Repurpose Drugs Used for Other Purposes

by: lim ju boo

Professor Dr Vythi, who is a friend of mine, sent me this link on  Drug Repurposing… and thought it might be useful for me to comment on. 

https://www.nytimes.com/2025/03/20/well/ai-drug-repurposing.html?unlocked_article_code=1._U4.EFNq.FLSQphk-N8uV&smid=nytcore-ios-share&referringSource=articleShare

First of all, I would like to thank Prof Dr Vythi for sending me the above link and asking for my opinion about drugs that  were used to treat other diseases than what was originally intended. 

It is always a joy for me to discuss any subject that ignites my academic and educational  interest . Thank you for bringing up this topic. Let me try to discuss this. 

We call this drug repurposing (also called drug repositioning) that has been a major area of success in medicine, taking medications developed for one condition and applying them to another, sometimes with surprising results.  Let me give a list of notable examples across various fields of medicine, including the reasons behind their repurposing:

1. Sildenafil (Viagra). The original use is to treat angina (chest pain due to ischemic heart disease). It was repurposed  for erectile dysfunction and later for pulmonary arterial hypertension (PAH). The reason was during clinical trials, patients reported improved erections. Further investigation showed it increased blood flow through vasodilation by inhibiting phosphodiesterase-5 (PDE5).

2. Minoxidil. The original use was as an antihypertensive (blood pressure control). OIt was repurposed for the treatment of androgenic alopecia (hair loss). The reason behind was, patients reported unexpected hair growth. It was found to stimulate hair follicles and improve blood supply to the scalp.

3. Thalidomide. The original use was a sedative and anti-nausea drug (infamously caused birth defects when used by pregnant women). Its repurposed use is for multiple myeloma and erythema nodosum leprosum. The reason is,  its immunomodulatory and anti-angiogenic properties were later found effective in cancer and inflammatory diseases.

4. Bupropion. original use was as an antidepressant (norepinephrine-dopamine reuptake inhibitor). Its repurposed use is smoking cessation aid (Zyban). The reason behind it was  found to reduce nicotine cravings and withdrawal symptoms by modulating dopaminergic pathways.

5. Aspirin. The original use was as a  painkiller and anti-inflammatory. Then it was repurposed as an  antiplatelet agent for cardiovascular disease prevention. The reason was it inhibits platelet aggregation by blocking COX-1, reducing risk of heart attacks and strokes.

6. Amantadin. The original use was as an antiviral against influenza A. Then it was repurposed for managing  Parkinson’s disease and drug-induced extrapyramidal symptoms. The reason behind it was it was found to increase dopamine release and reduce glutamatergic activity in the brain.

7. Propranolol. The original use was for hypertension and arrhythmias (beta-blocker). Then its repurposed use was for  migraine prevention, anxiety, infantile hemangiomas. The reason given was its ability to reduce adrenergic stimulation helps control physical anxiety symptoms and abnormal vascular proliferation in hemangiomas.

8. Methotrexate. The original use was as a chemotherapy for cancer. Then it was  repurposed for autoimmune diseases like rheumatoid arthritis and psoriasis. The reason behind, at low doses, methotrexate has anti-inflammatory and immunosuppressive effects.

9. Finasteride. The original use of this drug was for benign prostatic hyperplasia (BPH). Then its repurposed use was for male pattern baldness. The reason behind was, it  Inhibits 5-alpha -reductase, lowering DHT (dihydrotestosterone), which plays a role in both prostate growth and hair loss.

10. Gabapentin. The original use of this drug was for epilepsy (seizure control). Then it was repurposed for neuropathic pain, fibromyalgia. The reason given was, it modulates calcium channels and reduces hyperexcitability in nerve cells.

11. Rituximab. The original use of this drug was for non-Hodgkin’s lymphoma. Then its repurposed use was for autoimmune diseases, especially rheumatoid arthritis, vasculitis, and MS. The reason given was, it depletes B cells, which play a central role in autoimmunity.

12. Trazodone. The original use was as an  antidepressant. Then its repurposed use was for insomnia, the reason is the  sedative side effects due to antagonism at histamine and serotonin receptors.

 13. Zidovudine (AZT). Originally it was used as an anticancer drug (failed as a chemotherapy agent). Then it was repurposed as an antiretroviral for HIV/AIDS. The reason given was, it was found to inhibit reverse transcriptase, crucial for HIV replication.

14. Metformin. Originally it was  for Type 2 diabetes. Its repurposed potential was for polycystic ovarian syndrome (PCOS) and longevity/anti-aging research. The reason behind, it improves insulin sensitivity and may reduce oxidative stress and inflammation.

15. Ivermectin. The original use was  as an  anti-parasitic for river blindness (onchocerciasis). Its repurposed use was for scabies, rosacea, demodex infestations, and proposed (controversially) for COVID-19. The reason given was its broad antiparasitic and anti-inflammatory effects.

16. Dapoxetine. Originally used as an antidepressant (SSRI). Its repurposed use became the treatment for premature ejaculation. The reason given was it is short-acting SSRI found to delay ejaculation.

 17. Tamoxifen. Originally used for infertility and contraception (initial intention). Then it was repurposed for the treatment for breast cancer. The reason given was, it is a  selective estrogen receptor modulator (SERM), that blocks estrogen receptors in breast tissue.

18. Botulinum toxin (Botox). Originally used for muscle spasms and strabismus. Then its repurposed use was for cosmetic wrinkle treatment, chronic migraine, hyperhidrosis, urinary incontinence. The reason behind, it  blocks acetylcholine release, causing temporary paralysis and relief of overactivity in muscles/glands.

19. Naltrexone. Originally used for treating opioid and alcohol dependence. Then it was repurposed in low-dose (LDN) form, for autoimmune diseases, fibromyalgia, and chronic pain. The reason behind, was, it modulates the immune system and reduces inflammation.

20. Dimenhydrinate.  Originally this drug was an  antihistamine for motion sickness. Finally, its repurposed use was for the treatment for nausea in various conditions, including pregnancy. The reason given was its central antiemetic effects through vestibular suppression.

I think I have given more than enough examples - 20 of them how some of these drugs originally meant for treatment of a specific disease were directed to treat some other  diseases 

One of the most glaring examples I know was,  during the COVID-19 pandemic the antiparasitic drug Ivermectin was illegally used by doctors for this viral infection. Let me explain how Ivermectin works from parasite to virus?

Originally, Ivermectin is an antiparasitic agent discovered in the 1970s, famously used to treat onchocerciasis (river blindness) and other nematode infections. It works by binding to glutamate-gated chloride channels in parasites, causing an influx of chloride ions, leading to paralysis and death of the parasite. It is highly selective, as humans lack these channels. During COVID Ivermectin was theoretically believed to have antiviral properties, based on, in vitro studies (e.g., Caly et al., 2020) showing that it inhibited SARS-CoV-2 replication in monkey kidney cells.

The proposed antiviral mechanism is, by inhibiting importin α/β-mediated nuclear transport, which viruses use to dampen the host’s antiviral response (especially interferon production). This interferes with viral proteins entering the host nucleus to suppress immune defense.

However in reality, the in vitro concentrations needed to inhibit the virus were much higher than those safely achievable in human plasma. Secondly, large-scale, well-conducted clinical trials (e.g., TOGETHER Trial, NIH-supported studies) did not show significant benefit. Thirdly,  WHO, FDA, and CDC cautioned against its use outside of clinical trials.

So, while ivermectin has interesting biological effects, its antiviral application was not clinically validated for COVID-19.

If a drug has been repurposed for other applications wouldn't it not be profitable for a drug company to investigate and pursue further because by then that drug may have lost its patent rights for other therapeutic applications. If a drug was found useful for the management of other diseases, would the health authorities approve it without further intensive studies as it did for the original disease. What's my take on this should anyone ask me? 

 Let me explore them carefully, one at a time, with the seriousness and clarity they deserve.

Is it profitable for drug companies to investigate repurposing after patent expiry? This is a central dilemma in drug development and public health.

Patent and Profitability Issues:

A drug's patent typically lasts 20 years from the time of filing (not approval). By the time it’s repurposed, the patent might already have expired or be close to expiration. Once expired, generic versions flood the market, reducing profit margins drastically. Pharmaceutical companies often lack incentive to invest millions in repurposing studies when the market is not protected.

Some Workarounds Companies Use:

New Use Patents: File a patent for a new indication (even for the same compound), although these are weaker and easier to challenge. New Formulations: Reformulate the drug (e.g., extended-release), and patent that.

Orphan Drug Designation: 

For rare diseases, it gives 7 years of exclusivity in the U.S., even for older drugs. Yet despite these options, unless the return on investment is high, many big pharma companies avoid repurposing unless incentivized or supported by public-private partnerships.

Can Repurposed Drugs Be Approved Without Full Clinical Trials? This is another excellent question. The answer is, not usually - though some exceptions exist.

Normal Approval Pathway for Repurposing:

Even if a drug is already approved for one indication, to use it for a different disease, regulatory authorities like:

FDA (U.S.)
EMA (Europe)
NPRA (Malaysia)

still require:

1. Preclinical rationale for the new disease
2. Phase 2 and 3 clinical trials showing safety and efficacy in the new context
3. New labeling approval.

This is because:

Different diseases may have different risk-benefit profiles. Side effects that are acceptable in one population (e.g., cancer patients) may not be acceptable in others (e.g., children)
Dosages or durations might vary significantly.

Emergency Use Authorizations (EUA):

During pandemics (like COVID-19), authorities may grant temporary EUA based on early evidence. This happened with remdesivir, hydroxychloroquine (later withdrawn), vaccines, etc.

But EUA is not a full approval and is subject to withdrawal based on new evidence. 

Here are my take: 

Drug repurposing is scientifically efficient, economically logical (especially for governments or academia), and can save lives faster than new drug development.

However, the pharmaceutical business model based on exclusivity and patents discourages altruistic repurposing unless aligned with profit or supported by incentives.

Health authorities rightly demand solid evidence even for repurposed drugs, because lives are at stake, and assumptions about safety can be misleading.

This creates a gap: Life-saving, low-cost treatments may go underused due to lack of financial motivation and regulatory hurdles.

This is where government support, public funding, and academic medicine must step in, for the public good. A society that values health above profit can help usher in repurposed therapies responsibly and equitably.

 I think safety should not be an issue, because the drug had already been studied for its safety and toxicological profiles for its original purpose, unless of course it has to be given at a much higher dose than originally intended. 

But I fully agree  an old drug can be life saving for another disease without having to search for a new agent which is extremely time consuming and expensive. Ivermectin is a glaring example. I know of medical specialists friends of mine who prescribed it during the Covid-19 pandemic but was caught by the Ministry of Health enforcement team who raided his clinic and other clinics as well and was charged in court for prescribing Ivermectin for Covid, but was later found not guilty because the court ruled that a doctor has the discretion to prescribe any drug he wishes. But is this safe without safety protocol being studied first? 

Here are my take on this issue are: 

Safety and toxicological profiles of an already-approved drug are well-established through rigorous preclinical and clinical studies. This includes data on organ toxicity, metabolism, drug interactions, and adverse effects.

Hence, when used within the same dosage range, or with slight adjustments, repurposing should not generally pose serious safety issues. But regulatory agencies still request new clinical trials primarily for:

A drug used in a different patient population (e.g., children instead of adults, or healthy individuals instead of terminally ill patients) may alter the risk-benefit balance.
Some drugs can have rare adverse effects that were not apparent until broader or different populations are exposed.

Higher Doses:

Repurposing sometimes requires higher or longer-term dosing to achieve efficacy (as was the case in in vitro ivermectin studies), and this might breach the established therapeutic window, raising safety concerns.

So it's not that the drug is inherently unsafe, but regulatory prudence demands that we ensure it remains safe and effective in a new context.

The legal and ethical case of Ivermectin during COVID-19 is both sobering and illuminating. It brings up a crucial topic:

The physician’s right to prescribe off-label: 

Globally, off-label prescribing is legally and ethically permitted under medical discretion. 

Physicians can use approved drugs outside their original indication if:

1. There is a scientific rationale
2. It is in the patient’s best interest
3. The patient is informed and gives consent

This applies to antidepressants for pain, antipsychotics for insomnia, beta blockers for anxiety, and so on.

In Malaysia (and many countries):

1. The issue becomes contentious when the drug is used for a high-profile disease (like COVID-19) against national guidelines.

2. The MOH may investigate or act under the Private Healthcare Facilities and Services Act (PHFSA) or Dangerous Drugs Act—not because of the drug itself, but because of perceived public health risks or improper documentation.

3. But as the story shows, the court upheld the right of a doctor to prescribe based on clinical judgment. This is a powerful affirmation of medical autonomy, within reason.

It's tragic that such doctors were penalized, though ultimately vindicated. It shows how legal policy, medical science, and public fear can collide during crises.

 

The Bigger Picture: Medicine Beyond the Patent

Older drugs may be life-saving in new contexts—fast, cheap, and already proven. This calls for:

1. More academic research into repurposing

2. Support from governments and NGOs
Protecting ethical doctors from undue prosecution

3. Compassionate use policies in emergencies

We need a system that:

1. Doesn't punish doctors for innovative thinking
2. Encourages scientific inquiry, even with older agents
3. Values public health over commercial interest

My final reflection strikes at the heart of modern medicine’s struggle. The tension between rigid regulation, corporate influence, and the intelligent, ethical discretion of the individual doctor.

Personally, I think it is  the wisdom of experience, compassion, and medical philosophy.  However in scientific research, especially in medicine they demand large sampling sizes (population size) and have to be randomized with double-blind studies to actually prove a certain drug can be used for another purpose than originally studied.  Most of these agents for other medical uses than initially intended were discovered accidentally 

 

There is one word for this accidental discovery.  That word is called "serendipity" to describe a fortunate or unexpected discovery that happens by chance. It often involves recognizing the potential value of something that was not intentionally sought after. 

Serendipity  is a term I first came across when I was doing my PhD in Medicine in London. It speaks on accidental discoveries. Serendipity has played a profound role in scientific and medical advances. Some of the most powerful treatments we have today were stumbled upon in exactly this way, penicillin, warfarin, Viagra, even minoxidil, to name just a few. Each began as an unexpected observation that someone wise enough recognized as valuable. That's the beauty of the observant and open scientific mind.  

Serendipity has played a profound role in scientific and medical advances. Some of the most powerful treatments we have today were stumbled upon in exactly this way such as penicillin, warfarin, Viagra, even minoxidil, to name just a few. Each began as an unexpected observation that someone wise enough recognized as valuable. That's the beauty of the observant and open scientific mind.

Now, to a profound question. Do we still need double-blind randomized controlled trials (RCTs) for serendipitous discoveries?

Yes, in most cases, we do. Here's are my personal reasons as a former medical researcher who have led a team of clinicians and scientists before in conducting clinical trails:

Why RCTs Are Still Needed:

Firstly, to confirm efficacy – Just because something appears to work anecdotally or in an unintentional setting doesn’t prove it will work consistently or better than a placebo or standard care.

Secondly, to rule out bias since serendipitous findings often arise from uncontrolled environments. Without blinding, randomization, and control groups, it's hard to tell whether the results were real or due to chance, bias, or confounding variables.

Thirdly, to assess safety, especially in drug repurposing, we must study new dosages, durations, and populations. What’s safe for one condition might not be safe for another.

Fourthly, to build regulatory and clinical confidence – For approval by authorities like the FDA or EMA, or to convince physicians to adopt it, solid clinical evidence is usually needed.

 Can We Apply This to Drug Repurposing? Absolutely!

In fact, drug repurposing thrives on serendipity. It’s often how new uses for old drugs are uncovered.

A few notable examples:

Thalidomide: Once infamous, it's now used in multiple myeloma after careful study.

Metformin: Originally for diabetes, now being explored for aging and cancer.

Aspirin: From pain relief to heart attack prevention and even cancer reduction in some studies.

But after the initial "serendipitous spark," the journey must be followed by systematic investigation, which usually includes RCTs, especially if we’re looking to adopt the treatment widely.

Of course in a medical emergency we can give this an initial shot and see how a patient responds? But this could also be a placebo effect if the patient believes strongly what the doctor tells him. We all respond differently - it's not just its therapeutic or pharmacological effects on the (biological) body, but the mind too plays a profound effect on the body. The body is fearsomely and wonderfully made. 

On the Need for RCTs and large sample sizes. In medical research we use very high standards that are demanded from us when we conduct a clinical trial.

 

In modern medicine, Randomized Controlled Trials (RCTs), especially double-blind, placebo-controlled studies remain the gold standard for proving:

1. Efficacy (does the drug work?)

2. Safety (is it tolerable across diverse populations?)

3. Reproducibility (can we expect the same outcome consistently?)

This methodology:

1. Minimizes bias

2. Controls for placebo effects

3. Addresses variability in patient response

4. Helps ensure statistical power through large sample sizes What works in a small observational or anecdotal sample may not hold true across a larger, heterogeneous population.

Many repurposed drugs began with accidental discoveries. I have already given examples on: 

1. Minoxidil: Originally for hypertension → Found to cause hair growth in some users → Became Rogaine.
2. Sildenafil (Viagra): Originally for angina → Noticed to cause penile erection in some → Repurposed for erectile dysfunction.
3. Thalidomide: Initially a sedative → Caused birth defects → Later found to be effective in multiple myeloma and leprosy complications (with stricter controls).

Such serendipity is not sufficient proof as it opens the door for rigorous trials, not bypasses them.

 

On the Placebo Effect and the Power of the Mind

Here we enter a sacred realm, where science meets the soul. The placebo effect is not deception; it's a testament to the power of belief, of mind over matter, and how:

“The body responds not just to molecules, but to meaning.”

This I believe eloquently summarized the essence of psychoneuroimmunology - how:

Emotions
Beliefs
Trust in the doctor
Hope and expectation 

Can all modulate biological outcomes like pain, inflammation, immune responses, even cardiovascular dynamics can shift simply because of what the mind perceives. No wonder the Psalmist exclaimed:

"I am fearfully and wonderfully made."  (Psalm 139:14). 

To me, this reflection is a beautiful convergence of scientific observation and spiritual truth. The placebo response is not merely a nuisance to control in trials, but I personally think it is a divine hint that healing comes from more than chemicals. It comes from trust, connection, hope, and belief.

Emergencies and compassionate use in life-threatening scenarios, the doctrine of clinical judgment allows compassionate, off-label use, especially when:

1. Standard options are exhausted
2. The potential benefit outweighs the risk
3. The patient consents

This is not reckless, it is humane,  even hope alone may tilt the balance between life and death.

But of course, for public health policy and mass roll-out, we need data, trials, and surveillance. That’s the paradox we live with.

My summary thoughts from a Fellow Pilgrim in Science and Spirit are these four (4) virtues : 

1. I think  we need to be a rare soul as a physician-scientist with both a rigorous intellect and a reverent heart. What I shared touches on the deepest truths in medicine

2. That we must never sacrifice evidence for hope. But neither must we neglect hope because of the lack of evidence

3. And in all things, we must remember:

4. The human being is not just a machine to be fixed, but a mystery to be understood.