Conversely, excessive sleepiness, hallucinations, and
impulse control disorders are more likely to occur with
dopamine-receptor agonists than with levodopa.
g To avoid the potential for acute akinesia or
neuroleptic malignant syndrome, antiparkinsonian drug
concentrations should not be allowed to fall suddenly due to
poor absorption or abrupt withdrawal. h
g If a patient with Parkinson’s disease develops
dyskinesia or motor fluctuations, specialist advice should be
sought before modifying antiparkinsonian drug therapy.
Patients who develop dyskinesia or motor fluctuations
despite optimal levodopa therapy should be offered a choice
of non-ergotic dopamine-receptor agonists (pramipexole,
ropinirole, rotigotine), monoamine oxidase B inhibitors
(rasagiline or selegiline hydrochloride) or COMT inhibitors
(entacapone p. 412 or tolcapone p. 413) as an adjunct to
An ergot-derived dopamine-receptor agonist (bromocriptine
p. 419, cabergoline p. 421 or pergolide p. 422) should only be
considered as an adjunct to levodopa if symptoms are not
adequately controlled with a non-ergot-derived dopaminereceptor agonist.
If dyskinesia is not adequately managed by modifying
existing therapy, amantadine hydrochloride p. 418 should be
Drug management of non-motor symptoms in Parkinson’s
Daytime sleepiness and sudden onset of sleep
g Patients who experience daytime sleepiness or sudden
onset of sleep, should have their Parkinson’s drug treatment
adjusted under specialist medical guidance. If reversible
pharmacological and physical causes have been excluded,
modafinil p. 492 should be considered to treat excessive
daytime sleepiness, and treatment should be reviewed at
Patients with Parkinson’s disease who have daytime
sleepiness or sudden onset of sleep should be advised not to
drive, to inform the DVLA about their symptoms, and to
think about any occupational hazards. h
g When treating nocturnal akinesia in patients with
Parkinson’s disease, levodopa or oral dopamine-receptor
agonists should be considered as first-line options and
rotigotine p. 426 as second-line (if both levodopa or oral
dopamine-receptor agonists are ineffective). h
g Patients with Parkinson’s disease who develop postural
hypotension should have their drug treatment reviewed to
address any pharmacological cause. If drug therapy is
required, midodrine hydrochloride p. 188 should be
considered as the first option and fludrocortisone acetate
p. 676 [unlicensed indication] as an alternative. h
See Antidepressant drugs p. 359.
g Hallucinations and delusions need not be treated if
they are well tolerated. Otherwise, the dosage of any
antiparkinsonism drugs that might have triggered
hallucinations or delusions should be reduced, taking into
account the severity of symptoms and possible withdrawal
effects. Specialist advice should be sought before modifying
In Parkinson’s disease patients with no cognitive
impairment, quetiapine p. 401 [unlicensed indication] can be
considered to treat hallucinations and delusions. If standard
treatment is not effective, clozapine p. 396 should be offered
to treat hallucinations and delusions in patients with
Parkinson’s disease. hIt is important to acknowledge that
other antipsychotic medicines (such as phenothiazines and
butyrophenones) can worsen the motor features of
Rapid eye movement sleep behaviour disorder
g Clonazepam p. 337 [unlicensed indication] or
melatonin p. 489 [unlicensed indication] should be
considered to treat rapid eye movement sleep behaviour
disorder in Parkinson’s patients once possible
pharmacological causes have been addressed. h
g Drug treatment for drooling of saliva in patients with
Parkinson’s disease should only be considered if non-drug
treatment such as speech and language therapy is not
Glycopyrronium bromide p. 1335 [unlicensed indication]
should be considered as first-line treatment and botulinum
toxin type A p. 407 [unlicensed indication] as second-line.
Other antimuscarinic drugs, should only be considered if
the risk of cognitive adverse effects is thought to be minimal;
topical preparations, such as atropine[unlicensed indication],
should be used if possible to reduce the risk of adverse
g An acetylcholinesterase inhibitor should be offered to
patients with mild-to-moderate Parkinson’s disease
dementia and considered for patients with severe
Parkinson’s disease dementia [unlicensed indications apart
from rivastigmine capsules and oral solution p. 303 for the
treatment of mild-to-moderate dementia in patients with
Parkinson’s disease]. If acetylcholinesterase inhibitors are
not tolerated or contra-indicated, memantine hydrochloride
p. 304 [unlicensed indication] should be considered. hFor
further information see Dementia p. 300
g Patients with advanced Parkinson’s disease can be
offered apomorphine hydrochloride p. 418 as intermittent
injections or continuous subcutaneous infusions. To control
nausea and vomiting associated with apomorphine,
administration of domperidone p. 431 is usually started two
days before apomorphine therapy, and then discontinued as
soon as possible. To reduce the risk of serious arrhythmia
due to QT prolongation associated to the concomitant use of
domperidone p. 431 and apomorphine hydrochloride p. 418,
the MHRA recommends an assessment of cardiac risk factors
and ECG monitoring and to ensure that the benefits
outweighs the risks when initiating treatment. h
Levodopa-carbidopa intestinal gel is used for the
treatment of advanced levodopa-responsive Parkinson’s
disease with severe motor fluctuations and hyperkinesia or
dyskinesia. The gel is administered with a portable pump
directly into the duodenum or upper jejunum.
g Deep brain stimulation should only be considered for
patients with advanced Parkinson’s disease whose symptoms
are not adequately controlled by best drug therapy. h
Impulse control disorders (compulsive gambling,
hypersexuality, binge eating, or obsessive shopping) can
develop in a person with Parkinson’s disease who is on any
dopaminergic therapy at any stage in the disease course
particularly if the patient has a history of previous impulsive
behaviours, alcohol consumption, or smoking.g Patients
should be informed about the different types of impulse
control disorders and that dopamine-receptor agonist
therapy may be reduced or stopped if problematic impulse
patients should be monitored for symptoms of dopamine
agonist withdrawal. Specialist cognitive behavioural therapy
should be offered if modifying dopaminergic therapy is not
Parkinson’s disease in adults. National Institute for Health
and Care Excellence. NICE guideline 71. July 2017.
l DRUG ACTION Orphenadrine exerts its antiparkinsonian
action by reducing the effects of the relative central
cholinergic excess that occurs as a result of dopamine
Parkinsonism |Drug-induced extrapyramidal symptoms
▶ Adult: Initially 150 mg daily in divided doses, then
increased in steps of 50 mg every 2–3 days, adjusted
according to response; usual dose 150–300 mg daily in
divided doses; maximum 400 mg per day
▶ Elderly: Preferably dose at lower end of range
l CONTRA-INDICATIONS Acute porphyrias p. 1058 . gastrointestinal obstruction . myasthenia gravis
to abuse . prostatic hypertrophy . psychotic disorders . pyrexia
l INTERACTIONS → Appendix 1: orphenadrine
▶ Uncommon Confusion . constipation . coordination
▶ Rare or very rare Memory loss
l HEPATIC IMPAIRMENT Manufacturer advises caution.
l RENAL IMPAIRMENT Use with caution.
l TREATMENT CESSATION Avoid abrupt withdrawal in
patients taking long-term treatment.
Driving and skilled tasks May affect performance of skilled
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral solution
▶ Orphenadrine hydrochloride (Non-proprietary)
Orphenadrine hydrochloride 10 mg per 1 ml Orphenadrine
50mg/5ml oral solution sugar free sugar-free | 150 ml P £40.00
l DRUG ACTION Procyclidine exerts its antiparkinsonian
action by reducing the effects of the relative central
cholinergic excess that occurs as a result of dopamine
Parkinsonism | Extrapyramidal symptoms (but not tardive
▶ Adult: 2.5 mg 3 times a day, then increased in steps of
2.5–5 mg daily if required; increased if necessary up to
30 mg daily in 2–4 divided doses, to be increased at
2–3 day intervals. Maximum daily dose only to be used
in exceptional circumstances; maximum 60 mg per day
▶ Elderly: Lower end of range preferable
▶ BY INTRAMUSCULAR INJECTION, OR BY INTRAVENOUS
▶ Adult: 5–10 mg, occasionally, more than 10 mg, dose
usually effective in 5–10 minutes but may need
▶ Elderly: Lower end of range preferable
l CONTRA-INDICATIONS Gastro-intestinal obstruction . myasthenia gravis
l INTERACTIONS → Appendix 1: procyclidine
▶ Common or very common Constipation . dry mouth . urinary retention . vision blurred
▶ Rare or very rare Psychotic disorder
l PREGNANCY Use only if potential benefit outweighs risk.
l BREAST FEEDING No information available.
l HEPATIC IMPAIRMENT Manufacturer advises caution.
l RENAL IMPAIRMENT Use with caution.
l TREATMENT CESSATION Avoid abrupt withdrawal in
patients taking long-term treatment.
Driving and skilled tasks May affect performance of skilled
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension, oral
▶ Procyclidine hydrochloride (Non-proprietary)
Procyclidine hydrochloride 5 mg per 1 ml Procyclidine 10mg/2ml
solution for injection ampoules | 5 ampoule P £60.00–£78.75 DT =
BNF 78 Parkinson’s disease 411
▶ Procyclidine hydrochloride (Non-proprietary)
Procyclidine hydrochloride 500 microgram per 1 ml Procyclidine
2.5mg/5ml oral solution sugar free sugar-free | 150 ml P £11.00–
Procyclidine hydrochloride 1 mg per 1 ml Procyclidine 5mg/5ml
oral solution sugar free sugar-free | 150 ml P £17.00–£21.68 DT =
▶ Procyclidine hydrochloride (Non-proprietary)
Procyclidine hydrochloride 5 mg Procyclidine 5mg tablets |
28 tablet P £12.65 DT = £2.94 | 100 tablet P £8.94–£14.89 | 500 tablet P £44.63–£74.46
▶ Kemadrin (Aspen Pharma Trading Ltd)
Procyclidine hydrochloride 5 mg Kemadrin 5mg tablets | 100 tablet P £4.72 | 500 tablet P £23.62
l DRUG ACTION Trihexyphenidyl exerts its effects by
reducing the effects of the relative central cholinergic
excess that occurs as a result of dopamine deficiency.
Parkinson’s disease (if used in combination with cocareldopa or co-beneldopa)
▶ Adult: Maintenance 2–6 mg daily in divided doses, use
not recommended because of toxicity in the elderly and
the risk of aggravating dementia
Parkinsonism | Drug-induced extrapyramidal symptoms
▶ Adult: 1 mg daily, then increased in steps of 2 mg every
3–5 days, adjusted according to response; maintenance
5–15 mg daily in 3–4 divided doses, not recommended
for use in Parkinson’s disease because of toxicity in the
elderly and the risk of aggravating dementia; maximum
▶ Elderly: Lower end of range preferable, not
recommended for use in Parkinson’s disease because of
toxicity in the elderly and the risk of aggravating
l CONTRA-INDICATIONS Gastro-intestinal obstruction . myasthenia gravis
l INTERACTIONS → Appendix 1: trihexyphenidyl
l PREGNANCY Use only if potential benefit outweighs risk.
l HEPATIC IMPAIRMENT Manufacturer advises caution.
l RENAL IMPAIRMENT Use with caution.
l TREATMENT CESSATION Avoid abrupt withdrawal in
patients taking long-term treatment.
l DIRECTIONS FOR ADMINISTRATION Tablets should be
Driving and skilled tasks May affect performance of skilled
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension, oral
EXCIPIENTS: May contain Propylene glycol
▶ Trihexyphenidyl hydrochloride (Non-proprietary)
Trihexyphenidyl hydrochloride 1 mg per 1 ml Trihexyphenidyl
5mg/5ml oral solution | 200 ml P £24.00–£28.37 DT = £26.40
▶ Trihexyphenidyl hydrochloride (Non-proprietary)
Trihexyphenidyl hydrochloride 2 mg Trihexyphenidyl 2mg tablets
| 84 tablet P £4.20 DT = £3.46
Trihexyphenidyl hydrochloride 5 mg Trihexyphenidyl 5mg tablets
| 84 tablet P £17.91 DT = £17.91
DOPAMINERGIC DRUGS › CATECHOL-OMETHYLTRANSFERASE INHIBITORS
l DRUG ACTION Entacapone prevents the peripheral
Adjunct to co-beneldopa or co-careldopa in Parkinson’s
disease with ‘end-of-dose’ motor fluctuations (under
▶ Adult: 200 mg, dose to be given with each dose of
levodopa with dopa-decarboxylase inhibitor;
l CONTRA-INDICATIONS History of neuroleptic malignant
syndrome . history of non-traumatic rhabdomyolysis . phaeochromocytoma
l CAUTIONS Concurrent levodopa dose may need to be
reduced by about 10–30% . ischaemic heart disease
l INTERACTIONS → Appendix 1: entacapone
disease . movement disorders . nausea . sleep disorders . urine discolouration . vomiting
▶ Uncommon Myocardial infarction
▶ Rare or very rare Agitation . appetite decreased . skin
▶ Frequency not known Colitis . hair colour changes . hepatic
l PREGNANCY Avoid—no information available.
l BREAST FEEDING Avoid—present in milk in animal studies.
l HEPATIC IMPAIRMENT Manufacturer advises avoid.
l TREATMENT CESSATION Avoid abrupt withdrawal.
l PATIENT AND CARER ADVICE Patient counselling is advised
(may colour urine reddish-brown, concomitant iron
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension, oral
CAUTIONARY AND ADVISORY LABELS 14
▶ Entacapone (Non-proprietary)
▶ Comtess (Orion Pharma (UK) Ltd)
Entacapone 200 mg Comtess 200mg tablets | 30 tablet P £17.24 DT = £3.49 | 100 tablet P £57.45
Combinations available: Levodopa with carbidopa and
l DRUG ACTION Opicapone prevents the peripheral
Adjunct to co-beneldopa or co-careldopa in Parkinson’s
disease with ‘end-of-dose’ motor fluctuations (under
▶ Adult: 50 mg once daily, dose to be taken at bedtime, at
least one hour before or after levodopa combinations
l CONTRA-INDICATIONS Catecholamine-secreting
l CAUTIONS Concurrent levodopa dose may need to be
reduced . elderly over 85 years (limited information
l INTERACTIONS → Appendix 1: opicapone
▶ Uncommon Anxiety . appetite decreased . depression . dry
eye . dyspnoea . ear congestion . gastrointestinal
SIDE-EFFECTS, FURTHER INFORMATION Manufacturer
advises consider liver function tests in patients who
experience progressive anorexia, asthenia and weight
decrease within a relatively short period of time.
l PREGNANCY Manufacturer advises avoid—limited
l BREAST FEEDING Manufacturer advises avoid—no
l HEPATIC IMPAIRMENT Manufacturer advises avoid in
Dose adjustments Manufacturer advises use with caution
in moderate impairment—dose adjustment may be
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Ongentys (BIAL Pharma UK Ltd) A
Opicapone 50 mg Ongentys 50mg capsules | 30 capsule P £93.90 DT = £93.90
l DRUG ACTION Tolcapone prevents the peripheral
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)
▶ Adult: 100 mg 3 times a day (max. per dose 200 mg
3 times a day) continuing beyond 3 weeks only if
substantial improvement, leave 6 hours between each
dose; first daily dose should be taken at the same time
as levodopa with dopa-decarboxylase inhibitor, dose
maximum only in exceptional circumstances
l CONTRA-INDICATIONS Phaeochromocytoma . previous
history of hyperthermia . previous history of neuroleptic
malignant syndrome . previous history of rhabdomyolysis . severe dyskinesia
l CAUTIONS Most patients receiving more than 600 mg
levodopa daily require reduction of levodopa dose by
▶ 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
l INTERACTIONS → Appendix 1: tolcapone
disorders . syncope . upper respiratory tract infection . urine discolouration . vomiting
▶ Uncommon Hepatocellular injury
▶ Rare or very rare Eating disorders . neuroleptic malignant
l PREGNANCY Toxicity in animal studies—use only if
potential benefit outweighs risk.
l BREAST FEEDING Avoid—present in milk in animal studies.
l HEPATIC IMPAIRMENT Manufacturer advises avoid.
l RENAL IMPAIRMENT Caution if eGFR less than
l MONITORING REQUIREMENTS Test liver function before
treatment, and monitor every 2 weeks for first year, every
4 weeks for next 6 months and then every 8 weeks
thereafter (restart monitoring schedule if dose increased).
l TREATMENT CESSATION Avoid abrupt withdrawal.
l PATIENT AND CARER ADVICE Patients should be told 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
BNF 78 Parkinson’s disease 413
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 14, 25
▶ Tasmar (Meda Pharmaceuticals Ltd)
Tolcapone 100 mg Tasmar 100mg tablets | 100 tablet P £95.20
▶ BY MOUTH USING IMMEDIATE-RELEASE MEDICINES
▶ Adult: Initially 50 mg 3–4 times a day, then increased
in steps of 100 mg daily, dose to be increased once or
twice weekly according to response; maintenance
400–800 mg daily in divided doses
▶ Elderly: Initially 50 mg 1–2 times a day, then increased
in steps of 50 mg daily, dose to be increased every
3–4 days according to response
Parkinson’s disease (in advanced disease)
▶ BY MOUTH USING IMMEDIATE-RELEASE MEDICINES
▶ Adult: Initially 100 mg 3 times a day, then increased in
steps of 100 mg daily, dose to be increased once or
twice weekly according to response; maintenance
400–800 mg daily in divided doses
Parkinson’s disease (patients not taking levodopa/dopadecarboxylase inhibitor therapy)
▶ BY MOUTH USING MODIFIED-RELEASE MEDICINES
▶ Adult: Initially 1 capsule 3 times a day; maximum
Parkinson’s disease (patients transferring from
immediate-release levodopa/dopa-decarboxylase
▶ BY MOUTH USING MODIFIED-RELEASE MEDICINES
▶ Adult: Initially 1 capsule substituted for every 100 mg
of levodopa and given at same dosage frequency,
increased every 2–3 days according to response;
average increase of 50% needed over previous levodopa
dose and titration may take up to 4 weeks,
supplementary dose of immediate-release Madopar ®
may be needed with first morning dose; if response still
poor to total daily dose of Madopar ® CR plus
Madopar ® corresponding to 1.2 g levodopa—consider
DOSE EQUIVALENCE AND CONVERSION
▶ Dose is expressed as levodopa.
Treatment with levodopa is associated with impulse
control disorders, including pathological gambling,
binge eating, and hypersexuality. Patients and their
carers should be informed about the risk of impulse
control disorders. If the patient develops an impulse
control disorder, levodopa should be withdrawn or the
dose reduced until the symptoms resolve.
myocardial infarction with residual arrhythmia . history of
and discontinue if deterioration). severe cardiovascular
disease . severe pulmonary disease . susceptibility to
l INTERACTIONS → Appendix 1: levodopa
hypotension . sleep disorders .taste altered . vomiting
▶ Rare or very rare Leucopenia
discolouration . urine discolouration
l PREGNANCY Caution in pregnancy—toxicity has occurred
l BREAST FEEDING May suppress lactation; present in
l HEPATIC IMPAIRMENT Manufacturer advises caution in
mild to moderate impairment; avoid in decompensated
l RENAL IMPAIRMENT Use with caution.
l EFFECT ON LABORATORY TESTS False positive tests for
urinary ketones have been reported.
l TREATMENT CESSATION Avoid abrupt withdrawal (risk of
neuroleptic malignant syndrome and rhabdomyolysis).
l DIRECTIONS FOR ADMINISTRATION The dispersible tablets
can be dispersed in water or orange squash (not orange
l PRESCRIBING AND DISPENSING INFORMATION Cobeneldopa is a mixture of benserazide hydrochloride and
levodopa in mass proportions corresponding to 1 part of
benserazide and 4 parts of levodopa.
When transferring patients from another
levodopa/dopa-decarboxylase inhibitor preparation, the
previous preparation should be discontinued 12 hours
before (although interval can be shorter).
When switching from modified-release levodopa to
dispersible co-beneldopa, reduce dose by approximately
When administered as an adjunct to other
antiparkinsonian drugs, once therapeutic effect apparent,
the other drugs may be reduced or withdrawn.
l PATIENT AND CARER ADVICE Patients or carers should be
given advice on how to administer co-beneldopa
Dopamine dysregulation syndrome Manufacturer advises
patients and their carers should be informed of the risk of
developing dopamine dysregulation syndrome; addictionlike symptoms should be reported.
Driving and skilled tasks Sudden onset of sleep Excessive
daytime sleepiness and sudden onset of sleep can occur
Patients starting treatment with these drugs should be
warned of the risk and of the need to exercise caution
when driving or operating machinery. Those who have
experienced excessive sedation or sudden onset of sleep
should refrain from driving or operating machines until
these effects have stopped occurring.
Management of excessive daytime sleepiness should
focus on the identification of an underlying cause, such as
depression or concomitant medication. Patients should be
counselled on improving sleep behaviour.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension, oral
CAUTIONARY AND ADVISORY LABELS 10, 14, 21
▶ Madopar (Roche Products Ltd)
Benserazide (as Benserazide hydrochloride) 12.5 mg, Levodopa
50 mg Madopar 50mg/12.5mg dispersible tablets sugar-free | 100 tablet P £5.90 DT = £5.90
Benserazide (as Benserazide hydrochloride) 25 mg, Levodopa
100 mg Madopar 100mg/25mg dispersible tablets sugar-free | 100 tablet P £10.45 DT = £10.45
CAUTIONARY AND ADVISORY LABELS 5, 10, 14, 25
▶ Madopar CR (Roche Products Ltd)
Benserazide (as Benserazide hydrochloride) 25 mg, Levodopa
100 mg Madopar CR capsules | 100 capsule P £12.77 DT =
CAUTIONARY AND ADVISORY LABELS 10, 14, 21
▶ Co-beneldopa (Non-proprietary)
Benserazide (as Benserazide hydrochloride) 12.5 mg, Levodopa
50 mg Co-beneldopa 12.5mg/50mg capsules | 100 capsule P £4.71–£4.96 DT = £4.96
Benserazide (as Benserazide hydrochloride) 50 mg, Levodopa
200 mg Co-beneldopa 50mg/200mg capsules | 100 capsule P £11.78 DT = £11.78
▶ Madopar (Roche Products Ltd)
Benserazide (as Benserazide hydrochloride) 12.5 mg, Levodopa
50 mg Madopar 50mg/12.5mg capsules | 100 capsule P £4.96
Benserazide (as Benserazide hydrochloride) 25 mg, Levodopa
100 mg Madopar 100mg/25mg capsules | 100 capsule P £6.91
Benserazide (as Benserazide hydrochloride) 50 mg, Levodopa
200 mg Madopar 200mg/50mg capsules | 100 capsule P £11.78
▶ Adult: Initially 25/100 mg 3 times a day, then increased
in steps of 12.5/50 mg once daily or on alternate days,
alternatively increased in steps of 25/100 mg once daily
or on alternate days, dose to be adjusted according to
response; dose increased until 800 mg levodopa (with
200 mg carbidopa) daily in divided doses is reached,
then maintenance up to 200/2000 mg daily in divided
doses, adjusted according to response, when cocareldopa is used, the total daily dose of carbidopa
should be at least 70 mg. A lower dose may not achieve
full inhibition of extracerebral dopa-decarboxylase,
with a resultant increase in side-effects
Parkinson’s disease—alternative regimen
▶ Adult: Initially 12.5/50 mg 3–4 times a day,
alternatively initially 10/100 mg 3–4 times a day, then
increased in steps of 12.5/50 mg once daily or on
alternate days, adjusted according to response,
alternatively increased in steps of 10/100 mg once daily
or on alternate days, adjusted according to response,
dose increased until 800 mg levodopa (with up to
200 mg carbidopa) daily in divided doses is reached,
then maintenance up to 200/2000 mg daily in divided
doses, adjusted according to response, when cocareldopa is used, the total daily dose of carbidopa
should be at least 70 mg. A lower dose may not achieve
full inhibition of extracerebral dopa-decarboxylase,
with a resultant increase in side-effects
DOSE EQUIVALENCE AND CONVERSION
▶ The proportions are expressed in the form x/y where x
and y are the strengths in milligrams of carbidopa and
▶ 2 tablets Sinemet ® 12.5 mg/50 mg is equivalent to
1 tablet Sinemet ® Plus 25 mg/100 mg.
Parkinson’s disease (patients not receiving
levodopa/dopa-decarboxylase inhibitor preparations,
▶ BY MOUTH USING MODIFIED-RELEASE TABLETS
▶ Adult: Initially 100–200 mg twice daily, dose to be
given at least 6 hours apart; dose adjusted according to
response at intervals of at least 2 days
Parkinson’s disease (patients transferring from
immediate-release levodopa/dopa-decarboxylase
▶ BY MOUTH USING MODIFIED-RELEASE TABLETS
▶ Adult: Discontinue previous preparation at least
12 hours before first dose of Caramet ® CR; substitute
Caramet ® CR to provide a similar amount of levodopa
daily and extend dosing interval by 30–50%; dose then
adjusted according to response at intervals of at least
Severe Parkinson’s disease inadequately controlled by
▶ Adult: Administered as intestinal gel, for use with
enteral tube (consult product literature)
Parkinson’s disease (for fine adjustment of Sinemet ® CR
▶ Adult: (consult product literature)
Parkinson’s disease (patients not receiving
levodopa/dopa-decarboxylase inhibitor therapy)
▶ Adult: Initially 1 tablet twice daily, both dose and
interval then adjusted according to response at
intervals of not less than 3 days
Parkinson’s disease (patients transferring from
immediate-release levodopa/dopa-decarboxylase
▶ Adult: 1 tablet twice daily, dose can be substituted for a
daily dose of levodopa 300–400 mg in immediaterelease Sinemet ® tablets (substitute Sinemet ® CR to
provide approximately 10% more levodopa per day and
extend dosing interval by 30–50%); dose and interval
then adjusted according to response at intervals of not
Treatment with levodopa is associated with impulse
control disorders, including pathological gambling,
binge eating, and hypersexuality. Patients and their
carers should be informed about the risk of impulse
control disorders. If the patient develops an impulse
control disorder, levodopa should be withdrawn or the
dose reduced until the symptoms resolve.
myocardial infarction with residual arrhythmia . history of
and discontinue if deterioration). severe cardiovascular
BNF 78 Parkinson’s disease 415
disease . severe pulmonary disease . susceptibility to
l INTERACTIONS → Appendix 1: carbidopa . levodopa
▶ Rare or very rare Drowsiness . seizure . sleep disorders
dysregulation syndrome . dry mouth . dyskinesia (may be
abnormal . gastrointestinal discomfort. gastrointestinal
disorders . gastrointestinal haemorrhage . haemolytic
anaemia . hallucination . headache . Henoch-Schönlein
purpura . hiccups . hoarseness . Horner’s syndrome
syndrome (on abrupt discontinuation). oedema . on and
l PREGNANCY Use with caution—toxicity has occurred in
l BREAST FEEDING May suppress lactation; present in
l HEPATIC IMPAIRMENT Manufacturer advises use with
DUODOPA ® DOSE ADJUSTMENTS Manufacturer advises
titrate dose with caution in severe impairment.
l RENAL IMPAIRMENT Use with caution.
l EFFECT ON LABORATORY TESTS False positive tests for
urinary ketones have been reported.
l TREATMENT CESSATION Avoid abrupt withdrawal (risk of
neuroleptic malignant syndrome and rhabdomyolysis).
l PRESCRIBING AND DISPENSING INFORMATION Cocareldopa is a mixture of carbidopa and levodopa; the
proportions are expressed in the form x/y where x and y
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