Teva Neuroscience's Azilect

Author: Monica Holmberg, PharmD

Teva Neuroscience has received FDA approval for Azilect (rasagiline), the first once-daily treatment for Parkinson's disease (PD). A survey of patients with PD revealed that 83% of them take PD medications up to 5 times a day.1 Azilect is indicated for the treatment of PD in adults as both monotherapy and adjunct therapy to levodopa.2

Mechanism of Action

The exact mechanism of Azilect is unknown; however, it has been shown to be an irreversible monoamine oxidase (MAO) inhibitor. MAO exists in the nerve terminals, brain, liver, and intestinal mucosa in 2 forms: type A and type B. Inhibition of type B (MAO-B) is believed to increase the dopamine levels in the striatum, thus improving motor function. It is not yet determined if Azilect selectively inhibits MAO-B.2

Clinical Trials

Three clinical trials evaluated the safety and efficacy of Azilect. Azilect as monotherapy was studied in a doubleblind, randomized, fixed-dose parallelgroup study comparing Azilect with placebo in 404 patients who had PD for ~1 year. Patients were randomized to receive placebo, Azilect 1 mg daily, or Azilect 2 mg daily. Additional treatment with levodopa was not permitted in the study. After 6 months, patients using Azilect were shown to have significant benefit, compared with those using placebo.2

Two studies evaluated Azilect as adjunctive therapy to levodopa. Both studies consisted of patients who had PD for an average of 9 years and who had been using levodopa for an average of 8 years. Study 1 consisted of 472 patients in the United States and Canada and randomized patients to receive either placebo, Azilect 0.5 mg, or Azilect 1 mg, in addition to their levodopa regimen. Study 2 consisted of 687 patients in Europe, Argentina, and Israel who were randomized to take either placebo, Azilect 1 mg, or a catechol O-methyltransferase inhibitor, in addition to their levodopa/ decarboxylase inhibitor therapy. Both studies showed significant improvement in PD symptoms with the addition of Azilect.2

Safety

The use of Azilect is contraindicated with concomitant administration of meperidine, tramadol, methadone, propoxyphene, dextromethorphan, St. John's wort, mirtazapine, cyclobenzaprine, other monoamine oxidase inhibitors (MAOIs), or amphetamines. Azilect is contraindicated with sympathomimetics such as pseudoephedrine, phenylephrine, phenylpropanolamine, or ephedrine. Patients should not have elective surgery requiring general anesthesia or receive local anesthesia while using Azilect. Patients with pheochromocytoma should not use Azilect.

As with other MAOIs, consumption of tyramine-containing foods should be avoided while patients are using any dose of Azilect. Examples of tyraminerich foods include aged cheeses, air-dried meats, pickled herring, yeast extract, aged red wines, tap or draft beers, sauerkraut, and soy sauce. Azilect is metabolized by CYP1A2; its use with ciprofloxacin and other CYP1A2 inhibitors should be avoided if possible. Patients with moderate-to-severe hepatic disease or a tumor of the adrenal gland should not use Azilect.

Patients using Azilect should be evaluated regularly for melanoma, preferably by a dermatologist.1,2 Azilect is a Pregnancy Category C drug.2

Patient Education

Patients using Azilect and their caregivers should be educated about which foods contain tyramine and the importance of avoiding them. They should be counseled to inform their doctor of any prescription or OTC medication or dietary supplement they are taking both prior to initiation of therapy with Azilect and during treatment. Patients should understand the signs and symptoms of a hypertensive crisis (severe headache, blurred vision, difficulty thinking, chest pain, nausea and vomiting, signs and symptoms of a stroke). They should be advised to contact their health care professional immediately if any of these symptoms occur or at the onset of any other unusual symptoms.2

Side effects of Azilect include headache, joint pain, and indigestion. When it is taken with levodopa, side effects may include uncontrolled movements, accidental injury, nausea, weight loss, constipation, low blood pressure when standing, dry mouth, rash, and sleepiness.1

Dr. Holmberg is a pharmacist with Phoenix Children's Hospital, Phoenix, Ariz.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Rybovic, Pharmacy Times, Ascend Media Healthcare, 103 College Road East, Princeton, NJ 08540; or send an email request to: arybovic@ascendmedia.com.