We use cookies to ensure that we give you the best experience on our website. If you continue browsing our
website without changing your settings, we will assume that you are happy to receive all cookies on our site.

You can visit our Cookie Policy page to learn more about cookies and how to disable them, should you wish to withdraw your consent. Our Cookie Policy page explains what cookies are, lists the cookies used on this website, and outlines how you can manage them.

Continue
 
Subscribe to our regular email newsletter

Before you go...

Please give us your feedback on our site:

How useful was the site to
you today?




WRITTEN BY

Dr Michał Chojnicki
Dr Michał Chojnicki works in the Department of Biology and Environment Protection, Poznań University, Poznań, Poland

Dr Wojciech Leppert
Dr Wojciech Leppert is chair of the Department of Palliative Medicine, Poznań University of Medical Sciences, Poznań, Poland

Interactive case study

Opioid-induced constipation and pain in a cancer patient

Opioid-induced constipation and pain in a cancer patient
- a case study
 
 
 
 
 
 
 
The Case

A 77-year-old woman received treatment for a grade 2 adenocarcinoma of the right pulmonary hilum with probable left lung metastases.

Fatigue and loss of about 10% of her body weight within three months were observed, and periodic exacerbations of dyspnoea and cough had begun 10 months earlier.

Click the hotspots to
investigate the patient's
history and results of previous
investigations

 
 
 
 
Presentation

The patient declined the further oncological treatment that was recommended, including radiotherapy. This was because her late husband, who had died of lung cancer three years earlier, had an adverse experience of chemo-radiotherapy.

A CT scan showed complete closure of the right lobar bronchus but she did not consent to brachytherapy, which was recommended by her physician.

Six months after the patient had been diagnosed with lung cancer, her daughter referred her to a home hospice service.

Click the hotspots to find out
what was reported at her home
hospice visits

Medication
The patient's consultation with the palliative care team revealed that she was taking several medications.
Digoxin
 
The patient had been treated for atrial fibrillation for 16 years and was taking digoxin 250 microgram once-daily.
Buprenorphine
 
The patient's GP had prescribed transdermal buprenorphine
35 microgram/hour patches.
Valsartan
 
The patient was taking valsartan 80mg once-daily for hypertension.
Medication
The patient's consultation with the palliative care team revealed that she was taking several medications.
Beta-2 agonist and corticosteroid
 
Bronchial asthma had also been diagnosed six years previously, for which the patient was taking an inhaled long-acting beta-2 agonist and corticosteroid medication regimen.
Tramadol drops and paracetamol
 
The patient's GP had prescribed - temporarily - tramadol drops and paracetamol.
The clinical challenge
Her GP had prescribed transdermal buprenorphine 35 microgram/hour patches, and - temporarily - tramadol drops and paracetamol. She was unsatisfied with her analgesic therapy and asked the home hospice doctor for intensification of her pain relief along with a switch from patches to oral drugs.

During the examination, lung auscultation revealed a whistle together with the loss of vesicular murmur over the right upper lobe, and increased and symmetrical bronchial murmur. Palpation of the abdomen revealed faecal masses in the large intestine. No distal oedema or ascites were found.

She was given oral ibuprofen 400mg, which reduced the pain in her ribs to 2-3 out of 10 after 30 minutes.
What therapeutic strategies could be considered to treat this patient's pain
In more depth ...
What therapeutic strategies could be considered to treat this patient's pain
Start oral immediate-release (IR) or prolonged-release (PR) morphine
Start oral PR morphine
Start oral IR or PR oxycodone
Start oral PR oxycodone
Start oral PR oxycodone/PR naloxone
Morphine is a first-line oral opioid recommended for the management of patients with moderate to severe pain intensity. The IR formulation may be useful in the period of morphine titration and for the management of bouts of dyspnoea. However, when a stable dose of morphine is established it may be more convenient for the patient to take a PR formulation twice-daily instead of using IR morphine every 4-6 hours with IR morphine used for breakthrough pain and dyspnoea attacks.
What's another option?
The patient could start morphine treatment with regular PR morphine administration during the titration period, along with IR morphine formulation for breakthrough pain and dyspnoea episodes. The treatment may be continued after establishing a stable dosage of morphine.
What's another option?
Similar to morphine, oxycodone is recommended as a first-line therapeutic option for patients with moderate to severe pain. Oxycodone has similar analgesic efficacy to morphine, and it not only activates mu-opioid receptors (similar to morphine) but also kappa-opioid receptors.1 IR oxycodone may also be used for the management of dyspnoea attacks in this patient. Again, after establishing a stable dosage the patient may prefer to take PR oxycodone for background pain with IR oxycodone for control of breakthrough pain and bouts of dyspnoea.
What's another option?
The patient could start oxycodone treatment with regular PR oxycodone administration during the titration period along with IR oxycodone for the treatment of breakthrough pain and dyspnoea episodes. The treatment may be continued after establishing a stable dosage of oxycodone.
What's another option?
This option is attractive as the patient has a history of constipation in the past. This drug combination may provide effective analgesia through the action of oxycodone on opioid receptors in the central nervous system (CNS) while reducing opioid-induced constipation through the action of naloxone on opioid receptors in the gastrointestinal (GI) tract. The patient should also be prescribed an IR formulation of oxycodone or morphine to manage breakthrough pain and dyspnoea episodes. IR formulations might also be helpful during a titration phase.
What's another option?
In this case ...
The patient was prescribed prolonged-release oxycodone tablets 5mg twice-daily, increased after two days to two tablets twice-daily, and diclofenac retard 75mg twice-daily, with a proton pump inhibitor. Buprenorphine patches were discontinued. She was also prescribed oral morphine solution 2.5mg to be taken during bouts of dyspnoea. The physician recommended she take macrogol 10g twice-daily to prevent constipation.

This approach will cover effective background pain management and appropriate treatment of dyspnoea attacks.2,3

On the third day of this therapy, the patient telephoned the hospice service to report improvement in her pain control. On the seventh day of the therapy the hospice nurse was informed about the patient's cramp-like abdominal pain, characteristic of constipation.

The nurse recommended taking a one-off dose of metamizole and drinking senna tea, two tea bags in the evening. Within 36 hours the patient was able to have a bowel movement. It was then decided that she should constantly take macrogol 10g once-daily along with periodic consumption of senna tea.
Diagnosis of OIC
Opioid-induced constipation (OIC) is a common adverse event (AE) of opioid therapy in cancer patients who require regular opioid administration for pain.

However, clinicians often underestimate the problem of OIC, which is characterised by:4
  • Straining
  • Hard stools
  • Painful, infrequent and incomplete bowel movements.

Other symptoms can be equally distressing, such as anorexia, feeling bloated, nausea and overflow diarrhoea.
Read more about opioid-induced constipation
In more depth ...
Read more about opioid-induced constipation
How common is OIC?
What mechanisms underlie OIC?
How does OIC differ from other types of constipation?
OIC is a common phenomenon in patients receiving long-term opioid therapy. Although the incidence differs, most studies show that the prevalence ranges from 40% to 90% of patients treated with opioid analgesics.5 OIC may be present in patients treated with all opioid analgesics, by all routes of administration (oral, transdermal, parenteral and intrathecal).
What else should I know?
Opioid actions at opioid receptors in the myenteric plexus result in significant deterioration of peristalsis with concurrent increase in resting muscle tone, spasm and non-propulsive motility patterns. These mechanisms induce delayed gastric emptying and slow intestinal transit. The submucosal plexus controls the secretion of biliary and pancreatic juices and the absorption of the gut contents that are significantly reduced and increased, respectively, after opioid administration. As a consequence, the stool becomes hard and dry. Moreover, opioids increase the tone of all sphincters in the GI tract and reduce the defecation reflex.4
What else should I know?
OIC is a complex phenomenon that involves several underlying mechanisms that differ to those of other causes of constipation.4 However, it should be kept in mind that patients with OIC may also have other factors that exacerbate symptoms, such as comorbidities or concomitant medication. OIC should be also seen in a wider context of opioid-induced bowel dysfunction (OIBD) that comprises symptoms of the whole GI tract including dry mouth, gastroesophageal reflux, nausea and vomiting, gastroparesis, bloating, abdominal pain and constipation symptoms. Therefore, a comprehensive clinical assessment is mandatory for the appropriate management of patients with OIC.
What else should I know?
Symptoms of OIC
OIC Symptoms
Straining
Hard stools
Anorexia
Painful, infrequent and incomplete bowel movements
Bloating
Nausea
Overflow diarrhoea
 
 
Consequences
Management
 
Consequences
  • Constipation sometimes limits clinicians ability to deliver adequate analgesia6
  • Untreated or inappropriate management of OIC symptoms may lead to non-compliance with the opioid regimen and limited efficacy of opioid therapy6
Management
 
Management
  • The European Association for Palliative Care recommendations on the use of opioid analgesics in the treatment of cancer-related pain strongly support routine prescription of laxatives for management or prophylaxis of OIC.7
  • A combination of drugs with different modes of action is preferred in more difficult cases.
  • With a history of previous bowel movement problems, the clinician should pay particular attention to bowel function when considering opioid treatment in this case.
Consequences
Effective management
  • During the next visit by the home hospice doctor, 14 days later, considerable improvements in both pain control (rating 1-2) and dyspnoea were observed. The patient's largest problem was constipation and periodic abdominal pain.

  • Following intensification of therapy to oxycodone 10mg twice-daily, she had a bowel movement every seven days.
What treatment options could be considered to treat OIC?
In more depth ...
What treatment options could be considered to treat OIC?
Comprehensive clinical evaluation
Non-pharmacological measures
Treatment of specific OIBD symptoms
Opioid switching
Oral laxatives
Rectal measures
Targeted therapies
This is indicated as the first step and would include other symptoms, comorbidities and non-medical (psychological, social and spiritual) dimensions.
What's another option?
These might include possible dietary advice and also education of patients and carers.
What's another option?
Where there are specific OIBD symptoms, these should be addressed in the clinical management; for example in patients with gastroparesis and nausea and vomiting, prokinetics may be considered.
What's another option?
Opioid switching may be helpful for some patients, however, the evidence that this reduces OIC is limited.
What's another option?
Traditional oral laxatives still play a prominent role in prophylaxis of OIC; however, they do not address an underlying cause of OIC and are designed for short-term use.
What's another option?
Rectal measures might be useful although they are often unpleasant for patients.
What's another option?
Targeted therapies are promising agents as they address the underlying pathological mechanisms of OIBD and OIC, namely the actions of mu-opioid receptor agonists in the GI tract.
What's another option?
In this case ...
After consultations with her family it was decided to start prolonged-release oxycodone/naloxone combined tablet at a dosage of 10mg/5mg twice-daily. The discussion to start oxycodone/naloxone comprised two issues: one was the medical indication for oxycodone/naloxone, as OIC had developed during oxycodone treatment and the change of drug was expected to give a possible positive outcome. The second point was a financial issue, as at the time of the treatment of this patient oxycodone/naloxone was not reimbursed by the health system in Poland (it is now). The patient's family agreed to pay the cost of the oxycodone/naloxone.

The dyspnoea was now treated with subcutaneous morphine 2.5mg rather than the oral morphine solution, due to the unpleasant taste experienced by the patient. The non-steroidal anti-inflammatory medication was continued as previously described. In her second month of palliative treatment, steroidal therapy with dexamethasone was also implemented.
Outcome
  • In this patient, whose constipation worsened while taking a small dosage of oxycodone 10mg twice-daily to control severe pain, a switch to an equivalent dosage of oxycodone/naloxone (10mg/5mg twice-daily) was successful. She was able to continue this regimen for eight months until the end of her life, ensuring a constant and satisfactory level of analgesia.

  • Macrogol 10g once-daily was continued, as was the subcutaneous morphine for episodes of dyspnoea.

  • With the exception of one episode of severe constipation resulting from an increased administration of morphine (due to a bout of severe dyspnoea from bronchitis), the patient defecated every third day. She did not report any abdominal pain resulting from constipation. Despite increased appetite and food consumption, no other disturbances in bowel function were observed.
Summary and learning points
  • OIC is a common problem in cancer patients requiring regular opioid therapy.

  • Traditional laxatives can be ineffective because they do not address the underlying cause; targeted treatment options include peripheral mu-opioid receptor antagonists.

  • Cyclo-oxygenase (COX-) inhibitors can be useful in nociceptive somatic pain.
More information
Macrogol
More information
COX-inhibitors and opioid dosing
Summary and learning points
  • It should also be noted that the acceptable bowel function was achieved despite the use of rescue morphine for the control of dyspnoea attacks, which might itself have contributed to OIBD symptoms.

  • No safety issues were encountered, that is no adverse events were seen with the exception of constipation requiring use of macrogol once daily. However, several factors might have contributed to this apart from oxycodone/naloxone administration, for example additional morphine doses taken for the management of dyspnoea bouts or other factors such as immobility or insufficient food and fluid intake. The patient also had a history of constipation before her cancer developed.

  • Prolonged release oral oxycodone/naloxone (Targin®) is an effective strong opioid analgesic that can also counteract OIC; however, the literature on long-term use in cancer patients is currently limited.
More information
Oxycodone/NaloxonE
References

Authors: Dr Wojciech Leppert, chair, Department of Palliative Medicine, Poznań University of Medical Sciences, Poznań, Poland; Dr Michał Chojnicki, Department of Biology and Environment Protection, Poznań University, Poznań, Poland

Date of preparation: August 2015; MINT/PAEU-15003

Join in

Have a question? Ask an expert Join our experts: Become a contributor Share your experience: Submit a case study Get in touch: Contact us