Universal reference book for medicines
Product name: REMINYL В® (REMINYL В® )

Active ingredient: galantamine

Type: Selective inhibitor of brain acetylcholinesterase.
The drug for Alzheimer's disease
Manufacturer: JOHNSON & JOHNSON (Russia) manufactured by JANSSEN-CILAG (Italy)
Composition, form of production and packaging
Capsules of prolonged action
hard gelatinous, size 4, with an opaque case and a lid of white color with a printed symbol "G8";
the contents of the capsules are granules of white or almost white color.
1 caps.

galanthamine (in the form of hydrobromide) 8 mg

[PRING] sugar spheres (sucrose, corn starch), hypromellose 2910 5 mPa? S, macrogol 400, ethylcellulose 20 mPa? S, diethyl phthalate.

The composition of the capsule shell: gelatin, titanium dioxide.

7 pcs.
- blisters (1) from the combined material (PVC, polyethylene, polyvinylidene chloride and aluminum foil) - packs cardboard.
7 pcs.
- blisters (4) from the combined material (PVC, polyethylene, polyvinylidene chloride and aluminum foil) - packs cardboard.
300 pcs.
- polyethylene bottles (1) - cardboard packs.
Capsules of prolonged action hard gelatinous, the size 2, with an opaque case and a cover of light pink color with the printed symbol "G16";
the contents of the capsules are granules of white or almost white color.
1 caps.

galanthamine (in the form of hydrobromide) 16 mg

[PRING] sugar spheres (sucrose, corn starch), hypromellose 2910 5 mPa? S, macrogol 400, ethylcellulose 20 mPa? S, diethyl phthalate.

The composition of the capsule shell: gelatin, titanium dioxide, iron oxide red.

7 pcs.
- blisters (4) from the combined material (PVC, polyethylene, polyvinylidene chloride and aluminum foil) - packs cardboard.
7 pcs.
- blisters (8) of combined material (PVC, polyethylene, polyvinylidene chloride and aluminum foil) - packs of cardboard.
7 pcs.
- blisters (12) from the combined material (PVC, polyethylene, polyvinylidene chloride and aluminum foil) - packs cardboard.
300 pcs.
- polyethylene bottles (1) - cardboard packs.
Capsules of prolonged action hard gelatinous, size 1, with an opaque case and a cap of a pinkish-brown color with the printed symbol "G24";
the contents of the capsules are granules of white or almost white color.
1 caps.

galanthamine (in the form of hydrobromide) 24 mg

[PRING] sugar spheres (sucrose, corn starch), hypromellose 2910 5 mPa? S, macrogol 400, ethylcellulose 20 mPa? S, diethyl phthalate.

The composition of the capsule shell: gelatin, titanium dioxide, iron oxide red, iron oxide yellow.

7 pcs.
- blisters (2) from the combined material (PVC, polyethylene, polyvinylidene chloride and aluminum foil) - packs cardboard.
7 pcs.
- blisters (4) from the combined material (PVC, polyethylene, polyvinylidene chloride and aluminum foil) - packs cardboard.
7 pcs.
- blisters (8) of combined material (PVC, polyethylene, polyvinylidene chloride and aluminum foil) - packs of cardboard.
7 pcs.
- blisters (12) from the combined material (PVC, polyethylene, polyvinylidene chloride and aluminum foil) - packs cardboard.
300 pcs.
- polyethylene bottles (1) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2013.

PHARMACHOLOGIC EFFECT

Galantamine, being a tertiary alkaloid, is a selective competitive and reversible inhibitor of acetylcholinesterase.
In addition, galantamine enhances the effect of acetylcholine on nicotinic receptors, apparently due to binding to the allosteric portion of the receptor.
By increasing the activity of the cholinergic system, cognitive function can improve in patients with Alzheimer's dementia.

PHARMACOKINETICS

Galantamine is characterized by a slow clearance (clearance from the plasma is about 300 ml / min) and moderate V d (average V d in the stationary state is 175 liters).
Elimination of galantamine is bi-exponential, and the final T 1/2 is approximately 7-8 hours.
After a single oral intake of 8 mg galantamine, it is rapidly absorbed from the digestive tract;
its C max was reached after 1.2 hours and was 43 В± 13 ng / ml, and AUC0-? is 427 В± 102 ng h / ml. The absolute bioavailability of galantamine by oral administration is 88.5%. The intake of galantamine with food slows its absorption (C maxdecreases by 25%), but does not affect the amount of absorbed drug (AUC).
After repeated administration of galantamine at a dose of 12 mg twice a day, the average concentrations at the end of the dose period and C max in the plasma ranged from 30 to 90 ng / ml.
The pharmacokinetics of galantamine is linear in the dose range of 4-16 mg twice daily.
Within 7 days after a single oral intake of 4 mg of 3 H-galanthamine, 90-97% of radioactivity was excreted in the urine and 2.2-6.3% with feces.
After oral administration, 18-22% of the dose was excreted as unchanged galantamine in urine for 24 hours, the kidney clearance was about 65 ml / min, which is 20-25% of the total clearance from the plasma.
The main ways of metabolism are N-oxidation, N-demethylation, O-demethylation, glucuronization and epimerization.
In people with active metabolism of CYP2D6 substrates, the most important metabolic pathway is O-demethylation. The number of radioactive substances excreted in urine and feces in people with fast and slow metabolism did not differ. In vitro studies have shown that the main isoenzymes of the cytochrome P450 system involved in galantamine metabolism are 2D6 and 3A4.
In the plasma of people with fast and slow metabolism, the bulk of radioactive substances are unchanged galantamine and its glucuronide.
In the plasma of people with rapid metabolism, glucuronide O-desmethylgalanthamine is also found. After a single administration of galanthamine in the plasma of "fast and slow metabolizers," none of the active metabolites (norgalanthamn, O-demethyl-galantamine and O-demethyl-norgalanthamine) was present in the unconjugated form.Norgalantamine was detected in the plasma of patients after repeated administration of galantamine, but its amount was no more than 10% of the levels of galantamine.
The results of clinical trials have demonstrated that in patients with Alzheimer's disease the concentration of galantamine in blood plasma is 30-40% higher than in young healthy individuals.

Pharmacokinetic parameters of galantamine in patients with mild violations of liver function (5-6 points on the Child-Pugh scale) were similar to those of healthy individuals.
In patients with moderate impairment of liver function (7-9 on the Child-Pugh scale), AUC and T 1/2 galantamine were increased by approximately 30%.
The distribution of galantamine was studied in young patients with varying degrees of renal dysfunction.
The excretion of galantamine was weakened as the CC decreased. In patients with impaired renal function of moderate severity (KK 52-104 ml / min), the concentration of galantamine in blood plasma was increased by 38%, and in patients with severe impairment (CK 9-51 ml / min) - increased by 67% with healthy people of the same age and weight (CC> 121 ml / min). Population pharmacokinetic study and analysis using a number of models showed that in patients with Alzheimer's disease and renal dysfunction, the dose of galantamine should not be adjusted if creatinine clearance is at least 9 ml / min. the clearance of galantamine in patients with Alzheimer's disease is reduced.
Binding to plasma proteins: the degree of galantamine binding to plasma proteins is small and amounts to 17.7 В± 0.8%.
In whole blood, galantamine is predominantly in shaped elements (52.7%) and in plasma (39.0%), whereas its fraction bound to plasma proteins is only 8.4%. The ratio of galanthamine blood / plasma concentrations is 1.17.
In a comparative study of the bioavailability of Reminil В® in the form of capsules with a sustained release of the active substance taken at a dose of 24 mg once a day and in the form of immediate-release tablets taken at a dose of 12 mg twice a day, the bioequivalence of these dosages on indicators AUC 0-24 h and C min in the equilibrium state.
C max , achieved 4.4 hours after taking the capsules at a dose of 12 mg 1 time per day, was approximately 24% less than after taking the tablets at a dose of 12 mg 2 times a day. The intake of food did not affect the bioavailability of the drug Reminil В® in the form of capsules with a sustained release of the active substance in the equilibrium state. In the study of the dose dependence of pharmacokinetics of Reminil В® in the form of capsules with sustained release of active substance in healthy elderly and young people, the equilibrium plasma concentration in people of both age groups was achieved within 6 days at all doses (8, 16 or 24 mg). In both age groups, the pharmacokinetics in the equilibrium state directly depended on the dose in the investigated dose range (8-24 mg).
INDICATIONS

- dementia of the Alzheimer's type of mild or moderate degree, incl.
with chronic disorders of cerebral circulation.
DOSING MODE

Initial dose

Reminil В® in the form of prolonged-action capsules should be taken orally 1 time / day (in the morning), preferably during meals.
The recommended initial dose is 8 mg / day.
Patients already taking Reminil В® in other forms with immediate release of the active substance (tablets) may switch to Reminil В® in the form of prolonged-action capsules by taking the last dose of Reminil В® in the form of tablets in the evening and starting the preparation of Reminil В® in the form of capsules 1 time a day the next morning.

When switching from Reminil В® in the form of tablets with immediate release of the active substance taken 2 times a day to Reminil В® in the form of prolonged-action capsules, taken once a day, the total daily dose should remain unchanged.

During treatment, you must take a sufficient amount of fluid.

Maintenance dose

The initial maintenance dose is 16 mg / day, patients should take this dose for at least 4 weeks.

The question of increasing the maintenance dose to the maximum recommended 24 mg / day should be addressed after a comprehensive assessment of the clinical situation, in particular the effect achieved and tolerability.

After the abrupt withdrawal of Reminil (for example, when preparing for surgery), there is no aggravation of symptoms.
If you take a break for a few days, take the initial dose of Reminil В® and then increase the dose according to the above scheme to the previous maintenance dose.
There is no significant experience in using Reminil В® in children .

In patients with moderate to severe liver damage, plasma galantamine concentrations may be higher than in patients without such lesions.
In patients with moderate impairment of liver function, the initial dose (based on pharmacokinetic data) should be 8 mg 1 time / day every other day, it should be taken in the morning for at least one week. After this, patients can take 8 mg 1 time / day for at least 4 weeks. The daily dose should not exceed 16 mg.
Patients with severe impairment of liver function (more than 9 points on the Child-Pugh scale) Reminil В® is not recommended.

Patients with severe renal dysfunction (CC less than 9 mL / min) Reminil В® is not recommended (due to lack of data).
In patients with QC more than 9 ml / min dose of Remineral is not necessary to correct.
If the patient receives strong inhibitors of coenzymes CYP2D6 or CYP3A4, it may be necessary to reduce the dose of Reminil.

SIDE EFFECT

Nausea and vomiting - the most common adverse events in clinical trials - were observed with a dose selection, continued in most cases for less than 1 week and were mostly episodic.
The administration of antiemetics and the provision of sufficient fluid intake are most effective in such cases.
Side effects of Reminil В® in therapeutic doses are given with frequency distribution and organ systems.
The frequency of side effects was classified as follows: very frequent (> 1/10 cases), frequent (> 1/100, <1/10 cases), infrequent (> 1/1000 and <1/100 cases), rare (> 1 / 10000 and <1/1000 cases) and very rare (<1/10000 cases).
From the immune system: infrequently - hypersensitivity.

From the side of metabolism and nutrition: often - a decrease in appetite, anorexia;
infrequent - dehydration (including, in rare cases, serious, leading to kidney failure).
From the mental status: often - depression (very rarely with suicide), hallucinations;
infrequently - visual and auditory hallucinations.
From the nervous system: chasto - dizziness, headache, tremor, fainting, blocking, drowsiness;
infrequently - perversion of taste; hypersomnia; paresthesia.
From the side of the organ of vision: infrequently - blurred vision.

From the side of the organ of hearing and the labyrinth: very rarely - noise in the ears.

From the cardiovascular system: often - bradycardia;
infrequently - AV-blockade of the first degree, palpitation, supraventricular extrasystole, hot flashes, lowering blood pressure.
From the digestive tract: very often - nausea, vomiting;
often - diarrhea, abdominal pain, indigestion, gastrointestinal discomfort.
From the liver and biliary tract: very rarely - hepatitis.

From the skin and subcutaneous tissues: often - increased sweating.

From the osteomuscular system and connective tissue: often - muscle spasms;
infrequently - muscle weakness.
Common violations: often - fatigue, weakness.

Disorders of measurements and laboratory indicators: often - weight loss;
very rarely - an increase in the activity of liver enzymes.
In the placebo-controlled clinical studies of Reminil В® , the following undesirable effects were very rarely observed: hematuria, urinary tract infections, rhinitis, anemia, and increased blood pressure.

The incidence of these events in the placebo group is comparable to the frequency of occurrence in the group taking the drug Reminil В®, and thus the relationship of these phenomena with the use of Reminil В® is not proven.

CONTRAINDICATIONS

- renal failure of severe degree (CC <9 ml / min);

severe hepatic impairment;

- Hypersensitivity to galantamine hydrobromide or to any auxiliary substance that is part of this drug.

With caution should be used in general anesthesia, in patients with bronchial asthma, COPD, with bradycardia, AV-blockade, SSSU, unstable angina;
with concomitant therapy with drugs slowing heart rate (digoxin, beta-adrenoblockers), with peptic ulcer of stomach and duodenum, gastrointestinal obstruction, period after surgery on the gastrointestinal tract, epilepsy, obstruction of the urinary tract, in the period after the operation on the bladder.
PREGNANCY AND LACTATION

Studies of the safety of the use of Reminil В® during pregnancy have not been conducted.
Reminil В® can be prescribed during pregnancy only in those cases when the potential benefit of treatment for the mother exceeds the possible risk to the fetus.
It is not known whether galantamine with human milk is excreted in humans.
Women who receive Reminil В® should abstain from breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER

The drug is contraindicated for use in severe disorders of kidney function (QC less than 9 ml / min).

APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

The drug is contraindicated for use in severe violations of the liver (more than 9 points on the scale Child-Pugh).

APPLICATION FOR CHILDREN

Reminil В® is not recommended for the treatment of children.
Data on the efficacy and safety of Reminil in pediatric practice are not available.
SPECIAL INSTRUCTIONS

Use of Reminil in other types of dementia or other memory disorders

The positive effects of Reminil in patients with other types of dementia and other types of memory impairment have not been demonstrated.

Patients with Alzheimer's disease lose weight.
Treatment with acetylcholinesterase inhibitors, including galantamine, is accompanied by a decrease in the body weight of such patients, and therefore during the treatment it is necessary to monitor changes in body weight.
Like other cholinomimetics, Reminil В® should be used with caution in the following conditions:

Cardiovascular disease: due to its pharmacological action holinomimetiki can cause vagotonic effects from the heart (for example, bradycardia).
The consequences of such effects may be most serious in patients with SSSU and with other supraventricular conduction disorders, as well as in patients who simultaneously receive drugs that reduce heart rate such as digoxin or beta-blockers. Treatment with remineral was accompanied by a faint and rarely expressed bradycardia. Use with caution in unstable angina.
Gastrointestinal diseases: in patients with an increased risk of developing a peptic ulcer, for example having an anamnesis in history or predisposed to it, it is necessary to monitor the relevant symptoms.
It should be noted, however, that clinical trials did not reveal an increase in patients receiving Reminil В® , compared with patients who received placebo, the incidence of peptic ulcers and gastrointestinal bleeding. Reminil В® is not recommended for patients with gastrointestinal obstruction, as well as for patients who have recently had an operation on the digestive system.
Neurological diseases: it is believed that holinomimetiki have a certain ability to cause generalized convulsions.
It should be remembered, however, that convulsive activity may be a manifestation of Alzheimer's disease itself. In clinical trials, there was no increase in the frequency of seizures in patients taking Reminil В® , compared with patients receiving placebo.
Pulmonary diseases: due to cholinomimetic activity Reminil В® should be used with caution in patients suffering from severe bronchial asthma or obstructive pulmonary disease.

Genitourinary diseases: Reminyl В® is not recommended in patients with obstruction of the urinary tract of patients, and patients who have recently undergone surgery on the bladder.
Safety in patients with mild cognitive impairment
Reminyl В® is not intended for patients with mild cognitive impairment, ie for patients with isolated memory impairment, higher than the expected level for their age and education, but does not meet the criteria for Alzheimer's disease.
Impact on the ability to drive vehicles and manage mechanisms

Alzheimer's disease may impair the ability to drive a car and operate machinery. In addition, treatment with the drug Reminyl В® , like other cholinomimetics, can cause drowsiness and dizziness, which have a negative impact on driving and operating machinery, particularly in the first weeks after starting treatment with this drug.
OVERDOSE

Symptoms. It is assumed that the objective and subjective symptoms of severe overdosing of galantamine are similar to those of similar symptoms in overdose of other cholinomimetics. Mostly observed toxic effects from central nervous system, the parasympathetic nervous system and neuromuscular synapses. In addition to muscle weakness or fasciculations may experience some or all of the symptoms of cholinergic crisis: severe nausea, vomiting, abdominal cramping, salivation, lacrimation, incontinence, severe sweating, bradycardia, decreased blood pressure, collapse and convulsions. Severe muscle weakness in conjunction with tracheal mucosa hypersecretion and bronchospasm may cause blockade of lethal respiratory tract.
The communications received at the control post-marketing, describes the development of bidirectionally-spindle ventricular tachycardia, lengthening QT interval, ventricular tachycardia with transient loss of consciousness with a random reception Reminyl 32 mg per day.
Treatment.
As with any other drug overdose, it is necessary to carry out the usual supportive measures. In severe cases, as a general antidote can be used anticholinergic drugs such as atropine. Initially, advisable to introduce 0.5-1 mg / in the frequency and magnitude of subsequent doses depend on the dynamics of the patient's clinical condition.
Overdose treatment strategies are constantly being improved, so contact the nearest Poison Centers to obtain the latest recommendations concerning the treatment of galantamine overdose.
DRUG INTERACTION

Because of his mechanism of action of galantamine should not be used concomitantly with other holinomimetikami. Galanthamine is an antagonist anticholinergics. Like other cholinomimetics, galantamine can join pharmacodynamic interactions with drugs which reduce heart rate (e.g., digoxin and beta blockers). As cholinomimetics, galantamine may enhance the blockage of neuromuscular conduction type depolarization during anesthesia (e.g., when used as a peripheral muscle relaxant suxamethonium bromide).
Pharmacokinetic interactions
The elimination of galantamine involving different metabolic pathways and renal excretion. In vitro studies have shown that the main role in the metabolism of galantamine play coenzymes CYP2D6 and CYP3A4.
Inhibition of gastric acid secretion does not disturb the absorption of galantamine.
Drugs that are potent inhibitors of CYP2D6 coenzymes and CYP3A4, can increase AUC galanthamine. Pharmacokinetic studies with multiple drug administration showed that galanthamine AUC increased by 30% and 40 while applying it accordingly ketoconazole and paroxetine.
With simultaneous use of erythromycin, which is also an inhibitor of the enzyme CYP3A4, AUC galanthamine increases only by about 10%.
Pharmacokinetic studies in patients with Alzheimer's disease have shown that the clearance of galantamine decreased by about 25-33%, while the application of this preparation with such known inhibitors of CYP2D6 enzyme such as amitriptyline, fluoxetine, fluvoxamine, paroxetine and quinidine.
Thus, early treatment potent inhibitor of CYP2D6 and CYP3A4 enzymes may increase the frequency of cholinergic adverse events, primarily nausea and emesis. In these situations, depending on the particular patient tolerability of therapy, may be needed to reduce the maintenance dose of galantamine.
Receptor antagonist N-methyl-D-aspartate (NMDA) memantine in a dose of 10 mg / day for 2 days, then 10 mg of 2 times / day for 12 days did not affect the pharmacokinetics of galanthamine in the equilibrium state after a dose of 16 mg / day .
The influence of galanthamine on the metabolism of other drugs
Therapeutic doses of galantamine (12 mg, 2 times / day) had no effect on the kinetics of digoxin and warfarin. Galantamine did not affect the increased prothrombin time induced by warfarin.
Studies in vitro have shown that galanthamine has a very weak ability to inhibit the major human cytochrome P450.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

The drug should be stored out of the reach of children at a temperature of 15 В° to 30 В° C.
Shelf life - 2 years. Do not use after the expiry date printed on the package.
Alphabetical index of medicines:
A  B  V  G  D  E  J
Z  I  Y  K  L  M  N
O  P  R  S  T  U  F
H  C  CH  SH  E  U  Y

Privacy policy:
Copyright 2009 - 2017. Universal reference book of medicines. All rights reserved.
When using site materials, an active hyperlink is required!