Amantadine

Pharmacological properties

Amantadine has various pharmacological properties. it exhibits an indirect effect of a striatal dopamine receptor agonist. animal studies have shown that amantadine increases the extracellular concentration of dopamine by both increasing dopamine release and by blocking reuptake in presynaptic nerve cells. at therapeutic concentrations, amantadine inhibits the release of acetylcholine mediated by nmda receptors, and thus may cause an anticholinergic effect. amantadine has a synergistic effect with l-dopa.

Pharmacokinetics After oral administration, amantadine is rapidly and completely absorbed into the digestive tract. C_max in blood plasma is achieved approximately 2-8 hours after taking a single dose of the drug (100 mg) and is 0.15 μg / ml. When taking the drug at a dose of 200 mg / day, the state of equilibrium concentration is reached after 4–7 days at a plasma concentration of 400–900 ng / ml. Plasma clearance is defined as identical to renal clearance and is 17.7 ± 10 l / h in healthy adult volunteers. The conditional volume of distribution is 4.2 ± 1.9 l / kg and depends on the age of the patient; in adults - 6 l / kg.

T_½ is 10-30 hours (average 15 hours) and largely depends on the age of the patient. In elderly male patients (62–72 years) T_½ is 30 hours. In patients with renal failure, the final T_½ from blood plasma can be significantly extended (up to 68 ± 10 hours).

Amantadine binds to plasma proteins by approximately 67% (in vitro); about 33% is detected in blood plasma in an unbound form. Penetrates through the BBB using transport systems that are saturated. It is excreted in the urine almost unchanged (90% of a single dose), a small amount is excreted in the feces.

Amantadine has low dialysis capacity, about 5% per dialysis.

Amantadine is not metabolized in the human body.

Indications

Parkinsons syndrome: treating symptoms of Parkinsons disease, such as stiffness, tremors, hypokinesia, and akinesia.

Extrapyramidal side effects of antipsychotics and other drugs: early dyskinesia, akathisia and parkinsonism.

Application

Tablets should be taken by adults after meals with a small amount of liquid, preferably in the morning and / or afternoon. in connection with a possible activating effect on the central nervous system, the last dose of the drug is recommended to be taken no later than 16:00.

Before starting, as well as after 1 and 3 weeks of treatment, it is necessary to make an ECG (50 mm / s) and frequency correction of the Q – T (Q – Tc) time according to Bazett, which are determined manually.

Such an ECG must be done before each subsequent dose increase and 2 weeks after it. In the future, an ECG should be performed at least once a year. Treatment cannot be started or should be discontinued if the initial Q – Tc value does not exceed 420 ms, with an increase in Q – T by more than 60 ms during drug treatment, or if the Q – Tc value is more than 480 ms, as well as in patients with visible ECG U -waves.

Single and daily dose. Adhering to the above measures and taking into account contraindications, it is possible to prevent a life-threatening side reaction - a chaotic polymorphic ventricular tachycardia.

Treatment of patients with Parkinsons syndrome and impaired motor activity, which are caused by the use of drugs, must be carried out gradually, in accordance with the therapeutic effect. Treatment should be started with 1 tablet (100 mg of amantadine sulfate) of the drug Amantin per day for the first 4-7 days, followed by an increase in the daily dose of 1 tablet once a week until an effective dose is achieved.

Usually an effective dose is 1-3 tablets 2 times a day (200-600 mg of amantadine sulfate).

Elderly patients, in particular in states of agitation, confusion, or delirium syndromes, a daily dose of 100 mg (1 tablet) is recommended.If such a dose is ineffective, it can be carefully increased to 200 mg / day under the supervision of a doctor.

With combined treatment with other antiparkinsonian drugs, the dose should be selected individually.

For patients who have previously been treated with amantadine, r-rum for injection, the initial dose should be higher.

With a sharp deterioration in parkinsonian symptoms with an akinetic crisis, it is necessary to prescribe the administration of amantadine sulfate solution.

Patients with renal failure. Doses for patients with renal insufficiency must be adapted in accordance with the glomerular filtration rate (GFR), as shown in the table.

* Achieved by taking in turn 1 time in 1 tablet and 1 time in 2 tablets of 100 mg of amantadine sulfate.

GFR can be approximately calculated using the following equation:

where cl_cr - creatine clearance in ml / min and creatinine - plasma creatinine in mg / 100 ml.

The creatinine clearance, which is calculated in accordance with this expression, applies exclusively to men (the corresponding value for women is 85% of this value) and can be equated with the insulin clearance for determining GFR (120 ml / min for adults).

Amantadine is poorly dialyzed (about 5%).

The duration of treatment depends on the nature and severity of the course of the disease and is determined by the doctor. Patients should not interrupt treatment on their own.

Avoid abrupt cessation of treatment with the drug, because in such a case, patients with Parkinsons disease may experience an increase in extrapyramidal symptoms, which sometimes include an akinetic crisis, and the effect of cessation of admission can sometimes manifest as delirium.

Children. Experience with amantadine in children is not enough, so the drug is not used in this age category.

Contraindications

• Hypersensitivity to amantadine or any component of the drug; epilepsy and other seizures; severe renal failure; peptic ulcer; decompensated heart failure (stage iv by nyha); cardiomyopathy and myocarditis; av blockade of the II and III degrees; bradycardia (55 bpm); prolonged q – t interval (bazett q – tc420 ms) with either noticeable u-waves or with a congenital q – t syndrome in a family history; severe ventricular arrhythmia, including chaotic polymorphic ventricular tachycardia; simultaneous treatment with budipine or other drugs that extend the q – t interval (see interactions); reduced levels of potassium or magnesium in the blood.

Side effects

Adverse reactions to amantadine are often mild and transient. As a rule, they appear within 2-4 days from the start of treatment and pass quickly after stopping the drug. the incidence of adverse reactions was evaluated by the following criteria: very often (1/10); often (1/100, 1/10); infrequently (1/1000, 1/100); rarely (1/10 000, 1/1000); very rarely (1/10 000); frequency is unknown (impossible to estimate from existing data).

From the psyche: often - sleep disturbances and mental agitation.

In patients (especially the elderly), prone to mental disorders, when combined with anticholinergics, paranoid exogenous psychoses may begin, accompanied by visual hallucinations. Adverse reactions of this type can occur more often if the tablets are taken in combination with other anti-Parkinsonian drugs (such as levodopa, bromocriptine or memantine).

On the part of the blood and lymphatic system: leukopenia.

From the nervous system: often - motor impairment; infrequently - dizziness, orthostatic disorders; rarely - blurred vision; very rarely - epileptic seizures, usually after treatment with doses that exceed the recommended ones, symptoms of myoclonia and peripheral neuropathies; anxiety, headache, drowsiness, sleeplessness