PMID- 17825689 OWN - NLM STAT- MEDLINE DCOM- 20071009 LR - 20131121 IS - 0149-2918 (Print) IS - 0149-2918 (Linking) VI - 29 IP - 7 DP - 2007 Jul TI - A 2-week, multicenter, randomized, double-blind, double-dummy, add-on study of the effects of titration on tolerability of tramadol/acetaminophen combination tablet in Korean adults with knee osteoarthritis pain. PG - 1381-9 AB - BACKGROUND: Combined tramadol/acetaminophen is used to treat pain related to osteoarthritis. However, adverse events (AEs) leading to discontinuation can occur. Dose titration may decrease the risk for AEs. OBJECTIVE: The aim of this study was to assess the effect of tramadol/acetaminophen titration on the development of AEs leading to treatment discontinuation in patients with knee osteoarthritis. METHODS: This 2-week, multicenter, randomized, double-blind, double-dummy, add-on study was conducted at 12 tertiary referral university hospitals in the Republic of Korea. Patients aged 35 to 75 years with knee osteoarthritis receiving a stable dose of NSAIDs and with a daily mean pain-intensity score of > or = 4 on a numeric rating scale (NRS) (0 = no pain to 10 = worst pain) during the 48 hours prior to enrollment were eligible. Patients were randomly assigned to receive 1 tablet of tramadol/acetaminophen 37.5/325 mg QD and 1 placebo BID for 3 days, followed by 1 active tablet BID and 1 placebo QD for 4 days, followed by 1 active tablet TID for 7 days (titration group) or 1 tablet of combined tramadol 37.5 mg/acetaminophen 325 mg TID for 14 days (nontitration group). The primary outcome measure was the rate of treatment discontinuation due to AEs. Secondary outcome measures were time to discontinuation due to AEs, prevalences and characteristics of AEs, decrease from baseline in pain intensity as measured on the NRS, and change in the Korean version of the Western Ontario and McMaster Universities (K-WOMAC) index score (scale: 0 = best to 100 = worst). RESULTS: A total of 250 patients were enrolled (92.0% female; mean [SD] age, 60.2 [7.8] years; mean [SD] weight, 60.0 [9.2] kg [range, 37.5-90.7 kg]; all Korean). The discontinuation rate was significantly lower in the titration group than in the nontitration group (10.5% vs 26.2%; P < 0.001). The Kaplan-Meier survival curve showed that the rates of discontinuation due to AEs were similar in the 2 groups up to day 2, but thereafter the discontinuation rate was significantly lower in the titration group. The most common AEs were nausea (12.1% and 24.6% in the titration and nontitration groups, respectively; P = 0.008), vomiting (4.0% and 17.2%; P < 0.001), and dizziness (9.7% and 22.1%; P = 0.005). No serious AEs were reported in either group. Tramadol/acetaminophen use was associated with a similar decrease from baseline in pain in both the titration and nontitration groups (mean [SD] Delta: NRS, -1.60 [1.62] vs -1.68 [1.58]; total K-WOMAC, -12.86 [13.73] vs -12.52 [16.58]). CONCLUSIONS: In this population of Korean patients with knee osteoarthritis pain managed with a stable dose of NSAIDs, titration of tramadol/acetaminophen over 12 days was associated with improved tolerability and a significantly lower discontinuation rate compared with nontitration. Both regimens significantly reduced from baseline associated with osteoarthritis. FAU - Choi, Chan-Bum AU - Choi CB AD - Department of Internal Medicine, The Hospital for Rheumatic Diseases, Hanyang University College of Medicine, Seoul, Republic of Korea. FAU - Song, Jung Soo AU - Song JS FAU - Kang, Young Mo AU - Kang YM FAU - Suh, Chang Hee AU - Suh CH FAU - Lee, Jisoo AU - Lee J FAU - Choe, Jung-Yoon AU - Choe JY FAU - Lee, Choong Ki AU - Lee CK FAU - Shim, Seung Cheol AU - Shim SC FAU - Chung, Won Tae AU - Chung WT FAU - Song, Gwan Gyu AU - Song GG FAU - Kim, Hyun Ah AU - Kim HA FAU - Ji, Jong Dae AU - Ji JD FAU - Nam, Eon Jeong AU - Nam EJ FAU - Park, Sung-Hoon AU - Park SH FAU - Hong, Young Hoon AU - Hong YH FAU - Sheen, Dong Hyuk AU - Sheen DH FAU - Lim, Mi Kyoung AU - Lim MK FAU - Seo, Young Ii AU - Seo YI FAU - Sung, Yoon-Kyoung AU - Sung YK FAU - Kim, Tae-Hwan AU - Kim TH FAU - Lee, Jong-Tae AU - Lee JT FAU - Bae, Sang-Cheol AU - Bae SC LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Analgesics) RN - 0 (Drug Combinations) RN - 362O9ITL9D (Acetaminophen) RN - 39J1LGJ30J (Tramadol) SB - IM MH - Acetaminophen/administration & dosage/adverse effects/*therapeutic use MH - Adult MH - Aged MH - Analgesics/administration & dosage/adverse effects/*therapeutic use MH - Double-Blind Method MH - Drug Administration Schedule MH - Drug Combinations MH - Female MH - Humans MH - Korea MH - Male MH - Middle Aged MH - Osteoarthritis, Knee/*drug therapy/physiopathology MH - Pain/*drug therapy MH - Patient Dropouts MH - Tramadol/administration & dosage/adverse effects/*therapeutic use EDAT- 2007/09/11 09:00 MHDA- 2007/10/10 09:00 CRDT- 2007/09/11 09:00 PHST- 2007/05/25 00:00 [received] PHST- 2007/09/11 09:00 [pubmed] PHST- 2007/10/10 09:00 [medline] PHST- 2007/09/11 09:00 [entrez] AID - S0149-2918(07)00207-X [pii] AID - 10.1016/j.clinthera.2007.07.015 [doi] PST - ppublish SO - Clin Ther. 2007 Jul;29(7):1381-9. doi: 10.1016/j.clinthera.2007.07.015.