Trade Names:Exelon- Capsules 1.5 mg (as tartrate)- Capsules 3 mg (as tartrate)- Capsules 4.5 mg (as tartrate)- Capsules 6 mg (as tartrate)- Solution, oral 2 mg/mL (as tartrate)
Trade Names:Exelon- Patch, transdermal 4.6 mg per 24 h- Patch, transdermal 9.5 mg per 24 h
Unknown; however, may increase acetylcholine by inhibiting acetylcholinesterase, thereby increasing cholinergic function.
Rapidly and completely absorbed. T max is about 1 h. Bioavailability is 36% to 40%. Food delays absorption T max 90 min, lowers C max 30%, increases AUC 30%.Transdermal
There is a lag time of 0.5 to 1 h in absorption following the first application. C max is 8 to 16 h; after which, plasma concentration slowly decreases over the remainder of the 24-h period. Steady-state trough levels are 60% to 80% of peak levels. Fluctuations between C max and C min are lower with transdermal than oral administration. Intersubject variability in exposure is 43% to 49% with transdermal compared with 73% to 103% with oral. Exposure is highest when patch is applied to upper back, chest, or upper arm.
Widely distributed throughout the body, penetrates blood-brain barrier, and distributes equally between blood and plasma. Vd is 1.8 to 2.7 L/kg. Protein binding is 40%.
Rapidly and extensively metabolized, primarily via cholinesterase-mediated hydrolysis to the decarbamylated metabolite. CYP-450 is minimally involved. Shows linear pharmacokinetics up to 3 mg twice daily but is nonlinear at higher doses.
Eliminated in urine (97%; no parent drug detected) and feces (0.4%). Elimination t ½ is about 1.5 h.Transdermal
Elimination t ½ is approximately 3 h after patch removal. Renal Cl is about 2.1 to 2.8 L/h.
Mean oral Cl is 64% lower (oral administration).Severe renal function impairment
Mean oral Cl is 43% higher for unexplained reasons (oral administration).Hepatic Function Impairment
Mean oral Cl is 60% lower (oral administration).Elderly
Mean oral Cl was 30% lower.Nicotine users
Increased oral Cl 23%.
Treatment of mild to moderate dementia of the Alzheimer type; treatment of mild to moderate dementia associated with Parkinson disease.
Treatment of the behavioral symptoms in Lewy body dementia (oral).
Hypersensitivity to rivastigmine, inactive ingredients, or other carbamate derivatives.
Transdermal Start with 4.6 mg per 24 h patch. After a minimum of 4 wk at the initial dose, increase the dose to the 9.5 mg per 24 h patch (recommended max, 9.5 mg per 24 h). If adverse reactions (eg, diarrhea, nausea, vomiting) cause intolerance to treatment, stop treatment for several days then restart at the same or next lower dose. If treatment is stopped for more than several days, restart treatment with the 4.6 mg per 24 h patch and titrate to 9.5 mg per 24 h after a minimum of 4 wk.Dementia of the Alzheimer TypeAdults
PO 1.5 mg twice daily initially, then the dose may be increased by increments of 1.5 mg twice daily at intervals of 2 wk or more (max, 6 mg twice daily).Dementia Associated With Parkinson DiseaseAdults
PO 1.5 mg twice daily initially, then the dose may be increased by increments of 1.5 mg twice daily at intervals of 4 wk or more (max, 6 mg twice daily).Switching from Capsules or Oral Solution to Transdermal PatchAdults
Transdermal Patients receiving an oral dose of less than 6 mg of rivastigmine daily can be switched to the 4.6 mg per 24 h patch. Patients receiving an oral dose of rivastigmine 6 to 12 mg daily may be switched directly to the 9.5 mg per 24 h patch. When switching from oral administration to patch, it is recommended that the first patch be applied on the day following the last oral dose.
Store capsules, oral solution, and transdermal patch at 59° to 86°F. Store solution upright and protect from freezing. Keep patch in individual sealed pouch until use.
Succinylcholine-type muscle relaxation may be exaggerated during anesthesia.Anticholinergic drugs
Possible reduction in anticholinergic effects.Cholinesterase inhibitors, cholinomimetics
Synergistic effects may occur.
None well documented.
Hypertension, syncope (3%); angina pectoris, atrial fibrillation, bradycardia, cardiac failure, hypotension, MI, palpitation, postural hypotension (at least 1%).
Dizziness (21%); headache (17%); tremor (10%); fatigue, insomnia (9%); confusion (8%); asthenia, depression (6%); anxiety, malaise, somnolence (5%); hallucination (4%); aggressive reaction, worsening Parkinson disease (3%); Parkinsonism (2%); agitation, delusion, nervousness, paranoid reaction, vertigo (at least 2%); abnormal gait, ataxia, dyskinesia, paresthesia, seizures (at least 1%).Transdermal
Depression (4%); anorexia/decreased appetite, anxiety, headache (3%); asthenia, dizziness, fatigue (2%); insomnia (1%); tremor (at least 1%).
Increased sweating (4%); rash (general) (at least 2%); hot flushes, rash of various kinds including bullous, eczema, erythematous, exfoliative, maculopapular, and psoriasiform (at least 1%); Stevens-Johnson syndrome (postmarketing).Transdermal
Pruritus (at least 1%).
Rhinitis (4%); pharyngitis (at least 2%); cataract, epistaxis, tinnitus (at least 1%).Transdermal
Nasopharyngitis (at least 1%).
Nausea (47%); vomiting (31%); diarrhea (19%); anorexia (17%); abdominal pain (13%); dyspepsia (9%); constipation (5%); flatulence (4%); eructation (2%); fecal incontinence, gastritis (at least 1%).Transdermal
Nausea (7%); diarrhea, vomiting (6%); constipation, gastritis (at least 1%).
UTI (7%); urinary incontinence (at least 2%); hematuria (at least 1%).Transdermal
UTI (2%); urinary incontinence (at least 1%).
Anemia (at least 1%).
Weight decrease (3%); dehydration, hypokalemia (at least 1%).Transdermal
Decreased weight (3%); dehydration (at least 1%).
Arthralgia, back pain, bone fracture (at least 2%); arthritis, leg cramps, myalgia, rigors (at least 1%).
Bronchitis, coughing, upper respiratory tract infection (at least 2%); dyspnea (at least 1%).Transdermal
Pneumonia (at least 1%).
Accidental trauma (10%); influenza-like symptoms (3%); chest pain, infection, pain, peripheral edema (at least 2%); allergy, edema, fever (at least 1%).Transdermal
Abdominal pain (2%); upper abdominal pain (1%); falling (at least 1%).
Closely monitor for symptoms of active or occult GI bleeding, especially in patients at increased risk for developing ulcers (eg, patients receiving NSAIDs). Monitor weight and appetite.
Category B .
Safety and efficacy not established.
May have vagotonic effects on heart rate (eg, bradycardia).
Higher than recommended transdermal doses are associated with greater frequency of GI adverse reactions (eg, diarrhea, nausea, vomiting).
Urinary obstruction may occur.
Exacerbation of extrapyramidal symptoms may occur.
Use with caution in patients with a history of asthma or obstructive pulmonary disease.
May increase potential for seizures.
Patients weighing less than 50 kg (110 lbs) may experience more adverse reactions, especially with use of transdermal patches above the recommended maintenance dose (ie, 9.5 mg per 24 h).
Cholinergic crisis (eg, bradycardia, collapse, hypotension, muscle weakness, respiratory depression, salivation, seizures, severe nausea, sweating, vomiting), death.
Copyright © 2009 Wolters Kluwer Health.