Teva Neuroscience's Azilect

Pharmacy Times, Volume 0, 0

Teva Neuroscience has received FDAapproval for Azilect (rasagiline), the firstonce-daily treatment for Parkinson's disease(PD). A survey of patients with PDrevealed that 83% of them take PD medicationsup to 5 times a day.1 Azilect isindicated for the treatment of PD inadults as both monotherapy and adjuncttherapy to levodopa.2

Mechanism of Action

The exact mechanism of Azilect isunknown; however, it has been shown tobe an irreversible monoamine oxidase(MAO) inhibitor. MAO exists in the nerveterminals, brain, liver, and intestinalmucosa in 2 forms: type A and type B.Inhibition of type B (MAO-B) is believed toincrease the dopamine levels in the striatum,thus improving motor function. It isnot yet determined if Azilect selectivelyinhibits MAO-B.2

Clinical Trials

Three clinical trials evaluated the safetyand efficacy of Azilect. Azilect asmonotherapy was studied in a doubleblind,randomized, fixed-dose parallelgroupstudy comparing Azilect withplacebo in 404 patients who had PD for~1 year. Patients were randomized toreceive placebo, Azilect 1 mg daily, orAzilect 2 mg daily. Additional treatmentwith levodopa was not permitted in thestudy. After 6 months, patients usingAzilect were shown to have significantbenefit, compared with those using placebo.2

Two studies evaluated Azilect asadjunctive therapy to levodopa. Bothstudies consisted of patients who had PDfor an average of 9 years and who hadbeen using levodopa for an average of 8years. Study 1 consisted of 472 patientsin the United States and Canada and randomizedpatients to receive either placebo,Azilect 0.5 mg, or Azilect 1 mg, inaddition to their levodopa regimen. Study2 consisted of 687 patients in Europe,Argentina, and Israel who were randomizedto take either placebo, Azilect 1 mg,or a catechol O-methyltransferase inhibitor,in addition to their levodopa/decarboxylase inhibitor therapy.Both studies showed significant improvementin PD symptoms with theaddition of Azilect.2

Safety

The use of Azilect is contraindicatedwith concomitant administration ofmeperidine, tramadol, methadone, propoxyphene,dextromethorphan, St.John's wort, mirtazapine, cyclobenzaprine,other monoamine oxidase inhibitors(MAOIs), or amphetamines.Azilect is contraindicated with sympathomimeticssuch as pseudoephedrine,phenylephrine, phenylpropanolamine, orephedrine. Patients should not have electivesurgery requiring general anesthesiaor receive local anesthesia while usingAzilect. Patients with pheochromocytomashould not use Azilect.

As with other MAOIs, consumption oftyramine-containing foods should beavoided while patients are using anydose of Azilect. Examples of tyraminerichfoods include aged cheeses, air-driedmeats, pickled herring, yeast extract,aged red wines, tap or draft beers, sauerkraut,and soy sauce. Azilect is metabolizedby CYP1A2; its use with ciprofloxacinand other CYP1A2 inhibitorsshould be avoided if possible. Patientswith moderate-to-severe hepatic diseaseor a tumor of the adrenal gland shouldnot use Azilect.

Patients using Azilect should be evaluatedregularly for melanoma, preferablyby a dermatologist.1,2 Azilect is a PregnancyCategory C drug.2

Patient Education

Patients using Azilect and their caregiversshould be educated about whichfoods contain tyramine and the importanceof avoiding them. They should becounseled to inform their doctor of anyprescription or OTC medication or dietarysupplement they are taking both prior toinitiation of therapy with Azilect and duringtreatment. Patients should understandthe signs and symptoms of ahypertensive crisis (severe headache,blurred vision, difficulty thinking, chestpain, nausea and vomiting, signs andsymptoms of a stroke). They should beadvised to contact their health care professionalimmediately if any of thesesymptoms occur or at the onset of anyother unusual symptoms.2

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

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

For a list of references, send a stamped,self-addressed envelope to: ReferencesDepartment, Attn. A. Rybovic, PharmacyTimes, Ascend Media Healthcare, 103 CollegeRoad East, Princeton, NJ 08540; or send an emailrequest to: arybovic@ascendmedia.com.