COMT inhibitors Flashcards
MOA of entacapone
prevents the peripheral breakdown of levodopa, by inhibiting catechol-O-methyltransferase, allowing more levodopa to reach the brain.
indication - entacapone
Adjunct to co-beneldopa or co-careldopa in Parkinson’s disease with ‘end-of-dose’ motor fluctuations (under expert supervision)
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)
200mg daily, dose to be given with each dose of levodopa with dopa-decarboxylase inhibitor (e.g. benserazide)
max 2g day
when giving entacapone adjunct, concurrent levodopa dose may need to be reduced by …
about 10-30%
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.
MAOIs - antidepressants
isocarboxazid
phenelzine
tranylcypromine
patient and carer advice with entacapone - (2)
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
what colour does entacapone colour urine
red-brown
label for entacapone
this medicine may colour your urine. this is harmless
(red brown)
how does opicapone work
prevents peripheral breakdown of levodopa by inhibiting COMT, therefore allowing more levodopa to reach brain
indication for opicapone
Adjunct to co-beneldopa or co-careldopa in Parkinson’s disease with ‘end-of-dose’ motor fluctuations (under expert supervision)
dose for opicapone
50 mg once daily, dose to be taken at bedtime, at least one hour before or after levodopa combinations.
when should opicapone be taken relative to levodopa
at least one hour before or after levodopa combinations
COMT inhibitors - interactions for dopamine, adrenaline, noradrenaline
predicted to increase risk of CV adverse effects
monitor
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.
LFTs
name the 3 COMT inhibitors
opicapone
entacapone
tolcapone
MOA tolcapone
prevents peripheral breakdown of levodopa, by inhibiting catechol-O-methyltransferase, allowing more levodopa to reach the brain.
when is tolcapone indicated
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)
you should only continue tolcapone beyond …. if there has been substantial improvement
3 weeks
all COMT inhibitors are contraindicated in (3)
Phaeochromocytoma; previous history of neuroleptic malignant syndrome; previous history of rhabdomyolysis
if patients are receiving tolcapone and they have more than 600mg levodopa daily, they will require a dose reduction of levodopa by about
30%
use of tolcapone in HI
avoid!!
monitoring requirements for tolcapone
LFTs before treatment, every 2 weeks for 1st year, every 4 weeks for next 6 months, then every 8 weeks thereafter
patient and carer advice tolcapone
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.
a patient on a COMT inhibitor develops dark urine, pruritic, anorexia, nausea, vomiting, fatigue. what one are they taking?
tolcapone
tolcapone - cautions information for hepatotoxicity
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.
All COMT inhibitors interact with the following 5 drugs
MAOIs - phenelzine, trancylpromide, isocarboxazid - predicted to increase effects of these antidepressants. avoid
Adrenaline and nordareline - increase the effects, may cause CV adverse effects
