Rivastigmine

RIVASTIGMINE- rivastigmine patch, extended release
Sandoz Inc

1 INDICATIONS AND USAGE

1.1 Alzheimer’s Disease

Rivastigmine transdermal system is indicated for the treatment of dementia of the Alzheimer’s type (AD). Efficacy has been demonstrated in patients with mild, moderate, and severe Alzheimer’s disease.

1.2 Parkinson’s Disease Dementia

Rivastigmine transdermal system is indicated for the treatment of mild-to-moderate dementia associated with Parkinson’s disease (PDD).

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosing

Initial Dose

Initiate treatment with one 4.6 mg/24 hours rivastigmine transdermal system applied to the skin once daily [see Dosage and Administration (2.4)].

Dose Titration

Increase the dose only after a minimum of 4 weeks at the previous dose, and only if the previous dose has been tolerated. For mild-to-moderate AD and PDD patients, continue the effective dose of 9.5 mg/24 hours for as long as therapeutic benefit persists. Patients can then be increased to the maximum effective dose of 13.3 mg/24 hours dose. For patients with severe AD, 13.3 mg/24 hours is the effective dose. Doses higher than 13.3 mg/24 hours confer no appreciable additional benefit, and are associated with an increase in the incidence of adverse reactions [see Warnings and Precautions (5.2), Adverse Reactions (6.1)].

Mild-to-Moderate Alzheimer’s Disease and Mild-to-Moderate Parkinson’s Disease Dementia

The effective dosage of rivastigmine transdermal system is 9.5 mg/24 hours or 13.3 mg/24 hours administered once per day; replace with a new patch every 24 hours.

Severe Alzheimer’s Disease

The effective dosage of rivastigmine transdermal system in patients with severe Alzheimer’s disease is 13.3 mg/24 hours administered once per day; replace with a new patch every 24 hours.

Interruption of Treatment

If dosing is interrupted for 3 days or fewer, restart treatment with the same or lower strength rivastigmine transdermal system. If dosing is interrupted for more than 3 days, restart treatment with the 4.6 mg/24 hours rivastigmine transdermal system and titrate as described above.

2.2 Dosing in Specific Populations

Dosing Modifications in Patients with Hepatic Impairment

Consider using the 4.6 mg/24 hours rivastigmine transdermal system as both the initial and maintenance dose in patients with mild (Child-Pugh score 5 to 6) to moderate (Child-Pugh score 7 to 9) hepatic impairment [see Use in Specific Populations ( 8.6), Clinical Pharmacology (12.3)].

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 maintenance dose to the 4.6 mg/24 hours rivastigmine transdermal system if such toxicities develop.

2.3 Switching to Rivastigmine Transdermal System from Rivastigmine Tartrate Capsules or Rivastigmine Tartrate Oral Solution

Patients treated with rivastigmine tartrate capsules or oral solution may be switched to rivastigmine transdermal system as follows:

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A patient who is on a total daily dose of less than 6 mg of oral rivastigmine can be switched to the 4.6 mg/24 hours rivastigmine transdermal system.

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A patient who is on a total daily dose of 6 mg to 12 mg of oral rivastigmine can be switched to the 9.5 mg/24 hours rivastigmine transdermal system.

Instruct patients or caregivers to apply the first patch on the day following the last oral dose.

2.4 Important Administration Instructions

Rivastigmine transdermal system is for transdermal use on intact skin.

(a) Do not use the patch if the pouch seal is broken or the patch is cut, damaged, or changed in any way.

(b) Apply the rivastigmine transdermal system once a day.

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Press down firmly for 30 seconds until the edges stick well when applying to clean, dry, hairless, intact healthy skin in a place that will not be rubbed against by tight clothing.

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Use the upper or lower back as the site of application because the patch is less likely to be removed by the patient. If sites on the back are not accessible, apply the patch to the upper arm or chest.

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Do not apply to a skin area where cream, lotion, or powder has recently been applied.

(c) Do not apply to skin that is red, irritated, or cut.

(d) Replace the rivastigmine transdermal system with a new patch every 24 hours. Instruct patients to only wear 1 patch at a time (remove the previous day’s patch before applying a new patch) [see Warnings and Precautions (5.1), Overdosage (10)]. If a patch falls off or if a dose is missed, apply a new patch immediately, and then replace this patch the following day at the usual application time.

(e) Change the site of patch application daily to minimize potential irritation, although a new patch can be applied to the same general anatomic site (e.g., another spot on the upper back) on consecutive days. Do not apply a new patch to the same location for at least 14 days.

(f) May wear the patch during bathing and in hot weather. Avoid long exposure to external heat sources (excessive sunlight, saunas, solariums).

(g) Place used patches in the previously saved pouch and discard in the trash, away from pets or children.

(h) Wash hands with soap and water after removing the patch. In case of contact with eyes or if the eyes become red after handling the patch, rinse immediately with plenty of water, and seek medical advice if symptoms do not resolve.

3 DOSAGE FORMS AND STRENGTHS

Rivastigmine Transdermal System is available in 3 strengths. Each patch has a beige backing layer labeled as either:

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RIVASTIGMINE 4.6 mg/24 hours, AMCX

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RIVASTIGMINE 9.5 mg/24 hours, BHDI

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RIVASTIGMINE 13.3 mg/24 hours, CNFU

4 CONTRAINDICATIONS

Rivastigmine transdermal system is contraindicated in patients with:

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known hypersensitivity to rivastigmine, other carbamate derivatives, or other components of the formulation [see Description (11)].

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previous history of application-site reactions with rivastigmine transdermal patch suggestive of allergic contact dermatitis [see Warnings and Precautions (5.3)].

Isolated cases of generalized skin reactions have been described in postmarketing experience [see Adverse Reactions (6.2)].

5 WARNINGS AND PRECAUTIONS

5.1 Medication Errors Resulting in Overdose

Medication errors with rivastigmine transdermal system have resulted in serious adverse reactions; some cases have required hospitalization, and rarely, led to death. The majority of medication errors have involved not removing the old patch when putting on a new one and the use of multiple patches at one time.

Instruct patients and their caregivers on important administration instructions for rivastigmine transdermal system [see Dosage and Administration (2.4)].

5.2 Gastrointestinal Adverse Reactions

Rivastigmine transdermal system can cause gastrointestinal adverse reactions, including significant nausea, vomiting, diarrhea, anorexia/decreased appetite, and weight loss. Dehydration may result from prolonged vomiting or diarrhea and can be associated with serious outcomes. The incidence and severity of these reactions are dose-related [see Adverse Reactions (6.1)]. For this reason, initiate treatment with rivastigmine transdermal system at a dose of 4.6 mg/24 hours, and titrate to a dose of 9.5 mg/24 hours and then to a dose of 13.3 mg/24 hours, if appropriate [see Dosage and Administration (2.1)].

If treatment is interrupted for more than 3 days because of intolerance, reinitiate rivastigmine transdermal system with the 4.6 mg/24 hours dose to reduce the possibility of severe vomiting and its potentially serious sequelae. A postmarketing report described a case of severe vomiting with esophageal rupture following inappropriate reinitiation of treatment of an oral formulation of rivastigmine without retitration after 8 weeks of treatment interruption.

Inform caregivers to monitor for gastrointestinal adverse reactions and to inform the physician if they occur. It is critical to inform caregivers that if therapy has been interrupted for more than 3 days because of intolerance, the next dose should not be administered without contacting the physician regarding proper retitration.