Download Management of Parkinson`s Disease

CENTRAL NERVOUS SYSTEM
MANAGEMENT OF PARKINSON’S DISEASE
MANAGEMENT
Parkinson‟s Disease is classically determined by the triad or rest tremor (usually
starting in one arm) with bradykinesia (slowing of movement) and rigidity (which may
manifest as cogwheel rigidity particularly in the arms).
Patients often display a generalised lack of movement both in terms of facial
expression and general body movement. They often have reduced arm swing
(usually asymmetrical at the beginning) with festinate gait. They may have impaired
ability to correct their balance.
There is no treatment that has been definitely proven to slow down the progression of
Parkinson‟s disease and therefore patients will not be adversely affected by waiting
to commence treatment particularly if there is any doubt about the diagnosis.
Current drug therapy aims simply to correct the chemical imbalance. Although this
approach fails to prevent the progression of the disease, it greatly improves the
quality and expectancy of life of most patients.
About 5-10% (BNF) of patients are unresponsive to treatment.
All patients should have their medication reviewed to eliminate the possibility
of anti-dopaminergic drugs causing parkinsonian symptoms, for example
prochlorperazine, metoclopramide, chlorpromazine, trifluoperazine, haloperidol
and thioridazine.
Elderly: Antiparkinsonism drugs carry a special risk of inducing confusion in the
elderly. It is particularly important to initiate treatment with low doses and to use small
increments
REFERRAL
Patients with suspected Parkinson‟s Disease should be referred quickly and
untreated to a specialist with expertise in the differential diagnosis of this condition.
[1]
INITIATION OFTREATMENT
Treatment for Parkinson‟s Disease should be initiated by specialist only. Once
initiated, General Practitioners can titrate dosage according to patient‟s response and
adverse events.
The information contained in the Formulary is based on evidence available at the time of writing; it is issued for guidance
and advice only. For information on the cautions, contra-indications, side effects and doses of individual drugs, please
check the current SPC or BNF section for that drug. Prescribers remain responsible for their patients‟ care and
prescriptions signed.
Review date April 2012
1
DRUG CHOICES
Levodopa plus peripheral decarboxylase inhibitor preparations
Drug
Co-beneldopa
capsule (levodopa
and benserazide)
62.5mg, 125mg,
250mg
Dispersible tablet
62.5mg, 125mg
Madopar CR™ m/r
capsule 125mg
Co-careldopa
tablets(levodopa
and carbidopa)
62.5mg, 125mg,
275mg
Half Sinemet CRTM
m/r tablet 25/100
Sinemet CRTM m/r
tablet 50/200
Dose
Expressed as levodopa,
initially 50-100mg 3–4 times
daily, increased by 100 mg
daily once or twice weekly
according to response;
ELDERLY initially 50 mg
once or twice daily,
increased by 50 mg daily
every 3–4 days according to
response.
Expressed as levodopa,
initially 100 mg 3 times
daily, increased by 50–
100 mg daily or on alternate
days according to response,
up to 800 mg daily in
divided doses
Comments
Levodopa in combination with a dopadecarboxylase inhibitor is the treatment of choice
for patients disabled by idiopathic Parkinson‟s
disease. It should not be used for neurolepticinduced Parkinsonism.
Levodopa therapy should be initiated with low
doses and gradually increased, by small
increments, at intervals of 2-3 days. The final dose
is usually a compromise between increased mobility
and dose-limiting side effects.
Modified release preparations may help with “endof-dose” deterioration or nocturnal immobility and
rigidity.
At least 70 mg carbidopa daily is necessary to
achieve full inhibition of peripheral dopadecarboxylase; co-careldopa 25/100 should
therefore be used so that the daily dose of
carbidopa is at least 75mg.
Sudden onset of sleep:
Excessive daytime sleepiness and sudden onset of
sleep can occur with co-careldopa and cobeneldopa. Patients starting on treatment with
these drugs should be warned of the possibility of
these effects and of the need to exercise caution
when driving or operating machinery. Patients, who
have suffered excessive sedation or sudden onset
of sleep, should refrain from driving or operating
machines, until those effects have stopped.
The information contained in the Formulary is based on evidence available at the time of writing; it is issued for guidance
and advice only. For information on the cautions, contra-indications, side effects and doses of individual drugs, please
check the current SPC or BNF section for that drug. Prescribers remain responsible for their patients‟ care and
prescriptions signed.
Review date April 2012
2
Non-ergoline Dopamine Agonists
Drug
Dose
Pramipexole
Tablets
88 micrograms,
180 micrograms,
350 micrograms,
700 micrograms
Initially 88 micrograms 3
times daily, dose doubled
every 5–7 days if tolerated
to 350 micrograms 3 times
daily; max. 3.3 mg daily in 3
divided doses.
Ropinirole
Tablet
1mg, 2mg, 5mg
Starter pack
Follow-on pack
m/r tablets 2mg,
4mg, 8mg
Rotigotine
Patches
1mg, 2mg, 3mg,
4mg, 6mg, 8mg
Initially 750 micrograms
daily in 3 divided doses,
increase weekly by
750 micrograms to 3 mg
daily; further increments of
up to 3 mg at weekly
intervals according to
response; usual range 9–
16 mg daily (but higher
doses may be required if
used with levodopa); max.
24 mg daily
Monotherapy, 2 mg patch
daily; increased in steps of
2 mg daily at weekly
intervals if required; max.
8 mg/24 hours.
Adjunctive therapy with
levodopa, 4 mg patchdaily;
increased in steps of 2 mg
daily at weekly intervals if
required; max. 16 mg/24
hours
Comments
Doses of dopamine receptor agonists should be
increased slowly according to response and
tolerability. Treatment with dopamine receptor
agonists should not be withdrawn abruptly.
Hypotensive reactions:
Hypotensive reactions can occur in some
patients taking dopamine agonists; these can
be particularly problematic during the first few
days of treatment and care should be exercised
when driving or operating machinery.
Sudden onset of sleep:
Excessive daytime sleepiness and sudden
onset of sleep can occur with dopamine
receptor agonists. Patients starting on
treatment with these drugs should be
warned of the possibility of these effects
and of the need to exercise caution when
driving or operating machinery. Patients,
who have suffered excessive sedation or
sudden onset of sleep, should refrain from
driving or operating machines, until those
effects have stopped.
Compulsive behaviour:
There is growing evidence that suggests a link
between dopamine agonists and compulsive
behaviour. Examples of compulsive behaviour:
 Pathological gambling;
 Hypersexuality;
 Compulsive binge eating;
 Compulsive shopping;
 Compulsive hobbyism, etc.
Patients starting on treatment with these drugs
should be warned of the possibility of these
effects.
Apomorphine
Drug
Apomorphine
Injection
20mg/2ml,
50mg/5ml,
Apo-go penTM
Dose
Comments
By s/c injection: usual range
(after initiation3–30 mg daily in
divided doses
Should be initiated by specialist only
(secondary care setting)
By continuous s/c infusion
over 12 hours: initially
1 mg/hour daily increased
according to response.
Apomorphine is highly emetogenic; patients
must receive domperidone for at least 2 days
before starting treatment. Specialist supervision
is advisable throughout apomorphine treatment.
The information contained in the Formulary is based on evidence available at the time of writing; it is issued for guidance
and advice only. For information on the cautions, contra-indications, side effects and doses of individual drugs, please
check the current SPC or BNF section for that drug. Prescribers remain responsible for their patients‟ care and
prescriptions signed.
Review date April 2012
3
Monoamine-oxidase-B inhibitors
Drug
Dose
Comments
Selegiline Tablet
5mg, 10mg
Syrup 10mg in 5ml
10 mg in the morning, or
5 mg at breakfast and
midday; Elderly initiate at
2.5mg daily.
To avoid initial confusion and agitation, it
may be appropriate to start treatment with
a dose of 2.5 mg daily, particularly in the
elderly.
Rasagiline Tablet
1mg
1mg daily
Monotherapy or as an adjunct to
levodopa.
Catechol-O-methyltransferase inhibitors
Drug
Dose
Comments
Entacapone
Tablets 200mg
200 mg with each dose of
levodopa with dopadecarboxylase inhibitor;
max. 2 g daily
Entacapone is licensed for use as an
adjunct to co-beneldopa or co-careldopa for
patients with Parkinson‟s disease who
experience „end-of-dose‟ deterioration and
cannot be stabilized on these
combinations.
It is important than Entacapone and cobeneldopa or co-careldopa are taken
together at the same time of day.
Concurrent levodopa dose may need to be
reduced by about 10–30%.
Levodopa plus peripheral decarboxylase inhibitor with entacapone
Drug
Dose
Comments
Should be initiated by specialist only.
TM
Stalevo tablets
(levodopa with
carbidopa and
entacapone)
All strengths
Only 1 tablet to be
taken for each dose;
See BNF for specific
information for
maximum dose for
each strength.
Useful in reducing pill burden and end-of-dose
fluctuations not adequately controlled with
levodopa and dopa-decarboxylase inhibitor
treatment.
A mixture of levodopa, carbidopa and
entacapone; the proportions are
expressed in the form x/y/z where x, y and
z are the strengths in milligrams of
levodopa, carbidopa and entacapone
respectively.
The information contained in the Formulary is based on evidence available at the time of writing; it is issued for guidance
and advice only. For information on the cautions, contra-indications, side effects and doses of individual drugs, please
check the current SPC or BNF section for that drug. Prescribers remain responsible for their patients‟ care and
prescriptions signed.
Review date April 2012
4
Amantadine
Drug
Dose
Comments
Amantadine
capsules
100mg,
Syrup 50mg/5ml
100 mg daily increased
after one week to 100 mg
twice daily, usually in
conjunction with other
treatment; some patients
may require higher doses,
max. 400 mg daily
Amantadine is a weak dopamine agonist with
modest antiparkinsonian effects. It improves
mild bradykinetic disabilities as well as tremor
and rigidity. It may also be useful for
dyskinesias in more advanced disease.
Antimuscarinic drugs–e.g. orphenadrine, procyclidine and benxhexol
(trihexyphenidyl) No longer use routinely in treatment of Parkinson‟s Disease because
less effective that dopaminergic drugs and associated with cognitive impairment.
References
1. Parkinson‟s Disease: Diagnosis and management in primary and secondary care (CG35)
2. The British National Formulary - Latest version
3. Summary of Product Characteristics. Access by www.emc.medicines.org.uk.
4. Scottish Medicine Consortiums. Access by www.scottishmedicines.org.uk.
The information contained in the Formulary is based on evidence available at the time of writing; it is issued for guidance
and advice only. For information on the cautions, contra-indications, side effects and doses of individual drugs, please
check the current SPC or BNF section for that drug. Prescribers remain responsible for their patients‟ care and
prescriptions signed.
Review date April 2012
5