Reminil

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

At the same time, the drug potentiates the characteristic effect that acetylcholine has on nicotine endings (most likely due to the fact that it interacts with the allosteric segment of the end). Improving the functioning of the cholinergic system leads to increased cognitive function in people with dementia of Alzheimer's nature.

Indications Reminila

It is used in case of senile dementia of Alzheimer's character, which has light or moderate severity (this includes cases with disorders of cerebral blood flow on the background of cerebral blood flow).

[1],

Release form

The release of the component is implemented in capsules - 7 pieces inside the plate. In a pack - 4 such records.

[2]

Pharmacokinetics

Reminil has a low intraplasma clearance rate (about 300 ml per minute), as well as average values of the distribution volume (175 l at stationary values). Excretion has a biexponential form, and the final half-life is 7-8 hours.

After 1-time ingestion of 8 mg of the drug inside, absorption inside the gastrointestinal tract proceeds at a sufficiently high rate. Absolute bioavailability values are approximately 88.5%. The level of Swag is noted after 80 minutes and is 43 ± 13 ng / ml; however, the AUC is 427 ± 102 ng / h / ml.

Eating 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 a substance per day, the Cmax values inside the plasma and the average values are 30-90-ng / ml.

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

The main metabolic pathways of the drug are glucuronization, epimerization, and in addition N-oxidation with O-demethylation and N-demethylation. In persons with active metabolic processes of hemoprotein CYP2D6, O-demethylation is observed. Indicators of radioactive components excreted by the intestine and kidneys are not tied to the rate of exchange 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 speed of the metabolic processes, the main part of the radioactive elements inside the plasma are glucuronide with galantamine. At a high metabolic rate, glucuronide associated with O-desmethylgalentamine is also detected.

At 1-fold administration of Reminyl within the plasma (at any rate of metabolic processes), no metabolic components (norhalantamine and O-demethyl-galantamine with O-demethyl-nororgalantamine) having an unconjugated form are noted. Only with multiple use of drugs inside the plasma, norgalantamine is registered (its index does not exceed 10% of the value of drugs).

Clinical testing of the drug showed that plasma indicators of the active element in individuals with Alzheimer's are 30-40% higher than in healthy people.

In individuals with moderate renal impairment, AUC and half-life have been increased by approximately 30%.

In the case of liver-related diseases, the excretion of galantamine was weakened in accordance with a decrease in CC level. With moderate impairment of kidney function (the KK indicator in the range of 52-104 ml per minute), the intraplasma element values increased by 38%, and in the case of heavy (the KK level in the range of 9-51 ml per minute) - by 67%.

[3], [4], [5], [6]

Dosing and administration

The drug is recommended to use with food, applying the 1st capsule per day. During therapy, the patient should receive a sufficient amount of fluid.

First, it is required to use 8 mg of the drug per day (the duration of this cycle is 1 month) Further, a supporting daily portion of 16 mg of the substance is used (this course should last at least 1 month).

Increasing the size of the maintenance portion to the maximum (24 mg per day) is allowed only after completing the full clinical study (it is necessary to determine the personal tolerance of the drug and the effect exerted by the treatment).

In the case of an unplanned cancellation of therapy (for example, when preparing a patient for surgery), there was no exacerbation of the symptoms of the disease.

With the need to stop the therapy for several days, it is necessary to resume it with the use of the initial portion, and then increase the dosage according to the scheme indicated above.

In people with severe or moderate stages of liver diseases, the indicators of the drug inside the plasma increase.

In case of moderate hepatic impairment, the initial portion of the drug should be consumed within at least 1 week; it is 8 mg in 48 hours. Over the next month, you can use this portion already for 1 day. In general, a day is allowed to use no more than 16 mg of Reminyl.

In the case of severe stages of liver diseases and disorders of the kidneys (the level of QC below 9 ml per minute) use of the drug is prohibited.

Use Reminila during pregnancy

Special tests regarding the effects of the drug on nursing or pregnant women have not been performed, so it can not be prescribed during these periods.

Contraindications

Among the contraindications:

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

Caution is required when using drugs in such cases:

• performing general anesthesia;
• chronic stage of pulmonary pathology of obstructive nature;
• AND;
• bradycardia, AB blockade and CSSD;
• unstable angina;
• epilepsy;
• previous operations affecting the gastrointestinal tract and the bladder;
• ulcers affecting the gastrointestinal tract;
• use in combination with substances that inhibit heart rate indicators (digoxin, β-blockers, etc.);
• obstruction affecting the gastrointestinal tract or urinary ducts.

Side effects Reminila

Main adverse events:

• dehydration (sometimes has severe severity, which can cause the development of renal impairment);
• severe intolerance;
• depression (sometimes accompanied by suicidal mood), headaches and dizziness, and besides, fainting and hallucinations;
• anorexia, taste disturbances, loss of appetite, vomiting, abdominal pain, discomfort affecting the gastrointestinal tract, diarrhea, nausea, dyspepsia and weight loss;
• sense of inhibition, ear noise, bradycardia, tremor, drowsiness, paresthesia, visual misting and hypersomnia;
• feeling of heartbeat, reduction in blood pressure, AV block (grade 1), hot flashes, hyperhidrosis, and supraventricular extrasystole;
• fatigue and weakness or muscle spasm;
• increased activity of the functioning of the liver enzymes or hepatitis.

Most often, patients have vomiting with nausea, developing when determining the appropriate dosage portion; they often manifest themselves for at least the 1st week. In case of such violations, it is recommended to use as much liquid as possible, as well as to take antiemetic drugs - this will completely eliminate these symptoms.

[7], [8]

Overdose

It is believed that when galantamine poisoning manifestations of the violation will be similar to the symptoms that develop during intoxication with other cholinomimetics.

Toxic reactions associated with parasympathetic NS, CNS, and neuromuscular synapses usually develop. Along with muscle weakness or fasciculation, symptoms of a cholinergic disorder occur: severe nausea, lacrimation, hypersalivation, hyperhidrosis, a decrease in blood pressure, vomiting, seizures, and in addition to this pain, affecting the abdominal zone, collapse and incontinence to urinate and defecate.

Developing at the same time bronchial spasms, hypersecretion through the mucous membrane of the trachea and severe muscle weakness can lead to blockage of the respiratory ducts, as a result of which death can occur.

At the same time, when using 32 mg of galantamine, prolongation of the QT-interval values, loss of consciousness and polymorphic tachycardia of the ventricles, having a spindle character, occur.

In case of Reminil poisoning, it is necessary to perform standard supporting procedures for such situations (gastric lavage, induction of vomiting, use of sorbents).

In severe overdose, atropine is administered, which is a common antidote for cholinomimetics. At first, 0.5–1 mg of the substance is administered intravenously, and then the portions are adjusted according to the clinical picture.

Interactions with other drugs

When anesthesia is performed, galantamine can lead to potentiation of depolarizing neuromuscular conduction.

The drug has an antagonistic effect on anticholinergic drugs.

Use of the drug in combination with other cholinomimetics is prohibited.

The drug may enter into therapeutic interaction with agents that reduce the level of heart rate (for example, digoxin or β-blockers).

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

Combining with fluvoxamine, amitrptilin, and in addition with paroxetine, fluoxetine or quinidine causes a decrease in drug clearance by 25-33%, which, especially at the initial stage of treatment, increases the development of negative cholinergic symptoms (usually this is nausea, which is further goes into vomiting). This may require a decrease in the supporting portion Reminil.

When using the daily dosage of memantine, which is 10–20 mg, during the 12-day period, the pharmacokinetic parameters of galantamine, used in daily doses up to 16 mg, did not change.

With the introduction of a daily dosage of drugs not more than 24 mg, the pharmacokinetics of digoxin with warfarin does not change.

Galantamine only slightly slows down the main forms of human hemoprotein P-450.

[9], [10]

Storage conditions

It is necessary to keep reminil at temperature values within the limits of 15-30 ° С.

Shelf life

Reminyl can be used for a 2-year period from the moment of production of the drug.

Application for children

Due to the specifics of the indications for the use of Reminil, testing its effects on children was not performed.

Analogs

Analogues of drugs are the substances Alzepil, Servonex, Alzenorm, Divare with Donerum, Ekselon and Palixid-Richter with Aripezil, and in addition Almer, Yasnal, Rivastigmin Orion with Aricept and Ivastiklein.

[11], [12]