Schedule H

Oral, Transdermal

• Capsules: 1.5 mg, 3 mg, 4.5 mg, 6 mg

• Transdermal Patch: 4.6 mg/24 hr, 9.5 mg/24 hr, 13.3 mg/24 hr

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Alzheimer's Disease — Mild to Moderate

Oral Formulation:

Parameter Recommendation

Starting dose 1.5 mg orally twice daily with food

Titration Increase by 1.5 mg twice daily every 2 weeks (minimum) based on tolerability

Usual maintenance dose 3–6 mg twice daily

Maximum dose 6 mg twice daily (12 mg/day)

Transdermal Patch:

Parameter Recommendation

Starting dose 4.6 mg/24 hr patch applied once daily

Titration Increase to 9.5 mg/24 hr after minimum 4 weeks; may further increase to 13.3 mg/24 hr after another 4 weeks if tolerated and clinically indicated

Usual maintenance dose 9.5–13.3 mg/24 hr

Maximum dose 13.3 mg/24 hr

Clinical Notes:

• Administer oral formulation with morning and evening meals to reduce GI adverse effects

• Apply patch to clean, dry, hairless skin (upper back preferred); rotate application site daily to avoid irritation

• If therapy is interrupted for more than 3 days, re-titrate from the starting dose to avoid cholinergic crisis

• Patch formulation provides more stable plasma levels and better GI tolerability than oral

• Periodic cognitive assessment (MMSE or MoCA) recommended every 6 months to evaluate ongoing benefit

1. Parkinson's Disease Dementia — Mild to Moderate

Oral Formulation:

Parameter Recommendation

Starting dose 1.5 mg orally twice daily with food

Titration Increase by 1.5 mg twice daily every 2–4 weeks based on tolerability

Usual maintenance dose 3–6 mg twice daily

Maximum dose 6 mg twice daily (12 mg/day)

Transdermal Patch:

Parameter Recommendation

Starting dose 4.6 mg/24 hr patch applied once daily

Titration Increase to 9.5 mg/24 hr after minimum 4 weeks; may further increase to 13.3 mg/24 hr after another 4 weeks if tolerated

Usual maintenance dose 9.5–13.3 mg/24 hr

Maximum dose 13.3 mg/24 hr

Clinical Notes:

• Patch formulation preferred in Parkinson's disease dementia due to reduced GI adverse effects and tremor-related difficulty with oral medications

• Monitor for worsening of parkinsonian symptoms (tremor, rigidity) during initiation

• Cholinesterase inhibitors may provide benefit for visual hallucinations and cognitive fluctuations in PDD

Secondary Indications – Adults (Off-label, if any)

Indication Dose Duration Notes

Dementia with Lewy Bodies Oral: 1.5–6 mg twice daily OR Patch: 4.6–13.3 mg/24 hr (same titration as Alzheimer's) Long-term OFF-LABEL; Specialist only (Neurology/Geriatric Psychiatry); Evidence: RCTs support benefit; Similar pathology to PDD; Used in Indian tertiary centres

Vascular Dementia Same dosing as Alzheimer's disease Long-term OFF-LABEL; Specialist only; Limited evidence; May benefit mixed dementia or uncertain pathology

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

NOT APPROVED for use in children and adolescents below 18 years in India.

• Safety and efficacy not established in paediatric population

• Dementia syndromes requiring cholinesterase inhibitors are not typical in children

Secondary Indications – Paediatrics (Off-label, if any)

Indication Dose Notes

Niemann-Pick Disease Type C (Cognitive decline) Individualised; typically starting 1.5 mg twice daily with cautious titration OFF-LABEL; Specialist only (Paediatric Neurology); Very limited evidence from case series and small studies; Research setting only

Not recommended below 18 years except under specialist supervision in tertiary research centres for rare neurodegenerative conditions.

Moderate impairment (eGFR 30–59) Use with caution; slower titration; transdermal patch may provide more stable drug levels

Severe impairment (eGFR <30) Use only with specialist oversight; prefer patch formulation; slower titration

Haemodialysis Limited data; use with caution under specialist supervision

• Known hypersensitivity to rivastigmine or other carbamate derivatives

• Known hypersensitivity to any excipient in the formulation

• History of allergic contact dermatitis or application site reactions with rivastigmine patch (for patch formulation)

• Severe hepatic impairment

• Sick sinus syndrome, sinoatrial block, or atrioventricular block — risk of severe bradycardia

• Active peptic ulcer disease or history of GI bleeding — cholinergic stimulation increases gastric acid secretion

• History of seizure disorder — cholinergic drugs may lower seizure threshold

• Asthma or chronic obstructive pulmonary disease — risk of cholinergic bronchoconstriction

• Bladder outflow obstruction or prostatic hypertrophy

• Low body weight (<50 kg) — increased susceptibility to adverse effects; consider lower maximum dose

• Concurrent use of other cholinergic agents or cholinesterase inhibitors

• If therapy interrupted for more than 3 days — must re-titrate from starting dose

• Risk of severe vomiting with rapid dose escalation — can lead to oesophageal rupture (rare)

• Skin conditions that may affect patch adhesion or absorption

Parameter Details

Risk Category Limited human data; animal studies do not indicate significant teratogenicity but data insufficient

Recommendation Avoid during pregnancy; Alzheimer's disease and PDD are not typical in pregnancy age group

Preferred Alternatives Non-pharmacological cognitive interventions; defer drug therapy if possible

When May Be Used Only if potential benefit clearly outweighs risk; requires specialist input (extremely rare scenario)

Monitoring If exposure occurs, monitor fetal growth and development

Parameter Details

Compatibility Not recommended during breastfeeding

Drug Levels in Milk Unknown; excretion in human milk not studied

Preferred Alternatives Avoid rivastigmine during lactation; delay therapy or avoid breastfeeding if treatment essential

Infant Monitoring If inadvertent exposure, monitor infant for cholinergic effects (excessive salivation, diarrhoea, feeding difficulties, hypotonia)

Parameter Recommendation

Starting dose Oral: 1.5 mg twice daily; Patch: 4.6 mg/24 hr

Titration Slower titration recommended (every 4 weeks rather than 2 weeks); especially in frail elderly or those with multiple comorbidities

Special Risks Increased risk of falls (due to dizziness, syncope), bradycardia, orthostatic hypotension, weight loss, GI adverse effects

Monitoring Regular weight monitoring; heart rate and blood pressure; cognitive reassessment; falls risk assessment

Low Body Weight (<50 kg) Consider limiting maximum dose; increased adverse effect susceptibility

Note: Elderly patients are the primary population for this drug; most clinical trial data are from elderly patients.

Interacting Drug Mechanism / Effect Recommendation

Anticholinergic agents (oxybutynin, tolterodine, tricyclic antidepressants, antihistamines, antipsychotics with anticholinergic properties) Pharmacological antagonism; reduces rivastigmine efficacy Avoid combination; if essential, choose agent with least anticholinergic burden; review medication list for hidden anticholinergics

Beta-blockers (especially non-selective) Additive bradycardia and conduction abnormalities Monitor heart rate closely; use with caution; consider cardioselective beta-blocker at lowest dose

Digoxin Additive bradycardia Monitor heart rate; combination may be used with caution

Succinylcholine and similar neuromuscular blocking agents Prolonged neuromuscular blockade during anaesthesia Inform anaesthetist before surgery; dose adjustment of muscle relaxant may be needed

Metoclopramide Increased risk of extrapyramidal symptoms Avoid combination; use alternative antiemetic (ondansetron)

Other cholinesterase inhibitors (donepezil, galantamine, pyridostigmine) Therapeutic duplication; additive cholinergic toxicity Avoid combination; do not use concurrently

Interacting Drug Mechanism / Effect Recommendation

NSAIDs Increased risk of GI bleeding (cholinergic stimulation + NSAID gastrotoxicity) Co-prescribe PPI for gastroprotection if long-term use necessary

QT-prolonging drugs (macrolides, fluoroquinolones, antipsychotics, ondansetron) Rivastigmine may cause bradycardia; combined with QT-prolonging drugs increases arrhythmia risk ECG monitoring if combination essential

Antihypertensives Additive hypotensive effect; increased syncope risk Monitor blood pressure; falls risk counselling

CYP450 inducers (rifampicin, carbamazepine, phenytoin) Theoretical reduction in efficacy (minimal CYP involvement for rivastigmine but possible) Monitor cognitive response

Cholinergic agonists (bethanechol, pilocarpine) Additive cholinergic effects Avoid or use with caution; monitor for excess cholinergic effects

Oral Formulation:

• Nausea (most common; dose-related)

• Vomiting

• Diarrhoea

• Anorexia and weight loss

• Dizziness

• Headache

• Asthenia / fatigue

• Abdominal pain

• Insomnia

• Tremor

Transdermal Patch:

• Application site reactions (erythema, pruritus, oedema)

• Nausea (less common than oral)

• Vomiting (less common than oral)

• Dizziness

• Headache

• Weight loss

Note: GI adverse effects are significantly reduced with patch formulation compared to oral.

Adverse Effect Clinical Action

Severe bradycardia / Heart block / Syncope Discontinue immediately; ECG monitoring; cardiology referral if symptomatic

Severe nausea/vomiting with dehydration Discontinue; rehydration; may reinitiate at lower dose after recovery; rapid titration increases risk

Oesophageal rupture (rare; associated with severe vomiting) Emergency surgical consultation

Seizures Discontinue; neurological evaluation

GI bleeding / Peptic ulceration Discontinue; appropriate GI management

Stevens-Johnson Syndrome (very rare; oral formulation) Discontinue immediately; dermatology referral; supportive care

Allergic contact dermatitis (patch) Remove patch immediately; do not rechallenge with patch; may switch to oral if tolerated

Disseminated allergic dermatitis (patch; rare) Discontinue all rivastigmine formulations; dermatology referral

Extrapyramidal symptoms (worsening parkinsonism) Dose reduction or discontinuation may be required; neurology review

2–4 weeks post-initiation/dose change GI tolerability, heart rate, blood pressure, weight, CNS adverse effects (dizziness, headache)

For patch formulation Skin examination at application sites at each visit

Every 3 months Weight, heart rate, tolerability, falls risk assessment

Every 6 months Cognitive assessment (MMSE/MoCA), functional status, comprehensive adverse effects review, reassess ongoing benefit

Annually Hepatic function, renal function (in at-risk patients), comprehensive review of indication and benefit

Oral Formulations:

• Exelon (Novartis) — Capsules

• Rivamer (Sun Pharma) — Capsules

• Rivastig (Cipla) — Capsules

• Rivagen (Torrent) — Capsules

• Ristia (Intas) — Capsules

• Alzil-R (Generic manufacturers)

Transdermal Patch:

• Exelon Patch (Novartis)

• Rivamer Patch (Sun Pharma)

• Rivadem Patch (Intas)

Note: FDCs not applicable for rivastigmine.

• Not included in NLEM; pricing not NPPA-controlled

• Patch formulation significantly more expensive than oral

• Private market pricing; limited government supply

• Patch formulation is preferred over oral in patients with significant GI intolerance, swallowing difficulties, or Parkinson's disease dementia — provides more stable plasma levels and approximately 50% reduction in GI adverse effects

• Critical re-titration rule: If therapy is interrupted for more than 3 days, must restart from the lowest starting dose and re-titrate to avoid cholinergic crisis (severe nausea, vomiting, salivation, bradycardia)

• Weight monitoring is essential, particularly in frail elderly — anorexia and weight loss are common and may necessitate dose reduction or supplemental nutrition

• Unlike donepezil which inhibits only acetylcholinesterase, rivastigmine also inhibits butyrylcholinesterase — theoretical advantage in advanced disease but clinical significance uncertain

• For patch application: upper back is preferred site (out of patient's reach, reduces self-removal risk in confused patients); avoid arms in active patients; never cut patches

• Baseline ECG advisable in elderly patients with cardiac history or on other drugs affecting heart rate — significant bradycardia can occur and may be asymptomatic initially

• When switching from oral to patch: Oral 3–6 mg twice daily may be switched to 9.5 mg/24 hr patch; oral <3 mg twice daily may be switched to 4.6 mg/24 hr patch

Rivastigmine; Alzheimer's disease; dementia; Parkinson's disease dementia; cholinesterase inhibitor; cognitive enhancer; transdermal patch; elderly care; bradycardia risk; GI intolerance; Schedule H

RxIndia v1.0 — 12 Apr 2025

• CDSCO approved product information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI) 2021

• API Textbook of Medicine — Dementia chapter

• AIIMS Geriatric Medicine and Neurology Treatment Protocols

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Novartis India Product Insert (Exelon)

• Indian Psychiatric Society Clinical Practice Guidelines for Dementia