Professional Information

Rotigotine

Pronouncation: (roe-TIG-oh-teen)
Class: Antiparkinson agent

Trade Names:
Neupro
- Transdermal patch 2 mg
- Transdermal patch 4 mg
- Transdermal patch 6 mg

Pharmacology

Stimulates dopamine D ₂ receptors within the caudate-patamen in the brain; however, precise mechanism is unknown.

Pharmacokinetics

Absorption

Approximately 45% of applied patch is released within 24 h. Drug is detected in plasma 1 to 8 h after application. T _min and T _max between 0 and 7 h and 4 and 27 h postdose, respectively. Steady-state plasma concentrations achieved within 2 to 3 days of daily dosing.

Distribution

Vd approximately 84 L/kg. Plasma protein binding is approximately 90%.

Metabolism

Extensively metabolized by conjugation and N-dealkylation. Multiple CYP isoenzymes, sulfotransferases, and 2 UDP-glucuronosyltransferases catalyze the metabolism of rotigotine.

Elimination

After removal the patch, plasma levels decrease with a terminal t _½ of 5 to 7 h. Primarily eliminated (71%) in the urine as inactive conjugates. About 11% excreted in feces.

Indications and Usage

Treatment of signs and symptoms of early-stage idiopathic Parkinson disease.

Contraindications

Standard considerations.

Dosage and Administration

Adults

Transdermal Start at 2 mg per 24 h; based upon clinical response and tolerability, dosage may be increased by 2 mg per 24 h at weekly intervals (max, 6 mg per 24 h).

General Advice

Apply once daily at a convenient time for the patient.
Apply adhesive side of transdermal system to clean, dry, intact healthy skin on the front of the abdomen, thigh, hip, flank, shoulder, or upper arm. Do not apply to skin that is oily, irritated, or damaged, or where it will rub against tight clothing.
Move application site on a daily basis, not repeating application site more than once every 14 days.
If application to a hairy area is necessary, shave area at least 3 days prior to application.
Apply immediately upon removal from the pouch.
Press system in place for 20 to 30 seconds.
If transdermal system becomes dislodged or the patient forgets to replace the patch, another patch should be applied for remainder of the day.

Storage/Stability

Store at 59° to 86°F. Store in original pouch.

Drug Interactions

Dopamine antagonists

The efficacy of rotigotine may be decreased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (3%); purpura, syncope (at least 1%).

CNS

Somnolence (25%); dizziness (18%); headache, insomnia (14%); fatigue (8%); abnormal dreams (7%); hallucination, vertigo (3%); abnormal gait, ataxia, confusion, hypertonia, hypoesthesia, malaise, neuralgia, paresthesia (at least 1%).

Dermatologic

Erythematous rash (6%); increased sweating (4%); contact dermatitis, pruritus (at least 1%).

GI

Nausea (48%); vomiting (20%); constipation (5%); dyspepsia (4%); anorexia, dry mouth (3%).

Genitourinary

UTI (3%); urinary incontinence (at least 1%).

Hepatic

Increased gamma-glutamyl transferase (at least 1%).

Lab Tests

Decreased Hgb (8%); low blood glucose (7%).

Local

Application-site reactions (46%).

Metabolic-Nutritional

Extremity edema (7%); weight decrease (3%); weight increase (at least 1%).

Musculoskeletal

Back pain (6%); arthralgia (4%); myalgia (3%); leg pain (at least 1%).

Respiratory

Sinusitis (3%).

Miscellaneous

Accident (5%); abnormal vision (3%); fever (at least 1%).

Precautions

Monitor

Carefully monitor for signs and symptoms of postural hypotension, especially during dose escalation. Frequently monitor for melanoma.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

No dosage adjustment is recommended in severe renal function impairment.

Hepatic Function

No dosage adjustment is needed in moderate hepatic function impairment. Administration in severe hepatic function impairment has not been studied.

Sulfite Sensitivity

Contains sodium metabisulfite, which may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.

CV system

Use with caution because fluid retention, syncope, increased heart rate, and changes in BP have been reported.

Hallucinations

Have been reported.

Heat application

Avoid exposing patch to external sources of direct heat, such as heating pads, electric blankets, saunas, hot tubs, or prolonged direct sunlight.

Hypotension

Systemic regulation of BP may be impaired, resulting in postural hypotension, especially in dose escalation.

Magnetic resonance imaging (MRI) and cardioversion

To avoid skin burns, remove patch prior to MRI or cardioversion.

Melanoma

Patients with Parkinson disease have a higher risk of developing melanoma, compared with the general population. It is unclear if this is related to drug therapy.

Skin reactions

Application-site reactions were reported. Rotating sites alleviates most of these reactions. Generalized skin reactions or reactions spreading beyond application site may require discontinuation.

Somnolence

Commonly occurs in patients receiving rotigotine. Patients have reported falling asleep while engaged in activities of daily living, including operation of motor vehicles, sometimes without warning signs such as excessive drowsiness.

Tapering dose

At the end of treatment, it is recommended that the dose be tapered.

Weight gain

Weight gain associated with peripheral edema, suggesting fluid retention, has been reported.

Overdosage

Symptoms

No clinical reports. Because rotigotine is a transdermal system, overdosing is not likely.

Patient Information

Advise patient to read the patient information leaflet before using product the first time and with each refill.
Advise patient that product contains a sulfite.
Advise patient to wear patch continuously for 24 h and to apply patch at about the same time each day.
Advise patient to apply adhesive side of transdermal system to clean, dry, intact healthy skin on the front of the abdomen, thigh, hip, flank, shoulder, or upper arm. Do not apply to skin that is oily, irritated, or damaged, or where it will rub against tight clothing.
Advise patient to avoid applying patch on skin folds.
Advise patient to move application site on a daily basis, not repeating application site more than once every 14 days.
Instruct patient not to cut or damage the patch.
Instruct patient that if patch is applied to a hairy area, it is necessary to shave area at least 3 days prior to application.
Instruct patient to apply patch immediately upon removal from the pouch.
Advise patient not to apply creams, lotions, ointments, oils, or powders to skin area where patch will be placed.
Caution patient to avoid dislodging the patch while showering or bathing, or during physical activity.
Advise patient that if transdermal system becomes dislodged or patient forgets to replace the patch, another should be applied for the remainder of the day.
Instruct patient to remove patch prior to MRI or cardioversion in order to avoid a possible skin burn.
Alert patients to sedating effects. Inform patients that falling asleep while engaged in activities of daily living, including operation of motor vehicles, sometimes without warning signs such as excessive drowsiness, has been reported.
Instruct patients to wash their hands after applying the patch and to avoid touching their eyes.
Caution patient to avoid exposing patch to external sources of direct heat, such as heating pads, electric blankets, saunas, hot tubs, or prolonged direct sunlight.