Safety and Efficacy of Oral Nalbuphine on Postoperative Pain in Hemorrhoidectomy Patients: A Randomized, Double-blind, Placebo-controlled, Pivotal Trial.

OBJECTIVES: Severe postoperative pain requiring opioid treatment has been reported in 20-40% of hemorrhoidectomy patients. Compared to morphine, nalbuphine offers better hemodynamic stability, a lower risk of respiratory depression, and a lower potential for addiction. Nalbuphine was developed from intravenous form into an oral form (PHN131) to alleviate moderate-to-severe pain.

METHODS: A randomized, double-blind, placebo-controlled, multiple-dose, parallel-design trial was conducted to evaluate the safety and efficacy of PHN131 in patients undergoing hemorrhoidectomy. Eligible patients were randomly assigned to receive either PHN131 soft capsules containing nalbuphine hydrochloride 60 mg or placebo capsules. Intramuscular diclofenac was the rescue analgesic. Pain was measured by the area under the curve of mean Visual Analog Scale (VAS) pain intensity scores.

RESULTS: VAS results in patients receiving PHN131 were significantly lower than placebo group scores through 48 hours postoperatively (149.2±75.52 vs. 179.6±65.97; P=0.0301). According to Brief Pain Inventory Short Form scores, the impact of pain on quality of life was significantly smaller for the PHN131 group than for the placebo group. Time to the first use of diclofenac postoperatively was significantly longer in the PHN131 group than in the placebo group. The cumulative dosage of diclofenac in the PHN131 group was only around half of that in the placebo group (P<0.0001). Drug-related adverse events were mild-to-moderate and resolved by treatment end. No drug-related severe adverse events were observed.

DISCUSSION: Our findings demonstrate that PHN131 is effective and well-tolerated in the treatment of moderate-to-severe pain and may provide another option for patients to control their pain.