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4.9 Drugs used in Parkinsonism and related disorders

4.9 Drugs used in Parkinsonism and related disorders

4.9.1 Dopaminergic drugs used in parkinsonism

Levodopa with a dopa-decarboxylase inhibitor is the treatment of choice for patients disabled by idiopathic Parkinson's disease. 
Therapy should be initiated with low doses, gradually increased. Final dose may be a compromise between mobility and side-
effects.
 
GREEN         Co-beneldopa  (benserazide/levodopa) 
                      dispersible tablets 25/100 (Madopar 125®)
                      capsules m/r 25/100 (Madopar CR 125®)
GREEN         Co-careldopa (carbidopa/levodopa) 
                      tablets 10/100 (Sinemet-110®), 25/250 (Sinemet-275®)
                      tablets 25/100 (Sinemet-Plus®) 
                      tablets m/r 25/100 (Sinemet Half CR®), 50/200 (Sinemet CR®)
GREEN         Selegiline oral lyophilisates 1.25mg (Zelapar®) 
 
Other dopaminergic drugs
In Parkinson’s disease pramipexole is seen as the dopamine agonist of choice in the movement disorders clinic, with cabergoline
and ropinirole also seen as useful. Dose titration by GPs should be carried out in line with specialist nurse or clinician
recommendations after the initial prescription.
 
AMBER      Amantadine capsules 100mg & syrup 50mg/5mL
AMBER      Apomorphine injection (APO-go®)       Click here for shared care agreement
AMBER      Cabergoline tablets 1mg, 2mg, 4mg  
AMBER      Pramipexole (generic only) tablets 88mcg, 180mcg, 350mcg, 700mcg
AMBER      Pramipexole MR preparations (generic only)
                   260mcg, 520mcg, 1.05mg, 1.57mg, 2.1mg, 2.62mg, 3.15mg
                    (MR preparations are only for use only when there are compliance issues) 
 
AMBER     Rasagiline tablets 1mg
AMBER     Ropinirole tablets 250micrograms, 1mg, 2mg, 5mg 
                  Starter pack (42 x 0·25 mg, 42 x 0·5 mg, 21 x 1 mg).
                  Follow-on pack (42 x 0·5 mg, 42 x 1 mg, 63 x 2 mg)
AMBER     Ropinirole prolonged release, once daily tablets  
                  2mg, 4mg, 8mg.
                  
AMBER     Levodopa /carbidopa/ entacapone 
                  Stalevo®  Stanek® tablets 50/12.5/200
                  Stalevo®  Stanek® tablets 100/25/200
                  Stalevo®   Stanek® tablets 150/37.5/200
AMBER     Entacapone tablets 200mg 
RED            Tolcapone tablets –   Requires intensive LFT monitoring.
AMBER     Opicapone (Ongentys®) 50mg hard capsules 
 
Note: Opicapone is recommended as a second line catechol-o-methyltransferase inhibitor in adult patients with Parkinson's disease with
          'end of dose' motor fluctuations who cannot be stabilised on levodopa/DDCI inhibitors and who fail to respond to or are intolerant 
          of entacapone, where tolcapone is being considered. 
 
BLACK      Safinamide (Xadago®) 50mg and 100mg film-coated tablets
                  Click here to access New Medicines Recommendation


Rotigotine patches 
Rotigotine has shown inferiority to ropinirole and should not be used in preference to other dopamine agonists unless such alternative are not suitable (e.g. compliance issues,
need for social care to administer other oral therapies, dysphagia), not tolerated (GI disturbance), or ineffective. Rotigotine is recommended for use only within its licensed 
indications (i.e. both early and late stage Parkinson’s disease, as monotherapy or in combination).  Rotigotine requires dose titration.
 
Dose in early stage Parkinson’s disease, initiated at 2mg/24hr and patients should be initially prescribed a dose titration (starter pack) to ensure that the patient reaches the 
optimum dose of 6mg/day or 8mg/day (maximum dose) within 1 month.  Therapy should then be continued at this dose by the primary care prescriber unless the patient suffers
side effects, where dose reduction to 4mg/day or 6mg/day should be considered. 
 
Dose in advanced stage Parkinson’s disease with fluctuations, initiated at 4mg/24hr and increased weekly by  2mg/24hr weekly to maximum 16mg/24hr.
 
Prescribing responsibility may be passed to primary care prescribers following the specialist’s initial prescription, but response to treatment and the need for continued
therapy should be continuously monitored for by the specialist.
 
AMBER     Rotigotine patches 2mg, 4mg, 6mg, 8mg & starter pack  

4.9.1.1 Dopaminergic drugs used in restless leg syndrome

Diagnosis of restless legs syndrome (RLS) can be made if all of the following four criteria are met:
 
          >     a need to move the legs, usually accompanied or caused by uncomfortable, unpleasant sensations in the legs,
          >     symptoms are exclusively present or worsen during periods of inactivity/rest,
          >     symptoms are partially or totally relieved by movement such as walking or stretching at least as long as the activity 
                 continues.   
          >     symptoms are generally worse or exclusively occur in the evening or during the night 
 
Guidelines on the management of Restless Leg Syndrome in primary care can be accessed here
 
Once a diagnosis has been made, the patients severity of symptoms should be scored using the International Restless Leg
Syndrome (IRLS) rating scale. See appendix II.
 
Other secondary cases should be referred to a specialist for diagnosis (e.g. renal failure). Dopamine agonists are not licensed for 
the management of secondary RLS, only idiopathic RLS. Try to avoid drugs that can exacerbate symptoms (CNS stimulants, 
diuretics, tricyclic antidepressants, calcium antagonists, phenytoin). 
 
Patients with paroxsysmal RLS should be offered advice on sleep hygiene and other non-pharmacological measures which will 
reduce symptoms in some patients.  Should these measures fail, pramipexole may be offered on a ‘when required’ basis in line
with the recommendations below.
 
Patients with moderate to severe RLS (as rated on the IRLS scale, 15 to 40 points) should also be offered sleep hygiene advice and
non-pharmacological measures. Patients may consequently be offered treatment with pramipexole, which may be initiated by any
prescriber for the treatment of restless leg syndrome (RLS) in line with the product licence and the following recommendations;
 
          >     to be initiated in patients with primary (idiopathic) RLS only
          >     serum ferritin should be checked to exclude iron deficiency as a cause. If ferritin <20mcg/L then oral iron 
                 supplementation should be offered initially
 
Pramipexole – 1st Line Choice 
          >     treatment should be initiated at pramipexole 125micrograms/day. Many patients respond to this dose within one week.
                 Dose increases to pramipexole 125micrograms/day and pramipexole 500micrograms/day should be undertaken in one
                 week intervals only where necessary. Maximum dose of pramipexole 750micrograms/day should rarely be required.
                 The dose should be taken 2-3 hours before bedtime. [Doses stated relate to pramipexole dihydrochloride]
          >     Patients should be counselled that treatment with a dopamine agonist can in some patients exacerbate symptoms, or                       cause them to appear earlier in the day (augmentation). Some patients see a rebound in symptoms on cessation of
                 treatment. Relapse rates with long term treatment are also unknown at this stage. Dopamine agonists can also cause
                 sudden hypersomnia - patients should also be warned of this overwhelming sensation of sleepiness occurring with little
                 or no warning, and the need to exercise caution when driving or operating machinery. They are also rarely associated
                 with pathological gambling. 
          >     Treatment should be reviewed at 3 months and stopped if little or no benefit seen. Patients should be referred where
                 there is neurological comorbidity (if this requires assessment or seriously impedes diagnosis), failure of response to two
                 dopamine agonists, or augmentation occurs.
 
GREEN      Generic Pramipexole dihydrochloride  tabelts 125 micrograms, 250 micrograms
 
Ropinirole – 2nd Line Choice
Ropinirole may only be initiated for the treatment of RLS where the use of pramipexole is inappropriate, not tolerated or
ineffective. Efficacy data for the licence for ropinirole comes from those patients with an IRLS score of 24 or above (rather than 15
or above with pramipexole); dose titration is slower than with pramipexole and costs more at the average dose. Starter packs are 
available for initial dose titration up to 0.5mg/day.
 
GREEN      Ropinirole 
                   tablets 0.25mg, 0.5mg, 2mg & ‘starter pack’ 

4.9.2 Antimuscarinic drugs used in parkinsonism

Less effective than levopoda in idiopathic Parkinson's disease, but often supplement its action. Patients with mild symptoms,
particularly tremor, may be treated with antimuscarinics alone initially. Prolonged use may cause cognitive impairment.
 
GREEN      Trihexyphenidyl (benzhexol) 
                   tablets 2mg, 5mg
GREEN      Procyclidine 
                   tablets 5mg
                   syrup 2.5mg/5mL, 5mg/5mL
                   injection 10mg/2mL
 

4.9.3 Drugs used in essential tremor, chorea, tics and related disorders

Haloperidol is used for motor tics and choreas, propranolol and primidone for essential tremor and tetrabenazine to control 
movement disorders e.g. Huntington's Chorea.  Riluzole should be used as per NICE guidelines to treat the amytrophic lateral
sclerosis form of motor neurone disease.
 
RED             Botulinum A toxin (Consultant only) 
                   injection 100units  (Botox®) 
                   injection 500units  (Dysport®) 
                   [Brands are not interchangeable] 
AMBER       Clonidine tablets 25 micrograms 
GREEN        Haloperidol - see section 4.2.1 
AMBER       Primidone tablets 250mg (unlicensed)
GREEN       Propranolol -see section 4.7.4.2 
AMBER      Riluzole tablets 50mg (Consultant Neurologist  initiation only) 
AMBER      Tetrabenazine tablets 25mg
RED            Botulinum neurotoxin type A (Xeomin® 50unit, 100unit, 200unit powder for solution for injection)
                    [excessive salivation and drooling) caused by neurological conditions in adults]                                       CCG Commissioned, BlueTec Form 


 




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