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®)

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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 Selegiline tablets 5mg, 10mg

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 *Sastravi® tablets - NB: secondary care use only, who will prescribe and label generically.

*Primary Care Prescribers to issue as Stanek® or Stalevo®;

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

NICE TA934 Foslevodopa–foscarbidopa for treating advanced Parkinson's with motor symptoms

Foslevodopa–foscarbidopa is recommended as an option for treating advanced levodopa-responsive Parkinson's in adults whose

symptoms include severe motor fluctuations and hyperkinesia or dyskinesia, when available medicines are not working well

enough, only if:

> they cannot have apomorphine or deep brain stimulation, or these treatments no longer control symptoms, and

> the company provides foslevodopa–foscarbidopa according to the commercial arrangement.

RED Foslevodopa–foscarbidopa (Produodopa) 240 mg/12 mg per ml solution for infusion

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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

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4.9.1 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’

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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

Trihexphenidyl liquid

Use in dystonic symptoms in children with neurodevelopment conditions

AMBER Trihexphenidyl liquid

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®)

injection 200units (Xeomin®) 2nd line option when intolerance to Dysport® or Botox®

[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)

Shared Care

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

Infantile Haemangiomas see section 13

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All material in this section is aimed at health care professionals, but is information currently held in the public domain, members of the

public seeking advice on medicine-related matters are advised to speak with their GP, pharmacist, nurse or contact NHS111 Service.

Email: info.elmmb@nhs.net