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For people with ALS, from the start, prescribe Rilutek

Clinical Information

Rilutek offers an early survival benefit in ALS treatment 1,2,3

In 2 large, double-blind, placebo-controlled trials among ALS patients (N=1,114)1,2,3

  • Survival curves were significantly different for Rilutek vs placebo*†‡

— Survival defined as time until tracheostomy or death

  • During the 18-month study period, a 2- to 3-month increase in median survival time was observed with Rilutek vs placebo
  • There were no statistically significant differences in mortality at 18 months

— After 18 months, patients were followed for up to 60 months in open-label protocols4

Survival benefit seen early in both studies2,3

Study 1†
(N=155)

image of study 1 Adapted from
Bensimon G et al.
N Engl J Med. 1994.
 

Study 2†
(N=959)

image of study 2 Adapted from
Lacomblez L et al.
Lancet. 1996.

* Efficacy evaluated using intent-to-treat analysis.
† Study 1: At baseline, Rilutek n=77, placebo n=78; P=0.05 Wilcoxon test, P=0.12 Logrank test.
‡ Study 2: At baseline, patients treated with Rilutek received either 50 mg/day (n=237), 100 mg/day (n=236), or 200 mg/day (n=244); placebo (n=242). Clinical data show that the best benefit/risk ratio was for the 100 mg/day dose. P=0.05 Wilcoxon test, P=0.076 Logrank test

  • Rilutek is indicated for the treatment of patients with ALS1
  • Riluzole extends survival and/or time to tracheostomy or death.1


Rilutek is generally well-tolerated

Withdrawal from therapy due to adverse events in clinical trials§

Rilutek 100 mg/day

Placebo

18% (57/313)

13% (42/320)

Most common adverse events associated with Rilutek 100 mg/day

 

Rilutek
n=313

Placebo
n=320

Asthenia

19.2%

12.2%

Nausea

16.3%

10.6%

Lung function decrease
—Not associated with decreased vital capacity

10.2%

9.4%

ALT > 3 x upper limit of normal (ULN)

9.9%

3.8%

Headache

7.3%

6.6%

In clinical studies…

  • Maximum increases in serum ALT usually appeared within 3 months after starting Rilutek therapy and were usually transient when < 5 times ULN
§

Excluding death.

Lung function decrease is 1 of 7 standardized terms used to describe adverse experiences related to pulmonary function. The frequencies of adverse events recorded under the other 6 terms in the category (bronchitis, apnea, respiratory disorder, dyspnea, pneumonia, and lung disorder) were all comparable to or lower than placebo. Overall, respiratory adverse events occurred in 50% of patients treated with Rilutek and in 55% of placebo.

Glutamate inhibition and Rilutek

The glutamate hypothesis: one of several theories about the cause of ALS

Experimental studies have shown…

  • Glutamate is the primary excitatory neurotransmitter of the brain5
  • Elevated plasma glutamate levels have been observed in patients with early stage ALS6
  • Under certain conditions, excess glutamate can accumulate and lead to  degeneration and death of motor neurons7,8
image of Method of Action 1   image of Method of Action 2
Normally, when glutamate is released from presynaptic terminals, the postsynaptic receptors are briefly exposed to low levels appropriate for neurotransmission.7   In neurodegenerative diseases such as ALS, prolonged exposure to glutamate could cause degeneration and death of motor neurons.7

Click here to view the Glutamate Hypothesis  get flash button

Rilutek exhibited neuroprotective properties in preclinical studies1

  • Data suggest Rilutek protects motor neurons from degeneration and death

The effect of Rilutek may relate to reduced glutamatergic transmission1

Although the mechanism of action of Rilutek is not known, several pharmacologic properties contribute to blockade of glutamatergic transmission1

  • Inhibition of glutamate release
  • Inactivation of voltage-dependent sodium channels
  • Interference with intracellular events following binding of excitatory neurotransmitters
 
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Important Treatment Considerations

  • Evaluate serum ALT levels every month during the first 3 months of treatment, and every 3 months during the remainder of the first year. Thereafter, serum ALT levels should be periodically evaluated more frequently in patients who develop elevations. Rilutek should be discontinued if ALT levels increase to 5 times ULN or if clinical jaundice develops.
  • Advise patients about the potential for dizziness, vertigo, or somnolence and not to drive or operate machinery until they have sufficient experience on Rilutek.
  • Advise patients to report any febrile illness; measure WBCs.
  • Use Rilutek with caution in patients with concomitant liver insufficiency; caution should be exercised when prescribing Rilutek to patients taking drugs that are potentially hepatotoxic or highly protein bound:
    • Interactions may also occur when riluzole is given concurrently with agents that affect hepatic CYP 1A2 activity.*
*CYP 1A2 is the principal isoenzyme involved in the initial oxidative metabolism of riluzole. CYP 1A2 inhibitors, such as amitriptyline, caffeine, phenacetin, theophylline, or quinolones, may potentially decrease the rate of riluzole elimination. CYP 1A2 inducers, such as cigarette smoke, charcoal-broiled food, rifampicin, or omeprazole, may potentially increase the rate of elimination.
 
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The health information contained herein is provided for general educational purposes only. As a healthcare professional, you are the single best source of information regarding healthcare for your patients with ALS. Please contact sanofi-aventis if you have any questions or need more information about treating ALS.

 
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References

  1. Rilutek Prescribing Information.
  2. Bensimon G, Lacomblez L, Meininger V, and the ALS/Riluzole Study Group. A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med. 1994;330:585-591.
  3. Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V, for the Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Lancet. 1996;347:1425-1431.
  4. Data on file, sanofi-aventis.
  5. Rothstein JD, Martin LJ, Kuncl RW. Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N Engl J Med. 1992;326:1464-1468.
  6. Plaitakis A, Caroscio JT. Abnormal glutamate metabolism in amyotrophic lateral sclerosis. Ann Neurol. 1987;22:575-579.
  7. Choi DW. Amyotrophic lateral sclerosis and glutamate—too much of a good thing [editorial]? N Engl J Med. 1992;326:1493-1495.
  8. Greenamyre JT. The role of glutamate in neurotransmission and in neurologic disease. Arch Neurol . 1986;43:1058-1063
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US.RIL.07.07.001 Last Update: May 2007