Azilect - General Information
Azilect is an irreversible inhibitor of monoamine oxidase and is used as a monotherapy in early Parkinson's disease or as an adjunct therapy in more advanced cases.
Pharmacology of Azilect
Azilect, an irreversible inhibitor of monoamine oxidase (MAO). MAO, a flavin-containing enzyme, is classified into two major molecular species, A and B, and is localized in mitochondrial membranes throughout the body in nerve terminals, brain, liver and intestinal mucosa. MAO regulates the metabolic degradation of catecholamines and serotonin in the CNS and peripheral tissues. MAO-B is the major form in the human brain. In ex vivo animal studies in brain, liver and intestinal tissues rasagiline was shown to be a potent, irreversible monoamine oxidase type B (MAO-B) selective inhibitor. Azilect at the recommended therapeutic dose was also shown to be a potent and irreversible inhibitor of MAO-B in platelets. The selectivity of rasagiline for inhibiting only MAO-B (and not MAO-A) in humans and the sensitivity to tyramine during rasagiline treatment at any dose has not been sufficiently characterized to avoid restriction of dietary tyramine and amines contained in medications.
Azilect for patients
Patients and caregivers should be informed about which foods and beverages to avoid because of high tyramine content. They should be informed that a hypertensive crisis could occur after ingestion of certain foods (e.g., aged cheeses, pickled herring, yeast extract) or beverages (e.g. some red wines and certain beers) containing significant amounts of tyramine, or amines contained in some medications including some over-the-counter cough/cold medications. Foods high in tyramine content include those that have undergone protein change by aging, fermentation, pickling, or smoking to improve flavor such as aged cheeses, air dried meats, sauerkraut, soy sauce, tap/draft beers and red wines. The tyramine content of any protein rich food may be increased if stored for long periods or improperly refrigerated.
Patients and caregivers should be informed of the signs and symptoms associated with hypertensive crisis, including severe headache, blurred vision, difficulty thinking, seizures, chest pain, unexplained nausea or vomiting, or signs or symptoms of a stroke. Patients and caregivers should seek immediate medical attention for patients who develop any severe headache or other atypical or unusual symptoms not previously experienced.
Patients should inform their physician if they are taking, or planning to take, any prescription or over-the-counter drugs, especially antidepressants and over-the-counter cold medications, since there is a potential for interaction with Azilect. Patients should not use meperidine with AZILECT.
Patients taking AZILECT as adjunct to levodopa should be advised there is the possibility of increased dyskinesia and postural hypotension.
Patients are advised to monitor for melanomas frequently and on a regular basis. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).
Patients should be instructed to take AZILECT as prescribed. If a dose is missed, the patient should not double-up the dose of AZILECT. The next dose should be taken at the usual time on the following day.
Meperidine: Serious, sometimes fatal reactions have been precipitated with concomitant use of meperidine (e.g., Demerol and other tradenames) and MAO inhibitors including selective MAO-B inhibitors.
Dextromethorphan: The concomitant use of AZILECT and dextromethorphan was not allowed in clinical studies. The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behavior. Therefore, in view of AZILECTs MAO inhibitory activity, dextromethorphan should not be used concomitantly with AZILECT.
Sympathomimetic medications: The concomitant use of AZILECT and sympathomimetic medications was not allowed in clinical studies. Severe hypertensive reactions have followed the administration of sympathomimetics and non-selective MAO inhibitors. One case of hypertensive crisis has been reported in a patient taking the recommended doses of a selective MAO-B inhibitor and a sympathomimetic medication (ephedrine). Therefore, in view of AZILECTs MAO inhibitory activity, AZILECT should not be used concomitantly with sympathomimetics including nasal and oral decongestants and cold remedies.
MAO inhibitors: AZILECT should not be administered along with other MAO inhibitors because of the increased risk of non-selective MAO inhibition that may lead to a hypertensive crisis.
Selective serotonin reuptake inhibitors (SSRIs), tricyclic and tetracyclic antidepressants: Concomitant use of SSRI, tricyclic, and tetracyclic antidepressants with AZILECT is not recommended
Ciprofloxacin and Other CYP1A2 Inhibitors:Rasagiline plasma concentrations may increase up to 2 fold in patients using concomitant ciprofloxacin and other CYP1A2 inhibitors. This could result in increased adverse events.
No specific laboratory tests are required for the treatment of patients on AZILECT.
Meperidine and Other Analgesics: AZILECT is contraindicated for use with meperidine. Serious reactions have been precipitated with concomitant use of meperidine (e.g., Demerol and other tradenames) and MAO inhibitors including selective MAO-B inhibitors. These reactions have been characterized by coma, severe hypertension or hypotension, severe respiratory depression, convulsions, malignant hyperpyrexia, excitation, peripheral vascular collapse and death. At least 14 days should elapse between discontinuation of Azilect and initiation of treatment with meperidine.
For similar reasons, Azilect should not be administered with the analgesic agents tramadol, methadone, and propoxyphene.
Other Drugs: Azilect should not be used with the antitussive agent dextromethorphan. The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behavior. AZILECT is also contraindicated for use with St. Johns wort, mirtazapine (a tetracyclic antidepressant), and cyclobenzaprine (a tricyclic muscle relaxant).
Sympathomimetic Amines: Like other MAOIs, AZILECT is contraindicated for use with sympathomimetic amines, including amphetamines as well as cold products and weight-reducing preparations that contain vasoconstrictors (e.g., pseudoephedrine, phenylephrine, phenylpropanolamine, and ephedrine). Severe hypertensive reactions have followed the administrations of sympathomimetics and non-selective MAO inhibitors. At least one case of hypertensive crisis has been reported in a patient taking the recommended doses of a selective MAO-B inhibitor and a sympathomimetic medication (ephedrine).
MAO inhibitors: AZILECT should not be administered along with other MAO inhibitors because of the increased risk of non-selective MAO inhibition that may lead to a hypertensive crisis. At least 14 days should elapse between discontinuation of Azilect and initiation of treatment with MAO inhibitors.
Surgery: As with other MAOIs, patients taking AZILECTshould not undergo elective surgery requiring general anesthesia. Also, they should not be given cocaine or local anesthesia containing sympathomimetic vasoconstrictors. AZILECT should be discontinued at least 14 days prior to elective surgery. If surgery is necessary sooner, benzodiazepines, mivacurium, rapacuronium, fentanyl, morphine, and codeine may be used cautiously.
Pheochromocytoma: As with other MAOIs, AZILECT is contraindicated in patients with pheochromocytoma.
Additional information about Azilect
Azilect Indication: For the treatment of the signs and symptoms of idiopathic Parkinsons disease as initial monotherapy and as adjunct therapy to levodopa.
Mechanism Of Action: The precise mechanisms of action of rasagiline are unknown. One mechanism is believed to be related to its MAO-B inhibitory activity, which causes an increase in extracellular levels of dopamine in the striatum. The elevated dopamine level and subsequent increased dopaminergic activity are likely to mediate rasagilines beneficial effects seen in models of dopaminergic motor dysfunction.
Drug Interactions: Altretamine Risk of severe hypotension
Amitriptyline Possibility of severe adverse effects
Amoxapine Possibility of severe adverse effects
Clomipramine Possibility of severe adverse effects
Desipramine Possibility of severe adverse effects
Dextromethorphan Possible severe adverse reaction
Doxepin Possibility of severe adverse effects
Imipramine Possibility of severe adverse effects
Meperidine Potentiall fatal adverse effects
Nortriptyline Possibility of severe adverse effects
Protriptyline Possibility of severe adverse effects
Trimipramine Possibility of severe adverse effects
Venlafaxine Possible severe adverse reaction with this combination
Sertraline Possible severe adverse reaction with this combination
Paroxetine Possible severe adverse reaction with this combination
Nefazodone Possible severe adverse reaction with this combination
Mirtazapine Possible severe adverse reaction with this combination
Midodrine Possible severe adverse reaction with this combination
Methylphenidate Possible severe adverse reaction with this combination
Fluvoxamine Possible severe adverse reaction with this combination
Fluoxetine Possible severe adverse reaction with this combination
Escitalopram Possible severe adverse reaction with this combination
Duloxetine Possible severe adverse reaction with this combination
Citalopram Possible severe adverse reaction with this combination
Bupropion Possible severe adverse reaction with this combination
Atomoxetine Possible severe adverse reaction with this combination
Amphetamine Possible hypertensive crisis
Benzphetamine Possible hypertensive crisis
Buspirone Possible blood pressure elevation
Ciprofloxacin Ciprofloxacin increases effect/toxicity of rasagiline
Dextroamphetamine Possible hypertensive crisis
Dexfenfluramine Possible hypertensive crisis
Fenfluramine Possible hypertensive crisis
Diethylpropion Possible hypertensive crisis
Ginseng Ginseng increases the effect and toxicity of MAOI
Mazindol Possible hypertensive crisis
Methamphetamine Possible hypertensive crisis
Phendimetrazine Possible hypertensive crisis
Phenmetrazine Possible hypertensive crisis
Phentermine Possible hypertensive crisis
Tramadol Increased risk of seizures and serotonin syndrome
St. John's Wort Increased risk of toxicity with this association
Sibutramine Possible serotoninergic syndrome with this combination
Cyclobenzaprine Increased risk of toxicity with this association
Dobutamine Increased arterial pressure
Dopamine Increased arterial pressure
Ephedra Increased arterial pressure
Ephedrine Increased arterial pressure
Epinephrine Increased arterial pressure
Fenoterol Increased arterial pressure
Isoproterenol Increased arterial pressure
Mephentermine Increased arterial pressure
Metaraminol Increased arterial pressure
Methoxamine Increased arterial pressure
Norepinephrine Increased arterial pressure
Orciprenaline Increased arterial pressure
Terbutaline Increased arterial pressure
Salbutamol Increased arterial pressure
Pseudoephedrine Increased arterial pressure
Procaterol Increased arterial pressure
Pirbuterol Increased arterial pressure
Phenylephrine Increased arterial pressure
Phenylpropanolamine Increased arterial pressure
Food Interactions: Not Available
Generic Name: Rasagiline
Drug Category: Monoamine Oxidase Inhibitors; Neuroprotective Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Rasagiline: Azilect;
Absorption: Rasagiline is rapidly absorbed following oral administration. The absolute bioavailability of rasagiline is about 36%.
Toxicity (Overdose): Signs and symptoms of overdosage may include, alone or in combination, any of the following: drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonos, convulsions, and coma; rapid and irregular pulse, hypertension, hypotension and vascular collapse; precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, and cool, clammy skin.
Protein Binding: Plasma protein binding ranges from 88-94% with mean extent of binding of 61-63% to human albumin over the concentration range of 1-100 ng/ml.
Biotransformation: Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. In vitro experiments indicate that both routes of rasagiline metabolism are dependent on the cytochrome P450 (CYP) system, with CYP 1A2 being the major isoenzyme involved in rasagiline metabolism.
Half Life: Rasagiline has a mean steady-state half life of 3 hours but there is no correlation of pharmacokinetics with its pharmacological effect because of its irreversible inhibition of MAO-B.
Dosage Forms of Azilect: Tablet Oral
Chemical IUPAC Name: (1R)-N-prop-2-ynyl-2,3-dihydro-1H-inden-1-amine
Chemical Formula: C12H13N
Rasagiline on Wikipedia: http://en.wikipedia.org/wiki/Rasagiline
Organisms Affected: Humans and other mammals