Rivastigmine
Rivastigmine
Generic Name
Rivastigmine
Mechanism
- Rivastigmine is a *reversible* inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).
- By blocking these enzymes, it increases synaptic acetylcholine availability, enhancing cholinergic transmission in both cortical and limbic regions.
- The dual inhibition is advantageous in Alzheimer’s disease and Parkinson’s disease dementia, where BChE activity often rises as AChE declines.
Pharmacokinetics
| Parameter | Oral capsules | Transdermal patch (4.6 mg/24 h) |
| Absorption | ~60‑80 % bio‑available; peak trough at ~6 h after dose | Continuous steady‑state absorption; peak ~2 h after patch application |
| Half‑life | 1.2–1.4 h | 1.5–2.2 h (due to continuous release) |
| Distribution | Volume ≈ 13 L | 10–15 L |
| Metabolism | Primarily hepatic (Phase II) | Minor hepatic metabolism |
| Excretion | Renal (≈56 %); fecal (≈8 %) | Renal (≈70 %) |
| Food effect | Slows absorption; recommended with meals | None |
| Drug interactions | No major CYP interactions; caution with anticholinergics, β‑blockers, and agents causing bradycardia | Patch may increase skin sensitivity; no systemic drug interactions |
Indications
- Alzheimer’s disease dementia (mild–to‑moderate and severe).
- Parkinson’s disease dementia (mild–to‑moderate).
- Improves cognitive function, global clinical status, and activities of daily living.
Contraindications
- Hypersensitivity to rivastigmine or any excipient.
- Significant GI motility disorders (e.g., severe gastroparesis).
- Severe angina or uncontrolled arrhythmias (risk of bradycardia).
- Pregnancy/Lactation – not recommended; limited safety data.
- Pediatric use – not approved.
- Warnings – risk of cholinergic crisis (dyspnea, tremor, bradycardia); monitor vitals closely.
Dosing
| Formulation | Starting dose | Titration schedule | Maintenance dose | Notes |
| Oral capsule (1.5 mg) | 1.5 mg PO BID (after meals) | Increase by 1.5 mg BID every 4–6 weeks until 3 mg BID tolerated | 3 mg BID (max 6 mg BID) | Take with food to reduce GI upset |
| Transdermal patch | 4.6 mg/24 h (first patch) | Replace patch every 24 h; increase dose every 4 weeks if tolerated | 9.2 mg/24 h → 14.8 mg/24 h (max) | Do not cut or splice; apply to clean, dry, intact skin |
• Store at 20–25 °C, protected from light.
• For oral: do not triturate or crush.
• For patch: inspect dermal application site for erythema; discontinue if severe irritation.
Adverse Effects
Common (≥10 %)
• Nausea, vomiting, anorexia → weight loss
• Diarrhea, dyspepsia
• Dizziness, headache
• Fatigue, insomnia
Serious (≤1 %)
• Cholinergic crisis (bronchoconstriction, bradycardia, hypotension)
• Severe bradyarrhythmias or heart block
• Severe skin reactions (contact dermatitis) from the patch
• Severe constipation causing bowel obstruction (rare)
Monitoring for Serious AEs – check pulse, BP, heart rhythm, especially in patients with heart disease or on β‑blockers.
Monitoring
- Vitals: HR, BP at baseline, 1 wk, 4 wk, then every 3 months.
- Weight: baseline and every 4 weeks; address anorexia promptly.
- Cognitive Assessment: MMSE or MoCA at baseline, 3 mo, 6 mo, then quarterly.
- Dermatologic: patch site inspection at each clinic visit.
- Laboratory: baseline renal and hepatic panels if impaired function; adjust dose or monitor more often.
Clinical Pearls
- Patch Preference – Use the transdermal system in patients with gastric intolerance or when consistent oral dosing is difficult.
- Titration – A typical titration curve reaches target dose in ~2–4 months; patience reduces dropout from GI side effects.
- Abrupt Discontinuation – May precipitate sudden cognitive decline and cholinergic withdrawal; taper slowly when switching away.
- Weight Loss Management – Pair rivastigmine with high‑calorie nutritional support and consider appetite stimulants if needed.
- Cardiac Safety – Baseline ECG recommended in patients >65 y with cardiovascular disease; pause or reduce dose if bradyarrhythmias occur.
- Drug‑Drug Safety – Avoid concomitant anticholinergic medications (e.g., diphenhydramine, oxybutynin) that counteract therapeutic benefit and heighten GI upset.
- Compliance Aid – For memory‑impaired patients, use a daily pill organizer and reinforce with family caregivers.
- Skin Care – Rotate application sites; wash with mild soap if patch irritation develops; consider a lower‑dose patch if dermatitis persists.
- Pregnancy/Lactation – Data are lacking; generally avoid unless benefits outweigh theoretical risks.
- Research Note – Emerging evidence suggests rivastigmine may modestly improve gait disturbances in Parkinson’s disease; however, formal indications remain limited.
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