Natalie J. Carter

Live Attenuated Influenza Vaccine (FluMist®; Fluenz™)

Live attenuated influenza vaccine (LAIV) is an intranasally administered trivalent, seasonal influenza vaccine that contains three live influenza viruses (two type A [H1N1 and H3N2 subtypes] and one type B).LAIV was effective in protecting against culture-confirmed influenza caused by antigenically matched and/or distinct viral strains in children aged ≤71 months enrolled in three phase III trials. LAIV was superior to trivalent inactivated influenza vaccine (TIV) in protecting against influenza caused by antigenically-matching viral strains in a multinational phase III trial in children aged 6–59 months. LAIV was also significantly more effective than TIV in decreasing the incidence of culture-confirmed influenza illness in two open-label studies (in children with recurrent respiratory tract illnesses aged 6–71 months and in children and adolescents with asthma aged 6–17 years).LAIV did not differ significantly from placebo in preventing febrile illnesses in adults (primary endpoint) enrolled in a phase III trial. However, LAIV significantly reduced the incidence of febrile upper respiratory tract illnesses (URTI), severe febrile illnesses, febrile URTI-related work absenteeism and healthcare provider use. In another well designed trial in adults, LAIV significantly reduced the incidence of symptomatic, laboratory-confirmed influenza compared with placebo (but not intramuscular TIV).LAIV was generally well tolerated in most age groups, with the majority of adverse events being mild to moderate in severity, and runny nose/nasal congestion being the most common. In a large phase III trial, LAIV, compared with TIV, was associated with an increased incidence of medically significant wheezing in vaccine-naive children aged <24 months and an increased incidence of hospitalization in children aged 6–11 months; LAIV is not approved for use in children <24 months.LAIV was not always associated with high rates of seroconversion/seroresponse, particularly in older children and adults, or in subjects with detectable levels of haemagglutination-inhibiting antibodies at baseline. However, LAIV did elicit mucosal (nasal) IgA antibody responses and strong cell-mediated immunity responses. Only one confirmed case of LAIV virus transmission to a placebo recipient (who did not become ill) occurred in a transmission study conducted in young children. The immunogenic response to LAIV in young healthy children was not affected by concomitant administration with other commonly administered childhood vaccines.In conclusion, intranasal LAIV seasonal influenza vaccine is effective and well tolerated in children, adolescents and adults. LAIV was more effective than TIV in children, although this advantage was not seen in adults. In the US, LAIV is indicated for the active immunization of healthy subjects aged 2–49 years against influenza disease caused by virus subtypes A and type B contained in the vaccine.

Trabectedin : a review of its use in the management of soft tissue sarcoma and ovarian cancer.

Trabectedin (Yondelis); ET-743) is an antineoplastic agent that was originally derived from the Caribbean marine tunicate Ecteinascidia turbinata and is now produced synthetically. It binds to the minor groove of DNA, disrupting the cell cycle and inhibiting cell proliferation. Intravenous trabectedin administered once every 3 weeks is approved as monotherapy in Europe for use in patients with advanced soft tissue sarcoma (STS) after failure of standard therapy with anthracyclines or ifosfamide, or who are unsuited to receive these agents. It also has orphan drug status in STS in the US and in ovarian cancer in the US and Europe, and is under investigation as combination therapy in patients with recurrent ovarian cancer. In clinical trials, trabectedin showed efficacy in the treatment of patients with advanced or metastatic STS, especially those with leiomyosarcoma or liposarcoma, as well as in women with platinum-sensitive advanced or recurrent ovarian cancer. In addition, its tolerability profile was generally manageable. The introduction of trabectedin expands the currently limited range of effective treatment options for patients with advanced or metastatic STS; trabectedin also has the potential to be a beneficial treatment for advanced or recurrent ovarian cancer.

Pirfenidone: In Idiopathic Pulmonary Fibrosis

Pirfenidone is an orally administered pyridine that has orphan designation for the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF) in the EU. Pirfenidone 2403 mg/day for 72 weeks administered to patients with IPF was associated with a significantly lower mean decline in the percent predicted forced vital capacity than placebo (primary endpoint) according to data from one of two randomized, double-blind, multinational trials (studies 004 and 006 [also known as the CAPACITY trials]), and data from a pooled analysis of both trials. In another randomized, double-blind, multicentre Japanese trial, the adjusted mean in the change in vital capacity from baseline to week 52 was significantly lower in patients with IPF who received pirfenidone 1800 mg/day (considered to be comparable to the 2403 mg/day dose in studies 004 and 006 on a weight-normalized basis) than in those who received placebo (primary endpoint). Pirfenidone had an acceptable tolerability profile in clinical trials, with most adverse events being mild to moderate in severity.

Prepandemic Influenza Vaccine H5N1 (Split Virion, Inactivated, Adjuvanted) [Prepandrix™]

SummaryAbstractAlthough rare, influenza pandemics are a recurrent event, and influenza A/H5N1 is generally considered to be the most likely causative agent of the next pandemic. Vaccines are widely considered to be the first line of defense for protecting populations in advance of an influenza pandemic. Because it is not known beforehand which strain of influenza A/H5N1 virus could give rise to a pandemic, prepandemic vaccines that impart broad cross-reactive immunogenicity are required. In addition, low doses of H5 hemagglutinin are preferable in order to make antigen supplies go further towards meeting global demands for prepandemic vaccines.Prepandemic influenza vaccine H5N1 [Prepandrix™; AS03-H5N1 vaccine] is a split virion, inactivated vaccine containing H5 hemagglutinin antigen adjuvanted with a novel 10% oil-in-water emulsion-based adjuvant system (AS03). It is approved in the EU for use as an active immunization against H5N1 subtype influenza A virus (influenza A/H5N1 virus) in adults aged 18–60 years. The recommended dosage in this population is two doses of 0.5 mL containing 3.75 µg of H5 hemagglutinin, administered ≥21 days apart. Adjuvantation of H5N1 vaccine with AS03 allows for a reduction in the H5 hemagglutinin dose required to elicit an adequate immune response, and administration of two doses of the adjuvanted vaccine met all criteria for the licensure of influenza vaccines set out in European Committee for Proprietary Medicinal Products (CPMP) and US FDA documents.In two clinical trials, two doses of AS03-H5N1 vaccine containing 3.75 µg of H5 hemagglutinin induced an immune response in healthy volunteers aged 18–60 years against the homologous, clade 1 vaccine strain, A/Vietnam/1194/2004, and the heterologous, drifted, clade 2 nonvaccine strains, A/Anhui/1/2005, A/Indonesia/5/2005, and A/turkey/Turkey/1/2005. This cross-clade response persisted for ≥6 months following administration of the first vaccine dose in the majority of vaccine recipients. In addition, AS03-H5N1 vaccine protected against lethal challenge with A/Vietnam/1194/2004 or A/Indonesia/5/2005 in animal studies. The vaccine was generally well tolerated and adverse events were transient and predominantly of mild to moderate severity.AS03-H5N1 vaccine has demonstrated antigen dose-sparing properties and cross-clade reactive immunity in clinical trials and challenge studies in animal models. As a result, stockpiling AS03-H5N1 vaccine has the potential to protect populations against a pandemic caused by an influenza A/H5N1 virus and may represent an important measure in pandemic preparedness.ImmunogenicityAS03-H5N1 vaccine containing an H5 hemagglutinin dose of 3.75 µg elicited a satisfactory immune response against the homologous, clade 1, vaccine strain A/Vietnam/1194/2004 in a randomized, observer-blind, parallel-group, dose-finding trial and a phase III, lot-to-lot consistency trial in adult volunteers aged 18–60 years. In the dose-finding study, volunteers received AS03-H5N1 (n = 200) or nonadjuvanted-H5N1 (n = 200) vaccine containing 3.75, 7.5, 15.0, or 30.0 µg of H5 hemagglutinin. An H5-hemagglutinin dose-response effect was observed for antihemagglutinin antibody and neutralizing antibody titers over the dose range studied. All CPMP and FDA acceptance criteria for the licensure of influenza vaccines were met following two doses of AS03-H5N1 vaccine containing 3.75 µg of H5 hemagglutinin administered 21 days apart. This allowed for antigen dose sparing when compared with nonadjuvanted-H5N1 vaccine, which only met two of three CPMP criteria after two doses of vaccine containing 30 µg of H5 hemagglutinin. Based on the results of the dose-finding study, the phase III, lot-to-lot consistency study focused solely on the immunogenicity of AS03-H5N1 (n = 961) and nonadjuvanted-H5N1 (n = 245) vaccine containing 3.75 µg of H5 hemagglutinin. Where endpoints were reported, CPMP criteria were met with AS03-H5N1, but not nonadjuvanted-H5N1 vaccine, in the consistency study.Not only did AS03-H5N1 vaccine containing 3.75 µg of H5 hemagglutinin elicit an adequate immune response against the clade 1 vaccine strain A/Vietnam/1194/2004, but it also induced cross-clade immunity against the heterologous, drifted, clade 2 strains A/Anhui/1/2005 (subclade 2.3), A/Indonesia/5/2005 (subclade 2.1), and A/turkey/Turkey/1/2005 (subclade 2.2). In the dose-finding study, the neutralizing antibody serocon-version rate against these clade 2 strains following the second vaccine dose was 75%, 77%, and 85% for A/Anhui/1/2005, A/Indonesia/5/2005, and A/turkey/Turkey/1/2005, respectively; in the consistency study, the neutralizing antibody seroconversion rate was 91.4% for A/Indonesia/5/2005. In terms of neutralizing antibody seroconversion rates, 60–70% of recipients had retained a cross-neutralizing response against A/Anhui/1/2005 and A/turkey/Turkey/1/2005 and 40% had retained a cross-neutralizing response against A/Indonesia/5/2005 at 6 months after administration of the first vaccine dose.Because the efficacy of AS03-H5N1 vaccine cannot ethically be studied in the target population prior to the onset of a pandemic, animal studies are required; ferrets are widely considered to be the best proxy for humans in the study of influenza A/H5N1 vaccines. In two such studies, ferrets receiving AS03-H5N1 vaccine containing 0.6–15.0 µg of H5 hemagglutinin or either a control vaccine containing AS03 alone, phosphate-buffered saline, or nonadjuvanted-H5N1 vaccine containing 15.0 µg of H5 hemagglutinin, were challenged with a lethal dose of the homologous clade 1, vaccine influenza A/H5N1 strain A/Vietnam/1194/2004 or the heterologous, drifted, clade 2, nonvaccine strain A/Indonesia/5/2005. Challenge with the vaccine strain resulted in an H5 hemagglutinin-dose-dependent immune response in ferrets receiving AS03-H5N1 vaccine, with all ferrets receiving the 15 µg dose surviving the challenge. The majority of AS03-H5N1 vaccine-receiving ferrets (≥65%) had a low viral load (<102 50% tissue culture infective dose/g or mL) in lung tissue and on pharyngeal swabs.In addition, 74% and 61% of ferrets that were challenged with the clade 2, nonvaccine strain, A/Indonesia/5/ 2005, and received AS03-H5N1 vaccine, demonstrated a serologic response against the vaccine and nonvaccine viral strains. The majority (≥67%) of these ferrets had a low level of virus replication in lung tissue and on pharyngeal swabs, had a low rate of viral shedding, and survived until the end of the challenge period. This was in contrast to the control ferrets, none of which developed a serologic response, and all of which had a high level of virus replication and shedding, and either died or were euthanized because they were moribund during the challenge period. In addition, even in those ferrets receiving AS03-H5N1 vaccine that did not show a serologic response, the lung viral loads were generally lower than those seen with control animals.TolerabilityAS03-H5N1 vaccine containing 3.75, 7.5, 15.0, or 30.0 µg of H5 hemagglutinin administered as two doses 21 days apart was generally well tolerated in healthy adults aged 18–60 years.Regardless of H5 hemagglutinin dose, injection site pain was the most frequently reported solicited local adverse event associated with AS03-H5N1 vaccine in a dose-finding study in healthy adults aged 18–60 years, and in a phase III active comparator trial in healthy adults aged ≥18 years. In these studies, the incidence of pain was significantly higher in those who received AS03-H5N1 vaccine than in those who received nonadjuvanted-H5N1 or seasonal influenza vaccine/placebo. Other frequently reported solicited local adverse events associated with AS03-H5N1 vaccine included injection site redness, induration, swelling, and less commonly, ecchymosis. Fatigue, myalgia, and headache were the most frequently occurring solicited general adverse events associated with AS03-H5N1 vaccine. The majority of local and general adverse events were of mild to moderate severity; in addition, most local adverse events had resolved or decreased in intensity within 48 hours.Unsolicited adverse events, including grade 3 unsolicited adverse events, were reported with similar frequency in AS03-H5N1 vaccine recipients and seasonal influenza vaccine/placebo recipients. Lymph-node related adverse events were uncommon (≤3.5%), and those that were thought to be vaccine-related and of grade 3 severity had fully resolved within 2–4 days.

Trabectedin: A Review of its Use in Soft Tissue Sarcoma and Ovarian Cancer

Trabectedin (Yondelis) is a tetrahydroisoquinoline molecule that was originally derived from a marine organism. It is indicated in the EU and many other countries for use in patients with advanced soft-tissue sarcoma (STS) who have progressed despite receiving previous treatment with anthracyclines and ifosfamide or in those who are unable to receive these agents. It is also approved in the EU in combination with pegylated liposomal doxorubicin for the treatment of platinum-sensitive, recurrent ovarian cancer. In addition, trabectedin holds orphan drug status for the treatment of advanced, recurrent STS in the US, Switzerland and Korea, and for the treatment of advanced, recurrent ovarian cancer in the US and Switzerland. Clinical trials showed that intravenous trabectedin was effective in chemotherapy-experienced patients with advanced, recurrent liposarcoma or leiomyosarcoma, and results from a retrospective analysis suggest that the drug may be particularly effective in patients with advanced myxoid liposarcoma. In addition, coadministration of trabectedin with pegylated liposomal doxorubicin was associated with a significantly longer progression-free survival (6 weeks) than pegylated liposomal doxorubicin monotherapy in patients with recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy. The tolerability profile of trabectedin was manageable in clinical trials, and the tolerability profile of concomitant trabectedin and pegylated liposomal doxorubicin was generally consistent with that of each agent alone. Results to date indicate that trabectedin is a valuable addition to the group of second-line antineoplastic agents available for the treatment of advanced, recurrent STS, and that it is a beneficial treatment for recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy when administered in conjunction with pegylated liposomal doxorubicin.

Glatiramer acetate: a review of its use in relapsing-remitting multiple sclerosis and in delaying the onset of clinically definite multiple sclerosis.

Glatiramer acetate is a synthetic analogue of the multiple sclerosis (MS)-associated antigen, myelin basic protein. It is indicated in the EU, US and many other countries to reduce the frequency of relapses in patients with relapsing-remitting MS (RRMS), and for the treatment of patients who have experienced a well defined first clinical episode and are at high risk of developing clinically definite MS or have features of MS on MRI.The efficacy of glatiramer acetate in patients with RRMS has been shown in two randomized, double-blind, multicentre phase III trials. In one trial, glatiramer acetate was associated with a significantly lower mean relapse rate than placebo after 24 months’ treatment (primary endpoint). In an ongoing open-label extension to this trial, glatiramer acetate was associated with a sustained reduction in the relapse rate at the 6-, 8- and 15-year follow-ups. In the other trial, the mean cumulative number of gadolinium-enhancing lesions on T1-weighted MRI images was significantly lower in glatiramer acetate versus placebo recipients after 9 months’ treatment (primary endpoint).Glatiramer acetate also had generally similar efficacy to subcutaneous interferon (IFN)-β-1a or IFNβ-1b in two large randomized, open-label, multicentre phase III trials conducted over 96 weeks or ≥2 years. These data were supported by those from a smaller randomized, open-label phase IV trial that utilized a unique imaging protocol to evaluate the efficacy of glatiramer acetate versus that of IFNβ-1b over ≥2 years. In these trials, there was no significant difference between glatiramer acetate and IFNβ recipients in any of the clinical endpoints at study end (e.g. time to first relapse [primary endpoint of the REGARD trial] or risk of relapse [primary endpoint of the BEYOND trial]). Moreover, there was no significant difference between glatiramer acetate and IFNβ-1b recipients in the median number of combined active lesions per patient per monthly MRI scan during the first 12 months of treatment (primary endpoint of the BECOME trial). In general, there was no significant between-group difference in the majority of other MRI-assessed endpoints in any of the trials.The efficacy of glatiramer acetate in patients with clinically isolated syndrome (CIS) was established in a randomized, double-blind, double-dummy, multicentre phase III trial (the PreCISe trial). In this study, glatiramer acetate was associated with a significantly longer time to conversion to clinically definite MS than placebo (primary endpoint).Glatiramer acetate was generally well tolerated in clinical trials, with most adverse events being mild to moderate in severity. Injection site-related reactions and immediate post-injection systemic reactions were the most frequently observed adverse events associated with glatiramer acetate in clinical studies.In conclusion, glatiramer acetate is a valuable first-line option in the treatment of RRMS, as well as being an option in the treatment of CIS.

Duloxetine: a review of its use in the treatment of generalized anxiety disorder.

Duloxetine (Cymbalta(R)) is a potent serotonin and noradrenaline (norepinephrine) reuptake inhibitor (SNRI) in the CNS. It is indicated for the treatment of generalized anxiety disorder (GAD) as well as other indications. In patients with GAD of at least moderate severity, oral duloxetine 60-120 mg once daily was effective with regard to improvement from baseline in assessments of anxiety and functional impairment, and numerous other clinical endpoints. Longer-term duloxetine 60-120 mg once daily also demonstrated efficacy in preventing or delaying relapse in responders among patients with GAD. In addition, duloxetine was generally well tolerated, with most adverse events being of mild to moderate severity in patients with GAD in short- and longer-term trials. Additional comparative and pharmacoeconomic studies are required to position duloxetine among other selective serotonin reuptake inhibitors and SNRIs. However, available clinical data, and current treatment guidelines, indicate that duloxetine is an effective first-line treatment option for the management of GAD. Duloxetine is a potent and selective inhibitor of serotonin and noradrenaline transporters, and a weak inhibitor of dopamine transporters. It has a low affinity for neuronal receptors, such as alpha(1)- and alpha(2)-adrenergic, dopamine D(2), histamine H(1), muscarinic, opioid and serotonin receptors, as well as ion channel binding sites and other neurotransmitter transporters, such as choline and GABA transporters. It does not inhibit monoamine oxidase types A or B. The pharmacokinetics of duloxetine in healthy volunteers were dose proportional over the range of 40-120 mg once daily. Steady state was typically reached by day 3 of administration. Duloxetine may be administered without regard to food or time of day. Duloxetine is highly protein bound and is widely distributed throughout tissues. It is rapidly and extensively metabolized in the liver by cytochrome P450 (CYP) 1A2 and 2D6, and its numerous metabolites, which are inactive, are mainly excreted in the urine. The mean elimination half-life of duloxetine is approximately 12 hours. Duloxetine is a substrate for CYP1A2 and CYP2D6 and a moderate inhibitor of CYP2D6. Concomitant use of duloxetine and potent CYP1A2 inhibitors should be avoided and duloxetine should be used with caution in patients receiving drugs that are extensively metabolized by CYP2D6, particularly those with a narrow therapeutic index. Duloxetine was effective in the short-term treatment of patients with primary GAD of at least moderate severity. In four randomized, double-blind, placebo-controlled, multicentre, phase III trials, duloxetine 60-120 mg once daily for 9 or 10 weeks was significantly more effective than placebo with regard to the primary endpoint of mean change in Hamilton Anxiety Rating Scale (HAM-A) total score from baseline to study endpoint. In addition, all other endpoints were generally improved from baseline to a greater extent with duloxetine 60-120 mg once daily than with placebo. Duloxetine also improved patient role functioning (assessed using Sheehan Disability Scale global impairment functioning scores), health-related quality of life and patient well-being compared with placebo. Duloxetine was effective in patients with GAD who were aged >/=65 years. Pooled results of data from the two short-term efficacy trials that also included an active comparator arm showed that the mean change in HAM-A scores with duloxetine relative to placebo were of the same magnitude as those with venlafaxine extended release versus placebo. Duloxetine 60-120 mg once daily was also more effective than placebo in preventing or delaying relapse in responders to duloxetine in a longer-term study. In this study, patients with GAD received duloxetine during a 26-week, open-label, acute treatment phase and responders were then randomized to continue on duloxetine or receive placebo during a 26-week, double-blind, continuation phase. Time to relapse was significantly longer in duloxetine recipients than in placebo recipients. In addition, significantly fewer duloxetine recipients than placebo recipients relapsed during the double-blind phase of the trial and more duloxetine recipients achieved remission. Short- (9-10 weeks) and longer-term (52 weeks) treatment with duloxetine 60-120 mg once daily was generally well tolerated in patients with GAD, with the majority of adverse events being of mild to moderate severity. Nausea, dry mouth, headache, constipation, dizziness and fatigue were among the most common treatment-emergent adverse events. The adverse event profile of duloxetine did not differ with dose or treatment duration. Significantly more patients receiving short-term duloxetine than placebo discontinued treatment because of an adverse event, with nausea being the only event that resulted in significantly more treatment discontinuations in duloxetine recipients than in placebo recipients. Serious adverse events were uncommon with both short- and longer-term duloxetine treatment. Two episodes of attempted suicide and one episode of completed suicide occurred in duloxetine recipients during the 24-week open-label phase of a longer-term trial. No deaths or suicides were reported in any of the short-term trials. Discontinuation-emergent adverse events, most commonly nausea and dizziness, occurred in up to one-third of duloxetine recipients in the short-term trials.

Besifloxacin Ophthalmic Suspension 0.6

Besifloxacin is a novel fluoroquinolone that, like other fluoroquinolones, acts by inhibiting the essential bacterial enzymes DNA gyrase and topoisomerase IV. Topical besifloxacin ophthalmic suspension 0.6% is indicated for use in patients with bacterial conjunctivitis caused by susceptible bacteria.Besifloxacin had in vitro activity against a broad spectrum of Gram-positive and -negative bacteria that commonly cause ocular infections (e.g. Haemophilus influenzae, Staphylococcus aureus, S. epidermidis and Streptococcus pneumoniae), including drug-resistant strains.In two randomized, double-blind, multicentre trials, besifloxacin ophthalmic suspension 0.6% administered at the recommended dose for 5 days in patients aged ≥1 year with bacterial conjunctivitis was significantly (p<0.01) more effective than vehicle in terms of clinical resolution and microbial eradication rates (coprimary endpoints) at study visit two (day 5±1) or three (day 8 or 9) [primary timepoints].Besifloxacin ophthalmic suspension 0.6% was noninferior to moxifloxacin ophthalmic solution 0.5% in patients aged ≥1 year with bacterial conjunctivitis with regard to clinical resolution (58.3% vs 59.4%) and microbial eradication (93.3% vs 91.1%) rates on day 5±1 of treatment (coprimary endpoints) in a randomized, double-blind, multicentre trial; both drugs were administered at a dosage of one drop in the affected eye(s) three times daily for 5 days.Besifloxacin ophthalmic suspension 0.6% was generally well tolerated in clinical trials, with most adverse events being mild in severity. The tolerability profile of besifloxacin ophthalmic suspension 0.6% was similar to that of moxifloxacin ophthalmic solution 0.5%.

Extended-release intramuscular paliperidone palmitate: a review of its use in the treatment of schizophrenia.

Extended-release intramuscular paliperidone palmitate (Xeplion®; Invega® Sustenna®) [henceforth referred to as intramuscular paliperidone palmitate] is a long-acting injectable (LAI) formulation of the well established atypical anti-psychotic agent paliperidone (9-hydroxyrisperidone), which is the major active metabolite of risperidone. This article reviews, from an EU perspective, the therapeutic efficacy and tolerability of intramuscular paliperidone palmitate in the treatment of adults with schizophrenia, and the pharmacology of paliperidone that is relevant to the intramuscular formulation.Intramuscular paliperidone palmitate 25–150mg equivalents (mg eq.) effectively reduced symptoms of schizophrenia in most short-term (9–13 weeks) placebo-controlled trials, as demonstrated by improvements in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to endpoint that were significantly greater in intramuscular paliperidone palmitate than placebo recipients. The onset of clinical response was 8 days in patients who received the recommended initial 150mg eq. dose of intramuscular paliperidone palmitate into the deltoid muscle on day 1.In a longer-term (24-week maintenance phase and variable length double-blind phase) placebo-controlled trial, intramuscular paliperidone palmitate was associated with a significantly longer time to relapse than placebo in patients with schizophrenia at a preplanned interim analysis conducted after 68 relapse events. Because of these favourable results, the study was terminated early.In two 13-week trials, one of which was conducted in Chinese patients, intramuscular paliperidone palmitate administered using the recommended initiation dosage regimen was noninferior to LAI-risperidone in patients with schizophrenia in terms of the between-group treatment difference (intramuscular paliperidone palmitate vs LAI-risperidone) for the mean change from baseline to endpoint in PANSS total score.The tolerability of intramuscular paliperidone palmitate was generally acceptable in clinical trials of schizophrenia. No new safety concerns were revealed compared with oral paliperidone, except for injection site-related reactions.In conclusion, intramuscular paliperidone palmitate is a useful option for the treatment of patients with schizophrenia.

Micafungin: a review of its use in the prophylaxis and treatment of invasive Candida infections in pediatric patients.

Intravenous micafungin (Mycamine; Funguard) is an echinocandin indicated in Japan and the EU for the treatment of pediatric patients (including neonates) with invasive candidiasis and as prophylaxis against Candida infection in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In the EU, micafungin is also indicated in pediatric patients who are expected to have neutropenia for >/=10 days. In Japan, children may also receive micafungin for the treatment of, or as prophylaxis against, invasive Aspergillus infection. Micafungin is not currently approved for use in pediatric patients in the US. Micafungin has very good antifungal activity against a wide range of Candida spp. in vitro. It has a favorable pharmacokinetic profile allowing for once-daily administration, has few drug-drug interactions, and reports of resistance are rare. The results of pediatric substudies indicate that intravenous micafungin is effective in a majority of patients for the treatment of candidemia and other types of invasive candidiasis, and provides effective prophylaxis against invasive fungal infections in pediatric patients undergoing HSCT. The tolerability profile of micafungin in pediatric patients was generally acceptable. In the EU, micafungin is indicated for use when other antifungal medications are not appropriate. Therefore, micafungin provides an alternative to other antifungal agents used in the management of candidemia and invasive candidiasis in pediatric patients, or as prophylaxis against fungal infections in pediatric patients undergoing HSCT.