Pharmacology Update

Fentanyl Sublingual Tablets (Abstral®) CII

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.

The fda has approved a new formulation of fentanyl for the management of breakthrough pain in cancer patients. The fasting-acting, rapidly disintegrating, sublingual tablet is marketed by ProStrakan Inc. as Abstral®. It currently is approved in Sweden, the United Kingdom, France, and Germany.


Fentanyl sublingual tablets are indicated only for the management of adult cancer patients with breakthrough pain who are currently receiving opioid therapy for their underlying persistent cancer pain.1 Use is for opioid-tolerant patients, meaning that they are taking at least 60 mg/day of oral morphine, 25 mcg/hour of transdermal fentanyl, 30 mg/day of oxycodone, 8 mg of hydromorphone, and 25 mg of oxymorphine, or other equivalent opioid for a week or longer.1


The initial dose is 100 mcg (placed under the tongue on the floor of the mouth) and should be titrated to a tolerable effective dose. No more than two doses can be taken for each breakthrough pain episode.1 There should be at least a 2-hour period between treatment episodes and no more than 4 episodes per day once a successful dose is identified. All patients should be started at 100 mcg. Sublingual fentanyl should not be converted from other formulations of fentanyl on a mcg-per-mcg basis.

Fentanyl sublingual tablets are available as 100 mcg, 200 mcg, 300 mcg, 400 mcg, 600 mcg, and 800 mcg strengths.

Potential Advantages

Sublingual fentanyl is a potent analgesic with a rapid onset and short duration of action.

Potential Disadvantages

Sublingual fentanyl is contraindicated in opioid non-tolerant patients. Life-threatening respiratory depressant can occur at any fentanyl dose in these patients.1 In the clinical trial, approximately 40% withdrew during the titration phase either due to intolerance or inability to achieved an effective dose; only 60% of patients were able to successfully reach a stable and effective dose.2


Fentanyl is formulated as a rapid-onset sublingual tablet for the treatment of breakthrough cancer pain. Fentanyl is well absorbed from the oral mucosa. The efficacy was shown in a randomized, placebo-controlled, phase III study in adult patients with breakthrough cancer pain. This type of pain is characterized by rapid onset, short duration, and severe intensity. Study participants (n = 131) initially entered a 2-week titration phase to identify an effective dose (100-800 mcg). An effective dose was defined as pain relief for all episodes over 2 consecutive days. They then entered a 2-week, double-blind phase during which patients received 10 doses (seven doses of the identified effective dose and three matching placebo) taken in random order with placebo doses separated by at least one active dose. The primary endpoint was mean sum of pain intensity from baseline (SPID) over 30 minutes. Secondary endpoints include SPID over 60 minutes, pain intensity difference, percent responders (≥ 30% reduction in pain intensity in at least one episode), overall satisfaction, and use of rescue medication. The median dose was 600 mcg with a median of three doses per day. Sublingual fentanyl showed significant improvement in SPID at 30 minutes. This was evident within 10 min and was maintained over the 60-minutes assessment period. Approximately 47% of patients were satisfied or very satisfied with the formulation and 11% required rescue medication while on active drug compared to 27% on placebo. The percent responders were 87% vs 65%. The most frequently reported adverse effects were nausea (12%), vomiting (5.3%), and somnolence (4%). Patients have been treated for up to 12 months.3

Clinical Implications

Sublingual fentanyl offers a rapid onset and potent analgesic for breakthrough cancer pain. Enrollment in a Risk Evaluation and Mitigation Strategy program is required for any pharmacy, distributor, or health-care professional involved in the distribution or use of Abstral.


1. Abstral Prescribing Information. Bedminster, NJ: Pro-Strakan Inc.; January 2011.

2. Rauck RL, 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;25:2877-2885.

3. Nalamachu S, et al. Long-term safety and tolerability of sublngual fentanyl. American Academy of Pain Medicine 25th Annual Meeting; Honolulu, HI; Jan. 28-31, 2009.