Mirapex ER (pramipexole dihydrochloride) for Parkinson’s disease
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What is Mirapex ER for Parkinson’s disease?
Mirapex ER (pramipexole dihydrochloride) is an approved, extended-release oral therapy used to ease symptoms in people with Parkinson’s disease. It also can reduce off episodes, or periods when a medication wears off and disease symptoms are not well controlled.
The brand name therapy was developed by Boehringer Ingelheim and approved in the U.S. more than a decade ago, but a number of generic equivalents of Mirapex ER also are available; the first generic was approved in the U.S. in 2014.
Another formulation of Mirapex ER, designed to released the active substance immediately after dosing, was originally approved in the U.S. in 1997. However, these immediate-release tablets, which were sold as Mirapex and had different dosage strengths to Mirapex ER, were discontinued by the company for reasons not related to safety or efficacy.
In Europe, pramipexole-containing medicines are marketed under the brand names Mirapexin and Sifrol, with generics also available.
Therapy snapshot
| Brand Name: | Mirapex ER |
| Chemical Name: | Pramipexole dihydrochloride |
| Usage: | Used to ease symptoms of Parkinson’s disease; can reduce off episodes |
| Administration: | Extended-release oral tablets |
How does Mirapex ER work?
People with Parkinson’s have lower-than-normal levels of dopamine, a neurotransmitter or chemical messenger that sends signals between nerve cells in the brain. This is caused by the progressive death of nerve cells that produce dopamine. The resulting reduction of dopamine in the brain leads to a progressive loss of movement control as well as nonmotor symptoms.
Mirapex is part of a class of therapies called dopamine agonists, meaning its active ingredient mimics the activity of dopamine by binding to its receptor proteins in the brain. In so doing, it is expected to relieve some of the symptoms caused by low dopamine levels.
The therapy also is expected to reduce off episodes in Parkinson’s patients taking standard levodopa-based treatments, which provide the brain with raw material for making dopamine. Off episodes, which develop especially in more advanced stages of the disease, are periods when disease symptoms return before another dose of levodopa can be taken.
Who can take Mirapex ER?
Mirapex ER was approved by the U.S. Food and Drug Administration in 2010 to treat people with early Parkinson’s. That indication was extended in the same year for the treatment of advanced Parkinson’s.
The medication had been approved in Europe in the previous year for both early and advanced Parkinson’s disease patients, either alone or in combination with levodopa-based therapies.
Who should not take Mirapex ER?
The prescribing information for Mirapex ER lists no contraindications. However, the therapy is generally not recommended for patients with a major psychotic disorder, due to a risk of psychosis exacerbation.
Individuals with severe kidney impairment or those on hemodialysis, a procedure to filter waste from the blood when the kidneys are not functioning properly, also should not take Mirapex ER because the medication has not been studied in these patient populations.
How is Mirapex ER administered in Parkinson’s?
Mirapex ER is available as white tablets that come in seven strengths. All have an engraved “ER” on one side and an engraved number identifying the dose strength on the other: 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3 mg, 3.75 mg, and 4.5 mg.
Tablets of the two lower dose strengths are round and bevel-edged, while the remaining dose tablets have an oval form.
The recommended starting dose of Mirapex ER is 0.375 mg, taken orally once a day. That dose can be increased gradually every five to seven days, based on efficacy and tolerability, in 0.75 mg increments and up to a maximum of 4.5 mg per day.
People with moderate kidney problems should start Mirapex ER with every-other-day dosing. Close assessment of the therapy’s efficacy and tolerability should be performed in these patients before increasing to daily dosing one week later, and before any additional dose increase in 0.375 mg increments up to 2.25 mg per day.
The medication should be swallowed whole, and not split, crushed, or chewed. It can be taken with or without food.
Mirapex ER tablets should be discontinued gradually if the therapy is stopped. If a significant treatment interruption has occurred, readjustment of the therapy dose may be necessary.
Mirapex ER in clinical trials for Parkinson’s disease
In initial clinical trials, Mirapex immediate-release (IR) tablets, taken three times a day, were shown to be superior to a placebo at lessening symptoms in early-stage Parkinson’s patients. At the same time, they also were found effective in reducing daily off periods in advanced Parkinson’s patients on levodopa.
Approvals of once-daily Mirapex ER were mainly supported by data from two similar Phase 3 trials comparing the therapy’s safety and efficacy against Mirapex IR tablets and a placebo in early-stage and advanced Parkinson’s patients.
Early-disease trial
In a global Phase 3 trial (NCT00479401), early-stage Parkinson’s disease patients who had not been given previous levodopa treatment were randomly assigned to receive either Mirapex ER, Mirapex, or a placebo. The trial involved 539 adults treated for about 7.5 months. The first seven weeks of treatment were meant to find each patient’s optimal dose, which was then given for about six months.
The main goal of the trial was to assess combined changes in the second and third parts of the standard Unified Parkinson’s Disease Rating Scale (UPDRS). Part 2 of the UPDRS assesses a patient’s ability to perform daily activities, while Part 3 evaluates motor symptoms; in both, higher scores indicate worse disability.
The results showed that Mirapex ER was not inferior to Mirapex tablets at significantly reducing UPDRS scores. Both formulations resulted in a significantly greater reduction in UPDRS part 2 and 3 scores — by 8.7 for Mirapex ER and 8.2 for Mirapex — compared with a 1.2-point reduction among those given a placebo.
The superiority of the Mirapex formulations over the placebo also was observed in the study’s key secondary measures, with a significantly greater proportion of patients reporting health improvements (41.4%-45.1% vs. 20.6%), and being considered by clinicians to have improved (34.4%-32.4% vs. 16.5%).
Participants were allowed to receive levodopa treatment during the trial if their symptoms became too severe. A significantly higher proportion of patients on a placebo (21%) started levodopa compared with those given Mirapex ER (7%) or Mirapex (4%). Inclusion of these patients in efficacy analyses resulted in similar findings.
The safety profile of Mirapex ER was comparable to that of immediate-release tablets.
Advanced-disease trial
A second Phase 3 trial (NCT00466167), with a similar design to the first study, tested the therapy in 517 adults with advanced Parkinson’s. These patients were experiencing at least two hours daily of off periods despite stable levodopa-based treatment.
In this trial, participants also started with a daily dose of 0.375 mg. That dosage was adjusted over a seven-week period before patients received their optimal dose of either Mirapex ER, Mirapex, or a placebo for six months.
The study’s main goal also was to evaluate changes in combined UPDRS-Part 2 and 3 scores at 18 weeks, or about four months. The key secondary goal was to assess changes in diary-determined daily off time.
Data showed that Mirapex ER led to a nearly twofold greater reduction in UPDRS scores compared with a placebo — 11- versus 6.1-point reductions, a difference that was statistically significant. Similar effects were seen between Mirapex ER and the immediate-release formulation.
Mirapex ER also was associated with a significantly greater reduction in daily off time when compared with a placebo (2.1 vs. 1.4 hours), but a comparable drop relative to Mirapex IR (2.5 hours).
Again, both Mirapex formulations were safe and well tolerated.
Common side effects of Mirapex ER
The most common side effects of Mirapex ER in early Parkinson’s patients not taking levodopa include:
- sleepiness or daytime somnolence
- nausea
- constipation
- dizziness
- fatigue
- hallucinations
- dry mouth
- muscle spams
- swelling of the hands or feet.
In advanced disease patients who are on levodopa, the most frequently reported side effects are:
- dyskinesia or uncontrolled, involuntary movements
- nausea
- constipation
- hallucinations
- headache
- anorexia.
Falling asleep during daily activities
Mirapex ER can cause sleepiness or drowsiness, and there have been reports of people falling asleep during daily activities while on the therapy. This risk should be discussed with prescribing healthcare providers, who should assess for any potential factors for increased sleepiness, such as use of other medications, alcohol consumption, or sleep conditions.
Discontinuing treatment should be considered in patients experiencing considerable daytime sleepiness or sudden sleeping episodes. If treatment is not stopped in these patients, they should avoid driving and other activities where falling asleep unexpectedly can be dangerous.
Low blood pressure upon standing
Mirapex ER may reduce blood pressure and result in dizziness or lightheadedness when rising from sitting or lying down, a condition called orthostatic hypotension. Patients should be informed of this risk and be carefully monitored for evidence of orthostatic hypotension, especially during dose escalation periods.
Mental health, impulse control, and psychosis
Mirapex ER may affect patients’ mental health and cause problems with impulse control, such as urges to gamble or spend money, binge eating, and/or increased sexual urges. These urges may not feel abnormal to the person experiencing them. If patients experience these complications, dose reduction or therapy discontinuation should be considered.
The therapy also may cause hallucinations, or seeing or hearing things that are not real; a risk that increases with age. Patients also may experience confusion, aggressive behavior, and psychotic behaviors. Mirapex ER generally is not recommended for patients with a known psychotic disorder, as it can worsen psychotic symptoms.
Dyskinesia
Treatment with Mirapex ER may cause or exacerbate dyskinesias, or uncontrolled, involuntary movements.
Postural problems
Among certain patients starting or increasing a dose of Mirapex ER, there have been reports of posture abnormalities, such as severe forward flexion — a bending or stooping forward — of the neck or trunk, as well as lateral or sideways flexion of the trunk. If these postural problems do happen, healthcare providers should consider reducing the medication’s dose or discontinuing treatment.
Withdrawal problems
Rapidly reducing Mirapex ER treatment, or quickly discontinuing the medication altogether may cause apathy, anxiety, depression, fatigue, insomnia, sweating, or pain. Other symptoms, such as high fever and confusion, also have been reported following rapid dose reduction or discontinuation of other dopamine agonists. In cases of treatment discontinuation, the dose should be gradually reduced and patients should be closely monitored during and after stopping of the therapy.
Use in pregnancy and breastfeeding
Mirapex ER has not been well studied in women who are pregnant or breastfeeding. However, based on animal studies, the therapy may harm the developing fetus and may be present in breastmilk. Also, reduced lactation is expected with Mirapex ER treatment because it suppresses the secretion of prolactin, the hormone responsible for breast milk production.
Patients who are pregnant or nursing, or planning to become pregnant or breastfeed, should discuss this topic with their healthcare team and carefully weigh the potential benefits and risks of using Mirapex ER in these circumstances.
Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Mirapex
The U.S. Food and Drug Administration approved Mirapex ER in February 2010 for lessening signs and symptoms of early-stage Parkinson’s disease. That indication was then expanded to also include people with advanced disease. An earlier, immediate-release formulation of the therapy had been approved in 1997, but has since been discontinued.
Animal data has suggested that Mirapex ER may cause fetal harm. However, there are no clinical data on the medication’s effects on pregnant patients, so it is unclear whether the therapy is safe in this population. Patients should talk with their doctor about any plans for being pregnant while on Mirapex ER.
Some people on Mirapex ER may experience severe sleepiness or suddenly fall asleep during daily activities. Until patients know how the therapy affects them, those starting Mirapex ER are recommended to avoid driving or other activities that may be potentially dangerous if the individual becomes somnolent. If patients do experience such adverse events, they are advised to talk with their doctor.
In the trials that supported Mirapex ER’s approval, early Parkinson’s patients showed a significant reduction in motor impairment as early as 18 weeks, or about four months, after starting treatment. In advanced Parkinson’s patients, significant improvements in motor symptoms and daily off periods were seen as early as two and four weeks of treatment, respectively. However, each patient is unique, and as such, all are advised to talk with their healthcare team on how the therapy can help in their particular case.
While neither hair loss nor weight gain have been reported as side effects of Mirapex ER in clinical trials, some patients who received the drug or its older immediate-release formulation after their approval have experienced these effects. Also, weight loss has been reported in clinical trials of these formulations in early and advanced Parkinson’s patients. Patients should talk with their healthcare team if they experience any unanticipated effects of treatment.
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