Azilect

Rasagiline is used alone or in combination with another medication to treat the symptoms of Parkinson's disease (a slowly progressing disease of the nervous system causing a fixed face without expression, tremor at rest, slowing of movements, walking with shuffling steps, stooped posture and muscle weakness). Rasagiline is in a class of medications called monoamine oxidase (MAO) type B inhibitors. It works by increasing the amounts of certain natural substances in the brain.

Before taking rasagiline,

• tell your doctor and pharmacist if you are allergic to rasagiline, any other medications, or any of the ingredients in rasagiline tablets. Ask your pharmacist for a list of the ingredients.
• tell your doctor if you are taking cough and cold products containing dextromethorphan (DM; Delsym, Hold, Robitussin CoughGels, Vicks 44 Cough Relief, in Robitussin DM, others), cyclobenzaprine (Flexeril), meperidine (Demerol), methadone (Dolophine, Methadose), propoxyphene (Darvon, in Darvocet-N, others), St. John's wort, or tramadol (Ultram, in Ultracet). Also tell your doctor if you are taking MAO inhibitors such as phenelzine (Nardil), selegiline (Eldepryl), or tranylcypromine (Parnate) or have stopped taking them within the past two weeks. Your doctor may tell you not to take rasagiline if you are taking one or more of these medications.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: amphetamines (Adderall, Dexedrine, DextroStat); antidepressants; cimetidine (Tagamet); decongestants placed in the eye or nose; diet or weight-control products containing ephedrine; fluoroquinolone antibiotics including ciprofloxacin (Cipro), gatifloxacin (Tequin), levofloxacin (Levaquin), norfloxacin (Noroxin), and ofloxacin (Floxin); fluvoxamine (Luvox); medications to treat asthma; medications to treat high blood pressure; medications to treat mental illness; medications to treat pain; phenylpropanolamine (not available in the U.S.); pseudoephedrine (PediaCare, Sudafed, Suphedrine, others); and ticlopidine (Ticlid). Tell your doctor if you are taking fluoxetine (Prozac, Sarafem) or have stopped taking it within the past 5 weeks. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have or have ever had high blood pressure, mental illness or psychosis;kidney, or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking rasagiline, call your doctor.
• you should know that rasagiline may cause dizziness, lightheadedness, nausea, sweating, and fainting when you get up too quickly from a lying position. This is more common during the first 2 months of taking rasagiline. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that rasagiline may cause serious, life-threatening high blood pressure when taken with certain medications or foods. Carefully follow your doctor's instructions about medications and foods to be avoided. Call your doctor right away if you have a severe headache, blurred vision, or any of the other symptoms listed below as serious side effects.
• you should know that people who have Parkinson's disease have a higher risk of melanoma (a type of skin cancer) than people who do not have Parkinson's disease. It is not known whether this increased risk is caused by Parkinson's disease, medications used for Parkinson's disease such as rasagiline, or other factors. You should have regular visits with a dermatologist to examine your skin for melanoma.
• you should know that some people who took rasagiline or similar medications to treat Parkinson's disease experienced intense urges to gamble, increased sexual urges, and other urges that they were unable to control. Tell your doctor if you experience new or increased gambling urges, increased sexual urges, or other intense urges while taking rasagiline.

Rasagiline may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• mild headache
• joint or neck pain
• heartburn
• nausea
• vomiting
• stomach pain
• constipation
• diarrhea
• loss of appetite
• weight loss
• flu-like symptoms
• fever
• sweating
• red, swollen, and/or itchy eyes
• dry mouth
• swollen gums
• unsteadiness, wobbliness, or lack of coordination
• involuntary, repeated body movements
• lack of energy
• sleepiness
• abnormal dreams
• depression
• pain, burning, numbness, or tingling in the hands or feet
• rash
• bruising or purple discoloration on skin

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

• severe headache
• blurred vision
• seizures
• chest pain
• shortness of breath or difficulty breathing
• confusion
• unconsciousness
• slow or difficult speech
• dizziness or faintness
• weakness or numbness of an arm or leg
• hallucinating (seeing things or hearing voices that do not exist)
• extreme restlessness
• difficulty thinking clearly or understanding reality

Rasagiline may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

1. Azilect

Included as part of the PRECAUTIONS section.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Your dose may be different if you take rasagiline alone than if you take rasagiline with other Parkinson's medications. Follow your doctor's dosing instructions very carefully.

Rasagiline is only part of a complete program of treatment that may include a diet plan created for you by your doctor or nutrition counselor.

Call your doctor if your Parkinson's symptoms do not improve, or if they get worse while using rasagiline.

Do not stop using rasagiline suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using rasagiline.

Store at room temperature away from moisture and heat.

Rasagiline may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Drinking alcohol can increase certain side effects of rasagiline.

Also avoid eating foods that are high in tyramine, such as aged cheeses, sour cream, yogurt, avocados, bananas, soy sauce, and pepperoni or other dried meats. Eating tyramine while you are taking rasagiline can raise your blood pressure to dangerous levels which could cause life-threatening side effects.

Parkinsonian Syndrome

Symptomatic treatment of idiopathic parkinsonian syndrome.1 2

Used as initial monotherapy in patients with early disease1 2 5 or as adjunctive therapy to levodopa in patients with more advanced disease who exhibit a deteriorating response to levodopa/carbidopa.1 2 3 4

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of rasagiline in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of rasagiline in the elderly.

Pregnancy

Breast Feeding

Studies suggest that this medication may alter milk production or composition. If an alternative to this medication is not prescribed, you should monitor the infant for side effects and adequate milk intake.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amphetamine
• Apraclonidine
• Atomoxetine
• Benzphetamine
• Brimonidine
• Bupropion
• Carbamazepine
• Carbinoxamine
• Citalopram
• Clomipramine
• Codeine
• Cyclobenzaprine
• Cyproheptadine
• Desipramine
• Desvenlafaxine
• Deutetrabenazine
• Dexmethylphenidate
• Dextroamphetamine
• Dextromethorphan
• Diethylpropion
• Doxylamine
• Duloxetine
• Ephedrine
• Escitalopram
• Fluoxetine
• Fluvoxamine
• Guanadrel
• Guanethidine
• Hydroxytryptophan
• Imipramine
• Isocarboxazid
• Levomethadyl
• Levomilnacipran
• Linezolid
• Lisdexamfetamine
• Maprotiline
• Mazindol
• Meperidine
• Methadone
• Methamphetamine
• Methyldopa
• Methylphenidate
• Milnacipran
• Mirtazapine
• Nefopam
• Nortriptyline
• Opipramol
• Paroxetine
• Phendimetrazine
• Phenelzine
• Phenmetrazine
• Phentermine
• Phenylalanine
• Phenylephrine
• Phenylpropanolamine
• Procarbazine
• Propoxyphene
• Pseudoephedrine
• Reserpine
• Safinamide
• Selegiline
• Sertraline
• St John's Wort
• Sumatriptan
• Tapentadol
• Tetrabenazine
• Tramadol
• Tranylcypromine
• Trazodone
• Trimipramine
• Tryptophan
• Venlafaxine
• Vilazodone
• Vortioxetine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alfentanil
• Altretamine
• Amitriptyline
• Amoxapine
• Atropine
• Balofloxacin
• Besifloxacin
• Buprenorphine
• Butorphanol
• Ciprofloxacin
• Difenoxin
• Dihydrocodeine
• Diphenoxylate
• Dolasetron
• Dothiepin
• Doxepin
• Droperidol
• Enoxacin
• Epinephrine
• Ethchlorvynol
• Fentanyl
• Flumequine
• Frovatriptan
• Gatifloxacin
• Gemifloxacin
• Granisetron
• Guarana
• Hydrocodone
• Hydromorphone
• Iobenguane I 123
• Kava
• Levofloxacin
• Levorphanol
• Licorice
• Lofepramine
• Lomefloxacin
• Lorcaserin
• Ma Huang
• Mate
• Methylene Blue
• Metoclopramide
• Mibefradil
• Midodrine
• Morphine
• Morphine Sulfate Liposome
• Moxifloxacin
• Nadifloxacin
• Nalbuphine
• Naratriptan
• Nefazodone
• Norfloxacin
• Ofloxacin
• Oxycodone
• Oxymetazoline
• Oxymorphone
• Palonosetron
• Pazufloxacin
• Pefloxacin
• Peginterferon Alfa-2b
• Pentazocine
• Pixantrone
• Protriptyline
• Prulifloxacin
• Reboxetine
• Remifentanil
• Rufloxacin
• Sibutramine
• Sparfloxacin
• Sufentanil
• Tyrosine
• Valbenazine
• Ziprasidone

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acarbose
• Chlorpropamide
• Ginseng
• Glimepiride
• Glipizide
• Glyburide
• Insulin
• Insulin Aspart, Recombinant
• Insulin Bovine
• Insulin Degludec
• Insulin Detemir
• Insulin Glargine, Recombinant
• Insulin Glulisine
• Insulin Lispro, Recombinant
• Metformin
• Nateglinide
• Repaglinide
• Tolazamide
• Tolbutamide

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Avocado
• Bitter Orange
• Tobacco
• Tyramine Containing Food

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Dyskinesia (abnormal muscle movements) or
• Hypertension (high blood pressure) or
• Psychosis (mental disorder), or history of—Use with caution. May make these conditions worse.

• Liver disease, mild—Use with caution. The effects may be increased because of a slower removal of the medicine from the body.

• Liver problems, moderate or severe—Should not be used in patients with this condition.

• It is used to treat Parkinson's disease.
• It may be given to you for other reasons. Talk with the doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how Azilect affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Do not stop taking this medicine all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop Azilect, you will want to slowly stop it as ordered by your doctor.
• Some foods and drinks like cheese and red wine, when taken with this medicine, may cause very risky effects such as sudden high blood pressure. To avoid these problems, get a list of foods to avoid.
• Some people have fallen asleep during activities like driving, eating, or talking. Some people did not feel sleepy and felt alert right before falling asleep. This has happened up to 1 year after Azilect was started. If you fall asleep during activities, do not drive or do other tasks or actions that call for you to be alert while you take this medicine. Call your doctor right away if this happens or you feel very sleepy.
• High or low blood pressure may happen with Azilect. Have your blood pressure checked as you have been told by your doctor.
• If you are taking this medicine and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
• The chance of a type of skin cancer called melanoma may be raised in people with Parkinson's disease. It is not known if Azilect (rasagiline) may also raise the chance. Have skin exams while you take this medicine. Talk with your doctor.
• Talk with your doctor before you drink alcohol.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Azilect while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.

What do I do if I miss a dose?

• Skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of rasagiline in pregnant women. Azilect should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In a combined mating/fertility and embryo-fetal development study in pregnant rats, no effect on embryo-fetal development was observed at oral doses up to 3 mg/kg/day (approximately 30 times the plasma exposure (AUC) in humans at the maximum recommended human dose [MRHD, 1 mg/day]).

In pregnant rabbits administered rasagiline throughout the period of organogenesis at oral doses of up to 36 mg/kg/day, no developmental toxicity was observed. At the highest dose tested, the plasma AUC was approximately 800 times that in humans at the MRHD.

In pregnant rats administered rasagiline (0.1, 0.3, 1 mg/kg/day) orally during gestation and lactation, offspring survival was decreased and offspring body weight was reduced at 0.3 mg/kg/day and 1 mg/kg/day (10 and 16 times the plasma AUC in humans at the MRHD). No plasma data were available at the no-effect dose (0.1 mg/kg); however, that dose is similar to the MRHD on a mg/m2 basis. The effect of rasagiline on physical and behavioral development was not adequately assessed in this study.

Rasagiline may be given as an adjunct therapy to levodopa/carbidopa treatment. In pregnant rats administered rasagiline (0.1, 0.3, 1 mg/kg/day) and levodopa/carbidopa (80/20 mg/kg/day) (alone and in combination) orally throughout the period of organogenesis, there was an increased incidence of wavy ribs in fetuses from rats treated with rasagiline in combination with levodopa/carbidopa at 1/80/20 mg/kg/day (approximately 8 times the rasagiline plasma AUC in humans at the MRHD and similar to the MRHD of levodopa/carbidopa [800/200 mg/day] on a mg/m2 basis). In pregnant rabbits dosed orally throughout the period of organogenesis with rasagiline alone (3 mg/kg) or in combination with levodopa/carbidopa (rasagiline: 0.1, 0.6, 1.2 mg/kg, levodopa/carbidopa: 80/20 mg/kg/day), an increase in embryo-fetal death was noted at rasagiline doses of 0.6 and 1.2 mg/kg/day when administered in combination with levodopa/carbidopa (approximately 7 and 13 times, respectively, the rasagiline plasma AUC in humans at the MRHD). There was an increase in cardiovascular abnormalities with levodopa/carbidopa alone (similar to the MRHD on a mg/m2 basis) and to a greater extent when rasagiline (at all doses; 1-13 times the rasagiline plasma AUC in humans at the MRHD) was administered in combination with levodopa/carbidopa.

Nursing Mothers

In rats rasagiline was shown to inhibit prolactin secretion and it may inhibit milk secretion in humans.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Azilect is administered to a nursing woman.

Pediatric Use

The safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Approximately half of patients in clinical trials were 65 years and over. There were no significant differences in the safety profile of the geriatric and nongeriatric patients.

Hepatic Impairment

Rasagiline plasma concentration may be increased in patients with mild (up to 2 fold, Child-Pugh score 5-6), moderate (up to 7 fold, Child-Pugh score 7-9), and severe (Child-Pugh score 10-15) hepatic impairment. Patients with mild hepatic impairment should not exceed a dose of 0.5 mg/day. Azilect should not be used in patients with moderate or severe hepatic impairment [see Dosage and Administration (2.3), Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)].

Renal Impairment

Dose adjustment of Azilect is not required for patients with mild or moderate renal impairment because Azilect plasma concentrations are not increased in patients with moderate renal impairment. Rasagiline has not been studied in patients with severe renal impairment [see Clinical Pharmacology (12.3)].

In a dose escalation study in patients on chronic levodopa therapy treated with 10 mg of Azilect there were three reports of cardiovascular side effects (including hypertension and postural hypotension) which resolved following treatment discontinuation.

Although no cases of overdose have been observed with Azilect during the clinical development program, the following description of presenting symptoms and clinical course is based upon overdose descriptions of nonselective MAO inhibitors.

The signs and symptoms of nonselective MAOI overdose may not appear immediately. Delays of up to 12 hours after ingestion of drug and the appearance of signs may occur. The peak intensity of the syndrome may not be reached until for a day following the overdose. Death has been reported following overdose; therefore, immediate hospitalization, with continuous patient observation and monitoring for at least two days following the ingestion of such drugs in overdose, is strongly recommended.

The severity of the clinical signs and symptoms of MAOI overdose varies and may be related to the amount of drug consumed. The central nervous and cardiovascular systems are prominently involved.

Signs and symptoms of MAOI overdose may include: 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.

There is no specific antidote for Azilect overdose. The following suggestions are offered based upon the assumption that Azilect overdose may be modeled after nonselective MAO inhibitor poisoning. Treatment of overdose with nonselective MAO inhibitors is symptomatic and supportive. Respiration should be supported by appropriate measures, including management of the airway, use of supplemental oxygen, and mechanical ventilatory assistance, as required. Body temperature should be monitored closely. Intensive management of hyperpyrexia may be required. Maintenance of fluid and electrolyte balance is essential. For this reason, in cases of overdose with Azilect, dietary tyramine restriction should be observed for several weeks to reduce the risk of hypertensive tyramine reaction.

A poison control center should be called for the most current treatment guidelines.

A postmarketing report described a single patient who developed a nonfatal serotonin syndrome after ingesting 100 mg of Azilect in a suicide attempt. Another patient who was treated in error with 4 mg Azilect daily and tramadol also developed a serotonin syndrome. One patient who was treated in error with 3 mg Azilect daily experienced alternating episodes of vascular fluctuations consisting of hypertension and orthostatic hypotension.

If you miss a dose of this medicine, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Common side effects of Azilect include: dyskinesia. See below for a comprehensive list of adverse effects.

Experimental data has shown that this drug inhibits prolactin secretion and may therefore inhibit lactation.

Use with caution Excreted into human milk: Unknown