- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Tablets containing pramipexole (as pramipexole dihydrochloride monohydrate)
Moderate to severe idiopathic Restless Legs Syndrome: Symptomatic treatment
Parkinson's disease (adjunctive treatment - given with levodopa)
Starting dose 88 micrograms base (125 micrograms of salt) three times a day. Increase every 5 to 7 days.
Titrate dosage to achieve a maximal therapeutic effect, providing patients do not experience intolerable side effects.
Suggested dose schedule:
88 micrograms base (125 micrograms of salt) three times a day.
Total daily dose 264 micrograms (375 micrograms of salt).
180 micrograms base (250 micrograms of salt) three times a day.
Total daily dose 540 micrograms (750 micrograms of salt).
350 micrograms base (500 micrograms of salt) three times a day
Total daily dose 1.05 mg (1.5 mg of salt)
If a further increase is necessary, increase the total daily dose by 540 micrograms base (750 micrograms of salt) at weekly intervals up to a maximum daily dose of 3.3 mg pramipexole base (4.5 mg of salt) per day.
The incidence of somnolence is increased at doses higher than 1.5 mg/day.
The individual dose should be in the range of 264 micrograms of base (375 micrograms of salt) to a maximum of 3.3 mg of base (4.5 mg of salt) per day.
Doses higher than 1.05 mg (1.5 mg of salt) per day can be useful in patients with advanced disease where a reduction of the levodopa therapy is intended. It is recommended that the dosage of levodopa is reduced during both the dose escalation and the maintenance treatment with pramipexole, dependent on reactions in individual patients.
Restless Legs Syndrome (RLS)
The recommended starting dose is 88 micrograms of base (125 micrograms of salt) taken once daily 2 to 3 hours before bedtime. For patients who require additional symptomatic relief, the dose may be increased every 4 to 7 days to a maximum of 540 micrograms of base (750 micrograms of salt) daily.
Suggested dose schedule:
Titration Step 1:
88 micrograms base (125 micrograms of salt) once daily.
Titration Step 2 (if needed):
180 micrograms base (250 micrograms of salt) once daily.
Titration Step 3 (if needed):
350 micrograms base (500 micrograms of salt) once daily.
Titration Step 4 (if needed):
540 micrograms base (750 micrograms of salt) once daily.
Long term efficacy of pramipexole in the treatment of RLS has not been tested. Patient's response should be evaluated after 3 months treatment and the need for continued treatment should be reconsidered.
If treatment is interrupted for more than a few days it should be re-initiated by dose titration as described above.
(See Dosage; Adults)
Patients with Renal Impairment
The elimination of pramipexole is dependent on renal function.
The following dosage schedule is suggested for initiation of therapy:
Creatinine clearance between 20 and 50 ml/minute:
The initial daily dose should be administered in two divided doses, starting at 88 micrograms of base (125 micrograms of salt) twice a day. A maximum daily dose of 1.57 mg pramipexole base (2.25 mg of salt) should not be exceeded.
Creatinine clearance below 20 ml/minute:
The daily dose should be administered in a single dose, starting at 88 micrograms of base (125 micrograms of salt) once daily. A maximum daily dose of 1.05 mg pramipexole base (1.5 mg of salt) should not be exceeded.
If renal function declines during maintenance therapy, reduce the daily dose by the same percentage as the decline in creatinine clearance. The daily dose can be administered in two divided doses if the creatinine clearance is between 20 and 50 ml/minute, and as a single daily dose if creatinine clearance is less than 20 ml/minute.
Restless Legs Syndrome (RLS):
Creatinine clearance below 20 ml/minute:
Use has not been studied in patients with severe renal impairment or undergoing haemodialysis.
Patients with Hepatic Impairment
Dosage adjustment in patients with hepatic failure is unlikely to be necessary, as approximately 90% of absorbed drug is excreted through the kidneys. However, the potential influence of hepatic insufficiency on pramipexole pharmacokinetics has not been investigated.
Additional Dosage Information
Treatment discontinuation in Parkinson's Disease
Abrupt discontinuation of dopaminergic therapy can lead to the development of a neuroleptic malignant syndrome or dopamine agonist withdrawal syndrome. Therefore, pramipexole should be tapered off at a rate of 540 micrograms of base (750 micrograms of salt) per day until the daily dose has been reduced to 540 micrograms of base (750 micrograms of salt). Thereafter, the dose should be reduced by 264 micrograms of base (375 micrograms of salt) per day. Dopamine agonist withdrawal syndrome may appear during tapering, a temporary dose increase to the lowest effective dose may be necessary before tapering continues.
Treatment discontinuation in Restless Leg Syndrome
Pramipexole may be discontinued without dose tapering. However, rebound symptoms cannot be excluded.
Children under 18 years
Precautions and Warnings
Renal impairment - creatinine clearance below 50ml/minute
Severe cardiovascular disorder
Advise patient/carer risk of dopamine dysregulation syndrome (DDS)
Reduce dose in patients with creatinine clearance below 50ml/min
Advise impaired alertness may affect ability to drive or operate machinery
Advise patient that sudden onset sleep episodes may affect ability to drive
Not all available brands are licensed for all indications
Monitor blood pressure especially at the start of treatment
Monitor ophthalmic function
Monitor patients for impulse control disorders
Monitor patients for mania and delirium
Review treatment if impulse control disorders symptoms occur
Advise patient that postural hypotension may occur
Advise patient/carer to seek medical advice if mania &/or delirium develop
Dopamine agonists have been associated with pathological gambling
Patient should be made aware of possible adverse effects on mood/behaviour
Review treatment if dystonia occurs following initiation or dose increases
Treatment of Restless Legs Syndrome may result in augmentation of symptoms
Avoid abrupt withdrawal: Dopamine agonist withdrawal syndrome may occur
Avoid abrupt withdrawal: May cause signs of neuroleptic malignant syndrome
Consider dose reduction/tapered withdrawal if mania &/or delirium develop
Reduce dose or discontinue if sudden onset of sleep during daily activities
Reduce levodopa dosage during escalation and maintenance treatment
Advise patient to avoid alcohol during treatment
Advise patient/carer about symptoms of impulse control disorders
Advise patients that hallucinations can occur
Axial dystonia following treatment initiation or dose increases has been reported in patients using pramipexole for Parkinson's disease. Whilst dystonia is a symptom of Parkinson's disease itself, symptoms have been shown to improve following dose reduction or withdrawal. As such, medication regimes should be reviewed if dystonia occurs during initiation or following dose increases.
Pregnancy and Lactation
Use with extreme caution in pregnancy.
The absence of human pregnancy experience prevents an assessment of the human risk. It is not known whether pramipexole crosses the human placenta, but the low protein binding, low molecular weight and prolonged elimination half life suggest that it will. The limited animal data available does not suggest a significant risk of teratogenicity or toxicity. Toxicity was observed in rats but this was apparently caused by mechanisms not present in human pregnancy. Until more data becomes available on the effects on the human foetus, the use of pramipexole should be avoided during pregnancy. Its use, however, does not justify the termination of pregnancy or invasive diagnostic procedures. A detailed foetal ultrasound may be considered (Schaefer 2007).
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Pramipexole is contraindicated in breastfeeding.
As pramipexole treatment inhibits secretion of prolactin in humans it may inhibit lactation. The excretion of pramipexole into breast milk has not been studied in women. In rats, the concentration of drug-related radioactivity was higher in breast milk than in plasma. In the absence of human data, pramipexole should not be used during breastfeeding. However, if its use is unavoidable, breastfeeding should be discontinued.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Changes in libido
Dopamine agonist withdrawal syndrome
Inappropriate secretion of antidiuretic hormone
Paradoxical worsening of restless leg syndrome
Reduced visual acuity
Sudden sleep onset episodes
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: February 2014
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Joint Formulary Committee. British National Formulary. 66th ed. London: BMJ Group and Pharmaceutical Press; 2013.
Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.
Summary of Product Characteristics: Mirapexin 0.088 mg/0.18 mg/0.35 mg/0.7 mg/1.1 mg tablets. Boehringer Ingelheim Ltd. Revised February 2020.
Summary of Product Characteristics: Oprymea 0.7 mg tablets. Consillent Health Ltd. Revised September 2008.
Summary of Product Characteristics: Oprymea 0.35 mg tablets. Consillent Health Ltd. Revised September 2008.
Summary of Product Characteristics: Oprymea 0.18 mg tablets. Consillent Health Ltd. Revised September 2008.
Summary of Product Characteristics: Oprymea 0.088 mg tablets. Consillent Health Ltd. Revised September 2008.
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com [Accessed on [February 13, 2014]].
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Pramipexole. Last revised: September 7, 2013.
Last accessed: February 13, 2014.
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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