC code: N04BB01
Amantadine exhibits multiple pharmacological effects. Amantadine has an indirect agonistic action on the striatal dopaminergic receptor. Animal studies have shown that amantadine increases the extracellular concentration of dopamine, both by increasing the release of dopamine and by inhibiting its reuptake in presynaptic neurons.
At therapeutic concentrations, amantadine inhibits the NMDA receptor-mediated release of acetylcholine and may therefore cause anticholinergic effects. It shows synergistic effects with L-dopa.
05.2 "Pharmacokinetic properties -
Absorption:
Amantadine is rapidly and completely absorbed from the gastrointestinal tract following oral administration.
Distribution:
Maximum plasma concentrations are reached approximately 2 and 8 hours (tmax) after administration of a single dose.
Amantadine hydrochloride, which is readily soluble, achieves a Cmax of 0.5 mcg / ml following oral administration of a single 250 mg dose.
At a dosage of 200 mg / day, the equilibrium state is reached after 4-7 days, with plasma levels between 400 and 900 ng / ml.
Plasma clearance was identical to renal clearance; in healthy elderly volunteers it was 17.7 ± 10 l / h.
The apparent volume of distribution (4.2 ± 1.9 l / kg) is a function of age; in the elderly it is 6.0 l / kg.
Metabolism:
In humans, amantadine is not metabolized.
Elimination:
The elimination half-life (EE) is between 10 and 30 hours, on average it is about 15 hours and is strongly influenced by the age of the patients. Elderly male patients (62-72 years) show an EE of about 30 h. In patients with renal insufficiency, terminal EE is remarkably prolonged and equal to 68 ± 10 hours.
Amantadine binds to plasma proteins about 67% (in vitro), about 33% is found as a free fraction in the plasma. The blood brain barrier is crossed with the help of a saturable transport system.
Amantadine is almost completely excreted in the urine in unchanged form (90% of the single dose), in small amounts in the faeces.
The availability of amantadine hydrochloride for dialysis is scarce and is 5% for a single dialysis.
05.3 Preclinical safety data -
Amantadine has effects on the electrophysiology of the heart, among other things it prolongs the duration of action potentials by inhibiting repolarizing potassium currents. torsades de pointes arrhythmias) also in humans.
In chronic toxicity studies mainly CNS stimulation effects have been observed. Isolated cases of extrasystoles have been observed in dogs and monkeys, in dogs also slight adipose infiltrations into the myocardium.
In a mutagenicity study with established in vitro and in vivo tests, amantadine showed no signs of genotoxic potential.
There are no long-term studies on the carcinogenicity of amantadine.
Embryotoxicity studies conducted in rats, mice and rabbits showed embryolethal effects and malformations at high doses in the rat only. Edema, malposition of the hind legs and skeletal anomalies occurred more frequently. The effects on fertility have been insufficiently studied, there are signs of impaired fertility in the rat. No peri- / postnatal studies have been performed.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
starch; lactose; talc; magnesium stearate.
06.2 Incompatibility "-
Not relevant.
06.3 Period of validity "-
5 years.
06.4 Special precautions for storage -
No particular precautions for storage.
06.5 Nature of the immediate packaging and contents of the package -
PVC / Aluminum blisters.
Box of 20 tablets.
06.6 Instructions for use and handling -
No special instructions.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
BOEHRINGER INGELHEIM ITALIA S.p.A.
Via Lorenzini, 8
20139 Milan
08.0 MARKETING AUTHORIZATION NUMBER -
A.I.C. N ° 022309013
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
July 1971 / 01.06.2010
10.0 DATE OF REVISION OF THE TEXT -
October 2011
