Reminyl

Reminyl has anticholinesterase properties. Its active component is a tertiary alkaloid, the substance galantamine, which acts as a competitive reversible inhibitor of the element acetylcholinesterase (with selective activity).

At the same time, the drug potentiates the characteristic effect that acetylcholine has on nicotinic endings (most likely because it interacts with the allosteric segment of the ending). Improved cholinergic system function leads to increased cognitive function in people with Alzheimer's dementia.

Indications Reminyla

It is used for senile dementia of Alzheimer's nature, which is mild or moderate in severity (this also includes cases with accompanying cerebral blood flow disorders).

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Release form

The component is released in capsules - 7 pieces inside a plate. There are 4 such plates in a pack.

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Pharmacokinetics

Reminyl has a low rate of intraplasmic clearance (approximately 300 ml per minute) and moderate values of distribution volume (175 L at steady-state values). Excretion is biexponential, and the terminal half-life is 7-8 hours.

After a single oral administration of 8 mg of the drug, absorption in the gastrointestinal tract occurs at a fairly high rate. Absolute bioavailability values are approximately 88.5%. The Cmax level is noted after 80 minutes and is 43±13 ng/ml; while the AUC value is 427±102 ng/hour/ml.

Taking with food does not affect the AUC values, but inhibits the absorption of galantamine, reducing its Cmax level by 25%. With repeated use of 24 mg of the substance per day, the Cmax values in plasma and average values are 30-90 ng/ml.

With 2-fold daily use of 4-16 mg of the drug, its pharmacokinetics become linear. Within 7 days after the administration of 4 mg of the drug, 2.2-6.3% of radioactivity was excreted with feces, while 90-97% was excreted with urine. Together with urine, 18-22% of the unchanged active element is excreted per day. The recorded values of intrarenal clearance are equal to 65 ml per minute (amounting to 20-25% of the total intraplasmic clearance).

The main metabolic pathways of the drug are glucuronidation, epimerization, and also N-oxidation with O-demethylation and N-demethylation. In individuals with active metabolic processes of the CYP2D6 hemoprotein, the development of O-demethylation is noted. The indicators of radioactive components excreted by the intestine and kidneys are not tied to the rate of metabolic transformations. The results of in vitro tests showed that the main metabolic isoenzymes of galantamine within the P450 hemoprotein system are 3A4 with 2D6. Regardless of the rate of metabolic processes, the main part of radioactive elements in the plasma is glucuronide with galantamine. At a high metabolic rate, glucuronide associated with O-desmethylgalantamine is also detected.

With a single administration of Reminyl, no metabolic components (norgalantamine and O-demethyl-galantamine with O-demethyl-norgalantamine) in unconjugated form are observed inside the plasma (at any rate of metabolic processes). Only with repeated use of the drug, norgalantamine is registered inside the plasma (its value does not exceed 10% of the drug value).

Clinical trials of the drug have shown that plasma levels of the active element in people with Alzheimer's are 30-40% higher than in healthy people.

In subjects with moderate renal impairment, AUC and half-life values are increased by approximately 30%.

In the case of liver-related diseases, galantamine excretion was weakened in accordance with the decrease in the level of CC. In moderate renal dysfunction (CC in the range of 52-104 ml per minute), intraplasmic values of the element increased by 38%, and in severe cases (CC in the range of 9-51 ml per minute) - by 67%.

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Dosing and administration

The medication is recommended to be taken with food, using 1 capsule per day. During therapy, the patient should receive a sufficient amount of liquid.

At first, 8 mg of the drug is required per day (the duration of this cycle is 1 month). Then a maintenance daily dose of 16 mg of the substance is used (this course should last at least 1 month).

Increasing the size of the maintenance dose to the maximum (24 mg per day) is allowed only after a complete study of the clinical picture (it is necessary to determine the individual tolerance of the drug and the effect of the treatment).

In case of unplanned discontinuation of therapy (for example, when preparing a patient for surgery), no exacerbation of disease symptoms was observed.

If there is a need to stop therapy for several days, it is necessary to resume it by using the initial dose, and then increase the dosage according to the scheme indicated above.

In people with severe or moderate liver disease, plasma drug levels are elevated.

In case of moderate liver dysfunction, the initial dose of the drug should be taken within at least 1 week; it is equal to 8 mg per 48 hours. During the following month, the specified dose can be taken per day. In general, no more than 16 mg of Reminyl is allowed per day.

In case of severe stages of liver disease and kidney disorders (CC level below 9 ml per minute), the use of the drug is prohibited.

Use Reminyla during pregnancy

No specific tests have been performed on the effects of the drug on breastfeeding or pregnant women, so it should not be prescribed during these periods.

Contraindications

Among the contraindications:

• renal diseases of severe intensity (CC values below 9 ml per minute), as well as liver diseases;
• the presence of severe intolerance associated with galantamine or auxiliary components of the drug.

Caution is required when using drugs in the following cases:

• performing general anesthesia;
• chronic stage of obstructive pulmonary pathology;
• BA;
• bradycardia, AV block and SSSS;
• unstable angina;
• epilepsy;
• previous surgeries affecting the gastrointestinal tract and bladder;
• ulcers affecting the gastrointestinal tract;
• use in combination with substances that inhibit heart rate (digoxin, β-blockers, etc.);
• obstruction affecting the gastrointestinal tract or urinary tract.

Side effects Reminyla

Main side effects:

• dehydration (sometimes severe, which can lead to the development of renal failure);
• severe intolerance;
• depression (sometimes accompanied by suicidal tendencies), headaches and dizziness, as well as fainting and hallucinations;
• anorexia, taste disturbances, loss of appetite, vomiting, abdominal pain, discomfort affecting the gastrointestinal tract, diarrhea, nausea, dyspepsia and weight loss;
• feeling of lethargy, tinnitus, bradycardia, tremor, drowsiness, paresthesia, blurred vision and hypersomnia;
• feeling of palpitations, decrease in blood pressure, AV block (1st degree), hot flashes, hyperhidrosis and supraventricular extrasystole;
• rapid fatigue, as well as weakness or muscle spasms;
• increased activity of liver enzymes or hepatitis.

Most often, patients experience vomiting with nausea, which develops when determining the appropriate dosage portion; they often manifest themselves for at least 1 week. In such cases, it is recommended to drink as much liquid as possible, as well as take antiemetics - this will completely eliminate these symptoms.

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Overdose

It is believed that in case of poisoning with galantamine, the manifestations of the disorder will be similar to the symptoms that develop during intoxication with other cholinomimetics.

Usually toxic reactions associated with the parasympathetic NS, CNS and neuromuscular synapses develop. Together with muscle weakness or fasciculation, symptoms of cholinergic disorder occur: severe nausea, lacrimation, hypersalivation, hyperhidrosis, decreased blood pressure, vomiting, convulsions, and in addition pain affecting the abdominal area, collapse and urinary and defecation incontinence.

Simultaneous development of bronchial spasms, hypersecretion through the tracheal mucosa and severe muscle weakness can lead to blockage of the respiratory tract, which can result in death.

At the same time, when 32 mg of galantamine is used, prolongation of the QT interval, loss of consciousness and polymorphic ventricular tachycardia of a spindle-shaped nature occur.

In case of poisoning with Reminyl, it is necessary to carry out standard supportive procedures for such situations (gastric lavage, induction of vomiting, use of sorbents).

In case of severe overdose, atropine is administered, which is a general antidote for cholinomimetics. First, 0.5-1 mg of the substance is administered intravenously, and then the doses are adjusted taking into account the clinical picture.

Interactions with other drugs

When performing anesthesia, galantamine can lead to potentiation of depolarization neuromuscular conduction.

The drug has an antagonistic effect relative to anticholinergic drugs.

It is prohibited to use the drug in combination with other cholinomimetics.

The medication may interact therapeutically with agents that reduce heart rate (for example, digoxin or β-blockers).

Substances that powerfully inhibit coenzymes CYP3A4, as well as CYP2D6, can increase the AUC values of galantamine. Administration with paroxetine increases this value by 40%, with erythromycin - by 10%, and with ketoconazole - by 30%.

Combination with fluvoxamine, amitriptyline, and also with paroxetine, fluoxetine or quinidine causes a decrease in the clearance level of the drug by 25-33%, due to which, especially at the initial stage of treatment, the development of negative cholinergic symptoms increases (usually nausea, which then turns into vomiting). In this case, it may be necessary to reduce the maintenance dose of Reminyl.

When using a daily dose of memantine of 10-20 mg over a 12-day period, the pharmacokinetic parameters of galantamine, used in daily doses of up to 16 mg, did not change.

When administering a daily dose of the drug of no more than 24 mg, the pharmacokinetics of digoxin with warfarin does not change.

Galantamine only slightly inhibits the major forms of human hemoprotein P-450.

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Storage conditions

Reminyl must be stored at temperatures between 15-30°C.

Shelf life

Reminyl can be used for a period of 2 years from the date of manufacture of the drug.

Application for children

Due to the specific indications for the use of Reminyl, testing of its effects in children has not been performed.

Analogues

The analogs of the drug are Alzepil, Servonex, Alcenorm, Divare with Donerum, Exelon and Palixid-Richter with Aripezil, and in addition to this, Almer, Yasnal, Rivastigmine Orion with Aricept and Ivastiklein.

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