Total Cost
Free shipping on all orders

Powered by GeniusRx

rasagiline mesylate 0.5 mg tab generic azilect

Out of Stock Manufacturer ALVOGEN INC 47781013830
Out of Stock

Uses

Parkinsonian Syndrome

Rasagiline is used as initial monotherapy or as adjunctive therapy to levodopa for the symptomatic treatment of idiopathic parkinsonian syndrome.

Efficacy of rasagiline as initial monotherapy in the management of parkinsonian syndrome has been established in a randomized, double-blind, placebo-controlled study of up to 26 weeks' duration in patients with early disease who were not receiving dopaminergic antiparkinsonian agents or had not received any antiparkinsonian drug therapy. In this study, 404 patients were randomized to receive rasagiline (1 or 2 mg once daily) or placebo; patients were not permitted to use levodopa, dopamine agonists, selegiline, or amantadine but could receive stable dosages of an anticholinergic agent as needed. The primary efficacy measurement was the change from baseline in the total score (i.e., combined scores from part I [mentation], part II [activities of daily living], and part III [motor function]) of the Unified Parkinson's Disease Rating Scale (UPDRS); a reduction in the total score represented an improvement in mentation, activities of daily living, and/or motor function. Treatment with rasagiline was associated with substantially smaller increases in the UPDRS score (i.e., less functional decline) compared with treatment with placebo; efficacy of rasagiline dosages of 1 or 2 mg daily was comparable.

Efficacy of rasagiline as an adjunct to levodopa in the management of parkinsonian syndrome has been established in 2 multicenter, randomized, double-blind, placebo-controlled studies in patients with more advanced disease who were receiving long-term levodopa therapy (mean duration: 8 years; range: 5 months-32 years) in combination with a decarboxylase inhibitor and were experiencing motor fluctuations (e.g., end-of-dose '' wearing off'', sudden or random ''off'' phenomena). In the first study, 472 patients were randomized to receive rasagiline (0.5 or 1 mg daily) or placebo for 26 weeks; in the second study, 687 patients were randomized to receive rasagiline (1 mg daily), entacapone (200 mg with every levodopa dose), or placebo for 18 weeks. Patients in both studies continued receiving levodopa (average dosage: 700-800 mg daily) and were permitted to receive stable dosages of other antiparkinsonian agents; dopamine agonists were used in approximately 65% of patients in both studies, and entacapone was used in 35% of patients in the first study. The primary efficacy measurement was the change from baseline in the mean number of total daily hours spent in the ''off'' state (period of poor functioning and mobility), as measured by 24-hour home diaries. In these studies, therapy with rasagiline (1 mg daily) or entacapone was more effective than placebo in decreasing total daily ''off'' time; therapy with a lower dosage of rasagiline (0.5 mg daily) also resulted in decreased ''off'' time, but to a lesser extent. Duration of ''off'' time was reduced by a mean of 1.2-1.9, 1.4, 1.2, or 0.4-0.9 hours in patients receiving rasagiline 1 mg, rasagiline 0.5 mg, entacapone, or placebo, respectively. In addition, compared with placebo, treatment with rasagiline or entacapone was associated with substantial improvements in the UPDRS activities of daily living (ADL) score during the ''off'' period and the UPDRS motor function score during the ''on'' period. During the first 6 weeks of therapy, reduction in levodopa dosage was permitted if adverse dopaminergic effects (e.g., dyskinesia, hallucinations) occurred or worsened. In these studies, levodopa dosage was reduced in 9-17 or 6-8% of patients receiving rasagiline or placebo, respectively; levodopa dosage was reduced on average by about 9-13% in patients receiving rasagiline or about 7-13% in those receiving placebo.

Dosage and Administration

Administration

Rasagiline mesylate is administered orally once daily without regard to meals.

Dosage

The recommended adult dosage of rasagiline as initial monotherapy for the management of parkinsonian syndrome is 1 mg once daily.

The recommended initial adult dosage of rasagiline as adjunctive therapy with levodopa for the management of parkinsonian syndrome is 0.5 mg once daily. If an adequate response is not achieved, dosage may be increased to 1 mg once daily. During adjunctive therapy with levodopa, reduction in levodopa dosage may be considered if adverse dopaminergic effects (e.g., dyskinesia, hallucinations) occur. In clinical studies, approximately 9-17% of patients receiving 0.5 or 1 mg of rasagiline daily required a reduction in levodopa dosage; the average reduction in the daily levodopa dosage was about 9-13%.(See Uses: Parkinsonian Syndrome.)

Concomitant use of rasagiline with ciprofloxacin or other cytochrome P-450 (CYP) isoenzyme 1A2 inhibitors has been shown, or would be expected, to increase plasma rasagiline concentrations by up to twofold. Therefore, when used concomitantly with ciprofloxacin or other CYP1A2 inhibitors, the manufacturer of rasagiline states that rasagiline dosage should be limited to 0.5 mg once daily.

Special Populations

Patients with mild (Child-Pugh score of 5-6) hepatic impairment should receive a rasagiline dosage of 0.5 mg once daily; rasagiline should not be used in patients with moderate or severe (Child-Pugh score of 7 or greater) hepatic impairment.(See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)

No dosage adjustment is necessary in patients with mild or moderate renal impairment or in geriatric patients.

Cautions

Contraindications

Concomitant use with cyclobenzaprine, dextromethorphan, meperidine, methadone, propoxyphene (no longer commercially available in the US), tramadol, St. John's wort (Hypericum perforatum), or other monoamine oxidase (MAO) inhibitors.(See Drug Interactions.)

Warnings/Precautions

Concomitant Use with Antidepressant Agents or Certain Opiate Agonists

Concomitant use of selective (e.g., rasagiline, selegiline) or nonselective (e.g., phenelzine, tranylcypromine) MAO inhibitors with antidepressants (e.g., selective serotonin-reuptake inhibitors [SSRIs], selective serotonin- and norepinephrine-reuptake inhibitors [SNRIs], tricyclic or tetracyclic antidepressants, triazolopyridine-derivative antidepressants) or certain opiate agonists (i.e., meperidine, tramadol) has resulted in severe serotonin syndrome, which potentially may be fatal. Manifestations of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).

Because of the potential risk of severe, sometimes fatal, serotonin syndrome, concomitant use of rasagiline with certain opiate agonists (i.e., meperidine, methadone, propoxyphene [no longer commercially available in the US], tramadol) is contraindicated. (See Cautions: Contraindications and also see Drug Interactions: Opiate Agonists.) Although concomitant use of rasagiline with certain antidepressants (e.g., amitriptyline [less than 50 mg daily], trazodone [less than 100 mg daily], citalopram [less than 20 mg daily], sertraline [less than 100 mg daily], paroxetine [less than 30 mg daily]) was permitted during clinical trials, experience is insufficient to rule out the possibility of adverse effects from such concomitant use; therefore, the manufacturer states that it would be prudent, in general, to avoid concomitant use of rasagiline with any antidepressant agent (see Drug Interactions: Antidepressant Agents).

Concomitant Use with Ciprofloxacin or Other CYP1A2 Inhibitors

Concomitant use of rasagiline with ciprofloxacin or other cytochrome P-450 (CYP) isoenzyme 1A2 inhibitors has been shown, or would be expected, to increase plasma rasagiline concentrations by up to twofold. Adjustment of rasagiline dosage is recommended.(See Dosage and Administration: Dosage and also see Drug Interactions: Drugs Affecting Hepatic Microsomal Enzymes.)

Hypertensive Crisis

Hypertensive crisis (i.e., cheese reaction), manifested as marked elevations in systemic blood pressure, has been reported rarely following concomitant use of recommended dosages of a selective MAO-B inhibitor (including rasagiline) with foods containing large amounts of tyramine or drug preparations containing sympathomimetic amines. Hypertensive crisis may be fatal and requires immediate treatment or hospitalization. Concomitant use of rasagiline with preparations containing sympathomimetic amines should be employed with caution.(See Drug Interactions: Sympathomimetic Amines.) The manufacturer states that restriction of most tyramine-containing foods or beverages generally is not required during rasagiline therapy. However, because foods that contain very large amounts (i.e., more than 150 mg) of tyramine (e.g., aged cheeses, such as Stilton cheese) potentially can cause a hypertensive crisis in some patients (e.g., those with mildly increased sensitivity to tyramine) receiving recommended dosages of rasagiline, patients should be advised to avoid such tyramine-rich foods during rasagiline therapy. Patients also should be instructed on how to recognize manifestations of a hypertensive crisis and to immediately notify a clinician if such manifestations occur.(See Advice to Patients.)

At dosages exceeding the recommended daily dosage, selectivity of rasagiline for MAO-B diminishes, the drug will inhibit both MAO-B and MAO-A, and the likelihood of hypertensive reactions increases. Because of the increased risk of a hypertensive reaction at dosages exceeding 1 mg daily, patients should be advised not to exceed the recommended daily dosage of 1 mg (or 0.5 mg daily in patients with mild hepatic impairment or in patients receiving concomitant ciprofloxacin or other CYP1A2 inhibitors).

Melanoma

Data from epidemiologic studies indicate that patients with Parkinson's disease have a twofold to approximately sixfold greater risk of developing melanoma than the general population; however, it is unclear whether the observed increased risk is related to Parkinson's disease or other factors (e.g., drugs used to treat the disease).

Because of these findings, patients and clinicians should monitor for melanoma on a frequent and regular basis. The manufacturer recommends that dermatologic examinations be performed by qualified clinicians (e.g., dermatologists) periodically; the frequency of dermatologic examinations should be determined by the patient's dermatologist.

Exacerbation of Levodopa-associated Adverse Effects

When used as adjunctive therapy with levodopa, rasagiline may cause or exacerbate levodopa-associated adverse effects (e.g., dyskinesias), presumably by increasing dopaminergic activity; effects generally can be mitigated by reducing levodopa dosage.(See Dosage and Administration: Dosage.)

Orthostatic Hypotension and Lowering of Blood Pressure

Orthostatic hypotension, with or without manifestations such as dizziness, nausea, syncope, and sometimes sweating, has been reported in patients receiving rasagiline as adjunctive therapy with levodopa. In clinical studies, orthostatic hypotension was reported in 6 or 9% of patients receiving rasagiline 0.5 or 1 mg daily, respectively, and resulted in discontinuance of the drug in 0 or 0.7% of these patients, respectively. Orthostatic hypotension consisting of decreases in systolic and diastolic blood pressure of at least 30/20 mm Hg was reported in 13.4% of patients receiving rasagiline 1 mg daily as adjunctive therapy with levodopa, compared with 8.5% of those receiving placebo. Data from clinical studies indicate that orthostatic hypotension occurs most frequently during the first 2 months of rasagiline therapy (and less frequently over time) and may occur at any time following an increase in dosage. The risk of orthostatic hypotension appears to be increased in patients with preexisting postural hypotension for both systolic and diastolic blood pressure. Substantial decreases in blood pressure in the supine position also have been reported in some patients receiving rasagiline. Posttreatment hypotension (systolic blood pressure less than 90 mm Hg or diastolic blood pressure less than 50 mm Hg) combined with substantial decreases in blood pressure from baseline (decreases in systolic or diastolic blood pressure of greater than 30 or 20 mm Hg, respectively) occurred in more patients receiving rasagiline 1 mg daily (3.2%) compared with those receiving placebo (1.3%).

The risk of hypotension or orthostatic hypotension does not appear to be increased when rasagiline (1 mg daily) is used as monotherapy.

Elevation of Blood Pressure

Substantial increases in blood pressure (systolic blood pressure exceeding 180 mm Hg or diastolic blood pressure exceeding 100 mm Hg) have been reported in 4% of patients receiving rasagiline 1 mg daily as adjunctive therapy with levodopa compared with 3% of patients receiving placebo. Posttreatment hypertension (systolic blood pressure exceeding 180 mm Hg or diastolic blood pressure exceeding 100 mm Hg) combined with substantial increases in blood pressure from baseline (increases in systolic or diastolic blood pressure of greater than 30 or 20 mm Hg, respectively) occurred in more patients who received rasagiline 1 mg daily (2%) than in those who received placebo (1%).

The risk of hypertension does not appear to be increased when rasagiline (1 mg daily) is used as monotherapy.

Hallucinations and Psychotic-like Behavior

Hallucinations were reported in approximately 1.3% of patients receiving rasagiline 1 mg daily as monotherapy and resulted in discontinuance of the drug in 1.3% of patients. When rasagiline was used as adjunctive therapy with levodopa, hallucinations occurred in 4-5% of patients receiving rasagiline 0.5 or 1 mg daily and resulted in discontinuance of the drug in 1% of patients. Patients should be cautioned about the possibility of developing hallucinations and instructed to notify a clinician promptly should these manifestations occur.

New onset or exacerbation of psychotic-like behavior (manifested as paranoia, confusional state or confusion, psychotic disorder, agitation, delusion, and hallucinations) has been reported in some patients receiving antiparkinsonian agents that increase central dopaminergic tone, including rasagiline. Therefore, rasagiline should not be used in patients with a major psychotic disorder. Furthermore, concomitant use of rasagiline with antipsychotic agents that decrease central dopaminergic tone may result in decreased effectiveness of rasagiline.

Neuroleptic Malignant Syndrome

A symptom complex resembling neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability) has been reported in association with rapid dosage reduction, withdrawal of, or changes in drugs that increase central dopaminergic tone. Hyperpyrexia has not been reported following discontinuance of rasagiline.

Intense Urges

Intense urges (e.g., urge to gamble, increased sexual urges, other intense urges) and inability to control these urges have been reported in some patients receiving antiparkinsonian agents that increase central dopaminergic tone (including rasagiline). Although a causal relationship has not been established, these urges stopped in some cases when dosage was reduced or the drug was discontinued. Clinicians should ask patients whether they have developed new or increased gambling urges, sexual urges, or other urges while receiving rasagiline and should advise them of the importance of reporting such urges. If a patient develops such urges while receiving rasagiline, consideration should be given to reducing the dosage or discontinuing the drug.

Specific Populations

Pregnancy

Category C.

Lactation

Rasagiline inhibits prolactin secretion in rats; the drug may inhibit milk secretion in women. It is not known whether rasagiline is distributed into milk; caution is advised if the drug is administered in nursing women.

Pediatric Use

Safety and efficacy of rasagiline have not been established in pediatric patients younger than 18 years of age.

Geriatric Use

Approximately half of patients in clinical studies were 65 years of age or older. No overall differences in safety relative to younger adults were observed.

Hepatic Impairment

Following administration of rasagiline 1 mg daily for 7 days, the area under the plasma concentration-time curve (AUC) or peak plasma concentration of rasagiline was increased by twofold or 1.4-fold, respectively, in individuals with mild (Child-Pugh score of 5-6) hepatic impairment and by sevenfold or twofold, respectively, in individuals with moderate (Child-Pugh score of 7-9) hepatic impairment.

Dosage adjustment is recommended in patients with mild hepatic impairment.(See Dosage and Administration: Special Populations.) Use is not recommended in patients with moderate or severe (Child-Pugh score of 7 or greater) hepatic impairment.

Renal Impairment

Following administration of rasagiline 1 mg daily for 8 days, AUC of rasagiline was similar between individuals with moderate renal impairment and those with normal renal function, while AUC of the major metabolite 1-aminoindan increased by 1.5-fold in individuals with moderate renal impairment. Because 1-aminoindan is not an MAO inhibitor, no dosage adjustment is needed in patients with mild or moderate renal impairment. Data are not available for patients with severe renal impairment.

Common Adverse Effects

When rasagiline is used as initial monotherapy, the most common adverse effects (i.e., occurring at least 3% more frequently in patients receiving rasagiline than in those receiving placebo) include flu syndrome, arthralgia, depression, and dyspepsia. Other adverse effects reported in 2% or more of patients receiving rasagiline as initial monotherapy and occurring more frequently with rasagiline than with placebo include fall, headache, conjunctivitis, fever, gastroenteritis, rhinitis, arthritis, ecchymosis, malaise, neck pain, paresthesia, and vertigo.

When rasagiline is used as adjunctive therapy with levodopa, the most common adverse effects (i.e., occurring at least 3% more frequently in patients receiving rasagiline than in those receiving placebo) include dyskinesia, accidental injury, weight loss, orthostatic hypotension, vomiting, anorexia, arthralgia, abdominal pain, nausea, constipation, dry mouth, rash, abnormal dreams, and fall. Other adverse effects reported in 2% or more of patients receiving rasagiline as initial monotherapy and occurring more frequently with rasagiline than with placebo include ecchymosis, somnolence, paresthesia, headache, diarrhea, dyspepsia, hallucinations, ataxia, dyspnea, infection, neck pain, sweating, tenosynovitis, dystonia, gingivitis, hemorrhage, hernia, and myasthenia.

Drug Interactions

Rasagiline is extensively metabolized, mainly via hepatic cytochrome P-450 (CYP) 1A2 isoenzyme. The drug does not inhibit CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, 3A4, or 4A in vitro.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP1A2: Pharmacokinetic interaction observed during concomitant use with ciprofloxacin (increased plasma rasagiline concentrations). Dosage of rasagiline should be limited to 0.5 mg once daily in patients receiving the drug concomitantly with ciprofloxacin or other CYP1A2 inhibitors.

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP1A2: Pharmacokinetic interaction with theophylline or other substrates of CYP1A2 unlikely.

Substrates of 2A6, 2C9, 2C19, 2D6, 2E1, 3A4, or 4A: Pharmacokinetic interaction unlikely.

Antidepressant Agents

Potential pharmacologic interaction resembling serotonin syndrome.(See Concomitant Use with Antidepressant Agents or Certain Opiate Agonists under Cautions: Warnings/Precautions.) At least 14 days should elapse between discontinuance of rasagiline and initiation of an SSRI, SNRI, tricyclic or tetracyclic antidepressant, or triazolopyridine-derivative antidepressant. Because both fluoxetine and its principal metabolite have relatively long half-lives, the manufacturer of rasagiline recommends that at least 5 weeks (or longer with high-dose or long-term fluoxetine therapy) elapse between discontinuance of fluoxetine therapy and initiation of rasagiline.

Antipsychotic Agents

Concomitant use of rasagiline with antipsychotic agents that decrease central dopaminergic tone may result in decreased effectiveness of rasagiline.

Cyclobenzaprine

Concomitant use is contraindicated.(See Cautions: Contraindications.)

Dextromethorphan

Potential pharmacologic interaction (brief episodes of psychosis or bizarre behavior). Concomitant use is contraindicated.(See Cautions: Contraindications.)

Levodopa

Potential pharmacologic (increased adverse dopaminergic effects, increased risk of dyskinesia and orthostatic hypotension) and pharmacokinetic interaction (modest increase in plasma rasagiline concentrations). Reduction in levodopa dosage may be considered; adjustment of rasagiline dosage is not necessary.(See Dosage and Administration: Dosage.)

Monoamine Oxidase (MAO) Inhibitors

Potential pharmacokinetic interaction (increased risk of nonselective MAO inhibition, possibly resulting in a hypertensive crisis). Concomitant use is contraindicated.(See Cautions: Contraindications.) At least 14 days should elapse between discontinuance of rasagiline and initiation of other MAO inhibitors.

Opiate Agonists

Pharmacologic interaction resembling serotonin syndrome has been reported following concomitant use of MAO inhibitors, including selective MAO-B inhibitors, with meperidine. Serotonin syndrome has been reported in at least one patient receiving higher than recommended dosage of rasagiline (4 mg daily) concomitantly with tramadol.(See Concomitant Use with Antidepressant Agents or Certain Opiate Agonists under Cautions: Warnings/Precautions.) Therefore, concomitant use of rasagiline with meperidine, methadone, propoxyphene (no longer commercially available in the US), or tramadol is contraindicated.(See Cautions: Contraindications.) At least 14 days should elapse between discontinuance of rasagiline and initiation of meperidine.

St. John's wort (Hypericum perforatum)

Concomitant use is contraindicated.(See Cautions: Contraindications.)

Sympathomimetic Amines

Potential pharmacologic interaction (i.e., hypertensive crisis following concomitant use of selective MAO-B inhibitor with ephedrine, elevated blood pressure following concomitant use of rasagiline with tetrahydrozoline ophthalmic solution). Therefore, caution is advised when rasagiline is used concomitantly with preparations (including oral, nasal, and ophthalmic preparations) containing sympathomimetic amines (e.g., amphetamines, ephedrine, phenylephrine, pseudoephedrine).

Tyramine-rich Foods or Beverages

Pharmacologic interaction (substantially elevated blood pressure or hypertensive crisis).(See Hypertensive Crisis under Cautions: Warnings/Precautions.) The manufacturer states that while it generally is not necessary to restrict ingestion of most foods or beverages that may contain tyramine, ingestion of certain foods containing very large amounts (i.e., more than 150 mg) of tyramine (e.g., aged cheeses such as Stilton cheese) potentially may result in a hypertensive crisis and, thus, should be avoided during rasagiline therapy.

Write Your Own Review

Your meds on autopilot. Forever.