Morphine

Is morphine safe?

Morphine is the strong painkiller against which all others are measured, and still one of the most useful. In hospital, after major surgery or for cancer pain, it brings severe pain under control and the doses can be adjusted with care. But it is not a safe drug in the everyday sense. 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 with regular use, and addiction can develop even at prescribed doses. We score it 27, close to oxycodone (26) and hydrocodone (27).

Most of the risk sits in four situations: the first days of treatment or a dose increase, long-term daily use, mixing with alcohol or sedatives, and anyone other than the patient getting hold of it.

The yardstick for every other opioid

Doctors measure opioid doses in morphine milligram equivalents. The CDC's 2022 guideline gives morphine a factor of 1.0, oxycodone 1.5 and methadone 4.7, and asks prescribers to pause and reassess before going to 50 morphine milligram equivalents a day or more, because the risk of overdose climbs with the dose while the pain relief often does not.

The US labels set the starting points:

The MS Contin label limits single doses above 60 mg, or more than 120 mg a day, to people who are already tolerant, for example those who have taken at least 60 mg of oral morphine a day for a week or longer.

What the label says about long-term use

US opioid labels now include studies the FDA required from manufacturers. Among people starting long-term treatment with 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, about 1% to 6% newly met criteria for opioid 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, and about 17% of the first overdoses were fatal. A higher starting dose was the strongest predictor.

Constipation, nausea and sedation are the most common side effects on the MS Contin label, each affecting more than 10% of patients. Drowsiness and confusion are most likely at the start, and older people are more sensitive.

Kidneys and liquid morphine: two morphine-specific risks

Morphine is broken down in the liver into two active products, M3G and M6G, which leave the body through the kidneys. The label says both can build up to much higher levels in kidney failure, so people with poor kidney function start lower and are watched closely. Morphine is not processed by the 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 enzyme, which is why antibiotics and antifungals that raise oxycodone or fentanyl levels matter less here.

The second risk is the concentrated oral solution, 100 mg in every 5 mL. It has its own 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: confusing milligrams with millilitres, or one strength of liquid with another, can cause accidental overdose and death. It is meant only for patients already tolerant to opioids.

Mixing with other drugs

Like every opioid label since 2016, morphine's carries a 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 against combining it with benzodiazepines such as lorazepam or other sedatives, including alcohol, sleeping pills and gabapentinoids. Together they can cause profound sedation, slowed breathing, coma and death. The label says to reserve such combinations for patients with no adequate alternative. MAOIs, including linezolid, must not be used with morphine or within 14 days of stopping one.

Overdose: what to watch for

Signs include pinpoint pupils, extreme sleepiness or being impossible to wake, slow or shallow breathing, gurgling or snoring sounds, and blue or grey lips. Call emergency services and give naloxone if you have it; stay with the person, because naloxone can wear off before the morphine does. The label asks prescribers to discuss naloxone or nalmefene with every patient, and naloxone nasal spray is sold without a prescription in the US. US Poison Help is 1-800-222-1222.

Who should be careful

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

• have kidney or liver disease, sleep apnoea, asthma or COPD
• take a benzodiazepine, a sleeping pill, gabapentin or pregabalin, 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, since a single tablet can kill a child

Keep morphine locked away, never share it, and take leftovers to a pharmacy take-back point. After weeks of use, do not stop suddenly or change the dose on your own; withdrawal and uncontrolled pain are real risks, and a taper should be planned with your prescriber.

How we scored it

Track record (90) is the one strong factor: no opioid has been studied longer. Dependence (10), regulatory warnings (10) and 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) sit in the lowest band, and serious side effects (30) reflect fatal breathing problems and addiction at prescribed doses. Interactions (25) score a little better than for oxycodone because morphine avoids the 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 enzyme, but sedatives and alcohol remain dangerous.