Oral Fentanyl Effective for Use in Breakthrough Cancer Pain

FORT LAUDERDALE, Fla—Oral transmucosal fentanyl citrate (Actiq) provides superior analgesia, compared with immediate-release morphine sulfate, for the treatment of breakthrough cancer pain, according to a multicenter study presented at the 18th Annual Scientific Meeting of the American Pain Society.

“My personal experience with the drug has been gratifying,” said Lee Schwartzberg, MD, hematologist/oncologist with The West Clinic, Memphis, Tennessee; medical director of Response Oncology; and one of the authors of the study. “Both on study and in general practice since its approval, most patients prefer Actiq to previous breakthrough medications,” he said.

Actiq, a lozenge formulation of fentanyl citrate on a plastic stick, has a rapid onset of action (within 5 to 10 minutes) and a short duration, or clearance time, which closely aligns with what is required to relieve a typical breakthrough pain episode, defined as having a rapid onset (often less than 3 minutes), a moderate to severe intensity, and a relatively short duration.

Addressing Child Safety Concerns

Actiq is sometimes referred to as “fentanyl on a stick.” The lozenge on a handle design helps with the absorption of the medication; 25% is absorbed across the oral mucosa as the lozenge dissolves slowly in the mouth. The handle allows patients to remove the agent from the mouth if they experience signs of excessive opioid effects.

Because of the lollipop style design, the FDA had concerns about child safety. A series of child safety tests showed that the drug is not attractive to children. However, the manufacturer has instituted a number of safety features to satisfy the FDA’s concerns.

Each patient receives a fanny pack with a lockable zipper. “Inside the pack, among other things, is a small cylinder-like container,” Jana Chavez, RN, said at the American Pain Society meeting. “Patients are told that if, for whatever reason, they do not finish the unit, whether by choice or, say, if the phone rings, they are to put it in the childproof cylinder.” To her knowledge, she said, there have been no incidents to date regarding Actiq safety.

The study began with 134 patients who underwent pre-enrollment open-label titration to a stable and effective dose of intermediate-release morphine and Actiq for breakthrough pain.

Of these patients, 93 entered the enrollment phase of the study, a double-blind, double-dummy, multiple crossover comparison of the previously established stable and effective doses of the two agents for breakthrough pain.

 “The first patient was enrolled in September 1997, and the study concluded with the last patient in March 1999,” said Jana Chavez, RN, study coordinator for Dr. Paul Coluzzi, first author.

Each patient was treated for 10 individual breakthrough pain episodes with either active or placebo Actiq (5 episodes each) and corresponding active or placebo morphine. The patients rated their pain intensity and pain relief at 15, 30, 45, and 60 minutes after administration.

The study variables for pain intensity were as follows: 0 for “no pain” through 10 for “pain as bad as you can imagine.” Pain relief was charted as 0 = none; 1 = slight; 2 = moderate; 3 = lots; and 4 = complete.

“The study concluded that, across the board, Actiq gave superior analgesia at each time marking,” said Ms. Chavez, of the Breast Care Center, St. Joseph’s Medical Plaza, Orange, California. For example, the pain intensity difference at 15 minutes after drug administration was 1.865 for Actiq vs 1.456 for intermediate-release morphine.

Patients also rated global medication performance on a scale of 0 to 4 (poor to excellent). This was measured 60 minutes after administration of the study drug. Overall, Actiq showed superior performance in this area over morphine.

“It does take some manipulation of dose level to reach the optimal dose of Actiq,” Dr. Schwartzberg said. “However, once this occurs for the individual patient, dosing becomes easy, with one or two lozenges needed for near to complete breakthrough pain relief.”

One concern, Ms. Chavez said, is that, due to the medication’s quick pain relief action, patients may be inclined to take only a partial dosage and discard the rest as soon as they feel its effect. “We instructed the patients in the study to consume the entire unit,” Ms. Chavez said, and this is also the manufacturer’s recommendation.

At the conclusion of the study, 64 patients chose to continue using Actiq in a follow-up study in which they could use the medication of their choice. The medication appeared to improve their quality of life enough for them to want to continue using it.

For example, Dr. Schwartzberg described a patient with prostate cancer and painful bone metastasis who was essentially housebound because of inability to get his pain under control with oral medicines. “He had a significant improvement in his performance status with Actiq,” Dr. Schwartzberg said, “and was able to resume many of the activities he enjoyed.”

The main side effects of Actiq were those commonly associated with opioid use, that is, somnolence, nausea, and constipation.

Reimbursement Hotline

Dr. Schwartzberg believes that Actiq has been tested in a methodologically sound way that has previously been difficult for new pain medications, especially one with a different mode of administration. “I believe our most recent study and previously published data firmly support Actiq as an exciting new weapon in our armamentarium of medications for palliation of cancer pain,” he concluded.

While the cost of the medication could be a factor for some patients, Ms. Chavez said that the manufacturer has set up a reimbursement hotline that physicians and insurers can call toll free for assistance (1-877-229-1241).