Amantix

Leaflet attached to the packaging: patient information

AMANTIX, 200 mg/500 mL, solution for infusion

Amantadine sulfate

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is AMANTIX and what is it used for
• 2. Important information before using AMANTIX
• 3. How to use AMANTIX
• 4. Possible side effects
• 5. How to store AMANTIX
• 6. Contents of the pack and other information

1. What is AMANTIX and what is it used for

The medicine is a dopaminergic agent, which means it can increase the level of certain chemical compounds that transmit impulses in the nervous system, including the brain.
The medicine reduces the severity of Parkinson's disease symptoms (anti-Parkinsonian medicine).
The medicine is used:

• for initial and intensive treatment of severe and life-threatening Parkinson's disease symptoms, including sudden, complete immobility (akinetic crisis) caused by acute worsening of Parkinson's disease;
• for disorders of consciousness and wakefulness caused by various factors (as part of complex therapy in hospital settings).

2. Important information before using AMANTIX

When not to use AMANTIX:

• if the patient is allergic to amantadine or any of the other ingredients of this medicine (listed in section 6);
• if the patient has severe uncontrolled heart failure (NYHA grade IV);
• if the patient has heart diseases such as cardiomyopathy or myocarditis;
• if the patient has conduction disorders in the heart (second or third degree atrioventricular block);
• if the patient has a heart rate of less than 55 beats per minute;
• if the patient has changes in the electrocardiogram (ECG) such as prolonged QT interval or visible U waves or has a family history of congenital long QT syndrome;
• if the patient has severe heart rhythm disorders (ventricular arrhythmias, including torsades de pointes);
• if the patient has low potassium or magnesium levels in the blood;
• if the patient is taking medicines that prolong the QT interval (see section 2 - Interactions with other medicines).

Warnings and precautions

Before starting treatment, discuss it with your doctor or pharmacist.
Particular caution should be exercised when using the medicine in patients with:

• severe kidney impairment (creatinine clearance <10 ml min);< li>
• prostate enlargement (prostate hypertrophy);
• increased intraocular pressure (narrow-angle glaucoma);
• renal impairment of varying severity (risk of accumulation of the medicine due to impaired renal excretion) (see section 3);
• states of excitement or confusion (disorientation) currently or in the past;
• psychiatric disorders (delirium or exogenous psychoses in the past);
• diarrhea, vomiting, taking diuretics or insulin in emergency situations, with kidney disease or anorexia (risk of water and electrolyte imbalance);
• being treated with memantine (see section 2 - Interactions with other medicines).

Other important information about using AMANTIX

Before starting treatment and after 1 and 3 weeks of treatment, an ECG and the corrected QT interval (QTc) using the Bazett method should be performed. The ECG should also be performed before increasing the dose and 2 weeks after each dose increase. Further control ECGs should be performed at least once a year.
Treatment should be avoided or discontinued in patients who have: initial QTc values greater than 420 ms, an increase of more than 60 ms during treatment with the medicine or a QTc interval greater than 480 ms during treatment with the medicine and in patients with visible U waves. By following the above warnings and contraindications, a very rare but life-threatening side effect in the form of ventricular tachycardia (torsades de pointes) can be prevented.
If symptoms such as palpitations, dizziness, or fainting occur, the administration of the medicine should be discontinued and a doctor should be consulted to check the heart function (heart rhythm) through 24-hour monitoring. If the doctor does not find any heart function disorders, the administration of the medicine can be continued, taking into account contraindications and possible interactions (see section 4).
In patients with pacemakers, it is not possible to accurately determine the QT interval, so the decision to use the medicine should be made individually for each patient after consulting a cardiologist.
In patients with impaired renal function, accumulation of the medicine may occur due to impaired excretion by the kidneys. This can lead to the occurrence of symptoms related to overdose of the medicine. The doctor should carefully adjust the dose, measure, and monitor the glomerular filtration rate (see section 3).
Particular caution is recommended when the medicine is administered to patients with organic brain syndrome or a tendency to seizures, as the symptoms may worsen and seizures may occur (see sections 3 and 4).
Patients with current or a history of seizures and cardiovascular diseases, as well as patients who have had seizures in the past, must remain under constant medical supervision during treatment with the medicine.
In patients with Parkinson's disease, the medicine should not be suddenly discontinued, as this may lead to severe movement disorders, sometimes including inability to move.
Patients with Parkinson's disease treated with neuroleptic medicines (medicines used to treat psychiatric disorders) and the medicine are - in the event of sudden discontinuation of the medicine - at risk of developing a life-threatening condition - so-called malignant neuroleptic syndrome. This syndrome is accompanied by: sudden increase in temperature, muscle stiffness, and disorders of the autonomic nervous system.
In patients with Parkinson's disease, clinical symptoms such as decreased blood pressure, salivation, sweating, increased body temperature, fluid retention, and depression are often observed. When using the medicine in this group of patients, its side effects and interactions should be taken into account.
Patients who experience problems with urination should contact their doctor.
If a patient experiences blurred vision or other vision disturbances, they should immediately contact an ophthalmologist.
During treatment with amantadine, cases of suicidal thoughts and behaviors have been reported. If a patient has thoughts of self-harm or suicide or attempts to do so, they should immediately contact their doctor.
The doctor should be informed if the patient or their family members and/or caregivers notice that the patient has a desire or irresistible urge to behave in a way that is atypical for them and the patient is unable to resist these impulses, or a desire or temptation to behave in a way that could be harmful to the patient or others. These are so-called impulse control disorders, which may include behaviors such as compulsive gambling, overeating, or spending money, inappropriate or increased sexual urge or thoughts, or increased sexual feelings.
The doctor may modify the dose or discontinue the medicine.

Children and adolescents

There is no data on the use of the medicine in children and adolescents.

Elderly

In elderly patients, the dose should be chosen carefully, especially in the presence of excitement, confusion, or delirium (see section 3).

AMANTIX and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or plan to take.
The medicine must not be used with other medicines that prolong the QT interval, such as:

• certain medicines used to treat irregular heart rhythm (antiarrhythmic medicines of class IA, e.g., quinidine, disopyramide, procainamide, and class III, e.g., amiodarone, sotalol);
• certain medicines used to treat psychiatric disorders (antipsychotic medicines, e.g., thioridazine, chlorpromazine, haloperidol, pimozide);
• certain medicines used to treat depression (tricyclic and tetracyclic antidepressants, e.g., amitriptyline);
• certain medicines used to treat allergies, e.g., hay fever (antihistamines, e.g., astemizole, terfenadine);
• certain medicines used to treat bacterial infections (macrolide antibiotics, e.g., erythromycin, clarithromycin, and gyrase inhibitors, e.g., sparfloxacin);
• certain medicines used to treat fungal infections (azole antifungal medicines);
• other medicines, such as budipine, halofantrine, cotrimoxazole, pentamidine, cisapride, or bepridil.

The above list may not be exhaustive. Before using the medicine with another medicine, the doctor should check for the possibility of interactions caused by prolongation of the QT interval.
Concomitant treatment with the medicine and other medicines used in Parkinson's disease is possible. To eliminate side effects (e.g., psychotic reactions), it may be necessary to reduce the dose of the administered medicine or both medicines.
Amantadine should be avoided in the prophylaxis and treatment of influenza A virus infection due to the risk of overdose.
There are no specific studies on the occurrence of interactions after intravenous administration of the medicine in combination with other anti-Parkinsonian medicines (e.g., levodopa, bromocriptine, trihexyphenidyl, etc.) or with memantine (see section 4).
Concomitant use of the medicine and each of the types of medicines or active substances listed below may lead to the following interactions:

• Anticholinergic medicines
  Enhancement of side effects (confusion and hallucinations) of anticholinergic medicines (e.g., trihexyphenidyl, benzatropine, scopolamine, biperiden, orphenadrine).
• Sympathomimetics with indirect action on the central nervous system
  Enhancement of the central action of amantadine.
• Levodopa (medicine used in Parkinson's disease)
  Mutual enhancement of therapeutic effects (so levodopa can be administered concomitantly with the medicine).
• Memantine (medicine used in dementia)
  Memantine may enhance the effects and side effects of the medicine (see section 2 - Warnings and precautions).
• Other medicines
  Concomitant use of diuretics containing triamterene in combination with hydrochlorothiazide may reduce the plasma clearance of amantadine, leading to toxic concentrations in the serum. Therefore, concomitant use of amantadine and such medicines should be avoided.

The above interactions may also apply to medicines used in the recent past.

AMANTIX with food, drinks, and alcohol

Alcoholic beverages should be avoided during treatment with the medicine, as it reduces alcohol tolerance.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before using this medicine.
Pregnancy
There is insufficient experience with the use of the medicine during pregnancy. There are reports of healthy births, as well as complications during pregnancy and fetal development disorders. Animal studies have shown that amantadine, the active substance of the medicine, may cause fetal damage. The potential risk to humans is not known.
Amantadine during pregnancy may be used only when absolutely necessary.
During treatment with amantadine in the first trimester (first three months of pregnancy), ultrasound examinations should be performed.
Breastfeeding
Amantadine passes into breast milk. If its use is absolutely necessary during breastfeeding, the baby should be monitored for symptoms that may occur in connection with the use of the medicine (skin rash, urinary retention, vomiting), and breastfeeding should be discontinued if necessary.

Driving and using machines

The medicine may affect concentration and alertness, as well as eye accommodation (adaptation to seeing at different distances), especially in combination with the action of other medicines used in Parkinson's disease.
At the beginning of treatment, there may be a further worsening of the ability to drive vehicles and operate machines, greater than the impairment caused by the disease itself.
The patient may not be able to react quickly and decisively in unexpected and sudden situations.
Vehicles and machines should not be driven or operated without consulting a doctor.
It should be remembered that alcohol can enhance the worsening of the ability to drive vehicles.

AMANTIX contains sodium

The medicine contains 1770 mg of sodium (the main component of common salt) in each 500 mL vial. This corresponds to 88.5% of the maximum recommended daily intake of sodium in the diet for adults.
If the medicine is taken for a long time, patients, especially those controlling sodium intake in their diet, should consult a doctor, nurse, or pharmacist.

3. How to use AMANTIX

This medicine should always be used as directed by your doctor. If you are unsure, consult your doctor or pharmacist.

Duration of treatment

The duration of treatment will be determined by your doctor. It will depend on the indication for use of the medicine and the individual patient's response to treatment.

Route of administration

Intravenous.

Dosage

Parkinson's disease
For the severity of Parkinson's disease symptoms and in akinetic crisis, 200 mg of amantadine sulfate in 500 mL of solution should be administered 1-3 times a day by intravenous drip infusion.
The infusion rate should not exceed 55 drops/min, which corresponds to an infusion time of approximately 3 hours.
In elderly patients, especially those with excitement, confusion, or delirium, treatment should be started with a lower dose.
If the patient is also taking other anti-Parkinsonian medicines, the doctor should determine the dose of the medicine individually.
Disorders of consciousness
In the treatment of disorders of consciousness and wakefulness of various etiologies, an initial dose of 200 mg per day is used in a slow drip infusion (> 3 hours) for 3-5 days. Depending on the clinical condition, treatment may be continued (if possible in oral form) for up to 4 weeks at a dose of 200 mg of amantadine sulfate per day. If necessary, the daily dose can be increased to 600 mg.

Dosage in patients with impaired renal function

In patients with impaired renal function, the dosage should be adjusted according to the glomerular filtration rate (GFR), as shown in the table below:

The glomerular filtration rate (GFR) can be estimated using the following formula:
(140 - age) × body weight
Clcr = -------------------------------
72 × creatinine
where:
Clcr = creatinine clearance in mL/min
Creatinine = serum creatinine concentration in mg/100 mL
The creatinine clearance calculated using this formula applies only to men (the corresponding values in women are approximately 85% of these values) and may be equivalent to inulin clearance for determining GFR (120 mL/min in adults).
Amantadine is eliminated only to a small extent during dialysis (about 5%).

Use in children and adolescents

There is insufficient experience with the use of the medicine in children and adolescents.

Use of a higher than recommended dose of AMANTIX

In the event of administration of a dose higher than recommended or overdose due to too high an infusion rate, standard measures should be taken, as in cases of life-threatening overdose.
Acute poisoning and overdose are characterized by nausea, vomiting, agitation, tremors, unsteady gait, blurred vision, drowsiness, depression, speech disorders, and seizures. In one case, malignant cardiac arrhythmia was reported.
After concomitant administration of amantadine and other medicines used in Parkinson's disease, psychoses have been observed in the form of confusion with visual hallucinations, sometimes including coma and myoclonus.
Due to the fact that amantadine is eliminated to a small extent during dialysis (about 5%), hemodialysis is not recommended.
In the event of life-threatening poisoning, intensive therapy is necessary. The therapeutic approach should include: administration of fluids and acidification of urine to accelerate the elimination of the toxic substance, if possible sedation, administration of anticonvulsant and antiarrhythmic medicines (lidocaine intravenously).
There is no specific antidote or medicine known.
In the treatment of neurotoxicity symptoms (such as those described above), an attempt can be made to administer physostigmine intravenously in a dose of 1-2 mg every 2 hours in adults and 2 × 0.5 mg with a 5-10 minute interval, up to a maximum dose of 2 mg in children.
The doctor may recommend an ECG if they consider it necessary and monitor patients for QT interval prolongation and factors that predispose to cardiac arrhythmias, such as electrolyte disorders (especially decreased potassium or magnesium levels in the blood).

Discontinuation of AMANTIX

Under no circumstances should treatment be discontinued without consulting a doctor.
If a patient wants to discontinue treatment, e.g., due to intolerance to the medicine or worsening of disease symptoms, they should inform their doctor. Treatment should not be discontinued abruptly, as this may cause worsening of disease symptoms and withdrawal symptoms.
In case of any further doubts related to the use of this medicine, consult a doctor or pharmacist.

4. Possible side effects

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

Possible side effects:

If you experience any of the following side effects, tell your doctor, who will decide on further action.
Frequent (affects less than 1 in 10 people):

• sleep disorders
• psychic and motor restlessness
• urinary retention in patients with prostate enlargement (prostate hypertrophy)
• mottled discoloration of the skin (livedo reticularis), sometimes with swelling of the legs and ankles
• nausea
• dizziness
• dry mouth
• sudden drop in blood pressure when standing up from a lying or sitting position, which can cause dizziness or fainting (orthostatic hypotension)
• exogenous paranoid psychoses (behavioral and perceptual disorders) with visual hallucinations, especially in predisposed elderly patients.

Side effects of this type may occur more frequently during concomitant administration of the medicine with other medicines used in Parkinson's disease (e.g., levodopa, bromocriptine) or with memantine.
Uncommon (affects less than 1 in 100 people):
blurred vision
Rare (affects less than 1 in 1000 people):

• corneal damage, corneal edema, decreased visual acuity

Very rare (affects less than 1 in 10,000 people):

• sudden, generalized allergic reaction, with symptoms such as severe hypotension, tachycardia, difficulty breathing and swallowing, vomiting, abdominal pain, diarrhea, rash, itching, and swelling, occurring during intravenous administration of the medicine.
• leukopenia (decreased white blood cell count) and thrombocytopenia (decreased platelet count). These side effects occur less frequently during intravenous administration of the medicine.
• heart rhythm disorders, such as ventricular tachycardia, torsades de pointes, ventricular flutter, and QT interval prolongation. These disorders occur most frequently after exceeding the recommended doses or when amantadine is used in combination with other medicines with proarrhythmic effects or in the presence of other risk factors for heart rhythm disorders (see section 2 - "When not to use AMANTIX" and "Interactions with other medicines").
• transient loss of vision
• increased sensitivity to light
• seizures (usually after exceeding the recommended dose)
• muscle spasms
• disturbances of sensation in the limbs

Frequency not known (cannot be estimated from the available data):

• corneal edema (reversible after discontinuation of treatment)
• irresistible urge to behave in an atypical way - strong desire to gamble excessively, disturbed or increased sexual urge or thoughts, uncontrolled or increased eating or spending money, compulsive eating (eating more food than usual and more than needed to satisfy hunger)

In case of vision disturbances, such as blurred vision, contact a doctor to rule out corneal edema (see section 2).

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of the medicine.

5. How to store AMANTIX

Keep this medicine out of the sight and reach of children.
Do not use the medicine after the expiry date stated on the label and carton.
There are no special precautions for storage of the medicine.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What AMANTIX contains

The active substance of the medicine is amantadine sulfate.
One 500 mL vial of solution for infusion contains 200 mg of amantadine sulfate.
The other ingredients are sodium chloride and water for injections.

What AMANTIX looks like and contents of the pack

The medicine is a clear, particle-free solution for infusion.
The medicine is available in a cardboard box:
2 vials of 500 mL
10 vials of 500 mL
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Merz Pharmaceuticals GmbH
Eckenheimer Landstrasse 100
60318 Frankfurt/Main
Germany
Tel: +49 69 1503 0
e-mail: contact@merz.de

Manufacturer:

Merz Pharma GmbH & Co.KGaA
Eckenheimer Landstrasse 100
60318 Frankfurt/Main
Germany

Date of last revision of the leaflet: