Amantin

General characteristics. Structure:

Active agent: amantadina of sulfate of 100 mg;

Excipients: lactoses monohydrate, cellulose microcrystallic, potato starch, gelatin, povidone, sodium of a kroskarmeloz, talc, silicon dioxide colloid anhydrous, magnesium stearate, Opadry II White (polyethyleneglycol, polyvinyl alcohol, talc, titanium dioxide (Е 171)).

Pharmacological properties:

Pharmacodynamics. Protivoparkinsonichesky, antiviral means. Tricyclic symmetric адамантамин. Blocks glutamate NMDA receptors, reducing the excessive stimulating influence of cortical glutamate neurons on a neostriatum, developing against the background of insufficient release of dopamine and reducing thereby display of parkinsonism. Substantially influences constraint (rigidity and a bradykinesia). Eliminates extrapyramidal side effects of neuroleptics and other medicines: early dyskinesia, akathisia and parkinsonism. Besides, амантадин has also some anticholinergic activity.
Antiviral action is connected with ability of an amantadin to block penetration of an influenza virus of type A into cells.
The mechanism of action of Amantin in treatment of herpes zoster is completely not defined.

Pharmacokinetics. After intake амантадин it is well soaked up in a digestive tract. The maximum concentration in a blood plasma is reached approximately in 4 hours after reception of a single dose (100 mg) of drug and makes 0,15 mkg/ml. At administration of drug in a dose of 200 mg/day the condition of equilibrium concentration is reached in 4-7 days. The conditional volume of distribution makes 4,2±1,9 l/kg and depends on age; elderly people have 6 l/kg.

The elimination half-life makes 10-30 hours (on average 15 hours) and substantially depends on age of the patient. At male elderly patients (62-72 years) the elimination half-life makes 30 hours. At patients with a renal failure the final elimination half-life from plasma can be considerably extended (till 68±10 o'clock).

Amantadin contacts proteins of plasma approximately for 67% (in vitro); about 33% come to light in plasma in an untied form. Gets through a blood-brain barrier, a placental barrier, into breast milk. It is removed with urine practically in not changed look (90% of a single dose), the insignificant quantity is removed with a stake.
Ability to dialysis at an amantadin low, about 5% for one dialysis.

Indications to use:

- Parkinson's disease, parkinsonism of various etiology;
- neuralgia at shingles (Herpes zoster);
- prevention and treatment of flu A.

Route of administration and doses:

Pill needs to be taken inside, after food, with a small amount of liquid, it is desirable in the morning and/or in the afternoon. Due to the possible activating influence on the central nervous system (CNS) it is recommended to accept the last dose of drug no later than 16 hours.

Parkinson's disease. Dosing mode individual. The recommended initial dose for adults - 100 mg (1 tablet) of Amantin once a day for the first seven days with the subsequent increase in a dose of 100 mg 2 times a day. The dose should be increased gradually at an interval of a week before achievement effective therapeutic which should be accepted in 2 receptions. The doses exceeding 200 mg a day can provide additional therapeutic effect, but also can increase toxicity. The daily dose - 400 mg is maximum.
It is recommended to patients of advanced age (65 years are more senior) to appoint minimal effective doses in connection with a tendency to decrease in renal clearance and the subsequent increase in level of an amantadin in a blood plasma.
In certain cases continuous treatment amantadiny for several months efficiency can decrease. Efficiency can be increased by the termination of reception of an amantadin for 3-4 weeks. During this span it is necessary to continue the accompanying protivoparkinsonichesky therapy or to begin treatment with a low dose of a levodopa in case of clinical need.

Usually Amantin appoint in a combination with other protivoparkinsonichesky means. In that case Amantin's dose is selected individually.

Treatment by Amantin should be stopped gradually, for example, on ½ doses with week intervals. The sharp termination of treatment can worsen the course of parkinsonism, up to developing of akinetic crisis. In case of strengthening of side effects Amantin's dose should be reduced quicker. At the patients receiving high doses of anticholinergics or a levodopa the initiation of treatment Amantin should be postponed for 15 days.

For treatment of flu A by the adult appoint on 100 mg every the 12th hour, to patients 65 years - no more than 100 mg a day are more senior.

For treatment drug is used not later than in 18-24 hours after emergence of the first symptoms of flu, treatment duration - 5 days.

Amantin apply 100 mg a day within 2 - 4 weeks to prevention of flu A.

For treatment of neuralgia at shingles (Herpes zoster) appoint 100 mg twice a day within 14 days. Therapy should be begun as soon as possible after establishment of the diagnosis. In case of persistent post-herpetic pain treatment can be continued during the next 14 days.

Dosing for patients with a renal failure.

At patients with a renal failure the dose of an amantadin has to be reduced by decrease in the general daily dose or by increase in an interval between administrations of drug, depending on clearance of creatinine, as shown in the table:

Clearance of creatinine, ml/min.	Drug dosing, mg
<15	Amantin is contraindicated
15-35	100 mg every second or third day
> 35	100 mg daily

The general recommendations therefore the doctor has to continue to control a condition of patients concerning signs of undesirable effects are presented in the table.

Features of use:

It is necessary to adhere to extra care at use of drug for patients with:

- psychoses;
- agitation or confusion of consciousness;
- abnormal liver function and kidneys;
- heart failure;
- thyrotoxicosis;
- prostate hyperplasia;
- recurrent eczema;
- at simultaneous use with the medicines influencing TsNS (see the section "Interaction with Other Medicines and Other Types of Interactions").

Drug should be used with care to patients with cardiovascular diseases, including disturbances of a rhythm and conductivity, disturbances of electrolytic balance.

Treatment by Amantin cannot be stopped suddenly as it can lead to deterioration in a disease of Parkinson, emergence of the symptoms inherent in a malignant antipsychotic syndrome, and also development of cognitive disturbances, such as: catatonia, confusion of consciousness, disorientation, deterioration in a mental state, nonsense. It is not necessary to stop sharply Amantin's reception to the patients who are at the same time accepting neuroleptics in connection with possible risk of development of a malignant antipsychotic syndrome or the catatonia induced by a neuroleptic.

Reported about suicide attempts and suicide thoughts at patients at use of an amantadin. For the purpose of the prevention of emergence of suicide thoughts and intentions it is necessary to appoint drug in minimal effective doses.

Some patients at prolonged use of drug can have peripheral hypostases. It should be taken into account to persons with chronic heart failure.

Not to use drug at patients with closed-angle glaucoma.

Drug contains lactose therefore to patients with rare hereditary forms of intolerance of a galactose, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption it is impossible to apply Amantin.

Ability to influence speed of response at control of motor transport or work with other mechanisms.
Drug can reduce concentration of attention and speed of reaction, to cause dizziness, decrease in visual acuity therefore patients should be warned about potential danger during the driving or work with other mechanisms.

Side effects:

Side reactions on амантадин are more often than easy degree and have passing character. As a rule, appear within 2-4 days from an initiation of treatment and quickly pass after the termination of administration of drug.
From blood and lymphatic system: leukopenia.
From a nervous system: uneasiness, dizziness, headache, drowsiness, sleeplessness, weakness, excitement, fever, ataxy, muffled speech, deterioration in concentration of attention, irritability, depression, mialgiya, paresthesia, confusion of consciousness, disorientation, psychosis, tremor, spasms, dyskinesia, stupor, suicide thoughts and intentions, malignant antipsychotic syndrome, delirium, condition of a hypomania and mania, hallucination, nightmares. The paranoid exogenous psychoses which are followed by visual hallucinations are more often observed at combined use with anticholinergic drugs, and at the patients inclined to mental disorders.
From organs of sight: defeat of a cornea (pointed subepithelial opacification which can be connected with a superficial dot keratitis), cornea epithelium hypostasis, decrease in visual acuity, okulogorny crises, a mydriasis.
From cardiovascular system: orthostatic hypotension, cardiac arrhythmia, tachycardia, lengthening of an interval of QT, peripheral hypostases, heart failure, the "marble skin" (emergence of a mesh-bluish shade of skin) which is associated sometimes with hypostasis of an ankle joint. Can arise after reception of high doses of drug or use during the long period.
From a digestive tract: nausea, feeling of dryness in a mouth, anorexia, vomiting, a lock, a diarrhea, reversible increase in activity of liver enzymes.
From skin and hypodermic cellulose: skin rashes, feeling of an itch, the increased sweating, photosensitivity, eczematic dermatitis.
From urinogenital system: an ischuria at patients with a prostate hyperplasia, an urine incontience, change of a libido.
Others: reactions of hypersensitivity at intolerance of any component of drug.

Interaction with other medicines:

The combination of an amantadin with anticholinergics and with other protivoparkinsonichesky drugs is possible. In a combination with other protivoparkinsonichesky drugs mutual strengthening of therapeutic action is observed. However simultaneous use of an amantadin and anticholinergics or a levodopa can increase confusion of consciousness, a hallucination, nightmares, disturbances from a digestive tract or other atropinopodobny side effects. At the patients receiving амантадин and a levodopa, psychotic frustration can be observed.
It is necessary to avoid simultaneous use with memantiny.
In isolated cases deterioration in psychotic symptoms at the patients accepting at the same time амантадин and neuroleptics is possible.

Simultaneous use of an amantadin and the medicines or substances operating on TsNS (including alcohol-containing means), can strengthen toxic influence on it. In such cases careful observation of the patient is recommended. During treatment amantadiny it is impossible to take alcoholic beverages.

Simultaneous use of diuretics like Triamterenum/hydrochlorothiazide and Amantina can reduce removal of an amantadin from a blood plasma that will result in toxic concentration of the last in plasma. It is necessary to avoid a concomitant use of diuretics and Amantin.
Contraindicated simultaneous use of Amantin and the medicines extending a QT interval.

Contraindications:

Hypersensitivity to an amantadin or to any component of drug; epilepsy and other convulsive attacks; heavy renal failure, peptic ulcer.

Use during pregnancy or feeding by a breast.

Amantin it is contraindicated to accept during pregnancy and to the women planning pregnancy. Drug is contraindicated during feeding by a breast as it gets into breast milk. In case of need drug uses feeding by a breast should be stopped.

Children.

Experience of use of drug for treatment of children is not enough.

Overdose:

The overdose amantadiny can lead to death.

Symptoms. At overdose amantadiny symptoms of acute psychosis and neuromuscular disturbances rank high. A hyperreflexia, motive concern, spasms, the extrapyramidal phenomena, the torsion spasms, expansion of pupils, a dysphagy, confusion of consciousness, a disorientation, a delirium, visual hallucinations, a myoclonus, nausea, vomiting, dryness in a mouth, a hyperventilation, a fluid lungs, respiratory insufficiency, a respiratory distress syndrome, a hypertension, cardiac arrhythmia, tachycardia, a stenocardia attack, a stop of cordial activity. The renal failure, including increase in an urea nitrogen and decrease in clearance of creatinine, an ischuria is possible.

Treatment. There is no specific antidote. For preventing absorption of drug needs to provoke vomiting or to wash out a stomach (if the patient is in consciousness), to accept absorbent carbon; to provide support of the vital functions of an organism, adequate hydration. For bystry removal of drug provide acid reaction of urine. By means of a hemodialysis a small amount of drug is removed. Careful monitoring of arterial pressure, heart rate, an ECG, function of breath, body temperature, for early detection of development of hypotension and cardiac arrhythmia and, if necessary, their treatment is recommended. For reduction of expressiveness of symptoms from TsNS purpose of physostigmine in a dose of 1 mg intravenously, if necessary repeatedly, but no more than 2 mg an hour is recommended to adults. At an ischuria - it is necessary to carry out bladder catheterization.

Storage conditions:

To store in the place, unavailable to children, in original packaging at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister; on 3 or on 6 blisters in a pack cardboard.