Clinical efficacy and safety of tapentadol immediate release in the postoperative setting.

The appropriate treatment for postoperative pain remains a common dilemma for podiatric surgeons and patients undergoing surgery of the foot and ankle. The treatment of moderate to severe acute pain typically relies heavily on the use of opioid analgesics, such as hydrocodone and oxycodone, which are often associated with adverse effects, including nausea and vomiting. These adverse effects may have a negative impact on postoperative outcomes and reduce patient compliance with analgesic therapy. Tapentadol is a novel, centrally acting analgesic with two mechanisms of action--µ-opioid receptor agonism and norepinephrine reuptake inhibition--in a single molecule. Tapentadol immediate release has been evaluated in a series of clinical trials in patients with postoperative pain after bunionectomy. The results of these studies demonstrate that tapentadol immediate release is associated with an improved gastrointestinal tolerability profile relative to oxycodone immediate release at doses providing comparable analgesia. Therefore, tapentadol immediate release may offer an improved analgesic option for the relief of postoperative pain after podiatric surgery.

A phase 3, randomized, placebo-controlled trial of DepoFoam® bupivacaine (extended-release bupivacaine local analgesic) in bunionectomy.

BACKGROUND: DepoFoam® bupivacaine (Pacira Pharmaceuticals, Inc., San Diego, CA, USA), an extended-release liposomal bupivacaine-based analgesic, was compared with placebo for the prevention of pain after bunionectomy in a randomized, multicenter, double-blind phase 3 clinical study. METHODS: Patients received placebo (n = 96) or DepoFoam bupivacaine 120 mg (n = 97) via wound infiltration prior to closure. Pain intensity was assessed using a numeric rating scale (NRS) from time 0 through to 72 hours postsurgically. The primary efficacy measure was area under the curve (AUC) of NRS scores through 24 hours. Other efficacy measures included AUC of NRS at other time points, proportion of patients who were pain-free, time to first opioid use, and total postsurgical consumption of supplemental opioid medication. Adverse events were also assessed. RESULTS: The AUC for NRS scores was significantly less in patients treated with DepoFoam bupivacaine versus patients receiving placebo at 24 hours (P = 0.0005) and 36 hours (P < 0.0229). More patients treated with DepoFoam bupivacaine avoided use of opioid rescue medication during the first 24 hours (7.2% vs. 1%; P < 0.0404) and were pain-free (NRS ≤ 1) at 2, 4, 8, and 48 hours. Median time-to-first-opioid use was delayed in favor of DepoFoam bupivacaine (4.3 vs. 7.2 hours; P < 0.0001). Fewer adverse events were reported by patients treated with DepoFoam bupivacaine (59.8%) versus placebo (67.7%). CONCLUSIONS: DepoFoam bupivacaine, a long-acting local analgesic, provided extended pain relief and decreased opioid use after bunionectomy, compared with placebo.

Efficacy and safety of oxycodone HCl/niacin tablets for the treatment of moderate-to-severe postoperative pain following bunionectomy surgery.

OBJECTIVE: To evaluate the efficacy and safety of two dose strengths of oxycodone hydrochloride (HCl)/niacin tablets * for the treatment of moderate-to-severe postoperative pain following bunionectomy surgery. RESEARCH DESIGN AND METHODS: Randomized, double-blind, placebo-controlled, US multicenter, repeat-dose study (Clinicaltrials.gov: NCT00654069). A total of 606 patients aged ≥18 years with moderate-to-severe pain post-bunionectomy were screened, and 405 patients were randomized to receive placebo, 2 × 5/30 mg oxycodone HCl/niacin tablets, or 2 × 7.5/30 mg oxycodone HCl/niacin tablets administered every 6 hours for 48 hours. Ketorolac tromethamine was available as rescue medication. MAIN OUTCOME MEASURES: Primary efficacy endpoint was the sum of pain-intensity difference scores during the 48 hours (SPID(48)) following the initial dose of study drug. Secondary efficacy endpoints included a responder analysis and use of rescue medication. Safety evaluations included adverse events (AEs), vital signs, and clinical laboratory assessments. RESULTS: Both doses of oxycodone HCl/niacin tablets demonstrated superior reductions in pain intensity compared with placebo as evidenced by the SPID(48) (p < 0.0001 for both oxycodone HCl/niacin 2 × 5/30 mg and 2 × 7.5/30 mg). AEs were consistent with the known effects of oxycodone HCl and niacin. Most AEs were mild or moderate in intensity, and no serious AEs occurred. There were no discontinuations due to AEs in the placebo group; 2/135 (1.5%) discontinued due to AEs in the 2 × 5/30 mg group and 4/134 (3.0%) in the 2 × 7.5/30 mg group. A limitation of this study was that there was no active comparator arm. CONCLUSIONS: Oxycodone HCl/niacin tablets (5/30 mg and 7.5/30 mg) provide effective analgesia and are generally well tolerated in patients with moderate-to-severe pain following bunionectomy surgery.

Diclofenac potassium liquid-filled soft gelatin capsules for the treatment of postbunionectomy pain.

OBJECTIVE: Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) is a rapidly absorbed formulation of diclofenac approved for the treatment of mild to moderate acute pain in adults (≥18 years of age). The objective of this study was to investigate the efficacy and safety of DPSGC 25 mg in a multicenter, randomized, double-blind, placebo-controlled study in patients experiencing pain following first metatarsal bunionectomy. RESEARCH DESIGN AND METHODS: Patients experiencing a requisite level of pain (≥4 based on an 11-point numeric pain rating scale [NPRS]; 0 = no pain, 10 = worst pain possible) on the day following surgery were randomized to receive DPSGC 25 mg or placebo. Patients received a second dose (remedication) on request or at 8 hours postdose followed by additional doses every 6 hours through the end of postsurgery Day 4. Rescue medication (hydrocodone/acetaminophen) was available as needed after the second dose. CLINICAL TRIAL REGISTRATION: NCT00375934. MAIN OUTCOME MEASURE: The primary efficacy endpoint was the average NPRS score over the 48 hour inpatient multiple-dose period. RESULTS: DPSGC provided a significant improvement in mean 48 hour NPRS scores over placebo (3.29 vs 5.74, respectively; p < 0.0001), as well as for summed pain intensity difference (203.1 vs 86.6; p < 0.0001). Patients treated with DPSGC experienced a faster onset of meaningful pain relief compared with placebo (p = 0.0034). Rescue medication use on Day 1 and Day 2 was reduced in the DPSGC group compared with placebo (53.5% vs 92.1% on Day 1; 30.3% vs 67.3% on Day 2; p < 0.0001). DPSGC was well tolerated and no patients treated with DPSGC reported serious adverse events. As with any study, there are potential limitations including study design and patient population. CONCLUSION: These results indicate that DPSGC reduced pain in patients who underwent bunionectomy and this novel formulation of diclofenac potassium may be a practical option for treating mild to moderate acute pain.