rotigotine (Rx)

>10% (Early-stage Parkinson Disease)

Nausea (34-48%)

Application site reactions (including erythema, pruritus, irritation, burning, dermatitis, inflammation, papulae, vesicle, pain) (21-46%)

Dizziness (14-22%)

Somnolence (12-20%)

Vomiting (10-20%)

Fatigue (6-18%)

Insomnia (5-11%)

Hyperhidrosis (3-11%)

1-10% (Advanced-stage Parkinson Disease)

Application site reactions (36-46%)

Somnolence (32%)

Nausea (22-28%)

Dizziness (14-23%)

Dyskinesia (14-17%)

Edema peripheral (9-14%)

Insomnia (9-14%)

Hallucinations (7-14%)

Arthralgia (8-11%)

1-10% (Restless Legs Syndrome)

Application site reactions (23-43%)

Nausea (15-23%)

Headache (15-21%)

Asthenia (7-14%)

1-10% (Early-stage Parkinson Disease)

Abnormal dreams (2-7%)

Erythema (3-6%)

Anorexia (2-6%)

Depression (2-5%)

Edema peripheral (2-4%)

Dyspepsia (2-3%)

EKG, T- ave abnormal (2-3%)

Weight loss (2-3%)

Balance disorder (2-3%)

Tinnitus (2-3%)

Hiccups (2-3%)

Pruritic rash (2-3%)

Erectile dysfunction (2-3%)

Lethargy (1-2%)

Orthostatic hypotension (1-2%)

1-10% (Advanced-stage Parkinson Disease)

Vomiting (8-10%)

Headache (8-10%)

Constipation (5-9%)

Diarrhea (5-7%)

Hypertension (3-5%)

Nightmares (3-5%)

Paraesthesias/Dysesthesias (3-4%)

Tremor (3-4%)

Asthenia (3-4%)

Cough (3%)

Nasal Congestion (3%)

Sinus congestion (2-3%)

Erythema (2-3%)

Hyperhidrosis (1-3%)

Musculoskeletal pain (2%)

1-10% (Restless Legs Syndrome)

Nasopharyngitis (5-10%)

Somnolence (5-10%)

Insomnia (2-10%)

Dizziness (5-9%)

Pruritus (3-9%)

Xerostomia (3-7%)

Constipation (2-6%)

Hyperhidrosis (1-5%)

Vomiting (2-4%)

Muscle spasms (1-4%)

Hypertension (1-4%)

Hot flushes (1-4%)

Dyspepsia (1-3%)

Vertigo (1-3%)

Sinusitis (1-3%)

Abnormal dreams (1-3%)

Sleep attacks (1-2%)

Erythema (1-2%)

Contraindications

Hypersensitivity

Cautions

May cause sudden onset of sleep while engaging in activities of daily living, compulsive disorders (eg, pathologic gambling, hypersexuality, increased libido, repetitive meaningless actions), hallucinations, and psychotic-like behavior

Contains sodium metabisulfite that may cause allergic-type reactions Somnolence is common; falling asleep during activities of daily living observed

May cause symptomatic hypotension and syncope

May increase blood pressure and heart rate

Dose dependent increases in weight and fluid retention observed

May potentiate dopaminergic side effects of levodopa and cause or exacerbate dyskinesia

Avoid abrupt withdrawal; symptoms resembling neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, rhabdomyolysis, and/or autonomic instability) with no other obvious etiology, has been reported in association with rapid dose reduction

Application site reactions are frequent and dose related

Restless leg syndrome rebound/augmentation may occur as dose wears off

Remove patch before MRI; backing layer of patch contains aluminum

Heat may increase absorption; avoid exposure to external heat sources (eg, heating pads, electric blankets, sauna)

Fibrotic complication reported (eg, retroperitoneal fibrosis, pleural effusion, pericarditis)

Binding to melanin-pigmented tissues reported

Hallucinations/psychotic -like behavior and dyskinesia may occur

Monitor for melanoma; increased risk reported for patients receiving therapy

Pregnancy

There are no adequate data on developmental risk associated with use in pregnant women

Animal data

• In animal studies, drug was shown to have adverse effects on embryofetal development when administered during pregnancy at doses similar to or lower than those used clinically

Lactation

There are no data on presence of drug in human milk, effects on the breastfed infant, or on milk production; however, inhibition of lactation may occur because drug decreases secretion of prolactin in humans; studies have shown that rotigotine and/or its metabolite(s) are excreted in rat milk

The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for drug and any potential adverse effects on breastfed infant from drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Non-ergolinic D3/D2/D1 dopamine agonist

Effective in treating Parkinson disease by stimulating D2 receptors within the caudate-putamen in the brain

The precise mechanism of action for treating restless legs syndrome is unknown; thought to be related dopamine receptor stimulation

Absorption

Bioavailability: 37%

Peak plasma time: 15-18 hr

Release rate: 45% in 24 hr (0.2 mg/sq.cm/24 hr)

Distribution

Protein Bound: 92% (in vitro); 89.5% (in vivo)

Vd: 84 L/kg

Metabolism

Metabolized by N-dealkylation and direct/secondary conjugation

Elimination

Half-life, biphasic: 3 hr (initial); 5-7 hr (terminal)

Excretion: 71% urine; 23% feces

Topical Administration

Apply patch at same time qDay

Apply to clean, dry, intact skin on front of abdomen, high, hip, flank, shoulder, or upper arm

Press the patch firmly to the skin for 30 seconds; check the adherence to the skin, particularly around the edges

Rotate application site each day

Do not apply to the same site more than once every 14 days

Monitor: BP, ophthalmic function