Galantamine Canon (Tablets) Instructions for Use

Marketing Authorization Holder

Canonpharma Production, CJS (Russia)

ATC Code

N06DA04 (Galantamine)

Active Substance

Galantamine (Rec.INN registered by WHO)

Dosage Forms

	Galantamine Canon	Film-coated tablets, 4 mg: 7, 10, 14, 15, 28, 30, 56, 60 or 90 pcs.
		Film-coated tablets, 8 mg: 7, 10, 14, 15, 28, 30, 56, 60 or 90 pcs.
		Film-coated tablets, 12 mg: 7, 10, 14, 15, 28, 30, 56, 60 or 90 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – contour cell packaging (1) – cardboard packs.
14 pcs. – contour cell packaging (2) – cardboard packs.
14 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (6) – cardboard packs.
15 pcs. – contour cell packaging (1) – cardboard packs.

Clinical-Pharmacological Group

Selective inhibitor of acetylcholinesterase in the brain. A drug for the treatment of Alzheimer’s disease

Pharmacotherapeutic Group

Psychoanaleptics; agents for the treatment of dementia; anticholinesterase agents

Pharmacological Action

A selective, competitive, and reversible inhibitor of acetylcholinesterase. It stimulates nicotinic receptors and increases the sensitivity of the postsynaptic membrane to acetylcholine.

It facilitates the transmission of excitation in the neuromuscular synapse and restores neuromuscular conduction in cases of its blockade by non-depolarizing muscle relaxants. It increases the tone of smooth muscles, enhances the secretion of digestive and sweat glands, and causes miosis.

By increasing the activity of the cholinergic system, Galantamine improves cognitive functions in patients with dementia of the Alzheimer’s type, but does not affect the progression of the disease itself.

Pharmacokinetics

After oral administration, it is rapidly and completely absorbed in the gastrointestinal tract. The absolute bioavailability is high – up to 90%. Therapeutic concentration is achieved within 30 minutes after administration. C_max after an 8 mg dose is observed at the 2nd hour and is 1.2 mg/ml.

T_1/2 is 5 hours. After multiple doses, a steady-state concentration is established.

It binds to blood proteins to a small extent. It easily passes through the blood-brain barrier. It is metabolized to a small extent (about 10%) in the liver by demethylation.

It is excreted (unchanged and as metabolites), mainly in the urine (up to 74%). Renal clearance is approximately 100 ml/min.

In patients with Alzheimer’s disease, the plasma concentration of galantamine may be increased. In moderate and severe impairment of liver and kidney function, plasma concentrations of galantamine are increased.

Indications

• Mild to moderate dementia of the Alzheimer’s type;
• Poliomyelitis (immediately after the cessation of the febrile period, as well as in the recovery period and the period of residual effects);
• Myasthenia gravis, progressive muscular dystrophy, infantile cerebral palsy, neuritis, radiculitis, myopathy.

ICD codes

Dosage Regimen

Orally, with meals, with water.

Adults

The daily dose is 8-32 mg, divided into 2-4 doses.

For myasthenia gravis, the daily dose is divided into 3 doses.

For Alzheimer’s disease, it is recommended to start treatment with 4 mg tablets twice daily. Over 4 weeks, the daily dose can be gradually increased to 16 mg – one 8 mg tablet twice daily – in the morning and evening. During treatment with the drug, it is necessary to ensure adequate fluid intake. If treatment needs to be discontinued, treatment should be resumed at the lowest dose and gradually increased.

Patients with moderately impaired liver and kidney function

The initial dose is 4 mg once daily, taken in the morning, for at least 1 week, after which the dose is increased to 4 mg twice daily and taken for 4 weeks.

The total daily dose should not exceed 12 mg.

Children (from 9 years old)

Treatment of poliomyelitis, infantile cerebral palsy

from 9 to 11 years – daily dose – 4-12 mg, divided into 2-3 doses;

from 12 to 15 years – daily dose is 4-16 mg, divided into 2-4 doses.

Adverse Reactions

From the cardiovascular system decrease or increase in blood pressure, orthostatic collapse, heart failure, edema, atrioventricular block, atrial flutter or fibrillation, QT interval prolongation, ventricular and supraventricular tachycardia, supraventricular extrasystole, “hot flashes”, bradycardia, myocardial ischemia or infarction.

From the digestive system abdominal distension, dyspepsia, gastrointestinal discomfort, anorexia, diarrhea, abdominal pain, nausea, vomiting, gastritis, dysphagia, dry mouth, increased salivation, diverticulitis, gastroenteritis, duodenitis, hepatitis, perforation of the esophageal mucosa, bleeding from the upper and lower gastrointestinal tract.

From the musculoskeletal system muscle spasms, muscle weakness, fever.

Laboratory parameters increased activity of liver enzymes, anemia, hypokalemia, increased blood sugar or alkaline phosphatase levels.

Hematological thrombocytopenia, purpura.

From the urinary system urinary incontinence, hematuria, frequent urination, urinary tract infections, urinary retention, calculi, renal colic.

From the nervous system often tremor, syncope, lethargy, taste perversion, visual and auditory hallucinations, behavioral reactions, including agitation/aggression; transient cerebrovascular accident or stroke; headache, dizziness, seizures, muscle spasms, paresthesia, ataxia, hypo- or hyperkinesis, apraxia, aphasia, anorexia, drowsiness, insomnia.

From the senses rhinitis, nosebleed, visual disturbances, accommodation spasm, infrequently – tinnitus.

From the psyche depression (very rarely – with suicide), apathy, paranoid reactions, increased libido, delirium.

General chest pain, increased sweating, weight loss, feeling of tiredness, dehydration (in rare cases – with the development of renal failure), bronchospasm.

Contraindications

• Bronchial asthma;
• Bradycardia;
• Atrioventricular block;
• Arterial hypertension;
• Angina pectoris;
• Chronic heart failure;
• Epilepsy;
• Hyperkinesis;
• Severe renal (creatinine clearance – less than 9 ml/min) and hepatic (more than 9 points on the Child-Pugh scale) impairments;
• Mechanical intestinal obstruction;
• Chronic obstructive pulmonary disease;
• Obstructive diseases or recent surgical intervention on the gastrointestinal tract;
• Obstructive diseases or recent surgical treatment of the urinary tract or prostate;
• Children under 9 years of age;
• Pregnancy and lactation;
• Hypersensitivity to any component of the drug.

With caution

• Mild and moderate impairments of renal or liver function;
• Sick sinus syndrome and other supraventricular conduction disorders;
• Concomitant use of drugs that slow the heart rate (digoxin, beta-blockers);
• General anesthesia;
• Peptic ulcer of the stomach and duodenum, increased risk of erosive-ulcerative lesions of the gastrointestinal tract.

Use in Pregnancy and Lactation

Contraindicated during pregnancy. Breastfeeding should be discontinued during treatment.

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment. Use with caution in mild to moderate hepatic impairment.

Use in Renal Impairment

Contraindicated in severe renal impairment. Use with caution in mild to moderate renal impairment.

Pediatric Use

Contraindicated in children under 9 years of age.

Special Precautions

Treatment with acetylcholinesterase inhibitors is accompanied by weight loss. This is especially important to consider when treating patients with Alzheimer’s disease, who usually experience weight loss. Therefore, it is necessary to monitor the body weight of such patients.

During treatment, it is necessary to ensure adequate fluid intake. Like other cholinomimetics, the drug can cause vagotonic effects from the cardiovascular system (including bradycardia), which must be taken into account in patients with sick sinus syndrome and other conduction disorders, as well as with the simultaneous use of drugs that reduce heart rate (digoxin or beta-blockers).

During treatment with Galantamine, there is a risk of syncope, therefore it is necessary to monitor blood pressure more often, especially when taking the drug in higher doses (40 mg daily dose). To prevent such 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, i.e., with isolated memory impairment exceeding the expected level for their age and education, but not meeting the criteria for Alzheimer’s disease.

Effect on the ability to drive vehicles and machinery

During the treatment period, one should refrain from performing work that requires increased concentration and speed of psychomotor reactions, including driving a car.

Overdose

Symptoms depression of consciousness (up to coma), convulsions, increased severity of side effects, pronounced muscle weakness combined with hypersecretion of the glands of the tracheal mucosa and bronchospasm can lead to fatal airway obstruction.

Treatment gastric lavage, symptomatic therapy. As an antidote – intravenous administration of atropine in doses of 0.5-1 mg. 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 antagonist of opioids in terms of action on the respiratory center. It exhibits pharmacodynamic antagonism to m-cholinolytics (atropine, homatropine methylbromide, etc.), ganglion blockers, non-depolarizing muscle relaxants, quinidine, procainamide.

Aminoglycoside antibiotics may reduce the therapeutic effect of galantamine. Galantamine enhances neuromuscular blockade during general anesthesia (including when suxamethonium is used as a peripheral muscle relaxant). Drugs that reduce heart rate (digoxin, beta-blockers) increase the risk of worsening bradycardia. Cimetidine may increase the bioavailability of galantamine.

All drugs that inhibit the cytochrome P450 system isoenzymes (CYP2D6 and CYP3A4) may increase plasma concentrations of galantamine when used concomitantly, which may increase the frequency of cholinergic side effects (mainly nausea and vomiting). In this case, depending on the tolerability of therapy by a particular patient, it may be necessary to reduce the maintenance dose of galantamine.

Inhibitors of the CYP2D6 isoenzyme (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, zidovudine, erythromycin. It enhances the depressant effect on the central nervous system of ethanol and sedatives.

Storage Conditions

In a dry place, protected from light, at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 2 years. Do not use after the expiration date.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.