Can oral morphine be taken with liver cirrhosis?

From the Guidelines

Patients with cirrhosis should use oral morphine with caution and under medical supervision, as the liver's decreased function can lead to higher blood levels and prolonged effects, increasing the risk of side effects and toxicity. According to the 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma 1, morphine has an analgesic effect of its own, and over 90% is excreted via the kidney after being metabolized by conjugation in the liver. However, its half-life is increased by about two-fold in patients with liver cirrhosis, and its bioavailability is four-fold in patients with HCC compared to that in healthy individuals.

Key considerations for patients with cirrhosis taking oral morphine include:

• The dose should be reduced, and the dosing interval should be increased 1.5- to 2-fold in cirrhotic patients 1
• Alternative pain medications that are less dependent on liver metabolism, such as fentanyl, might be safer options 1
• Patients should watch for signs of opioid toxicity, including excessive drowsiness, confusion, slowed breathing, and pinpoint pupils
• Never adjust doses without medical guidance, as the margin between effective pain control and dangerous side effects is narrower in cirrhosis patients

It is essential to note that the severity of cirrhosis matters, and patients with mild cirrhosis may tolerate small doses with careful monitoring, while those with severe cirrhosis face much higher risks. A multidisciplinary approach involving experts in palliative care is needed to effectively manage acute, recurrent, and chronic pain in patients with cirrhosis 1.

From the FDA Drug Label

Morphine pharmacokinetics are altered in patients with cirrhosis. Clearance was found to decrease with a corresponding increase in half-life The M3G and M6G to morphine AUC ratios also decreased in these subjects, indicating diminished metabolic activity. Morphine pharmacokinetics have been reported to be significantly altered in patients with cirrhosis. Start these patients with a lower than usual dosage of morphine sulfate tablets and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension

Key Considerations:

• Morphine pharmacokinetics are altered in patients with cirrhosis
• Clearance decreases and half-life increases in patients with cirrhosis
• Patients with cirrhosis should be started with a lower than usual dosage of morphine sulfate tablets
• Dosage should be titrated slowly while monitoring for signs of respiratory depression, sedation, and hypotension 2, 2

Answer: Morphine can be taken orally with cirrhosis, but with caution and under close monitoring. The dosage should be started lower than usual and titrated slowly to avoid adverse effects.

From the Research

Oral Morphine with Cirrhosis

• The use of oral morphine in patients with cirrhosis is problematic due to the increased risk of toxicity, particularly in patients with hypoalbuminemia 3.
• Opioids, including morphine, have an increased risk of precipitating hepatic encephalopathy in patients with severe liver disease, and their use should be cautious and carefully monitored 4, 5.
• The pharmacokinetic properties of morphine must be taken into account when adjusting the dose in patients with liver cirrhosis, as the bioavailability of morphine increases and the clearance decreases after oral application 6, 5.
• Lower doses and/or longer administration intervals should be used when morphine is administered to patients with liver disease to avoid the risk of accumulation and the potential increase of adverse effects 5.
• Morphine is not recommended as a first-line treatment for pain management in patients with liver cirrhosis, and other options such as paracetamol, tramadol, fentanyl, and hydromorphone may be considered 3, 4, 7.

Key Considerations

• Patients with cirrhosis require individualized pain management, taking into account the severity of liver disease, history of opioid dependence, and potential drug interactions 3, 4.
• The use of opioids, including morphine, should be limited to short-acting agents for short duration, and co-prescription of laxatives is mandatory to avoid constipation and encephalopathy 3, 4.
• Adjuvant analgesics such as tricyclic antidepressants and anti-convulsants may be used cautiously for cirrhotic patients with neuropathic pain, and gabapentin or pregabalin may be better tolerated in cirrhosis due to non-hepatic metabolism and a lack of anti-cholinergic side effects 3, 7.