COMT inhibitors

Question 1

MOA of entacapone

Answer 1

prevents the peripheral breakdown of levodopa, by inhibiting catechol-O-methyltransferase, allowing more levodopa to reach the brain.

Question 2

indication - entacapone

Answer 2

Adjunct to co-beneldopa or co-careldopa in Parkinson’s disease with ‘end-of-dose’ motor fluctuations (under expert supervision)

Question 3

what is the dose of entacapone for adjunct to co-beneldopa or co-careldopa in Parkinson’s disease with ‘end-of-dose’ motor fluctuations (under expert supervision)

Answer 3

200mg daily, dose to be given with each dose of levodopa with dopa-decarboxylase inhibitor (e.g. benserazide)
max 2g day

Question 4

when giving entacapone adjunct, concurrent levodopa dose may need to be reduced by …

Answer 4

about 10-30%

Question 5

entacapone interacts with this drug class - it is predicted to increase the effects of this drug class = risk of elevated BP when given with these three drugs. avoid.

Answer 5

MAOIs - antidepressants
isocarboxazid
phenelzine
tranylcypromine

Question 6

patient and carer advice with entacapone - (2)

Answer 6

oral Entacapone is predicted to decrease the absorption of oral Iron. Manufacturer advises separate administration by at least 2 hours.
may colour urine reddish brown

Question 7

what colour does entacapone colour urine

Answer 7

red-brown

Question 8

label for entacapone

Answer 8

this medicine may colour your urine. this is harmless

(red brown)

Question 9

how does opicapone work

Answer 9

prevents peripheral breakdown of levodopa by inhibiting COMT, therefore allowing more levodopa to reach brain

Question 10

indication for opicapone

Answer 10

Adjunct to co-beneldopa or co-careldopa in Parkinson’s disease with ‘end-of-dose’ motor fluctuations (under expert supervision)

Question 11

dose for opicapone

Answer 11

50 mg once daily, dose to be taken at bedtime, at least one hour before or after levodopa combinations.

Question 12

when should opicapone be taken relative to levodopa

Answer 12

at least one hour before or after levodopa combinations

Question 13

COMT inhibitors - interactions for dopamine, adrenaline, noradrenaline

Answer 13

predicted to increase risk of CV adverse effects
monitor

Question 14

opicapone - manufacturer advised to consider the following in patients who experience progressive anorexia, asthenia (weakness) and weight decrease within a relatively short period of time.

Answer 14

LFTs

Question 15

name the 3 COMT inhibitors

Answer 15

opicapone
entacapone
tolcapone

Question 16

MOA tolcapone

Answer 16

prevents peripheral breakdown of levodopa, by inhibiting catechol-O-methyltransferase, allowing more levodopa to reach the brain.

Question 17

when is tolcapone indicated

Answer 17

Adjunct to co-beneldopa or co-careldopa in Parkinson’s disease with ‘end-of-dose’ motor fluctuations if another inhibitor of peripheral catechol-O-methyltransferase inappropriate (under expert supervision)

Question 18

you should only continue tolcapone beyond …. if there has been substantial improvement

Answer 18

3 weeks

Question 19

all COMT inhibitors are contraindicated in (3)

Answer 19

Phaeochromocytoma; previous history of neuroleptic malignant syndrome; previous history of rhabdomyolysis

Question 20

if patients are receiving tolcapone and they have more than 600mg levodopa daily, they will require a dose reduction of levodopa by about

Answer 20

30%

Question 21

use of tolcapone in HI

Answer 21

avoid!!

Question 22

monitoring requirements for tolcapone

Answer 22

LFTs before treatment, every 2 weeks for 1st year, every 4 weeks for next 6 months, then every 8 weeks thereafter

Question 23

patient and carer advice tolcapone

Answer 23

how to recognise signs of liver disorder and advised to seek immediate medical attention if symptoms such as anorexia, nausea, vomiting, fatigue, abdominal pain, dark urine, or pruritus develop.

Question 24

a patient on a COMT inhibitor develops dark urine, pruritic, anorexia, nausea, vomiting, fatigue. what one are they taking?

Answer 24

tolcapone

Question 25

tolcapone - cautions information for hepatotoxicity

Answer 25

Potentially life-threatening hepatotoxicity including fulminant hepatitis reported rarely, usually in women and during the first 6 months, but late-onset liver injury also reported; discontinue if abnormal liver function tests or symptoms of liver disorder; do not re-introduce tolcapone once discontinued.

Question 26

All COMT inhibitors interact with the following 5 drugs

Answer 26

MAOIs - phenelzine, trancylpromide, isocarboxazid - predicted to increase effects of these antidepressants. avoid

Adrenaline and nordareline - increase the effects, may cause CV adverse effects