Rivastigmine

Oral
Alzheimer's dementia
Adult: In patient with mild to moderately severe cases: As rivastigmine hydrogen tartrate: Initially, 1.5 mg bid, increased in steps of 1.5 mg bid at intervals of at least 2 weeks, according to response and tolerance. Usual dose: 3-6 mg bid. Max: 6 mg bid. Retitrate from 1.5 mg bid, if treatment is interrupted for several days.

Oral
Dementia associated with Parkinson's disease
Adult: In patient with mild to moderately severe cases: As rivastigmine hydrogen tartrate: Initially, 1.5 mg bid, increased in steps of 1.5 mg bid at intervals of at least 2 weeks, according to response and tolerance. Usual dose: 3-6 mg bid. Max: 6 mg bid. Retitrate from 1.5 mg bid, if treatment is interrupted for several days.

Transdermal
Alzheimer's dementia
Adult: In patient with mild to moderately severe cases. As patch: Initially, 4.6 mg/24 hours, increased after at least 4 weeks, if tolerated to 9.5 mg/24 hours for Min 6 months. Then, may increase to 13.3 mg/24 hours, according to response. Retitrate from 4.6 mg/24 hours, if treatment is interrupted for more than 3 days. Apply patch to dry, clean, and hairless skin on the upper or lower back, upper arm or chest. Place patch on different area each day allowing 14 days to elapse before using the same area.
Hepatic impairment: Mild to moderate (Child Pugh class A and B): Initial and max dose of 4.6 mg/24 hours.

Transdermal
Dementia associated with Parkinson's disease
Adult: In patient with mild to moderate cases. As patch: Initially, 4.6 mg/24 hours, increased to 9.5 mg/24 hours, after at least 4 weeks, if tolerated. May further increase to 13.3 mg/24 hours, according to response. Retitrate from 4.6 mg/24 hours, if treatment is interrupted for more than 3 days. Apply patch to dry, clean, and hairless skin on the upper or lower back, upper arm or chest. Place patch on different area each day allowing 14 days to elapse before using the same area.
Hepatic impairment: Mild to moderate (Child Pugh class A and B): Initial and max dose of 4.6 mg/24 hours.

Special Populations: Patient weighing <50 kg: Tab/solution: Reduce dose if toxicities develop. Patch: Reduce maintenance dose to 4.6 mg/24 hours if toxicities develop.

Should be taken with food.

Patient with sick sinus syndrome, bradycardia, or conduction defects; risk of ulcer disease; respiratory diseases (e.g. COPD, asthma); history of seizure disorder; bladder outlet obstruction, prostatic hyperplasia; body weight <50 kg. Mild to moderate hepatic impairment. Pregnancy and lactation. Patient Counselling This drug may impair physical and mental abilities, if affected, do not drive or operate machinery. Monitoring Parameters Monitor cognitive function periodically; body weight, and symptoms of gastrointestinal intolerance.

Significant: Allergic dermatitis (patch); CNS depression, extrapyramidal symptoms, nausea, vomiting, diarrhoea, anorexia, weight loss, decreased appetite, bradycardia, heart block. Gastrointestinal disorders: Abdominal pain, dyspepsia. General disorders and administration site conditions: Application site erythema, fatigue. Injury, poisoning and procedural complications: Falling. Nervous system disorders: Dizziness, headache, tremor, drowsiness, agitation, seizures. Psychiatric disorders: Insomnia, confusion, depression.

Symptoms: Cholinergic crisis (e.g. miosis, flushing, nausea, vomiting, diarrhoea, abdominal pain, salivation, sweating, bradycardia, bronchospasm, involuntary urination/defecation, lacrimation, hypotension); severe nicotinic effects (e.g. muscular weakness, fasciculations, respiratory depression, and convulsions); dizziness, tremor, headache, somnolence, confusional state, hypertension, hallucination, and malaise. Management: Symptomatic and supportive treatment. May administer antiemetics for severe nausea and vomiting Remove patch immediately in asymptomatic cases. May give 0.03 mg/kg of atropine sulphate IV in massive overdose.

Additive effect with succinylcholine-type muscle relaxants during anaesthesia; cholinometric substances (e.g. oxybutynin, tolterodine). Additive effect and increased risk of bradycardia with beta-blockers (e.g. atenolol). Increased risk of torsade de pointes with phenothiazines (e.g. chlorpromazine); benzamides (e.g. sulpiride, sultopride), pimozide, cisapride.

Food delays absorption.

Rivastigmine increases acetylcholine present in CNS by reversibly inhibiting hydrolysis of acetylcholine by cholinesterases.
Duration: Approx 10 hours.
Absorption: Readily and completely absorbed from the gastrointestinal tract. Food delays absorption. Bioavailability: 36%. Time to peak plasma concentration: Approx 1 hour (oral); 8 to 16 hours (transdermal).
Distribution: Widely distributed in the body. Readily crosses the blood-brain barrier. Volume of distribution: 1.8 to 2.7 L/kg. Plasma protein-binding: Approx 40%.
Metabolism: Rapidly and extensively metabolised in the brain via cholinesterase-mediated hydrolysis to weakly active decarbamylated metabolite; further metabolised in the liver via N-demethylation and/or sulphate conjugation.
Excretion: Mainly via urine (97% as metabolites); faeces (0.4%). Half-life elimination: 1.5 hours (oral); approx 3 hours (transdermal).

Neurodegenerative Disease Drugs

N06DA03 - rivastigmine ; Belongs to the class of anticholinesterases. Used in the management of dementia.