Rasagiline Medisorb (Tablets) Instructions for Use

Marketing Authorization Holder

Medisorb, JSC (Russia)

ATC Code

N04BD02 (Rasagiline)

Active Substance

Rasagiline (Rec.INN registered by WHO)

Dosage Form

Rasagiline Medisorb

Tablets 1 mg: 7, 10, 14, 20, 21, 28, 30, 35, 40, 42, 49, 50, 56, 60, 63, 70, 80, 84, 90, 98, 100, 112 or 126 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, round, flat-cylindrical, with a bevel on both sides.

Excipients: mannitol, potato starch, pregelatinized starch, talc, magnesium stearate.

7 pcs. – contour cell packaging (1) – cardboard packs.
7 pcs. – contour cell packaging (2) – cardboard packs.
7 pcs. – contour cell packaging (3) – cardboard packs.
7 pcs. – contour cell packaging (4) – cardboard packs.
7 pcs. – contour cell packaging (5) – cardboard packs.
7 pcs. – contour cell packaging (6) – cardboard packs.
7 pcs. – contour cell packaging (7) – cardboard packs.
7 pcs. – contour cell packaging (8) – cardboard packs.
7 pcs. – contour cell packaging (9) – cardboard packs.
7 pcs. – contour cell packaging (10) – cardboard packs.
10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (5) – cardboard packs.
10 pcs. – contour cell packaging (6) – cardboard packs.
10 pcs. – contour cell packaging (7) – cardboard packs.
10 pcs. – contour cell packaging (8) – cardboard packs.
10 pcs. – contour cell packaging (9) – cardboard packs.
10 pcs. – contour cell packaging (10) – cardboard packs.
14 pcs. – contour cell packaging (1) – cardboard packs.
14 pcs. – contour cell packaging (2) – cardboard packs.
14 pcs. – contour cell packaging (3) – cardboard packs.
14 pcs. – contour cell packaging (4) – cardboard packs.
14 pcs. – contour cell packaging (5) – cardboard packs.
14 pcs. – contour cell packaging (6) – cardboard packs.
14 pcs. – contour cell packaging (7) – cardboard packs.
14 pcs. – contour cell packaging (8) – cardboard packs.
14 pcs. – contour cell packaging (9) – cardboard packs.
14 pcs. – contour cell packaging (10) – cardboard packs.
30 pcs. – polymer jars (1) – cardboard packs.
50 pcs. – polymer jars (1) – cardboard packs.
100 pcs. – polymer jars (1) – cardboard packs.

Clinical-Pharmacological Group

Antiparkinsonian drug – selective MAO type B inhibitor

Pharmacotherapeutic Group

Antiparkinsonian drugs; dopaminergic agents; monoamine oxidase type B inhibitors

Pharmacological Action

Antiparkinsonian agent, a selective irreversible inhibitor of MAO type B. Rasagiline is 30-80 times more active against MAO type B compared to MAO type A.

As a result of the inhibitory effect on MAO type B in the CNS, the level of dopamine increases, and the formation of toxic free radicals, the excess of which is observed in Parkinson’s disease, decreases. Rasagiline also has a neuroprotective effect.

Unlike non-selective MAO inhibitors, Rasagiline in therapeutic doses does not block the metabolism of dietary biogenic amines (e.g., tyramine), and therefore does not cause tyramine-induced hypertensive syndrome (“cheese” effect).

Pharmacokinetics

Rasagiline is rapidly absorbed after oral administration, C_max in plasma is reached within 0.5 hours. Absolute bioavailability after a single dose is about 36%. Food does not affect the time to reach C_max of rasagiline in the blood, but when consuming fatty foods, C_max and AUC decrease by 60% and 20%, respectively.

The pharmacokinetics of rasagiline is linear in the dose range of 0.5-2 mg.

Plasma protein binding ranges from 60% to 70%.

Rasagiline is almost completely metabolized in the liver. Biotransformation occurs through N-dealkylation and/or hydroxylation to form the main biologically low-active metabolite – 1-aminoindan, as well as two other metabolites – 3-hydroxy-N-propargyl-1-aminoindan and 3-hydroxy-1-aminoindan. Metabolism occurs with the participation of the CYP1A2 isoenzyme.

Rasagiline is excreted mainly by the kidneys (more than 60%) and to a lesser extent through the intestines (more than 20%). Less than 1% of the dose is excreted unchanged. T_1/2 is 0.6-2 hours.

The pharmacokinetic parameters of rasagiline practically do not change in patients with mild to moderate renal failure.

In mild hepatic insufficiency, an increase in AUC and C_max parameters by 80% and 38% may be observed, and in patients with moderate liver dysfunction, these parameters reach more than 500% and 80%, respectively.

Indications

Treatment of Parkinson’s disease (as monotherapy or in combination with levodopa).

ICD codes

Dosage Regimen

Take orally once daily, with or without food.

For monotherapy in early Parkinson’s disease, the recommended dose is 1 mg once daily.

For adjunctive therapy to levodopa, the recommended dose is 0.5 mg once daily.

If a sufficient clinical response is not achieved with the 0.5 mg dose, the dose may be increased to 1 mg once daily.

Administer the total daily dose at the same time each day to maintain consistent plasma levels.

Do not exceed the maximum recommended daily dose of 1 mg.

In patients with mild hepatic impairment (Child-Pugh score 5-6), initiate therapy at a dose of 0.5 mg once daily.

Do not use in patients with moderate or severe hepatic impairment (Child-Pugh score 7 or greater).

No dosage adjustment is required for patients with renal impairment or in the elderly.

Swallow the tablet whole with a glass of water; do not crush or chew.

Continue treatment long-term as directed by a physician.

Adverse Reactions

With rasagiline monotherapy

Nervous system disorders: headache, depression, dizziness, anorexia, convulsions, hallucinations; rarely – cerebrovascular accident.

Digestive system disorders: decreased appetite, dyspeptic phenomena.

Musculoskeletal system disorders: arthralgia, arthritis, neck pain.

Dermatological reactions: vesiculobullous rash, contact dermatitis; rarely – skin carcinoma.

Cardiovascular system disorders: angina pectoris; rarely – myocardial infarction.

Other: flu-like syndrome, fever, leukopenia, rhinitis, general weakness, conjunctivitis, acute urinary system disorders, allergic reactions.

When combined with levodopa

Nervous system disorders: dyskinesia, muscle dystonia, anorexia, unusual dreams, ataxia, hallucinations; rarely – cerebrovascular accident, confusion.

Digestive system disorders: constipation, vomiting, abdominal pain, dry mouth.

Musculoskeletal system disorders: arthralgia, neck pain, tenosynovitis.

Dermatological reactions: rash; rarely – skin melanoma.

Cardiovascular system disorders: postural hypotension; rarely – angina pectoris.

Other: accidental falls, weight loss, allergic reactions.

Contraindications

Moderate or severe hepatic insufficiency (Child-Pugh class B and C); pheochromocytoma; concomitant therapy with pethidine or other MAO inhibitors (the interval between discontinuation of rasagiline and initiation of therapy with these drugs should be at least 14 days); co-administration with sympathomimetics (including drugs containing them), other decongestants, dextromethorphan, as well as with medicinal products containing them; children and adolescents under 18 years of age; pregnancy; lactation period (risk of inhibition of milk production due to inhibition of prolactin formation); hypersensitivity to rasagiline.

Use with caution in mild hepatic insufficiency, concomitantly with selective serotonin reuptake inhibitors, tricyclic and tetracyclic antidepressants, active inhibitors of the CYP1A2 isoenzyme.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and during lactation (breastfeeding).

Special Precautions

The use of rasagiline at the recommended therapeutic dose does not cause tyramine syndrome (“cheese” effect), which allows patients to use foods containing significant amounts of tyramine (cheeses, chocolate) in their diet without restrictions.

There is evidence that Parkinson’s disease, and not the use of any drug, including rasagiline, is a risk factor for the development of skin cancer, in particular melanoma. The patient should be warned about the need to consult a doctor if any pathological changes in the skin appear.

It should be borne in mind that symptoms such as hallucinations and confusion that appear during treatment with rasagiline can be interpreted both as a manifestation of Parkinson’s disease and as adverse reactions to rasagiline.

Influence on the ability to drive vehicles and mechanisms

Given the possibility of significant side effects from the central nervous system, during treatment with rasagiline, caution should be exercised when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Due to the fact that the mechanism of action of rasagiline is associated with inhibition of MAO, it should not be used simultaneously with other inhibitors of this enzyme due to the risk of developing a hypertensive crisis.

With the simultaneous use of rasagiline with serotonin reuptake inhibitors (including fluoxetine, fluvoxamine), tricyclic and tetracyclic antidepressants, MAO inhibitors, the development of serotonin syndrome is possible, manifested in confusion of consciousness, hypomanic state, motor restlessness, chills, tremor, diarrhea. It is not recommended to prescribe such drugs to patients receiving Rasagiline. If combination therapy is necessary, caution is required.

It is also not recommended to use rasagiline concomitantly with sympathomimetic drugs, including ephedrine, pseudoephedrine, contained in drugs for the treatment of rhinitis or colds. In addition, the use of rasagiline with dextromethorphan and combination products containing it is not recommended.

Since the CYP1A2 isoenzyme is involved in the metabolism of rasagiline, active inhibitors of this enzyme (for example, ciprofloxacin) may increase the concentration of rasagiline in plasma, so caution is required with such combinations.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.