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Supportive Care in Cancer

, Volume 25, Issue 2, pp 661–675 | Cite as

The use of opioids in cancer patients with renal impairment—a systematic review

  • Tonje A. SandeEmail author
  • Barry J. A. Laird
  • Marie T. Fallon
Review Article

Abstract

Purpose

Opioids are recommended for moderate to severe cancer pain; however, in patients with cancer, impaired renal function can affect opioid metabolism. The aim of this systematic review was to evaluate the current evidence for the use of opioids in cancer patients with renal impairment.

Methods

A systematic review was conducted and the following databases were searched: MEDLINE (1966 to 2015), EMBASE (1980 2015) and Cochrane Central Register of Controlled Trials (up to 2015). Eligible studies met the following criteria: patients with cancer pain taking an opioid (defined as per the WHO ladder); >18 years; renal impairment (serum creatinine > normal range (study dependent), creatinine clearance (CrCl) or glomerular filtration rate (GFR) measurements <90 ml/min, or as per the study definition); clinical outcome related to renal impairment. All eligible studies were appraised using the Grading of Recommendation Assessment, Development and Evaluations (GRADE) system.

Results

Eighteen studies (n = 2422) were eligible but heterogeneity meant meta-analysis was not possible. Morphine was examined in eight studies (n = 1418), oxycodone in two studies (n = 325), and fentanyl, alfentanil or sufentanil were discussed in six studies in total (n = 442). No recommendations could be formulated on the preferred opioid in patients with renal impairment.

Conclusion

There is lack of consensus within the existing literature on the relationship between morphine, creatinine levels and morphine-related side effects. Based on the current evidence, morphine should be used with caution; however, more evidence is needed. Fentanyl, alfentanil and sufentanil are recommended in patients with renal impairment based on pharmacokinetics and clinical experience. However, the present systematic review found very little clinical evidence for this. Overall, the quality of the existing evidence on opioid treatment in cancer patients with renal impairment is low. There remains a need for high-quality clinical studies examining opioids in patients with renal impairment.

Keywords

Opioids Renal impairment Cancer Pain 

Notes

Acknowledgments

Harriet Harris assisted with the retrieval of manuscripts.

Compliance with ethical standards

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

520_2016_3447_MOESM1_ESM.docx (64 kb)
ESM 1 (DOCX 64 kb)

References

  1. 1.
    Launay-Vacher V, Oudard S, Janus N et al (2007) Prevalence of renal insufficiency in cancer patients and implications for anticancer drug management: the renal insufficiency and anticancer medications (IRMA) study. Cancer 110:1376–1384CrossRefPubMedGoogle Scholar
  2. 2.
    Ventafridda V, Tamburini M, Caraceni A, De Conno F, Naldi F (1987) A validation study of the WHO method for cancer pain relief. Cancer 59:850–856Google Scholar
  3. 3.
    Broadbent A, Khor K, Heaney A (2003) Palliation and chronic renal failure: opioid and other palliative medications—dosage guidelines. Prog Palliat Care 11:183–190CrossRefGoogle Scholar
  4. 4.
    Caraceni A, Hanks G, Kaasa S et al (2012) Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. Lancet Oncol 13:e58–e68CrossRefPubMedGoogle Scholar
  5. 5.
    Droney J, Levy J, Quigley C (2007) Prescribing opioids in renal failure. J Opioid Manag 3:309–316PubMedGoogle Scholar
  6. 6.
    Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group (2012) KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2:1–138CrossRefGoogle Scholar
  7. 7.
    Atkins D, Best D, Briss PA et al (2004) Grading quality of evidence and strength of recommendations. Br Med J 328:1490–1494CrossRefGoogle Scholar
  8. 8.
    Ashby M, Fleming B, Wood M, Somogyi A (1997) Plasma morphine and glucuronide (M3G and M6G) concentrations in hospice inpatients. J Pain Symptom Manag 14:157–167CrossRefGoogle Scholar
  9. 9.
    Kaiko RF, Foley KM, Grabinski PY et al (1983) Central nervous system excitatory effects of meperidine in cancer patients. Ann Neurol 13:180–185CrossRefPubMedGoogle Scholar
  10. 10.
    Kirkham SR, Pugh R (1995) Opioid analgesia in uraemic patients. Lancet 345:1185CrossRefPubMedGoogle Scholar
  11. 11.
    Klepstad P, Borchgrevink PC, Dale O et al (2003) Routine drug monitoring of serum concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide do not predict clinical observations in cancer patients. Palliat Med 17:679–687PubMedGoogle Scholar
  12. 12.
    Kurita GP, Lundstrom S, Sjogren P et al (2015) Renal function and symptoms/adverse effects in opioid-treated patients with cancer. Acta Anaesthesiol Scand 59:1049–1059CrossRefPubMedGoogle Scholar
  13. 13.
    Lee MA, Leng ME, Tiernan EJ (2001) Retrospective study of the use of hydromorphone in palliative care patients with normal and abnormal urea and creatinine. Palliat Med 15:26–34CrossRefPubMedGoogle Scholar
  14. 14.
    Melilli G, Samolsky Dekel BG, Frenquelli C, Mellone R, Pannuti F (2014) Transdermal opioids for cancer pain control in patients with renal impairment. J Opioid Manag 10:85–93CrossRefPubMedGoogle Scholar
  15. 15.
    Narabayashi M, Saijo Y, Takenoshita S et al (2008) Opioid rotation from oral morphine to oral oxycodone in cancer patients with intolerable adverse effects: an open-label trial. Jpn J Clin Oncol 38:296–304CrossRefPubMedGoogle Scholar
  16. 16.
    Paramanandam G, Prommer E, Schwenke DC (2011) Adverse effects in hospice patients with chronic kidney disease receiving hydromorphone. J Palliat Med 14:1029–1033CrossRefPubMedGoogle Scholar
  17. 17.
    Riley J, Ross JR, Rutter D et al (2004) A retrospective study of the association between haematological and biochemical parameters and morphine intolerance in patients with cancer pain. Palliat Med 18:19–24CrossRefPubMedGoogle Scholar
  18. 18.
    Riley J, Ross JR, Rutter D et al (2006) No pain relief from morphine? Individual variation in sensitivity to morphine and the need to switch to an alternative opioid in cancer patients. Support Care Cancer 14:56–64CrossRefPubMedGoogle Scholar
  19. 19.
    Somogyi AA, Nation RL, Olweny C et al (1993) Plasma concentrations and renal clearance of morphine, morphine-3-glucuronide and morphine-6-glucuronide in cancer patients receiving morphine. Clin Pharmacokinet 24:413–420CrossRefPubMedGoogle Scholar
  20. 20.
    Tiseo PJ, Thaler HT, Lapin J et al (1995) Morphine-6-glucuronide concentrations and opioid-related side effects: a survey in cancer patients. Pain 61:47–54CrossRefPubMedGoogle Scholar
  21. 21.
    Urch CE, Carr S, Minton O (2004) A retrospective review of the use of alfentanil in a hospital palliative care setting. Palliat Med 18:516–519CrossRefPubMedGoogle Scholar
  22. 22.
    White C, Hardy J, Boyd A, Hall A (2008) Subcutaneous sufentanil for palliative care patients in a hospital setting. Palliat Med 22:89–90CrossRefPubMedGoogle Scholar
  23. 23.
    Wood MM, Ashby MA, Somogyi AA, Fleming BG (1998) Neuropsychological and pharmacokinetic assessment of hospice inpatients receiving morphine. J Pain Symptom Manag 16:112–120CrossRefGoogle Scholar
  24. 24.
    Twomey F, Douglas C, Anthony A (2006) A retrospective study of prescribing in palliative care patients with renal failure (abstract from the 4th research forum of the EAPC). Palliat Med 20:274Google Scholar
  25. 25.
    Mazzocato C, Beauverd M, Anwar D (2006) Subcutaneous fentanyl in severely ill patients with renal failure (abstract from the 4th research forum of the EAPC). Palliat Med 20:301Google Scholar
  26. 26.
    Böger RH (2006) Renal impairment: a challenge for opioid treatment? The role of buprenorphine. Palliat Med 20:s17–s23CrossRefPubMedGoogle Scholar
  27. 27.
    Cherny NI, Fallon MT, Kaasa S, Portenoy RK, Currow DC (2015) Oxford textbook of palliative medicine. Oxford University Press, United KingdomCrossRefGoogle Scholar
  28. 28.
    Murphy EJ (2005) Acute pain management pharmacology for the patient with concurrent renal or hepatic disease. Anaesth Intensive Care 33:311–322PubMedGoogle Scholar
  29. 29.
    King S, Forbes K, Hanks GW, Ferro CJ, Chambers EJ (2011) A systematic review of the use of opioid medication for those with moderate to severe cancer pain and renal impairment: a European palliative care research collaborative opioid guidelines project. Palliat Med 25:525–552CrossRefPubMedGoogle Scholar
  30. 30.
    Bruera E, Belzile M, Pituskin E et al (1998) Randomized, double-blind, cross-over trial comparing safety and efficacy of oral controlled-release oxycodone with controlled-release morphine in patients with cancer pain. J Clin Oncol 16:3222–3229PubMedGoogle Scholar
  31. 31.
    Mucci-LoRusso P, Berman BS, Silberstein PT et al (1998) Controlled-release oxycodone compared with controlled-release morphine in the treatment of cancer pain: a randomized, double-blind, parallel-group study. Eur J Pain 2:239–249CrossRefPubMedGoogle Scholar
  32. 32.
    Hanks GW, Conno F, Cherny N et al (2001) Morphine and alternative opioids in cancer pain: the EAPC recommendations. Br J Cancer 84:587–593CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Kirvela M, Lindgren L, Seppala T, Olkkola KT (1996) The pharmacokinetics of oxycodone in uremic patients undergoing renal transplantation. J Clin Anesth 8:13–18CrossRefPubMedGoogle Scholar
  34. 34.
    Grape S, Schug SA, Lauer S, Schug BS (2010) Formulations of fentanyl for the management of pain. Drugs 70:57–72CrossRefPubMedGoogle Scholar
  35. 35.
    Meuldermans W, Van Peer A, Hendrickx J et al (1988) Alfentanil pharmacokinetics and metabolism in humans. Anesthesiology 69:527–534CrossRefPubMedGoogle Scholar
  36. 36.
    Davies G, Kingswood C, Street M (1996) Pharmacokinetics of opioids in renal dysfunction. Clin Pharmacokinet 31:410–422CrossRefPubMedGoogle Scholar
  37. 37.
    Davison SN, Mayo PR (2008) Pain management in chronic kidney disease: the pharmacokinetics and pharmacodynamics of hydromorphone and hydromorphone-3-glucuronide in hemodialysis patients. J Opioid Manag 4:335–336 339-44PubMedGoogle Scholar
  38. 38.
    Bruera E, Sweeney C (2002) Methadone use in cancer patients with pain: a review. J Palliat Med 5:127–138CrossRefPubMedGoogle Scholar
  39. 39.
    Bruera E, Palmer JL, Bosnjak S et al (2004) Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study. J Clin Oncol 22:185–192CrossRefPubMedGoogle Scholar
  40. 40.
    Smyth B, Jones C, Saunders J (2016) Prescribing for patients on dialysis. Aust Prescr 39:21–24CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Douglas CA (2014) Palliative care for patients with advance chronic kidney disease. J Royal Coll Physicians Edinb 44:224–231CrossRefGoogle Scholar
  42. 42.
    Dean M (2004) Opioids in renal failure and dialysis patients. J Pain Symptom Manag 28:497–504CrossRefGoogle Scholar
  43. 43.
    Levey AS, Coresh J, Balk E et al (2003) National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 139:137–147CrossRefPubMedGoogle Scholar
  44. 44.
    Somogyi AA, Barratt DT, Coller JK (2007) Pharmacogenetics of opioids. Clin Pharmacol Ther 81:429–444CrossRefPubMedGoogle Scholar
  45. 45.
    Klepstad P (2010) Pharmacogenetic considerations in the treatment of cancer pain. In: Bruera E, Portenoy RK (eds) Cancer pain. Cambridge University Press, New York, pp. 180–194Google Scholar
  46. 46.
    Crain SM, Shen KF (1998) Modulation of opioid analgesia, tolerance and dependence by Gs-coupled, GM1 ganglioside-regulated opioid receptor functions. Trends Pharmacol Sci 19:358–365CrossRefPubMedGoogle Scholar
  47. 47.
    Thompson SJ, Koszdin K, Bernards CM (2000) Opiate-induced analgesia is increased and prolonged in mice lacking P-glycoprotein. Anesthesiology 92:1392–1399CrossRefPubMedGoogle Scholar
  48. 48.
    Amanzio M, Pollo A, Maggi G, Benedetti F (2001) Response variability to analgesics: a role for non-specific activation of endogenous opioids. Pain 90:205–215CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Tonje A. Sande
    • 1
    • 2
    Email author
  • Barry J. A. Laird
    • 1
  • Marie T. Fallon
    • 1
  1. 1.Institute of Genetics and Molecular MedicineUniversity of EdinburghEdinburghUK
  2. 2.Edinburgh Cancer Research Centre (CR UK Building)Western General HospitalEdinburghUK

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