Oxymorphone

Is oxymorphone safe?

Oxymorphone is a strong opioid for severe pain that other treatments have not controlled, and it is one of the less forgiving ones. Milligram for milligram it is three times as strong as morphine and twice as strong as oxycodone, and on top of the usual opioid risks of addiction and fatal slowed breathing, its blood levels jump with alcohol, food and liver disease. Its best-known brand, Opana ER, was removed from the US market in 2017 after the FDA asked for it. We score it 24, below oxycodone and hydromorphone (both 26).

Three things that change the dose you actually get

Most opioids have a predictable relationship between the pill and the amount in your blood. Oxymorphone's is unusually easy to disturb.

The liver. Only about 10% of a swallowed dose reaches the blood, because the liver clears most of it on the first pass. When the liver is damaged, that filter fails. In a label study with extended-release tablets, exposure rose 1.6-fold in mild liver impairment, 3.7-fold in moderate impairment and 12.2-fold in the one patient with severe disease. The label rules it out for moderate or severe liver impairment and starts everyone else with liver problems at 5 mg.

Alcohol. Any sedative adds to an opioid's effect on breathing. With oxymorphone, alcohol also pushes up the amount of drug in the blood. Healthy volunteers who took a 40 mg extended-release tablet with 240 mL of 40% alcohol had peak levels 70% higher on average, and up to 270% higher in some people. The mechanism is unknown, which is why the label says to avoid alcohol completely, including medicines that contain it.

Food. In label studies, eating raised peak levels from extended-release tablets by about 50%. Both tablet types are taken on an empty stomach, at least 1 hour before or 2 hours after a meal.

Kidney problems and age matter too. Moderate to severe kidney impairment raised exposure by 57% to 65%, and people over 65 had levels about 40% higher.

Two tablets, the same strengths

Immediate-release oxymorphone comes in 5 mg and 10 mg tablets, taken every 4 to 6 hours. Extended-release tablets, taken every 12 hours, come in 5, 7.5, 10, 15, 20, 30 and 40 mg. The label warns pharmacists and prescribers about this overlap. Getting a 10 mg extended-release tablet where an immediate-release one was meant is a different dose over a different time, and crushing or chewing an extended-release tablet releases it all at once.

What happened to Opana ER

Opana ER was approved in June 2006. In December 2011 the FDA approved a new version, meant to resist crushing for snorting or injecting, and Endo took the original off the market. The FDA never let Endo label the new tablet as abuse-deterrent, because the data did not show it would reduce abuse.

What followed was a shift from snorting to injecting. In 2015, Scott County in rural Indiana, a place that normally saw fewer than five HIV diagnoses a year, had 181 new cases between November 2014 and November 2015. 87.8% of those patients said they had injected extended-release oxymorphone, and 92.3% also had hepatitis C. Indiana declared a public health emergency and opened its first syringe programme. Doctors in other states reported people with kidney failure from thrombotic microangiopathy, a clotting disorder, after injecting the dissolved tablets; some needed dialysis.

On 8 June 2017 the FDA asked Endo to withdraw the reformulated Opana ER, saying its benefits might no longer outweigh the public health consequences of abuse. Endo agreed on 6 July. Generic copies of the original formula stayed on sale, because the FDA had ruled in 2013 that the original was not withdrawn for safety reasons.

Who should be careful

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

• have any liver or kidney disease
• drink alcohol, or take a benzodiazepine, sleeping pill, gabapentin or pregabalin
• have sleep apnoea, asthma or COPD, or are over 65
• have had problems with alcohol or drugs
• are pregnant, because long-term use can cause withdrawal in the newborn
• live with children: one tablet can kill a child

Check whether each new bottle is immediate- or extended-release, and swallow extended-release tablets whole. Signs of overdose are pinpoint pupils, extreme sleepiness and slow or shallow breathing; call 911, give naloxone if you have it and stay with the person. US Poison Help is 1-800-222-1222. A low score does not mean you should stop a medicine you have been prescribed, and stopping suddenly after weeks of use causes withdrawal, so plan any taper with your prescriber.

How we scored it

Regulatory warnings (5) match fentanyl and methadone at the bottom of the scale, because the FDA asked for one of its brands to be removed. 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 (12) sits between oxycodone and hydromorphone, pulled down by its strength and its sensitivity to liver disease. Interactions (20) are lower than morphine's because alcohol raises blood levels as well as adding sedation. Dependence (10) and serious side effects (30) match the other 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 opioids, and track record (78) reflects decades on the market but much narrower use.