Rivastigmina

Uses

Symptomatic treatment of mild to moderately severe Alzheimer's dementia. Symptomatic treatment of mild to moderately severe dementia in patients with Idiopathic Parkinson's disease.

Rivastigmina is also used to associated treatment for these conditions: Diffuse Lewy Body Disease, Mild Dementia due to Parkinson's disease, Mild Dementia of the Alzheimer's Type, Moderate Alzheimer's Type Dementia, Moderate Dementia due to Parkinson's disease

How Rivastigmina works

Rivastigmina is a carbamate derivative that is structurally related to physostigmine, but not to donepezil and tacrine. The precise mechanism of rivastigmine has not been fully determined, but it is suggested that rivastigmine binds reversibly with and inactivates chlolinesterase (eg. acetylcholinesterase, butyrylcholinesterase), preventing the hydrolysis of acetycholine, and thus leading to an increased concentration of acetylcholine at cholinergic synapses. The anticholinesterase activity of rivastigmine is relatively specific for brain acetylcholinesterase and butyrylcholinesterase compared with those in peripheral tissues.

Dosage

Rivastigmina dosage

Initial dose: Rivastigmina 1.5 mg twice a day.

Dose titration: The starting dose is Rivastigmina 1.5 mg twice aday. If this dose is well tolerated after a minimum of two weeks of treatment, the dosemay be increased to Rivastigmina 3 mg twice a day. Subsequentincreases to 4.5 mg and then 6 mg twice a day should also be based on good tolerabilityof the current dose and may be considered after a minimum of two weeks of treatment atthat dose level.

Maintenance dose: The effective dose is 3 mg to 6 mg twice a day; to achieve maximum therapeutic benefit patients should be maintained on their highest well tolerated dose. The recommended maximumdaily dose is 6 mg twice a day. Maintenance treatment can becontinued for as long as a therapeutic benefit for the patient exists.

Re-initiation of therapy: If treatment is interrupted for more than several days, it shouldbe re-initiated at 1.5 mg twice daily. Dose titration should then be carried out as described above.

Renal and hepatic impairment: Due to increased exposure in moderate renal and mild tomoderate hepatic impairment, dosing recommendations to titrate according to individual tolerability should be closely followed

Children: Rivastigmina is not recommended for use in children.

Rivastigmina should be administered twice a day, with morning and evening meals.

Side Effects

The most commonly reported adverse reactions are gastrointestinal, including nausea (38%) and vomiting (23%), especially during titration. Female patients in clinical studies were found to be more susceptible than male patients to gastrointestinal adverse reactions and weight loss.

Precaution

Patients with sick sinus syndrome or conduction defects, resp diseases. Cholinergic stimulation may increase gastric acid secretion. May exacerbate urinary obstruction and seizures. Pregnancy. Renal impairment, mild to moderate hepatic impairment. Monitor body wt. Asthma or obstructive pulmonary disease. May worsen extrapyramidal symptoms. Lactation.

Interaction

As a cholinesterase inhibitor, Rivastigmina may exaggerate the effects of succinylcholine-type muscle relaxants during anaesthesia. Caution is recommended when selecting anaesthetic agents. Possible dose adjustments or temporarily stopping treatment can be considered if needed. In view of its pharmacodynamic effects, rivastigmine should not be given concomitantly with other cholinomimetic substances and might interfere with the activity of anticholinergic medicinal products. No pharmacokinetic interaction was observed between rivastigmine and digoxin, warfarin, diazepam or fluoxetine in studies in healthy volunteers. The increase in prothrombin time induced by warfarin is not affected by administration of rivastigmine. No untoward effects on cardiac conduction were observed following concomitant administration of digoxin and Rivastigmina.

Food Interaction

• Take with food. Administering rivastigmine capsules with food delays absorption but increases the AUC.

Rivastigmina Drug Interaction

Moderate: donepezil, escitalopram, metoprolol, quetiapineUnknown: aspirin, aspirin, docusate, apixaban, omega-3 polyunsaturated fatty acids, polyethylene glycol 3350, mirabegron, memantine, memantine, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, alprazolam, rivaroxaban

Rivastigmina Disease Interaction

Major: bradycardia, bronchospasm, parkinsonism, PUD, seizures

Volume of Distribution

• 1.8 to 2.7 L/kg

Half Life

1.5 hours

Clearance

• renal cl=2.1-2.8 L/hr

Elimination Route

Rivastigmina 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.

Pregnancy & Breastfeeding use

For Rivastigmina no clinical data are available. Rivastigmina should not be used during pregnancy unless clearly necessary. In animals, rivastigmine is excreted into milk. It is not known if rivastigmine is excreted into human milk. Therefore, women on rivastigmine should not breast-feed.

Contraindication

The use of this medicinal product is contraindicated in patients with hypersensitivity to the active substance or other carbamate derivatives.

Acute Overdose

Most cases of accidental overdose have not been associated with any clinical signs or symptoms and almost all of the patients concerned continued rivastigmine treatment. Where symptoms have occurred, they have included nausea, vomiting and diarrhoea, hypertension or hallucinations. Due to the known vagotonic effect of cholinesterase inhibitors on heart rate, bradycardia and/or syncope may also occur. Ingestion of 46 mg occurred in one case; following conservative management the patient fully recovered within 24 hours. As rivastigmine has a plasma half-life of about 1 hour and a duration of acetylcholinesterase inhibition of about 9 hours, it is recommended that in cases of asymptomatic overdose no further dose of rivastigmine should be administered for the next 24 hours. In overdose accompanied by severe nausea and vomiting, the use of antiemetics should be considered. Symptomatic treatment for other adverse reactions should be given as necessary. In massive overdose, atropine can be used. An initial dose of 0.03 mg/kg intravenous atropine sulphate is recommended, with subsequent doses based on clinical response. Use of scopolamine as an antidote is not recommended.

Storage Condition

Store in a cool and dry place, protected from light.

Innovators Monograph

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