ADLARITY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ADLARITY (ADLARITY).
ADLARITY is a transdermal formulation of donepezil, a reversible acetylcholinesterase inhibitor that increases acetylcholine levels in the central nervous system, improving cholinergic neurotransmission in the cerebral cortex.
| Metabolism | Metabolized by cytochrome P450 enzymes CYP3A4 and CYP2D6, and undergoes glucuronidation. |
| Excretion | Renal: ~60% as unchanged donepezil and metabolites (primarily donepezil, 6-O-desmethyl donepezil, and donepezil-N-oxide); fecal: ~15-20% (biliary excretion of metabolites); minor via urine as conjugates. |
| Half-life | Terminal half-life approximately 70 hours (range 50-100 hours); steady-state achieved within 14-21 days; once-daily dosing due to long half-life. |
| Protein binding | Approximately 96% bound to plasma proteins, mainly albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | Vd approximately 5-10 L/kg (central compartment ~1 L/kg, extensive tissue distribution); high Vd indicates extensive extravascular distribution, including brain penetration. |
| Bioavailability | Oral: absolute bioavailability ~100% (no first-pass effect); transdermal (ADLARITY): bioavailability approximately 30% compared to oral donepezil (due to lower dose and transdermal delivery rate). |
| Onset of Action | Oral: Clinical improvement may be observed within 3-6 weeks; cognitive enhancement detectable as early as 2-4 weeks in some patients. |
| Duration of Action | Duration is approximately 24 hours due to once-daily dosing; clinical effect sustained over 24 hours with steady-state concentrations; no acute tolerance reported. |
10 mg transdermal patch applied once daily to clean, dry, hairless skin on the back, chest, or upper arm.
| Dosage form | SYSTEM |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min; not recommended for severe renal impairment (GFR <30 mL/min). |
| Liver impairment | No dose adjustment required for Child-Pugh A or B; not recommended for Child-Pugh C. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required for elderly patients; monitor for increased anticholinergic side effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ADLARITY (ADLARITY).
| Breastfeeding | It is not known whether donepezil is excreted in human breast milk. No M/P ratio is available. Due to the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | ADLARITY (donepezil transdermal system) is classified as Pregnancy Category C. Animal studies have shown an increased incidence of stillbirths and decreased offspring survival at doses 21 times the maximum recommended human dose (MRHD). There are no adequate and well-controlled studies in pregnant women. In the first trimester, risk cannot be ruled out; second and third trimester risks are undetermined but potential fetal harm exists based on animal data. |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
["Hypersensitivity to donepezil or piperidine derivatives","History of severe bradycardia or sick sinus syndrome"]
| Precautions | ["Potential for cholinergic effects (e.g., bradycardia, syncope)","Weight loss","Gastrointestinal bleeding risk (especially with NSAIDs)","Risk of seizures","Pulmonary effects (e.g., exacerbation of asthma/COPD)","Fertility impairment"] |
| Food/Dietary | No specific food interactions, but take with food to reduce gastrointestinal side effects like nausea and diarrhea; avoid excessive alcohol due to potential additive central nervous system effects. |
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| Fetal Monitoring | Monitor maternal vital signs, including heart rate and blood pressure, as donepezil can cause bradycardia and hypotension. Assess for signs of gastrointestinal bleeding or ulceration. In the fetus, monitor growth and development via ultrasound if clinically indicated, though no specific fetal monitoring is mandated. |
| Fertility Effects | In animal studies, donepezil did not impair fertility in rats at doses up to 21 times the MRHD. No human studies on fertility effects are available. Based on its cholinergic mechanism, theoretical effects on reproductive function cannot be excluded but are not well-documented. |
| Clinical Pearls |
| Adlarity (donepezil transdermal system) is the first once-weekly transdermal patch for Alzheimer's disease. Apply to clean, dry, hairless skin on the back, thigh, or upper arm. Rotate sites. Avoid exposure to external heat sources (e.g., heating pads, sun) which can increase absorption. Assess for adverse effects: nausea, vomiting, diarrhea, insomnia, muscle cramps, fatigue, and weight loss. Monitor for bradycardia, especially in patients with sick sinus syndrome or concurrent beta-blockers. Cholinergic effects may exacerbate asthma, COPD, or urinary obstruction. Taper if discontinuing. |
| Patient Advice | Apply one patch to the back, thigh, or upper arm once every 7 days. · Choose a hairless area of clean, dry, intact skin; avoid irritated or oily skin. · Press firmly for 10 seconds to ensure adhesion; do not apply to areas with cuts or rashes. · Avoid exposing the patch to direct heat sources like heating pads, electric blankets, or prolonged sun. · If the patch falls off, apply a new one in a different site and continue the same weekly schedule. · Do not cut or trim the patch; use as is. · Common side effects include nausea, vomiting, diarrhea, and loss of appetite; report severe or persistent symptoms. · Contact your doctor if you experience very slow heartbeat, fainting, or difficulty urinating. · Do not wear multiple patches at once; remove the old patch before applying a new one. · Keep the patch away from children and pets; dispose of used patches by folding adhesive sides together and discarding in trash. |