Open Access Open Access  Restricted Access Subscription or Fee Access

Factors influencing the prescribed dose of opioid analgesics in cancer patients

Momoyo Hashimoto, MPharm, Kazuki Aogaki, BPharm, Chikako Numata, PhD, Kensuke Moriwaki, PhD, Yoshinobu Matsuda, MD, Ryouhei Ishii, MD, PhD, Ikuko Tanaka, BPharm, Yoshiaki Okamoto, PhD


The dose of opioids prescribed for cancer pain does not always correlate with the actual pain severity. However, there is little evidence to explain this observation. In the present study, we sought to determine factors that influence the dose of opioid analgesics. A total of 227 patients who were administered opioids between August 2012 and May 2016 and later expired within the Department of Palliative Care at Ashiya Municipal Hospital were included, and the following variables were examined: age, sex, type of cancer, Verbal Rating Scale before and after the administration of the maximum prescribed dose of opioids, type of opioids and route of administration, blood test results, pain severity, and use of adjuvants. Data were analyzed using step-wise multiple linear regression. Median of the maximum prescribed dose of opioids, expressed in oral morphine equivalent, was 68.6, 60.0, and 39.2 mg for patients aged <65, 65-74, and 75 years, respectively. Step-wise multiple linear regression analysis further demonstrated that an increase in age by 1 year decreased the maximum prescribed dose of opioids by 0.98-fold (p = 0.006). Other factors that influenced the maximum prescribed dose of opioids included the use of analgesic adjuvants (1.91-fold, p = 0.001), oral administration (0.54-fold, p = 0.016), and elevated level of bilirubin (0.95-fold by 0.1 mg/dL increase, p = 0.013). Opioids examined in the study are metabolized in the liver by cytochromes P450 or by glucuronidation. Thus, if reduced drug metabolism causes the reduction in the maximum prescribed dose of opioids, liver function may contribute to this effect. Based on our findings that old age is associated with a lower prescribed dose of opioids, future studies should examine additional variables included in laboratory tests in more detail and measure hepatic blood flow to determine the cause of this association.


opioid analgesic, cancer patient, geriatric patient, cancer pain

Full Text:



Morita T, Tsunoda J, Inoue S, et al.: Contributing factors to physical symptoms in terminally-ill cancer patients. J Pain Symptom Manage 1999; 18(5): 338-346.

Hall S, Gallagher RM, Gracely E, et al.: The terminal cancer patient: Effects of age, gender, and primary tumor site on opioid dose. Pain Med. 2003; 4(2): 125-134.

Mercadante S, Dardanoni G, Salvaggio L, et al.: Monitoring of opioid therapy in advanced cancer pain patients. Pain Symptom Manage. 1997; 13(4): 204-212.

Rees WD: Opioid Needs of terminal care patients: Variations with age and primary site. Clin. Oncol. 1990; 2(2): 79-83.

Macintyre PE, Jarvis DA: Age is the best predictor of postoperative morphine requirements. Pain. 1996; 64(2): 357-364.

Mercadante S, Casuccio A, Pumo S, et al.: Factors influencing the opioid response in advanced cancer patients with pain followed at home: The effects of age and gender. Support Care Cancer. 2000; 8(2): 123–130.

Goldberg JG, Mor V, Wiemann M, et al.: Analgesic use in terminal care patients: Report from the National Hospice Study. J Chronic Dis. 1986; 39(1): 37–45.

Lemmens HJM, Bovill JG, Hennis PJ, et al.: Age has no effect on the pharmacodynamics of alfentanil. Anesth Analg 1988; 67(10): 956-960.

Schludermann E, Zudec JP: Effects of age on pain sensitivity. Percept Mot Skills. 1962; 14: 296-301.

Abernethy DR: An overview of the pharmacokinetics and pharmacodynamics of amlodipine in elderly persons with systemic hypertension. Am J Cardiol. 1994; 73(10): 10A-17A.

Gauvin A, Pinguet F, Culine S, et al.: Bayesian estimate of vinorelbine pharmacokinetic parameters in elderly patients with advanced metastatic cancer. Clin Cancer Res. 2000; 6(7): 2690-2695.

Sotaniemi EA, Anttila MI: Influence of age on toremifene pharmacokinetics. Cancer Chemother Pharmacol. 1997; 40(2): 185-188.

Nagashima M, Katoh R, Sato Y, et al.: Is there genetic polymorphism evidence for individual human sensitivity to opiates? Curr Pain Headache Rep. 2007; 11(2): 115-123.

Zubieta JK, Heitzeg MM, Smith YR, et al.: COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. 2003; 299(5610): 1240-1243.

Mercadante S, Dardanoni G, Salvaggio L, et al.: Monitoring of opioid therapy in advanced cancer pain patients. J Pain Symptom Manage. 1997 ; 13(4): 204-212.



  • There are currently no refbacks.