FORT LAUDERDALE, FlaOral 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.
Because of the lollipop style design, the FDA had concerns about
Each patient receives a fanny pack with a lockable zipper.
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. Josephs 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
One concern, Ms. Chavez said, is that, due to the medications
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 manufacturers
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.
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