Reminyl - instructions for use, tablets, capsules, analogues, reviews, price

Release form and composition

Dosage forms of Reminyl:

Film-coated tablets: biconvex, round, engraved “JANSSEN” on one side: 4 mg each – almost white or white, engraved on the other side “G4”; 8 mg each - pink, engraved on the other side - “G8”; 12 mg each - orange-brown, engraved on the other side - “G12” (14 pieces in blisters, 1, 2 or 4 blisters in a cardboard pack);
Extended-release capsules: hard gelatin, with an opaque body; the capsules contain almost white or white granules; 8 mg each – size No. 4, white cap with the symbol “G8”; 16 mg each – size No. 2, light pink cap with the symbol “G16”; 24 mg each - size No. 1, pinkish-brown cap with the symbol “G24” (300 pieces in polyethylene bottles, 1 bottle in a cardboard box; 7 pieces in blisters, 1 or 4 blisters (8 mg each ), either 4, 8 or 12 blisters (16 mg each), or 2, 4, 8 or 12 blisters (24 mg each) in a cardboard box).

Composition of 1 film-coated tablet:

Active substance: galantamine – 4, 8 or 12 mg (galantamine hydrobromide – 5.127/10.254/15.38 mg);
Auxiliary components: microcrystalline cellulose, lactose monohydrate (premix in a ratio of 25% and 75%, respectively), magnesium stearate, crospovidone, anhydrous colloidal silicon dioxide;
Shell: hypromellose 2910 (viscosity 5 mPa×s), propylene glycol, titanium dioxide (E171), talc; additionally: 4 mg each – yellow iron oxide (E172); 8 mg each – red iron oxide (E172); 12 mg each – red iron oxide (E172), orange-yellow dye S (E110).

Composition of 1 capsule of prolonged action:

Active substance: galantamine – 8, 16 or 24 mg (in the form of hydrobromide);
Auxiliary components: ethylcellulose 20 mPa×s, macrogol 400, sugar spheres (corn starch, sucrose), hypromellose 2910 5 mPa×s, diethyl phthalate;
Shell: gelatin, titanium dioxide; additionally: 16 mg each – red iron oxide; 24 mg each – red and yellow iron oxide.

Compound

1 tablet may contain 4/8/12 mg of galantamine , the active ingredient.
Additional Ingredients: Colloidal silicon dioxide, microcrystalline cellulose, crospovidone, lactose monohydrate, magnesium stearate. Shell: propylene glycol, hydroxypropyl methylcellulose, talc, titanium dioxide, iron oxide. 1 capsule may contain 8/16/24 mg of galantamine , the active ingredient. Additional ingredients: sugar spheres (corn starch, sucrose), ethylcellulose 20 mPa×s, macrogol 400, diethyl phthalate, hypromellose 2910 5 mPa×s. Shell: titanium dioxide, iron oxide, gelatin.

Pharmacodynamics and pharmacokinetics

Galantamine is a reversible, selective, competitive inhibitor of the enzyme acetylcholinesterase. It also enhances the effect of acetylcholine on nicotinic receptors. Due to increased activity of the cholinergic system, it is possible to improve cognitive function in patients with Alzheimer's disease.

Galantamine has a moderate volume of distribution (Vd) and slow clearance. The elimination of galantamine is biexponential. The terminal half-life is 7–8 hours. After a single oral dose of 8 mg of Reminyl, it is rapidly absorbed from the gastrointestinal tract, the maximum concentration of galantamine is reached after 1.2 hours. The absolute bioavailability of the active substance when administered orally is 88.5%. Taking the drug with food slows down its absorption, but this does not affect the amount of galantamine absorbed.

The main metabolic pathways of Reminyl are: O-demethylation, N-demethylation, N-oxidation, epimerization and glucuronidation. The amount of radioactive substances excreted in feces and urine did not differ between patients with slow and fast metabolizers.

In the plasma of people with slow and fast metabolism, the main part of the radioactive substances is unchanged galantamine and its glucuronide. In people with rapid metabolism, O-desmethylgalantamine glucuronide is also found in the plasma. After repeated administration of galantamine, norgalantamine was detected in the plasma, but its amount was no more than 10% of the amount of galantamine.

Clinical trials have shown that plasma concentrations of galantamine are 30–40% higher in people with Alzheimer's disease than in healthy young individuals.

In patients with mild liver dysfunction, pharmacokinetic parameters are similar to those in healthy people. In moderate liver dysfunction, the half-life and AUC of galantamine increase by approximately 30%.

As creatinine clearance (creatinine clearance) decreases, galantamine excretion is weakened. In case of moderate renal impairment (creatinine clearance 52–104 ml/min), the plasma concentration of galantamine increases by 38%; in severe renal impairment (creatinine clearance 9–51 ml/min) – by 67% compared with healthy individuals of the same weight and age (with CC more than 121 ml/min).

The degree of binding of galantamine to plasma proteins is about (17.7±0.8)%. In whole blood it is found predominantly in plasma (39%) and in formed elements (52.7%). Only 8.4% of galantamine binds to plasma proteins.

Reminyl analogs

Level 4 ATX code matches:
Nivalin

Exelon

Alzepil

Axamon

Galantamine

Arisept

Alzepil;
Diware;
Exelon;
Almer;
Palixid-Richter;
Alcenorm;
Yasnal;
Arisept;
Donerum;
Servonex;
Rivastigmine Orion;
Aripezil;
Ivastiklein.

Contraindications

Absolute:

Severe functional renal impairment (with creatinine clearance <9 ml/min);
Severe liver dysfunction (for capsules) or severe liver dysfunction (>9 points on the Child-Pugh scale) (for tablets);
Hypersensitivity to the components of the drug.

Relative (Reminyl in capsule form should be prescribed with caution in the presence of the following diseases/conditions):

Bronchial asthma, chronic obstructive pulmonary disease;
General anesthesia;
The period after surgery on the gastrointestinal tract and bladder;
Unstable angina, bradycardia, sick sinus syndrome, AV block;
Obstruction of the gastrointestinal tract, peptic ulcer of the stomach and duodenum;
Combined use with drugs that help slow the heart rate (beta-blockers, digoxin);
Urinary tract obstruction;
Epilepsy.

During pregnancy, Reminyl is prescribed only after assessing the balance of benefits and risks for the health of the mother and child. For women during lactation, when prescribing the drug, breastfeeding is recommended to be interrupted.

It is not recommended to prescribe Reminil to children (the safety profile for this age group of patients has not been studied).

Reviews of Reminyl

Unfortunately, modern medicine has not yet created drugs that can reverse or at least significantly improve the manifestations of such a severe pathology as Alzheimer's disease . This disease, as a rule, develops at an advanced age and progresses quite quickly. It is in order to delay the final destruction of personality that drugs based on galantamine were created that can slow down the development of symptoms of the disease and, to some extent, preserve a person’s mental abilities.

Instructions for use of Reminyl: method and dosage

tablets are taken orally.

The frequency of administration is 2 times a day, preferably simultaneously with meals in the morning and evening.

The daily dose is: initial (taken for 4 weeks) - 8 mg, maintenance (taken for 4 weeks) - 16 mg (after a comprehensive assessment of the clinical situation, in particular, tolerability and the achieved effect, it may be increased to 24 mg).

If creatinine clearance is >9 ml/min, the dose of Reminyl should not be adjusted.

The initial dose for moderate functional liver disorders is 4 mg in 1 dose (in the morning). After a week, it is possible to increase the frequency of administration to 2 times a day (for at least 4 weeks).

When combined with strong inhibitors of CYP3A4 or CYP2D6 isoenzymes, it may be necessary to reduce the dose of the drug.

capsules are taken orally, 1 time per day, preferably in the morning along with food.

The initial daily dose is 8 mg.

When switching from taking Reminyl tablets, the capsule should be taken the next morning. The daily dose should not change.

During therapy, you need to take a sufficient amount of fluid.

The initial maintenance daily dose is 16 mg. It is taken for at least 4 weeks. Increasing the dose to 24 mg is possible after a comprehensive assessment of the clinical picture, in particular, tolerability and therapeutic effect.

After abrupt cessation of treatment, symptoms usually do not worsen. After a break in taking Reminyl for several days, it is resumed from the initial dose, after which it is increased according to the above scheme.

For moderate and severe liver damage, an initial dose of 8 mg is prescribed every other day for a week, after which the frequency of administration is increased to 1 time per day for a course of at least 4 weeks. Such patients should not exceed a daily dose of more than 16 mg.

When combined with strong inhibitors of CYP3A4 or CYP2D6 isoenzymes, it may be necessary to reduce the dose of the drug.

Side effects

Pills

Central nervous system: often - insomnia or drowsiness, dizziness, weakness, headache, sudden falls, confusion; rarely – fainting, tremor;
Digestive system: often - vomiting, anorexia, nausea, abdominal pain, dyspepsia (anorexia, nausea and vomiting were more common in women);
Others: often - urinary tract infections, weight loss, rhinitis, injuries; rarely – severe bradycardia.

Capsules Most often, nausea and vomiting were observed while taking Reminil. As a rule, these violations occur during dose selection. Their duration was at least 7 days, they were mostly periodic. The most effective treatment in such cases is to prescribe antiemetic medications and ensure adequate fluid intake.

In addition, the following adverse reactions may occur during therapy (>1/10 - very often, >1/100, <1/10 - often, >1/1000 and <1/100 - uncommon, >1/10,000 and <1/1000 – rare, <1/10,000 – very rare):

Cardiovascular system: often – bradycardia; uncommon – rapid heartbeat, first degree AV block, hot flashes, supraventricular extrasystole, decreased blood pressure;
Nervous system: often - fainting, dizziness, lethargy, tremor, headache, drowsiness; infrequently – hypersomnia, taste perversion, paresthesia;
Immune system: uncommon – hypersensitivity;
Digestive system: very often – vomiting, nausea; often – dyspepsia, diarrhea, gastrointestinal discomfort, abdominal pain;
Musculoskeletal system and connective tissue: often – muscle spasms; infrequently – muscle weakness;
Liver and biliary tract: very rarely - hepatitis;
Psychiatry: often – hallucinations, depression (very rarely with suicide); infrequently – auditory and visual hallucinations;
Metabolism and nutrition: often – anorexia, decreased appetite; uncommon – dehydration (including, in some cases, severe, which can lead to renal failure);
Organ of vision and hearing: infrequently – blurred vision; very rarely - tinnitus;
Skin and subcutaneous tissues: often – increased sweating;
Laboratory indicators: often – loss of body weight; very rarely - increased activity of liver enzymes;
General disorders: often – weakness, fatigue.

Very rarely, in placebo-controlled clinical studies, the following adverse events were observed: rhinitis, hematuria, anemia, urinary tract infections, increased blood pressure (a cause-and-effect relationship with therapy has not been proven).

Overdose

In cases of possible overdose of Reminyl, subjective and objective symptoms are presumably similar to those of overdose of other cholinomimetics. Toxic effects are mainly observed at the neuromuscular junction, central nervous system and parasympathetic nervous system. In addition to spontaneous contraction of muscle fibers and muscle weakness, some or all signs of a cholinergic crisis may be observed: increased salivation, vomiting, lacrimation, severe nausea, fecal and urinary incontinence, cramping abdominal pain, severe sweating, decreased blood pressure, convulsions, bradycardia and collapse. Severe muscle weakness and simultaneous bronchospasm with increased secretion of the tracheal mucosa can lead to airway blockage and death.

In a post-marketing study, random ingestion of 32 mg of Reminyl per day resulted in QT prolongation, torsade de pointes (TdP), and torsade de pointes (TdP) with brief loss of consciousness.

Treatment for an overdose of Reminyl consists of standard supportive measures. In severe cases, atropine can be used as a general antidote. It is administered intravenously at a dose of 0.5–1 mg, the size and frequency of subsequent doses depend on the patient’s condition.

special instructions

During the period of therapy, it is necessary to monitor changes in the patients' weight, since weight loss may be a symptom of Alzheimer's disease or occur due to taking Reminyl.

Most adverse reactions develop as the dose of Reminyl is gradually increased.

The drug is not intended for patients with mild cognitive impairment, i.e. for patients with isolated memory impairment beyond the expected level for their education and age, but who do not meet the criteria for Alzheimer's disease.

It must be taken into account that taking Reminyl may negatively affect the ability to drive vehicles and operate machinery.

Reminyl®

Application of Reminyl

®
for other types of dementia or other memory impairments
The beneficial effects of Reminyl® in patients with other types of dementia and other types of memory impairment have not been demonstrated.

Safety in patients with mild cognitive impairment (MCI)

Reminyl® is not intended for patients with mild cognitive impairment (MCI), i.e. for patients with isolated memory impairment exceeding the expected level for their age and education, but not meeting the criteria for Alzheimer's disease.

Two two-year studies in patients with SCI found no effectiveness of the drug. A higher (compared with placebo) mortality from various adverse reactions was shown (about half of the cases were associated with reactions from the cardiovascular system). Given the data obtained from the significant proportion of patients who discontinued treatment before completion of the double-blind period, there is no reason to believe that the risk of death increases over time in patients treated with Reminyl®. More patients in the placebo group than in the galantamine group discontinued treatment before death, which may explain the difference in mortality initially reported.

The results of studies of SCI differ from the results of studies of Alzheimer's disease. In the pooled Alzheimer's disease studies (n = 4614), the mortality rate was numerically higher in the placebo group than in the Reminyl® treatment group.

Diagnosis should be made in accordance with current Alzheimer's disease guidelines. Therapy should be carried out under the supervision of a physician and can only be started if the caregiver is able to ensure continuous use of the drug.

Weight control

Alzheimer's patients lose weight. Treatment with acetylcholinesterase inhibitors, including galantamine, is associated with weight loss in these patients and therefore changes in body weight should be monitored during treatment.

Severe skin reactions Severe skin reactions (Stevens-Johnson syndrome and acute generalized exentematous pustulosis) have been observed in patients taking Reminyl®. It is recommended to inform patients about the signs of severe skin reactions and the need to discontinue use of Reminyl® at the first appearance of a skin rash.

As with other cholinomimetics, Reminyl® should be used with caution in the following conditions:

Cardiac disorders:

Due to their pharmacological action, cholinomimetics can cause vagotonic effects on the heart (for example, bradycardia). The consequences of such effects may be most severe in patients with sick sinus syndrome and other supraventricular conduction disorders, in patients who are concomitantly receiving drugs that lower heart rate such as digoxin or beta-blockers, and in patients with electrolyte disturbances ( for example, with hyperkalemia, hypokalemia). Caution should be exercised when using galantamine in patients with cardiovascular diseases, including in the period after a recent myocardial infarction, acute atrial fibrillation, AV block of the second degree or higher, chronic heart failure (especially functional class III-IV according to NYHA classification).

Treatment with Reminyl® was accompanied by fainting and, rarely, severe bradycardia. Should be used with caution in unstable angina.

Gastrointestinal diseases:

Patients at increased risk of developing peptic ulcers, such as those with a history of or predisposed to peptic ulcers, including those taking non-steroidal anti-inflammatory drugs, should be monitored for symptoms. It should be noted, however, that clinical studies did not show an increase in the incidence of peptic ulcers and gastrointestinal bleeding in patients receiving Reminyl® compared to patients receiving placebo. Reminyl® is not recommended for use in patients with gastrointestinal obstruction or in patients who have recently undergone gastrointestinal surgery.

Neurological diseases:

Convulsions have been observed when using Reminyl®. It should be remembered, however, that seizure activity can be a manifestation of Alzheimer's disease itself. In rare cases, increased cholinergic tone may lead to worsening of Parkinson's disease. Analysis of pooled data from placebo-controlled studies showed that cerebrovascular events were infrequently observed in patients with dementia of the Alzheimer's type treated with galantamine. This should be taken into account when using galantamine in patients with cerebrovascular pathologies.

Pulmonary diseases:

Due to its cholinomimetic activity, Reminyl® should be used with caution in patients suffering from severe bronchial asthma, obstructive pulmonary disease or acute pulmonary infections.

Genitourinary diseases:

Reminyl® is not recommended for use in patients with urinary tract obstruction or in patients who have recently undergone bladder surgery.

Surgical and medical procedures:

galantamine, which is a cholinomimetic, is likely to enhance succinylcholine-type muscle relaxation during anesthesia, especially in patients with pseudocholinesterase deficiency.

Safety in patients with mild cognitive impairment (MCI)

Drug interactions

When Reminyl is used in combination with certain medications/substances, the following effects may be observed:

Inhibitors of the CYP2D6 isoenzyme (fluvoxamine, amitriptyline, fluoxetine, quinidine, paroxetine): decreased clearance of galantamine;
Anticholinergic drugs: development of antagonism;
Other cholinomimetics: enhancing their action (the combination is not recommended);
Peripheral muscle relaxants of the depolarizing type (during anesthesia): increased neuromuscular blockade;
Drugs that reduce heart rate (for example, beta-blockers and digoxin): increased effect;
Strong inhibitors of CYP2D6 and CYP3A4 isoenzymes: increased incidence of adverse reactions (mainly vomiting and nausea) (a reduction in the maintenance dose of Reminyl may be required).

Interaction

During anesthesia (anesthesia), galantamine is able to increase depolarizing neuromuscular conduction.

Galantamine exhibits antagonistic effects towards anticholinergic drugs .

Due to its mechanism of action, the use of Reminyl with other cholinomimetics is not allowed.

Reminyl has the ability to pharmacodynamically interact with drugs that lower heart rate (for example, beta-blockers and Digoxin ).

Strong inhibitors of coenzymes CYP3A4 and CYP2D6 may increase the AUC of galantamine . Combined use with Paroxetine increases this indicator by 40%, with Ketoconazole by 30%, with Erythromycin by 10%.

Parallel use with Amitriptyline , Fluvoxamine , Fluoxetine , Paroxetine or Quinidine led to a decrease in galantamine clearance by 25-33%, and therefore, especially at the beginning of therapy, cholinergic negative manifestations (usually nausea , leading to vomiting ) may be observed more often. In such cases, it may be necessary to adjust the maintenance dose of Reminyl downward.

A daily dose of of memantine taken for 12 days had no effect on the pharmacokinetics of galantamine in daily doses of up to 16 mg.

A daily dose of Reminil up to 24 mg does not affect the kinetics of Warfarin and Digoxin .

Galantamine is characterized by weak inhibition of the main forms of human cytochrome P-450 .