What is Cognex (tacrine)?

Cognex (tacrine) is a cholinesterase inhibitor used to treat patients with mild to moderate dementia associated with Alzheimer’s disease. 

Cholinesterase inhibitors block the action of acetylcholinesterase, the enzyme responsible for the destruction of acetylcholine. Acetylcholine is one of several neurotransmitters in the brain. Reduced levels of acetylcholine in the brain are believed to be responsible for some of the symptoms of Alzheimer’s disease. 

By blocking the enzyme that destroys acetylcholine, Cognex increases the concentration of acetylcholine in the brain, and this increase is believed to be responsible for the improvement in thinking seen with tacrine. The brand name Cognex is discontinued in the U.S.

Common side effects of Cognex include:

Serious side effects of Cognex include:

  • increases in a liver test called alanine aminotransferase (ALT) as a result of liver damage.
    • When a patient starts taking Cognex, blood is drawn on a weekly basis to measure ALT. 

Drug interactions of Cognex include drugs with anticholinergic properties and cross into the brain, which produce opposite effects of Cognex and should be avoided, such as:

Unlike donezepril, Cognex does not reduce the elimination of other drugs, increasing their levels in blood and the likelihood of their side effects. 

Animal reproduction studies have not been done with Cognex. It is unknown if Cognex causes fetal harm when taken by a pregnant woman. 

Cognex may pass into breast milk and be harmful to the nursing infant; it should not be used while breastfeeding.

What are the important side effects of Cognex (tacrine)?

The most common side effect of tacrine is an increase in a liver test called alanine aminotransferase (ALT) as a result of liver damage. When a patient starts taking tacrine, blood is drawn on a weekly basis to measure ALT. If there is an increase in blood ALT, the dosage of tacrine can be reduced. Other side effects of tacrine include:

Cognex (tacrine) side effects list for healthcare professionals

Common Adverse Events Leading to Discontinuation

In clinical trials, approximately 17% of the 2706 patients who received Cognex (tacrine) and 5% of the 1886 patients who received placebo withdrew permanently because of adverse events. It should be noted that some of the placebo-treated patients were exposed to Cognex (tacrine) prior to receiving placebo due to the variety of study designs used, including crossover studies.

Transaminase elevations were the most common reason for withdrawals during Cognex (tacrine) treatment (8% of all Cognex (tacrine) -treated patients, or 212 of 456 patients withdrawn). The controlled clinical trial protocols required that any patient with an ALT/SGPT elevation > 3 X ULN be withdrawn, because of concern about potential hepatotoxicity. Apart from withdrawals due to transaminase elevations, 244 patients (9%) withdrew for adverse events while receiving Cognex (tacrine) .

Other adverse events that most frequently led to the withdrawal of tacrine-treated patients in clinical trials were:

  • nausea and/or vomiting (1.5%),
  • agitation (0.9%),
  • rash (0.7%),
  • anorexia (0.7%), and
  • confusion (0.5%).

These adverse events also most frequently led to the withdrawal of placebo-treated patients, although at lower frequencies (0.1% to 0.2%).

Most Frequent Adverse Clinical Events Seen in Association With the Use of Tacrine

The events identified here are those that occurred at an absolute incidence of at least 5% of patients treated with Cognex (tacrine), and at a rate at least 2-fold higher in patients treated with Cognex (tacrine) than placebo.

The most common adverse events associated with the use of Cognex (tacrine) were:

Of these events, nausea and/or vomiting, diarrhea, dyspepsia, and anorexia appeared to be dose-dependent.

Adverse Events Reported in Controlled Trials

The events cited in the tables below reflect experience gained under closely monitored conditions of clinical trials with a highly selected patient population. In actual clinical practice or in other clinical trials, these frequency estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients treated may differ.

Table 3 lists treatment-emergent signs and symptoms that occurred in at least 2% of patients with Alzheimer's disease in placebo-controlled trials and who received the recommended regimen for dose introduction and titration of Cognex.

Table 3. Adverse Events Occurring in at Least 2% of Patients Receiving Cognex (tacrine) at a Starting Dose of 40 mg/day with Titration in 40 mg/day Increments Every 6 Weeks in Controlled Clinical Trials [Number (%) of Patients]

Adverse Events
N = 634
N = 342
  Elevated Transaminasea184 (29)5 (2)
  Headache67 (11)52 (15)
  Fatigue26 (4)9 (3)
  Chest Pain24 (4)18 (5)
  Weight Decrease21 (3)4 (1)
  Back Pain15 (2)14 (4)
  Asthenia15 (2)7 (2)
  Nausea and/or Vomiting178 (28)29 (9)
  Diarrhea99 (16)18 (5)
  Dyspepsia57 (9)22 (6)
  Anorexia54 (9)11 (3)
  Abdominal Pain48 (8)24 (7)
  Flatulence22 (4)5 (2)
  Constipation24 (4)8 (2)
  Purpura15 (2)8 (2)
  Myalgia54 (9)18 (5)
  Dizziness73 (12)39 (11)
  Confusion42 (7)24 (7)
  Ataxia36 (6)12 (4)
  Insomnia37 (6)18 (5)
  Somnolence22 (4)11 (3)
  Tremor14 (2)2 (<1)
  Agitation43 (7)30 (9)
  Depression22 (4)14 (4)
  Thinking Abnormal17 (3)14 (4)
  Anxiety16 (3)7 (2)
  Hallucination15 (2)12 (4)
  Hostility15 (2)5 (2)
  Rhinitis51 (8)22 (6)
  Upper Respiratory Infection18 (3)11 (3)
  Coughing17 (3)18 (5)
  Rashb46 (7)18 (5)
  Facial Flushing, Skin Flushing16 (3)3 (<1)
  Urination Frequency21 (3)12 (4)
  Urinary Tract Infection21 (3)20 (6)
  Urinary Incontinence16 (3)9 (3)
aALT or AST value of approximately 3 X ULN or greater orthat resulted in a change in patient management. Patients were monitored weekly.
bIncludes COSTART terms: rash, rash-erythematous,rash-maculopapular, urticaria, petechialrash, rash-vesiculobullous, and pruritus.

Other Adverse Events Observed During All Clinical Trials

Cognex (tacrine) has been administered to 2706 individuals during clinical trials. A total of 1471 patients were treated for at least 3 months, 1137 for at least 6 months, and 773 for at least 1 year. Any untoward reactions that occurred during these trials were recorded as adverse events by the clinical investigators using terminology of their own choosing.

To provide a meaningful estimate of the proportion of individuals having similar types of events, the events were grouped into a smaller number of standardized categories using a modified COSTART dictionary. These categories are used in the listing below. The frequencies represent the proportion of the 2706 individuals exposed to Cognex (tacrine) who experienced that event while receiving Cognex (tacrine).

All adverse events are included except those already listed on the previous table and those COSTART terms too general to be informative. Events are further classified by body system categories and listed using the following definitions:

  • frequent adverse events are defined as those occurring in at least 1/100 patients;
  • infrequent adverse events are those occurring in 1/100 to 1/1000 patients; and
  • rare adverse events are those occurring in less than 1/1000 patients. These adverse events are not necessarily related to Cognex (tacrine) treatment.

Only rare adverse events deemed to be potentially important are included.

Body As a Whole 

Frequent: Chill, fever, malaise, peripheral edema.

Infrequent: Face edema, dehydration, weight increase, cachexia, edema (generalized), lipoma.

Rare: Heat exhaustion, sepsis, cholingeric crisis, death.

Cardiovascular System

Frequent: Hypotension, hypertension.

Infrequent: Heart failure, myocardial infarction, angina pectoris, cerebrovascular accident, transient schemic attack, phlebitis, venous insufficiency, abdominal aortic aneurysm, atrial fibrillation or flutter, palpitation, tachycardia, bradycardia, pulmonary embolus, migraine, hypercholesterolemia.

Rare: Heart arrest, premature atrial contractions, A-V block, bundle branch block.

Digestive System

Infrequent: Glossitis, gingivitis, mouth or throat dry, stomatitis, increased salivation, dysphagia, esophagitis, gastritis, gastroenteritis, GI hemorrhage, stomach ulcer, hiatal hernia, hemorrhoids, stools bloody, diverticulitis, fecal impaction, fecal incontinence, hemorrhage (rectum), cholelithiasis, cholecystitis, increased appetite.

Rare: Duodenal ulcer, bowel obstruction.

Endocrine System

Infrequent: Diabetes.

Rare: Hyperthyroid, hypothyroid.

Hemic and Lymphatic

Infrequent: Anemia, lymphadenopathy.

Rare: Leukopenia, thrombocytopenia, hemolysis, pancytopenia.


Frequent: Fracture, arthralgia, arthritis, hypertonia.

Infrequent: Osteoporosis, tendinitis, bursitis, gout.

Rare: Myopathy.

Nervous System

Frequent: Convulsions, vertigo, syncope, hyperkinesia, paresthesia.

Infrequent: Dreaming abnormal, dysarthria, aphasia, amnesia, wandering, twitching, hypesthesia, delirium, paralysis, bradykinesia, movement disorder, cogwheel rigidity, paresis, neuritis, hemiplegia, Parkinson's disease, neuropathy, extrapyramidal syndrome, reflexes decreased/absent.

Rare: Tardive dyskinesia, dysesthesia, dystonia, encephalitis, coma, apraxia, oculogyric crisis, akathisia, oral facial dyskinesia, Bell's palsy, exacerbation of Parkinson 's disease.

Psychobiologic Function

Frequent: Nervousness.

Infrequent: Apathy, increased libido, paranoia, neurosis.

Rare: Suicidal, psychosis, hysteria.

Respiratory System

Frequent: Pharyngitis, sinusitis, bronchitis, pneumonia, dyspnea.

Infrequent: Epistaxis, chest congestion, asthma, hyperventilation, lower respiratory infection.

Rare: Hemoptysis, lung edema, lung cancer, acute epiglottitis.

Skin and Appendages

Frequent: Sweating increased.

Infrequent: Acne, alopecia, dermatitis, eczema, skin dry, herpes zoster, psoriasis, cellulitis, cyst, furunculosis, herpes simplex, hyperkeratosis, basal cell carcinoma, skin cancer.

Rare: Desquamation, seborrhea, squamous cell carcinoma, ulcer (skin), skin necrosis, melanoma.

Urogenital System

Infrequent: Hematuria, renal stone, kidney infection, glycosuria, dysuria, polyuria, nocturia, pyuria, cystitis, urinary retention, urination urgency, vaginal hemorrhage, pruritus (genital), breast pain, impotence, prostate cancer.

Rare: Bladder tumor, renal tumor, renal failure, urinary obstruction, breast cancer, epididymitis, carcinoma (ovary).

Special Senses

Frequent: Conjunctivitis.

Infrequent: Cataract, eyes dry, eye pain, visual field defect, diplopia, amblyopia, glaucoma, hordeolum, deafness, earache, tinnitus, inner ear infection, otitis media, unusual taste.

Rare: Vision loss, ptosis, blepharitis, labyrinthitis, inner ear disturbance.

Post introduction Reports

Voluntary reports of adverse events temporally associated with Cognex (tacrine) that have been received since market introduction, that are not listed above, and that may have no causal relationship with the drug include the following: pancreatitis, perforated peptic ulcer, and falling.

What drugs interact with Cognex (tacrine)?

Possible metabolic basis for interactions

Tacrine is primarily eliminated by hepatic metabolism via cytochrome P450 drug metabolizing enzymes. Drug-drug interactions may occur when Cognex (tacrine) is given concurrently with agents such as theophylline that undergo extensive metabolism via cytochrome P450 IA2.


Coadministration of tacrine with theophylline increased theophylline elimination half-life and average plasma theophylline concentrations by approx-i mately 2-fold. Therefore, monitoring of plasma theophylline concentrations and appropriate reduction of theophylline dose are recommended in patients receiving tacrine and theophylline concurrently. The effect of theophylline on tacrine pharmacokinetics has not been assessed.


Cimetidine increased the Cmax and AUC of tacrine by approximately 54% and 64%, respectively.


Because of its mechanism of action, Cognex (tacrine) has the potential to interfere with the activity of anticholinergic medications.

Cholinomimetics and Cholinesterase Inhibitors 

A synergistic effect is expected when Cognex (tacrine) is given concurrently with succinylcholine, cholinesterase inhibitors, or cholinergic agonists such as bethanechol.


In a study of 13 healthy, male volunteers, a single 40 mg dose of tacrine added to fluvoxamine 100 mg/day administered at steady-state was associated with five- and eight-fold increases in tacrine Cmax and AUC, respectively, compared to the administration of tacrine alone. Five subjects experienced nausea, vomiting, sweating, and diarrhea following coadministration, consistent with the cholinergic effects of tacrine.

Other Interactions

Rate and extent of tacrine absorption were not influenced by the coadministration of an antacid containing magnesium and aluminum. Tacrine had no major effect on digoxin or diazepam pharmacokinetics or the anticoagulant activity of warfarin.


Cognex (tacrine) is a cholinesterase inhibitor used to treat patients with mild to moderate dementia associated with Alzheimer’s disease. Common side effects of Cognex include nausea, indigestion, vomiting, diarrhea, abdominal pain, and skin rash. Serious side effects of Cognex include increases in a liver test called alanine aminotransferase (ALT) as a result of liver damage. When a patient starts taking Cognex, blood is drawn on a weekly basis to measure ALT. Animal reproduction studies have not been done with Cognex. It is unknown if Cognex causes fetal harm when taken by a pregnant woman. Cognex may pass into breast milk and be harmful to the nursing infant; it should not be used while breastfeeding.

Treatment & Diagnosis

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Medically Reviewed on 5/7/2020
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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.