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Specially created pediatric formulations have the potential to improve the acceptability, effectiveness, and accuracy of dosing of artemisinin-based combination therapy (ACT) in young children, a patient group that is inherently vulnerable to malaria. Artemether-lumefantrine (AL) Dispersible is a pediatric formulation of AL that is specifically tailored for the treatment of children with uncomplicated Plasmodium falciparum malaria, offering benefits relating to efficacy, convenience and acceptance, accuracy of dosing, safety, sterility, stability, and a pharmacokinetic profile and bioequivalence similar to those of crushed and intact AL tablets. However, despite being the first pediatric antimalarial to meet World Health Organization (WHO) specifications for use in infants and children who are ≥5 kg in body weight and its inclusion in WHO Guidelines, there are few publications that focus on AL Dispersible. Based on a systematic review of the recent literature, this paper provides a comprehensive overview of the clinical experience with AL Dispersible to date. A randomized, phase 3 study that compared the efficacy and safety of AL Dispersible to those of crushed AL tablets in 899 African children reported high PCR-corrected cure rates at day 28 (97.8% and 98.5% for AL Dispersible and crushed tablets, respectively), and the results of several subanalyses of these data indicate that this activity is observed regardless of patient weight, food intake, and maximum plasma concentrations of artemether or its active metabolite, dihydroartemisinin. These and other clinical data support the continued use of pediatric antimalarial formulations in all children

Nonsteroidal anti-inflammatory drugs (NSAIDs) are established as treatment for managing pain associated with primary dysmenorrhea. However, the efficacy and tolerability of lumiracoxib 200 mg once daily (q.d.) has not previously been examined in primary dysmenorrhea.Two randomized, multicenter, double-blind, placebo-controlled, crossover studies of similar design have assessed the efficacy and tolerability of two regimens of lumiracoxib compared with placebo (Study 1) or naproxen and placebo (Study 2) in women (aged 18-45 years) with moderate to severe primary dysmenorrhea. In Study 1 (n = 132), patients received lumiracoxib 200 mg q.d., lumiracoxib 200 mg with a 200 mg redose (p.r.n.) on day 1, or placebo. In Study 2 (n = 144), patients received lumiracoxib 200 mg q.d., lumiracoxib 200 mg with a 200 mg redose p.r.n. on day 1, naproxen 500 mg twice daily (b.i.d.), or placebo. Patients recorded study medication use, efficacy assessments, and rescue medication use.The primary efficacy variable, summed (time-weighted) pain intensity difference (categorical scale) over the first 8 hours (SPID-8), was similar between all active treatments (e.g., p = 0.939 for naproxen 500 mg b.i.d. vs. lumiracoxib 200 mg q.d. in Study 2), and all active treatments were superior to placebo (p0.001). Median time-to-onset of analgesia was similar between lumiracoxib 200 mg q.d. and naproxen 500 mg b.i.d. Similar trends were observed for all other secondary efficacy variables. All treatments were well tolerated.Short-term administration of lumiracoxib 200 mg q.d. is effective and well tolerated and provides an alternative treatment option for the management of moderate to severe pain associated with primary dysmenorrhea.

Background Pediatric artemisinin-based combination therapy formulations have the potential to improve the effectiveness and accuracy of dosing in young children. Coartem (artemether-lumefantrine; AL) Dispersible was developed and launched in partnership with the Medicines for Malaria Venture for the treatment of uncomplicated Plasmodium falciparum malaria and is the first pediatric antimalarial to receive Swissmedic approval and meet WHO specifications for use in infants and children ≥5 kg.

Introduction Cryopyrin-associated periodic syndrome (CAPS) represents a spectrum of three auto-inflammatory syndromes, familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular syndrome (NOMID/CINCA) with etiology linked to mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1β) release. CAPS is a rare hereditary auto-inflammatory disease, which may start early in childhood and requires a life-long treatment. Canakinumab, a fully human anti-IL-1β antibody, produces sustained selective inhibition of IL-1β. This study was conducted to assess the efficacy, safety, and pharmacokinetics of canakinumab in the treatment of pediatric CAPS patients. Methods Seven pediatric patients (five children and two adolescents) with CAPS were enrolled in a phase II, open-label study of canakinumab in patients with CAPS. Canakinumab was administered at a dose of 2 mg/kg subcutaneously (s.c.) (for patients with body weight ≤ 40 kg) or 150 mg s.c. (for patients with body weight > 40 kg) with re-dosing upon each relapse. The primary efficacy variable was time to relapse following achievement of a complete response (defined as a global assessment of no or minimal disease activity and no or minimal rash and values for serum C-reactive protein (CRP) and/or serum amyloid A (SAA) within the normal range, < 10 mg/L). Results All patients achieved a complete response within seven days after the first dose of canakinumab and responses were reinduced on retreatment following relapse. Improvements in symptoms were evident within 24 hours after the first dose, according to physician assessments. The estimated median time to relapse was 49 days (95% CI 29 to 68) in children who received a dose of 2 mg/kg. Canakinumab was well tolerated. One serious adverse event, vertigo, was reported, but resolved during treatment. Conclusions Canakinumab, 2 mg/kg or 150 mg s.c., induced rapid and sustained clinical and biochemical responses in pediatric patients with CAPS. Trial registration number ClinicalTrials.gov: NCT00487708

Contains fulltext : 70565.pdf (Publisher’s version ) (Closed access) The 52-week Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) investigated the gastrointestinal and cardiovascular safety profile of lumiracoxib 400 mg once daily compared with 2 traditional nonsteroidal anti-inflammatory drugs (NSAIDs): ibuprofen 800 mg 3 times daily and naproxen 500 mg twice daily. Data from TARGET were analyzed to examine the effect of lumiracoxib compared with ibuprofen and naproxen on blood pressure (BP), incidence of de novo and aggravated hypertension, prespecified edema events, and congestive heart failure. Lumiracoxib resulted in smaller changes in BP as early as week 4. Least-squares mean change from baseline at week 4 for systolic BP was +0.57 mm Hg with lumiracoxib compared with +3.14 mm Hg with ibuprofen (P

Summary Background The large (n = 18 325) Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) study demonstrated a significant gastrointestinal benefit with lumiracoxib 400 mg o.d. (4× the recommended dose in osteoarthritis) vs. naproxen 500 mg b.d. or ibuprofen 800 mg t.d.s. Aim To investigate how early a reduction in ulcer complications could be detected with lumiracoxib vs. nonselective nonsteroidal anti-inflammatory drugs in TARGET. Methods Pointwise 95% confidence intervals were generated for the between-treatment differences in Kaplan–Meier estimates for definite or probable upper gastrointestinal ulcer complications (ulcer complications) and for all ulcers. Results In patients not on aspirin, there was a significant reduction in all ulcers by day 8 and in ulcer complications by day 16 with lumiracoxib compared with both nonselective nonsteroidal anti-inflammatory drugs combined, by day 6 (all ulcers) and day 14 (ulcer complications) vs. naproxen and by day 32 (all ulcers) and day 33 (ulcer complications) vs. ibuprofen. Conclusion Even with short-term use, there are gastrointestinal safety benefits for lumiracoxib vs. nonselective nonsteroidal anti-inflammatory drugs.

Background & Aims: Selective cyclooxygenase-2 inhibitors were developed to reduce the gastrointestinal risk associated with nonsteroidal anti-inflammatory drugs (NSAIDs). The Therapeutic Arthritis Research and Gastrointestinal Event Trial was the largest study to evaluate primarily the gastrointestinal safety outcomes of selective cyclooxygenase-2 inhibitors. Data from the Therapeutic Arthritis Research and Gastrointestinal Event Trial were used to identify risk factors and investigate the safety of lumiracoxib in subgroups. Methods: Patients with osteoarthritis (age, ≥50 y) were randomized to receive lumiracoxib 400 mg once daily, naproxen 500 mg twice daily, or ibuprofen 800 mg 3 times daily for 12 months. Events were categorized by a blinded adjudication committee. The primary end point was all definite or probable ulcer complications. Results: For patients taking NSAIDs, factors associated with an increased risk of ulcer complications were age 65 years or older (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.48–3.59), previous history of gastrointestinal bleed or ulcer (HR, 3.61; 95% CI, 1.86–7.00), non-Caucasian racial origin (HR, 2.10; 95% CI, 1.35–3.27), and male sex (HR, 1.70; 95% CI, 1.08–2.68). With lumiracoxib, significant risk factors were age 65 years or older (HR, 3.18; 95% CI, 1.40–7.20), male sex (HR, 2.60; 95% CI, 1.25–5.40), non-Caucasian racial origin (HR, 2.16; 95% CI, 1.02–4.59), and concomitant aspirin use (HR, 2.89; 95% CI, 1.40–5.97). Increased risks in patients age 65 years and older were increased further if other risk factors were present. Lumiracoxib maintained an advantage over NSAIDs across all subgroups except aspirin use. Conclusions: Lumiracoxib was associated with a reduced risk of ulcer complications compared with NSAIDs in all significant subgroups except aspirin users.

Background Lumiracoxib is a selective cyclooxygenase-2 inhibitor effective in the treatment of osteoarthritis (OA) with a superior gastrointestinal (GI) safety profile as compared to traditional non-steroidal anti-inflammatory drugs (NSAIDs, ibuprofen and naproxen). This safety study compared the GI tolerability, the blood pressure (BP) profile and the incidence of oedema with lumiracoxib and rofecoxib in the treatment of OA. Rofecoxib was withdrawn worldwide due to an associated increased risk of CV events and lumiracoxib has been withdrawn from Australia, Canada, Europe and a few other countries following reports of suspected adverse liver reactions. Methods This randomised, double-blind study enrolled 309 patients (aged greater than or equal to 50 years) with primary OA across 51 centres in Europe. Patients were randomly allocated to receive either lumiracoxib 400 mg od (four times the recommended dose in OA) (n = 154) or rofecoxib 25 mg od (n = 155). The study was conducted for 6 weeks and assessments were performed at Weeks 3 and 6. The primary safety measures were the incidence of predefined GI adverse events (AEs) and peripheral oedema. The secondary safety measures included effect of treatment on the mean sitting systolic and diastolic blood pressure (msSBP and msDBP). Tolerability of lumiracoxib 400 mg was assessed by the incidence of AEs. Results Lumiracoxib and rofecoxib displayed similar GI safety profiles with no statistically significant difference in predefined GI AEs between the two groups (43.5% vs. 37.4%, respectively). The incidence and severity of individual predefined GI AEs was comparable between the two groups. The incidence of peripheral oedema was low and identical in both the groups (n = 9, 5.8%). Only one patient in the lumiracoxib group and three patients in the rofecoxib group had a moderate or severe event. At Week 6 there was a significantly lower msSBP and msDBP in the lumiracoxib group compared to the rofecoxib group (p < 0.05). A similar percentage of patients in both groups showed an improvement in target joint pain and disease activity. The tolerability profile was similar in both the treatment groups. Conclusion Lumiracoxib 400 mg od (four times the recommended dose in OA) provided a comparable GI safety profile to rofecoxib 25 mg od (therapeutic dose). However, lumiracoxib was associated with a significantly better BP profile as compared to rofecoxib. Trial registration number - NCT00637949