IMPORTANT SAFETY INFORMATION
AZILECT® (rasagiline tablets) is contraindicated with meperidine, tramadol, methadone, propoxyphene, dextromethorphan, St. John’s wort, cyclobenzaprine, or another (selective or non-selective) MAOI. Read More Important Safety Information

AZILECT demonstrated add-on efficacy and tolerability as Parkinson's disease progresses1-4

  • Reduced “off” time by nearly 2 hours in levodopa-treated patients2
  • Across AZILECT as add-on to levodopa studies:
    • Approximately 20% of patients were taking levodopa only5
    • Approximately 65% of patients were also taking a dopamine agonist4
    • Approximately 35% of patients were also taking a COMT inhibitor with the majority of those also on a dopamine agonist4
  • Improved ADLs during “off” time4
  • Improvement in total UPDRS* score at 18 weeks when added to a dopamine agonist1,4
  • Demonstrated safety and tolerability1-4

*The UPDRS (Unified Parkinson's Disease Rating Scale), a commonly used research tool in PD, is a multi-item rating scale that measures the ability of a patient to perform mental and motor tasks as well as activities of daily living. Total UPDRS is measured on a scale of 0-176, with a reduction in score demonstrating improvement.6

See results from the 4 Class 1 clinical studies for AZILECT:


How AZILECT works

AZILECT has a mechanism of action that is complementary to various treatment regimens.4 See how it works in the brain.

AZILECT is part of a rational polypharmacy strategy

Rational polypharmacy is a treatment strategy when monotherapy is suboptimal.7,8

Goals:

  • Optimize symptomatic control
  • Minimize risk of side effects and motor complications

Opportunities:

  • Delay levodopa
  • Maintain low doses of dopamine agonists and levodopa

STRIDE-PD post hoc analysis of risk of motor complications

Frequency of wearing off and dyskinesia at study termination

STRIDE-PD post hoc analysis: Blinded assessment of dyskinesia and wearing off in 745 patients performed at 3-month intervals for the randomized, prospective, double-blind, 134- to 208-week STRIDE-PD study comparing the risk of developing dyskinesia in patients receiving either levodopa/carbidopa or levodopa/carbidopa/entacapone.8

  • Recent data suggest a levodopa threshold effect8
    • Risks of dyskinesia and wearing off are markedly increased at ≥400 mg/day
  • LD polypharmacy using concurrent drugs, such as dopamine agonists and MAO-B inhibitors, may be preferable to continuously increasing the levodopa dose8
  • AZILECT is an effective add-on to DA and levodopa4
  • AZILECT has a mechanism of action that is complementary to various PD treatment regimens4

AZILECT demonstrated efficacy and tolerability in moderate and advanced PD

AZILECT reduced “off” time by nearly 2 hours when added to levodopa2,4

Difference in total daily off time over 6 months, AZILECT® and placebo

PRESTO: 26-week, double-blind, randomized, fixed-dose, parallel-group study of 472 levodopa-treated patients experiencing motor fluctuations.2,4

  • 29% reduction (nearly 2 hours) in “off” time for levodopa-treated patients with motor fluctuations taking AZILECT 1 mg/day2
  • AZILECT complements various levodopa treatment regimens4
  • AZILECT demonstrated tolerability as add-on therapy4

Similar “off” time results were seen in the LARGO study

  • 21% reduction (-1.2 hours) in “off” time for levodopa-treated patients with motor fluctuations taking AZILECT 1 mg/day3,4

LARGO: 18-week, double-blind, multicenter study of 687 levodopa-treated patients experiencing motor fluctuations.3,4

Cognitive and behavioral adverse events were comparable to placebo when AZILECT was added to levodopa9†


Most frequent cognitive and behavioral AEs PRESTO9 AZILECT 1 mg + levodopa % of patients
(n=149)
Placebo + levodopa % of patients
(n=159)
Sleep disorder/insomnia 8.1 6.9
Somnolence 6 4.4
Depression 4.7 6.3
Hallucinations 4 3.1
Confusion 1.3 0.6
  • Low discontinuation rate due to adverse events as adjunct therapy (9% for 0.5 mg and 7% for 1 mg vs 6% for placebo)4

Based on UPDRS Part I (mentation, behavior, and mood).6

AZILECT and “off” time

By blocking MAO-B, AZILECT preserves dopamine and reduces “off” time.

AZILECT demonstrated efficacy and tolerability in early and moderate PD

AZILECT provides additional symptom control when added to a DA alone1,4

Mean change from baseline in total UPDRS at week 18, AZILECT® and placebo

ANDANTE: 18-week, randomized, double-blind, placebo-controlled study of 328 patients not adequately controlled on dopamine agonist monotherapy. Of the 328 randomized patients, 321 patients were part of the modified intent-to-treat (mITT) population, defined as having taken at least one dose of study medication and completing both baseline and at least one post-baseline efficacy assessment.1,4

  • AZILECT demonstrated a -2.4-unit improvement in total UPDRS scores at 18 weeks as compared to placebo (P=0.012)1,4
  • Adding AZILECT to a dopamine agonist (DA) provides another option for symptom control before increasing the DA or adding levodopa1
  • AZILECT has a mechanism of action that is complementary to DA therapy1,4
ANDANTE patient demographics at baseline1:
Average duration of disease 2 years
Average age 63 years
Mean total UPDRS score 31
Mean ropinirole dose 8 mg/day
Mean pramipexole dose 1.5 mg/day

Adverse events were compared with placebo when AZILECT was added to a DA


Adverse events in ANDANTE1,4,‡ AZILECT 1mg + DA % of patients
(n=162)
Placebo + DA % of patients
(n=164)
Peripheral edema 7 4
Somnolence 7 7
Nausea 6 4
Fall 6 1
Arthralgia 5 2
Cough 4 1
Insomnia 4 1
Orthostatic hypotension 3 1

The most commonly observed adverse reactions were those in which the treatment difference for the incidence in AZILECT-treated patients was at least 3% greater than the incidence in placebo-treated patients. Potential dopaminergic AEs include: peripheral edema, somnolence, nausea, and orthostatic hypotension.

Of the 328 randomized patients, 326 were part of the safety population, defined as having taken at least one dose of study medication.

  • Low discontinuation rate due to adverse events as add-on to DA therapy (8% for AZILECT 1 mg vs 4% for placebo)4

The ANDANTE study

AZILECT's mechanism of action complements DA therapy.

AZILECT demonstrated efficacy and tolerability in early PD

Improves symptoms of PD over 6 months4,10

Difference over 6 months in total UPDRS, AZILECT® and placebo

TEMPO: 26-week, double-blind, randomized, fixed-dose, parallel-group study of 404 early patients not yet receiving dopaminergic therapy.4,10 The TEMPO study was conducted by the Parkinson Study Group (PSG).10

  • AZILECT demonstrated a -3.85-unit improvement in total UPDRS score at 6 months as compared to placebo (P=0.0001)5,10
  • AZILECT demonstrated tolerability similar to placebo4

AZILECT monotherapy demonstrated a low incidence of dopaminergic side effects10


Dopaminergic side effects in TEMPO10 AZILECT 1 mg
% of patients
(n=149)
Placebo
% of patients
(n=151)
Nausea 4.0 7.3
Postural hypotension 2.7 4.6
Vomiting 1.3 0.7
Hallucinations 1.3 0.7
Peripheral edema 1.3 2.6
Somnolence 0.7 1.3
  • AZILECT is effective and safe in the elderly4,11
  • Long-term safety profile (5 years) similar to that observed with shorter duration of exposure4,5
  • Low incidence of postural hypotension4
  • Low discontinuation rate due to adverse events as monotherapy (5% vs 2% for placebo)4
  • AZILECT shown to be selective for MAO-B at recommended doses4
    • No dietary tyramine restriction required when AZILECT is taken at recommended doses

Early treatment with AZILECT

Setting treatment expectations for patients when they start AZILECT is important. There is a difference between the onset of action of AZILECT and that of levodopa.


INDICATION
AZILECT® (rasagiline tablets) is indicated for the treatment of Parkinson’s disease (PD).

IMPORTANT SAFETY INFORMATION
  • AZILECT is contraindicated with meperidine, tramadol, methadone, propoxyphene, dextromethorphan, St. John’s wort, cyclobenzaprine, or another (selective or non-selective) MAOI
  • Exacerbation of hypertension may occur during treatment with AZILECT. Monitor patients for new-onset hypertension or hypertension that is not adequately controlled after starting AZILECT
  • Dietary tyramine restriction is not required during treatment with recommended doses of AZILECT. However, patients should be advised to avoid foods containing a very high amount of tyramine because of the potential for severe increases in blood pressure, also referred to as hypertensive urgency, crisis, or emergency
  • Concomitant use of AZILECT and antidepressants is not recommended; serotonin syndrome has been reported with concomitant use with an antidepressant or MAO inhibitors
  • Patients treated with AZILECT and other dopaminergic medications have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles. Prescribers should monitor patients for drowsiness or sleepiness
  • Patients with moderate to severe hepatic impairment should not take AZILECT. AZILECT should not exceed 1 mg/day or 0.5 mg/day for patients with mild hepatic impairment or in patients using ciprofloxacin or another CYP1A2 inhibitor
  • Patients receiving AZILECT with adjunct therapy have reported orthostatic hypotension, especially in the first two months of treatment
  • Dyskinesia (or exacerbations of dyskinesia), hallucinations or psychotic-like behavior, impulse control or compulsive behaviors, withdrawal-emergent hyperpyrexia/confusion, and melanoma are potentially associated with AZILECT
  • The most common side effects as monotherapy (AZILECT 1 mg, placebo, respectively [%]) include flu syndrome (5, 1), arthralgia (7, 4), depression (5, 2), and dyspepsia (7, 4)
  • The most common side effects as adjunct to dopamine agonists (AZILECT 1 mg, placebo, respectively [%]) include peripheral edema (7, 4), fall (6, 1), arthralgia (5, 2), cough (4, 1), and insomnia (4, 1)
  • The most common side effects as adjunct to levodopa therapy (AZILECT 1 mg, 0.5 mg, and placebo, respectively [%]) include dyskinesia (18, 18, 10), accidental injury (12, 8, 5), weight loss (9, 2, 3), postural hypotension (9, 6, 3), vomiting (7, 4, 1), anorexia (5, 2, 1), arthralgia (8, 6, 4), abdominal pain (5, 2, 1), nausea (12, 10, 8), constipation (9, 4, 5), dry mouth (6, 2, 3), rash (6, 3, 3), abnormal dreams (4, 1, 1), fall (11, 12, 8), and tenosynovitis (3, 1, 0)
  • Please see full Prescribing Information.

REFERENCES

1. Hauser RA, Silver D, Choudhry A, Eyal E, Isaacson S; for the ANDANTE study investigators. Randomized, controlled trial of rasagiline as an add-on to dopamine agonists in Parkinson's disease [published online June 11, 2014]. Mov Disord. doi: 10.1002/mds.25877.
2. The Parkinson Study Group. A randomized, placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch Neurol. 2005;62:241-248.
3. Rascol O, Brooks DJ, Melamed E, et al. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet. 2005;365(9463):947-954.
4. AZILECT Prescribing Information, May 2014.
5. Data on file, Teva Pharmaceuticals USA, Inc.
6. Fahn S, Elton RL; UPDRS Development Committee. Unified Parkinson's Disease Rating Scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M, eds. Recent Developments in Parkinson's Disease. Florham Park, NJ: Macmillan; 1987:153-163,293-304.
7. Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.
8. Olanow CW, Kieburtz K, Rascol O, et al, for the Stalevo Reduction in Dyskinesia Evaluation in Parkinson’s Disease (STRIDE-PD) Investigators. Factors predictive of the development of Levodopa-induced dyskinesia and wearing-off in Parkinson’s disease. Mov Disord. 2013;28:1064-1072.
9. Elmer L, Schwid S, Eberly S, et al. Rasagiline-associated motor improvement in PD occurs without worsening of cognitive and behavioral symptoms. J Neurol Sci. 2006;248(1-2):78-83.
10. Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: the TEMPO study. Arch Neurol. 2002;59(12):1937-1943.
11. Goetz CG, Schwid SR, Eberly SW, et al. Safety of rasagiline in elderly patients with Parkinson disease. Neurology. 2006;66:1427-1429.