Tacrine hydrochloride
(THA, Tetrahydro-aminoacridine)
Tacrine hydrochloride (Cognex)
THA (Cognex)
Tetrahydroaminoacridine (Cognex)
Tacrine hydrochloride
( TAH-krin)
Pregnancy Category: C Cognex (Rx)

Classification: Psychotherapeutic drug for Alzheimer's disease

Action/Kinetics: During early stages of Alzheimer's disease, cholinergic neuronal pathways that project from the basal forebrain to the cerebral cortex and hippocampus may be affected. Symptoms of dementia may be due to a deficiency of acetylcholine. As a reversible CNS cholinesterase inhibitor, tacrine elevates acetylcholine levels in the cerebral cortex. There is no evidence tacrine alters progression of dementia. Rapidly absorbed after PO administration. Maximal plasma levels: 1-2 hr. Food will affect the bioavailability of tacrine. Extensively metabolized in the liver. Undergoes first-pass metabolism; can be overcome by increasing the dose. Elimination t 1/2: 2-4 hr. The average plasma levels are about 50% higher in females. Also, the mean tacrine levels in smokers are about one-third the levels of nonsmokers.

Uses: Treatment of mild to moderate dementia of the Alzheimer's type.

Contraindications: Hypersensitivity to tacrine or acridine derivatives. Use in clients previously treated with tacrine who developed jaundice (elevated total bilirubin > 3 mg/dL).

Special Concerns: May cause bradycardia--important in sick sinus syndrome. Use with caution in clients at risk for developing ulcers as the drug increases gastric acid secretion. Use with caution in clients with a history of abnormal liver function as indicated by abnormalities in serum ALT, AST, bilirubin, and GGT levels. Use with caution in clients with a history of asthma. There may be worsening of cognitive function following abrupt discontinuation of the drug. Safety and efficacy have not been determined in children with dementing illness.

Side Effects: Hepatic: Increased transaminase levels (most common reason for stopping the drug during treatment). GI: N&V;, diarrhea, dyspepsia, anorexia, abdominal pain, flatulence, constipation, glossitis, gingivitis, dry mouth or throat, stomatitis, increased salivation, dysphagia, esophagitis, gastritis, gastroenteritis, GI hemorrhage stomach ulcer, hiatal hernia, hemorrhoids, bloody stools, diverticulitis, fecal impaction, fecal incontinence, rectal hemorrhage cholelithiasis, cholecystitis, increased appetite. Musculoskeletal: Myalgia, fracture, arthralgia, arthritis, hypertonia, osteoporosis, tendinitis, bursitis, gout, myopathy. CNS: Precipitation of seizures (may also be due to Alzheimer's), dizziness, confusion, ataxia, insomnia, somnolence, tremor, agitation, depression, abnormal thinking, anxiety, hallucinations, hostility, migraine, convulsions vertigo, syncope, hyperkinesia, paresthesia, abnormal dreams, dysarthria, aphasia, amnesia, twitching, hypesthesia, delirium, paralysis, bradykinesia, movement disorders, cogwheel rigidity, paresis, neuritis, hemiplegia, Parkinson's disease, neuropathy, extrapyramidal syndrome, decreased or absent reflexes, tardive dyskinesia, dysesthesia, dystonia, encephalitis, coma apraxia, oculogyric crisis, akathisia, oral facial dyskinesia, Bell's palsy, nervousness, apathy, increased libido, paranoia, neurosis, suicidal episodes psychosis, hysteria. Respiratory: Rhinitis, URI, coughing, pharyngitis, sinusitis, bronchitis, pneumonia, dyspnea, epistaxis, chest congestion, asthma, hyperventilation, lower respiratory infection, hemoptysis, lung edema, lung cancer, acute epiglottitis. CV: Hypotension, hypertension, heart failure, MI, CVA angina pectoris, TIA, phlebitis, venous insufficiency, abdominal aortic aneurysm, atrial fibrillation or flutter, palpitation, tachycardia, bradycardia, pulmonary embolus, heart arrest premature atrial contractions, AV block bundle branch block. Dermatologic: Rash, facial and skin flushing, increased sweating, acne, alopecia, dermatitis, eczema, dry skin, herpes zoster, psoriasis, cellulitis, cyst, furunculosis, herpes simplex, hyperkeratosis, basal cell carcinoma, skin cancer, desquamation, seborrhea, squamous cell carcinoma, skin ulcer, skin necrosis, melanoma. GU: Bladder outflow obstruction, urinary frequency, urinary incontinence, UTI, hematuria, renal stone, kidney infection, glycosuria, dysuria, polyuria, nocturia, pyuria, cystitis, urinary retention, urinary urgency, vaginal hemorrhage genital pruritus, breast pain, urinary obstruction, impotence, prostate cancer, bladder tumor, renal tumor, renal failure, breast cancer, ovarian carcinoma epididymitis. Body as a whole: Headache, fatigue, chest pain, weight decrease, back pain, asthenia, chill, fever, malaise, peripheral edema, facial edema, dehydration, weight increase, cachexia, lipoma, heat exhaustion, sepsis, cholinergic crisis, death. Hematologic: Anemia, lymphadenopathy, leukopenia, thrombocytopenia, hemolysis, pancytopenia. Ophthalmologic: Conjunctivitis, cataract, dry eyes, eye pain, visual field defect, diplopia, amblyopia, glaucoma, hordeolum, vision loss, ptosis, blepharitis. Otic: Deafness, earache, tinnitus, inner ear infection, otitis media, labyrinthitis, inner ear disturbance. Miscellaneous: Purpura, hypercholesterolemia, diabetes mellitus, hypothyroid, hyperthyroid, unusual taste.

Overdose Management: Symptoms: Cholinergic crisis characterized by severe N&V;, sweating, bradycardia, salivation, hypotension, collapse, seizures, and increased muscle weakness (may paralyze respiratory muscles leading to death). Treatment: General supportive measures. IV atropine sulfate, titrated to effect, may be given in an initial dose of 1-2 mg IV with subsequent doses based on the response.

Drug Interactions: Anticholinergic drugs / Tacrine interferes with action of these drugs Bethanechol / Synergistic effects Cholinesterase inhibitors / Synergistic effects Cimetidine / Maximum tacrine levels Succinylcholine / Muscle relaxation Theophylline / Plasma theophylline levels; dose recommended.

How Supplied: Capsule: 10 mg, 20 mg, 30 mg, 40 mg

Dosage
?Capsules Alzheimer's disease.
Initial: 10 mg q.i.d. for at least 6 weeks; then, after 6 weeks, increase the dose to 20 mg q.i.d., providing there are no significant transaminase elevations and the client tolerates the treatment. Based on the degree of tolerance, the dose may be titrated, at 6-week intervals, to 30 or 40 mg q.i.d.
If transaminase elevations occur, modify the dose as follows:  If transaminase levels are less than or equal to 2 x ULN, continue treatment according to recommended titration and monitoring schedule. If transaminse levels are greater than 2 but equal to or less than 3 x ULN, treatment is continued according to recommended titraiton but levels are monitored weekly until they return to normal levels. If transaminase levels are more than 3 but equal to or less than 5 x ULN, the daily dose is reduced by 40 mg/day. Monitor ALT/SGPT levels weekly. Dose titration is resumed and every other week monitoring is undertaken when levels return to within normal limits. If transaminase levels are greater than 5 x ULN, stop treatment. Monitor closely for signs and symptoms associated with hepatitis; monitor levels until they are within normal limits.
Clients who are required to stop treatment due to elevated transaminase levels may be rechallenged once levels return to within normal range. Weekly monitoring of serum ALT/SGPT levels should be undertaken after rechallenging occurs. If rechallenged, the initial dose is 10 mg t.i.d. with levels monitored weekly. After 6 weeks on this dose, the client may begin dose titration if transaminase levels are acceptable.