4.9.1 Dopaminergic drugs used in Parkinson's disease

Dopamine receptor agonists

Amantadine
  • Capsules 100mg (£45.54 = 56 capsules)
Apomorphine
  • Injection 10mg/ml

Notes

  1. Apomorphine is a very potent dopamine agonist administered subcutaneously by either intermittent injection or continuous infusion. It should only be initiated by a specialist and long-term specialist supervision is advisable throughout treatment. However, once established, patients may safely continue on treatment for many years in the community.
  2. MHRA Drug Safety Alert (April 2016): Patients receiving apomorphine and domperidone require an assessment of cardiac risk factors and ECG monitoring to reduce the risk of serious arrhythmia related to QT-prolongation.
    1. Before starting treatment, carefully consider whether the benefits of concomitant apomorphine and domperidone treatment outweigh the small increased risk of cardiac side effects
    2. Discuss the benefits and risks of apomorphine with patients and carers and advise them to contact their doctor immediately if they develop palpitations or syncopal symptoms during treatment
    3. Check the QT-interval before starting domperidone, during the apomorphine initiation phase and if clinically indicated thereafter (eg if a QT-prolonging or interacting drug is started or if symptoms of cardiac side effects are reported)
    4. Regularly review domperidone treatment to ensure patients take the lowest effective dose for the shortest duration
    5. Advise patients to inform their doctor of any changes that could increase their risk of arrhythmia, such as:
      • symptoms of cardiac or hepatic disorders
      • conditions that could cause electrolyte disturbances (eg, gastroenteritis or starting a diuretic)
      • starting any other medicines
Pramipexole
  • Tablets 88 micrograms, 180 micrograms, 700 micrograms (pramipexole base) (£32.59 = 360 micrograms three times daily)
  • Pipexus® tablets m/r 260 micrograms, 520 micrograms, 1.05mg, 1.57mg, 2.1mg, 2.62mg, 3.15mg (£64.98 = 1.05mg daily)

Indications

  • Parkinson's disease, used alone or as an adjunct to co-beneldopa or co-careldopa

Dose

  • Parkinson's disease, initially 88 micrograms 3 times daily, dose doubled every 5–7 days if tolerated to 350 micrograms 3 times daily; further increased if necessary by 180 micrograms 3 times daily at weekly intervals; maximum 3.3mg daily in 3 divided doses
  • Modified release: Parkinson's disease (with or without co-beneldopa or co-careldopa), initially 260 micrograms once daily, dose doubled every 5–7 days to 1.05mg once daily; further increased if necessary by 520 micrograms daily at weekly intervals; maximum 3.15mg once daily

Notes

  1. Exercise caution when prescribing, dispensing and administering pramipexole as the packs also express dose as the dihydrochloride and print both doses in milligrams.
Ropinirole
  • Tablet 0.25mg, 0.5mg, 1mg, 2mg, 5mg (£3.91 = 15mg daily)
  • Starter pack (250 micrograms, 500 micrograms and 1mg tablets) (£40.10)
  • Follow-on pack (500 micrograms, 1mg and 2mg tablets) (£74.40)
  • Ipinnia® XL modified release tablets 2mg, 3mg, 4mg, 6mg, 8mg (£37.90 = 16mg daily)

Indications

  • Parkinson's disease, either used alone or as adjunct to co-beneldopa or co-careldopa

Dose

  • Initially 750 micrograms daily in 3 divided doses, increased by increments of 750 micrograms daily at weekly intervals to 3mg daily in 3 divided doses; further increased by increments of 1.5–3mg daily at weekly intervals according to response; usual range 9–16mg daily in 3 divided doses (but higher doses may be required if used with levodopa); maximum 24mg daily in 3 divided doses
  • Modified release: initial treatment of Parkinson's disease, 2mg once daily for 1 week, then 4mg once daily; increased according to response by 2mg at intervals of at least 1 week up to 8mg once daily; if still no response, increase by 2–4mg at intervals of at least 2 weeks as necessary; maximum 24mg once daily
Rotigotine
  • Patches 1mg/24 hours, 2mg/24 hours, 3mg/24 hours, 4mg/24 hours, 6mg/24 hours, 8mg/24 hours (£149.93 = 8mg/24 hours)

Notes

  1. Transdermal rotigotine should only be prescribed for patients unable to take oral medication or for patients with motor complications who have failed therapy with other dopamine agonists.

Levodopa

Patients with Parkinson's disease may be very susceptible to small changes in drug therapy and we therefore recommended brand name prescribing for all levodopa preparations. This also helps reduce confusion regarding the different combinations of strengths in which these preparations are available.

There is rarely any immediate need to commence therapy and patients should be referred to the movement disorder team for confirmation of diagnosis.

When therapy is started the patient will be commenced on the lowest dose and increased slowly in divided doses.

Co-beneldopa
  • Madopar® capsules 62.5mg, 125mg, 250mg (£11.78 = 250mg x 100 capsules)
  • Madopar® dispersible tablets 62.5mg, 125mg (£10.45 = 125mg x 100 tablets)

Notes

  1. Dispersible tablets may be useful for the first early morning dose, as 'rescue medication' at other times of the day, and in patients who find it difficult to swallow tablets or capsules.
Co-careldopa
  • SInemet® tablets 62.5mg, 110mg, 125mg (Sinemet Plus®), 275mg (£18.29 = 100 x 25/250mg)
Modified release

Modified release levodopa preparations are mainly for patients with significant nocturnal hypokinesia. There may also be some beneficial effects left by the following morning so that the patient has a longer period of sleep benefit.

Co-careldopa MR 25/100
  • Half Sinemet CR® tablets (£11.60 = 60 tablets)
Co-careldopa MR 50/200
  • Sinemet CR® tablets (£11.60 = 60 tablets)

Notes

  1. Patients who require the dose provided by a Half Sinemet CR® should be discouraged from breaking a Sinemet CR® in half to obtain the dose. The preparation should be prescribed as Half Sinemet CR® to avoid confusion.
With entacapone
Sastravi®
  • Levodopa / Carbidopa / Entacapone tablets (50, 12.5, 200), (75, 18.75, 200), (100, 25, 200), (125, 31.25, 200), (150, 37.5, 200), (175, 43.75, 200), (200, 50, 200) (£34.66 = 100 tablets (all strengths))

Indications

  • For Parkinson's disease and end-of-dose motor fluctuations not adequately controlled with levodopa and dopa-decarboxylase inhibitor treatment

Dose

  • Only 1 tablet to be taken for each dose; maximum 10 tablets daily (50-150mg levodopa), maximum 8 tablets daily (175mg levodopa), maximum 7 tablets daily (200mg levodopa)

Monoamine-oxidase-B inhibitors

Selegiline
  • Tablets 5mg, 10mg (£9.02 = 10mg)

Dose

  • 10mg at breakfast or 5mg at breakfast and noon

Notes

  1. Doses may be initiated at 2.5mg to minimise side effects in older patients.
  2. It is recommended that selegiline is only initiated by those experienced in the management of PD and familiar with the characteristics of the drug.
  3. Afternoon doses are not advised due to the alerting effects of the drug.
  4. Selegiline has a number of drug interactions, particularly with CNS active drugs.
  5. Sudden withdrawal of selegiline may exacerbate symptoms.
  6. Evidence found by the UK Parkinson's Disease Research Group (PDRGUK) that selegiline was associated with an increased mortality, has not been supported by meta-analysis of 5 long term studies and 4 other studies. Selegiline is regarded as a safe option for the adjunct treatment of Parkinson's.

Catechol-O-methyltransferase inhibitors

Entacapone
  • Tablets 200mg (£5.03 = 30 tablets)

Dose

  • Usually taken with each dose of levodopa product. Max 10 tablets per day

Notes

  1. The dose should be increased or decreased slowly.
  2. It may be necessary to reduce the concurrent levodopa dose by 10-30%.
  3. COMTIs may be used appropriately for patients experiencing end-of-dose wearing off effects or other motor fluctuations.
  4. The COMTI tolcapone may prescribed by specialists working in the Exeter Movement Clinic. Prescribers should be aware of the monitoring schedule required for this drug (see BNF for further details)

 

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