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P A R T 4
Drugs acting on the central and peripheral nervous systems
ADJUNCTIVE AGENTS
Adjunctive agents used to improve response to tradi-
tional therapy include entacapone (
Comtan
), rasagiline
(
Azilect
) (not available in New Zealand), tolcapone
(
Tasmar
) (not available in Australia) and selegiline
(
Eldepryl, Selgene
). See Table 24.3 for additional
information.
Entacapone is used with carbidopa–levodopa
to increase the plasma concentration and duration
of action of levodopa. It does this by inhibiting
catecholamine-
O
-methyl transferase (COMT), a natur
ally occurring enzyme that eliminates catecholamines,
including dopamine. It is given with the carbidopa–
levodopa at a dose of 200 mg PO, with a maximum
of eight doses a day. It is readily absorbed from the GI
tract, metabolised in the liver and excreted in urine and
faeces. Women of childbearing age should be encour-
aged to use barrier contraceptives while taking this
drug, which crosses the placenta and could have adverse
effects on the fetus.
Rasagiline is an irreversible MAO type B selective
inhibitor and its mechanism of action in Parkinson’s
disease is not understood. It is believed that MAO inhib
ition leads to elevated dopamine levels and promotes
increased extracellular dopamine levels in the striatum.
It is rapidly absorbed with peak levels achieved in
approximately half an hour. It undergoes hepatic metab-
olism after GI absorption and is excreted in the urine
and faeces. Being a MAO inhibitor, there is a risk of
development of hypertensive crisis. When combined
with antidepressant treatment, there is an increased risk
of serotonin syndrome. As prolactin secretion is blocked,
rasagiline may inhibit breastfeeding.
Tolcapone works in a similar way with carbidopa–
levodopa to further increase plasma levels of levodopa.
Tolcapone also blocks the enzyme COMT, which is
responsible for the breakdown of dopamine. Because this
drug has been associated with fulminant and potentially
fatal liver damage, it is contraindicated in the presence
of liver disease. Tolcapone is reserved for use in later
stages of Parkinson’s disease, when carbidopa–levodopa
is losing its effectiveness. It undergoes hepatic metabo-
lism after GI absorption and is excreted in the urine and
faeces. It is given in doses of 100 or 200 mg PO three
times a day, up to a maximum of 600 mg/day. Women
of childbearing age should be encouraged to use barrier
contraceptives while taking this drug, which crosses the
placenta and could have adverse effects on the fetus.
Selegiline is used with carbidopa–levodopa after
people have shown signs of deteriorating response to
this treatment. Its mechanism of action is not under-
stood. It does irreversibly inhibit MAO, which has an
important role in the breakdown of catecholamines,
including dopamine. The maximum daily dose of the
drug is 10 mg, and the dose of levodopa needs to be
reduced when this drug is started. It is well absorbed
from the GI tract, extensively metabolised in the liver
and excreted in urine. It is not known whether this drug
crosses the placenta, but it should be used in pregnancy
only if the benefits to the mother clearly outweigh any
potential risks to the fetus. Because of the risk of MAO
inhibitor–induced hypertensive effects, people should be
urged to immediately report severe headache and any
other unusual symptoms which they have not experi-
enced before.
TABLE 24.3
DRUGS IN FOCUS Adjunctive antiparkinsonism drugs
Drug name
Dosage/route
Usual indications
entacapone (Comtan)
200 mg PO taken with levodopa–carbidopa,
maximum of eight doses per day
Adjunctive treatment of idiopathic Parkin
son’s disease with levodopa–carbidopa
for people who are experiencing
“wearing off” of drug effects
rasagiline (Azilect)
1 mg PO once daily with or without levodopa
Adjunctive treatment or treatment of
idiopathic Parkinson’s disease
selegiline (Selgene,
Eldepryl)
5 mg PO b.d. (at breakfast and lunch); attempt
to decrease levodopa–carbidopa dose after
2–3 days
Adjunctive treatment of idiopathic Parkin
son’s disease with levodopa–carbidopa
in people whose response to that therapy
has decreased
tolcapone (Tasmar)
100 mg PO t.d.s.; maximum daily dose 600 mg Adjunctive treatment of idiopathic Parkin
son’s disease with levodopa–carbidopa
Care considerations for
people receiving adjunctive agents
Care considerations for people receiving the drugs
listed in this section are similar to those for people
receiving the dopaminergic drugs. Details related
to each individual drug can be found in the specific
drug monograph in your drug guide.
