Mirapex 0.5 mg Tablets

Brand Name

This therapeutic product is marketed under the trade name Mirapex, a designation widely recognized in the treatment of neurological and motor conditions.

International Non-Proprietary Name

The active ingredient is identified globally as pramipexole, following the standardized naming system for pharmaceutical substances.

Form of Release

The drug is available in two oral formulations to meet diverse patient needs. It comes as immediate-release tablets in strengths of 0.125 milligrams, 0.25 milligrams, 0.5 milligrams, 1 milligram, and 1.5 milligrams. An extended-release tablet version is offered in doses of 0.375 milligrams, 0.75 milligrams, 1.5 milligrams, 3 milligrams, and 4.5 milligrams, designed for once-daily administration.

Composition

The primary component is pramipexole dihydrochloride monohydrate, which delivers its effects through receptor stimulation. Immediate-release tablets include excipients like mannitol, corn starch, colloidal silicon dioxide, povidone, and magnesium stearate to ensure stability and disintegration. Extended-release tablets incorporate a controlled-release matrix with hypromellose and additional fillers like microcrystalline cellulose, maintaining consistent drug release over time.

Pharmacologic Properties

Pharmacodynamics

This medication acts as a non-ergot dopamine agonist, selectively stimulating D2 and D3 dopamine receptors in the brain. By mimicking dopamine’s action, it compensates for the neurotransmitter deficiency seen in certain disorders, particularly in the striatum, a region critical for motor control and reward processing. Its high affinity for D3 receptors may also influence mood and behavior, distinguishing it from other agonists.

Clinical data demonstrate its ability to reduce motor symptoms like tremors and rigidity, while also addressing non-motor aspects such as restlessness. The effect stems from enhanced dopaminergic signaling, offering symptom relief without altering disease progression. Its receptor specificity minimizes broader neurological disruption, providing a targeted therapeutic benefit.

Pharmacokinetics

After oral administration, the medication absorbs rapidly from the gastrointestinal tract, with peak plasma levels reached in 1 to 3 hours for immediate-release forms and 6 hours for extended-release versions. Food may delay absorption slightly, especially with high-fat meals, but does not reduce overall bioavailability, which exceeds 90 percent. This efficient uptake supports flexible dosing schedules.

The substance distributes widely, with a volume of distribution around 500 liters, indicating extensive tissue penetration, though it minimally crosses the blood-brain barrier relative to its receptor targets. It binds to plasma proteins at less than 20 percent, leaving most of the drug free to act. Metabolism is negligible, with over 90 percent remaining unchanged in the body. The half-life is 8 to 12 hours for immediate-release and up to 24 hours for extended-release, influenced by renal function.

Excretion occurs almost entirely through urine, with more than 90 percent eliminated unchanged via renal tubular secretion. Clearance is highly dependent on kidney performance, necessitating adjustments in patients with impaired renal capacity. A small fraction may exit via feces, but this route is minor compared to urinary elimination.

Indications for Use

Conditions and Disorders

The medication is prescribed for Parkinson’s disease, a chronic condition characterized by dopamine loss in the brain. It manages early-stage symptoms like stiffness, tremors, and bradykinesia as monotherapy, and in advanced stages, it complements levodopa to reduce motor fluctuations. It is also indicated for moderate to severe restless legs syndrome, alleviating the urge to move and associated discomfort.

Mirapex provides effective relief across these applications, improving mobility and quality of life. Its dual approval reflects its versatility in addressing dopamine-related issues, though its primary role remains tied to these specific diagnoses, with limited evidence supporting broader use.

Contraindications

Conditions Prohibiting Use

The drug is contraindicated in patients with hypersensitivity to pramipexole or its components, as reactions could range from skin irritation to severe allergic responses. Severe renal failure, with creatinine clearance below 15 milliliters per minute, prohibits its use due to risks of accumulation and toxicity, unless dialysis is employed.

It should not be used in individuals with a history of psychosis or uncontrolled compulsive behaviors, as dopaminergic stimulation may exacerbate these conditions. Significant cardiovascular disease, such as recent myocardial infarction or severe hypotension, also restricts administration, given potential blood pressure effects.

Method of Administration and Dosage

Administration Guidelines

The medication is taken orally, with immediate-release tablets typically administered three times daily and extended-release tablets once daily, preferably in the morning. It can be taken with or without food, though meals may reduce nausea if consumed alongside. Tablets should be swallowed whole with water, avoiding splitting or crushing, especially for extended-release forms.

Dosage for Adults and Children

For adults with Parkinson’s, immediate-release starts at 0.125 milligrams three times daily, increasing every 5 to 7 days by 0.25 milligrams per dose to a usual range of 1.5 to 4.5 milligrams daily. Extended-release begins at 0.375 milligrams daily, titrating weekly by 0.375 milligrams to a maximum of 4.5 milligrams. For restless legs syndrome, immediate-release dosing is 0.125 milligrams once daily, 2 to 3 hours before bedtime, escalating to 0.5 milligrams if needed. Pediatric use is not approved, as safety and efficacy in children remain unestablished.

Dose Adjustments for Specific Conditions

In moderate renal impairment (creatinine clearance 30 to 50 milliliters per minute), immediate-release maximum is 1.5 milligrams daily, and extended-release is 2.25 milligrams daily. Severe impairment (15 to 29 milliliters per minute) limits immediate-release to 0.125 milligrams twice daily and extended-release to 0.375 milligrams daily. Hepatic impairment rarely requires adjustment, as metabolism is minimal, but caution is advised in severe cases.

Side Effects

Potential Adverse Reactions

Common effects include nausea, dizziness, and drowsiness, often linked to dopaminergic stimulation and most prominent during initial use or dose increases. Fatigue, dry mouth, and peripheral edema may also occur, typically resolving with continued therapy. Some patients report orthostatic hypotension, causing lightheadedness upon standing.

Less frequent reactions involve hallucinations, confusion, or impulse control issues like compulsive gambling, particularly at higher doses or in susceptible individuals. Rarely, severe sleep attacks or worsening motor symptoms emerge, requiring immediate medical review. Significant behavioral changes or allergic responses warrant urgent attention.

Overdose

Symptoms of Excessive Intake

Overdosing may lead to agitation, hallucinations, and low blood pressure, reflecting excessive dopamine activity. Severe cases can progress to confusion, irregular heart rhythms, or unconsciousness, with respiratory depression posing a critical risk. Symptoms vary based on the amount ingested and patient tolerance.

First Aid Measures

Cease administration and seek emergency care promptly. Activated charcoal may limit absorption if given within an hour, provided the patient is alert. No specific antidote exists, so treatment focuses on supportive care, such as stabilizing blood pressure and monitoring vitals. Professional intervention is essential to manage severe effects.

Drug Interactions

Effects on Other Medications

The medication can enhance the effects of other dopaminergic agents, like levodopa, increasing risks of dyskinesia or hypotension. It may reduce the efficacy of dopamine antagonists, such as antipsychotics, by opposing their action. Drugs cleared by renal tubular secretion, like cimetidine, could raise its levels by competing for elimination pathways.

Mirapex may amplify sedation with central nervous system depressants, such as benzodiazepines, or heighten side effects with alcohol. Caution is needed with cytochrome P450 inhibitors or inducers, though their impact is limited due to minimal hepatic metabolism.

Compatibility with Alcohol and Food

Alcohol may intensify drowsiness or dizziness, so moderation is recommended to avoid excessive sedation. Food can delay absorption slightly but may ease nausea, offering a practical option for administration. No specific dietary restrictions apply beyond general caution with high-fat meals.

Special Precautions

Use During Pregnancy and Breastfeeding

Limited data exist on pregnancy use, with no clear human evidence of safety or harm. Animal studies suggest potential fetal risks, so the drug should only be used if benefits outweigh uncertainties, under strict oversight. It may pass into breast milk, so nursing mothers should consult a physician, possibly pausing lactation during therapy.

Impact on Driving and Machinery Operation

The medication may cause drowsiness, sudden sleep onset, or dizziness, particularly early in treatment or at higher doses. Patients should assess their response before driving or operating machinery, avoiding these activities if impaired. Caregivers may need to monitor those at risk of abrupt sleep episodes.

Considerations for Elderly and Pediatric Patients

Elderly patients tolerate it well in most cases, though reduced renal function may require dose adjustments in moderate to severe impairment. Mirapex is not approved for children, as its role in pediatric conditions lacks evidence, restricting use to adults.