Re: Entacapone & liver monitoring

[dominic marchese <athenapss@xxxxxxxxxxxxxxxx>]

Comtan, also known as entacapone, has recently completed its phase III
trials to determine the safety and efficacy as an additional therapy to
manage Parkinson's disease.  According to the manufacturer, a New Drug
Application has been sent to the FDA.  The FDA is currently reviewing the
safety, efficacy, and dosage recommendations for entacapone.

Entacapone is in the class of medications called
catechol-O-methyltransferase (COMT) inhibitors.   Currently, the only COMT
inhibitor approved by the FDA is Tasmar (tolcapone.)  Like tolcapone,
entacapone is thought to increase the therapeutic activity of levodopa.
Sinemet (carbidopa/levodopa) is considered to be the most effective
treatment for Parkinson's disease.  However, long-term and increasing
frequency of carbidopa/levodopa administration is often associated with
motor fluctuations called "on-off" and "wearing-off" effects.  It is thought
that by inhibiting the enzymes that break down levodopa, motor fluctuations
may be stabilized.  Entacapone works by preventing the enzyme COMT from
converting levodopa into an inactive substance.

 In the support group setting, several questions arise as to the adverse
effects of entacapone.  Will the side effect profile resemble tolcapone and
also have the possibility of liver problems?  A study of 700 patients who
had received entacapone for 6 to 12 months had no evidence of abnormal liver
function tests as a result of entacapone administration.  Until the product
is approved, it is unknown whether liver function tests will be required and
monitored by the FDA.  In addition, as with all new drugs, in a larger
population of patients other unpredictable side effects may occur.  Until
the FDA reviews the safety and effectiveness, this data is inconclusive.

Dominic Marchese, RPh.
Athena Rx Home Pharmacy
1-800-5-ATHENA


----- Original Message -----
From: J. R. Bruman <jrbruman@xxxxxxxxxxx>
To: <PARKINSN@xxxxxxxxxxxxxxxxxxxx>
Sent: Saturday, September 18, 1999 11:51 AM
Subject: Re: Entacapone & liver monitoring


> judith richards wrote:
> >
> > Camilla Flintermann wrote:
> > >Dear friends-- Here are a few items from the talk which Dominic
> > Marchese
> > >gave to our support group (Oxford,Ohio) last week.
> >
> > >*Comtan / Comtess (Entacapone) is soon to be available in the US , and
> > like
> > >Tasmar, will probably still require some liver monitoring
> >
> >     It was my understanding that Entacapone would not require liver
> > monitoring. Joe Bruman...where are you?
>
> That's my understanding too. I expect the results discussed by Drs.
> Heinonen and Watkins will be mentioned in the entacapone Product
> Description when it becomes available here.
> The fact that entacapone and tolcapone have alliterative names and
> are both COMT inhibitors doesn't imply any similarity in liver effects.
> The sinister thing about the very rare type of liver failure caused by
> hepatitis B virus and by certain drugs is that the ALT monitoring
> provides only an indirect warning, which may or may not appear in
> time to avoid a crisis. I believe there have been cases (unrelated
> to tolcapone) where the elevated ALT levels actually declined,
> just before the liver crisis appeared. Cheers,
> Joe
> --
> J. R. Bruman   (818) 789-3694
> 3527 Cody Road
> Sherman Oaks, CA 91403-5013