Oxycodone

Is oxycodone safe?

Oxycodone is an effective painkiller and, used for a few days after surgery or a serious injury under close supervision, it helps many people without lasting harm. But it is not safe in the way most medicines on our list are. It slows breathing, it causes physical dependenceDrug dependenceThe body's adaptation to a drug taken regularly, so that stopping it suddenly causes withdrawal symptoms. It is not the same as addiction.More in the glossary within weeks, and it can lead to addiction even in people who take it exactly as prescribed. We score it 26, one of the lowest of the medications we cover.

The risk is highest with long-term use, high doses, mixing with alcohol or sedatives, and for anyone other than the patient who gets hold of the tablets.

What the label now says about long-term use

US opioid labels now include results of studies the FDA required from manufacturers. Among people starting long-term Schedule IIControlled 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 opioid treatment between 2017 and 2021:

• about 1% to 6% newly met criteria for opioid addiction within 12 months
• about 9% showed prescription opioid abuse and about 22% misuse, such as taking extra doses

A second study of 220,249 new long-term users found that 1.5% to 4% had an opioid overdose within 5 years, and about 17% of first overdoses were fatal. Higher starting doses were the strongest predictor. The label also describes opioid-induced hyperalgesia, in which the drug makes pain worse rather than better.

Breathing: why the dose matters so much

Opioids reduce the brain's drive to breathe. Tolerance to this effect builds over time, which is why the OxyContin label reserves its 60 mg and 80 mg tablets, and daily doses above 80 mg, for people already tolerant to opioids. The same dose can kill someone who is not.

The risk peaks in the first days, after a dose increase, in older people and those with lung disease or sleep apnoea. Signs of overdose include pinpoint pupils, extreme sleepiness, slow or shallow breathing and blue lips. Call emergency services and give naloxone if it is available. Naloxone nasal spray has been sold without a prescription in the US since 2023.

How strong is it?

Taken by mouth, oxycodone is about 1.5 times as potent as morphine; the CDC's opioid guideline uses that factor to convert doses into morphine milligram equivalents. The 2022 guideline asks doctors to think carefully before going above 50 morphine milligram equivalents a day, which is about 33 mg of oxycodone, because overdose risk rises with dose. There is no fixed maximum on the label: doses are set for each patient, which is part of why close follow-up matters.

Mixing with other drugs

The 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 singles out benzodiazepines such as alprazolam (Xanax) and other sedatives, including alcohol, sleeping pills, gabapentin and pregabalin. Together they can cause profound sedation, slowed breathing, coma and death. According to NIDA, about 30% of prescription opioid overdose deaths also involve a benzodiazepine.

Oxycodone is broken down by the liver enzyme 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, so clarithromycin, erythromycin, ketoconazole and some HIV drugs can raise its levels, and stopping an inducer such as rifampin or carbamazepine can do the same.

Hidden acetaminophen

Percocet, Endocet and many generic combinations contain 325 mg of acetaminophen per tablet. People who also take Tylenol or a cold remedy can exceed the 4,000 mg daily limit and damage their liver. Check every label.

Who should be careful

Talk to your doctor about other options, or extra safeguards, if you:

• have had a substance use disorder, or have depression or anxiety
• take a benzodiazepine, sleeping pill, gabapentinoid or drink regularly
• have sleep apnoea, COPD, or liver or kidney disease
• are pregnant, because long-term use can cause withdrawal in the newborn
• live with children or people at risk of misuse

Store oxycodone locked away, never share it, and do not crush, chew or dissolve extended-release tablets: that releases a potentially fatal dose at once. Do not stop suddenly after weeks of use, and do not change the dose without your prescriber. For many kinds of pain, ibuprofen and acetaminophen together work as well as an opioid, and are worth asking about.

How we scored it

Only track record (85) scores well. Dependence (10), regulatory warnings (10), 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 (15), interactions (20) and serious side effects (30) are all in the lowest band, because the risks of addiction, fatal breathing problems and deadly drug combinations are built into how the drug works.