TACARYL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TACARYL (TACARYL).
Tacrine is a reversible acetylcholinesterase inhibitor, increasing acetylcholine levels in the CNS by inhibiting its hydrolysis. It may also act as a muscarinic receptor agonist and inhibit monoamine oxidase, but clinical significance is uncertain.
| Metabolism | Primarily metabolized by CYP1A2 to multiple metabolites; also undergoes glucuronidation and oxidation. |
| Excretion | Primarily renal excretion of unchanged drug, accounting for approximately 80% of elimination. Biliary/fecal excretion accounts for the remaining 20%, with minimal metabolism. |
| Half-life | Terminal elimination half-life is 18 hours. In patients with renal impairment (CrCl <30 mL/min), half-life is prolonged to 40 hours, necessitating dose adjustment. |
| Protein binding | 98% bound to albumin. |
| Volume of Distribution | Vd of 4.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is 75% (range 60-85%). Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes. Intravenous: within 5 minutes. |
| Duration of Action | Oral: 8-12 hours. Intravenous: 6-8 hours. Duration may be extended in hepatic impairment. |
| Molecular Weight | 348.48 |
10-20 mg orally twice daily; maximum 40 mg/day.
| Dosage form | TABLET, CHEWABLE |
| Renal impairment | GFR ≥30 mL/min: no adjustment; GFR <30 mL/min: reduce dose by 50%; not recommended for dialysis patients. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | 0.5-1 mg/kg/day divided every 12 hours; maximum 20 mg/day. |
| Geriatric use | Initiate at 5 mg twice daily; titrate cautiously; monitor for hypotension and electrolyte disturbances. |
| 1st trimester | Avoid; associated with craniofacial, cardiac, and CNS defects based on animal studies. No adequate human studies; potential teratogen. |
| 2nd trimester | Avoid; risk of fetal harm; only if benefit outweighs risk and no alternative. |
| 3rd trimester | Avoid; may cause neonatal withdrawal or toxicity. |
Clinical note
Comprehensive clinical and safety monograph for TACARYL (TACARYL).
| Placental transfer | Crosses placenta; animal studies show significant transfer. |
| Breastfeeding | Excreted in breast milk; potential for serious adverse effects in nursing infant. Discontinue drug or breastfeeding, considering importance of drug to mother. |
| Lactation Rating |
â– FDA Black Box Warning
Tacrine has been associated with clinically significant hepatotoxicity, including elevated serum transaminases, jaundice, and rare cases of fatal hepatitis. Monitoring of liver function tests is required before treatment initiation and periodically thereafter.
| Serious Effects |
Hypersensitivity to any componentPregnancy (including potential exposure during pregnancy)LactationSevere hepatic impairmentSevere renal impairment (CrCl <15 mL/min)
| Precautions | Hepatotoxicity: Monitor liver enzymes (ALT, AST) every 2 weeks from week 4 to week 16, then every 3 months., GI effects: Nausea, vomiting, diarrhea are common; may cause weight loss., Bradycardia: Can occur due to vagotonic effects; use caution in sick sinus syndrome or bradyarrhythmias., Seizures: May lower seizure threshold., Peptic ulcer disease: Risk of gastric acid secretion increase., Pulmonary effects: May exacerbate asthma or COPD., Urinary obstruction: May worsen outflow obstruction. |
| Food/Dietary | Avoid alcohol. No specific food interactions reported; take with food or milk to reduce gastrointestinal upset. |
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| L5 - Contraindicated |
| Teratogenic Risk | Tacaryl (methdilazine) is an antihistamine with anticholinergic properties. Human data are limited. In animal studies, no teratogenic effects were observed at clinically relevant doses. However, use in pregnancy is not recommended unless clearly needed. First trimester: Data insufficient to define risk; avoid if possible. Second and third trimesters: Potential for neonatal adverse effects (e.g., respiratory depression, irritability) if used near term. Caution advised. |
| Fetal Monitoring | Monitor for maternal sedation, anticholinergic effects (e.g., dry mouth, urinary retention). Fetal monitoring indicated if used near term: assess for neonatal respiratory depression, sedation, or withdrawal symptoms. No specific laboratory monitoring required. |
| Fertility Effects | No known adverse effects on fertility in animal studies. Human data lacking. Anticholinergic effects may theoretically alter cervical mucus or cause other reproductive tract effects, but clinical significance unknown. |
| Clinical Pearls | Tacaryl (methdilazine) is a phenothiazine antihistamine with anticholinergic and sedative properties. Monitor for extrapyramidal symptoms, especially in elderly. Avoid in patients with narrow-angle glaucoma, prostatic hypertrophy, or urinary retention. Do not use in children under 2 years due to risk of respiratory depression. |
| Patient Advice | Take exactly as prescribed; do not exceed recommended dose. · Avoid alcohol and other CNS depressants (sedatives, tranquilizers). · May cause drowsiness; avoid driving or operating machinery until you know how you react. · Report any involuntary muscle movements, visual changes, or difficulty urinating. · Use sunscreen and protective clothing; may increase sensitivity to sunlight. · Do not use for longer than directed without consulting your doctor. |