(ra SA ji leen)
Parkinson disease: Treatment of Parkinson disease
Concomitant use of an MAO inhibitor (including selective MAO-B inhibitors), meperidine, methadone, propoxyphene, or tramadol within 14 days of rasagiline; concomitant use with cyclobenzaprine, dextromethorphan, or St John 's wort
Parkinson disease: Oral:
Monotherapy or adjunctive therapy (not including levodopa): 1 mg once daily (maximum: 1 mg once daily)
Adjunctive therapy with levodopa: Initial: 0.5 mg once daily; may increase to 1 mg once daily based on response and tolerability (maximum: 1 mg once daily)
Note: When added to existing levodopa therapy, a dose reduction of levodopa may be required to avoid exacerbation of dyskinesias; typical dose reductions of ~9% to 13% were employed in clinical trials.
Dose reduction with concomitant ciprofloxacin or other CYP1A2 inhibitors: Maximum dose: 0.5 mg once daily
Refer to adult dosing.
US labeling:
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied).
Canadian labeling:
Mild impairment: No dosage adjustment necessary.
Moderate to severe impairment: Use is not recommended (manufacturer cites lacks of safety data)
Mild impairment (Child-Pugh score 5 to 6): Maximum dose: 0.5 mg once daily
Moderate to severe impairment (Child-Pugh score 7 to 15): Use is not recommended.
Administer without regard to meals.
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 2]).
May be taken without regard to meals. Avoid products containing high amounts of tyramine (>150 mg), such as aged cheeses (eg, Stilton cheese). Restriction of tyramine-containing products with lower amounts (<150 mg) of tyramine is not necessary in patients taking recommended doses. Some examples of tyramine-containing products include aged or matured cheese, air-dried or cured meats (including sausages and salamis), fava or broad bean pods, tap/draft beers, Marmite concentrate, sauerkraut, soy sauce and other soybean condiments. Food 's freshness is also an important concern; improperly stored or spoiled food can create an environment where tyramine concentrations may increase.
Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Azilect: 0.5 mg, 1 mg
Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy
Alcohol (Ethyl): May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Alpha-/Beta-Agonists (Indirect-Acting): MAO Inhibitors may enhance the hypertensive effect of Alpha-/Beta-Agonists (Indirect-Acting). While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Avoid combination
Alpha1-Agonists: MAO Inhibitors may enhance the hypertensive effect of Alpha1-Agonists. While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Avoid combination
Altretamine: May enhance the orthostatic hypotensive effect of MAO Inhibitors. Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Amphetamines: MAO Inhibitors may enhance the hypertensive effect of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Antidepressants (Serotonin Reuptake Inhibitor/Antagonist): MAO Inhibitors may enhance the adverse/toxic effect of Antidepressants (Serotonin Reuptake Inhibitor/Antagonist). While methylene blue and linezolid are expected to interact, specific recommendations for their use differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Apraclonidine: MAO Inhibitors may enhance the adverse/toxic effect of Apraclonidine. MAO Inhibitors may increase the serum concentration of Apraclonidine. Avoid combination
AtoMOXetine: MAO Inhibitors may enhance the neurotoxic (central) effect of AtoMOXetine. Avoid combination
Atropine (Ophthalmic): MAO Inhibitors may enhance the hypertensive effect of Atropine (Ophthalmic). Avoid combination
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Beta2-Agonists: MAO Inhibitors may enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy
Betahistine: MAO Inhibitors may increase the serum concentration of Betahistine. Monitor therapy
Bezafibrate: MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid combination
Blood Glucose Lowering Agents: MAO Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Brimonidine (Ophthalmic): MAO Inhibitors may enhance the adverse/toxic effect of Brimonidine (Ophthalmic). MAO Inhibitors may increase the serum concentration of Brimonidine (Ophthalmic). Monitor therapy
Brimonidine (Topical): MAO Inhibitors may enhance the adverse/toxic effect of Brimonidine (Topical). MAO Inhibitors may increase the serum concentration of Brimonidine (Topical). Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Buprenorphine: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
BuPROPion: MAO Inhibitors may enhance the hypertensive effect of BuPROPion. Avoid combination
BusPIRone: May enhance the adverse/toxic effect of MAO Inhibitors. Specifically, blood pressure elevations been reported. Avoid combination
Cannabis: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy
CarBAMazepine: May enhance the adverse/toxic effect of MAO Inhibitors. Management: Avoid concurrent use of carbamazepine during, or within 14 days of discontinuing, treatment with a monoamine oxidase inhibitor. Avoid combination
Codeine: MAO Inhibitors may enhance the adverse/toxic effect of Codeine. Monitor therapy
COMT Inhibitors: May enhance the adverse/toxic effect of MAO Inhibitors. Consider therapy modification
Cyclobenzaprine: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
CYP1A2 Inducers (Strong): May increase the metabolism of CYP1A2 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Monitor therapy
CYP1A2 Inhibitors (Strong): May increase the serum concentration of Rasagiline. Management: Limit rasagiline dose to 0.5 mg once daily in patients taking strong CYP1A2 inhibitors. Consider therapy modification
Cyproheptadine: MAO Inhibitors may enhance the anticholinergic effect of Cyproheptadine. Cyproheptadine may diminish the serotonergic effect of MAO Inhibitors. Avoid combination
Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy
Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination
Deferasirox: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy
Dexmethylphenidate: MAO Inhibitors may enhance the hypertensive effect of Dexmethylphenidate. Avoid combination
Dextromethorphan: MAO Inhibitors may enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Avoid combination
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Diethylpropion: MAO Inhibitors may enhance the hypertensive effect of Diethylpropion. Avoid combination
Domperidone: MAO Inhibitors may enhance the adverse/toxic effect of Domperidone. MAO Inhibitors may diminish the therapeutic effect of Domperidone. Domperidone may diminish the therapeutic effect of MAO Inhibitors. Monitor therapy
Doxapram: MAO Inhibitors may enhance the hypertensive effect of Doxapram. Monitor therapy
EPINEPHrine (Nasal): MAO Inhibitors may enhance the hypertensive effect of EPINEPHrine (Nasal). Monitor therapy
EPINEPHrine (Oral Inhalation): MAO Inhibitors may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Avoid combination
Epinephrine (Racemic): MAO Inhibitors may enhance the hypertensive effect of Epinephrine (Racemic). Monitor therapy
EPINEPHrine (Systemic): MAO Inhibitors may enhance the hypertensive effect of EPINEPHrine (Systemic). Monitor therapy
FentaNYL: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
HYDROcodone: MAO Inhibitors may enhance the adverse/toxic effect of HYDROcodone. Management: Consider alternatives to this combination when possible. Consider therapy modification
HYDROmorphone: MAO Inhibitors may enhance the adverse/toxic effect of HYDROmorphone. Avoid combination
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Isometheptene: MAO Inhibitors may enhance the adverse/toxic effect of Isometheptene. Avoid combination
Levodopa: May enhance the adverse/toxic effect of MAO Inhibitors. Of particular concern is the development of hypertensive reactions when levodopa is used with nonselective MAOI. Management: The concomitant use of nonselective monoamine oxidase inhibitors (MAOIs) and levodopa is contraindicated. Discontinue the nonselective MAOI at least two weeks prior to initiating levodopa. Monitor patients taking a selective MAOIs and levodopa. Consider therapy modification
Levonordefrin: MAO Inhibitors may enhance the hypertensive effect of Levonordefrin. Avoid combination
Linezolid: MAO Inhibitors may enhance the adverse/toxic effect of Linezolid. Avoid combination
Lithium: MAO Inhibitors may enhance the adverse/toxic effect of Lithium. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification
MAO Inhibitors: May enhance the hypertensive effect of other MAO Inhibitors. MAO Inhibitors may enhance the serotonergic effect of other MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Maprotiline: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Meperidine: MAO Inhibitors may enhance the serotonergic effect of Meperidine. This may cause serotonin syndrome. Avoid combination
Mequitazine: MAO Inhibitors may enhance the anticholinergic effect of Mequitazine. Avoid combination
Metaraminol: MAO Inhibitors may enhance the hypertensive effect of Metaraminol. Monitor therapy
Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Methyldopa: MAO Inhibitors may enhance the adverse/toxic effect of Methyldopa. Avoid combination
Methylene Blue: MAO Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Avoid combination
Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination
Methylphenidate: MAO Inhibitors may enhance the hypertensive effect of Methylphenidate. Avoid combination
Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Monitor therapy
Mianserin: MAO Inhibitors may enhance the neurotoxic effect of Mianserin. Avoid combination
Mirtazapine: MAO Inhibitors may enhance the neurotoxic (central) effect of Mirtazapine. While methylene blue and linezolid are expected to interact, specific recommendations for their use differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Moclobemide: MAO Inhibitors may enhance the adverse/toxic effect of Moclobemide. Avoid combination
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Morphine (Liposomal): MAO Inhibitors may enhance the adverse/toxic effect of Morphine (Liposomal). Avoid combination
Morphine (Systemic): MAO Inhibitors may enhance the adverse/toxic effect of Morphine (Systemic). Avoid combination
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nefopam: MAO Inhibitors may enhance the adverse/toxic effect of Nefopam. Avoid combination
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Norepinephrine: MAO Inhibitors may enhance the hypertensive effect of Norepinephrine. Monitor therapy
Obeticholic Acid: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
Osimertinib: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy
OxyCODONE: MAO Inhibitors may enhance the adverse/toxic effect of OxyCODONE. Management: Per Canadian labeling, use of oxycodone is contraindicated in patients who either are receiving MAO inhibitors or have used them within 14 days. Though not contraindicated in U.S. prescribing information, consider alternatives when possible. Consider therapy modification
OxyMORphone: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Peginterferon Alfa-2b: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Pheniramine: May enhance the anticholinergic effect of MAO Inhibitors. Avoid combination
Pholcodine: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Pindolol: MAO Inhibitors may enhance the hypotensive effect of Pindolol. Management: Canadian labeling for pindolol states that concurrent use with a monoamine oxidase inhibitor is not recommended. Consider therapy modification
Pipamperone [INT]: Anti-Parkinson Agents (Monoamine Oxidase Inhibitor) may diminish the therapeutic effect of Pipamperone [INT]. Pipamperone [INT] may diminish the therapeutic effect of Anti-Parkinson Agents (Monoamine Oxidase Inhibitor). Monitor therapy
Pizotifen: MAO Inhibitors may enhance the anticholinergic effect of Pizotifen. Avoid combination
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Reboxetine: MAO Inhibitors may enhance the adverse/toxic effect of Reboxetine. Avoid combination
Reserpine: MAO Inhibitors may enhance the adverse/toxic effect of Reserpine. Existing MAOI therapy can result in paradoxical effects of added reserpine (e.g., excitation, hypertension). Management: Monoamine oxidase inhibitors (MAOIs) should be avoided or used with great caution in patients who are also receiving reserpine. Consider therapy modification
Selective Serotonin Reuptake Inhibitors: MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Serotonin 5-HT1D Receptor Agonists: MAO Inhibitors may decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Exceptions: Eletriptan; Frovatriptan; Naratriptan. Avoid combination
Serotonin Modulators: Anti-Parkinson Agents (Monoamine Oxidase Inhibitor) may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity if selegiline or rasagiline is combined with a serotonin modulator. Use of transdermal selegiline with serotonin modulators is contraindicated. Exceptions: Nicergoline. Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: MAO Inhibitors may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Tapentadol: May enhance the adverse/toxic effect of MAO Inhibitors. Specifically, the additive effects of norepinephrine may lead to adverse cardiovascular effects. Tapentadol may enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Teriflunomide: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy
Tetrabenazine: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Tetrahydrozoline (Nasal): MAO Inhibitors may enhance the hypertensive effect of Tetrahydrozoline (Nasal). Avoid combination
Tricyclic Antidepressants: MAO Inhibitors may enhance the serotonergic effect of Tricyclic Antidepressants. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Tryptophan: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Vemurafenib: May increase the serum concentration of CYP1A2 Substrates. Management: Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. Consider therapy modification
Blood pressure; symptoms of parkinsonism; new or worsening mental status and behavioral changes ; somnolence and falling asleep during activities of daily living; skin examination for presence of melanoma (higher incidence in Parkinson 's patients- drug causation not established)
Unless otherwise noted, the following adverse reactions are as reported for monotherapy. Spectrum of adverse events was generally similar with adjunctive therapy, though the incidence tended to be higher. Frequency not always defined.
>10%:
Cardiovascular: Orthostatic hypotension (adjunctive therapy 3% to 13%, adjunctive therapy dose-related 6% to 9%; adjunctive therapy, 1 mg dose 3%; mild to moderate systolic blood pressure decrease [ ≥20 mmHg], 1 mg dose 44%; mild to moderate diastolic blood pressure decrease [ ≥10 mmHg], 1 mg dose 40%; severe diastolic blood pressure decrease [ ≥20 mmHg], 1 mg dose 9%; severe systolic blood pressure decrease [ ≥40 mmHg], 1 mg dose 7%), hypotension (3% post-treatment [systolic <90 mmHg or diastolic <50 mmHg combined with significant decrease from baseline, systolic >30 mmHg or diastolic >20 mmHg])
Central nervous system: Headache (14%; adjunctive therapy 6% to 11%)
Gastrointestinal: Nausea (adjunctive therapy 6% to 12%)
Neuromuscular & skeletal: Dyskinesia (adjunctive therapy 18%)
Miscellaneous: Trauma (adjunctive therapy 8% to 12%)
1% to 10%:
Cardiovascular: Peripheral edema (7%), increased blood pressure (adjunctive therapy, significant increase, >180 mmHg systolic or >100 mmHg diastolic 4%; adjunctive therapy, post-treatment [>180 mmHg systolic or >100 mmHg diastolic combined with significant increase from baseline >30 mmHg systolic or >20 mmHg diastolic] 2%), angina, bundle branch block, chest pain
Central nervous system: Dizziness (7%), drowsiness (adjunctive therapy 4% to 6%), ataxia (adjunctive therapy 3% to 6%), depression (5%), falling (5%; adjunctive therapy 6% to 12%), abnormal dreams (adjunctive therapy 1% to 4%), dystonia (adjunctive therapy 2% to 3%), malaise (2%), paresthesia (2%; adjunctive therapy 2% to 5%), insomnia (adjunctive therapy 4%), hallucinations (1%; adjunctive therapy 4% to 5%), myasthenia (adjunctive therapy 2%), vertigo (2%), anxiety
Dermatologic: Skin rash (adjunctive therapy 3% to 6%), ecchymosis (2%; adjunctive therapy 2% to 5%), diaphoresis (adjunctive therapy 2% to 3%), alopecia, skin carcinoma, vesiculobullous rash
Endocrine & metabolic: Weight loss (adjunctive therapy, dose-related 2% to 9%), impotence, libido decreased
Gastrointestinal: Constipation (adjunctive therapy 4% to 9%), dyspepsia (7%; adjunctive therapy 4% to 5%), diarrhea (adjunctive therapy 5% to 7%), vomiting (adjunctive therapy 4% to 7%), xerostomia (adjunctive therapy, dose-related 2% to 6%), abdominal pain (adjunctive therapy 2% to 5%), anorexia (adjunctive therapy 2% to 5%), gastroenteritis (3%), gingivitis (adjunctive therapy 1% to 2%), hernia (adjunctive therapy 1% to 2%), gastrointestinal hemorrhage
Genitourinary: Hematuria, urinary incontinence
Hematologic and oncologic: Hemorrhage (adjunctive therapy 1% to 2%), leukopenia
Hepatic: Liver function tests increased
Infection: Infection (adjunctive therapy 2% to 3%)
Neuromuscular & skeletal: Arthralgia (7%; adjunctive therapy 5% to 8%), back pain (adjunctive therapy 4%), neck pain (2%; adjunctive therapy 1% to 3%), tenosynovitis (adjunctive therapy 1% to 3%), arthritis (2%), abnormal gait, hyperkinesias, hypertonia, neuropathy, weakness
Ophthalmic: Conjunctivitis (3%)
Renal: Albuminuria
Respiratory: Flu-like symptoms (5%), dyspnea (adjunctive therapy 3% to 5%), cough (adjunctive therapy 4%), upper respiratory tract infection (adjunctive therapy 4%), rhinitis (3%), asthma
Miscellaneous: Fever (3%), allergic reaction
<1% (Limited to important or life-threatening): Acute kidney failure, aggressive behavior, agitation, amyotrophy, aphasia, apnea, arterial thrombosis, atrial arrhythmia, atrioventricular block, bigeminy, blepharitis, blepharoptosis, blindness, cardiac failure, cerebral hemorrhage, cerebral ischemia, deafness, deep vein thrombophlebitis, delirium, delusions, diplopia, disorientation, dysautonomia, dysesthesia, emphysema, esophageal ulcer, exacerbation of hypertension, excessive daytime sleepiness (including during operation of motor vehicles), exfoliative dermatitis, facial paralysis, gastric ulcer, genitourinary disorders, glaucoma, gynecomastia, hematemesis, hemiplegia, hostility, hypocalcemia, hypotension (while supine), impulse control disorder (pathological gambling, hypersexuality, intense urges to spend money, binge eating, and/or other intense urges and the inability to control the urges), interstitial pneumonitis, intestinal obstruction, intestinal perforation, intestinal stenosis, jaundice, keratitis, large intestine perforation, laryngeal edema, laryngismus, leukoderma, leukorrhea, macrocytic anemia, manic depressive reaction, mania, megacolon, menstrual abnormalities, myelitis, myocardial infarction, nephrolithiasis, neuralgia, neuritis, (a complex resembling) neuroleptic malignant syndrome (associated with rapid dose reduction, withdrawal of or changes in medication; includes autonomic insufficiency, hyperthermia, impaired consciousness, muscle rigidity), nocturia, oral paresthesia, osteonecrosis, paranoia, personality disorder, pleural effusion, pneumothorax, polyuria, psychiatric disturbance (new or worsening mental status and behavioral changes that may be severe, including psychotic-like behavior during or after starting or increasing doses), psychoneurosis, psychotic symptoms, psychotic depression, pulmonary fibrosis, purpura, retinal degeneration, retinal detachment, seizure, strabismus, stupor, thrombocythemia, tongue edema, ventricular fibrillation, ventricular tachycardia, vestibular disturbance, visual field defect, vulvovaginal candidiasis
In patients with mild hepatic impairment (Child-Pugh score 5 to 6), AUC and Cmax are increased 2- and 1.4-fold, respectively. In patients with moderate hepatic impairment (Child-Pugh score 7 to 9), the AUC and Cmax are increased 7- and 2-fold, respectively.
Concerns related to adverse effects:
- CNS effects: May cause new or worsening mental status and behavioral changes, which may be severe, including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium after starting or increasing the dose of rasagiline. Intense urges to gamble or spend money, increased sexual urges, binge eating, and/or other intense urges, as well as the inability to control these urges, have also been reported. Monitor for these symptoms. If symptoms develop, consider dose reduction or discontinue of therapy.
- Dyskinesia: Dyskinesia, exacerbation of preexisting dyskinesia, or increased dopaminergic side effects may occur when used as an adjunct to levodopa. Decreasing the dose of levodopa may mitigate these side effects.
- Hypertension: May cause exacerbation of hypertension; monitor for new onset hypertension or hypertension not adequately controlled after starting rasagiline. Medication adjustment may be necessary if blood pressure elevation is sustained.
- Melanoma: Risk of melanoma may be increased with rasagiline, although increased risk has been associated with Parkinson 's disease itself; patients should have regular and frequent skin examinations.
- Orthostatic hypotension: May cause orthostatic hypotension, particularly in combination with levodopa. Orthostatic hypotension occurs most frequently during the first 2 months of therapy and decreases over time.
- Serotonin syndrome/neuroleptic malignant syndrome-like reactions: Serotonin syndrome (SS) has been reported with concomitant antidepressant (eg, SSRI, SNRI, TCA, tetracyclic and triazolopyridine antidepressants) use; concomitant use is not recommended within 14 days of rasagiline administration (within 5 weeks for antidepressants with long half-lives such as fluoxetine). SS has also been reported with concomitant use of MAO inhibitors (including selective MAO-B inhibitors), meperidine, methadone, propoxyphene, and tramadol; concomitant use within 14 days of rasagiline administration is contraindicated. A symptom complex resembling neuroleptic malignant syndrome (NMS) has been reported in association with rapid dose reduction, withdrawal of, or changes in drugs that increase central dopaminergic tone. Identification and differentiation of SS (eg, tremor, myoclonus, agitation) and more severe NMS-like reactions (eg, hyperthermia, muscle rigidity, autonomic instability, mental status changes) can be complex; monitor patients closely for either syndrome. The diagnosis of SS can be made using the Hunter Serotonin Toxicity Criteria (Dunkley, 2003). Discontinue treatment (and any concomitant antidepressants) immediately if signs/symptoms arise.
- Somnolence: Somnolence and falling asleep while engaged in activities of daily living (including operation of motor vehicles) have been reported; some cases reported that there were no warning signs for the onset of symptoms. Symptom onset may occur well after initiation of treatment; some events have occurred >1 year after initiation of rasagiline. Prior to treatment initiation, evaluate for factors that may increase these risks such as concomitant sedating medications, the presence of sleep disorders, and concomitant medications that increase rasagiline plasma levels (eg, ciprofloxacin). Monitor for drowsiness or sleepiness. If significant daytime sleepiness or episodes of falling asleep during activities that require active participation occur (eg, driving, conversations, eating), discontinue rasagiline. There is insufficient information to suggest that dose reductions will eliminate these symptoms. If therapy is continued, advise patient to avoid driving and other potentially dangerous activities.
Disease-related concerns:
- Hepatic impairment: Use with caution in patients with mild hepatic impairment; dose reduction recommended. Avoid use in patients with moderate-to-severe impairment.
- Psychotic disorders: Avoidance of use is recommended in patients with major psychotic disorder due to the risk of exacerbating psychosis with an increase in central dopaminergic tone. Many treatments for psychosis that decrease central dopaminergic tone may also decrease the effectiveness of rasagiline.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Surgical patients: According to many of the MOA inhibitor manufacturers, use within 10 days prior to elective surgery is contraindicated. The decision to continue or withhold MAO inhibitors must be done in collaboration with the patients psychiatrist. Currently, an MAO-safe anesthetic technique which excludes the use of meperidine and indirect-acting adrenergic agonists is recommended for patients requiring continued MAO inhibitor therapy (Huyse, 2006).
Special handling:
- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 2]).
Other warnings/precautions:
- Tyramine-containing products: In patients taking recommended doses of rasagiline, dietary restriction of most tyramine-containing products is not necessary; however, certain foods (eg, aged cheeses) may contain high amounts (>150 mg) of tyramine and could lead to hypertensive crisis. Avoid concomitant use with foods high in tyramine. Rasagiline is a selective inhibitor of MAO-B at the recommended doses; however, MAO-B selectivity diminishes in a dose-related manner above the recommended daily doses.
C
Adverse effects have been observed in animal reproduction studies.
Potent, irreversible and selective inhibitor of brain monoamine oxidase (MAO) type B, which plays a major role in the catabolism of dopamine. Inhibition of dopamine depletion in the striatal region of the brain reduces the symptomatic motor deficits of Parkinson 's disease. There is also experimental evidence of rasagiline conferring neuroprotective effects (antioxidant, antiapoptotic), which may delay onset of symptoms and progression of neuronal deterioration.
Rapid
Vdss: 87 L
Hepatic N-dealkylation and/or hydroxylation via CYP1A2 to multiple inactive metabolites
Urine (62%, <1% of total dose as unchanged drug); feces (7%)
~1 hour
~1 week (irreversible inhibition)
~3 hours (no correlation with biologic effect due to irreversible inhibition)
88% to 94%,primarily to albumin
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience flu-like symptoms, headache, nausea, vomiting, constipation, diarrhea, dry mouth, lack of appetite, abdominal pain, weight loss, nightmares, or joint pain. Have patient report immediately to prescriber narcolepsy, severe fatigue, abnormal movements, twitching, change in balance, dysphagia, difficulty speaking, tremors, difficulty moving, rigidity, severe dizziness, passing out, uncontrollable urges, skin growths, mole changes, angina, behavioral changes, mood changes, shortness of breath, burning or numbness feeling, swelling of arms or legs, or signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, arrhythmia, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.