Tapentadol Prolonged Release for Chronic Pain: A Review of Clinical Trials and 5 Years of Routine Clinical Practice Data.

Tapentadol prolonged release (PR) for the treatment of moderate to severe chronic pain combines 2 modes of action. These are µ-opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule that allow higher analgesic potency through modulation of different pharmacological targets within the pain transmitting systems. At the same time, this can also serve as a clue for modulation of different pain-generating mechanisms according to nociceptive, neuropathic, or mixed pain conditions. Tapentadol PR has now been on the market for 5 years, with over 4.6 million people treated worldwide. A panel of pain specialists convened in Germany to review the clinical program and to discuss the role of tapentadol PR in the management of chronic pain. The clinical study program demonstrated effective and generally well-tolerated treatment for up to 2 years in a broad range of chronic pain conditions, including those with neuropathic pain components. This was confirmed in routine clinical practice observations. Head-to-head studies with World Health Organization (WHO) III opioids such as oxycodone controlled release and oxycodone/naloxone PR showed at least comparable pain relief in the treatment of moderate-to-severe musculoskeletal pain. Rotation from poorly tolerated WHO III opioids to tapentadol PR provided effective pain relief and better symptom control for musculoskeletal pain compared to previous medication. Functionality, health status and quality of life also improved under tapentadol PR treatment. The gastrointestinal tolerability profile was more favorable compared to other tested WHO III opioids. Tapentadol PR has a good safety profile and no evidence of acquired tolerance from the long-term data so far collected. Overall, tapentadol PR represents an effective and generally well-tolerated alternative to "classical" opioidergic drugs.

Safety and immunogenicity of an AS03-adjuvanted A(H1N1)pmd09 vaccine administered simultaneously or sequentially with a seasonal trivalent vaccine in adults 61 years or older: data from two multicentre randomised trials.

During the 2009-2010 Northern Hemisphere influenza season, both seasonal and pandemic influenza vaccines were expected to be administered to elderly people, which is an important target group for influenza vaccination. Two multicentre randomised clinical studies were conducted in participants aged ≥61 years to assess the immunogenicity and reactogenicity following vaccination with two doses of an AS03-adjuvanted A(H1N1)pmd09 vaccine when either sequentially administered (21 days before first dose [N=73] or 21 days after second dose [N=72]) or co-administered (first dose [N=84] or second dose [N=84]) with a licensed trivalent seasonal influenza vaccine (TIV). Overall, 313 participants from 2 centres in Sweden (ClinicalTrials.gov, NCT00968890) and 6 centres in Germany (NCT00971425) were randomised to one of the four treatment groups. The AS03-adjuvanted A(H1N1)pmd09 vaccine elicited a good immune response against A(H1N1)pmd09-like virus in all treatment groups after the first and second dose, meeting and exceeding the European licensing criteria for pandemic influenza vaccines. After one dose of the AS03-adjuvanted A(H1N1)pmd09 vaccine, haemagglutination inhibition seroconversion rates ranged from 85% (95% confidence interval: 74-93%) to 93% (85-97%), seroprotection rates from 87% (76-94%) to 96% (90-99%) and geometric mean fold rise from 15 (11-19) to 20 (16-25). The haemagglutination inhibition immune responses to the AS03-adjuvanted A(H1N1)pmd09 vaccine seemed lower when TIV was administered 3 weeks before, while immune responses to TIV seemed not affected by either vaccination schedule. Solicited symptoms were more frequently reported following administration of the AS03-adjuvanted A(H1N1)pmd09 vaccine compared to TIV, but these were mainly mild to moderate in intensity and transient in the four treatment groups. These results suggest that sequential or co-administration of the AS03-adjuvanted A(H1N1)pmd09 vaccine and TIV induced a good immune response to both vaccines and had a clinically acceptable safety profile in people aged ≥61 years.