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Pronunciation(ri va STIG meen)
U.S. Brand NamesExelon®
SynonymsENA 713; Rivastigmine Tartrate; SDZ ENA 713
Generic AvailableNo
Canadian Brand NamesExelon®
UseMild to moderate dementia from Alzheimer's disease
Pregnancy Risk FactorB
Pregnancy ImplicationsThere are no adequate and well-controlled studies in pregnant women. Should be used only if the benefit outweighs the potential risk to the fetus.
LactationExcretion in breast milk unknown/use caution
ContraindicationsHypersensitivity to rivastigmine, other carbamate derivatives, or any component of the formulation
Warnings/PrecautionsSignificant nausea, vomiting, anorexia, and weight loss are associated with use; occurs more frequently in women and during the titration phase. If treatment is interrupted for more than several days, reinstate at the lowest daily dose. 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.
Adverse Reactions>10%:
Central nervous system: Dizziness (21%), headache (17%)
Gastrointestinal: Nausea (47%), vomiting (31%), diarrhea (19%), anorexia (17%), abdominal pain (13%)
2% to 10%:
Cardiovascular: Syncope (3%), hypertension (3%)
Central nervous system: Fatigue (9%), insomnia (9%), confusion (8%), depression (6%), anxiety (5%), malaise (5%), somnolence (5%), hallucinations (4%), aggressiveness (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 diaphoresis (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 infection, infection, cough, pharyngitis, bronchitis, rash, urinary incontinence.
<2% (Limited to important or life-threatening symptoms; 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, hyperkinesia, hypertonia, hypokinesia, migraine, neuralgia, peripheral neuropathy, hypothyroidism, peptic ulcer, gastroesophageal reflux, GI hemorrhage, intestinal obstruction, pancreatitis, colitis, atrial fibrillation, bradycardia, AV block, bundle branch block, sick sinus syndrome, cardiac arrest, supraventricular tachycardia, tachycardia, abnormal hepatic function, cholecystitis, dehydration, arthritis, angina pectoris, MI, epistaxis, hematoma, thrombocytopenia, purpura, delirium, emotional lability, psychosis, anemia, bronchospasm, apnea, rash (maculopapular, eczema, bullous, exfoliative, psoriaform, erythematous), urticaria, acute renal failure, peripheral ischemia, pulmonary embolism, thrombosis, thrombophlebitis, intracranial hemorrhage, conjunctival hemorrhage, diplopia, glaucoma, lymphadenopathy, leukocytosis.
Postmarketing and/or case reports: Stevens-Johnson syndrome, severe vomiting with esophageal rupture (following inappropriate reinitiation of dose)
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Overdosage/ToxicologyIn 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.
Drug InteractionsAnticholinergics: 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: Effects may be increased with rivastigmine
Cigarette use increases the clearance of rivastigmine by 23%
Digoxin: Increased risk of bradycardia with concurrent use
Neuromuscular blockers: Depolarizing neuromuscular blocking agents effects may be increased with rivastigmine
NSAIDs: Although not seen in clinical studies, patients may be at increased risk for peptic ulcers or gastrointestinal bleeding with concomitant use; monitor
Ethanol/Nutrition/Herb InteractionsCigarette use: Increases the clearance of rivastigmine by 23%.
Ethanol: Avoid ethanol (due to risk of sedation; may increase GI irritation).
Food: Food delays absorption by 90 minutes, lowers Cmax by 30% and increases AUC by 30%.
StabilityStore below 25°C (77°F); store solution in an upright position and protect from freezing
Mechanism of ActionA 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
Pharmacodynamics/KineticsAbsorption: Fasting: Rapid and complete within 1 hour
Distribution: Vd: 1.8-2.7 L/kg
Protein binding: 40%
Metabolism: Extensively via cholinesterase-mediated hydrolysis in the brain; metabolite undergoes N-demethylation and/or sulfate conjugation hepatically; CYP minimally involved; linear kinetics at 3 mg twice daily, but nonlinear at higher doses
Bioavailability: 40%
Half-life elimination: 1.5 hours
Time to peak: 1 hour
Excretion: Urine (97% as metabolites); feces (0.4%)
DosageAdults: Mild to moderate Alzheimer's dementia: 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. If treatment is interrupted for longer than several days, restart the treatment at the lowest dose and titrate as previously described. 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.
Dosage adjustment in renal impairment: Dosage adjustments are not recommended, however, titrate the dose to the individual's tolerance.
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.
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AdministrationShould be administered with meals (breakfast or dinner). Capsule should be swallowed whole. Liquid form is available for patients who cannot swallow capsules (can be swallowed directly from syringe or mixed with water, milk, or juice). Stir well and drink within 4 hours of mixing.
Monitoring ParametersCognitive function at periodic intervals
Dietary ConsiderationsShould be taken with meals.
Patient EducationThis drug is not a cure for Alzheimer's disease, but it may reduce the symptoms. Use as directed; do not increase dose or discontinue without consulting prescriber. Swallow capsule whole with meals (do not crush or chew). Liquid can be swallowed directly from syringe or mixed with water, milk, or juice; stir well and drink within 4 hours of mixing. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. Avoid alcohol. May cause dizziness, drowsiness, or postural hypotension (rise slowly from sitting or lying position and use caution when driving or climbing stairs); vomiting or loss of appetite (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); diarrhea (buttermilk, boiled milk, or yogurt may help); or constipation (increased exercise, fluids, fruit, or fiber may help); or urinary frequency. Report persistent abdominal discomfort, diarrhea, or constipation; significantly increased salivation, sweating, tearing, or urination; chest pain, palpitations, acute headache; CNS changes (eg, excessive fatigue, agitation, insomnia, dizziness, confusion, aggressiveness, depression); increased muscle, joint, or body pain; vision changes or blurred vision; shortness of breath, coughing, or wheezing; skin rash; or other persistent adverse reactions. Breast-feeding precaution: Consult prescriber if breast-feeding.
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Nursing ImplicationsEducate patient or caregiver about medicine.
Cardiovascular ConsiderationsBecause of the cholinergic activity due to inhibition of acetylcholinesterase, rivastigmine may induce significant bradycardia. Caution is especially indicated in patients with sick sinus syndrome and pre-existing cardiac conduction abnormalities. Interactions with beta-blockers, calcium channel blockers, and digoxin may potentiate bradycardia and may predispose to significant hypotension.
Dental Health: Effects on Dental TreatmentNo significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic PrecautionsNo information available to require special precautions
Dosage FormsCapsule: 1.5 mg, 3 mg, 4.5 mg, 6 mg
Solution, oral: 2 mg/mL (120 mL) [contains sodium benzoate]
International Brand NamesExelon® (AR, AT, AU, BE, BR, CA, CH, CL, CO, CR, CZ, DE, DK, DO, EC, ES, FI, FR, GB, GT, HN, HR, HU, ID, IE, IL, IN, IT, MX, NL, NO, NZ, PA, PL, PT, RO, RU, SE, SG, SI, SV, TH, TR, YU, ZA); Prometax® (ES, IT, PT)
The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-
A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited. |
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