Side effects and safety

Adverse effects^1,2

The following adverse reactions have been reported during use of MIRAPEX® in the clinical trials and in the post-marketing experience.¹

Post-marketing Reports²

The following adverse reactions have been identified during post-approval use of immediate-release (IR) MIRAPEX® tablets, primarily in Parkinson’s disease (PD) patients. Similar types of events were grouped into a smaller number of standardized categories using the MedDRA terminology: abnormal behavior, abnormal dreams, accidents (including fall), blackouts, cardiac failure, compulsive shopping, fatigue, hallucinations (all kinds), headache, hypotension (including postural hypotension), inappropriate antidiuretic hormone secretion, increased eating (including binge eating, compulsive eating, and hyperphagia), libido disorders (including increased and decreased libido, and hypersexuality), pathological gambling, pruritus, syncope, vomiting, and weight increase. In a pharmacoepidemiological study, MIRAPEX® use was associated with an increased risk of cardiac failure compared with non-use of MIRAPEX®.²

Warnings and precautions

Postural (Orthostatic) Hypotension²

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. 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.¹ Accordingly, caution patients against rising rapidly after sitting or lying down, especially if they have been doing so for prolonged periods and especially at the initiation of treatment with MIRAPEX prolonged- release (PR)®.²

Augmentation in restless legs syndrome (RLS)²

Reports in the literature indicate that treatment of RLS with dopaminergic medications can result in augmentation.Augmentation refers to the earlier onset of symptoms in the evening (or even the afternoon), increase in symptoms, and spread of symptoms to involve other extremities.²

Sudden onset of sleep and somnolence¹

Falling Asleep During Activities of Daily Living:
Patients treated with MIRAPEX have reported falling asleep while engaged in activities of daily living.¹ Since somnolence is a frequent adverse event with potentially serious consequences, patients should neither drive a car nor operate other complex machinery until they have gained sufficient experience with MIRAPEX to gauge whether or not it affects their mental and/or motor performance adversely.¹ If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), MIRAPEX should ordinarily be discontinued.¹

Melanoma^1,2

Epidemiologic studies have shown that patients with PD have a higher risk of developing melanoma than the general population.^{1, 2} Whether the increased risk observed was due to Parkinson’s disease or other factors, such as drugs used to treat PD, is unclear. For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using MIRAPEX® tablets for any indication.² Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).²

Fibrotic complications¹

Although not reported with MIRAPEX® in the clinical development program, cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, and pleural thickening have been reported in some patients treated with ergot-derived dopaminergic agents. While these complications may resolve when the drug is discontinued, complete resolution does not always occur.¹

Cardiac failure¹

In clinical studies and post-marketing experience cardiac failure has been reported in patients with MIRAPEX®. In a pharmacoepidemiological study MIRAPEX® use was associated with an increased risk of cardiac failure compared with non-use of MIRAPEX®. A causal relationship between MIRAPEX® and cardiac failure has not been demonstrated.¹

Dyskinesia^1,2

MIRAPEX® or MIRAPEX® PR tablets may potentiate the dopaminergic side effects of levodopa and may cause or exacerbate preexisting dyskinesia.^1,2

Drug Withdrawal symptoms^1,2

A drug withdrawal syndrome has been reported during or after discontinuation of dopamine agonists including MIRAPEX®. Risk factors may include high cumulative dopaminergic exposure. Withdrawal symptoms do notrespond to levodopa, and may include apathy, anxiety, depression, fatigue, sweating and pain. Prior to discontinuation, patients should be informed about potential withdrawal symptoms, and closely monitored during and after discontinuation. In case of severe withdrawal symptoms, temporary re-administration of a dopamine agonist at the lowest effective dose may be considered.^1,2

Patients with psychotic disorders

Patients with psychotic disorders should be treated with dopamine agonists only if the potential benefits outweigh the risks. Co-administration of antipsychotic medicinal products with MIRAPEX® is not recommended, e.g. if dopamine-antagonistic effects can be expected.^1,2

Use in specific populations

Pregnancy and Lactation¹

There are no adequate data on the developmental risk associated with therapy in pregnant women; MIRAPEX® was not teratogenic in rats and rabbits but was embryotoxic in the rat at maternotoxic doses. MIRAPEX® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.¹ The excretion of MIRAPEX into the breast milk has not been studied in women.¹