Acetylcholinesterase Inhibitor (Central)

Mild to moderate dementia from Alzheimer's disease

B

There are no adequate studies in pregnant women. Should be used only if the benefit outweighs the potential risk to the fetus. It is unknown if rivastigmine is excreted in human breast milk. There is no indication for use in nursing mothers.

Hypersensitivity to rivastigmine, other carbamate derivatives, or other components of the formulation

Significant nausea, vomiting, anorexia, and weight loss are associated with use; occurs more frequently in women and during the titration phase. Use caution in patients with a history of peptic ulcer disease or concurrent NSAID use. Caution in patients undergoing anesthesia who will receive succinylcholine-type muscle relaxation, patients with sick sinus syndrome, bradycardia or supraventricular conduction conditions, urinary obstruction, seizure disorders, or pulmonary conditions such as asthma or COPD. There are no trials evaluating the safety and efficacy in children.

>10%:

Central nervous system: Dizziness (21%), headache (17%)

Gastrointestinal: Nausea (47%), vomiting (31%), diarrhea (19%), anorexia (17%), abdominal pain (13%)

2% to 10%:

Central nervous system: Fatigue (9%), insomnia (9%), confusion (8%), depression (6%), anxiety (5%), malaise (5%), somnolence (5%), hallucinations (4%), aggressiveness (3%)

Cardiovascular: Syncope (3%), hypertension (3%)

Gastrointestinal: Dyspepsia (9%), constipation (5%), flatulence (4%), weight loss (3%), eructation (2%)

Genitourinary: Urinary tract infection (7%)

Neuromuscular & skeletal: Weakness (6%), tremor (4%)

Respiratory: Rhinitis (4%)

Miscellaneous: Increased sweating (4%), flu-like syndrome (3%)

>2% but frequency equal to placebo: Chest pain, peripheral edema, vertigo, back pain, arthralgia, pain, bone fracture, agitation, nervousness, delusion, paranoid reaction, upper respiratory tract infections, infection, coughing, pharyngitis, bronchitis, rash, urinary incontinence.

<2% (Limited to significant or life-threatening; reactions may be at a similar frequency to placebo): Fever, edema, allergy, periorbital or facial edema, hypothermia, hypotension, postural hypotension, cardiac failure, ataxia, convulsions, apraxia, aphasia, dysphonia, hyperkinesias, hypertonia, hypokinesia, migraine, neuralgia, peripheral neuropathy, hypothyroidism, peptic ulcer, gastroesophageal reflux, GI hemorrhage, intestinal obstruction, pancreatitis, colitis, atrial fibrillation, bradycardia, A-V block, bundle branch block, sick sinus syndrome, cardiac arrest, supraventricular tachycardia, tachycardia, abnormal hepatic function, cholecystitis, dehydration, arthritis, angina pectoris, myocardial infarction, epistaxis, hematoma, thrombocytopenia, purpura, delirium, emotional lability, psychosis, anemia, bronchospasm, apnea, rashes (maculopapular, eczema, bullous, exfoliative, psoriaform, erythematous), urticaria, acute renal failure, peripheral ischemia, pulmonary embolism, thrombosis, thrombophlebitis, intracranial hemorrhage, conjunctival hemorrhage, diplopia, glaucoma, lymphadenopathy, leukocytosis.

In cases of asymptomatic overdoses, rivastigmine should be held for 24 hours. Cholinergic crisis, caused by significant acetylcholinesterase inhibition, is characterized by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse, and convulsions. Treatment is supportive and symptomatic. Dialysis would not be helpful.

Anticholinergic agents effects may be reduced with rivastigmine.

Beta-blockers without ISA activity may increase risk of bradycardia.

Calcium channel blockers (diltiazem or verapamil) may increase risk of bradycardia.

Cholinergic agonists (bethanachol) effects may be increased with rivastigmine.

Cigarette use increases the clearance of rivastigmine by 23%.

Digoxin may increase risk of bradycardia.

Succinylcholine and other depolarizing neuromuscular blocking agents' effects may be increased with rivastigmine.

Store below 77°F (25°C); store solution in an upright position and protect from freezing

A deficiency of cortical acetylcholine is thought to account for some of the symptoms of Alzheimer's disease; rivastigmine increases acetylcholine in the central nervous system through reversible inhibition of its hydrolysis by cholinesterase

Absorption: Rapid and complete within 1 hour when administered in the fasting state.

Distribution: V_d: 1.8-2.7 L/kg

Protein binding: 40%

Metabolism: Extensively metabolized by cholinesterase-mediated hydrolysis in the brain. The metabolite undergoes N-demethylation and/or sulfate conjugation in the liver. Cytochrome P-450 minimally involved. Linear kinetics at 3 mg twice daily, but non-linear at higher doses.

Bioavailability: 40%

Half-life: 1.5 hours

Time to peak: 1 hour

Elimination: 97% recovered in urine as metabolites; 0.4% in feces.

Adults: Oral: Initial: 1.5 mg twice daily to start; if dose is tolerated for at least 2 weeks then it may be increased to 3 mg twice daily; increases to 4.5 mg twice daily and 6 mg twice daily should only be attempted after at least 2 weeks at the previous dose; maximum dose: 6 mg twice daily. If adverse events such as nausea, vomiting, abdominal pain, or loss of appetite occur, the patient should be instructed to discontinue treatment for several doses then restart at the same or next lower dosage level; antiemetics have been used to control GI symptoms.

Dosage adjustment in hepatic impairment: Clearance is significantly reduced in mild to moderately impaired patients. Although dosage adjustments are not recommended, use lowest possible dose and titrate according to individual's tolerance. May consider waiting >2 weeks between dosage adjustments.

Elderly: Clearance is significantly lower in patients older than 60 years of age, but dosage adjustments are not recommended. Titrate dose to individual's tolerance.

Take with food

Cognitive function at periodic intervals

Take with meals at breakfast and dinner. Swallow capsule whole. Do not chew, break, or crush capsule. A liquid (solution) is available for patients who cannot swallow capsules. Monitor for nausea, vomiting, loss of appetite, or weight loss; notify healthcare provider if any of these occur. See instructions for use of oral solution. Can swallow solution directly from syringe or mix with water, juice, or soda. Stir well and drink all of mixture within 4 hours of mixing. Do not mix with other liquids. Avoid concurrent ethanol use.

Educate patient or caregiver about medicine.

Capsule: 1.5 mg, 3 mg, 4.5 mg, 6 mg

Solution, oral: 2 mg/mL (120 mL)