rivastigmine EXELON
Class: Dual Cholinesterase InhibitorFDA Indications: Alzheimer's Dementia, Mild To Moderate Dementia Associated With Parkinson's Disease
Off-Label Use: Vascular Dementia
Prescribing
Forms: 1.5, 3, 4.5, 6mg capsule; 2mg/mL po soln; Transdermal–4.6 mg/24 hours or 9.5 mg/24 hours or 13.3 mg/24 hoursDose Range: 3-12 mg/day
Starting: Initial Dose: Initiate treatment with 1.5 mg twice a day.
Dose Titration: After a minimum of 2 weeks, if tolerated, increase dose to 3 mg twice a day and further to 4.5 mg twice a day and 6 mg twice a day if tolerated with a minimum of 2 weeks at each dose.
Recommend administer with food.
Precautions
Contraindications: Known hypersensitivity to a specific drug or its derivatives is the only true contraindication. Cautious administration of cholinesterase inhibitors is advised in patients who have a previous history of allergy or adverse reactions to prior cholinesterase inhibitors, severe liver disease, preexisting bradycardia, peptic ulcer disease, current alcoholism, asthma, or chronic obstructive pulmonary disease.Side Effects: nausea, vomiting, anorexia, dyspepsia, weakness/asthenia
Pharmacodynamics
1° MOA: "pseudo-irreversible", carbamate-type, brain-selective, dual cholinesterase inhibitorTarget: AChE >> BuChE
Pharmacokinetics
t½: 1.5 (1.4-1.7)° TMAX: 0.5-1.7°Substrate of: Hepatic esterases
Inhibits: ∅ ; Induces: ∅
Active Metabolites: NAP 226-90
DDIs
- - AChEIs have the potential to interfere with the activity of anticholinergic medications
- - A synergistic effect may be expected with concomitant administration of succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists
Misc
- - high rate of nausea (47%) and vomiting (31%); dose cautiously to avoid this
- - displays nonlinear pharmacokinetics
- - when administered with food, the time to maximum concentration is increased, resulting in a ↓ in Cmax of ∼30%
- - when switching from oral to patch, 6 mg po ≈ 4.6 mg/24h patch; 6-12 mg po ≈ 9.5 mg/24h patch
- - PK profile showed that compared with the oral formulation, transdermal patch provides smoother and continuous as well as controlled drug delivery over 24h, thereby resulting in fewer side effects
Special Populations
Category B—No reports describing the use of rivastigmine in human pregnancy have been located. Because of its indication, such reports would be rare. Moreover, the animal data suggest that the risk to the embryofetus is low. Therefore, inadvertent exposure to rivastigmine during pregnancy should not be a reason for pregnancy termination.
No reports describing the use of rivastigmine during human lactation have been located. The molecular weight (about 250 for the free base) and moderate protein binding (about 40%) suggest that the drug will be excreted into breast milk. The very short elimination half-life should decrease the amount of drug available for excretion. The effect of this exposure on a nursing infant is unknown.
Patients with moderate to severe renal impairment may be able to only tolerate lower doses.
Patients with moderate to severe hepatic impairment may be able to only tolerate lower doses.