Rivastigmine

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include the following:

• nausea
• vomiting
• increased saliva
• sweating
• slow heart beat
• inability to hold urine
• slowed thinking and movement
• dizziness
• fainting
• blurred vision
• difficulty breathing
• loss of consciousness
• seizure

Rivastigmine is a prescription medication used to treat dementia in people with Alzheimer's disease or Parkinson's disease. Rivastigmine belongs to a group of drugs called acetylcholinesterase inhibitors. It works by increasing the amount of certain natural subtances to improve mental function. 

Rivastigmine is a prescription medicine used to treat dementia in people with Alzheimer's disease or Parkinson's disease.

You should not take oral rivastigmine if you have ever had severe redness, itching, or skin irritation caused by wearing a rivastigmine transdermal skin patch.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include severe nausea, vomiting, salivation, sweating, slow heartbeats, weak or shallow breathing, fainting, or seizure (convulsions).

Dosing in Alzheimer's Disease

Rivastigmine tartrate capsules should be taken with meals in divided doses in the morning and evening.

The recommended dosage of Rivastigmine tartrate capsules in Alzheimer's disease is 6 mg to 12 mg per day, administered twice a day (daily doses of 3 mg to 6 mg twice a day). There is evidence from the clinical trials that doses at the higher end of this range may be more beneficial.

Initial Dose

Initiate treatment with the 1.5 mg twice a day with Rivastigmine tartrate capsules.

Dose Titration

After a minimum of 2 weeks and if well tolerated, increase the dose to 3 mg twice a day. Subsequent increases to 4.5 mg twice a day and 6 mg twice a day should be attempted after a minimum of 2 weeks at the previous dose and if well tolerated. The maximum dose is 6 mg twice a day (12 mg per day).

Dosing in Parkinson's Disease Dementia

Rivastigmine tartrate capsules should be taken with meals in divided doses in the morning and evening.

The dosage of Rivastigmine tartrate capsules shown to be effective in the single controlled clinical trial conducted in dementia associated with Parkinson's disease is 3 mg to 12 mg per day, administered twice a day (daily doses of 1.5 mg to 6 mg twice a day).

Initial Dose

Initiate treatment with the 1.5 mg twice a day with Rivastigmine tartrate capsules.

Dose Titration

After a minimum of 4 weeks and if well tolerated, increase the dose to 3 mg twice a day. Subsequent increases to 4.5 mg twice a day and 6 mg twice a day should be attempted after a minimum of 4 weeks at the previous dose and if well tolerated. The maximum dose is 6 mg twice a day (12 mg per day).

Interruption of Treatment

If adverse effects (e.g., nausea, vomiting, abdominal pain, loss of appetite) cause intolerance during treatment, the patient should be instructed to discontinue treatment for several doses and then restart at the same or next lower dose level.

If dosing is interrupted for 3 days or fewer, restart treatment with the same or lower dose of Rivastigmine tartrate capsules. If dosing is interrupted for more than 3 days, treatment should be restarted with 1.5 mg twice a day and titrated as described above [see Warnings and Precautions (5.1)].

Dosing in Specific Populations

Dosing Modifications in Patients with Renal Impairment

Patients with moderate and severe renal impairment may be able to only tolerate lower doses.

Dosing Modifications in Patients with Hepatic Impairment

Patients with mild (Child-Pugh score 5 to 6) and moderate (Child-Pugh score 7 to 9) hepatic impairment may be able to only tolerate lower doses. No data are available on the use of Rivastigmine in patients with severe hepatic impairment.

Dosing Modifications in Patients with Low Body Weight

Carefully titrate and monitor patients with low body weight (less than 50 kg) for toxicities (e.g., excessive nausea, vomiting), and consider reducing the dose if such toxicities develop.

Important Administration Instructions

Rivastigmine tartrate oral solution and Rivastigmine tartrate capsules may be interchanged at equal doses.

Metoclopramide

Due to the risk of additive extrapyramidal adverse reactions, the concomitant use of metoclopramide and Rivastigmine tartrate is not recommended.

Cholinomimetic and Anticholinergic Drugs

Rivastigmine tartrate may increase the cholinergic effects of other cholinomimetic medications and may also interfere with the activity of anticholinergic medications (e.g., oxybutynin, tolterodine). Concomitant use of Rivastigmine tartrate with medications having these pharmacologic effects is not recommended unless deemed clinically necessary [see Warnings and Precautions (5.3)].

Beta-blockers

Additive bradycardic effects resulting in syncope may occur when Rivastigmine tartrate is used concomitantly with beta-blockers, especially cardioselective beta-blockers (including atenolol). Concomitant use of Rivastigmine tartrate with beta-blockers is not recommended.

Because strategies for the management of overdose are continually evolving, it is advisable to contact a Poison Control Center to determine the latest recommendations for the management of an overdose of any drug.

As Rivastigmine has a short plasma half-life of about 1 hour and a moderate duration of acetylcholinesterase inhibition of 8 to 10 hours, it is recommended that in cases of asymptomatic overdoses, no further dose of Rivastigmine tartrate should be administered for the next 24 hours.

As in any case of overdose, general supportive measures should be utilized.

Overdosage with cholinesterase inhibitors can result in cholinergic crisis characterized by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Atypical responses in blood pressure and heart rate have been reported with other drugs that increase cholinergic activity when coadministered with quaternary anticholinergics such as glycopyrrolate. Additional symptoms associated with Rivastigmine overdose are diarrhea, abdominal pain, dizziness, tremor, headache, somnolence, confusional state, hyperhidrosis, hypertension, hallucinations and malaise. Due to the short half-life of Rivastigmine, dialysis (hemodialysis, peritoneal dialysis, or hemofiltration) would not be clinically indicated in the event of an overdose.

In overdoses accompanied by severe nausea and vomiting, the use of antiemetics should be considered. A fatal outcome has been rarely reported with Rivastigmine.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

In oral carcinogenicity studies conducted at doses up to 1.1 mg-base/kg/day in rats and 1.6 mg-base/kg/day in mice, Rivastigmine was not carcinogenic. These doses are less than the maximum recommended human dose (MRHD) of 12 mg per day on a mg/m2 basis.

Mutagenesis

Rivastigmine was clastogenic in in vitro chromosomal aberration assays in mammalian cells in the presence, but not the absence, of metabolic activation. Rivastigmine was negative in an in vitro bacterial reverse mutation (Ames) assay, an in vitro HGPRT assay, and in an in vivo mouse micronucleus test.

Impairment of Fertility

Rivastigmine had no effect on fertility or reproductive performance in rats at oral doses up to 1.1 mg-base/kg/day, a dose less than the MRHD on a mg/m2 basis.

Rx only

NDC 75834-133-60

Rivastigmine Tartrate
Capsules USP

1.5 mg*

60 CAPSULES

NIVAGEN
PHARMACEUTICALS

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Exelon: 1.5 mg [DSC], 3 mg [DSC], 4.5 mg [DSC], 6 mg [DSC]

Generic: 1.5 mg, 3 mg, 4.5 mg, 6 mg

Patch 24 Hour, Transdermal:

Exelon: 4.6 mg/24 hr (1 ea, 30 ea); 9.5 mg/24 hr (1 ea, 30 ea); 13.3 mg/24 hr (1 ea, 30 ea)

Generic: 4.6 mg/24 hr (30 ea); 9.5 mg/24 hr (1 ea, 30 ea); 13.3 mg/24 hr (30 ea)

Solution, Oral:

Exelon: 2 mg/mL (120 mL [DSC])

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

Absorption

Oral: Fasting: Rapid and complete within 1 hour; Transdermal patch: Within 30 to 60 minutes

Distribution

Vd: 1.8 to 2.7 L/kg; penetrates blood-brain barrier (CSF levels are ~40% of plasma levels following oral administration)

Metabolism

Extensively via cholinesterase-mediated hydrolysis in the brain; metabolite undergoes N-demethylation and/or sulfate conjugation hepatically; minimal CYP involvement; linear kinetics at 3 mg twice daily, but nonlinear at higher doses

Excretion

Urine (97% as metabolites); feces (0.4%)

Time to Peak

Oral: 1 hour; Transdermal patch: 8 to 16 hours following first dose

Mean oral clearance is 64% lower.

Mean oral clearance is 43% higher for unexplained reasons.

Alzheimer dementia:

Oral: Treatment of mild to moderate dementia of the Alzheimer type.

Transdermal: Treatment of mild, moderate, and severe dementia of the Alzheimer type.

Parkinson disease dementia: Treatment of mild to moderate dementia associated with Parkinson disease.

Hypersensitivity to rivastigmine, other carbamate derivatives, or any component of the formulation; history of application-site reactions with rivastigmine patch

Canadian labeling: Additional contraindications (not in US labeling): Severe hepatic impairment; history of severe skin reactions (eg, allergic dermatitis [disseminated], Stevens-Johnson syndrome) with oral or transdermal rivastigmine

Cognitive function at periodic intervals, symptoms of GI intolerance, weight

MILD TO MODERATE ALZHEIMER'S DISEASE:
ORAL:
-Initial dose: 1.5 mg orally twice a day
-Maintenance dose: After a minimum of 2 weeks of treatment, if the initial dosage is well tolerated, it can be increased to 3 mg twice a day; subsequent increases to 4.5 mg and 6 mg twice a day should be attempted only after a minimum of 2 weeks at the previous dosage

TRANSDERMAL PATCH:
-Initial Dose: 4.6 mg/24 hour patch applied to the skin once daily
-Maintenance Dose: After a minimum of 4 weeks of treatment at the initial dose, and if well tolerated, the dose can be increased to 9.5 mg/24 hours for as long as this dose is beneficial; the dose can then be increased to 13.3 mg/24 hours
-Maximum Dose: 13.3 mg/24 hour patch applied to skin daily; higher doses confer no appreciable additional benefit, and are associated with significant increase in the incidence of adverse events

SEVERE ALZHEIMER'S DISEASE:
TRANSDERMAL PATCH:
-Recommended dose: 13.3 mg/24 hours transdermal patch applied to skin once daily; replace with a new patch every 24 hours

Use: For the treatment of mild, moderate, or severe dementia of the Alzheimer's type (AD)

Data not available.