Rotigotine

Dose-dependent application site reactions, potentially severe, have been observed; daily rotation of application sites has been shown to decrease incidence of reactions. If a generalized (nonapplication site) skin reaction occurs; discontinue therapy.

Rare cases of pleural effusion, pleural thickening, pulmonary infiltrates, retroperitoneal fibrosis, pericarditis and/or cardiac valvulopathy have been reported in patients treated with ergot-derived dopamine agonists. The potential of rotigotine, a nonergot derived dopamine agonist, to cause similar fibrotic complications is unknown. Discontinuation of therapy may resolve complications, but not in all cases.

Weight gain and fluid retention have been reported, primarily associated with development of peripheral edema in Parkinson disease patients; use caution and monitor for weight gain in patients with concomitant illnesses (eg, heart failure or renal insufficiency).

May cause hallucinations (dose-related) and other psychotic-like behaviors (eg, agitation, delirium, delusions, aggression). In general, avoid use in patients with preexisting major psychotic disorders.

Dopamine agonists used for Parkinson disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/addictions and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases.

Risk for melanoma development is increased in Parkinson disease patients; drug causation or factors contributing to risk have not been established. Patients receiving therapy for any indication should be monitored closely and periodic skin examinations should be performed.

Dopamine agonists may cause orthostatic hypotension and syncope; Parkinson disease patients appear to have an impaired capacity to respond to a postural challenge. Use with caution in patients at risk of hypotension (such as those receiving antihypertensive drugs) or where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Parkinson and RLS patients being treated with dopaminergic agonists ordinarily require careful monitoring for signs and symptoms of postural hypotension, especially during dose escalation, and should be informed of this risk.

Use is commonly associated with somnolence. In addition, falling asleep during activities of daily living, including while driving, has also been reported and may occur without significant warning signs. Monitor for daytime somnolence or pre-existing sleep disorder. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Use with caution in patients receiving other CNS depressants or psychoactive agents; discontinue if significant daytime sleepiness or episodes of falling asleep occur. Effects with other sedative drugs or ethanol may be potentiated. Disease-related concerns:

Use with caution in patients with pre-existing cardiovascular disease; therapy has been associated with increases in blood pressure (as well as orthostatic hypotension), which may be significant (>40 mm Hg or ≥20 mm Hg increase in systolic or diastolic measurements, respectively), increased heart rate, syncope, and weight gain/fluid retention.

Use with caution in patients with preexisting dyskinesia; therapy may cause or exacerbate dyskinesia. Special populations:

Augmentation (earlier onset of symptoms each day and/or an overall increase in symptom severity) may occur in some restless leg syndrome (RLS) patients. Risk factors for dopaminergic-induced augmentation include higher doses of dopaminergic agents, use of shorter-acting dopamine agonists (ie, pramipexole, ropinirole) or levodopa, low iron stores, and increased severity of symptoms prior to treatment initiation. To minimize risk of augmentation, use the lowest effective dose and avoid exceeding recommended doses. Patients may also be switched to alternative therapy if augmentation occurs (Garcia-Borreguero 2016). End-of-dose rebound (reappearance of symptoms in the early morning hours) may also occur. Consider dosage adjustment or discontinuation of treatment if rebound symptoms occur. Dosage form specific issues:

Patch contains aluminum; remove patch prior to magnetic resonance imaging or cardioversion to avoid skin burns.

Avoid exposure of application site to any direct external heat sources (eg, hair dryers, heating pads, electric blankets, saunas, hot tubs, direct sunlight); heat exposure has not been studied with the rotigotine patch, but an increase in the rate and extent of absorption has been observed with other transdermal products.

Patch contains sodium metabisulfite which may cause allergic reaction in susceptible individuals. Other warnings/precautions:

Taper treatment when discontinuing therapy; do not stop abruptly. Other dopaminergic agents have been associated with a syndrome resembling neuroleptic malignant syndrome on withdrawal and/or significant dosage reduction.