Dopaminergic Drugs Used in Parkinson’s Disease

Prescribing Notes:

• Dopamine agonists should be avoided in severe cardiovascular disease.

• All dopamine agonists can cause confusion and hallucinations, dizziness and postural hypotension and sudden onset of sleep events. Prescribers should ensure patients have been provided sufficient information on the management of these side effects.

• Treatment with dopamine-receptor agonists has been associated with impulse control disorders. Patients and their carers should be informed about the risk of impulse control disorders.

• All dopamine agonists are emetogenic. Upon initiation patients may be advised to take with meals to reduce the incidence. Although not routinely used, domperidone can be started at the same time as the dopamine agonist. In May 2014, the MHRA advised that domperidone should be used for the shortest possible time period. However the overall safety profile (in particular domperidone’s cardiac risks and potential interactions with other medications) should be taken into account if there is a clinical need to use it at doses or durations greater than those authorised (e.g. to control the side-effects of medication for PD).

• Cyclizine, prochlorperazine and metoclopramide should be avoided since they may exacerbate or induce parkinsonism.

Ropinirole

• May be used as monotherapy in idiopathic PD or as adjunctive therapy in addition to levodopa to control ‘on-off’ fluctuations. When administered as an adjunct to levodopa, the concurrent dose of levodopa may be reduced by approximately 20%.

• Substitution of ropinirole immediate-release tablets with ropinirole prolonged release tablets should be supervised by appropriate specialists in PD.

• There have been instances where risperidone and ropinirole have been confused. Healthcare professionals should take care and ensure that the correct drug is supplied.

• Manufacturer advises if treatment is interrupted for one day or more, re-initiation by dose titration should be considered - consult product literature.

• Prolonged release preparations are significantly more cost-effective than standard ropinirole tablets and once daily dosing may improve patient compliance. Therefore, substitution of ropinirole immediate-release tablets with ropinirole prolonged release tablets should considered by appropriate specialists in PD once patients are on a stable dose.

Pramipexole

• May be used as monotherapy in idiopathic PD or as adjunctive therapy in addition to levodopa to control ‘on-off’ fluctuations.

• Dosing can be expressed as either base or salt and this should be clearly documented when prescribing.

Other preparations

• Rotigotine transdermal patch should be reserved for patients with swallowing difficulties or delayed gastric emptying.

• Other oral dopamine agonists (cabergoline, pergolide) are licensed as adjunctive therapy to levodopa in established cases, but it is recommended that the introduction of such medications follows specialist advice.

• Ergot derivatives (bromocriptine, cabergoline and pergolide) have rarely been associated with pulmonary, retroperitoneal, pericardial and valvular fibrotic reactions and require regular clinical monitoring. They are no longer recommended as first line treatment.

• Amantadine improves mild bradykinetic disabilities, tremor and rigidity. It may also be useful in dyskinesias in more advanced disease. It has few side effects but can provoke fits or confusional states at high dosage.

Prescribing Notes:

• To reduce the risk of nausea, levodopa should be taken with food in the early stages and the dose increased slowly. Care should be taken as protein rich food may interfere with its absorption.

• It may colour urine red.

• 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.

• Modified-release formulations of levodopa are not recommended for initiation of therapy. They may be useful for end-of-dose deterioration or nocturnal immobility and rigidity.

• Dispersible Madopar^® may be useful for patients with swallowing difficulties, or where rapid absorption is desired, for example first thing in the morning. Often an inactive sediment remains.

• Sinemet-110^® is not usually recommended for initiation of therapy since the dose of carbidopa may be inadequate for full inhibition of dopa-decarboxylase. Sinemet-110^®may have a use in patients on more than 700mg levodopa.

Prescribing Notes:

• MAO-B inhibitors may be used alone or as adjunct to co-beneldopa or co-careldopa for 'end-of-dose' fluctuations.
• Cautions
  • When combined with levodopa, MAO-B inhibitors should be avoided or used with great caution in postural hypotension.
  • Drug interaction between MAOB inhibitors and antidepressants (risk of serotonin syndrome):
    • SSRIs, venlafaxine or duloxetine should not be used by people taking rasagiline or selegiline.
    • Tricyclic antidepressants should not be used without specialist advice by people taking rasagiline or selegiline.

Prescribing Notes:

• COMT inhibitors are not recommended as first line agents for PD.  There is no evidence to support their use as neuroprotective therapies.

Entacapone

• Entacapone is licensed for use as an adjunct to co-beneldopa or co-careldopa for the management of ‘end of dose’ motor fluctuations associated with PD.
• Entacapone enhances the action of levodopa and the dose of levodopa may need to be reduced by about 10%-30%.
• May colour urine reddish-brown.

Stanek^®

• Stanek^® is a combination preparation allowing dosing with a single tablet.
• Patients receiving standard-release co-careldopa or co-beneldopa alone should have Stanek^® initiated at a dose that provides a similar (or slightly lower) amount of levodopa. 

Opicapone 

• Opicapone is indicated as adjunctive therapy to preparations of levodopa/ DOPA decarboxylase inhibitors in adult patients with Parkinson's disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations.
• Opicapone differs to Entacapone in that Opicapone is a once daily preparation. Opicapone is taken at bedtime, at least one hour before or after levodopa combinations.