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Alternatives to Oral Opioids for Cancer Pain

Alternatives to Oral Opioids for Cancer Pain

The practicing medical oncologist is faced with several options when selecting opioid analgesics. As Drs. Mercadante and Fulfaro underscore, when all routes of administration are available, the oral route is preferred.

The most commonly used opioids, morphine and oxycodone, are available as long-acting preparations and are often preferred initially to transdermal systems because of their ability to be titrated. These formulations allow for rapid titration to effect (usually 24 to 48 hours) and enable the use of a companion short-acting analgesic to provide analgesia during the titration period. This concept of “oral patient-controlled analgesia” is both clinically efficacious and cost-effective.[1]

Intravenous or Subcutaneous Routes

The authors also underscore the need for alternative delivery systems for patients unable to swallow. In general oncology and hospice practice settings, the use of intravenous or subcutaneous morphine or hydromorphone is the gold standard when the oral route is unavailable. Again, these routes allow for both baseline and bolus dosing (patient-controlled analgesia) and rapid titration. They may prove to be expensive and burdensome to the ambulatory patient and family for long-term use, however.

Rectally Administered Morphine

The authors appropriately point out that practitioners can use long-acting morphine tablets or capsules rectally in patients unable to swallow. The pharmacokinetics that the authors discuss support this use for a limited time, as along as the practitioner realizes that multiple absorption and dosing variables do not support the routine use of this route. It is my practice to use rectally administered long-acting morphine only when the patient has several days to a week to live. This approach ensures reasonable analgesia without the need to switch to a transdermal system, which may takes days to titrate, or to an interventional subcutaneous or intravenous route.

Transdermal and Transmucosal Fentanyl

The most commonly used, effective alternative delivery method for opioid analgesics in outpatients who are unable to swallow is transdermal fentanyl (Duragesic). Similar in efficacy to long-acting morphine and oxycodone, transdermal fentanyl cannot be titrated rapidly and often takes up to 72 hours to attain a steady state. This limitation may be to patients’ detriment if their pain is changing rapidly.

In addition, while subcutaneous reservoirs are saturating, a supplemental medication, usually morphine or hydromorphone, must be given. Transdermal fentanyl is most appropriate for patients with chronic, stable pain who are unable to swallow or tolerate long-acting morphine or oxycodone.

In the near future, oral transmucosal fentanyl citrate (OTFC [Actiq]) will allow for adequate analgesia during initial dosing and titration of transdermal fentanyl. Oral transmucosal fentanyl citrate is the only oral transmucosal opioid that affords rapid pain relief during breakthrough episodes of pain. It is also the only short-acting opioid analgesic whose titration is based on a clinically investigated schedule.

In addition, OTFC can be safely and effectively paired with long-acting morphine and oxycodone without affecting the baseline analgesic requirements.[2] Whether OTFC is more effective for episodic pain than the currently available oral morphine products is unknown; this question is currently under study in a multicenter, double-blind trial.

The use of OTFC in minimally conscious or comatose patients has not been investigated. This information is of particular importance, given the increasing popularity of the use of “sublingual” morphine in terminally ill patients. Patients and nurses often report “immediate” relief of pain with hypercon- centrated formulations of morphine sulfate (ie, 20 mg/mL) taken sublingually. Several scientific studies question the scientific likelihood that a hydrophilic product, such as morphine, can be absorbed through the oral mucosa.[3] Oral transmucosal fentanyl citrate promises to offer dependable transmucosal delivery of an opioid for severe episodic pain and may replace the sublingual delivery of other opioids.


1. Coluzzi P: Oral patient controlled analgesia and breakthrough pain. Semin Oncol 24(suppl):516-542, 1997.

2. Christie J, Simmonds M, Dalt R, et al : Dose titration, multicenter study of oral transmucosal fentanyl citrate for treatment of breakthrough pain in cancer patients using transdermal fentanyl for persistent pain. J Clin Oncol 16(10):3238-3245, 1998.

3. Coluzzi P: Sublingual morphine: Efficacy reviewed. J Pain Symptom Management 16(3): 187-192, 1998.

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