Sublingual Fentanyl Preferred, But Less Effective Than Subcutaneous Morphine

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In recent years, transmucosal fentanyl formulations have been shown to be superior to immediate-release oral morphine.
In recent years, transmucosal fentanyl formulations have been shown to be superior to immediate-release oral morphine.

Fentanyl sublingual tablets (FST) are preferred over subcutaneous morphine (SCM) in patients with severe breakthrough cancer pain, but FST may not be as effective as SCM, according to a study published in the Journal of Clinical Oncology.1

Patients who require scheduled opioids to control cancer pain often have acute flares of severe pain, or breakthrough pain.2 Fast-acting agents that are effective for breakthrough pain include immediate-release oral morphine, SCM injections, and intravenous morphine.1

In recent years, transmucosal fentanyl formulations — via oral and nasal routes — have been shown to be superior to immediate-release oral morphine.1 Limited data suggest that intravenous morphine is more effective than transmucosal fentanyl.3 While FST has been shown to be superior to placebo, it had not been compared with parenteral morphine.1,4

Ernesto Zecca, MD and colleagues from Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy evaluated the safety and efficacy of FST compared with SCM for breakthrough pain in patients with cancer pain.1

A total of 114 patients were randomly assigned to receive FST (fentanyl 100 µg plus placebo) or SCM (morphine 5 mg plus placebo). Pain intensity, assessed on a scale of 0 to 10 (0 = no pain; 10 = worst pain imaginable), was measured at 10, 20, 30, and 60 minutes after treatment.

FST did not reach the noninferiority threshold in this study. SCM reduced pain intensity to a greater extent than FST, although this finding was not significant (mean difference, -0.49).

However, both FST and SCM reduced pain intensity by one-third or more in 71% of patients at 30 minutes, although SCM was more likely than FST to reduce pain intensity by 50% at that time point.

Nearly half of patients receiving FST required a second dose after 30 minutes, compared with 37% of patients receiving SCM.

Almost all patients indicated that they preferred the sublingual route of administration to the subcutaneous route.

No serious adverse events occurred with either treatment. Adverse events included moderate nausea in 1 patient in the FST group and a moderate skin reaction in 1 patient in the SCM group.

Summary and Clinical Applicability

Patients who regularly take opioids for severe cancer pain often require fast-acting agents for episodes of breakthrough pain. Several transmucosal fentanyl formulations have been shown to be superior in efficacy to immediate-release oral morphine, but not parenteral morphine. Researchers examined whether FST was noninferior to SCM for severe breakthrough pain in cancer patients.

While FST did not meet noninferiority criteria, it did provide effective pain relief at 30 minutes and was shown to be equally as safe as SCM. In addition, patients preferred the sublingual route of administration to the subcutaneous route. “The sublingual route of administration provides a practical advantage for FST,” Dr Zecca said in an interview with Clinical Pain Advisor.

Limitations and Disclosures

According to Dr Zecca, several factors may have contributed to their finding that FST did not demonstrate noninferiority to SCM: “A prompter titration schedule of FST may have provided more effective analgesia and possibly results comparable with SCM. In addition, the relative efficacy of the two drugs may have depended on the opioid dosage for baseline pain control,” he said.

Dr Zecca has received honoraria from Molteni, Italfarmaco, and Amgen.

 

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References

  1. Zecca E, Brunelli C, Centurioni F, Manzoni A, Pigni A, Caraceni A. Fentanyl sublingual tablets versus subcutaneous morphine for the management of severe cancer pain episodes in patients receiving opioid treatment: a double-blind, randomized, noninferiority trial [published online January 23, 2017]. J Clin Oncol. JCO2016699504. doi:10.1200/JCO.2016.69.9504 
  2. Davies AN, Dickman A, Reid C, Stevens AM, Zeppetella G; Science Committee of the Association for Palliative Medicine of Great Britain and Ireland. The management of cancer-related breakthrough pain: recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland. Eur J Pain. 2009;13(4):331-338. doi:10.1016/j.ejpain.2008.06.014
  3. Mercadante S, Villari P, Ferrera P, Casuccio A, Mangione S, Intravaia G. Transmucosal fentanyl vs intravenous morphine in doses proportional to basal opioid regimen for episodic-breakthrough pain. Br J Cancer. 2007;96(12):1828-1833. doi:10.1038/sj.bjc.6603811
  4. Rauck RL, Tark M, Reyes E, et al. Efficacy and long-term tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain. Curr Med Res Opin. 2009;25(12):2877-2885. doi:10.1185/03007990903368310
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