Availability - Formulation

Tablets

• MIRAPEXIN^®0.088 mg tablets - contain 0.088 mg of pramipexole base (as 0.125 mg of pramipexole dihydrochloride monohydrate).
• MIRAPEXIN^® 0.18 mg tablets - contain 0.18 mg of pramipexole base (as 0.25 mg of pramipexole dihydrochloride monohydrate).
• MIRAPEXIN^® 0.35 mg tablets - contain 0.35 mg of pramipexole base (as 0.5 mg of pramipexole dihydrochloride monohydrate).
• MIRAPEXIN^® 0.7 mg tablets - contains 0.7 mg of pramipexole base (as 1.0 mg of pramipexole dihydrochloride monohydrate).

Please note: Pramipexole doses as published in the literature refer to the salt form. Therefore, doses will be expressed in terms of both pramipexole base and pramipexole salt (in brackets).

All tablets can be divided into equal halves (with the exception of the 0.088/0.125 mg tablet).

All tablets are white and have a code embossed.

Strength (mg base/mg salt)	Appearance
0.125	flat, round, 6 mm diameter, no score
0.25	flat, oval, 7.86 x 5.63 mm, scores on both sides
0.5	flat, oval, 10.59 x 7.59 mm, scores on both sides
1.0	flat, round, 9 mm diameter, scores on both sides
1.5	flat, round, 11 mm diameter, scores on both sides

 

For a full list of excipients, see Pharmaceutical Particulars.

Therapeutic Indications

• MIRAPEXIN^® is indicated for treatment of the signs and symptoms of idiopathic Parkinson's disease, alone (without levodopa) or in combination with levodopa, i.e. over the course of the disease, through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or “on off” fluctuations).
• MIRAPEXIN^® is indicated for symptomatic treatment of moderate to severe idiopathic Restless Legs Syndrome.

How To Take MIRAPEXIN^®

Parkinson's Disease

• The tablets should be taken orally, swallowed with water, and can be taken either with or without food. The daily dosage is administered in equally divided doses 3 times a day.
• You should be cautious while drinking alcohol during treatment with MIRAPEXIN^®.
• Always take MIRAPEXIN^® exactly as your doctor tells you. He/she will prescribe a suitable dose for you. The dose depends on your individual symptoms and your response to MIRAPEXIN^®.
• Tell your doctor if you have (had) or develop any medical conditions or symptoms, especially any of the following:
  • kidney disease
  • hallucinations (seeing, hearing or feeling things that are not there)
    Most hallucinations are visual.
  • dyskinesia (e.g. abnormal, uncontrolled movements of the limbs)
    If you have advanced Parkinson’s disease and are also taking levodopa, you might develop dyskinesia during the uptitration of MIRAPEXIN^®.
  • sleepiness and episodes of suddenly falling asleep
  • behavioural changes (e. g. pathological gambling), increased libido (e.g. increased sexual desire), binge eating.
  • psychosis, (e.g. comparable with symptoms of schizophrenia)
  • vision impairment
    You should have regular eye examinations during treatment with MIRAPEXIN^®.
  • severe heart or blood vessels disease
    You will need to have your blood pressure checked regularly, especially at the beginning of treatment. This is to avoid postural hypotension (a fall in blood pressure on standing up)
  • augmentation
    You may experience that symptoms start earlier than usual, be more intense and involve other limbs.

Initial treatment:

• Dosages should be increased gradually from a starting dose and then increased every 5 - 7 days. Providing there are no intolerable side-effects, the dosage should be titrated to achieve a maximal therapeutic effect.
• If a further dose increase is necessary the daily dose should be increased at weekly intervals up to a maximum dose of 3.3 mg of base (4.5 mg of salt) per day.
• However, it should be noted that the incidence of somnolence is increased at doses higher than 1.5 mg/ day (see Undesirable Effects).

Maintenance treatment:

• Dose adjustments should be done based on the clinical response and the occurrence of undesirable effects.
• It is recommended that the dosage of levodopa is reduced during both the dose escalation and the maintenance treatment with MIRAPEXIN^®, depending on reactions in individual patients.

Treatment discontinuation:

• Do not stop taking MIRAPEXIN^® without first talking to your doctor.
• Abrupt discontinuation of dopaminergic therapy can lead to the development of a neuroleptic malignant syndrome (symptoms like fever, rigidity, increased heart rate and/or disturbance of consciousness can occur). Therefore, the daily dose of pramipexole should be tapered off (see Special warnings and precautions for use).

Dosing in patients with renal impairment:

• The elimination of pramipexole is dependent on renal function.
• If renal function declines during maintenance therapy, reduce MIRAPEXIN^®daily dose by the same percentage as the decline in creatinine clearance, i.e. if creatinine clearance declines by 30%, then reduce the MIRAPEXIN^® daily dose by 30%. The daily dose can be administered in two divided doses if creatinine clearance is between 20 and 50 ml/min, and as a single daily dose if creatinine clearance is less than 20 ml/min.

Dosing in patients with hepatic impairment

• Dose adjustment in patients with hepatic failure is probably not necessary, as approx. 90% of absorbed active substance is excreted through the kidneys. However, the potential influence of hepatic insufficiency on MIRAPEXIN^®pharmacokinetics has not been investigated.

Dosing in children and adolescents

• MIRAPEXIN^® is not recommended for use in children and adolescents below 18 years due to a lack of data on safety and efficacy.

Restless Legs Syndrome

Please refer to the MIRAPEXIN^® Product Information and SIFROL^® Product Information links (Product Information Downloads) for further information.

Contra-indications (When Not To Use)

• Hypersensitivity (allergy) to the active substance pramipexole or to any of the excipients.

Special Warning & Precautions For Use

• When prescribing MIRAPEXIN^® in a patient with Parkinson's disease with renal impairment a reduced dose is suggested.
• Hallucinations are known as a side-effect of treatment with dopamine agonists and levodopa. Patients should be informed that (mostly visual) hallucinations can occur.
• In advanced Parkinson's disease, in combination treatment with levodopa, dyskinesia can occur during the initial titration of MIRAPEXIN^®. If they occur, the dose of levodopa should be decreased.
• MIRAPEXIN^® has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson's disease. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported uncommonly. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with MIRAPEXIN^®. Patients who have experienced somnolence and/oran episode of sudden sleep onset must refrain from driving or operating machines. Furthermore a reduction of dosage or termination of therapy may be considered. Because of possible additive effects, caution should be advised when patients are taking other sedating medicinal products or alcohol in combination with pramipexole (see Effects on Ability to Drive and Use Machines and Undesirable Effects).
• Pathological gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists for Parkinson's disease, including MIRAPEXIN^®. Furthermore, patients and caregivers should be aware of the fact that behavioural changes can occur. Dose reduction/taper discontinuation should be considered.
• Patients with psychotic disorders should only be treated with dopamine agonists if the potential benefits outweigh the risks.
• Coadministration of antipsychotic medicinal products with pramipexole should be avoided (see Interaction with other medicinal products and other forms of interaction).
• Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.
• In case of severe cardiovascular disease, care should be taken. It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the general risk of postural hypotension associated with dopaminergic therapy.
• Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy.
• Reports in the literature indicate that treatment of Restless Legs Syndrome with dopaminergic medicinal products can result in augmentation. Augmentation refers to the earlier onset of symptoms in the evening (or even the afternoon), increase in symptoms, and spread of symptoms to involve other extremities. The controlled trials of MIRAPEXIN^® in patients with Restless Legs Syndrome were generally not of sufficient duration to adequately capture augmentation phenomena. The frequency of augmentation after longer use of MIRAPEXIN^® and the appropriate management of these events have not been evaluated in controlled clinical trials.

Interactions With Other Medicinal Products & Other Forms of Interaction

• Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines, herbal remedies, health foods or supplements that you have obtained without a prescription.
• You should avoid taking MIRAPEXIN^® together with antipsychotic medicines.
• Take care if you are taking the following medicines:
  • cimetidine (to treat excess stomach acid and stomach ulcers)
  • amantadine (which can be used to treat Parkinson’s disease)
    
    Reduction of the pramipexole dose should be considered when these medicinal products are administered concomitantly with MIRAPEXIN^®.
• When MIRAPEXIN^® is given in combination with levodopa, it is recommended that the dosage of levodopa is reduced and the dosage of other anti-parkinsonian medicinal products is kept constant while increasing the dose of MIRAPEXIN^®.
• There is no pharmacokinetic interaction with selegiline and levodopa.
• Because of possible additive effects, caution should be advised when patients are taking other sedating medicinal products or alcohol in combination with pramipexole.
• Coadministration of antipsychotic medicinal products with pramipexole should be avoided (see Special warnings and precautions for use), e.g. if antagonistic effects can be expected.

Pregnancy and Lactation

• The effect on pregnancy and lactation has not been investigated in humans. MIRAPEXIN^® should not be used during pregnancy unless clearly necessary, i.e. if the potential benefit justifies the potential risk to the foetus.
• As MIRAPEXIN^® treatment inhibits secretion of prolactin in humans, inhibition of lactation is expected. The excretion of MIRAPEXIN^® into breast milk has not been studied in women.
• In the absence of human data, MIRAPEXIN^® should not be used during breast-feeding. However, if its use is unavoidable, breast-feeding should be discontinued.

Effects on Ability to Drive and Use Machines

• MIRAPEXIN^® can have a major influence on the ability to drive and use machines.
• Hallucinations or somnolence can occur.
• Patients being treated with MIRAPEXIN^® and presenting with somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (e.g. operating machines) until such recurrent episodes and somnolencehave resolved (see also Special Warning and precautions for use, Interactions with other medicinal producs and other forms of interaction, and Undesirable Effects).

Undesirable Effects of MIRAPEXIN^®

The following adverse reactions are expected under the use of MIRAPEXIN^®:

• abnormal dreams
• confusion
• constipation
• delusion
• dizziness
• dyskinesia
• fatigue
• hallucinations
• headache
• hyperkinesia
• hypotension
• increased eating (binge eating, hyperphagia)
• insomnia
• libido disorders
• nausea
• peripheral oedema
• paranoia
• pathological gambling, hypersexuality and other abnormal behaviour
• somnolence, weight increase, sudden onset of sleep
• pruritus and rash and other hypersensitivity.

MIRAPEXIN^® is associated with somnolence and has been associated uncommonly with excessive daytime somnolence and sudden sleep onset episodes. See also Special warnings and precautions for use.

Patients treated with dopamine agonists for Parkinson's disease, including MIRAPEXIN^®, especially at high doses, have been reported as exhibiting signs of pathological gambling, increased libido and hypersexuality, generally reversible upon reduction of the dose or treatment discontinuation.

Overdose

• If you accidentally took too many tablets, you should get medical help immediately either by calling your doctor or by going to the nearest hospital accident and emergency department (do not drive yourself). Always take the labelled medicine container with you whether or not there are any MIRAPEXIN^® tablets left.
• There is no clinical experience with massive overdosage. The expected adverse events would be those related to the pharmacodynamic profile of a dopamine agonist, including nausea, vomiting, hyperkinesia, hallucinations, agitation and hypotension. There is no established antidote for overdosage of a dopamine agonist. If signs of central nervous system stimulation are present, a neuroleptic agent may be indicated. Management of the overdose may require general supportive measures, along with gastric lavage, intravenous fluids, administration of activated charcoal and electrocardiogram monitoring.

If you forget to take your tablets:

• If you forget to take a dose, take your next dose at the right time. Do not try to make up for the missed dose.

Pharmaceutical Particulars

List of Excipients

• Mannitol - This may have a mild laxative (bowel loosening) effect.
• Maize starch
• anhydrous colloidal silica
• Povidone
• Magnesium stearate

Shelf Life

• 3 years

Special precautions for storage

• Do not store above 30°C.
• Store in the original package in order to protect from light.

Special precautions for disposal

• No special requirements