General Information

Butrans is a transdermal patch formulation of buprenorphine. Buprenorphine is a partial agonist at mu opioid receptors, an antagonist at kappa opioid receptors, an agonist at delta opioid receptors, and a partial agonist at ORL-1 (nociceptin) receptors. Its clinical actions result from binding to the opioid receptors. The transdermal patch formulation was designed to provide the systemic delivery of buprenorphine continuously for 7 days.

Butrans is specifically indicated for the management of moderate to severe chronic pain in patients requiring a continuous, around-the-clock opioid analgesic for an extended period of time.

The recommended initial dose of the Butrans patch is as follows:
Opioid-Naïve Patients
Butrans 5 mcg/hour. Thereafter, individually titrate at minimum intervals of 72 hours. The maximum dose is 20 mcg/hour.
Conversion from Other Opioids to Butrans
Patient’s current around-the-clock opioids sould be tapered for up to 7 days to no more than 30 mg of morphine or equivalent per day before beginning treatment with Butrans. For patients whose daily dose was less than 30 mg of oral morphine or equivalent, initiate treatment with Butrans 5 mcg/hour. For patients whose daily dose was 30 and 80 mg morphine equivalents, initiate treatment with Butrans 10 mcg/hour. Thereafter, individually titrate at minimum intervals of 72 hours. The maximum dose is 20 mcg/hour.

Mechanism of Action

Butrans is a transdermal patch formulation of buprenorphine. Buprenorphine is a partial agonist at mu opioid receptors, an antagonist at kappa opioid receptors, an agonist at delta opioid receptors, and a partial agonist at ORL-1 (nociceptin) receptors. Its clinical actions result from binding to the opioid receptors. The transdermal patch formulation was designed to provide the systemic delivery of buprenorphine continuously for 7 days.

Side Effects

Adverse events associated with the use of Butrans may include, but are not limited to, the following:

• nausea
• headache
• application site pruritus
• dizziness
• constipation
• somnolence
• vomiting
• application site erythema
• dry mouth
• application site rash

The Butrans drug label comes with the following Black Box Warning: Butrans exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient’s risk before prescribing, and monitor for these behaviors and conditions. To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Serious, life-threatening or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Instruct patients on proper administration of Butrans to reduce the risk. Accidental exposure to Butrans, especially in children, can result in fatal overdose of buprenorphine. Prolonged use of Butrans during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If prolonged opioid use is required in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

Clinical Trial Results

The FDA approval was based on four 12-week double-blind, controlled clinical trials in opioid-naïve and opioid-experienced patients with moderate to severe chronic low back pain or osteoarthritis. Two of these studies, seen below, demonstrated efficacy in patients with low back pain. One study in low back pain failed to show efficacy. One study in osteoarthritis, that included an active comparator, failed to show efficacy for Butrans and the active comparator.
12-Week Study in Opioid-Naïve Patients with Chronic Low Back Pain
A total of 1,024 patients with chronic low back pain who were suboptimally responsive to their non-opioid therapy entered an open-label, dose-titration period for up to four weeks. Patients initiated therapy with three days of treatment with Butrans 5 mcg/hour. After three days, if adverse events were tolerated but the pain persisted (=5 on an 11-point, 0 to 10 Numerical Rating Scale), the dose was increased to Butrans 10 mcg/hour. If adverse effects were tolerated but adequate analgesia was not reached, the dose was increased to Butrans 20 mcg/hour for an additional 10-12 days. Patients who achieved adequate analgesia and tolerable adverse effects on Butrans were then randomized to remain on their titrated dose of Butrans or matching placebo. Of the patients who entered the open-label titration period, 53% were able to titrate to a tolerable and effective dose and were randomized into a 12-week, double-blind treatment period. The score for average pain over the last 24 hours at the end of the study (Week 12/Early Termination) was statistically significantly lower for patients treated with Butrans compared with patients treated with placebo.
12-Week Study in Opioid-Experienced Patients with Chronic Low Back Pain
A total of 1,160 patients on chronic opioid therapy (total daily dose 30-80 mg morphine equivalent) entered an open-label, dose-titration period with Butrans for up to 3 weeks, following taper of prior opioids. Patients initiated therapy with Butrans 10 mcg/hour for three days. After three days, if the patient tolerated the adverse effects, the dose was increased to Butrans 20 mcg/hour for up to 18 days. Patients with adequate analgesia and tolerable adverse effects on Butrans 20 mcg/hour were randomized to remain on Butrans 20 mcg/hour or were switched to a low-dose control (Butrans 5 mcg/hour) or an active control. Of the subjects who entered the open-label titration period, 57% were able to titrate to and tolerate the adverse effects of Butrans 20 mcg/hour and were randomized into a 12-week double-blind treatment phase. The score for average pain over the last 24 hours at Week 12 was statistically significantly lower for subjects treated with Butrans 20 mcg/hour compared to subjects treated with Butrans 5 mcg/hour. A higher proportion of Butrans 20 mcg/hour patients (49%) had at least a 30% reduction in pain score from screening to study endpoint when compared to Butrans 5 mcg/hour patients (33%).