What are the side effects of Cognex? An examination of a discontinued Alzheimer's medication

October 8, 2025 •

4 min read

In clinical trials, approximately one-third of patients treated with tacrine, the active ingredient in Cognex, experienced reversible liver damage. For those interested in what are the side effects of Cognex, this serious issue, alongside other adverse reactions, ultimately led to the medication being withdrawn from the market.

Quick Summary

Cognex (tacrine), a discontinued Alzheimer's medication, was associated with a high incidence of adverse effects, most notably significant and often dose-limiting liver toxicity. Other common side effects included gastrointestinal issues like nausea and diarrhea. These safety concerns led to its replacement by newer, better-tolerated drugs.

Key Points

Significant Liver Damage: The most severe side effect of Cognex was a high risk of dose-limiting hepatotoxicity (liver damage), which required intensive and frequent monitoring of liver enzymes.
Gastrointestinal Distress: Many patients experienced frequent and severe gastrointestinal side effects, including nausea, vomiting, and diarrhea, which often led to treatment discontinuation.
Neurological and Psychological Effects: Common adverse reactions included dizziness, headaches, agitation, confusion, and clumsiness, which could impact a person's daily life.
Discontinued Due to Safety: The drug was voluntarily withdrawn from the market in 2013 by the manufacturer due to significant safety concerns and the availability of safer, more effective treatment options.
Cholinergic Overdose Risk: Overdosing on Cognex could cause a life-threatening cholinergic crisis, characterized by severe sweating, muscle weakness, and seizures.
Drug Interactions: Cognex could interact with a wide range of other medications, including anticholinergics and drugs processed by the CYP450 liver enzyme pathway, increasing toxicity risks.

What is Cognex?

Cognex, known by its generic name tacrine, was the first acetylcholinesterase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of mild to moderate dementia associated with Alzheimer's disease. Approved in 1993, its mechanism of action involved blocking the enzyme that breaks down acetylcholine, a neurotransmitter important for memory and learning. By increasing acetylcholine levels in the brain, it was intended to improve cognitive function. However, its use was short-lived due to a poor safety profile and the subsequent development of safer alternatives.

Tacrine was available in capsules of various strengths and typically taken four times daily. Despite providing modest benefits for some patients, the frequency and severity of its side effects made it a challenging medication to manage. Regular blood tests were required to monitor for liver toxicity, a significant burden for patients and their families.

Common side effects of Cognex

Many patients who took Cognex experienced common side effects, primarily related to its effect on cholinergic activity throughout the body. These reactions were often dose-dependent, meaning they became more frequent and pronounced at higher doses.

Common side effects included:

Gastrointestinal issues: Nausea, vomiting, diarrhea, indigestion (dyspepsia), abdominal pain, and loss of appetite were frequently reported. Nausea and vomiting were particularly common reasons for patients to stop taking the drug.
Neurological symptoms: Dizziness, headache, clumsiness, and unsteadiness were common, and in some cases could impair a person's ability to think or react normally. Insomnia and drowsiness were also noted.
Musculoskeletal pain: Some patients experienced muscle aches and pain (myalgia) or joint pain (arthralgia).
Psychological effects: Agitation, confusion, and anxiety were observed, contributing to the challenging side effect profile.
Other common effects: Increased sweating, skin rash, fatigue, and weight loss were also common complaints.

Serious side effects and warnings

While common side effects were uncomfortable, the serious adverse events associated with Cognex were the primary reason for its eventual withdrawal from the market.

Liver toxicity (hepatotoxicity)

This was the most serious and defining risk of Cognex. A significant percentage of patients, particularly females, experienced elevated liver enzymes, specifically alanine aminotransferase (ALT). While liver injury was typically detected early due to weekly monitoring and often resolved when the drug was stopped, some cases involved clinically evident jaundice. Monitoring for liver damage was a major part of the treatment protocol. Any patient who developed an ALT elevation of more than 3 times the upper limit of normal was typically withdrawn from the drug. Patients with a history of jaundice related to tacrine were permanently prohibited from re-treatment.

Neurological events

In addition to the more common neurological symptoms, some patients experienced seizures while on Cognex. These convulsions could also be a manifestation of the underlying Alzheimer's disease. Abruptly stopping the medication or significantly reducing the dose could also lead to a sudden worsening of cognitive function.

Cardiovascular issues

Due to its vagotonic effects, Cognex could cause a slowing of the heart rate (bradycardia) and other conduction abnormalities. This was a particular concern for patients with existing heart conditions or sick sinus syndrome.

Cholinergic crisis

An overdose of Cognex could lead to a severe medical emergency known as a cholinergic crisis, a life-threatening condition caused by overstimulation of the nervous system. Symptoms include severe nausea and vomiting, excessive sweating, profuse salivation, slow heart rate, low blood pressure, muscle weakness, and seizures.

Comparison with modern alternatives

Because of its poor safety profile, Cognex was voluntarily removed from the market in 2013. Safer and better-tolerated acetylcholinesterase inhibitors are now the standard of care. Below is a comparison of Cognex with one of its modern successors, Aricept (donepezil).


Feature	Cognex (tacrine)	Aricept (donepezil)
Discontinuation	Yes, in 2013 due to safety concerns, particularly liver toxicity.	No, remains a standard treatment for Alzheimer's.
Hepatotoxicity	Significant risk, requiring frequent and intensive liver function monitoring.	Minimal risk, does not typically require intensive liver monitoring.
Common Side Effects	High incidence of gastrointestinal issues (nausea, vomiting, diarrhea), dizziness, and agitation.	Lower incidence of side effects; common issues include diarrhea, nausea, insomnia, and headaches.
Ease of Dosing	Required a more complex four-times-a-day dosing schedule.	Simpler, once-daily dosing regimen.
Withdrawal Rate	A high percentage of patients withdrew from trials due to adverse effects.	Generally better tolerated, leading to fewer patient withdrawals from treatment.

For more information on tacrine-related liver toxicity, the National Institutes of Health provides a resource through the LiverTox project: https://www.ncbi.nlm.nih.gov/books/NBK547868/.

Drug interactions

Cognex was known to interact with several other medications, which could either increase the risk of side effects or diminish its therapeutic effects.

Anticholinergics: Medications with anticholinergic properties (e.g., atropine) could interfere with Cognex's mechanism of action and should have been avoided.
Cholinomimetics: Taking Cognex with other cholinesterase inhibitors or cholinergic agonists could result in synergistic effects, potentially leading to a cholinergic crisis.
CYP450 pathway medications: Tacrine is metabolized by the cytochrome P450 enzyme system, specifically the CYP1A2 isoenzyme. This meant drugs also metabolized by this pathway, such as theophylline, could interact with and alter tacrine's concentration in the body.
Fluvoxamine: Coadministration with fluvoxamine significantly increased tacrine levels, heightening the risk of cholinergic side effects.

Conclusion

The side effects of Cognex were a major factor in its withdrawal from the market in 2013. Although it represented an early step in treating Alzheimer's, the significant risk of hepatotoxicity and frequent gastrointestinal and neurological adverse events made it a difficult and potentially dangerous medication to manage. Its poor safety profile, coupled with the development of safer and more effective alternatives like Aricept (donepezil), led to its obsolescence. For anyone concerned about medications for Alzheimer's or older prescription drugs, it is essential to consult a healthcare professional and consider only currently approved treatments with more favorable risk-benefit profiles.

Frequently Asked Questions

Cognex was discontinued primarily due to significant safety concerns, most notably a high risk of hepatotoxicity (liver damage) that required intensive monitoring. Its discontinuation was accelerated by the availability of newer, better-tolerated, and more effective Alzheimer's medications.

The most serious side effect of Cognex is hepatotoxicity, or liver damage. Many patients in clinical trials experienced elevated liver enzymes, and while this was often reversible upon discontinuation, the risk and need for constant monitoring were significant.

Yes, in most cases, the liver enzyme elevations caused by Cognex were found to be reversible upon stopping the medication. However, continued use could result in more serious complications.

Safer alternatives, such as donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), have replaced Cognex as standard treatments for Alzheimer's disease. These medications are better tolerated and have a more favorable safety profile.

Yes, an overdose of Cognex can lead to a potentially fatal cholinergic crisis. Symptoms include severe nausea, vomiting, excessive sweating, muscle weakness, seizures, and a dangerously slow heart rate.

Yes, Cognex interacted with several other medications. For example, it could have dangerous synergistic effects with other cholinergic drugs and interfered with the metabolism of certain other medicines like theophylline and fluvoxamine.

Abrupt discontinuation of Cognex or a large reduction in dosage could cause a sudden worsening of cognitive symptoms in some patients. It is crucial for anyone taking this type of medication to be guided by a doctor.