Alzenorm - instructions for use, doses, side effects, contraindications

Excipients: cellulose microcrystalline 57,18 / 114,36 / 171,54 / 228,72 mg, silicon dioxide colloid 0,12 / 0,24 / 0,36 / 0,48 mg, magnesium stearate 0,3 / 0,6 / 0 , 9 / 1.2 mg;

hard gelatin capsule: lid: gelatin 14,857 / 18,689 / 30,056 / 37,965 mg, titanium dioxide (E-171) 0.203 / 0.384 / 0.243 / 0.307 mg, dye sunset yellow 0.001 / 0.127 / 0.055 / 0.070 mg; dye quinoline yellow 0.140 mg (for 1.5 mg); dye azorubin 0.046 mg (for 4.5 mg) and 0.058 (for 6.0 mg);

body: gelatin 22,285 / 28,034 / 45,084 / 56,068 mg, titanium dioxide (E-171) 0.304 / 0.576 / 0.365 / 1.152 mg, dye sunset yellow 0.001 / 0.190 / 0.083 / 0.380 mg; dye quinoline yellow 0.210 mg (for 1.5 mg); dye azorubin 0.068 (for 4.5 mg); The paint used to inscribe the capsules; red ink (for 1.5 mg, 3.0 mg and 6.0 mg) - shellac, propylene glycol, concentrated ammonia solution, red iron oxide dye (E-172), potassium hydroxide, ethanol, isopropanol,butanol, water; white ink (for 4.5 mg) - shellac, propylene glycol, titanium dioxide (E-171), sodium hydroxide, ethanol, isopropanol, butanol, povidone.

Description:

The contents of the capsules are a powder or a compacted mass from white to almost white.

For 1.5 mg: Hard gelatinous, opaque capsules with a size of 4. The color of the body and the lid is yellow. On the capsule there is an inscription in red ink "RV1.5".

For 3.0 mg: Hard gelatinous, opaque capsules with the size of 3. The color of the body and the lid is orange. On the capsule there is an inscription in red ink "RV 3".

For 4.5 mg: Hard gelatinous, opaque capsules with the size of 1. The color of the body and the cap are red. On the capsule there is an inscription in white ink "RV 4.5".

For 6.0 mg: Hard gelatinous, opaque capsules with the size of 0. The color of the body is orange, the caps are red. On the body there is an inscription in red ink "RV 6".

Pharmacotherapeutic group:Cholinesterase inhibitor

ATX: & nbsp

N.06.D.A Cholinesterase inhibitors

N.06.D.A.03 Rivastigmine

Pharmacodynamics:

Rivastigmine is a selective inhibitor of brain acetyl and butyrylcholinesterase, it slows down the destruction of acetylcholine produced by functionally preserved neurons and improves neurotransmission. Wherein rivastigmine selectively increases the content of acetylcholine in the cerebral cortex and hippocampus, and thus contributes to the improvement of the cholinergic nervous transmission. Rivastigmine can have a positive effect in reducing the cognitive function associated with acetylcholine deficiency, particularly in dementia associated with Alzheimer's disease and Parkinson's disease. In addition, there is evidence that inhibition of cholinesterases may slow the formation of protein amyloid precursor beta fragments participating in amyloidogenesis, and thus slow the formation of amyloid plaques, which are one of the main pathological signs of Alzheimer's disease.

Rivastigmine interacts with the target enzyme to form a covalent bond, which leads to a temporary inactivation of the enzyme. In young healthy men, after taking the drug at a dose of 3 mg, the activity of acetylcholinesterase in the cerebrospinal fluid (CSF) decreases by approximately 40% during the first 1.5 hours. After reaching the maximum inhibitory effect, the enzyme activity returns to the baseline level after about 9 hours.The activity of butyrylcholinesterase in CSF in young healthy volunteers is reversibly reversed and restored to baseline after 3.6 hours. In patients with Alzheimer's disease inhibition of rivastigmine acetylcholinesterase activity in CSF has a dose-dependent character in the studied dose range (namely, to the highest dose of 6 mg 2 times / day). Inhibition of butyrylcholinesterase is also dose-dependent; a dose of 6 mg 2 times / day causes a decrease in the activity of the enzyme by more than 60% compared to the initial one. This effect of rivastigmine persisted for 12 months of therapy (the maximum period studied). A statistically significant correlation was found between the extent to which rivastigmine inhibited both enzymes in CSF and changes in cognitive function in patients with Alzheimer's disease; while the inhibition of butyrylcholinesterase in CSF is significantly and stably correlated with improvements in memory test results, attention and reaction speed. The efficacy of rivastigmine therapy for dementia in Alzheimer's disease and for dementia associated with Parkinson's disease has been shown in patients with mild to moderate dementia (score on a short scale of assessment of mental status - 10-24). Rivastigmine leads to a significant improvement in cognitive functions (attention, memory, speech), functional status and activity in everyday life, as well as to reducing the severity of the disease and the severity of mental and behavioral manifestations.

Pharmacokinetics:

Rivastigmine is rapidly and completely absorbed. The maximum concentration (Cmax) in the plasma is reached after about 1 h. Due to interaction with the target enzyme, with an increase in the dose of rivastigmine, its bioavailability increases by 1.5 times that expected (for a given dose increase). After taking a 3 mg dose, the absolute bioavailability is about 36%. When taken together with food, the absorption slows down (the time of reaching C max is increased by 90 min); Cmax decreases; while the area under the concentration-time curve (AUC) increases by approximately 30%. Rivastigmine binds to plasma proteins to a low degree (approximately 40%). Easily penetrates the blood-brain barrier. The apparent volume of distribution (Vd) is 1.8-2.7 l / kg. Fast and largely metabolized (T1 / 2 from the plasma is about 1 hour), mainly by hydrolysis with cholinesterase to form a decarbamylated metabolite.In vitro, this metabolite has a minimal ability to inhibit acetylcholinesterase (less than 10%). According to the data obtained in vitro and in experimental studies, the main isoenzymes of cytochrome P450 are involved in the metabolism of rivastigmine to a minimal extent. It is excreted mainly by kidneys in the form of metabolites; in the unchanged form in urine is not found out. After 24 hours after taking more than 90% of the dose. With feces less than 1% of the dose is excreted. In patients with Alzheimer's disease, no cumulation of rivastigmine or its decarbamated metabolite is noted.

In elderly patients

Although the bioavailability of rivastigmine in elderly patients is higher than that of healthy young volunteers, nevertheless, in patients with Alzheimer's disease aged 50 to 92 years, clinical studies have not revealed changes in bioavailability associated with age.

In patients with impaired liver function

In individuals with a slight or moderate impairment of liver function, compared with healthy volunteers, Cmax rivastigmine was almost 60% higher, and the AUC value was almost twice that.

In patients with impaired renal function

In individuals with moderate renal impairment compared to healthy volunteers, the values of C max and AUC of rivastigmine were twice as high, in individuals with severe renal dysfunction the values of Cmax and AUC did not change.

Indications:

Weak and moderately severe dementia of the Alzheimer's type.

Weakly and moderately expressed dementia in Parkinson's disease.

Contraindications:Hypersensitivity to the active ingredient, other carbamate derivatives, or to any other component of the drug, severe hepatic insufficiency, lactation period, children under 18 years of age.

Carefully:Stomach and duodenal ulcer, sinus node weakness syndrome, conduction disorders (sinoatrial and atrioventricular), bronchial asthma and chronic obstructive pulmonary disease (history), urinary tract obstruction (history), convulsive syndrome (history), simultaneous administration of other holinomimeticheskih medicines, pregnancy.

Pregnancy and lactation:

The safety of rivastigmine during pregnancy in humans has not been established so far, therefore, the drug can be administered during pregnancy only in those cases when the expected success of treatment exceeds the potential risk for the fetus.Experimental studies have shown that rivastigmine does not have teratogenic properties.

It is not known whether rivastigmine with breast milk. Therefore, during the use of the drug should be abandoned breastfeeding.

Dosing and Administration:

Inside, with meals, 2 times a day. Capsule must be swallowed completely, without violating its integrity.

The initial dose for adults is 1.5 mg per reception.

With good tolerability (no earlier than 2 weeks), the dose can be increased to 3 mg and then to 4.5-6 mg twice a day.

The maintenance dose is 3-6 mg twice a day.

The maximum daily dose is 12 mg.

If the drug was interrupted for several days, the treatment should be resumed from the initial dose of 1.5 mg 2 times a day, gradually increasing the dose.

In patients with impaired renal and hepatic function, dose adjustment is not required.

Side effects:

Side effects are classified according to the following frequency: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%, including isolated cases.

Infections: very rarely - urinary tract infections.

From the nervous system: very often - dizziness, often - agitation, confusion, headache, drowsiness, tremor; infrequently - insomnia, depression, fainting; rarely convulsions; very rarely - hallucinations.

From the cardiovascular system: rarely - angina pectoris; very rarely, a-bradycardia, atrio-ventricular block, atrial fibrillation, tachycardia, marked increase in blood pressure.

From the digestive system: very often - nausea, vomiting, diarrhea, anorexia; often - dyspepsia and abdominal pain; rarely - stomach ulcers and 12 duodenal ulcers; very rarely - bleeding from the gastrointestinal tract, pancreatitis (slightly pronounced), isolated cases of severe vomiting associated with rupture of the esophagus.

From the skin: often - increased sweating; rarely - a rash.

Other: often - increased fatigue, asthenia, general malaise, weight loss, infrequent - accidental falls.

Overdose:

Symptoms: nausea, vomiting, diarrhea, marked increase in blood pressure, hallucinations. Given the vagotonic effect of cholinesterase inhibitors on the heart rate, bradycardia and / or syncope can not be ruled out.In one case, 46 mg of the drug was taken; after a conservative treatment at 24 h, complete recovery was observed.

Treatment: since the half-life of rivastigmine from the plasma is about 1 hour, and the duration of inhibition of acetylcholinesterase is about 9 hours, in cases of asymptomatic overdose it is recommended not to apply rivastigmine within the next 24 hours. If an overdose is accompanied by severe nausea and vomiting, consideration should be given to the use of anti-emetics. If necessary, conduct symptomatic therapy. If there is a significant overdose, atropine sulfate can be used, the initial dose of which is 0.03 mg / kg intravenously; the subsequent dosing depends on the clinical effect. Scopolamine is not recommended as an antidote.

Interaction:

Rivastigmine is metabolized predominantly by hydrolysis with the participation of esterases. Metabolism of the drug with the participation of the main isoenzymes of cytochrome P450 occurs to a minimum. Therefore, it is not necessary to expect pharmacokinetic interactions with other drugs metabolized with the participation of these enzymes.

In healthy volunteers, there was no pharmacokinetic interaction between rivastigmine and digoxin, warfarin, diazepam, or fluoxetine. The increase in prothrombin time caused by warfarin in the appointment of rivastigmine did not change. With simultaneous application of rivastigmine and digoxin, there was no adverse effect on intracardiac conductivity.

The simultaneous use of rivastigmine with such commonly used drugs as antacids, antiemetics, hypoglycemic agents, central antihypertensives, beta-blockers, slow calcium channel blockers, drugs that have a positive inotropic effect, antianginal drugs, nonsteroidal anti-inflammatory drugs, estrogens, analgesics, benzodiazepines and antihistamines, was not accompanied by any changes in the kinetics of rivastigmine or by an increase risk of adverse events. Rivastigmine, as an inhibitor of cholinesterase, can enhance the effect of depolarizing muscle relaxants (muscle relaxants succinylcholine type) during anesthesia.

Rivastigmine should not be used concomitantly with cholinomimetic drugs, but with simultaneous administration with anticholinergic drugs, consideration should be given to the multidirectionality of their action.

Special instructions:

Cholinergic stimulation can increase the secretion of hydrochloric acid in the stomach.

During pregnancy should be used only in those cases when the expected benefit of treatment exceeds the potential risk to the fetus.

The severity of nausea and vomiting, usually observed during the initial treatment period and / or during the increased dose of rivastigmine, can be reduced by lowering the dose of rivastinamine.

In patients with Alzheimer's disease, body weight may decrease. During treatment with rivastigmine, the patient's body weight should be monitored.

As well as in the case of other cholinergic drugs, rivastigmine can cause an increase in the secretion of gastric juice. The drug should be used with caution in patients with chronic ulcers of the stomach or duodenum, as well as patients who are predisposed to these diseases.

Cholinesterase inhibitors should be used with caution in patients with bronchial asthma or with other ailments of the respiratory system in the anamnesis. Cholinomimetic drugs can provoke, or exacerbate obstruction of the urinary tract and convulsive syndrome. The drug should be used with caution in patients with a predisposition to these diseases. The use of rivastigmine in patients with severe dementia in Alzheimer's disease and Parkinson's disease, in other types of dementia and other types of memory impairment (for example, age-related impairments of cognitive functions) has not been investigated.

As well as other cholinomimetic drugs, rivastigmine may enhance or cause a disruption in coordination. Increased motor fluctuations (including slow motion, dyskinesia, gait disturbance) and increased tremor were observed in patients with dementia in Parkinson's disease. In severe cases, these circumstances may require discontinuation of treatment with rivastigmine.

Effect on the ability to drive transp. cf. and fur:When using the Alzenorm, especially at the beginning of treatment and when changing the dose of the drug,it is possible to develop adverse reactions from the nervous system, which reduce the attention and speed of psychomotor reactions. The ability of a patient with dementia who takes Alzensorm, drive vehicles and / or control mechanisms should be evaluated regularly by the attending physician.

Form release / dosage:Capsules 1.5 mg, 3.0 mg, 4.5 mg, 6.0 mg.

Packaging:

For 14 capsules in a blister of PVC / aluminum foil.

For 2, 4 or 8 blisters together with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-009012/10

Date of registration:31.08.2010 / 18.05.2012

Expiration Date:Unlimited

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Operations Poland, Sp. z o.o. Poland

Representation: & nbspTeva Teva Israel

Information update date: & nbsp27.07.2017

Illustrated instructions

Instructions

Alzenorm (Alcenorm)