Plain-language summary, compiled from the cited regulatory records
Pramipexole is a medication classified as a dopamine agonist [1]. It is approved for the treatment of Parkinson's disease [1]. Parkinson's disease is a neurological disorder that affects movement [1]. Pramipexole works by mimicking the effects of dopamine, a neurotransmitter that is deficient in people with Parkinson's disease [1].
This medication is available in an extended-release tablet formulation [1]. It is sold under various brand names [1].
This is not medical advice. Consult a qualified healthcare professional.
GBOfficial regulatory label· revised May 15, 2026[1]
e. over the course of the disease, through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or “on off” fluctuations). 2)
How to take
GB
CACanada· Health Canada
11 products
Uses
CAOfficial regulatory label· revised March 22, 2025[2]
PRAMIPEXOLE (pramipexole dihydrochloride monohydrate) is indicated for adults, as: • treatment of the signs and symptoms of idiopathic Parkinson’s disease. PRAMIPEXOLE may be used both as early therapy, without concomitant levodopa, and as an adjunct to levodopa.
• symptomatic treatment of moderate to severe idiopathic Restless Legs Syndrome. The effectiveness of pramipexole dihydrochloride used for longer than 12 weeks has not been systematically evaluated in controlled trials for Restless Legs Syndrome.
The physician who elects to prescribe PRAMIPEXOLE for an extended time should periodically re-evaluate the long-term usefulness for the individual patient. 1 Pediatrics Pediatrics (< 18 years of age): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.
2 Geriatrics Geriatrics (> 65 years of age): The majority of pramipexole (88%) is cleared via renal secretion. Due to age-related reduction in renal function, the elderly have a slower clearance of pramipexole (approximately 25 – 30% lower).
EUEuropean Union· EMA
4 products
Uses
EUOfficial regulatory label· revised September 2, 2024[3]
e. over the course of the disease, through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or “on off” fluctuations). 2).
How to take
EU
USUnited States· FDA
2 products
Uses
USOfficial regulatory label· revised December 8, 2023[4]
1 Parkinson's Disease Pramipexole dihydrochloride tablets are indicated for the treatment of Parkinson’s disease.
How to take
US
Drug interactions
Known interactions involving Pramipexole. Select one for details. This list is informational and not a complete interaction checker.
Showing 240 of 426. Type above to find a specific drug.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[2]Health Canada (DPD) · 02309122 · revised March 22, 2025
[3]European Medicines Agency · EMEA/H/C/000940 · revised September 2, 2024
[4]FDA DailyMed · 0a3ed933-ef5b-40… · revised December 8, 2023 [PDF]
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
Posology Parkinson’s disease The daily dose is administered in equally divided doses 3 times a day. 375 mg of salt) per day and then increased every 5 - 7 days. Providing patients do not experience intolerable undesirable effects, the dose should be titrated to achieve a maximal therapeutic effect.
5 mg of salt) per day. 8). 5 mg of salt) per day. 5 mg of salt). Further dose adjustments should be done based on the clinical response and the occurrence of adverse reactions. 5 mg of salt). 5 mg of salt) per day can be useful in patients where a reduction of the levodopa therapy is intended.
5). Treatment discontinuation Abrupt discontinuation of dopaminergic therapy can lead to the development of a neuroleptic malignant syndrome or a dopamine agonist withdrawal syndrome. 75 mg of salt). 4). 4). Renal impairment The elimination of pramipexole is dependent on renal function.
The following dose schedule is suggested for initiation of therapy:
Patients with a creatinine clearance above 50 mL/min require no reduction in daily dose or dosing frequency. 25 mg of salt daily). 25 mg of salt) should not be exceeded. 125 mg of salt) daily. 5 mg of salt) should not be exceeded. e. if creatinine clearance declines by 30%, then the Pramipexole daily dose should be reduced by 30%.
The daily dose can be administered in two divided doses if creatinine clearance is between 20 and 50 mL/min, and as a single daily dose if creatinine clearance is less than 20 mL/min. Hepatic impairment Dose adjustment in patients with hepatic failure is probably not necessary, as approx.
90% of absorbed active substance is excreted through the kidneys. However, the potential influence of hepatic insufficiency on Pramipexole pharmacokinetics has not been investigated. Paediatric population The safety and efficacy of pramipexole in children below 18 years have not been established.
There is no relevant use of Pramipexole in the paediatric population in Parkinson’s disease. 125 mg of salt) taken once daily 2-3 hours before bedtime. 75 mg of salt) per day (as shown in the table below). The lowest effective dose should be used (see section
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised May 15, 2026[1]
Based on the analysis of pooled placebo-controlled trials, comprising a total of 1 923 patients on pramipexole and 1 354 patients on placebo, adverse drug reactions were frequently reported for both groups. 63% of patients on pramipexole and 52% of patients on placebo reported at least one adverse drug reaction.
The majority of adverse drug reactions usually start early in therapy and most tend to disappear even as therapy is continued. Within the system organ classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories: very common (≥1/10); common (≥1/100 to < 1/10); uncommon (≥1/1 000 to < 1/100); rare (≥1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).
Parkinson’s disease, most common adverse reactions The most commonly (≥5%) reported adverse drug reactions in patients with Parkinson’s disease more frequent with pramipexole treatment than with placebo were nausea, dyskinesia, hypotension, dizziness, somnolence, insomnia, constipation, hallucination, headache and fatigue.
2). A more frequent adverse drug reaction in combination with levodopa was dyskinesia. Hypotension may occur at the beginning of treatment, especially if pramipexole is titrated too fast.
Table 1:
Parkinson’s disease System Organ Class Adverse Drug Reaction Infections and infestations Uncommon pneumonia Endocrine disorders Uncommon inappropriate antidiuretic hormone secretion1 Psychiatric disorders Common abnormal dreams, behavioural symptoms of impulse control disorders and compulsions; confusion, hallucinations, insomnia Uncommon binge eating1, compulsive shopping, delusion, hyperphagia1, hypersexuality, libido disorder, paranoia, pathological gambling, restlessness, delirium Rare mania Nervous system disorders Very common dizziness, dyskinesia, somnolence Common headache Uncommon amnesia, hyperkinesia, sudden onset of sleep, syncope Eye disorders Common visual disturbance including diplopia, vision blurred and visual acuity reduced.
Cardiac disorders Uncommon cardiac failure1 Vascular disorders Common hypotension Respiratory, thoracic and mediastinal disorders Uncommon dyspnoea, hiccups Gastrointestinal disorders Very common nausea Common constipation, vomiting Skin and subcutaneous tissue disorders Uncommon hypersensitivity, pruritus, rash Reproductive system and breast disorders Rare spontaneous penile erection General disorders and administration site conditions Common fatigue, peripheral oedema Not known dopamine agonist withdrawal syndrome including apathy, anxiety, depression, fatigue, sweating and pain Investigations Common weight decrease including decreased appetite Uncommon weight increase 1 This side effect has been observed in post-marketing experience.
With 95% certainty, the frequency category is not greater than uncommon, but might be lower. A precise frequency estimation is not possible as the side effect did not occur in a clinical trial database of 2 762 patients with Parkinson’s Disease treated with pramipexole.
Restless Legs Syndrome, most common adverse reactions The most commonly (≥ 5%) reported adverse drug reactions in patients with Restless Legs Syndrome treated with pramipexole were nausea, headache, dizziness and fatigue. 3%, respectively).
Table 2Restless Legs Syndrome System Organ Class Adverse Drug Reaction Infections and infestations Uncommon pneumonia1 Endocrine disorders Uncommon inappropriate antidiuretic hormone secretion1 Psychiatric disorders Common abnormal dreams, insomnia Uncommon behavioural symptoms of impulse control disorders and compulsions1 such as, binge eating, compulsive shopping, hypersexuality, and pathological gambling1; delusion1, hyperphagia1, paranoia1, confusion, hallucinations, libido disorder, restlessness, mania1, delirium1 Nervous system disorders Very common Restless legs augmentation syndrome Common dizziness, headache, somnolence Uncommon amnesia1, dyskinesia, hyperkinesia1, sudden onset of sleep, syncope Eye disorders Uncommon visual disturbance including diplopia, vision blurred and visual acuity reduced.
Cardiac disorders Uncommon cardiac failure1 Vascular disorders Uncommon hypotension Respiratory, thoracic and mediastinal disorders Uncommon dyspnoea, hiccups Gastrointestinal disorders Very common nausea Common constipation, vomiting Skin and subcutaneous tissue disorders Uncommon hypersensitivity, pruritus, rash Reproductive system and breast disorders Rare spontaneous penile erection General disorders and administration site conditions Common fatigue Uncommon peripheral oedema Not known dopamine agonist withdrawal syndrome including apathy, anxiety, depression, fatigue, sweating and pain Investigations Uncommon weight decrease including decreased appetite, weight increase 1 This side effect has been observed in post-marketing experience.
With 95% certainty, the frequency category is not greater than uncommon, but might be lower. A precise frequency estimation is not possible as the side effect did not occur in a clinical trial database of 1 395 patients with Restless Legs Syndrome treated with pramipexole.
4). Libido disorders Pramipexole may uncommonly be associated with libido disorders (increased or decreased). Impulse control disorders Pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including […]
GBOfficial regulatory label· Warnings and precautions· revised May 15, 2026[1]
4 Restless legs augmentation syndrome). 75 ∗ if needed Patient’s response should be evaluated after 3 months treatment and the need for treatment continuation should be reconsidered. If treatment is interrupted for more than a few days it should be re-initiated by dose titration carried out as above.
75 mg of salt) Pramipexole Mylan can be discontinued without tapering off. In a 26-week placebo controlled trial, rebound of RLS symptoms (worsening of symptom severity as compared to baseline) was observed in 10% of patients (14 out of 135) after abrupt discontinuation of treatment.
This effect was found to be similar across all doses. Renal impairment The elimination of pramipexole is dependent on renal function. Patients with a creatinine clearance above 20 mL/min require no reduction in daily dose. The use of Pramipexole Mylan has not been studied in haemodialysis patients, or in patients with severe renal impairment.
Hepatic impairment Dose adjustment in patients with hepatic failure is not required, as approx. 90% of absorbed active substance is excreted through the kidneys. Paediatric population Pramipexole Mylan is not recommended for use in children and adolescents below 18 years due to a lack of data on safety and efficacy.
Tourette Disorder Paediatric population Pramipexole Mylan is not recommended for use in children and adolescents below 18 years since the efficacy and safety has not been established in this population. 1). Method of administration For oral use.
The tablets should be taken orally, swallowed with water, and can be taken either with or without food. 1. 2. Hallucinations Hallucinations are known as a side-effect of treatment with dopamine agonists and levodopa. Patients should be informed that (mostly visual) hallucinations can occur.
Dyskinesia In advanced Parkinson’s disease, in combination treatment with levodopa, dyskinesia can occur during the initial titration of Pramipexole. If they occur, the dose of levodopa should be decreased. Dystonia Axial dystonia including antecollis, camptocormia and pleurothotonus (Pisa Syndrome) has occasionally been reported in patients with Parkinson’s disease following initiation or incremental dose increase of pramipexole.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised May 15, 2026[1]
1.
This is not medical advice. Consult a qualified healthcare professional.
1. 4 Geriatrics).
How to take
CAOfficial regulatory label· revised March 22, 2025[2]
125 mg strength. 1 Dosing Considerations In all clinical studies, dosage was initiated at a subtherapeutic level to avoid orthostatic hypotension and severe adverse effects. PRAMIPEXOLE should be titrated gradually in all patients. The dosage should be increased to achieve maximal therapeutic effect, balanced against the principal adverse reactions of dyskinesia, nausea, dizziness and hallucinations.
5 mg per day. PRAMIPEXOLE is not recommended at the 6 mg per day dose since the incidence of some adverse reactions is higher. 375 mg/day given in three PRAMIPEXOLE (Pramipexole Dihydrochloride Tablets) Page 6 of 68 divided doses and should not be increased more frequently than every 5 to 7 days.
5 mg/day, administered in equally divided doses three times per day, as monotherapy or in combination with levodopa (approximately 800 mg/day). 5 mg/day. 5 mg/day, higher doses can result in additional therapeutic benefit. 75 mg. 375 mg per day.
Prior to tapering or discontinuation, patients should be informed about potential withdrawal symptoms and closely monitored thereafter (see 7 WARNINGS AND PRECAUTIONS, Neurologic, Dopamine Agonist Withdrawal Syndrome, and Neuroleptic Malignant Syndrome).
Dosing in patients with concomitant levodopa therapy In patients with concomitant levodopa therapy it is recommended that the dosage of levodopa is reduced during both dose escalation and maintenance treatments with PRAMIPEXOLE. In the controlled study in advanced Parkinson’s disease, the dosage of levodopa was reduced by an average of 27% from baseline.
This may be necessary in order to avoid excessive dopaminergic stimulation. 3 Pharmacokinetics, Renal Insufficiency), the following dosage recommendation should be considered: PRAMIPEXOLE (Pramipexole Dihydrochloride Tablets) Page 7 of 68 Patients with a creatinine clearance above 50 mL/min require no reduction in daily dose or dosing frequency.
25 mg daily). 25 mg pramipexole should not be exceeded. 125 mg daily. 5 mg pramipexole should not be exceeded. Pramipexole has not been adequately studied in patients with very severe renal impairment (creatinine Cl < 15 mL/min and hemodialysis patients) and its administration to patients with end stage renal disease is not recommended.
, if creatinine clearance declines by 30%, then reduce PRAMIPEXOLE daily dose by 30%. The daily dose can be administered in two divided doses if creatinine clearance is between 20 and 50 mL/min and as a single daily dose if creatinine clearance is less than 20 mL/min.
Patients with hepatic impairment Dose reduction not considered necessary. 125 mg taken once daily 2 - 3 hours before bedtime. 75 mg per day, albeit with a higher rate of adverse reactions. 625 mg per day) may be used. Prior to treatment, patients should be informed that augmentation may occur (see 7 WARNINGS AND PRECAUTIONS, Augmentation and Rebound in Restless Legs Syndrome).
Patients should be re- PRAMIPEXOLE (Pramipexole Dihydrochloride Tablets) Page 8 of 68 assessed periodically, and the dose adjusted accordingly. Treatment discontinuation Due to the chronic and fluctuating nature of restless legs syndrome (RLS), continuous treatment may not be necessary.
If discontinuation is desirable, tapering in 4 – 7 day intervals is recommended whenever possible. 5 Post-market adverse reactions). In a 26 week placebo controlled clinical trial, rebound of RLS symptoms (worsening of symptom severity as compared to baseline) was observed in 10% of […]
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised March 22, 2025[2]
1 Adverse Reaction Overview Parkinson’s Disease During the premarketing development of pramipexole dihydrochloride monohydrate, patients enrolled in clinical trials had either early or advanced Parkinson’s disease. Apart from the severity and duration of their disease, the two populations differed in their use of concomitant levodopa therapy.
Namely, patients with early disease did not receive concomitant levodopa therapy during treatment with pramipexole dihydrochloride, while those with advanced Parkinson’s disease did. Because these two populations may have differential risk for various adverse events, adverse event data will be presented for both populations.
All controlled clinical trials performed during premarketing development (except one fixed dose study) used a titration design. Consequently, it was impossible to adequately evaluate the effects of a given dose on the incidence of adverse events.
The most commonly reported adverse reactions in patients with either early or advanced Parkinson’s disease more frequent with pramipexole dihydrochloride treatment than with placebo were nausea, dyskinesia, hypotension, dizziness, somnolence, insomnia, constipation, hallucination and confusion (see 3 SERIOUS WARNINGS AND PRECAUTION BOX, 7 WARNINGS AND PRECAUTIONS).
PRAMIPEXOLE (Pramipexole Dihydrochloride Tablets) Page 18 of 68 Restless Legs Syndrome The most commonly reported adverse reactions with pramipexole dihydrochloride in patients with Restless Legs Syndrome were nausea and somnolence (see 3 SERIOUS WARNINGS AND PRECAUTION BOX).
2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. Parkinson’s Disease Adverse Reactions Leading to Discontinuation of Treatment Early Parkinson’s disease Approximately 12% of 388 patients treated with pramipexole dihydrochloride and 11% of 235 patients treated with placebo discontinued treatment due to adverse events.
4% on placebo). Advanced Parkinson’s disease Approximately 12% of 260 patients treated with pramipexole dihydrochloride and 16% of 264 patients treated with placebo discontinued treatment due to adverse events. 1% on placebo)). Most Frequent Adverse Events Adverse events occurring with an incidence of greater than, or equal to, 10% and listed in decreasing order of frequency, were as follows: Early Parkinson’s disease: nausea, dizziness, somnolence, insomnia, asthenia and constipation.
Advanced Parkinson’s disease: postural [orthostatic] hypotension, dyskinesia, insomnia, dizziness, hallucinations, accidental injury, dream abnormalities, constipation and confusion. PRAMIPEXOLE (Pramipexole Dihydrochloride Tablets) Page 19 of 68 Incidence of Adverse Events in Placebo Controlled Trials Table 5, lists treatment-emergent adverse events that were reported in the double-blind, placebo- controlled studies by ≥1% of patients treated with pramipexole dihydrochloride and were numerically more frequent than in the placebo group.
Adverse events were usually mild or moderate in intensity. Table 5- ADVERSE EVENTS FROM PLACEBO-CONTROLLED STUDIES IN EARLY AND ADVANCED PARKINSON’S DISEASE (INCIDENCE OF EVENTS ≥1% IN PATIENTS TREATED WITH PRAMIPEXOLE DIHYDROCHLORIDE AND NUMERICALLY MORE FREQUENT THAN IN PATIENTS TREATED WITH PLACEBO) Therapy for Early Parkinson’s Disease Therapy for Advanced Parkinson’s Disease Body System/Adverse Event Pramipexole dihydrochloride N = 388 % occurrence Placebo N = 235 % occurrence Pramipexole dihydrochloride† N = 260 % occurrence Placebo† N = 264 % occurrence Body as a Whole 14 12 10 8Asthenia General edema 5 3 4 3 Malaise 2 1 3 2 Reaction unevaluable 2 1 - - Fever 1 0 - - Chest pain - - 3 2 Accidental injury - - 17 15 Cardiovascular System Postural hypotension - - 53 48 Digestive System 28 14 4 2 - 18 6 2 0 - - 10 - - 7 - 9 - - 3 Nausea Constipation Anorexia Dysphagia Dry Mouth Metabolic & Nutritional System Peripheral edema Decreased weight Increased creatine PK 5 2 - 4 0 - 2 - 1 1 - 0 PRAMIPEXOLE (Pramipexole Dihydrochloride Tablets) Page 20 of 68 Therapy for Early Parkinson’s Disease Therapy for Advanced Parkinson’s Disease Body System/Adverse Event Pramipexole dihydrochloride N = 388 % occurrence Placebo N = 235 % occurrence Pramipexole dihydrochloride† N = 260 % occurrence Placebo† N = 264 % occurrence Musculoskeletal System - - 3 1Arthritis - - Twitching - - 2 0 Bursitis - - 2 0 Myasthenia 1 0 Nervous System 25 24 26 25Dizziness Somnolence 22 9 9 6 Insomnia 17 12 27 22 Hallucinations 9 3 17 4 Confusion 4 1 10 7 Amnesia 4 2 6 4 Hyperesthesia 3 1 - - Dystonia 2 1 8 7 Thinking abnormalities 2 0 3 2 Decreased libido 1 0 - - Myoclonus 1 0 - - Hypertonia - - 7 6 Paranoid […]
CAOfficial regulatory label· Warnings and precautions· revised March 22, 2025[2]
, Driving and Operating Machinery 11/2024 7 WARNINGS AND PRECAUTIONS, Psychiatric 11/2024 7 WARNINGS AND PRECAUTIONS, Neurologic 11/2024 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed.
2 PART I: HEALTH PROFESSIONAL INFORMATION ................................................................... 4 1 INDICATIONS ....................................................................................................................
9 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ........................................ 1 Physical Characteristics ........................................................................................................ 9 7 WARNINGS AND PRECAUTIONS ......................................................................................
1 Special Populations ............................................................................................................ 1 Pregnant Women ..........................................................................................................................
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CAOfficial regulatory label· Contraindications· revised March 22, 2025[2]
PRAMIPEXOLE (Pramipexole dihydrochloride monohydrate) is contraindicated in patients who have demonstrated hypersensitivity to pramipexole or the excipients of the drug product (see 4 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING).
This is not medical advice. Consult a qualified healthcare professional.
Posology Parkinson’s disease The daily dose is administered in equally divided doses 3 times a day. 375 mg of salt) per day and then increased every 5-7 days. Providing patients do not experience intolerable undesirable effects, the dose should be titrated to achieve a maximal therapeutic effect.
5 mg of salt) per day. 8). 5 mg of salt) per day. 5 mg of salt). Further dose adjustments should be done based on the clinical response and the occurrence of adverse reactions. 5 mg of salt). 5 mg of salt) per day can be useful in patients where a reduction of the levodopa therapy is intended.
5). Treatment discontinuation Abrupt discontinuation of dopaminergic therapy can lead to the development of a neuroleptic malignant syndrome or a dopamine agonist withdrawal syndrome. 75 mg of salt). 4). 4). 4 Renal impairment The elimination of pramipexole is dependent on renal function.
The following dose schedule is suggested for initiation of therapy:
Patients with a creatinine clearance above 50 mL/min require no reduction in daily dose or dosing frequency. 25 mg of salt daily). 25 mg of salt) should not be exceeded. 125 mg of salt) daily. 5 mg of salt) should not be exceeded. e. if creatinine clearance declines by 30 %, then the Pramipexole Teva daily dose should be reduced by 30 %.
The daily dose can be administered in two divided doses if creatinine clearance is between 20 and 50 mL/min, and as a single daily dose if creatinine clearance is less than 20 mL/min. Hepatic impairment Dose adjustment in patients with hepatic failure is probably not necessary, as approx.
90 % of absorbed active substance is excreted through the kidneys. However, the potential influence of hepatic insufficiency on Pramipexole Teva pharmacokinetics has not been investigated. Paediatric population The safety and efficacy of Pramipexole Teva in children below 18 years has not been established.
There is no relevant use of Pramipexole Teva in the paediatric population for the indication of Parkinson’s Disease. 125 mg of salt) taken once daily 2-3 hours before bedtime. 75 mg of salt) per day (as shown in the table below). The lowest effective dose should be used (see section
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised September 2, 2024[3]
Based on the analysis of pooled placebo-controlled trials, comprising a total of 1 923 patients on pramipexole and 1 354 patients on placebo, adverse drug reactions were frequently reported for both groups. 63 % of patients on pramipexole and 52 % of patients on placebo reported at least one adverse drug reaction.
The majority of adverse drug reactions usually start early in therapy and most tend to disappear even as therapy is continued. Within the system organ classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).
Parkinson’s disease, most common adverse reactions The most commonly (≥ 5 %) reported adverse drug reactions in patients with Parkinson’s disease more frequent with pramipexole treatment than with placebo were nausea, dyskinesia, hypotension, dizziness, somnolence, insomnia, constipation, hallucination, headache and fatigue.
2). A more frequent adverse drug reaction in combination with levodopa was dyskinesia. Hypotension may occur at the beginning of treatment, especially if pramipexole is titrated too fast.
Table 1:
Parkinson’s disease Body System Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1 000 to < 1/100) Rare (≥ 1/10 000 to < 1/1 000) Not known Infections and infestations pneumonia Endocrine disorders inappropriate antidiuretic hormone secretion1 Psychiatric disorders insomnia hallucinations abnormal dreams confusion behavioural symptoms of impulse control disorders and compulsions compulsive shopping pathological gambling restlessness hypersexuality delusion libido disorder paranoia delirium binge eating1 hyperphagia1 mania 9 Nervous system disorders somnolence dizziness dyskinesia headache sudden onset of sleep amnesia hyperkinesia syncope Eye disorders visual impairment including diplopia vision blurred visual acuity reduced Cardiac disorders cardiac failure1 Vascular disorders hypotension Respiratory, thoracic, and mediastinal disorders dyspnoea hiccups Gastrointestinal disorders nausea constipation vomiting Skin and subcutaneous tissue disorders hypersensitivity pruritus rash Reproductive system and breast disorders spontaneous penile erection General disorders and administration site conditions fatigue peripheral oedema dopamine agonist withdrawal syndrome including apathy, anxiety, depression, fatigue, sweating and pain.
Investigations weight decrease including decreased appetite weight increase 1 This side effect has been observed in post-marketing experience. With 95 % certainty, the frequency category is not greater than uncommon, but might be lower.
A precise frequency estimation is not possible as the side effect did not occur in a clinical trial database of 2 762 patients with Parkinson’s Disease treated with pramipexole. Restless Legs Syndrome, most common adverse reactions The most commonly (≥ 5 %) reported adverse drug reactions in patients with Restless Legs Syndrome treated with pramipexole were nausea, headache, dizziness and fatigue.
3 %, respectively). 10 Table 2: Restless Legs Syndrome Body System Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1 000 to < 1/100) Rare (≥ 1/10 000 to < 1/1 000) Not known Infections and infestations pneumonia1 Endocrine disorders inappropriate antidiuretic hormone secretion1 Psychiatric disorders insomnia abnormal dreams restlessness confusion hallucinations libido disorder delusion1 hyperphagia1 paranoia1 mania1 delirium1 behavioural symptoms of impulse control disorders and compulsions1 (such as: compulsive shopping, pathological gambling, hypersexuality, binge eating) Nervous system disorders Restless legs augmentation syndrome headache dizziness somnolence sudden onset of sleep syncope dyskinesia amnesia1 hyperkinesia1 Eye disorders visual impairment including visual acuity reduced diplopia vision blurred Cardiac disorders cardiac failure1 Vascular disorders hypotension Respiratory, thoracic, and mediastinal disorders dyspnoea hiccups Gastrointestinal disorders nausea constipation vomiting Skin and subcutaneous tissue disorders hypersensitivity pruritus rash Reproductive system and spontaneous penile 11 breast disorders erection General disorders and administration site conditions fatigue peripheral oedema dopamine agonist withdrawal syndrome including apathy, anxiety, depression, fatigue, sweating and pain Investigations weight decrease including decreased appetite weight increase 1 This side effect has been observed in post-marketing experience.
With 95 % certainty, the frequency category is not greater than uncommon, but might be lower. A precise frequency estimation is not possible as the side effect did not occur in a clinical trial database of 1 395 patients with Restless Legs Syndrome treated with pramipexole.
4). Libido disorders Pramipexole may uncommonly be associated with libido disorders (increased or decreased). 4). 6% of all patients receiving […]
EUOfficial regulatory label· Warnings and precautions· revised September 2, 2024[3]
4 Restless legs augmentation syndrome). 75 * if needed Patient’s response should be evaluated after 3 months treatment and the need for treatment continuation should be reconsidered. If treatment is interrupted for more than a few days it should be re-initiated by dose titration carried out as above.
75 mg of salt) Pramipexole Teva can be discontinued without tapering off. In a 26 week placebo 5 controlled trial, rebound of RLS symptoms (worsening of symptom severity as compared to baseline) was observed in 10% of patients (14 out of 135) after abrupt discontinuation of treatment.
This effect was found to be similar across all doses. Renal impairment The elimination of pramipexole is dependent on renal function. Patients with a creatinine clearance above 20 mL/min require no reduction in daily dose. The use of Pramipexole Teva has not been studied in haemodialysis patients, or in patients with severe renal impairment.
Hepatic impairment Dose adjustment in patients with hepatic failure is not required, as approx. 90% of absorbed active substance is excreted through the kidneys. Paediatric population Pramipexole Teva is not recommended for use in children and adolescents below 18 years due to a lack of data on safety and efficacy.
Tourette Disorder Paediatric population Pramipexole Teva is not recommended for use in children and adolescents below 18 years since the efficacy and safety has not been established in this population. 1). Method of administration The tablets should be taken orally, swallowed with water, and can be taken either with or without food.
1. 2. Hallucinations Hallucinations are known as a side effect of treatment with dopamine agonists and levodopa. Patients should be informed that (mostly visual) hallucinations can occur. Dyskinesia In advanced Parkinson’s disease, in combination treatment with levodopa, dyskinesia can occur during the initial titration of Pramipexole Teva.
If they occur, the dose of levodopa should be decreased. Dystonia Axial dystonia including antecollis, camptocormia and pleurothotonus (Pisa Syndrome) has occasionally been reported in patients with Parkinson’s disease following initiation or incremental dose increase of pramipexole.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised September 2, 2024[3]
1.
This is not medical advice. Consult a qualified healthcare professional.
5 * Doses should not be increased more frequently than every 5 to 7 days. Titrate to effective dose. If used with levodopa, may need to reduce levodopa dose. 1 General Dosing Considerations Pramipexole dihydrochloride tablets are taken orally, with or without food.
If a significant interruption in therapy with pramipexole dihydrochloride tablets has occurred, re-titration of therapy may be warranted. 2 Dosing for Parkinson's Disease In all clinical studies, dosage was initiated at a subtherapeutic level to avoid intolerable adverse effects and orthostatic hypotension.
Pramipexole dihydrochloride tablets should be titrated gradually in all patients. The dose should be increased to achieve a maximum therapeutic effect, balanced against the principal side effects of dyskinesia, hallucinations, somnolence, and dry mouth.
375 mg/day given in three divided doses and should not be increased more frequently than every 5 to 7 days. 5 mg/day administered in equally divided doses three times per day with or without concomitant levodopa (approximately 800 mg/day).
5 mg/day. However, in the same fixed-dose study, the following adverse events were dose related: postural hypotension, nausea, constipation, somnolence, and amnesia. The frequency of these events was generally 2-fold greater than placebo for pramipexole doses greater than 3 mg/day.
5 mg/day was comparable to placebo. When pramipexole dihydrochloride tablets are used in combination with levodopa, a reduction of the levodopa dosage should be considered. In a controlled study in advanced Parkinson’s disease, the dosage of levodopa was reduced by an average of 27% from baseline.
Dosing in Patients with Renal Impairment The recommended dosing of pramipexole dihydrochloride tablets in Parkinson’s disease patients with renal impairment is provided in Table 2. 5 once a day Very severe impairment (creatinine Cl <15 mL/min and hemodialysis patients) The use of pramipexole dihydrochloride tablets has not been adequately studied in this group of patients.
75 mg. 9)].
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised December 8, 2023[4]
1) ] . 2) ] . 3) ]. 4) ] . 5) ] . 7) ] . 8) ] . 9) ] . 1). 1). 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Parkinson’s Disease During the premarketing development of pramipexole, patients with either early or advanced Parkinson’s disease were enrolled in clinical trials. Apart from the severity and duration of their disease, the two populations differed in their use of concomitant levodopa therapy.
Patients with early disease did not receive concomitant levodopa therapy during treatment with pramipexole; those with advanced Parkinson’s disease all received concomitant levodopa treatment. Because these two populations may have differential risks for various adverse reactions, this section will, in general, present adverse-reaction data for these two populations separately.
Because the controlled trials performed during premarketing development all used a titration design, with a resultant confounding of time and dose, it was impossible to adequately evaluate the effects of dose on the incidence of adverse reactions.
Early Parkinson’s Disease In the three double-blind, placebo-controlled trials of patients with early Parkinson’s disease, the most common adverse reactions (>5%) that were numerically more frequent in the group treated with pramipexole dihydrochloride tablets were nausea, dizziness, somnolence, insomnia, constipation, asthenia, and hallucinations.
Approximately 12% of 388 patients with early Parkinson’s disease and treated with pramipexole dihydrochloride tablets who participated in the double-blind, placebo-controlled trials discontinued treatment due to adverse reactions compared with 11% of 235 patients who received placebo.
4% on placebo]). Adverse- reaction Incidence in Controlled Clinical Studies in Early Parkinson's Disease: Table 4 lists adverse reactions that occurred in the double-blind, placebo-controlled studies in early Parkinson’s disease that were reported by ≥1% of patients treated with pramipexole dihydrochloride tablets and were numerically more frequent than in the placebo group.
In these studies, patients did not receive concomitant levodopa. 5 mg/day to 6 mg/day: postural hypotension, nausea, constipation, somnolence, and amnesia. The frequency of these reactions was generally 2-fold greater than placebo for pramipexole doses greater than 3 mg/day.
5 mg/day was comparable to that reported for placebo. Advanced Parkinson’s Disease In the four double-blind, placebo-controlled trials of patients with advanced Parkinson’s disease, the most common adverse reactions (>5%) that were numerically more frequent in the group treated with pramipexole dihydrochloride tablets and concomitant levodopa were postural (orthostatic) hypotension, dyskinesia, extrapyramidal syndrome, insomnia, dizziness, hallucinations, accidental injury, dream abnormalities, confusion, constipation, asthenia, somnolence, dystonia, gait abnormality, hypertonia, dry mouth, amnesia, and urinary frequency.
Approximately 12% of 260 patients with advanced Parkinson’s disease who received pramipexole dihydrochloride tablets and concomitant levodopa in the double-blind, placebo-controlled trials discontinued treatment due to adverse reactions compared with 16% of 264 patients who received placebo and concomitant levodopa.
1% on placebo]). Adverse-reaction Incidence in Controlled Clinical Studies in Advanced Parkinson's Disease : Table 5 lists adverse reactions that occurred in the double-blind, placebo-controlled studies in advanced Parkinson’s disease that were reported by ≥1% of patients treated with pramipexole dihydrochloride tablets and were numerically more frequent than in the placebo group.
In these studies, pramipexole dihydrochloride tablets or placebo was administered to patients who were also receiving concomitant levodopa. Table 5 Adverse-Reactions in Double-Blind, Placebo-Controlled Trials With Pramipexole Dihydrochloride Tablets in Advanced Parkinson's Disease Body System/ Adverse Reaction Pramipexole Dihydrochloride (N=260) % Placebo (N = 264) % Nervous System Dyskinesia 47 31 Extrapyramidal syndrome 28 26 Insomnia 27 22 Dizziness 26 25 Hallucinations 17 4 Dream abnormalities 11 10 Confusion 10 7 Somnolence 9 6 Dystonia 8 7 Gait abnormalities 7 5 Hypertonia 7 6 Amnesia 6 4 Akathisia 3 2 Thinking abnormalities 3 2 Paranoid reaction 2 0 Delusions 1 0 Sleep disorders 1 0 Cardiovascular System Postural hypotension 53 48 Body as a Whole Accidental injury 17 15 Asthenia 10 8 General edema 4 3 Chest pain 3 2 Malaise 3 2 Digestive System Constipation 10 9 Dry mouth 7 3 Urogenital System Urinary frequency 6 3 Urinary tract infection 4 3 Urinary incontinence 2 1 Respiratory System Dyspnea 4 3 Rhinitis 3 1 Pneumonia 2 0 Special Senses Accommodation Abnormalities 4 2 Vision abnormalities 3 1 Diplopia 1 0 Musculoskeletal System Arthritis 3 1 Twitching 2 0 Bursitis 2 0 Myasthenia 1 0 Metabolic & Nutritional System Peripheral edema 2 1 Increased creatine PK 1 0 Skin & Appendages Skin disorders 2 1 Adverse Reactions: Relationship to Age, Gender, and Race Among the adverse reactions in patients treated with pramipexole dihydrochloride tablets, hallucination appeared to exhibit a positive relationship to age in patients with Parkinson’s disease.
Although no gender-related differences were observed in Parkinson’s disease patients. Less than 4% of patients enrolled were non-Caucasian: therefore, an evaluation of adverse reactions related to race is not possible. Laboratory Tests During the development of pramipexole dihydrochloride tablets, no systematic abnormalities on routine laboratory testing were noted.
2 Post Marketing Experience In addition to the adverse events reported during clinical trials, the following adverse reactions have been identified during post-approval use of pramipexole dihydrochloride tablets, primarily in Parkinson’s disease patients.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to pramipexole tablets.
Similar types of reactions were grouped into a smaller number of standardized categories using the MedDRA terminology: cardiac failure, inappropriate antidiuretic hormone secretion (SIADH), skin reactions (including erythema, rash, pruritus, urticaria), syncope, vomiting, and weight increase.
USOfficial regulatory label· Warnings and precautions· revised December 8, 2023[4]
3) · Hallucinations and Pschyotic-like Behaviour: May occur; risk increases with age. 1 Falling Asleep During Activities of Daily Living and Somnolence Patients treated with pramipexole have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles which sometimes resulted in accidents.
Although many of these patients reported somnolence while on pramipexole tablets, some perceived that they had no warning signs (sleep attack) such as excessive drowsiness, and believed that they were alert immediately prior to the event.
Some of these events had been reported as late as one year after the initiation of treatment. 5 mg three times a day) for Parkinson’s disease. It has been reported that falling asleep while engaged in activities of daily living usually occurs in a setting of pre-existing somnolence, although patients may not give such a history.
For this reason, prescribers should reassess patients for drowsiness or sleepiness, especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities.
3) ]. ), pramipexole dihydrochloride tablets should ordinarily be discontinued. If a decision is made to continue pramipexole dihydrochloride tablets, advise patients not to drive and to avoid other potentially dangerous activities that might result in harm if the patients become somnolent.
While dose reduction reduces the degree of somnolence, there is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living. 2 Symptomatic Orthostatic Hypotension Dopamine agonists, in clinical studies and clinical experience, appear to impair the systemic regulation of blood pressure, with resulting orthostatic hypotension, especially during dose escalation.
Parkinson’s disease patients, in addition, appear to have an impaired capacity to respond to an orthostatic challenge. For these reasons, Parkinson’s disease patients being treated with dopaminergic agonists ordinarily require careful monitoring for signs and symptoms of orthostatic hypotension, especially during dose escalation, and should be informed of this risk.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised December 8, 2023[4]
4 CONTRAINDICATIONS None. None (4)
This is not medical advice. Consult a qualified healthcare professional.
Although dystonia may be a symptom of Parkinson’s disease, the symptoms in these patients have improved after reduction or withdrawal of pramipexole. If dystonia occurs, the dopaminergic medication regimen should be reviewed and an adjustment in the dose of pramipexole considered.
Sudden onset of sleep and somnolence Pramipexole has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson’s disease. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported uncommonly.
Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with Pramipexole. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines.
Furthermore a reduction of dose or termination of therapy may be considered. 8). Impulse control disorders Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including Pramipexole.
Dose reduction/tapered discontinuation should be considered if such symptoms develop. Mania and delirium Patients should be regularly monitored for the development of mania and delirium. Patients and carers should be made aware that mania and delirium can occur in patients treated with pramipexole.
Dose reduction/tapered discontinuation should be considered if such symptoms develop. Patients with psychotic disorders Patients with psychotic disorders should only be treated with dopamine agonists if the potential benefits outweigh the risks.
5). Ophthalmologic monitoring Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur. Severe cardiovascular disease In case of severe cardiovascular disease, care should be taken. It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the general risk of postural hypotension associated with dopaminergic therapy.
3 Less Common Clinical Trial Adverse Reactions .................................................................. 5 Post-Market Adverse Reactions .........................................................................................
27 9 DRUG INTERACTIONS...................................................................................................... 2 Drug Interactions Overview ...............................................................................................
7 Drug-Laboratory Test Interactions ..................................................................................... 32 10 CLINICAL PHARMACOLOGY ...........................................................................................
1 Mechanism of Action ....................................................................................................... 2 Pharmacodynamics ..........................................................................................................
3 Pharmacokinetics ............................................................................................................. 35 11 STORAGE, STABILITY AND DISPOSAL .............................................................................
38 12 SPECIAL HANDLING INSTRUCTIONS ............................................................................... 38 PART II: SCIENTIFIC INFORMATION.....................................................................................
39 13 PHARMACEUTICAL INFORMATION ................................................................................ 39 14 CLINICAL TRIALS............................................................................................................
1 Clinical Trials by Indication […]
Although dystonia may be a symptom of Parkinson’s disease, the symptoms in these patients have improved after reduction or withdrawal of pramipexole. If dystonia occurs, the dopaminergic medication regimen should be reviewed and an adjustment in the dose of pramipexole considered.
6 Sudden onset of sleep and somnolence Pramipexole has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson’s disease. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported uncommonly.
Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with Pramipexole Teva. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines.
Furthermore a reduction of the dose or termination of therapy may be considered. 8). Impulse control disorders Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including Pramipexole Teva.
Dose reduction/tapered discontinuation should be considered if such symptoms develop. Mania and delirium Patients should be regularly monitored for the development of mania and delirium. Patients and carers should be made aware that mania and delirium can occur in patients treated with pramipexole.
Dose reduction/tapered discontinuation should be considered if such symptoms develop. Patients with psychotic disorders Patients with psychotic disorders should only be treated with dopamine agonists if the potential benefits outweigh the risks.
5). Ophthalmologic monitoring Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur. Severe cardiovascular disease In case of severe cardiovascular disease, care should be taken. It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the general risk of postural hypotension associated with dopaminergic therapy.
2). 8). To discontinue treatment in patients with Parkinson’s disease, pramipexole should be tapered off (see section […]
In clinical trials of pramipexole, however, and despite clear orthostatic effects in normal volunteers, the reported incidence of clinically significant orthostatic hypotension was not greater among those assigned to pramipexole tablets than among those assigned to placebo.
This result, especially with the higher doses used in Parkinson’s disease, is clearly unexpected in light of the previous experience with the risks of dopamine agonist therapy. While this finding could reflect a unique property of pramipexole, it might also be explained by the conditions of the study and the nature of the population enrolled in the clinical trials.
Patients were very carefully titrated, and patients with active cardiovascular disease or significant orthostatic hypotension at baseline were excluded. 3 Impulse Control/Compulsive Behaviors Case reports and the results of a cross-sectional study suggest that patients can experience intense urges to gamble, increased sexual urges, intense urges to spend money uncontrollably, binge eating, and/or other intense urges and the inability to control these urges while taking one or more of the medications, including pramipexole dihydrochloride tablets, that increase central dopaminergic tone and that are generally used for the treatment of Parkinson’s disease.
In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with pramipexole dihydrochloride tablets.
Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking pramipexole dihydrochloride tablets. 6% (6 of 235) of patients receiving placebo. 8% (10 of 264) of patients receiving placebo.
4% of placebo patients in both populations. Age appears to increase the risk of hallucinations attributable to pramipexole. 8 times greater than placebo in patients older than 65 years. 2 times greater than placebo in patients older than 65 years.
Postmarketing reports with medication used to treat Parkinson’s disease, including pramipexole dihydrochloride tablets, indicate that patients may experience new or worsening mental status and behavioral changes, which may be severe, including psychotic-like behavior during treatment with pramipexole dihydrochloride tablets or after starting or increasing the dose of pramipexole dihydrochloride tablets.
Other drugs prescribed to improve the symptoms of Parkinson’s disease can have similar effects on thinking and behavior. This abnormal thinking and behavior can consist of one or more of a variety of manifestations including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.
Patients with a major psychotic disorder should ordinarily not be treated with dopamine agonists, including pramipexole dihydrochloride tablets, because of the risk of exacerbating the psychosis. 1)]. 5 Dyskinesia Pramipexole dihydrochloride tablets may potentiate the dopaminergic side effects of levodopa and may cause or exacerbate preexisting dyskinesia.
3) ]. 7 Rhabdomyolysis A single case of rhabdomyolysis occurred in a 49-year-old male with advanced Parkinson’s disease treated with pramipexole dihydrochloride tablets. The patient was hospitalized with an elevated CPK (10,631 IU/L).
The symptoms resolved with discontinuation of the medication. 8 Retinal Pathology Human Data A two-year open-label, randomized, parallel-group safety study of retinal deterioration and vision compared pramipexole dihydrochloride tablets and immediate-release ropinirole.
5 mg/day) were evaluated using a panel of clinical ophthalmological assessments. Of 234 patients who were evaluable, 196 had been treated for two years and 29 were judged to have developed clinical abnormalities that were considered meaningful (19 patients in each treatment arm had received treatment for less than two years).
There was no statistical difference in retinal deterioration between the treatment arms; however, the study was only capable of detecting a very large difference between treatments. In addition, because the study did not include an untreated comparison group (placebo treated), it is unknown whether the findings reported in patients treated with either drug are greater than the background rate in an aging population.
Animal Data Pathologic changes (degeneration and loss of photoreceptor cells) were observed in the retina of albino rats in the 2-year carcinogenicity study. While retinal degeneration was not diagnosed in pigmented rats treated for 2 years, a thinning in the outer nuclear layer of the retina was slightly greater in rats given drug compared with controls.
Evaluation of the retinas of albino mice, monkeys, and minipigs did not reveal similar changes. 2) ]. 9 Events Reported with Dopaminergic Therapy Although the events enumerated below may not have been reported in association with the use of pramipexole in its development program, they are associated with the use of other dopaminergic drugs.
The expected incidence of these events, however, is so low that even if pramipexole caused these events at rates similar to those attributable to other dopaminergic therapies, it would be unlikely that even a single case would have occurred in a cohort of the size exposed to pramipexole in studies to date.
Hyperpyrexia and Confusion Although not reported with pramipexole in the clinical development program, a symptom complex resembling the neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in dopaminergic therapy.
If possible, avoid sudden discontinuation or rapid dose reduction in patients taking pramipexole dihydrochloride tablets. 2) ]. Fibrotic Complications Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis, and cardiac valvulopathy have been reported in patients treated with ergot-derived dopaminergic agents.
While these complications may resolve when the drug is discontinued, complete resolution does not always occur. Although these adverse events are believed to be related to the ergoline structure of these compounds, whether other, nonergot-derived dopamine agonists can cause them is unknown.
Cases of possible fibrotic complications, including peritoneal fibrosis, pleural fibrosis, and pulmonary fibrosis have been reported in the post marketing experience with pramipexole dihydrochloride tablets. While the evidence is not sufficient to establish a causal relationship between pramipexole dihydrochloride tablets and these fibrotic complications, a contribution of pramipexole dihydrochloride tablets cannot be completely ruled out.
Melanoma Epidemiological studies have shown that patients with Parkinson’s disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population. Whether the observed increased risk was due to Parkinson’s disease or other factors, such as drugs used to treat Parkinson’s disease, is unclear.
For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using pramipexole dihydrochloride tablets for any indication. , dermatologists).