Hydromorphone

Is hydromorphone safe?

Hydromorphone works well for severe pain, and in hospitals it is often the opioid of choice after surgery or for cancer pain. But it is one of the strongest opioids sold as tablets, and that strength is its main hazard. It carries every risk of morphine: slowed breathing, 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 and addiction even at prescribed doses. It adds a narrower margin for error, because a few milligrams too many is a large overdose. We score it 26, level with oxycodone and one point below morphine.

Why the strength matters

The CDC's 2022 opioid guideline gives hydromorphone a conversion factor of 5: 1 mg by mouth does the work of about 5 mg of morphine. Oxycodone's factor is 1.5. The same guideline asks doctors to pause before going above 50 morphine milligram equivalents a day, which is only 10 mg of oral hydromorphone, or two and a half of the 4 mg tablets.

That ratio is what makes mistakes dangerous. Morphine and hydromorphone have similar names, and patient safety groups count them among the drug pairs most often mixed up; US packs, including Dilaudid injection labels, print the name as HYDROmorphone to make it stand out. 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 on the Dilaudid oral liquid (1 mg per mL) warns that confusing milligrams with millilitres can cause a fatal overdose. The injection comes in a high-potency 10 mg/mL form meant only for people already tolerant to opioids, and the label warns that confusing it with standard strengths has caused overdose and death.

A study of US poison centre data from 2010 to 2016 found that serious outcomes per kilogram of drug dispensed followed potency almost in a straight line. Hydromorphone had the highest rate of the seven opioids studied, 8.02 serious events per 100 kg, and tapentadol the lowest, 0.27. Potency explained 96% of the spread, so the figures show how little hydromorphone it takes to do harm, not a higher risk per prescription.

Doses on the US label

The extended-release tablets are taken once a day, and only by people who have taken at least 8 mg of oral hydromorphone a day, 60 mg of oral morphine or an equivalent for a week or longer. Swallow them whole. Crushing or chewing releases the full day's dose at once.

What the label says about addiction

The label includes the results of studies the FDA required from opioid makers. 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, about 1% to 6% newly met criteria for addiction within 12 months, and about 9% showed prescription opioid abuse. In a second study of 220,249 new long-term users, 1.5% to 4% had an opioid overdose within 5 years. The label describes a high potential for misuse, and notes that injecting drugs meant for the mouth spreads hepatitis and HIV.

Mixing with alcohol and other drugs

Hydromorphone is cleared by the liver through glucuronidation rather than the CYP enzymes, so it has fewer enzyme interactions than oxycodone or fentanyl. The dangerous combinations are the same as for any strong opioid: benzodiazepines such as lorazepam, alcohol, sleeping pills, gabapentin and pregabalin, muscle relaxants and other opioids. MAOIs are not recommended with it or within 14 days of stopping one.

Alcohol has a history with this drug. Palladone, a once-a-day capsule, was approved in the US in September 2004 and withdrawn in July 2005 after a study showed that alcohol could make the capsule release its hydromorphone too fast.

Who should be careful

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

• have kidney or liver disease: the label starts these patients at a quarter to a half of the usual dose
• have sleep apnoea, asthma or COPD, or are older or frail
• take a benzodiazepine, sleeping pill, gabapentinoid or drink regularly
• have had problems with alcohol or drugs
• are pregnant, because long-term use can cause withdrawal in the newborn
• live with children: one dose can kill a child

Check the strength on every new box or bottle, use the oral syringe that comes with the liquid, and ask the pharmacist if the tablets look different. Signs of overdose include pinpoint pupils, extreme sleepiness, slow or shallow breathing and blue lips. Call emergency services, give naloxone if you have it and stay with the person. US Poison Help is 1-800-222-1222. Do not stop suddenly after weeks of use; plan any taper with your prescriber.

How we scored it

Track record (85) is the only strong factor. 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 (10) is lower than morphine's because of the drug's strength and its record of dose and name mix-ups. Dependence (10) and regulatory warnings (10) sit in the lowest band, and serious side effects (30) reflect fatal breathing problems and addiction at prescribed doses. Interactions (25) match morphine, since neither depends on CYP enzymes.