When you're prescribed azathioprine for an autoimmune condition like lupus, rheumatoid arthritis, or inflammatory bowel disease, you're usually told about the big risks: liver damage, low white blood cell counts, or increased infection risk. But there’s one side effect that rarely gets mentioned-myositis. It’s not common, but when it happens, it can be serious. And if you’re on azathioprine and suddenly feel like your muscles are turning to lead, you need to know what to look for.
What is azathioprine, really?
Azathioprine is an immunosuppressant. It’s been around since the 1960s and works by slowing down your immune system. That’s useful when your immune system turns on your own body-like in Crohn’s disease, ulcerative colitis, or autoimmune hepatitis. It’s cheap, widely available, and often used as a long-term maintenance drug. Many people take it for years without issues.
But it’s not harmless. Your body breaks azathioprine down into 6-mercaptopurine, which interferes with DNA production in rapidly dividing cells-like immune cells. That’s why it works. But it also affects other fast-growing cells, like those in your bone marrow or, rarely, your muscle tissue.
What is myositis?
Myositis means inflammation of the muscles. It’s not just soreness after a workout. True myositis causes progressive weakness, especially in your shoulders, hips, and thighs. You might find it hard to stand up from a chair, climb stairs, or lift your arms above your head. Some people also get muscle pain, swelling, or even a rash-especially if it’s dermatomyositis.
There are different types: polymyositis, dermatomyositis, and inclusion body myositis. But when it’s caused by a drug like azathioprine, we call it drug-induced myositis. It’s rare, but it’s real. And it can happen even after months or years of taking the drug without problems.
How common is azathioprine-induced myositis?
Studies show drug-induced myositis is uncommon. In large patient databases, only about 1 in 1,000 people on azathioprine develop muscle inflammation severe enough to be diagnosed. But that number might be low. Many cases are missed because doctors don’t connect the dots.
A 2023 review in Arthritis & Rheumatology analyzed 47 confirmed cases of azathioprine-related myositis. The average time from starting the drug to symptoms was 14 months. Some people developed it after just 3 months. Others didn’t notice anything until they’d been on it for 5 years. There’s no clear pattern.
What’s more, symptoms often get mistaken for something else-like aging, overtraining, or even the original disease flaring up. That’s why it’s underdiagnosed.
Who’s most at risk?
Not everyone on azathioprine gets myositis. But some people are more likely to.
- People with a genetic variation in the TPMT enzyme. This enzyme breaks down azathioprine. If you have low TPMT activity, the drug builds up in your system, increasing side effects. About 1 in 300 people have this variant.
- Those already taking other drugs that affect muscles-like statins, hydroxychloroquine, or colchicine. The combination can be dangerous.
- People with existing autoimmune muscle conditions. If you’ve had myositis before, azathioprine might trigger a relapse.
- Older adults. Muscle tissue naturally weakens with age. Adding a drug that stresses muscle cells can tip the balance.
There’s no routine genetic test before starting azathioprine in most places. But if you’ve had unexplained muscle weakness before, or if your family has a history of autoimmune disorders, it’s worth mentioning to your doctor.
What are the signs you should watch for?
Don’t wait for muscle pain to become unbearable. Look for these early warning signs:
- Progressive weakness in your shoulders or thighs-especially if it’s getting worse over weeks, not days.
- Difficulty rising from a chair or climbing stairs without using your hands.
- Unexplained fatigue that doesn’t improve with rest.
- Muscle tenderness or swelling, especially if it’s symmetrical (both sides).
- Difficulty swallowing or speaking-this can happen if throat muscles are affected.
If you notice any of these, don’t assume it’s just getting older or your arthritis flaring. Ask your doctor for a blood test. Elevated creatine kinase (CK) levels are a red flag. Normal CK is under 200 U/L. Levels over 1,000 U/L are strongly suggestive of muscle damage.
What happens if you get drug-induced myositis?
The first step is stopping azathioprine. Most people start to feel better within 2 to 6 weeks after stopping the drug. But recovery isn’t always quick.
In severe cases, doctors may prescribe corticosteroids like prednisone to calm the inflammation. Physical therapy helps rebuild strength. Some people need months of rehab.
Here’s the good news: in most cases, muscle function returns fully. A 2022 study of 31 patients with azathioprine-induced myositis found that 87% regained normal muscle strength within 6 months after stopping the drug.
But if you ignore it? Muscle damage can become permanent. In rare cases, people develop chronic weakness or even require a wheelchair.
What are the alternatives to azathioprine?
If you’ve had myositis on azathioprine-or if you’re at high risk-there are other options.
| Drug | Myositis Risk | Typical Use | Monitoring Needed |
|---|---|---|---|
| Methotrexate | Very low | Rheumatoid arthritis, psoriasis | Liver enzymes, blood counts |
| Mycophenolate mofetil | Low | Lupus, kidney transplants | Blood counts, liver function |
| Belimumab | Minimal | Lupus | Infusion reactions, infections |
| Anti-TNF agents (e.g., adalimumab) | Very low | Crohn’s, rheumatoid arthritis | Tuberculosis screening, infections |
Methotrexate is often the first alternative. It’s effective, well-studied, and has almost no reported cases of drug-induced myositis. Mycophenolate is another good option, especially for inflammatory bowel disease. Biologics like belimumab or anti-TNF drugs are more expensive but carry lower risks for muscle damage.
The choice depends on your condition, your insurance, and your tolerance for side effects. Talk to your rheumatologist or gastroenterologist about switching.
Should you get tested before starting azathioprine?
In the UK and EU, testing for TPMT enzyme activity is not routine-but it should be. In the U.S., guidelines from the American College of Gastroenterology recommend testing before starting azathioprine. It’s a simple blood test. If your TPMT is low, your doctor can prescribe a much lower dose or choose a different drug entirely.
Even if you don’t get tested, pay attention to your body. If you start feeling unusually weak or tired after starting azathioprine, don’t brush it off. Get a CK test. It’s cheap, fast, and could prevent serious damage.
What to do if you’re already on azathioprine
If you’ve been on azathioprine for months or years, here’s what you can do:
- Know your baseline. Ask your doctor for a copy of your last CK level. If you don’t have one, get one now.
- Check in every 3 to 6 months. Blood tests for liver function and blood counts are standard. Ask for CK too.
- Track your muscle strength. Can you still do the same number of squats or push-ups as last year? If not, note it.
- Report any new weakness-even if it’s mild. Don’t wait until you can’t climb stairs.
Don’t stop the drug on your own. If you suspect myositis, contact your doctor. Stopping abruptly can cause your original condition to flare.
Bottom line
Azathioprine saves lives. But it’s not risk-free. Myositis is rare-but it’s preventable if you catch it early. The key is awareness. If you’re on this drug, know the signs. Ask for a CK test if something feels off. And if you’ve had unexplained muscle weakness before, tell your doctor before you start.
You’re not overreacting if you speak up. You’re being smart.
Can azathioprine cause permanent muscle damage?
Yes, but it’s rare. If azathioprine-induced myositis is caught early and the drug is stopped, most people recover fully. However, if muscle inflammation continues unchecked for months, it can lead to permanent weakness or scarring of muscle tissue. Early diagnosis and stopping the drug are critical.
How long after starting azathioprine can myositis develop?
It can happen anytime-from as early as 3 months to more than 5 years after starting the drug. There’s no set timeline. Most cases occur between 6 and 18 months, but delayed onset is common. That’s why ongoing monitoring matters, even if you’ve been on the drug for years without issues.
Is myositis from azathioprine the same as polymyositis?
Clinically, they look very similar-both cause muscle weakness and elevated CK levels. But drug-induced myositis is triggered by a medication, while polymyositis is an autoimmune condition with no clear external trigger. The treatment is similar (stop the drug, use steroids), but drug-induced cases usually resolve faster once the trigger is removed.
Should I avoid azathioprine if I’m an athlete?
Athletes aren’t at higher risk just because they exercise. But intense training can mask early muscle weakness. If you’re an athlete on azathioprine, pay close attention to unusual fatigue or loss of strength that doesn’t improve with rest. A simple CK blood test can help distinguish between exercise-induced soreness and drug-induced inflammation.
Can I take statins while on azathioprine?
Combining statins with azathioprine increases the risk of muscle damage, including myositis. Both drugs can affect muscle cells. If you need cholesterol-lowering medication, your doctor may choose a lower-dose statin or switch to a different type like ezetimibe. Never combine them without close monitoring.
All Comments
Richard Kang October 28, 2025
Wait, so you're telling me I've been taking this stuff for 3 years and my muscles just feel like wet noodles because the drug is slowly turning me into a zombie???
And NO ONE told me this???
I thought I was just getting old, or maybe I need more protein!!
My knees creak like a haunted house now-I’m 42, not 82!!!
Also, my doctor just shrugs and says ‘it’s lupus flaring’-yeah, right, buddy.
And now I find out I could’ve been tested for TPMT???
Why isn’t this on the damn pill bottle???
Like, I get it’s cheap, but this is a LIFE-CHANGING side effect!
Someone should sue the pharma companies for not putting a skull-and-crossbones on this thing.
And why do I feel like I’m the only one who noticed???
My yoga instructor said I’ve been ‘off’ for months-now I know why.
I’m getting my CK tested tomorrow. If it’s high, I’m done with azathioprine.
Also, who else is mad they didn’t get this info BEFORE they started?
TL;DR: AZATHIOPRINE IS A SILENT MUSCLE KILLER. ASK FOR A CK TEST. NOW.
And stop blaming your muscles on ‘aging’-you’re not old, you’re poisoned.
Wendy Stanford October 28, 2025
It’s terrifying how medicine still operates on the assumption that patients are just passive recipients of protocols, not sentient beings with bodies that scream when something’s wrong.
We’re told to trust the system, to believe that if a drug has been around since the 60s, it must be safe-when in reality, safety is a statistical afterthought, not a moral imperative.
Myositis isn’t a footnote-it’s a betrayal.
Our bodies are not lab rats, yet we’re treated as if our suffering is just noise in the data stream.
And yet, when we speak up, we’re labeled ‘anxious,’ ‘hysterical,’ or ‘overreacting’-as if pain is a choice, not a signal.
The fact that we have to beg for a CK test, that it’s not standard, that it’s considered ‘extra’-that’s not medicine, that’s negligence dressed in white coats.
They don’t want to admit how little they know.
They’d rather you suffer quietly than admit their algorithms missed a pattern.
I’ve watched my mother go from hiking every weekend to needing help to stand up from her couch.
She was on azathioprine for 11 years.
They never tested her TPMT.
She didn’t know to ask.
And now, her muscles are permanently scarred.
This isn’t rare.
This is systemic.
Gavin McMurdo October 29, 2025
Oh, so now we’re supposed to panic because a drug that’s saved thousands of lives has a 0.1% risk of something that’s treatable if caught early?
Let me guess-next you’ll tell us that aspirin causes brain rot because one guy in 1987 had a stroke after taking two.
Statistically, azathioprine is safer than driving to the pharmacy.
And yet, here we are, turning a rare, reversible side effect into a horror story.
Do you know how many people are on methotrexate right now who are terrified of liver toxicity?
Or how many biologics cause serious infections?
Every drug has trade-offs.
The problem isn’t azathioprine.
The problem is the culture of fear-mongering that turns every medical article into a Netflix docu-drama.
Yes, check your CK if you’re worried.
Yes, get TPMT tested if you’re high-risk.
But don’t stop taking a life-saving drug because some guy on Reddit screamed about muscle weakness.
Medicine isn’t TikTok.
And if you’re going to write a 2000-word essay on a 1-in-1000 risk, at least have the decency to mention that 99.9% of people don’t get it.
Just saying.
Jessica Glass October 30, 2025
Oh sweet mercy, another ‘I didn’t know’ post.
Let me guess-you’re the same person who thought ‘statins cause muscle pain’ meant you could eat 3 pizzas a week and blame the drug?
Newsflash: if you’re on immunosuppressants, you don’t get to ignore your body.
It’s not magic.
You don’t get to take a drug that shuts down your immune system and then act surprised when weird stuff happens.
And yes, TPMT testing should be routine.
But guess what? It’s not because doctors are evil.
It’s because most patients don’t ask.
They don’t read the pamphlets.
They don’t Google.
They just take the pill and wait for the miracle.
Well, here’s the miracle: your body is not a black box.
It talks.
You just have to listen.
And if you’re too lazy to learn about your own meds?
Then don’t cry when things go wrong.
Lilly Dillon October 31, 2025
I’ve been on azathioprine for 4 years. No issues. But I started getting tired after walking up one flight of stairs.
I thought it was stress.
Then I saw this post.
Got my CK tested last week.
Level was 180.
Normal.
Still, I asked my rheumatologist to check it every 6 months now.
It’s not paranoia.
It’s just… being smart.
Thanks for the reminder.
Rohit Nair November 2, 2025
Bro, I'm from India and my cousin is on azathioprine for lupus.
He didn't know any of this either.
He just took the pills and said 'doctor said so, so it's fine'.
But last month he couldn't lift his grocery bag.
Thought it was tiredness.
Then he read this.
Went to doctor.
CK was 1400.
Stopped azathioprine.
Now on mycophenolate.
Three months later? He's back to lifting weights.
So yeah, this isn't just a 'Western problem'.
It's a global blind spot.
Thanks for writing this.
Sharing it with everyone I know.
Krishna Kranthi November 3, 2025
Man, azathioprine is like that one friend who’s chill for years then randomly steals your last slice of pizza and says ‘you didn’t say it was yours’
It’s been chill for 5 years, then BAM-muscles turning to jelly
And no warning?
Bro, that’s not a drug, that’s a betrayal
Also, TPMT test? Why isn’t that like, the first thing they do?
Like, you wouldn’t give someone a Ferrari without checking if they have a license
But we give this drug like it’s candy
And then we act shocked when someone crashes
Also, statins + azathioprine? That’s like putting diesel in a gasoline engine
Just say no
Alex Grizzell November 3, 2025
Hey, if you're on azathioprine and you're feeling off-don't wait.
Get your CK checked.
It's a simple blood test.
It takes 10 minutes.
It could save your mobility.
You don't have to be dramatic.
You just have to be proactive.
And if your doctor pushes back? Say: 'I read a study. I want a baseline.'
You're not being difficult.
You're being responsible.
And if you're an athlete? You're even more at risk because you'll blame soreness on training.
Don't let pride cost you your strength.
You got this.
John Bob November 3, 2025
Of course this is a ‘hidden danger’-because the FDA doesn’t want you to know that Big Pharma is secretly using your muscles as test subjects.
Did you know that azathioprine was originally developed as a chemical weapon?
They just repackaged it as a ‘life-saving drug’ to sell to the gullible.
And now they’re hiding myositis because if people knew, they’d stop taking it.
And then the profits would drop.
It’s all a scam.
They don’t care if you lose your legs.
They care about quarterly earnings.
And the ‘87% recovery rate’? That’s just the people who didn’t die.
And why do you think TPMT testing isn’t mandatory?
Because it costs money.
And if they tested everyone, they’d have to switch to expensive biologics.
It’s not medicine.
It’s capitalism.
Emilie Bronsard November 5, 2025
This is so important.
Thank you for writing this.
My sister was misdiagnosed for 8 months because they thought her weakness was from her RA.
She almost lost the ability to walk.
Now she’s on methotrexate and doing great.
Everyone deserves to know this.
Rodrigo Ferguson November 6, 2025
It’s fascinating how the modern medical establishment has turned patient autonomy into a performative gesture.
You’re told to ‘ask questions,’ yet the information required to ask meaningful questions is deliberately obfuscated behind layers of jargon, inertia, and profit-driven protocol.
Azathioprine is not a drug.
It is a symptom of a system that prioritizes scalability over safety.
The fact that TPMT testing is not universal in the U.S. is not an oversight.
It is a policy decision.
One that values cost-efficiency over individual biological integrity.
And now we are expected to be grateful for the crumbs of awareness scattered in Reddit posts.
How tragic.
How profoundly human.
And how utterly predictable.
Shiv Sivaguru November 8, 2025
Wow, someone actually wrote a whole essay on this?
Guess I'll just keep taking my pill and hoping for the best.
Also, I don't have time to get blood tests.
My boss doesn't care if my legs are weak.
TL;DR: life's too short to care.
Peter Feldges November 10, 2025
As a physician practicing in the U.S., I must commend the author for highlighting a critical, underrecognized adverse effect.
That said, the tone of this post risks inducing iatrogenic anxiety among patients who are otherwise stable.
While drug-induced myositis is a documented phenomenon, its incidence remains exceedingly low-far lower than the risk of uncontrolled autoimmune disease.
My recommendation remains unchanged: for patients with appropriate indications, azathioprine remains a first-line agent.
However, I now routinely order baseline CK and TPMT testing prior to initiation, and repeat CK every 6 months in long-term users.
Knowledge empowers.
But fear, without context, is a poor physician.
Thank you for the dialogue.
Jesse Weinberger November 11, 2025
Everyone’s freaking out about azathioprine like it’s the plague.
Meanwhile, nobody’s talking about how methotrexate causes liver fibrosis in 12% of long-term users.
Or how mycophenolate causes spontaneous abortions.
Or how biologics make you susceptible to TB and fungal infections.
It’s not the drug.
It’s the fact that every single immunosuppressant has a dark side.
So why are we treating azathioprine like a villain?
Because it’s cheap.
And cheap things are easy to blame.
Meanwhile, the $100,000-a-year biologics? They’re heroes.
How convenient.
George Johnson November 11, 2025
My uncle had this.
Stopped the drug.
Got better.
Now he's on a biologic.
He's alive.
And he can still carry his own groceries.
So yeah.
Listen to the post.
Don't panic.
But don't ignore it either.
Richard Kang November 12, 2025
Wait-so if I’m on azathioprine and my CK is normal, I’m safe?
What if it spikes tomorrow?
Do I just wait until I can’t get off the toilet?
And why is the only ‘solution’ to switch to a drug that costs 10x more and requires infusions?
This isn’t prevention.
This is privilege.
If you’re poor, you take the cheap drug.
And hope.
That’s not healthcare.
That’s gambling.