リバスチグミン

Adverse effects of rivastigmine have received thorough study as it has been on the market for some time. The main adverse effects associated with the use of rivastigmine are gastrointestinal. The primary symptoms are nausea and vomiting. These acute effects primarily occur during the initial dose-escalation phase of therapy with upward dose titration of the drug to achieve a therapeutic dose. These events can be minimized using a slow titration schedule and taking the medication with food if prescribing an oral formulation. In a study done to analyze the safety and tolerability of cholinesterase inhibitors used to treat Alzheimer dementia, researchers found rivastigmine to be the drug to have the highest rate of gastrointestinal side effects.；Common adverse effects include extrapyramidal symptoms, sleep disturbances, muscle cramps, and weakness. These issues are less frequent during the maintenance phase of therapy when the dose is not adjusted, but when the drug is being taken for an extended period, central nervous system effects can occur. However, these central nervous system effects are rather rare in rivastigmine and are more common with its counterpart drug, donepezil.；Studies have shown that using the transdermal patch to deliver rivastigmine is associated with fewer reports of nausea and vomiting. Rivastigmine also has a rare case of angioedema related to its use, although overall very uncommon. While the transdermal route offers decreased rates of gastrointestinal effects, reactions like contact dermatitis are prevalent. Also, allergic reactions to the transdermal patch can manifest as vesicles and edema beyond the boundaries of the patch.；Long-term use of rivastigmine has also been associated with an increased risk of death compared to patients treated with donepezil.

Toxicity to the drug, while rare, should be carefully monitored. Common toxicity manifestations include severe gastrointestinal reactions, allergic cutaneous reactions, and central nervous system effects. All cutaneous reactions due to usage of the patch should prompt immediate removal of the patch for at least 48 hours before reapplying in a new area. Therapy should be discontinued if symptoms last longer than 48 hours or a severe cutaneous reaction occurs.；In addition to serious manifestations of common side effects, clinical staff members should always look for cholinergic crises whenever prescribing anticholinergic medications. Classic manifestations of a patient in crisis can be remembered by the mnemonic DUMBELS - diarrhea, urination, miosis, bradycardia, excitability, lacrimation, salivation/excessive sweating before treatment. Patients experiencing a cholinergic crisis should have atropine followed by pralidoxime to reverse the anticholinergic effects of rivastigmine. While the usual treatment of the crisis involves giving atropine before pralidoxime, a case study done in 2009 showed a successful reversal of cholinergic crisis with just pralidoxime without atropine pretreatment.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

rivastigmine

DILI Positive

Oral

DOI:10.1016/j.drudis.2019.09.022

Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.

Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.

Rivastigmine is extensively metabolized primarily via cholinesterase-mediated hydrolysis to the decarbamylated metabolite NAP226-90. Renal excretion of the metabolites is the major route of elimination. Less than 1% of the administered dose is excreted in the feces.

1.8 to 2.7 L/kg

renal cl=2.1-2.8 L/hr