Correspondence

Methemoglobinemia Due to Riluzole

N Engl J Med 2000; 343:665-666August 31, 2000

Article

To the Editor:

We report a case of intentional riluzole poisoning in a patient with amyotrophic lateral sclerosis.

A 43-year-old woman with amyotrophic lateral sclerosis had been treated with riluzole for two years, during which she had lost 8 kg in weight. She was able to walk with support, she could feed herself and had rare difficulty swallowing, and she had mild dysarthria. Her forced vital capacity was 47 percent of the predicted value, and she was depressed. She was hospitalized six hours after deliberately ingesting 2.8 g of riluzole. On admission, physical examination revealed dyspnea, a pulse rate of 100 per minute, an arterial blood pressure of 130/80 mm Hg, peripheral cyanosis, and a Glasgow Coma Score of 13. The whole-blood methemoglobin concentration was 18.3 percent (Figure 1Figure 1Whole-Blood Concentrations of Methemoglobin and Serum Concentrations of Riluzole during the First 50 Hours after Admission for an Overdose of Riluzole.). No phenobarbital, benzodiazepine, salicylate, tricyclic antidepressant, phenothiazine, acetaminophen, or alcohol was detected in serum. Except for the presence of drowsiness, findings on the neurologic examination had not changed from previous examinations. The electrocardiogram and chest x-ray film were normal. Arterial blood gas analysis revealed a pH of 7.38, a partial pressure of arterial carbon dioxide of 47 mm Hg, a partial pressure of arterial oxygen of 73 mm Hg, and oxygen saturation of 95 percent.

After gastric lavage, 50 g of activated charcoal was administered. Because of symptomatic hypoxia, 50 mg of methylene blue was given intravenously. Clinical and laboratory studies revealed no metabolic disorder, no hemolysis, no neutropenia, no infectious diseases, and no impairment of hepatic, renal, or cardiac function. The results of hemoglobin electrophoresis were normal. The red-cell glucose-6-phosphate concentration was normal (5.9 IU per gram of total hemoglobin). On day 3, mechanical ventilation was initiated because the patient had alveolar hypoventilation. On day 5, she was weaned from the ventilator, but acute respiratory distress recurred on day 7. Because of the underlying disease, it was decided to withhold aggressive treatment. The patient died on day 7 of respiratory failure related to amyotrophic lateral sclerosis.

This patient had methemoglobinemia after taking a high dose of riluzole. Riluzole1,2 or one of its metabolites could act as an oxidant, since it is an aminic compound, as are some other products that induce methemoglobinemia.3

Alain Viallon, M.D.
Yves Page, M.D.
Jean Claude Bertrand, M.D.
Hôpital Bellevue, 42055 Saint Etienne CEDEX 2, France

3 References

1. 1

   Bryson HM, Fulton B, Benfield P. Riluzole: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in amyotrophic lateral sclerosis. Drugs 1996;52:549-563
   CrossRef | Web of Science | Medline

2. 2

   Rhône Poulenc Rorer and Specia. Riluzole. Monographie 1997;Ch 7.2.
   

3. 3

   Mansouri A, Lurie AA. Concise review: methemoglobinemia. Am J Hematol 1993;42:7-12
   CrossRef | Web of Science | Medline

Author/Editor Response

The above letter was referred to Aventis Pharmaceuticals, the manufacturer of riluzole, which offers the following reply:

To the Editor: Viallon et al. describe a case of deliberate, massive overdose of riluzole in a patient who was being treated for amyotrophic lateral sclerosis. The authors report that methemoglobinemia, which occurred soon after the overdose, was successfully treated with intravenous methylene blue. The patient subsequently died of pulmonary insufficiency related to amyotrophic lateral sclerosis.

The product labeling for riluzole was amended to describe this case and includes the possibility of methemoglobinemia with a large overdose. We estimate that the total level of exposure to riluzole is 536,000 patient-months. To date, this case represents the only reported case of substantial toxicity of riluzole and the only reported case of methemoglobinemia associated with the use of riluzole.

James E. Shipley, M.D.
Veronique Kugener, M.D.
Aventis Pharmaceutical Products, Bridgewater, NJ 08807-0800

Citing Articles (8)

Citing Articles

1. 1

   Mark C. Bellingham. (2011) A Review of the Neural Mechanisms of Action and Clinical Efficiency of Riluzole in Treating Amyotrophic Lateral Sclerosis: What have we Learned in the Last Decade?. CNS Neuroscience & Therapeutics 17:1, 4-31
   CrossRef

2. 2

   Paul Grant, Jane Y. Song, Susan E. Swedo. (2010) Review of the Use of the Glutamate Antagonist Riluzole in Psychiatric Disorders and a Description of Recent Use in Childhood Obsessive-Compulsive Disorder. Journal of Child and Adolescent Psychopharmacology 20:4, 309-315
   CrossRef

3. 3

   Carlos A Zarate, Husseini K Manji. (2008) Riluzole in psychiatry: a systematic review of the literature. Expert Opinion on Drug Metabolism & Toxicology 4:9, 1223-1234
   CrossRef

4. 4

   Christopher Pittenger, Vladimir Coric, Mounira Banasr, Michael Bloch, John H Krystal, Gerard Sanacora. (2008) Riluzole in the Treatment of Mood and Anxiety Disorders. CNS Drugs 22:9, 761-786
   CrossRef

5. 5

   Gilbert Bensimon, Adam Doble. (2004) The tolerability of riluzole in the treatment of patients with amyotrophic lateral sclerosis. Expert Opinion on Drug Safety 3:6, 525-534
   CrossRef

6. 6

   Rachel Ash-Bernal, Robert Wise, Scott M. Wright. (2004) Acquired Methemoglobinemia. Medicine 83:5, 265-273
   CrossRef

7. 7

   (2000) Current Awareness. Pharmacoepidemiology and Drug Safety 9:7, 615-630
   CrossRef

8. 8

   &NA;. (2000) Riluzole overdose. Reactions Weekly &NA;:818, 11-12
   CrossRef