Codeine

Is codeine safe?

For most adults taking a few days of a low dose, codeine is reasonably safe, but it is less predictable than most painkillers. Codeine itself does little. The liver enzyme CYP2D6CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary turns part of it into morphine, and how much depends on your genes. Some people get almost no pain relief; a few turn it into morphine so quickly that a normal dose becomes an overdose. Children and breastfed babies have died this way. We score it 42, above tramadol (34) and oxycodone (26).

Ultra-rapid metabolisers

The US label estimates that 1% to 10% of white people, 3% to 4% of Black people and 1% to 2% of East Asians are ultra-rapid metabolisers, and more than 10% in some groups, including people of North African, Middle Eastern and Ashkenazi Jewish origin. The MHRA's 2013 review cited rates of up to 29% in Ethiopian populations. At the other end, 7% to 10% of white people are poor metabolisers who make very little morphine.

Most people do not know their CYP2D6CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary type, which is why regulators restrict codeine by age rather than by test:

• US (April 2017): contraindicatedContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary for pain or cough in children under 12, and for pain after tonsil or adenoid removal under 18; to be avoided in teenagers with obesity, sleep apnoea or severe lung disease; breastfeeding not recommended.
• UK and EU (2013): only for acute moderate pain in children over 12 when paracetamol or ibuprofen alone fail; contraindicated after tonsil or adenoid surgery for sleep apnoea under 18, in known ultra-rapid metabolisers and in breastfeeding mothers. The review followed three deaths and one life-threatening case in children after such surgery.

Over-the-counter codeine

Codeine used to be sold freely in low-dose combinations in many countries, and regulators have steadily pulled it back because of addiction.

Australia made all codeine prescription-onlyPrescription-only medicineA medicine that can be supplied only with a prescription from a doctor or another authorised prescriber.More in the glossary on 1 February 2018, ending pharmacy sales of low-dose combinations.

The UK has kept pharmacy sales of low-dose products such as co-codamol 8/500, but since 2009 the MHRA has required the pack warning "Can cause addiction. For three days use only", limited them to short-term acute moderate pain not relieved by paracetamol, ibuprofen or aspirin alone, and ended pharmacy sale of packs larger than 32. Codeine linctus for cough moved to prescription-only in 2024, after deaths involving codeine in England and Wales rose from 88 in 2011 to 200 in 2021. In 2024, codeine was mentioned on 246 such death certificates (ONS).

The US keeps codeine on prescription in almost every form. Codeine cough syrups such as promethazine with codeine are Schedule VControlled substanceA medicine or drug that the law restricts because it can be misused or cause dependence. Countries group them into schedules or classes.More in the glossary and approved only for adults.

Hidden acetaminophen and doses

Most codeine is sold with acetaminophen (paracetamol). Tylenol with Codeine No. 3 has 300 mg of acetaminophen and 30 mg of codeine; UK co-codamol has 500 mg of paracetamol with 8, 15 or 30 mg of codeine.

Product	Usual adult dose	Daily limit
Codeine (US label)	15 to 60 mg every 4 hours as needed	360 mg codeine
Acetaminophen in US combinations	300 to 1,000 mg per dose	4,000 mg
Co-codamol (NHS)	1 or 2 tablets up to 4 times a day	8 tablets; 3 days if bought

Taking a separate paracetamol or cold remedy on top is the commonest way to overdose on the acetaminophen in these products, which can cause liver failure.

Interactions that change the dose you actually get

Because codeine depends on two liver enzymes, other drugs change its effect. CYP3A4CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary inhibitors such as erythromycin, ketoconazole and ritonavir push more codeine towards morphine and can cause fatal breathing depression. CYP2D6 inhibitors such as fluoxetine, paroxetine and bupropion do the opposite and can leave pain uncontrolled. Like all opioids, codeine with benzodiazepines such as alprazolam, alcohol or gabapentinoids can stop breathing.

Who should be careful

Talk to your doctor or pharmacist before taking codeine if you are breastfeeding, have asthma, COPD or sleep apnoea, take an antidepressant, sedative or antibiotic, drink alcohol, have liver or kidney disease, or have ever had a problem with opioids. Never give codeine to a child without medical advice, and if you have bought it, stop after 3 days and ask for help if the pain continues.

How we scored it

Track record (92) is strong after more than a century of use. Regulatory warnings (15) are in the lowest band because of the opioid boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary and child restrictions. Interactions (30), dependence (35), overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (40) and serious side effects (45) reflect an opioid whose strength varies from person to person.