AZILECT- rasagiline mesylate tablet
DESCRIPTION
AZILECT? tablets contain rasagiline (as the mesylate), propargylamine-based drug indicated for the treatment of idiopathic Parkinson?s disease. It is designated chemically as: 1H-Inden-1-amine, 2, 3-dihydro-N-2-propynyl-, (1R)-, methanesulfonate. The empirical formula of rasagiline mesylate is (C12 H13 N)CH4 SO3 and its molecular weight is 267.34.
Rasagiline mesylate is white to off-white powder, freely soluble in water or ethanol and sparingly soluble in isopropanol. Each AZILECT tablet for oral administration contains rasagiline mesylate equivalent to 0.5 mg or mg of rasagiline base.
Each AZILECT tablet also contains the following inactive ingredients: mannitol, starch, pregelatinized starch, colloidal silicon dioxide, stearic acid and talc.
Mechanism of Action
AZILECT is selective, irreversible MAO-B inhibitor indicated for the treatment of idiopathic Parkinson?s disease. The results of clinical trial designed to examine the effects of AZILECT on blood pressure when it is administered with increasing doses of tyramine indicates the functional selectivity can be incomplete when healthy subjects ingest large amounts of tyramine while receiving recommended doses of AZILECT. The selectivity for inhibiting MAO-B diminishes in dose-related manner
Tyramine Challenge Test
Results of tyramine challenge study indicate that rasagiline at recommended doses is relatively selective for inhibiting MAO-B and can be used without dietary tyramine restriction. However, certain foods (e.g., aged cheeses, such as Stilton cheese) may contain very high amounts of tyramine (i.e., 150 mg or greater) and could potentially cause severe hypertension caused by tyramine interaction in patients taking AZILECT due to mild increased sensitivity to tyramine at recommended doses. Relative selectivity of AZILECT for inhibiting MAO-B diminished in dose-related manner as the dose progressively increased above the highest recommended daily dose g)
INDICATIONS AND USAGE
? AZILECT (rasagiline tablets) is indicated for the treatment of Parkinson?s disease (PD).
2 DOSAGE AND ADMINISTRATION
2.1 General Dosing Recommendations
? When AZILECT is prescribed as monotherapy or as adjunct therapy in patients not taking levodopa, patients may start AZILECT at the recommended dose of mg administered orally once daily.
? In patients taking levodopa, with or without other PD drugs (e.g., dopamine agonist, amantadine, anticholinergics), the recommended initial dose of AZILECT is 0.5 mg once daily. If the patient tolerates the daily 0.5 mg dose, but sufficient clinical response is not achieved, the dose may be increased to mg once daily. When AZILECT is used in combination with levodopa, reduction of the levodopa dose may be considered, based upon individual response.
? The recommended doses of AZILECT should not be exceeded because of risk of hypertension [see Warnings and Precautions 5.1 )].
2.2 Patients Taking Ciprofloxacin or Other CYP1A2 Inhibitors
Patients taking concomitant ciprofloxacin or other CYP1A2 inhibitors should not exceed dose of AZILECT 0.5 mg once daily [see Warnings and Precautions , Drug Interactions , and Clinical Pharmacology (12.3)].
2.3 Patients with Hepatic Impairment
Patients with mild hepatic impairment should not exceed dose of AZILECT 0.5 mg once daily. AZILECT should not be used in patients with moderate or severe hepatic impairment [see Warnings and Precautions , Use in Specific Populations , and Clinical Pharmacology (12.3)].
3 DOSAGE FORMS AND STRENGTHS
AZILECT 0.5 mg Tablets: White to off-white, round, flat, beveled tablets, debossed with ?GIL 0.5? on one side and plain on the other side containing, as the active ingredient, rasagiline mesylate equivalent to 0.5 mg of rasagiline base.
AZILECT mg Tablets: White to off-white, round, flat, beveled tablets, debossed with ?GIL 1? on one side and plain on the other side containing, as the active ingredient, rasagiline mesylate equivalent to mg of rasagiline base.
4 CONTRAINDICATIONS
AZILECT is contraindicated for use with meperidine, tramadol, methadone, propoxyphene and MAO inhibitors (MAOIs), including other selective MAO-B inhibitors, because of risk of serotonin syndrome [See Warnings and Precautions ]. At least 14 days should elapse between discontinuation of AZILECT and initiation of treatment with these medications.
AZILECT is contraindicated for use with St. John?s wort and with cyclobenzaprine.
AZILECT is contraindicated for use with dextromethorphan because of risk of episode of psychosis or bizarre behavior.
5 WARNINGS AND PRECAUTIONS
5.1 Hypertension
Serotonin Syndrome
Falling Asleep During Activities of Daily Living and Somnolence
Ciprofloxacin or Other CYP1A2 Inhibitors
Hepatic Impairment
Hypotension Orthostatic Hypotension
Dyskinesia
Hallucinations Psychotic-Like Behavior
Impulse Control Compulsive Behaviors
Withdrawal-Emergent Hyperpyrexia and Confusion
Melanoma
DRUG INTERACTIONS
Meperidine
Dextromethorphan
MAO Inhibitors
Sympathomimetic Medications
Antidepressants
Ciprofloxacin or Other CYP1A2 Inhibitors
Tyramine/Rasagiline Interaction
Dopaminergic Antagonists
Pregnancy
Pregnancy Category C
HOW SUPPLIED/STORAGE AND HANDLING
AZILECT 0.5 mg Tablets:
White to off-white, round, flat, beveled tablets, debossed with ?GIL 0.5? on one side and plain on the other side. Supplied as bottles of 30 tablets (NDC 68546-142-56).
AZILECT mg Tablets:
White to off-white, round, flat, beveled tablets, debossed with ?GIL 1? on one side and plain on the other side. Supplied as bottles of 30 tablets (NDC 68546-229-56).
Storage:
Store at 25?C (77?F) with excursions permitted to 15?-30?C (59?-86?F).
