Drug information of Rotigotine

Rotigotine is a nonergot dopamine agonist with specificity for D3-, D2-, and D1-dopamine receptors. Although the precise mechanism of action of rotigotine is unknown, it is believed to be due to stimulation of postsynaptic dopamine D2-type auto receptors within the substantia nigra in the brain, leading to improved dopaminergic transmission in the motor areas of the basal ganglia, notably the caudate nucleus/putamen regions.

Metabolism

Extensive via conjugation and N-dealkylation; multiple CYP isoenzymes, sulfotransferases, and two UDP-glucuronosyltransferases involved in catalyzing the metabolism

Time to reach the peak

15 to 18 hours; can occur 4 to 27 hours post application

Distribution

Vd: ~84 L/kg

Half life

After removal of patch: ~5 to 7 hours

Excretion

Urine (~71% as inactive conjugates and metabolites, <1% as unchanged drug); feces (~23%)

1-Treatment of Parkinson's disease

2-Treatment of moderate-to-severe primary Restless Legs Syndrome

Usual Adult Dose for Parkinson's Disease:

Initial doses:

Early-stage Parkinson's disease: Apply 2 mg topically once a day

Advanced-stage Parkinson's disease: Apply 4 mg topically once a day

Maintenance dose: Increase weekly in 2 mg/24 hours increments if additional therapeutic effect is needed

Lowest effective dose: 4 mg/24 hours

Maximum dose for Early-stage Parkinson's disease: 6 mg/24 hours

Maximum dose for Advanced-stage Parkinson's disease: 8 mg/24 hours

Usual Adult Dose for Restless Legs Syndrome:

Initial dose: Apply 1 mg topically once a day

Maintenance dose: Increase weekly in 1 mg/24 hours increments if additional therapeutic effect is needed

Lowest effective dose: 1 mg/24 hours

Maximum dose: 3 mg/24 hours

1-Safety and efficacy have not been established in patients younger than 18 years.

2-Hypersensitivity to rotigotine or any component of the formulation

>10%:

Cardiovascular: Systolic hypotension (13% to 32%), orthostatic hypotension (8% to 29%), peripheral edema (3% to 14%)

Central nervous system: Drowsiness (5% to 32%), dizziness (5% to 23%), headache (10% to 21%), fatigue (6% to 18%), malaise (≤14%), sleep disorder (disturbance in initiating/maintaining sleep; 2% to 14%), hallucination (3% to 13%)

Dermatologic: Hyperhidrosis (1% to 11%)

Endocrine & metabolic: Decreased serum glucose (1% to 15%)

Gastrointestinal: Nausea (15% to 48%), vomiting (2% to 20%)

Hematologic & oncologic: Decreased hematocrit (8% to 17%), decreased hemoglobin (8% to 15%)

Local: Application site reaction (21% to 46%)

Neuromuscular & skeletal: Dyskinesia (14% to 17%), asthenia (≤14%), arthralgia (8% to 11%)

1% to 10%:

Cardiovascular: Increased diastolic blood pressure (4% to 8%), systolic hypertension (5%), hypertension (1% to 5%), atrioventricular block (3%), hypoesthesia (3%), abnormal T waves on ECG (2% to 3%)

Central nervous system: Abnormal dreams (1% to 7%), nightmares (3% to 5%), paresthesia (3% to 4%), vertigo (3% to 4%), depression (2% to 3%), equilibrium disturbance (2% to 3%), irritability (1% to 3%), sudden onset of sleep (1% to 2%)

Dermatologic: Pruritus (4% to 9%), erythema (2% to 6%)

Endocrine & metabolic: Weight gain (2% to 9%), change in libido (4% to 6%), hot flash (3% to 4%), low serum ferritin (2%), menstrual disease (1% to 2%)

Gastrointestinal: Constipation (5% to 9%), anorexia (2% to 9%), xerostomia (7%), diarrhea (5% to 7%), dyspepsia (2% to 3%), viral gastroenteritis (1% to 2%)

Hematologic & oncologic: Basal cell carcinoma (3%), leukocyturia (3%)

Infection: Herpes simplex infection (3%), influenza (1% to 3%)

Neuromuscular & skeletal: Tremor (4%), muscle spasm (3% to 4%)

Ophthalmic: Visual disturbance (3% to 5%)

Otic: Tinnitus (2% to 3%)

Renal: Increased blood urea nitrogen (3% to 11%)

Respiratory: Nasopharyngitis (8% to 10%), cough (3%), nasal congestion (3%), paranasal sinus congestion (2% to 3%), sinusitis (2% to 3%)

Alcohol (Ethyl), Alfuzosin, Alizapride, Amifostin,Amisulpride, Antipsychotic Agents (First Generation [Typical]), Antipsychotic Agents (Second Generation [Atypical]), Blood Pressure Lowering Agents, Brimonidine (Topical), Bromopride, Bromperidol, BuPROPion, CNS Depressants, Diazoxide, DULoxetine, Herbs (Hypotensive Properties), Hypotension-Associated Agents, Levodopa-Containing Products, Lormetazepam, Methylphenidate, Metoclopramide, Molsidomine, Naftopidil, Nicergoline, Nicorandil, Nitroprusside, Obinutuzumab, Pentoxifylline,Pholcodine, Phosphodiesterase 5 Inhibitors, Prostacyclin Analogues, Quinagolide, Solriamfetol,Sulpiride

1-Drinking alcohol with rotigotine can increase side effects.

2-Avoid applying a patch to skin that is irritated, or to skin where you have applied lotion, oil, cream, ointment, or powder.

3-Do not expose the skin patch to heat while you are wearing it. This includes a hot tub, heating pad, sauna, or heated water bed. Heat can increase the amount of drug absorbed through your skin and may cause harmful effects.

1-Tell your doctor if you have ever had:

-asthma or a sulfite allergy

-high or low blood pressure

-heart problems

-kidney disease

-schizophrenia, bipolar disorder, or psychosis

-narcolepsy or other sleep disorder

-if you feel light-headed or nauseated when you stand up

2-Apply the patch to clean, dry, and hairless skin. Avoid placing the patch where it will be rubbed by a waistband or tight clothing. Press the patch firmly into place for about 30 seconds. You may leave the patch on while bathing, showering, or swimming.

3-Remove the skin patch after 24 hours and replace it with a new one. Choose a different place on your body to wear the patch each time you put on a new one. Do not use the same skin area twice within 14 days.

4-If a patch falls off, put a new patch on a different place on your body and wear it the rest of the day. Then replace the patch the next day at your regular time.

5-The rotigotine patch may burn your skin if you wear the patch during an MRI (magnetic resonance imaging). Remove the patch before undergoing such a test.

6-Do not stop using rotigotine suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using rotigotine.

7-Upon discontinuation, reduce the daily dose by a maximum of 2 mg every 24 hours, if possible; reduce the dose every other day until withdrawal is complete.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15ºC and 30ºC (59ºF and 86ºF). Store in original pouch until application.

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