NIVALIN (Pills)

Active material: Galantamin
When ATH: N06DA04
CCF: Cholinesterase inhibitor
ICD-10 codes (testimony): A80, F00, G30, G70.2, G71.0, G80, M54.1, M79.2
When CSF: 02.11.02.01
Manufacturer: SOPHARMA AD (Bulgaria)

Pharmaceutical form, composition and packaging

Pills white, flat, round, chamfered on both sides and notched on one side.

Excipients: lactose monohydrate, wheat starch, talc, magnesium stearate, calcium hydrogen phosphate dihydrate, microcrystalline cellulose (type 101).

10 PC. – blisters (1) – packs cardboard.
20 PC. – blisters (1) – packs cardboard.
20 PC. – blisters (3) – packs cardboard.

Pills white, flat, round, chamfered on both sides and notched on one side.

Excipients: lactose monohydrate, wheat starch, talc, magnesium stearate, microcrystalline cellulose (type 101).

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (2) – packs cardboard.

Pharmacological action

Reversible inhibitor of acetylcholinesterase. Stimulates n-cholinergic receptors and increases the sensitivity of the postsynaptic membrane to acetylcholine. Facilitates the conduction of excitation in the neuromuscular synapse and restores neuromuscular conduction in cases of its blockade by muscle relaxants of a non-depolarizing type of action. Increases the tone of smooth muscles, enhances the secretion of the digestive and sweat glands, causes miosis. By increasing the activity of the cholinergic system, galantamine improves cognition in patients with dementia of the Alzheimer's type, but does not affect the development of the disease itself.

Pharmacokinetics

Absorption

Once inside, quickly and completely absorbed in the gastrointestinal tract. Absolute bioavailability is high – to 90%. Therapeutic concentration is reached through 30 minutes after administration. C_max after administration at a dose 10 mg is reached 2 h and is 1.2 mg / ml.

Distribution

After repeated reception, C is established_ss galantamine. Slightly binds to blood proteins. Easily passes through the BBB.

Metabolism

To a small extent (about 10%) metabolized in the liver by demethylation.

Deduction

T_1/2 – 5 no. Displayed (in unchanged form and as metabolites) mainly in the urine (to 74%). The renal clearance is approximately 100 ml / min.

Pharmacokinetics in special clinical situations

Plasma concentrations of galantamine may be elevated in patients with Alzheimer's disease..

Plasma concentrations of galantamine are increased in moderate to severe hepatic and renal impairment..

Testimony

- mild to moderate dementia of the Alzheimer's type;

— poliomyelitis (immediately after the end of the febrile period, as well as in the recovery period and the period of residual effects);

— myasthenia gravis;

- progressive muscular dystrophy;

- cerebral palsy;

- Neuritis;

— sciatica;

- Myopathy.

Dosage regimen

The drug is prescribed inside, mealtime. The tablets should be taken with water.

Adults drug administered in a daily dose 10-40 mg, razdelennoy of 2-4 admission.

At myasthenia gravis the daily dose is divided into 3 admission.

At Alzheimer treatment is recommended to start 5 mg 2 times / day. Within 4 weeks, the daily dose can be gradually increased to 20 mg (by 10 mg 2 times / day, in the morning and in the evening). During treatment with the drug, it is necessary to ensure the intake of a sufficient amount of liquids.. If you need to stop taking the drug during treatment, then the restoration of treatment should begin with the lowest dose and gradually increase it.

At polio treatment, cerebral palsy children between the ages of 9 to 11 years daily dose is 5-15 mg, razdelennaya of 2-3 admission; in age from 12 to 15 years – 5-20 mg, razdelennaya of 2-4 admission.

To patients with moderate hepatic and renal dysfunction starting dose is 5 mg 1 time / day (morning) for not less than 1 of the week, then – by 5 mg 2 times / day for 4 weeks. The total daily dose should not exceed 15 mg.

Side effect

Cardio-vascular system: reduction or increase in blood pressure, Orthostatic hypotension, heart failure, swelling, AV блокада, flutter or atrial fibrillation, QT prolongation, ventricular and supraventricular tachycardia, supraventricular arrhythmias, tides, bradycardia, ischemia or myocardial infarction.

From the digestive system: abdominal distention, dyspepsia, discomfort in the gastrointestinal tract, anorexia, diarrhea, abdominal pain, nausea, vomiting, gastritis, dysphagia, dry mouth, increased salivation, diverticulitis, gastroenteritis, duodenitis, hepatitis, perforation of the mucous membrane of the esophagus, bleeding from upper and lower gastrointestinal tract, increase in liver enzymes, increase in alkaline phosphatase.

On the part of the musculoskeletal system: muscle spasms, muscular weakness, fever.

From the central and peripheral nervous system: often – tremor, syncope, lethargy, dysgeusia, visual and auditory hallucinations, behavioral responses, including arousal/aggression; transient ischemic attack or stroke; headache, dizziness, convulsions, muscle spasms, paraesthesia, ataxia, Hypo- or hyperkinesis, apraxia, afazija, anorexia, drowsiness, insomnia, depression (very rarely suicidal), apathy, paranoid reaction, increased libido, delirium.

From the senses: rhinitis, nose bleed, visual impairment, cyclospasm; infrequently – noise in ears.

From the urinary system: urinary incontinence, hematuria, frequent urination, urinary tract infection, urinary retention, calculosis, počečnaâ how.

From the hematopoietic system: thrombocytopenia, purpura, anemia.

Laboratory findings: kaliopenia, giperglikemiâ.

Other: chest pain, increased perspiration, weight loss, feeling tired, degidratatsiya (in rare cases with the development of renal failure), bronchospasm.

Contraindications

- Bronchial asthma;

- Bradycardia;

- AV блокада;

- Arterial hypertension;

- Angina;

- Congestive heart failure;

- Epilepsy;

- Hyperkinesis;

- Severe renal insufficiency (CC less than 9 ml / min);

- severe hepatic (more 9 points on the Child-Pugh) infringement;

- Mechanical intestinal obstruction;

- Chronic obstructive pulmonary disease;

- obstructive diseases or recent surgery on the gastrointestinal tract;

- obstructive disease or recent surgical treatment of the urinary tract or prostate;

- Children up to age 9 years;

- Pregnancy;

- Lactation (breast-feeding);

- Hypersensitivity to the drug.

FROM caution the drug should be prescribed for mild to moderate impairment of kidney or liver function, sick sinus syndrome and other disorders of supraventricular conduction, while taking drugs, slowing down the heart rate (Digoxin, beta blockers), general anesthesia, gastric ulcer and duodenal ulcer, increased risk of developing erosive and ulcerative lesions of the gastrointestinal tract, gluten enteropathy (Contains wheat starch), lactase deficiency, galaktozemii, malabsorption syndrome glucose / galactose (the composition of the drug includes lactose).

Pregnancy and lactation

The drug is contraindicated in pregnancy and lactation (breast-feeding).

Cautions

Treatment with acetylcholinesterase inhibitors is accompanied by weight loss. This is especially true when treating patients with Alzheimer's disease., who usually experience weight loss. In this regard, it is necessary to monitor body weight.

During treatment, it is necessary to ensure sufficient fluid intake..

Like other cholinomimetics, the drug can cause vagotonic effects from the cardiovascular system (incl. ʙradikardiju), what to consider in patients with sick sinus syndrome and other conduction disorders, as well as when used simultaneously with drugs, reducing heart rate (digoxin or beta blockers).

When treated with Nivalin^® there is a risk of syncope, in this connection, more frequent monitoring of blood pressure, especially when taking the drug in higher doses (daily dose – 40 mg). To prevent these side effects, it is necessary to carefully select the dose of the drug at the beginning of treatment.

The effectiveness of the drug in patients with other types of dementia and memory impairment has not been established.. The drug is not intended for the treatment of patients with mild cognitive impairment., ie. with isolated memory impairment, higher than expected for their age and education, but not meeting the criteria for Alzheimer's disease.

Effects on ability to drive vehicles and management mechanisms

During the period of treatment, you should refrain from performing work., require high concentration and speed of psychomotor reactions, incl. driving.

Overdose

Symptoms: depression of consciousness (up to coma), convulsions, increased severity of side effects. Severe muscle weakness in combination with hypersecretion of the tracheal mucosa and bronchospasm, can lead to lethal airway blockage.

Treatment: gastric lavage, simptomaticheskaya therapy. Atropine is used as an antidote in doses 0.5-1 mg / in. Subsequent doses of atropine are determined depending on the therapeutic response and the patient's condition..

Drug Interactions

It is not recommended to combine with other cholinomimetics.

It is an opioid antagonist by action on the respiratory center.

Shows pharmacodynamic antagonism to m-anticholinergics (atropine, homatropin methyl bromide), ganglioblocker, non-depolarizing muscle relaxants, quinine, procainamide.

Aminoglycoside antibiotics may reduce the therapeutic effect of galantamine.

Galantamine enhances neuromuscular blockade during general anesthesia (incl. when used as a peripheral muscle relaxant suxamethonium).

Drugs, reducing heart rate (Digoxin, beta-blockers) aggravate bradycardia.

Cimetidine may increase the bioavailability of galantamine. All drugs, which inhibit enzymes and isoenzymes of the cytochrome P450 system (CYP2D6, CYP3A4), may increase plasma concentrations of galantamine when administered concomitantly, resulting in an increased incidence of cholinergic side effects (mainly, nausea and vomiting). In this case, depending on the tolerability of therapy by a particular patient, maintenance dose of galantamine may need to be reduced. CYP2D6 isoenzyme inhibitors (Amitriptyline, fluoxetine, fluvoxamine, paroxetine, quinidine) reduce the clearance of galantamine by 25-30%. For this reason, it is not recommended to prescribe simultaneously with ketoconazole., drywall, Erythromycin.

Enhances the inhibitory effect on the central nervous system of ethanol and sedatives.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

A List. The drug should be stored in a dry, protected from light, inaccessible to children at temperature not exceeding 25 ° C. Shelf life – 5 years.