Rivastigmine dosing

Anorexia In the controlled clinical trials, of the patients treated with a rivastigmine dose of 6 to 12 mg/day, 17% developed anorexia compared with 3% of the placebo patients. Neither the time course nor the severity of the anorexia is known. 

Rivastigmine is approved for the treatment of mild to moderate dementia of AD at an initial dose of 1.5 mg twice daily if this dose is tolerated for at least 2 weeks, then the dose can be increased to 3 mg twice daily. Increases to 4.5 mg twice daily and 6 mg twice daily should be attempted only after at least 2 weeks at the previous dose. Tolerability and absorption are improved when the dose is given with food. 

The recommended starting dose of rivastigmine is 1.5 mg twice a day. If dose is well tolerated, after a minimum of 2 weeks of treatment, the dose may be increased to 3 mg twice a day. Subsequent increases to 4.5 and 6 mg twice/day should be attempted after a minimum of 2 weeks at the previous dose. If adverse effects (eg, nausea, vomiting, abdominal pain, loss of appetite) cause intolerance during treatment, instruct the patient to discontinue treatment for several doses and then restart at the same or next lower dose level. If treatment is interrupted for longer than several days, reinitiate treatment with the lowest daily dose and titrate as described above. The maximum dose is 6 mg twice/day (12 mg/day). 

Oral solution Each dose of rivastigmine may be swallowed directly from the syringe or first mixed with a small glass of water, cold fruit juice, or soda. Instruct patients to stir and drink the mixture. 

Rivastigmine oral solution and capsules may be interchanged at equal doses. Storage/Stability When rivastigmine oral solution is combined with cold fruit juice or soda, the mixture is stable at room temperature for 4 hours. 

Absorption - Rivastigmine is rapidly and completely absorbed with an absolute bioavailability of approximately 36% (3 mg dose). Peak plasma concentrations are reached in approximately 1 hour. 

Rivastigmine Transdermal (Exelon Patch) [Cholinesterase Inhibitor/Anti-Alzheimer Agent] Uses MUd/mod Alzheimer and Parkinson Dz dementia Action Acetylcholinesterase inhibitor Dose Initial 4.6-mg patch/d applied to back, chest, upper arm, T 9.5 mg after 4 wk if tolCTated Caution [ ] Sick sinus synd, conduction defects, asthma, COPD, urinary obst, Sz Contra Hypersensitivity to rivastigmine, other carbamates Disp Transdermal patch 5 cm (4.6 mg/24 h), 10 cm (9.5 mg/24 h) SE NA /D EMS See Rivastigmine OD See Rivastigmine... 

Randomized, double blind, placebo controlled trials (RCT) demonstrated that treatment for periods of 6 months and one year, with donepezil, galanta-mine or rivastigmine at the recommended dose for people with mild, moderate or severe dementia due... 

Roskos LK, Boudinot ED Effects of dose and sex on the pharmacokinetics of piroxicam in the rat. Biopharm Drug Dispos 11 215-225, 1990 Rosier M, Anand R, Cici-Sain A, et al Efficacy and safety of rivastigmine in patients with Alzheimer s disease international randomized controlled trial. BMJ 318 633-640, 1999... 

Rivastigmine Exelon Administer 1.5 mg po bid (preferably with meals) for 4 weeks, then increase in increments of 1.5 mg/dose every 2-4 weeks, as tolerated, to a maximum dose of 6 mg po hid. Target daily dose range 3-6 mg po hid 1.5-, 3-, 4.5-, 6-mg capsules 2 mg/mL oral solution (in bottles of 120-mL with dosing syringe)... 

Forette F, Anand R, Gharabawi G A phase II study in patients with Alzheimer s disease to assess the preliminary efficacy and maximum tolerated dose of rivastigmine (Exelon). Eur J Neurol 6 423 29, 1999... 

Rivastigmine is a pseudo-irreversible inhibitor of both acetyl and butyryl cholinesterases. Thus although the drug initially blocks the enzymes, it is metabolized by them thereby giving the drug a relatively short half-life. The top dose is often necessary to achieve therapeutic efficacy, at which dose the central and peripheral cholinergic side effects become apparent. 

The LD50 value of rivastigmine can be raised by the muscarinic blocker atropine almost 11-fold, while the value for the other carbamates in this series is usually about 3 (except for 5.8 for the dimethyl derivative). The quaternary drug atropine methylnitrate, which cannot penetrate the brain, raises the value about two-fold in all cases. This not only adds a safety feature to the use of rivastigmine, but also indicates that rivastigmine s activity - even at high and toxic doses - is more focused than the others in central mechanisms that either directly or indirectly stem from activation of muscarinic receptors. This might contribute to the clinical results if it is assumed that those unexplored nonmuscarinic effects are mostly detrimental to the AD treatment. 

Molecules a, b, c, in Fig. 12.8 manifest the same structure of the carbamic moiety as rivastigmine, but their phenolic part is modified, with regard to both the distance of the amine from the aromatic ring, and the exact N-substituents. This led to compounds that, beside their central ACh E-blocking activity remindful of rivastigmine (albeit at a higher dose), also possess a new pharmacological feature. 

Rivastigmine (1) was the second drug after donepezil in a class of second-generation acetylcholinesterase inhibitors to become commercially available. It is now marketed in over 60 countries worldwide, including those in Europe and South America and the United Kingdom. It has central selectivity, suggesting fewer peripheral adverse effects. These include nausea, vomiting, abdominal pain, and anorexia (2,3). Daily doses up to 12 mg were tolerated and produced improvement in patients with Alzheimer s disease (4). 

Severe vomiting with esophageai rupture may occur if rivastigmine therapy is resumed without re-titrating the drug to fuii dosing... 

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