Amantix

Package leaflet: Information for the patient

AMANTIX, 200 mg/500 mL, infusion solution
Amantadini sulfas
Please read all of this leaflet carefully before using this medicine because it contains
important information for you.

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

Contents of this leaflet:

1. What AMANTIX is and what it is 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 AMANTIX is and what it is used for

AMANTIX is a dopaminergic agent, meaning it may increase levels of certain chemical substances that transmit impulses in the nervous system, including in the brain. The medicine reduces the severity of symptoms of Parkinson's disease (an antiparkinsonian agent).

AMANTIX is used:

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

2. Important information before using AMANTIX

Do not use AMANTIX:

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

Warnings and precautions

Talk to your doctor or pharmacist before starting treatment with AMANTIX. Use this medicine with particular caution in patients with:

• Severe renal impairment (creatinine clearance < 10 mL/min);
• Benign prostatic hyperplasia (enlarged prostate);
• Increased intraocular pressure (narrow-angle glaucoma);
• Impaired kidney function of varying severity (risk of drug accumulation due to reduced renal filtration) (see section 3);
• Current or past states of agitation or confusion (disorientation);
• Psychiatric disorders (history of delirium or exogenous psychoses);
• Diarrhea, vomiting, those taking diuretics or insulin acutely in emergency conditions, or those with kidney disease or anorexia (risk of water-electrolyte imbalance);
• Patients concurrently treated with memantine (see section 2 – AMANTIX and other medicines).

Other important information about using AMANTIX

Before starting treatment and again after 1 and 3 weeks of therapy, an ECG should be performed and the QT interval corrected by Bazett’s method (QTc) should be determined. An ECG should also be performed before any dose increase and 2 weeks after each dose increase. Subsequent follow-up ECGs should be performed at least once a year.

Treatment should be avoided or discontinued in patients who have: baseline QTc values greater than 420 ms, an increase of more than 60 ms during infusion therapy, QTc values exceeding 480 ms during infusion therapy, or visible U waves. Observing these warnings and contraindications can prevent the very rare but life-threatening adverse effect of ventricular tachycardia torsade de pointes.

If symptoms such as palpitations, dizziness, or fainting occur, stop administering the medicine and contact your doctor to check heart function (heart rhythm) via 24-hour monitoring. If the doctor finds no cardiac disturbances, treatment may be continued, taking into account contraindications and possible interactions (see section 4).

In patients with cardiac pacemakers, accurate determination of the QT interval duration is not possible; therefore, the decision on using the medicine should be made individually for each patient after consultation with a cardiologist.

In patients with impaired kidney function, accumulation of the drug may occur due to reduced renal excretion. This may lead to symptoms associated with drug overdose. The doctor should carefully adjust the dose and monitor glomerular filtration rate (see section 3).

Particular caution is advised when administering AMANTIX to patients with organic brain syndrome or seizure predisposition, as symptoms may worsen and seizures may occur (see section 3 and section 4).

Patients currently experiencing seizures, those with cardiovascular diseases, or those with a history of seizures must remain under continuous medical supervision during treatment.

In patients with Parkinson's disease, treatment with AMANTIX should not be abruptly discontinued, as this may lead to severe movement disorders, sometimes including complete immobility.

Patients with Parkinson's disease treated concomitantly with neuroleptics (medicines used to treat psychiatric disorders) and AMANTIX are at risk of developing a life-threatening condition known as neuroleptic malignant syndrome if treatment is suddenly stopped. This syndrome is characterized by sudden high fever, muscle rigidity, and autonomic nervous system disturbances.

In patients with Parkinson's disease, clinical symptoms such as low blood pressure, drooling, sweating, elevated body temperature, fluid retention, and depression are commonly observed. When using AMANTIX in this group, its side effects and interactions should be particularly considered.

Patients experiencing difficulty urinating should contact their doctor.

If blurred vision or other visual disturbances occur, contact an ophthalmologist immediately.

Suicidal thoughts and behaviors have been reported during amantadine treatment. If you experience thoughts of self-harm or suicide or attempt such actions, contact your doctor immediately.

Inform your doctor if you or your family members or caregivers notice that you develop urges or irresistible desires to behave in ways that are unusual for you and that you cannot resist, or if you experience urges or cravings to act in ways that could be harmful to you or others. These are known as impulse control disorders and may include behaviors such as compulsive gambling, excessive eating or spending, abnormally increased sexual drive, or intensified sexual thoughts or feelings. Your doctor may adjust the dose or discontinue the medicine.

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

Elderly patients
Dosage should be carefully selected in elderly patients, especially if agitation, confusion, or delirium is present (see section 3).

AMANTIX and other medicines

Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take.

AMANTIX must not be used concomitantly with other medicines that prolong the QT interval, such as:

• Certain medicines used to treat irregular heart rhythms (Class IA antiarrhythmics, e.g., quinidine, disopyramide, procainamide, and Class III antiarrhythmics, e.g., amiodarone, sotalol);
• Certain medicines used to treat psychiatric disorders (antipsychotics, 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 antifungals);
• Other medicines such as budipine, halofantrine, cotrimoxazole, pentamidine, cisapride, or bepridil.

The above list may not be complete. Before using AMANTIX with another medicine, your doctor should check for possible interactions due to QT interval prolongation.

Concomitant treatment with AMANTIX and other medicines used for Parkinson's disease is possible. To avoid adverse effects (e.g., psychotic reactions), it may be necessary to reduce the dose of AMANTIX or both medicines.

Amantadine should not be used for prophylaxis or treatment of influenza A virus infection due to the risk of overdose.

There are no specific studies on interactions when AMANTIX is administered intravenously in combination with other antiparkinsonian medicines (e.g., levodopa, bromocriptine, trihexyphenidyl, etc.) or with memantine (see section 4).

Concomitant use of AMANTIX and any of the following medicines or active substances may lead to the following interactions:

Anticholinergic medicines
Increased anticholinergic side effects (confusion, hallucinations) when used with anticholinergics (e.g., trihexyphenidyl, benztropine, scopolamine, biperiden, orphenadrine).

Indirectly acting sympathomimetics affecting the central nervous system
Enhanced central effects of amantadine.

Levodopa (a medicine used in Parkinson's disease)
Mutual enhancement of therapeutic effect (therefore, levodopa may be administered concomitantly with AMANTIX).

Memantine (a medicine used in dementia)
Memantine may enhance the effects and side effects of AMANTIX (see section 2 – Warnings and precautions).

Other medicines
Concomitant use of diuretics containing triamterene combined with hydrochlorothiazide may reduce amantadine plasma clearance, leading to toxic serum concentrations. Therefore, concomitant use of amantadine and such medicines should be avoided.

Note that the interactions listed above may also apply to medicines used recently.

AMANTIX with food, drink, and alcohol
Avoid consuming alcoholic beverages during treatment with AMANTIX, as this medicine reduces alcohol tolerance.

Pregnancy and breastfeeding

If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before using this medicine.

Pregnancy
There is insufficient experience with the use of AMANTIX during pregnancy. Reports exist of both healthy births and pregnancy complications, as well as fetal developmental disorders. Animal studies have shown that amantadine, the active substance of AMANTIX, may cause fetal damage. The potential risk in humans is unknown.

Amantadine may be used during pregnancy only if absolutely necessary. During 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 infant should be monitored for symptoms related to the medicine (skin rash, urinary retention, vomiting), and breastfeeding should be discontinued if necessary.

Driving and operating machinery

The effect of AMANTIX on concentration, wakefulness, and eye accommodation (the eye's ability to adjust for viewing at different distances) cannot be ruled out, especially when combined with other medicines used in Parkinson's disease treatment.

At the beginning of treatment, the ability to drive and operate machinery may be further impaired beyond the impairment caused by the disease itself.

You may not be able to react quickly and decisively in unexpected or sudden situations.

Do not drive or operate machinery or electrical devices without consulting your doctor.

Remember that alcohol may worsen the impairment of driving ability.

AMANTIX contains sodium
This medicine contains 1770 mg of sodium (the main component of table salt) in each 500 mL bottle. This corresponds to 88.5% of the maximum recommended daily dietary sodium intake for adults. Patients, especially those monitoring their dietary sodium intake, should consult their doctor, nurse, or pharmacist if long-term treatment is required.

3. How to use the medicine AMANTIX

This medicine should always be used as directed by the physician. In case of doubt, consult a doctor or pharmacist.
Duration of treatment
The duration of treatment will be determined by the physician. It will depend on the indication for use and the individual patient's response to treatment.
Route of administration
Intravenous.
Dosage
Parkinson's disease
For severe symptoms of Parkinson's disease and during akinetic crisis, 200 mg of amantadine sulfate in 500 mL of solution should be administered 1–3 times daily by intravenous infusion.
The infusion rate should not exceed 55 drops/min., which corresponds to an infusion time of approximately 3 hours.
In elderly patients, particularly those experiencing agitation, confusion, or delirium symptoms, treatment should be initiated with a lower dose.
If the patient is concurrently using other anti-Parkinson drugs, the physician should determine the dose individually.
Disorders of consciousness
For the treatment of disorders of consciousness and arousal states of various etiologies, an initial dose of 200 mg per day administered by slow intravenous infusion (> 3 hours) is recommended for 3–5 days. Depending on the clinical condition, treatment may be continued (preferably orally if possible) for up to 4 weeks at a dose of 200 mg of amantadine sulfate per day. If necessary, the daily dose may be increased up to 600 mg.
Dosage in patients with impaired renal function
In patients with impaired renal function, dosage should be adjusted according to renal clearance (determined by 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 according to this formula applies only to males (corresponding values in females are approximately 85% of these values) and may be equivalent to inulin clearance for determining GFR (120 mL/min in adults).
Amantadine is only minimally removed during dialysis (about 5%).
Use in children and adolescents
There is insufficient experience with the use of the drug in children and adolescents.
Administration of a higher than recommended dose of AMANTIX
Following administration of a dose higher than recommended or overdose due to too rapid infusion, standard measures for life-threatening overdose should be initiated.
Acute intoxication and overdose are characterized by nausea, vomiting, hyperexcitability, tremors, unsteady gait, blurred vision, drowsiness, depression, speech disturbances, and cerebral seizures. Malignant cardiac arrhythmia has been reported in one case.
When amantadine was administered concomitantly with other drugs used in Parkinson's disease, psychoses with visual hallucinations were observed, sometimes including coma and myoclonus.
Because amantadine is only minimally eliminated during dialysis (approx. 5%), hemodialysis is not recommended.
In cases of life-threatening poisoning, intensive therapy is required. Therapeutic management should include: administration of fluids and acidification of urine to enhance elimination of the toxic substance, sedation if possible, administration of anticonvulsant and antiarrhythmic drugs (intravenous lidocaine).
There is no known specific drug or antidote.
In the treatment of neurotoxic symptoms (such as those described above), an attempt may be made to administer physostigmine intravenously at 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 physician may recommend performing an ECG if deemed necessary and monitoring patients for QT interval prolongation and factors predisposing to cardiac rhythm disturbances, e.g. electrolyte imbalances (particularly decreased blood potassium or magnesium levels) or impaired cardiac function.
Discontinuation of AMANTIX treatment
Under no circumstances should treatment be discontinued without consulting a physician.
If the patient wishes to discontinue treatment, e.g. due to drug intolerance or worsening of disease symptoms, they should inform the physician. Treatment should not be abruptly discontinued, as this may lead to worsening of disease symptoms and withdrawal symptoms.
In case of any further doubts regarding the use of this medicinal product, consult a physician or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine may cause adverse reactions, although not everyone experiences them.
Possible adverse reactions:
If any of the adverse reactions listed below occur in a patient, a doctor should be informed immediately, who will decide on further management.
Common (affects less than 1 in 10 people):

• sleep disturbances
• mental and motor restlessness
• urinary retention in patients with benign prostatic hyperplasia (enlarged prostate)
• livedo reticularis (mottled red-blue skin discoloration forming a net-like pattern), sometimes accompanied by swelling of the lower legs and ankles
• nausea
• dizziness
• dry mouth
• sudden drop in arterial blood pressure when rising quickly from a lying or sitting position. This may cause dizziness or a feeling of fainting (orthostatic hypotension)
• exogenous paranoid psychoses (behavioral disturbances and altered perception of stimuli) accompanied by visual hallucinations, especially in predisposed elderly patients.

These types of adverse reactions may occur more frequently when the medicine is administered concomitantly with other drugs 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 1,000 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 rapid drop in blood pressure, increased heart rate, breathing and swallowing difficulties, vomiting, abdominal pain, diarrhea, rash, itching, and swelling, occurring during intravenous administration of the medicine.
• leukopenia (reduced white blood cell count) and thrombocytopenia (reduced platelet count). These adverse reactions occur less frequently during intravenous administration of the medicine.
• cardiac arrhythmias, such as ventricular tachycardia, torsade de pointes, ventricular fibrillation, and QT interval prolongation. These disturbances occur most frequently after exceeding the recommended doses, or when amantadine is used concomitantly with other drugs with proarrhythmic effects, or in the presence of other risk factors for cardiac arrhythmias (see section 2. – "When not to use the medicine" and "Medicines and other medicines").
• transient loss of vision
• increased sensitivity to light
• seizures (usually after exceeding the recommended dose)
• muscle cramps
• sensory disturbances in the limbs

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

• corneal edema (resolves after discontinuation of treatment)
• irresistible urge to behave in an unusual manner – strong compulsion to gamble excessively, disturbed or increased sexual drive, uncontrolled excessive spending or shopping, binge eating (consuming large amounts of food in a short time), or compulsive overeating (consuming more food than usual and more than needed to satisfy hunger)

If visual disturbances occur, such as loss of visual acuity or blurred vision, a doctor should be consulted to rule out corneal edema (see section 2).
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions may also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store AMANTIX medicine

Keep the medicine out of the sight and reach of children.
Do not use the medicine after the expiry date stated on the label and packaging.
There are no special requirements for storage conditions of this medicine.
Medicines must 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 package and other information

What AMANTIX contains
The active substance is amantadine sulfate.
One 500 mL bottle of infusion solution 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
AMANTIX is a clear, sediment-free infusion solution.
The medicine is available in cardboard packaging containing:

• 2 bottles of 500 mL
• 10 bottles of 500 mL
  Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Merz Pharmaceuticals GmbH
Eckenheimer Landstrasse 100
60318 Frankfurt/Main
Germany
Tel: +49 69 1503 0
e-mail: [email protected]

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