Azilect- Improving motor function in Parkinson’s patients

September 14, 2006

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Company:

Teva Neuroscience

Pharmacologic class:

Antiparkinson agent (MAO-B inhibitor)

Active ingredient:

Rasagiline 0.5 mg, 1 mg; tabs.

Indication:

Idiopathic Parkinson’s disease, as initial monotherapy and as an adjunct to levodopa.

Pharmacology:

Rasagiline is an irreversible inhibitor of monoamine oxidase type B (MAOI-B). The inhibition of this enzyme causes an increase in extracellular levels of dopamine in the brain. This may mediate the beneficial effects seen in models of dopaminergic dysfunction such as parkinsonism. The extent to which rasagiline is selective for MAO-B (rather than MAO-A) has not been fully determined; therefore patients taking this drug should avoid tyramine-rich foods, beverages, and medications containing amines.

Clinical trials:

In a monotherapy study, rasagiline was shown to have a significant beneficial effect compared with placebo on mentation, motor function, and activities of daily living in patients receiving six months of treatment and who were not on dopaminergic therapy. In two trials conducted to evaluate the use of this drug as adjunctive therapy, rasagiline 1 mg once daily was shown to reduce “off” time when added to levodopa in patients experiencing motor fluctuations. The first of these adjunctive studies compared rasagiline 1 mg/day, rasagiline 0.5 mg/day, and placebo in levodopa-treated Parkinson’s disease patients who were having motor fluctuations. The second adjunct study compared therapy with rasagiline 1 mg/day, a catechol O-methyltransferase inhibitor with levodopa/decarboxylase inhibitor, or placebo. Improvements in motor function and activities of daily living were seen with rasagiline as well.

Adults:

Monotherapy: 1 mg once daily. Adjunctive therapy: initially 0.5 mg once daily; may increase to 1 mg once daily (consider reducing levodopa dose if side effects increase). Mild hepatic impairment (Child-Pugh score 5-6) or concomitant CYP1A2 inhibitors: 0.5 mg once daily.

Children:

Not recommended.

Contraindications:

During or within two weeks of meperidine, tramadol, propoxyphene, methadone, MAOIs. Concomitant dextromethorphan, St. John’s wort, mirtazapine, sympathomimetic amines, amphetamines, cyclobenzaprine, local anesthetics with vasoconstrictors (cocaine). Elective surgery with general anesthesia. Pheochromocytoma.

Precautions:

Avoid tyramine-rich foods (see literature). Mild hepatic impairment: reduce dose; moderate to severe hepatic impairment (Child-Pugh score >7): not recommended. Monitor for melanoma. Pregnancy (Cat. C). Nursing mothers.

Interactions:

See Contraindications. Possible hypertensive crisis with excess dietary tyramine (see literature). Potentiated by CYP1A2 inhibitors (e.g., ciprofloxacin). Severe CNS toxicity (hyperpyrexia, death) with tricyclics, SSRIs, SNRIs, and MAOIs (both nonselective and type B selective); allow at least 14 days after discontinuing rasagiline before starting SSRI, tricyclic, or SNRI; allow five weeks after discontinuing fluoxetine before starting rasagiline.

Adverse reactions:

As monotherapy: postural hypotension, flu syndrome, arthralgia, depression, GI upset, falls. With levodopa: also dyskinesia, accidental injury, weight loss, abdominal pain, dry mouth, rash, bruising, somnolence, numbness, tingling.