Of the 13 cases reported as of May 1996, 11 resulted in death or liver transplantation, usually within four weeks of the onset of signs and symptoms of liver failure. The ear-liest onset of hepatic abnormalities occurred six months after initiation of Cylert. Although some reports described dark urine and nonspecific prodromal symptoms (e.g., anorexia, malaise, and gastrointestinal symp-toms), in other reports it was not clear if any prodromal symptoms preceded the onset of jaundice. It is also not clear if the recom-mended baseline and periodic liver function testing are predictive of these instances of acute liver failure. Cylert should be dis-continued if clinically significant hepatic dysfunction is observed during its use.

Drug Interactions:

Precautions:

Clinical experience suggests that in psychotic children administration of Cylert may exacerbate symptoms of behavior disturbance and thought disorder.

Cylert should be administered with caution to patients with significantly impaired renal function.

Since Cylert's market introduction. there have been reports of elevated liver enzymes associated with its use. Many of these patients had this increase detected several months after starting Cylert. Most patients were asymptomatic, with the increase in liver enzymes returning to normal after Cylert was discontinued. Liver function tests should be performed prior to and periodically during therapy with Cylert. Treatment with Ctlert should be initiated only in individual without liver disease and with normal baseline liver function tests.

The relationship, if any, between reversible elevations in liver function tests and the occurrence of life threatening hepatic failure in patients on long-term therapy with Cylert is not known. Liver function testing may not predict the onset of acute liver failure. Nonetheless, Cylert should be discontinued if clinically significant liver function test abnormalities are revealed at any time during therapy with this drug

Adverse Reactions:

The following are adverse reactions in decreasing order of severity within each category associated with Cylert:

Hepatic: There have been reports of hepatic dysfunction, ranging from asymptomatic reversible increases in liver enzymes to hepatitis, jaundice and life- threatening hepatic failure, in patients taking Cylert.

Hematopoietic: There have been isolated reports of aplastic anemia.

Central Nervous System: The following CNS effects have been reported with the use of Cylert: convulsive seizures: literature reports indicate that Cylert may precipitate attacks of Gilles de la Tourette syndrome; hallucinations; dyskinetic movements of the tongue, lips, face and extremities: abnorrnal oculomotor function including nystagmus and oculogyric crisis; mild depression; dizziness; increased irritability; headache; and drowsiness.

Insomnia is the most frequently reported side effect of Cylert, it usually occurs early in therapy prior to an optimum therapeutic response. In the majority of cases it is transient in nature or responds to a reduction in dosage.

Gastrointestinal: Anorexia and weight loss may occur during the first weeks of therapy. In the majority of cases it is transient in nature; weight gain usually resumes within three to six months.

Nausea and stomach ache have also been reported.

Miscellaneous: Suppression of growth has been reported with the long- term use of stimulants in children. Skin rash has been reported with Cylert.

Mild adverse reactions appearing early during the course of treatment with Cylert often remit with continuing therapy. If adverse reactions are of a significant or protracted nature, dosage should be reduced or the drug discontinued.

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