Tacrine HCl (Tetrahydroaminoacridine; THA)

A to Z Drug Facts

 Action Believed to inhibit (reversibly) cholinesterase in CNS, leading to increased concentrations of acetylcholine.

 Indications Treatment of mild-to-moderate dementia of Alzheimer's type.

 Contraindications Hypersensitivity to acridine derivatives; previous treatment with tacrine that resulted in jaundice (confirmed by elevated total bilirubin > 3 mg/dl).

 Route/Dosage

ADULTS: Initial dose: PO 40 mg/day (10 mg 4 times daily). Maintain this dose for ³ 4 weeks with every other week monitoring of transaminase levels beginning at week 4 of therapy. Titration: PO Increase the dose to 80 mg/day (20 mg 4 times daily), providing there are no significant transaminase elevations and the patient is tolerating treatment. Titrate patients to higher doses (120 and 160 mg/day in divided doses on a 4 times daily schedule) at 4–week intervals on the basis of tolerance.

 Interactions

Cimetidine: Increased tacrine concentrations. Levodopa: The antiparkinsonism effects of levodopa may be inhibited. Theophylline: Increased theophylline concentrations.

 Lab Test Interferences None well documented.

 Adverse Reactions

CV: Hypotension; hypertension; chest pain; edema; heart failure; MI; cerebrovascular accident; pulmonary embolism. CNS: Headache; dizziness; agitation; confusion; ataxia; insomnia; depression; anxiety; drowsiness; tremor; convulsions; fainting; hyperkinesia; tingling; coma. DERM: Rash; facial and skin flushing; sweating. EENT: Conjunctivitis; sinusitis; pharyngitis. GI: Nausea; vomiting; diarrhea; upset stomach; anorexia; abdominal pain; flatulence; constipation; GI hemorrhage. GU: Urinary frequency; UTI; urinary incontinence; urinary retention. HEMA: Purpura; anemia; lymphadenopathy; leukopenia; thrombocytopenia; hemolysis; pancytopenia. HEPA: Elevated transaminases. RESP: Cough; bronchitis; pneumonia; shortness of breath. OTHER: Fatigue; weight decrease; back or muscle pain; cholinergic crisis.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. Children: Safety and efficacy not established in any dementing illness. Anesthesia: Use of muscle relaxants (eg, succinylcholine) during anesthesia, while receiving tacrine, may lead to exaggerated effects. Carcinogenesis: May be carcinogenic. Concomitant medical conditions: Increases cholinergic activity and therefore can affect other organ systems, possibly leading to bradycardia, bladder outflow obstruction, increased gastric acid secretion, or bronchoconstriction. Use drug with caution in patients susceptible to these effects. Hepatic effects: Use drug with caution in patients with history of abnormal liver function. Neurologic conditions: Drug may contribute to seizures. Cognitive function may worsen after discontinuation or large dose reductions.

 Administration/Storage

• Give between meals when possible. May be taken with meals to minimize GI irritation; however, food reduces absorption.
• Check to see that medication is swallowed.
• Store in tight, light-resistant container.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies.
• Determine whether jaundice developed when patient was previously treated with tacrine or whether patient has history of hepatic dysfunction.
• Assess baseline mental status: sensorium, appearance, behavior, mood and short-term and long-term memory.
• Obtain baseline weight, heart rate, and BP.
• Monitor for weight gain and fluctuations in vital signs. Report abnormal findings immediately to physician.
• Monitor mental status frequently.
• Determine baseline hepatic function (especially transaminase levels, bilirubin). Monitor serum tacrine level and hepatic function weekly for first 18 weeks and then every 3 months. Observe for evidence of hepatic damage. Return to weekly testing for 6 weeks after every dose increase or as results warrant. Total bilirubin > 3 mg/dl indicates tacrine intolerance; withhold drug and notify physician. Notify physician if transaminase levels are noted to be ³ 3 times upper limit of normal.
• Monitor daily bowel activity and stool quality (eg, consistency, color, presence of blood). Expect loose stool; explain this to patient/family. Report abnormal findings immediately to physician.
• Inspect oropharynx (eg, lips, mouth, tongue, gums, throat) for irritation/ulceration. Provide frequent mouth care.
• Monitor serum transaminase levels (specifically ALT) every other week from at least week 4 to week 16 following initiation of treatment, after which monitoring may be decreased to every 3 months. Repeat a full monitoring sequence in the event that a patient suspends treatment with tacrine for > 4 weeks.
• Continue to monitor ALT levels weekly for a total of 16 weeks, then decrease to monthly for 2 months and to every 3 months thereafter.

 Patient/Family Education

• Instruct patient/family to administer medication at regular intervals and between meals if possible. Drug may be taken with meals if GI upset occurs. Encourage consistency in dosage schedule (eg, every dose with meals or every dose between meals) because drug level can be decreased when taken with food. Instruct family to ensure that medication is swallowed.
• Caution patient/family that drug dosage changes will be required during therapy and not to discontinue this medication abruptly or change dose without direct physician order.
• Emphasize need for continued monitoring of physical and mental status of patient. Home care or supervised living arrangements must be made prior to discharge.
• Instruct family to modify fluid and bulk in patient's diet to offset diarrhea/constipation.
• Advise patient to carry identification (Medi-Alert bracelet or written drug regimen in wallet) indicating drug regimen and condition.
• Instruct patient to notify other physicians and dentist prior to other therapy or surgery.
• Explain to patient/family that this drug is not cure but that it may slow progressive memory loss of Alzheimer's type.
• Emphasize importance of regular medical follow-up to monitor lab values and evaluate effectiveness of drug.
• Instruct family or persons responsible for patient to report the following symptoms to the physician: Changes in cognitive function (eg, decreased alertness, deterioration of previous intact memory, behavior change, mood swings), rash, flushing of skin/face, wheezing, and yellowing of skin and whites of eyes (jaundice).
• Tell patient to take sips of water frequently; suck on ice chips or sugarless hard candy or chew sugarless gum if dry mouth occurs.
• Advise patient/family that drug may cause dizziness and drowsiness and to use caution while driving or performing other tasks requiring mental alertness.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts