Tacrine

Oral
Alzheimer's dementia

Adjustment in tacrine dose in serum aminotransferase elevations: ≤2 times the upper limit of normal: Continue treatment. >2 but ≤3 times the upper limit of normal: Continue treatment but with wkly monitoring of LFT till levels return to normal. >3 times but ≤5 times the upper limit of normal: Reduce dose by 40 mg daily and monitor LFT wkly until levels return to within normal limits, after which resume usual dosage titration. >5 times the upper limit of normal: Withhold tacrine and monitor for signs and symptoms of hepatitis until LFT return to within normal limits, after which may consider rechallenge.

Should be taken on an empty stomach.

Hypersensitivity to tacrine or acridine derivatives. History of jaundice with tacrine therapy. Lactation.

Monitor serum-alanine aminotransferase concentration. Avoid abrupt withdrawal or large dose reduction. Impaired liver function or history of liver function abnormalities, epilepsy, bronchial asthma, bradycardia, CV conduction disorders, GI or urinary tract obstruction, recent intestinal or bladder surgery, risk of peptic ulcer. Pregnancy. Smoking may reduce serum tacrine levels.

Dizziness, headache, nausea, vomiting, diarrhoea, myalgia, ataxia.
Potentially Fatal: Hepatotoxicity.

PO: C

Cholinergic crisis characterised by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, collapse, convulsions, and muscle weakness. May result in death if respiratory muscles are involved. General supportive treatment and IV atropine sulfate. Adults: Initial dose of 1-2 mg IV atropine with subsequent doses based on clinical response.

Increased serum tacrine levels with coadmin of cimetidine, fluvoxamine, quinolones and HRT. Increased theophylline levels with concurrent tacrine use. Increased cholinergic side effects with other cholinergic agents, cholinesterase inhibitors, and succinylcholine. Antagonise effects of anticholinergic drugs. Increased risk of bradycardia with β-blockers and calcium channel blockers.

Food reduces absorption.

Description:
Mechanism of Action: Tacrine acts centrally and binds reversibly and inactivates cholinesterase, inhibiting hydrolysis of acetylcholine, prolonging their action in the brain.
Pharmacokinetics:
Absorption: Rapidly absorbed but large variations in oral bioavailability reported. Food reduces the absorption of tacrine by about 30-40%.
Distribution: Peak plasma concentrations achieved within 1-2 hr. About 55% bound to plasma proteins.
Metabolism: Undergoes extensive first-pass effect in the liver. Metabolised by the cytochrome P450 system (primarily CYP1A2) to various metabolites, with the main metabolte being 1-hydroxy metabolite velnacrine.
Excretion: Elimination half-life is 2-4 hr; little unchanged drug is excreted in the urine.

Store at 20-25°C.

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