Dosing and uses of Mirapex, Mirapex ER (pramipexole)
Adult dosage forms and strengths
tablet
- 0.125mg
- 0.25mg
- 0.5mg
- 0.75mg
- 1mg
- 1.5mg
tablet, extended release
- 0.375mg
- 0.75mg
- 1.5mg
- 2.25mg
- 3mg
- 3.75mg
- 4.5mg
Parkinson Disease
Immediate-release: 0.125 mg PO q8hr initially; gradually titrated upward at weekly intervals to target range of 1.5-4.5 mg/day PO divided q8hr
Extended-release: 0.375 mg/day PO initially; if necessary, may be increased every 5-7 days, first to 0.75 mg/day and then by increments of 0.75 mg/day; not to exceed 4.5 mg/day
Restless Legs Syndrome
0.125 mg/day PO 2-3 hr before bedtime initially; may be increased every 4-7 days up to 0.5 mg/day (every 14 days if CrCl 20-60 mL/min)
Dosage modifications
Hepatic impairmet: No dosage adjustments provided in the manufacturer's labeling; adjustment not expected; undergoes minimal hepatic metabolism
Renal Impairment
Parkinson disease
- Immediate release
- CrCl >50 mL/min: Dosage adjustment not necessary
- CrCl 30-50 mL/min: 0.125 mg twice daily initially; not to exceed 0.75 mg TID
- CrCl 15-29 mL/min: 0.125 mg qDay; not to exceed 1.5 mg qDay
- CrCl <15 mL/min: Dosage adjustment not provided in manufacturer's labeling; not studied
- ESRD requiring hemodialysis: Dosage adjustment not provided in manufacturer's labeling; not studied
- Extended release
- CrCl >50 mL/min: Dosage adjustment not necessary
- CrCl 30-50 mL/min: 0.375 every other day; may increase to 0.375 mg qDay no sooner than 1 wk after initiating therapy; may increase by 0.375 mg/dose not more frequently than every 7 days; not to exceed 2.25 mg qDay
- CrCl <30 mL/min: Not recommended
- ESRD requiring hemodialysis: Not recommended
Restless legs syndrome
- Immediate release
- CrCl >60 mL/min: Dosasge adjustment not necessary
- CrCl 20-60 mL/min: Dosage adjustment not necessary but duration between titration should be increased to 14 days
- CrCl<20 mL/min: Dosage adjustment not provided by manufacturer's labeling; not studied
Dosing Considerations
May switch overnight from immediate-release to extended-release tablets at same daily dose; dose adjustments may be required for some patients
Administration
Extended-release: Swallow whole; do not chew, crush, or divide
Discontinuing immediate- or extended-release: Taper off at a rate of 0.75 mg/day until the daily dose has been reduced to 0.75 mg; thereafter, the dose may be reduced by 0.375 mg/day
Pediatric dosage forms and strengths
tablet
- 0.125mg
- 0.25mg
- 0.5mg
- 0.75mg
- 1mg
- 1.5mg
tablet, extended release
- 0.375mg
- 0.75mg
- 1.5mg
- 2.25mg
- 3mg
- 3.75mg
- 4.5mg
Tourette Syndrome (Orphan)
Treatment of Tourette syndrome in pediatric patients
Orphan indication sponsor
- Boehringer-Ingelheim Pharmaceuticals, Inc; 900 Ridgebury Road; Ridgefield, CT 06877
Mirapex, Mirapex ER (pramipexole) adverse (side) effects
Some variations between early Parkinson, advanced Parkinson, and restless legs syndrome
Incidence of some adverse drug reactions (eg, dizziness, accidental injury) >10% but comparable to placebo
>10%
Somnolence
Dyskinesia
Hallucinations
Insomnia
Dizziness
Postural hypotension
Nausea
Constipation
1-10% (partial list)
Abnormal dreams, thoughts, or vision
Amnesia
Confusion
Paranoia or delusion
Akathisia
Asthenia
Dry mouth
Urinary frequency
Postmarketing Reports
Neurologic: Abnormal behavior, abnormal dreams, compulsive shopping, fatigue, hallucinations (all kinds), headache, pathologic gambling
Cardiovascular: Hypotension (including syncope and postural hypotension)
Metabolic: Increased eating (including binge eating, compulsive eating, and hyperphagia), weight gain, SIADH
Dermatologic: Skin reactions, including rythema, rash, pruritus, urticaria
Gastrointestinal: Vomiting
Genitourinary: Libido disorders (including increased or decreased libido and hypersexuality)
Warnings
Contraindications
Hypersensitivity
Cautions
May cause sudden daytime "sleep attacks;" inquire about factors that may increase risk of falling asleep, including sleep disorders or taking sedating medications; caution patients about performing tasks requiring mental alertness; discontinue if there is evidence of sleep attacks; if decision is made to continue therapy, advice patient not to perform dangerous activities requiring mental alertness
Orthostatic hypotension may occur, particularly during dose escalation; monitor closely Parkinson patients being treated with dopaminergic agonists, especially during dose escalation
Possibility of unusual behavioral impulse patterns (eg, compulsive gambling) may occur; hallucinations and psychotic-like behavior may occur; risk increases with age; dose reduction or discontinuation may reverse these behaviors but not in all cases
In early Parkinson, dosages higher than 1.5 mg q8hr provided no additional benefit but increased adverse events
Use with caution in renal impairment; dose adjustment may be necessary; do not administer extended release tablets to patients with CrCl<30 mL/min or ESRD requiring hemodialysis
Augmentation or rebound of restless legs syndrome (RLS) may occur with therapy in RLS patients
The elderly may be more prone to adverse effects
Swallow whole; do not chew, crush, or divide extended release tablets
Events reported with dopaminergic therapy include hyperpyrexia and confusion
Fibrotic complications reported with use; monitor closely for signs and symptoms of fibrosis; discontinuation of therapy may resolve complications but not in all cases
Rsk of melanoma increases in Parkinson disease patients; monitor closely and perform periodic skin examination
Pathologic degenerative changes observed in retinas of albino rats during studies; significance in humans unclear
May cause or exacerbate dyskinesia; use with caution in patients with preexisting dyskinesias
Symptoms resembling neuroleptic malignant syndrome, including elevated temperature, muscular rigidity, altered consciousness, and autonomic instability reported with rapid dose reduction, discontinuation, or changes in therapy; taper dose to decrease risk of hyperpyrexia and confusion
Gradual discontinuance required over period of 1 week or longer; symptoms resembling neuroleptic malignant syndrome may occur on abrupt withdrawaL
Risk of new-onset heart failure undergoing FDA evaluation (FDA safety announcement 9/19/2012)
Pregnancy and lactation
There are no adequate data on the developmental risk associated with therapy in pregnant women; no adverse developmental effects reported in animal studies in which pramipexole was administered to rabbits during pregnancy; effects on embryofetal development could not be adequately assessed in pregnant rats; however, postnatal growth was inhibited at clinically relevant exposures
In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively; background risk of major birth defects and miscarriage for the indicated population is unknown
Lactation: Not known if drug secreted in breast milk; may inhibit milk production; discontinue drug, or do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Mirapex, Mirapex ER (pramipexole)
Mechanism of action
Non-ergot dopamine D2 receptor agonist; strong affinity for D2 and D3 receptors; binding to these receptors increases dopamine activity on nerves of striatum and substantia nigra
Absorption
Bioavailability: >90%
Peak plasma time: Immediate release, 2 hr; extended release, 6 hr
Distribution
Protein bound: 15%
Vd: 500 L
Metabolism
<10% metabolized
Elimination
Half-life: 8.5 hr (12 hr in elderly)
Renal clearance: 400 mL/min
Excretion: Urine (90%)