No

Acetylcholinesterase Inhibitor (Central)

Treatment of mild to moderate dementia of the Alzheimer's type

C

Patients previously treated with the drug who developed jaundice; hypersensitivity to tacrine or acridine derivatives

The use of tacrine has been associated with elevations in serum transaminases; serum transaminases (specifically ALT) must be monitored throughout therapy; use extreme caution in patients with current evidence of a history of abnormal liver function tests; use caution in patients with urinary tract obstruction (bladder outlet obstruction or prostatic hypertrophy), asthma, and sick-sinus syndrome (tacrine may cause bradycardia). Also, patients with cardiovascular disease, asthma, or peptic ulcer should use cautiously. Use with caution in patients with a history of seizures. May cause nausea, vomiting, or loose stools. Abrupt discontinuation or dosage decrease may worsen cognitive function. May be associated with neutropenia.

>10%

Central nervous system: Headache, dizziness

Gastrointestinal: Nausea, vomiting, diarrhea

Miscellaneous: Elevated transaminases

1% to 10%

Cardiovascular: Flushing

Central nervous system: Confusion, ataxia, insomnia, somnolence, depression, anxiety, fatigue

Dermatologic: Rash

Gastrointestinal: Dyspepsia, anorexia, abdominal pain, flatulence, constipation, weight loss

Neuromuscular & skeletal: Myalgia, tremor

Respiratory: Rhinitis

General supportive measures; can cause a cholinergic crisis characterized by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions; increased muscle weakness is a possibility and may result in death if respiratory muscles are involved

Tertiary anticholinergics, such as atropine, may be used as an antidote for overdosage. I.V. atropine sulfate titrated to effect is recommended; initial dose of 1-2 mg I.V. with subsequent doses based upon clinical response. Atypical increases in blood pressure and heart rate have been reported with other cholinomimetics when coadministered with quaternary anticholinergics such as glycopyrrolate.

CYP1A2 enzyme substrate; CYP1A2 inhibitor

Tacrine in combination with beta blockers may produce additive bradycardia

Smoking may reduce tacrine plasma levels via enzyme induction (CYP1A2)

Fluvoxamine, enoxacin, and cimetidine increase tacrine concentrations via enzyme inhibition (CYP1A2)

Tacrine may worsen Parkinson's disease and inhibit the effects of levodopa

Tacrine may prolong the effect of succinylcholine

Tacrine may inhibit the metabolism of theophylline resulting in elevated plasma levels; dose adjustment will likely be needed

Tacrine may antagonize the therapeutic effect of anticholinergic agents (benztropine, trihexphenidyl)

Centrally-acting cholinesterase inhibitor. It elevates acetylcholine in cerebral cortex by slowing the degradation of acetylcholine.

Onset of effect: May require weeks of treatment

Peak plasma concentrations: 1-2 hours

Plasma bound: 55%

Serum half-life, elimination: 2-4 hours, steady-state achieved in 24-36 hours

Adults: Initial: 10 mg 4 times/day; may increase by 40 mg/day adjusted every 6 weeks; maximum: 160 mg/day; best administered separate from meal times.

ALT less than or equal to 3 x ULN*: Continue titration

ALT >3 to less than or equal to 5 x ULN*: Decrease dose by 40 mg/day, resume when ALT returns to normal

ALT >5 x ULN*: Stop treatment, may rechallenge upon return of ALT to normal

*ULN = upper limit of normal

Patients with clinical jaundice confirmed by elevated total bilirubin (>3 mg/dL) should not be rechallenged with tacrine

ALT (SGPT) levels and other liver enzymes weekly for at least the first 18 weeks, then monitor once every 3 months

In clinical trials, serum concentrations >20 ng/mL were associated with a much higher risk of development of symptomatic adverse effects

No information available to require special precautions

No effects or complications reported

This medication will not cure the disease, but may help reduce symptoms. Use as directed; do not increase dose or discontinue without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). May cause dizziness, sedation, or hypotension (rise slowly from sitting or lying position and use caution when driving or climbing stairs); vomiting or loss of appetite (frequent small meals, frequent mouth care, or chewing gum, or sucking lozenges may help); or diarrhea (boiled milk, yogurt, or buttermilk may help). Report persistent abdominal discomfort; significantly increased salivation, sweating, tearing, or urination; flushed skin; chest pain or palpitations; acute headache; unresolved diarrhea; excessive fatigue, insomnia, dizziness, or depression; increased muscle, joint, or body pain; vision changes or blurred vision; shortness of breath or wheezing; or signs of jaundice (yellowing of eyes or skin, dark colored urine or light colored stool, abdominal pain, or easy fatigue). Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Monitor ALT levels and other liver enzymes weekly for at least the first 18 weeks, then monitor once every 3 months

Capsule, as hydrochloride: 10 mg, 20 mg, 30 mg, 40 mg

Byrne J and Arie T, "Tetrahydroaminoacridine (THA) in Alzheimer's Disease," BMJ, 1989, 298(6677):845-6.

Crismon ML, "Tacrine: First Drug Approved for Alzheimer's Disease," Ann Pharmacother, 1994, 28(6):744-51.

Davis KL and Powchik P, "Tacrine," Lancet, 1995, 345(8950):625-30.

Davis KL, Thal LJ, Gamzu ER, et al, "A Double-Blind, Placebo-Controlled Multicenter Study of Tacrine for Alzheimer's Disease," N Engl J Med, 1992, 327(18):1253-9.

Eagger SA, Levy R, Sahakian BJ, et al, "Tacrine in Alzheimer's Disease," Lancet, 1991, 338(8758):50-1.

Farlow M, Gracon SI, Hershey LA, et al, "A Controlled Trial of Tacrine in Alzheimer's Disease," JAMA, 1992, 268(18):2523-9.

Knapp MJ, Knopman DS, Solomon PR, et al, "A 30-Week Randomized Controlled Trial of High-Dose Tacrine in Patients With Alzheimer's Disease," JAMA, 1994, 271(13):985-91.

Madden S, Spaldin V, and Park BK, "Clinical Pharmacokinetics of Tacrine," Clin Pharmacokinet, 1995, 28(6):449-57.

Watkins PB, Zimmerman HJ, Knapp MJ, et al, "Hepatotoxic Effects of Tacrine Administration in Patients With Alzheimer's Disease," JAMA, 1994, 271(13):992-8.