Riluzole

trade name: Rilutek; drug class: glutamate antagonist; action: inhibits presynaptic release of glutamic acid in central nervous system; use: treatment of amyotrophic lateral sclerosis (Lou Gehrig disease).

Brand names: Rilutek®

Chemical formula:

Drug Forms:
• Riluzole tablets (below)
• Riluzole Oral tablet

Español:
• Tabletas de riluzol
• Riluzol, Tableta oral

Riluzole tablets

What are riluzole tablets?

RILUZOLE (Rilutek®) slows down the progression of amyotrophic lateral sclerosis (also known as Lou Gehrig's disease). Riluzole helps to delay the loss of muscle strength and limb function for several months; it is not a cure. It can slow the loss of respiratory function. Generic riluzole tablets are approved, but are not yet marketed in the US.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
• heart disease or high blood pressure
• kidney disease
• liver disease
• lung disease
• tobacco smoker
• an unusual or allergic reaction to riluzole, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I take this medicine?

Take riluzole tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. It is best to take riluzole on an empty stomach, at least 1 hour before or 2 hours after meals. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking except on your prescriber's advice.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?

What drug(s) may interact with riluzole?

• allopurinol
• amitriptyline
• barbiturate medicines for inducing sleep or treating seizures (convulsions)
• caffeine
• carbamazepine
• certain antibiotics called quinolones
• methyldopa
• omeprazole
• rifampin
• sulfasalazine
• tacrine
• theophylline

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What should I watch for while taking riluzole?

Visit your prescriber or health care professional for regular checks on your progress. Check with your prescriber or health care professional if your symptoms get worse. Tell your prescriber or health care professional if you have a fever, chills, or other signs of infection; do not treat yourself.

Avoid alcohol and tobacco smoking while you are taking riluzole. Alcohol can increase the risk of getting liver damage. Tobacco smoking can affect how riluzole is handled by your body. Ask your prescriber or health care professional for ways to help you stop smoking or drinking.

You may get dizzy or lose your balance. Do not drive, use machinery, or do anything that needs mental alertness until you know how riluzole affects you.

What side effects may I notice from taking riluzole?

Side effects that you should report to your prescriber or health care professional as soon as possible:
• fever, chills or infection
• breathing difficulty, or shortness of breath
• yellowing of the skin or eyes

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
• back pain
• cough
• diarrhea
• dizziness
• drowsiness
• increased blood pressure
• loss of appetite
• loss of balance from giddiness or dizziness
• nausea, vomiting
• stomach pain
• tingling, pricking, or burning sensation around the mouth
• weakness and tiredness

Where can I keep my medicine?

Keep out of reach of children in a container that small children cannot open.

Store at room temperature between 20 and 25 degrees C (68—77 degrees F). Protect from light. Throw away any unused medicine after the expiration date.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

Riluzole

Systematic (IUPAC) name
6-(trifluoromethoxy)benzothiazol-2-amine
Identifiers
CAS number	1744-22-5
ATC code	N07XX02
PubChem	5070
DrugBank	APRD00145
Chemical data
Formula	C8H5F3N2OS
Mol. mass	234.199 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?
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Riluzole is a drug used to treat amyotrophic lateral sclerosis. It delays the onset of ventilator-dependence or tracheostomy in selected patients and may increase survival by approximately 3–5 months.

It is marketed by sanofi-aventis with the brand name Rilutek.

Riluzole preferentially blocks TTX sensitive sodium channels, which are associated with damaged neurons.^[1] This reduces influx of calcium ions and indirectly prevents stimulation of glutamate receptors. Together with direct glutamate receptor blockade, the effect of the neurotransmitter glutamate on motor neurons is greatly reduced.

However, the action of riluzole on glutamate receptors has been controversial, as no binding of the molecule has been shown on any known receptor.^[2] In addition as its antiglutamate action is still detectable in the presence of sodium channel blockers, it is also uncertain whether or not it acts via this way. Rather, its potent glutamate uptake activator activity seems to mediate many of its effects.^{[3] [4]}

Contents 1 Studies of efficacy 2 Clinical use 3 References 4 External links

Studies of efficacy

A Cochrane Library review states a 9% gain in the probability of surviving one year. In secondary analyses of survival at separate time points, there was a significant survival advantage with riluzole 100 mg at six, nine, 12 and 15 months, but not at three or 18 months.^[5] There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. There were no data on quality of life, but patients treated with riluzole remained in a more moderately affected health state significantly longer than placebo-treated patients.

Clinical use

While riluzole has been proven to slow down ALS, patients do not report any subjective improvement. Approximately 10% of patients experience side effects such as nausea and fatigue which lead them to discontinue treatment. Safety monitoring includes regular liver function tests and people with liver disease such as hepatitis should be monitored especially carefully.

In the UK riluzole has been available through the NHS since 1997 at a standard dosage of 50 mg twice daily. There has been some evidence to show that higher doses might produce more significant improvements in ALS patients but at £5 a tablet it is at risk of being prohibitively expensive given the modest benefit to patients. One study in the Netherlands found that riluzole is metabolised differently by males and females, and its levels in plasma are decreased in patients who smoke cigarettes.^[6]

A number of recent case studies have also indicated that riluzole may have clinical use in mood and anxiety disorders. It has been shown to have antidepressant properties in the treatment of refractory depression^[7] and as an anxiolytic in Obsessive-compulsive disorder^[8] and in GAD.^[9]

References

1. ^ Song JH, Huang CS, Nagata K, Yeh JZ, Narahashi T (1 August 1997). "Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels". J Pharmacol Exp Ther. 282 (2): 707–14. PMID 9262334. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9262334. 
2. ^ Wokke J (September 1996). "Riluzole". Lancet 348 (9030): 795–9. doi:10.1016/S0140-6736(96)03181-9. PMID 8813989. 
3. ^ Azbill RD, Mu X, Springer JE (July 2000). "Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes". Brain Res. 871 (2): 175–80. doi:10.1016/S0006-8993(00)02430-6. PMID 10899284. http://linkinghub.elsevier.com/retrieve/pii/S0006-8993(00)02430-6. 
4. ^ Dunlop J, Beal McIlvain H, She Y, Howland DS (1 March 2003). "Impaired spinal cord glutamate transport capacity and reduced sensitivity to riluzole in a transgenic superoxide dismutase mutant rat model of amyotrophic lateral sclerosis". J Neurosci. 23 (5): 1688–96. PMID 12629173. http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=12629173. 
5. ^ Miller RG, Mitchell JD, Lyon M, Moore DH (2007). "Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)". Cochrane Database Syst Rev (1): CD001447. doi:10.1002/14651858.CD001447.pub2. PMID 17253460. 
6. ^ van Kan HJ, Groeneveld GJ, Kalmijn S, Spieksma M, van den Berg LH, Guchelaar HJ (March 2005). "Association between CYP1A2 activity and riluzole clearance in patients with amyotrophic lateral sclerosis". Br J Clin Pharmacol 59 (3): 310–3. doi:10.1111/j.1365-2125.2004.02233.x. PMID 15752377. 
7. ^ Zarate CA, Payne JL, Quiroz J, et al. (January 2004). "An open-label trial of riluzole in patients with treatment-resistant major depression". Am J Psychiatry 161 (1): 171–4. doi:10.1176/appi.ajp.161.1.171. PMID 14702270. http://ajp.psychiatryonline.org/cgi/content/full/161/1/171. 
8. ^ Coric V, Taskiran S, Pittenger C, et al. currently a study is underway at the NIH in bethesda using riluzol for the treatment of OCD by Dr Grant (September 2005). "Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial". Biol Psychiatry 58 (5): 424–8. doi:10.1016/j.biopsych.2005.04.043. PMID 15993857. 
9. ^ Mathew SJ, Amiel JM, Coplan JD, Fitterling HA, Sackeim HA, Gorman JM (December 2005). "Open-label trial of riluzole in generalized anxiety disorder". Am J Psychiatry 162 (12): 2379–81. doi:10.1176/appi.ajp.162.12.2379. PMID 16330605. 

External links

• National Institute for Health and Clinical Excellence (NICE) guidelines for prescription of riluzole in the UK [1]
• Manufacturer's website [2]
• Riluzole (patient information)

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v • d • e Other nervous system drugs (N07X) Stroke Tirilazad ALS Riluzole · Xaliproden · Arimoclomol† · Mecasermin rinfabate† Other Hydroxybutyric acid · Amifampridine · hyperkinesis (Tetrabenazine) †Undergoing clinical trials, not FDA approved.

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