Drugs

Phan, Hanna; Moeller, Matthew; Nahata, Milap

doi: 10.2165/9884960-000000000-00000pmid: 19943707

Allergic rhinitis (AR) affects a large percentage of paediatric patients. With the wide array of available agents, it has become a challenge to choose the most appropriate treatment for patients. Second-generation anti-histamines have become increasingly popular because of their comparable efficacy and lower incidence of adverse effects relative to their first-generation counterparts, and the safety and efficacy of this drug class are established in the adult population. Data on the use of the second-generation anti-histamines oral cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, and the leukotriene receptor antagonist montelukast as well as azelastine nasal spray in infants and children are evaluated in this review.

Nudelman, Yuliya; Tunkel, Allan

doi: 10.2165/11530590-000000000-00000pmid: 19943708

Bacterial meningitis continues to be an important disease throughout the world and can be a life-threatening emergency if not suspected, appropriately diagnosed and managed expeditiously. The epidemiology of bacterial meningitis has changed dramatically over the last 20 years, primarily as a result of the introduction of conjugate vaccines against the common meningeal pathogens, such that in the developed world where vaccination is routinely utilized, bacterial meningitis has become a disease of adults rather than of infants and children. The management approach to patients with suspected or proven bacterial meningitis includes emergent cerebrospinal fluid analysis and initiation of appropriate antimicrobial and adjunctive therapies. The choice of empirical antimicrobial therapy is based on the patient’s age and underlying disease status; once the infecting pathogen is isolated, antimicrobial therapy can be modified for optimal treatment. Many patients with suspected or proven bacterial meningitis should also receive adjunctive dexamethasone therapy. This is based on experimental animal model data which demonstrated that the subarachnoid space inflammatory response that results from antimicrobial-induced bacterial lysis can contribute to morbidity and mortality. Clinical studies have demonstrated the benefit of adjunctive dexamethasone in infants and children with Haemophilus influenzae type B meningitis, and adults with pneumococcal meningitis, in which mortality and adverse outcome are reduced. Use of adjunctive dexamethasone in adults ith meningitis caused by other bacteria, and in infants and children with pneumococcal meningitis, is controversial. To be effective, adjunctive dexamethasone should be administered concomitant with or just prior to the first antimicrobial dose for maximal effect on the subarachnoid space inflammatory response.

Lyseng-Williamson, Katherine; Blick, Stephanie

doi: 10.2165/10481380-000000000-00000pmid: 19943710

▴ Telavancin is the first available lipoglycopeptide antibacterial agent. It is active against Gram-positive bacteria, including meticillin/oxacillin-resistant Staphylococcus aureus (MRSA) strains associated with complicated skin and skin structure infections (cSSSIs). ▴ In randomized, double-blind trials, intravenous telavancin 10 mg/kg once daily (administered as a 1-hour infusion) was effective in the treatment of adult patients with cSSSIs, including those with infections caused by MRSA, as shown by clinical cure rates in clinically evaluable, all-treated and microbiologically evaluable populations at the test-of-cure (TOC) visit. ▴ Telavancin 10 mg/kg once daily was noninferior to intravenous vancomycin 1 g every 12 hours, with clinical cure rates of 88% versus 87% at the TOC visit in pooled data from the clinically evaluable population (n=1489) of two phase III trials. ▴ Pooled clinical cure rates in telavancin recipients at the TOC visit were also not significantly different from those in vancomycin recipients in the all-treated or microbiologically evaluable populations, including microbiologically evaluable subgroups with baseline infections caused by MRSA, meticillin-susceptible S. aureus or other Gram-positive pathogens. ▴ Telavancin was generally well tolerated in patients with cSSSIs, with most adverse events being of mild or moderate severity.

Moen, Marit

doi: 10.2165/11202850-000000000-00000pmid: 19943711

▴ Topical diclofenac solution (Pennsaid®) is a liquid formulation containing the NSAID diclofenac sodium (1.5% w/w). The solution base contains 45% w/w dimethyl sulfoxide (DMSO) to enhance the absorption of diclofenac through the skin. Topical diclofenac solution is applied directly to the knee for treatment of symptoms associated with osteoarthritis of the knee. ▴ In well designed 4- to 12-week trials in patients with primary osteoarthritis of the knee, topical diclofenac solution (40 drops four times daily) was significantly more effective than placebo or vehicle control (carrier solution without diclofenac) for improving Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain and physical function, and improving patient global assessment (PGA) and/or patient overall health assessment scores from baseline to the final assessments. ▴ Topical diclofenac solution (50 drops three times daily) was as effective as oral diclofenac 150 mg/day for improving WOMAC pain and physical function and PGA scores in a 12-week double-blind study in patients with osteoarthritis of the knee. ▴ Topical diclofenac solution was generally well tolerated. The most common treatment-emergent adverse event experienced by topical diclofenac solution recipients was dry skin at the application site. Gastrointestinal adverse events and abnormal laboratory parameters were less common with topical diclofenac solution than with oral diclofenac.

Duggan, Sean; Curran, Monique

doi: 10.2165/11202780-000000000-00000pmid: 19943709

▴ Granisetron is a highly selective serotonin 5-HT3 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. The trans-dermal granisetron system delivers continuous granisetron (3.1 mg/day) into the systemic circulation (via passive diffusion) for up to 7 days. ▴ In a large phase III trial in cancer patients receiving multi-day (3–5 days) moderately or highly emetogenic chemotherapy, transdermal granisetron applied 24–48 hours prior to chemotherapy and remaining in place for 7 days was noninferior to oral granisetron 2 mg once daily administered for 3–5 days 1 hour prior to chemotherapy. Efficacy was assessed according to the proportion of patients achieving complete response (no vomiting and/or retching, no more than mild nausea, no rescue medication) from the first day, until 24 hours after the start of the last day, of administration of the chemotherapy regimen. ▴ In a phase II trial in patients with cancer receiving single-day, moderately-emetogenic chemotherapy, transdermal granisetron applied at least 24 hours prior to chemotherapy and removed after 5 days was as effective as a single oral dose of granisetron 2 mg in achieving total control (no nausea, no vomiting/retching, no use of rescue medication and no study withdrawal) during the delayed (24–120 hours; primary endpoint) period after chemotherapy. ▴ Transdermal granisetron was generally well tolerated in clinical trials, with few adverse events being treatment related.

Keating, Gillian

doi: 10.2165/11203660-000000000-00000pmid: 19943712

doi: 10.2165/11532510-000000000-00000pmid: N/A

Gusani, Niraj; Jiang, Yixing; Kimchi, Eric; Staveley-O’Carroll, Kevin; Cheng, Hua; Ajani, Jaffer

doi: 10.2165/11530870-000000000-00000pmid: 19943706

Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm and fourth leading cause of cancer death worldwide. The survival for patients with advanced HCC is extremely poor. This is largely attributed to the lack of effective screening methods, advanced stage at presentation, limited utility of surgical intervention and ineffective medical therapy. Over the past 30 years, many conventional cytotoxic agents have been tested and have failed to confer a survival benefit. Recently, sorafenib, a multi-tyrosine kinase inhibitor, was approved by the US FDA as first-line therapy in HCC as the first agent demonstrating survival benefit in this disease. Although the survival benefit demonstrated by sorafenib is moderate, molecular targeted therapy has brought new hope in the management of HCC.