Pramipexole oral modified release
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Prolonged release tablets containing pramipexole (as pramipexole dihydrochloride monohydrate)
Drugs List
Therapeutic Indications
Uses
Parkinson's disease
Parkinson's disease (adjunctive treatment - given with levodopa)
Dosage
Patients already taking standard release pramipexole tablets may be switched to prolonged release tablets overnight, at the same total daily dose. After switching to prolonged release, the dose may be adjusted depending on the patient's therapeutic response.
Adults
Initial treatment
Dose should be started at 260 micrograms base (375 micrograms of salt) per 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:
Week 1 - 260 micrograms base (375 micrograms salt) daily.
Week 2 - 520 micrograms base (705 micrograms salt) daily.
Week 3 - 1.05 mg base (1.5 mg salt) daily.
If a further dose increase is necessary, increase the daily dose by 520 micrograms base (750 micrograms of salt) at weekly intervals up to a maximum dose of 3.15 mg base (4.5 mg of salt) per day.
The incidence of somnolence is increased at doses higher than 1.05 mg base (1.5 mg of salt) per day.
Maintenance treatment
The individual dose should be in the range of 260 micrograms base (375 micrograms of salt) to a maximum of 3.15 mg base (4.5 mg of salt) per day.
Doses higher than 1.05 mg base (1.5 mg of salt) per day can be useful in patients with advanced disease where a reduction of levodopa therapy is intended. It is recommended that the dose of levodopa is reduced during both dose escalation and the maintenance treatment with pramipexole, depending on reactions in individual patients.
Elderly
(See Dosage; Adults)
Patients with Renal Impairment
Creatinine clearance 30 to 50 ml/minute
Initiate treatment with 260 micrograms base (375 micrograms of salt) every other day. Use with caution and assess therapeutic response and tolerability before increasing to daily dosing after one week. If a further dose increase is necessary, increase by 260 micrograms base (375 micrograms of salt) at weekly intervals up to a maximum dose of 1.57 mg base (2.25 mg of salt) per day.
Creatinine clearance below 30 ml/minute
Not recommended. Consider use of standard release pramipexole instead.
If renal function declines during maintenance therapy, the recommendations above should be followed.
Additional Dosage Information
Treatment discontinuation
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 520 micrograms base (750 micrograms of salt) per day until the daily dose has been reduced to 520 micrograms base (750 micrograms of salt). Thereafter, the dose should be reduced by 260 micrograms 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.
Missed dose
When a dose is missed, pramipexole prolonged release tablets should be taken within 12 hours of the regularly scheduled time. After 12 hours, the missed dose should be left out and the next dose taken on the following day at the next regularly scheduled time.
Contraindications
Children under 18 years
Breastfeeding
Renal impairment - creatinine clearance below 30 ml/minute
Precautions and Warnings
Pregnancy
Psychosis
Renal impairment - creatinine clearance 30-50ml/minute
Severe cardiovascular disorder
Advise patient/carer risk of dopamine dysregulation syndrome (DDS)
Reduce dose in patients with creatinine clearance of 30-50ml/min
Advise impaired alertness may affect ability to drive or operate machinery
Advise patient that sudden onset sleep episodes may affect ability to drive
If visual disturbances occur, perform ophthalmic evaluation
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
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
Pregnancy
Use pramipexole 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 (Briggs 2015). 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 2015).
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 ).
Lactation
Pramipexole is contraindicated in breastfeeding.
As pramipexole treatment inhibits secretion of prolactin in humans it most probably will inhibit lactation. The excretion of pramipexole into breast milk has not been studied in women and so very little data is available. In rats, the concentration of drug-related radioactivity was found to be higher in breast milk than in plasma. Due to the highly limited amount of human data, its recommended 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
Side Effects
Amnesia
Anxiety
Apathy
Behavioural disturbances
Binge eating
Blurred vision
Cardiac failure
Changes in libido
Compulsive disorders
Confusion
Constipation
Decreased appetite
Delirium
Delusions
Depression
Diplopia
Dizziness
Dopamine agonist withdrawal syndrome
Dream abnormalities
Drowsiness
Dyskinesia
Dyspnoea
Fatigue
Hallucinations
Headache
Hiccups
Hyperkinesia
Hyperphagia
Hypersensitivity reactions
Hypersexuality
Hypotension
Inappropriate secretion of antidiuretic hormone
Insomnia
Mania
Nausea
Pain
Paranoia
Pathological gambling
Peripheral oedema
Pneumonia
Postural hypotension
Pruritus
Rash
Reduced visual acuity
Restlessness
Somnolence
Sudden sleep onset episodes
Sweating
Syncope
Visual disturbances
Vomiting
Weight changes
Overdosage
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 ).
Further Information
Last Full Review Date: December 2016
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 14 December 2016.
Martindale: The Complete Drug Reference. 38th Edition. London: Brayfield A (ed). Pharmaceutical Press; 2014.
Summary of Product Characteristics: Mirapexin prolonged release tablets. Boehringer Ingelheim Ltd. Revised February 2020.
Summary of Product Characteristics: Oprymea 0.26 mg prolonged release tablets. Consilient Health Ltd. Revised November 2013.
Summary of Product Characteristics: Oprymea 0.52 mg prolonged release tablets. Consilient Health Ltd. Revised November 2013.
Summary of Product Characteristics: Oprymea 1.05 mg prolonged release tablets. Consilient Health Ltd. Revised November 2013.
Summary of Product Characteristics: Oprymea 1.57 mg prolonged release tablets. Consilient Health Ltd. Revised November 2013.
Summary of Product Characteristics: Oprymea 2.1 mg prolonged release tablets. Consilient Health Ltd. Revised November 2013.
Summary of Product Characteristics: Oprymea 2.62 mg prolonged release tablets. Consilient Health Ltd. Revised November 2013.
Summary of Product Characteristics: Oprymea 3.15 mg prolonged release tablets. Ethypharm UK Ltd. Revised June 2016.
Summary of Product Characteristics: Pipexus prolonged-release tablets. Consilient Health Ltd. Revised November 2013.
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:10 March 2015.
Last accessed: 14 December 2016
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