CYP2D6 deficiency+Prozac=child's death

February 13, 2002

Found this on a site (alertpubs.com/may2000psych.htm) as I was looking

for bupropion toxicity - note the fact that it is stated that " About

7–10% of Caucasians are estimated to be genetically deficient in

CYP2D6. " Key word here being estimated. I've got to find out to find

out - (with the 12 extra hours I do not have in a day that I need) -

what the estimates are in other nationalities. This is totally

ridiculous. I KNOW they have known of this defiency for a long time -

I just know it...article follows:

CYP2D6 Deficiency-Related Death

In 1995, the FDA reported on the death of a 9-year old boy who at

various times had received clonidine, fluoxetine, and

methylphenidate, and who was found to have extremely high fluoxetine

blood levels. The medical examiner concluded that an

intentional fluoxetine overdose had been administered by his adoptive

parents.

Some follow-up information on this case concerning a

psychopharmacologic evaluation and genetic testing has been made

available. It appears that the boy had an autosomal recessive defect

in cytochrome P450 2D6 (CYP2D6), which can result in

poor metabolism and elevated levels of fluoxetine. The accusation of

intentional overdose was subsequently abandoned.

The 9-year old (55-lb) boy died following the onset of nausea,

flu-like symptoms, and a seizure that led to cardiopulmonary

arrest. The patient's medical history shows that at age 5 he was

diagnosed with fetal alcohol syndrome, ADHD, and

Tourette's disorder, and that he was treated with 0.6 mg/day clonidine

for his tics. He was noted to be extremely

hyperactive, with violent outbursts. At age 6, fluoxetine, 5 mg/day

was added to 0.9 mg/day clonidine, and fluoxetine was

gradually increased to 30 mg/day. The patient experienced vomiting and

diarrhea at this dosage and was hospitalized for

dehydration. The combination was discontinued during hospitalization

and then resumed with a fluoxetine increase to 40

mg/day. The patient experienced 2 more episodes of vomiting and

diarrhea.

At age 8, the patient was receiving fluoxetine and clonidine for

Tourette's disorder and OCD, and 60 mg/day

methylphenidate was added to treat ADHD. The patient was also

receiving

25 mg/day promethazine for nausea. Fluoxetine was increased to 80

mg/day, and he experienced a seizure. One month later,

fluoxetine was increased to 100 mg/day. Subsequently, 3 episodes of

dizziness, nausea, and low-grade fever occurred. He

experienced 2 seizures, followed by status epilepticus and

cardiopulmonary arrest wherein he could not be resuscitated.

This appears to be the first report of toxicity and death in a child

with confirmed polymorphism of CYP2D6. About 7–10%

of Caucasians are estimated to be genetically deficient in CYP2D6.

This deficiency, combined with the 100 mg/day dose of

fluoxetine, probably contributed to fluoxetine toxicity and death in

this patient. The possible effect of the other medications is

unknown, and many questions remain about this unfortunate case.

Sallee F, DeVane C, Ferrell R: Fluoxetine-related death in a child

with cytochrome P450 2D6 genetic deficiency. Journal of Child and

Adolescent

Psychopharmacology 2000;10 (Spring):27–34. From the University of

Cincinnati, Ohio; and other institutions. See Related Story in

Psychiatry Drug Alerts

1996;10 (June):48.

Drug Trade Names: clonidine—Catapres; fluoxetine—Prozac;

methylphenidate—Ritalin;

promethazine—Phenergan, Prometh

February 13, 2002