CYP2D6 Metabolizer Risk Calculator
How Your Genes Affect Codeine Safety
This tool estimates your risk of being a CYP2D6 ultrarapid metabolizer based on your ethnicity. People with this genetic profile convert codeine to morphine too quickly, risking overdose even at standard doses.
Your risk will appear here after calculation
Codeine is one of the most commonly prescribed pain relievers and cough suppressants - but for a small group of people, even a single pill can be deadly. It’s not because they took too much. It’s because their body turns codeine into morphine too fast. This isn’t rare. In Australia, about 3% of people have a genetic quirk that makes them ultrarapid metabolizers of codeine. For them, standard doses can cause respiratory failure, coma, or death - often within hours.
How Codeine Turns Into a Silent Killer
Codeine itself doesn’t relieve pain. It’s a prodrug - meaning it’s inactive until your body converts it. That conversion happens through an enzyme called CYP2D6. In most people, this process is slow and steady. But in ultrarapid metabolizers, the CYP2D6 enzyme works at lightning speed. They have extra copies of the gene that makes this enzyme, so they turn codeine into morphine 3.5 to 4.5 times faster than normal.
The result? Blood morphine levels skyrocket. A normal dose meant for a 70kg adult can produce morphine concentrations seen only in opioid addicts on high-dose IV therapy. The body can’t handle it. Breathing slows. Then stops. Heart rate drops. In children, this often happens after routine surgeries like tonsillectomies. In adults, it can happen after taking codeine for a toothache or back pain.
The FDA Warning That Changed Everything
In 2013, the U.S. Food and Drug Administration issued a stark warning: codeine can kill children who are ultrarapid metabolizers. They reviewed 64 case reports. Of those, 24 people died. Twenty-one of them were under 12. In 15 cases where blood levels were tested, 13 showed morphine levels far above the safe range.
One case, published in the New England Journal of Medicine, involved a 15-month-old boy who died after receiving codeine following adenoid surgery. Post-mortem testing confirmed he was an ultrarapid metabolizer. His morphine levels were lethal. He never had a chance.
The FDA didn’t just issue a warning - they forced drugmakers to add a boxed warning to every codeine label. It’s the strongest type of warning they can give. It says clearly: Respiratory depression and death have occurred in children who received codeine following tonsillectomy or adenoidectomy, and had evidence of being CYP2D6 ultrarapid metabolizers.
Who’s at Risk? It’s Not Random
This isn’t about age, weight, or liver health. It’s about genes. Your CYP2D6 genotype determines how you process codeine. There are four main types:
- Ultrarapid metabolizers (UMs): Activity score >2.25. These people have multiple functional gene copies. They convert codeine to morphine too fast. Risk of overdose is real.
- Normal metabolizers: Score 1.25-2.25. This is the majority. Codeine works as expected.
- Intermediate metabolizers: Score 0.25-1.0. Codeine may not work well for pain relief.
- Poor metabolizers: Score 0. Codeine does nothing. They get no pain relief.
The problem? Most doctors don’t test for this. They prescribe codeine the same way they did 20 years ago. And they’re not alone. Even today, only 15-20% of major U.S. hospitals routinely test for CYP2D6 status before prescribing.
But the risk isn’t evenly spread. In Australia, about 3% of people are ultrarapid metabolizers. In North Africa and Ethiopia, that number jumps to nearly 30%. In East Asia, it’s closer to 1%. So if you’re from a North African background and your doctor prescribes codeine for your child’s sore throat, you’re facing a risk that’s 10 times higher than someone from East Asia.
What Happens When It Goes Wrong
The signs of morphine toxicity from codeine aren’t subtle. They’re sudden and terrifying:
- Extreme drowsiness - so deep they can’t be woken up
- Slow, shallow breathing - or no breathing at all
- Blue lips or fingertips
- Cold, clammy skin
- Low blood pressure, weak pulse
- Loss of consciousness
These symptoms can appear within 30 minutes to 2 hours after taking codeine. In children, they often happen overnight. Parents find their child unresponsive in bed. Emergency services arrive too late.
One Australian study found that among patients with codeine use disorder, those with normal or ultrarapid metabolizer status were more likely to develop addiction - not because they were abusing it, but because their bodies were producing high morphine levels on standard doses. They didn’t need to take more. Their body was already giving them a powerful opioid rush.
What Should You Do Instead?
If you’re prescribed codeine, ask: Is there a safer option?
There are plenty. The Clinical Pharmacogenetics Implementation Consortium (CPIC) says clearly: Do not use codeine or tramadol in ultrarapid metabolizers. Instead, use:
- Morphine - already active, doesn’t need CYP2D6
- Hydromorphone - direct-acting, no metabolic conversion needed
- Fentanyl - works through different pathways
- Paracetamol (acetaminophen) - effective for mild to moderate pain
- Ibuprofen - good for inflammation-related pain
Even hydrocodone and oxycodone - often seen as safer - still get partially converted by CYP2D6 into stronger opioids (hydromorphone and oxymorphone). So while they’re better than codeine, they’re not risk-free for ultrarapid metabolizers.
For children under 12, the American Academy of Pediatrics and the FDA agree: avoid codeine entirely. Use paracetamol or ibuprofen first. If you need stronger pain relief, ask for morphine or hydromorphone. These drugs don’t rely on your genes to work.
Can You Get Tested?
Yes. CYP2D6 genetic testing is available through most hospital labs and private genetic testing companies. A simple cheek swab or blood sample can tell you your metabolizer status. Turnaround time? Usually 3 to 14 days. Cost? Around $200-$500. Insurance often requires prior authorization.
But here’s the catch: testing isn’t routine. Unless you ask for it, or your doctor has a pharmacogenomics program, you won’t get tested. And most GPs don’t think to order it.
Some hospitals - especially children’s hospitals and cancer centers - now do pre-emptive testing for multiple genes, including CYP2D6, before prescribing any medication. But it’s still the exception, not the rule.
There’s promising research underway. The NIH is funding a $2.5 million project at Vanderbilt University to develop point-of-care CYP2D6 testing that could give results in under two hours. If that works, we could one day test a patient in the ER before giving them codeine - and know instantly if it’s safe.
Why This Matters More Than You Think
Codeine isn’t just a painkiller. It’s a genetic trap. Millions of people have taken it without knowing their risk. The deaths weren’t accidents. They were preventable.
Pharmacogenetics - using your genes to guide drug choices - isn’t science fiction. It’s here. And codeine is one of the clearest examples of why it matters. For some, it’s the difference between relief and death. For others, it’s the difference between no pain relief and a wasted prescription.
The future of medicine isn’t one-size-fits-all. It’s one-size-for-you. And until we start testing, we’re just guessing.
Can codeine kill you even if you take the right dose?
Yes. If you’re a CYP2D6 ultrarapid metabolizer, your body turns even a standard dose of codeine into a lethal amount of morphine. You don’t need to overdose - your genes do it for you. This has caused deaths in children and adults who took exactly what their doctor prescribed.
How do I know if I’m an ultrarapid metabolizer?
You need a genetic test for CYP2D6. It’s done with a cheek swab or blood sample. Most people don’t know their status unless they’ve been tested for another reason. If you’ve had codeine cause extreme drowsiness or breathing problems in the past, or if you’re from a population with high UM rates (like North Africa), you should consider testing.
Is codeine banned for children?
Not officially banned, but strongly restricted. The FDA, Australian Therapeutic Goods Administration, and European Medicines Agency all advise against codeine for children under 12, especially after tonsil or adenoid surgery. Many hospitals now refuse to prescribe it to children at all.
Are there safer painkillers than codeine?
Yes. For mild pain, paracetamol or ibuprofen are first-line. For moderate to severe pain, morphine, hydromorphone, or fentanyl are safer options because they don’t rely on CYP2D6 to become active. These drugs work directly and predictably, no matter your genes.
Why hasn’t codeine been pulled from the market?
It’s still used in some countries for coughs and mild pain, and it’s cheap. But its use is declining. In the U.S., pediatric codeine prescriptions dropped by 50% between 2012 and 2015 after the FDA warning. Experts predict codeine will become obsolete in the next 10 years as genetic testing becomes more common and safer alternatives are widely adopted.
13 Comments
So let me get this straight - we’re still giving out a drug that can kill people based on their DNA, and the only thing stopping it is a warning label? That’s not safety, that’s negligence with a side of bureaucracy.
My cousin took codeine after a wisdom tooth extraction and slept for 14 hours straight. No one knew why. Now I know. She’s fine, but what if she wasn’t?
This isn’t rare. It’s systemic. And it’s not just kids - adults get hit too. I’ve seen ER docs shrug and say ‘it’s just codeine.’ Like it’s aspirin.
Why isn’t this test part of routine blood work? We test for everything else - why not the enzyme that turns a painkiller into a death sentence?
It’s not about cost. It’s about priorities. We spend billions on cancer screenings, but a $300 genetic test that prevents overdose? Meh. Let’s just hope you’re not one of the 3%.
And don’t get me started on how this disproportionately affects people of African descent. We’re talking 30% in some regions. That’s not a fluke. That’s a public health crisis wrapped in genetic luck.
Doctors aren’t evil. They’re just trained in a system that ignores pharmacogenomics like it’s sci-fi. Time to update the curriculum.
I’m not a doctor. But if I were prescribed codeine tomorrow, I’d demand a CYP2D6 test before I swallowed a single pill. No excuses.
If you’re reading this and you’ve ever had codeine make you weirdly sleepy or dizzy - get tested. You might be one of the lucky ones who survived.
And yeah, I’m telling my mom to stop using codeine for her back pain. She’s from Nigeria. She’s probably a UM. She doesn’t even know it.
It’s 2024. We have DNA sequencing in our phones. We can’t keep pretending genes don’t matter.
Oh great. Another ‘your genes might kill you’ post that does nothing but scare people and blame doctors.
Let’s be real - if you’re dumb enough to take codeine without asking questions, you deserve what you get.
And yes, I’m talking to you, the people who still think ‘natural’ means ‘safe.’ Codeine is a semi-synthetic opioid. It’s not herbal tea.
Stop pretending this is some mysterious genetic conspiracy. It’s basic pharmacology. Learn it. Or don’t take the pill.
Also, why are we still talking about this? The FDA warned us in 2013. Ten years later, and people are still acting surprised?
Blame the system? Fine. But also blame the patients who don’t read the damn label.
Paracetamol exists. Ibuprofen exists. Why are we still using a drug that’s basically a genetic Russian roulette?
Answer: because it’s cheap. And someone’s making money off your ignorance.
So next time your doctor prescribes it, say ‘no.’ Or better yet - ask for the test. Don’t wait for your kid to stop breathing before you care.
I had no idea about this until I read this post. I’m so glad I did.
My sister got codeine after her C-section and was barely responsive for two days. We thought it was just the pain meds. Turns out she’s an ultrarapid metabolizer. She didn’t know either.
Now she takes morphine for any serious pain. And she’s been fine ever since.
I’m getting tested next week. I’m from Ethiopia - I’ve got a 1 in 3 shot of being a UM.
Why isn’t this standard before surgery? Why aren’t ERs doing this on admission?
It’s not just about codeine. It’s about how medicine still treats people like they’re all the same.
I’m telling everyone I know. This needs to be common knowledge.
Thank you for writing this. I feel like I just learned something that could save my life.
Okay, I need to sit down. This is one of those posts that makes you feel like you’ve been living in a parallel universe where everyone else knows the rules but you.
I took codeine for a toothache last year. Felt like I was underwater. Couldn’t wake up. Thought I was just really tired. Turns out I might’ve been seconds away from stopping breathing.
I’m half Nigerian. Half Irish. My mom’s side? High UM rates. My dad’s? Probably not. So I’m a genetic lottery ticket.
And now I’m terrified to take any painkiller. I don’t even trust ibuprofen anymore. What if my liver processes it weirdly too?
Why isn’t this on every prescription bottle? Like a big red flashing sign: ‘YOUR GENES MAY TURN THIS INTO A DEADLY OPIOID.’
I’m calling my doctor tomorrow. I need that test. I’m not waiting for another near-death experience to make me care.
And if you’re reading this and you’ve ever felt ‘too sleepy’ after codeine - please, please, please get tested. Don’t be like me. Don’t wait for the worst.
I’m scared. But I’m also angry. Why did it take a stranger on the internet to tell me this?
And why does it cost $500? Shouldn’t this be covered by insurance? It’s literally life or death.
I’m telling my whole family. Everyone. Even my 70-year-old uncle who still takes codeine for his arthritis.
This isn’t science. This is survival.
So codeine = bad for some people. Got it.
What’s the test called? CYP2D6? Can I get it at Walgreens?
How long does it take? Can I do it while I wait for my prescription?
Is it covered by insurance?
What if I don’t know my family history?
Can I just ask my doctor to skip codeine and give me something else?
Why isn’t this common knowledge?
Does this apply to tramadol too?
What about my kid’s tonsil surgery next month?
Should I bring this up or will they think I’m weird?
Can I get a printout of this post to show my doctor?
OMG I had no idea 😳
I took codeine after my wisdom teeth and felt like I was floating on clouds… for 8 hours. I thought it was just really good pain relief.
Now I’m scared. I’m from India - is that high risk?
I’m getting tested ASAP. Like, tomorrow.
My mom still takes it for her back. I’m sending her this link.
Why isn’t this on the box??
Also, I think I’m an ultra metabolizer. I’ve always been super sensitive to meds. Even a tiny bit of ibuprofen makes me dizzy.
Thank you for sharing this. I feel like I just dodged a bullet.
PS: I’m telling my whole family. Everyone. Even my cousin in Nigeria.
Why are we even still using codeine? It’s a relic from the 1950s.
Every time I see someone on Reddit saying ‘codeine cough syrup is the best’ I want to scream.
This isn’t about genetics - it’s about lazy medicine.
Doctors don’t want to think. They just prescribe.
And the FDA? They wait until kids die before they act.
Meanwhile, people in Africa and the Middle East are dying because their doctors don’t even know this exists.
It’s not a genetic problem. It’s a Western medical system problem.
Stop blaming the genes. Start blaming the system.
And if you’re white and from the US and you’re shocked by this - you’ve been privileged.
People of color have been dying from this for decades. You just didn’t hear about it.
Wake up.
So… what’s the point of medicine if your genes decide if a pill kills you or not?
Are we just rolling dice every time we take a drug?
What’s next? Do I need a DNA test before I take Tylenol?
Feels like we’re living in a sci-fi movie where your genome is your prison sentence.
Codeine’s not the problem. The system is.
Why not just ban it? If it’s this dangerous, why is it still on the shelf?
Maybe we should just stop prescribing drugs entirely and let people figure it out.
Or… maybe we should just accept that biology is messy.
And maybe… we’re all just one bad gene away from being a statistic.
✌️
This is exactly why I became a pharmacist.
I’ve seen too many patients get hurt because we treat meds like they’re one-size-fits-all.
I always ask about family history - but even then, I can’t predict CYP2D6 without a test.
I’ve started asking every patient: ‘Have you ever had codeine make you too sleepy?’ If they say yes - I switch them immediately.
And I always mention genetic testing. Even if they don’t ask.
It’s not my job to scare people. It’s my job to protect them.
And honestly? I wish every prescriber had to take a pharmacogenomics course before they could write a script.
We’re not just giving pills. We’re giving genetic outcomes.
Let’s stop pretending we can guess.
Let’s start testing.
I’m from Ethiopia. I’ve seen this firsthand.
My uncle died after a minor surgery. They gave him codeine. He never woke up.
No one knew about CYP2D6. No one tested him.
They said it was ‘complications.’
It wasn’t.
Now I make sure everyone in my family gets tested before any surgery.
It’s expensive. It’s hard to find. But we do it.
And I tell every Ethiopian friend I have: don’t take codeine. Ever.
It’s not worth the risk.
And if your doctor says it’s safe - ask them if they’ve ever tested a patient for CYP2D6.
If they say no - walk out.
Codeine dangerous for ultrarapid metabolizers. Test CYP2D6 before use. Simple.
I read this and immediately called my mom.
She’s 68. Has been taking codeine for 20 years for her arthritis.
She said she never felt ‘too sleepy’ - but she always fell asleep after dinner. Thought it was just old age.
Turns out she’s from Jamaica. High UM prevalence.
I got her scheduled for a test. She’s nervous. But she’s doing it.
Thank you for writing this. I didn’t know I needed to hear it until I did.
And now I’m telling my whole family. Even my dad who thinks ‘if it’s prescribed, it’s safe.’
Genes don’t care about prescriptions.
They just work.
Why do we need science to tell us that drugs are dangerous
Human body is complex
But we still give pills like candy
And then cry when someone dies
It’s not the gene
It’s the arrogance
We think we control nature
We don’t
Codeine is not the villain
Our ignorance is
Stop blaming enzymes
Start blaming doctors
And the system
And the greed
And the laziness
And the silence