Spotlight on VSL#3 probiotic mixture in chronic inflammatory bowel diseases.

VSL#3 (VSL#3) is a high-concentration probiotic preparation of eight live freeze-dried bacterial species that are normal components of the human gastrointestinal microflora, including four strains of lactobacilli (Lactobacillus casei, L. plantarum, L. acidophilus, and L.

VSL#3 probiotic mixture: a review of its use in chronic inflammatory bowel diseases.

VSL#3 (VSL#3) is a high-concentration probiotic preparation of eight live freeze-dried bacterial species that are normal components of the human gastrointestinal microflora, including four strains of lactobacilli (Lactobacillus casei, L. plantarum, L. acidophilus and L.

Linezolid: a pharmacoeconomic review of its use in serious Gram-positive infections.

Linezolid (Zyvox), the first available oxazolidinone antibacterial agent, has good activity against Gram-positive pathogens, including multidrug-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Randomised multicentre trials in patients with various types of serious Gram-positive infections showed that clinical cure rates with linezolid were similar to those with vancomycin or teicoplanin. In some subgroup analyses, which must be interpreted with a degree of caution, clinical advantages were noted for linezolid (e.

Acamprosate: a review of its use in the maintenance of abstinence in patients with alcohol dependence.

Acamprosate (Campral delayed-release tablet), a synthetic compound with a similar structure to that of the neurotransmitter GABA and the neuromodulator taurine, facilitates the maintenance of abstinence in detoxified alcohol-dependent patients. Although the precise mechanism(s) of action of the drug remains to be fully elucidated, it appears that it most likely involves beneficial modulation of the glutamatergic neurotransmitter system, including antagonism of the mGLu5 metabotropic glutamate receptor, to counteract the imbalance between the glutamatergic and GABAergic systems associated with chronic alcohol exposure and alcohol withdrawal. In several double-blind, placebo-controlled trials of up to 12 months' duration, acamprosate effectively maintained complete abstinence in detoxified alcohol-dependent patients, irrespective of disease severity or the type of psychosocial support.

Pregabalin: as adjunctive treatment of partial seizures.

Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5-methylhexanoic acid, possesses anticonvulsant activity. Pregabalin binds with high affinity and specificity to voltage-gated calcium channel alpha(2)-delta proteins. The putative mechanism of action of the drug is reduced excitatory neurotransmitter release caused by binding to the alpha(2)-delta protein, resulting in allosteric modulation of P/Q-type voltage-gated calcium channels.

Oxaliplatin: in operable colorectal cancer.

Oxaliplatin is available in numerous countries for the treatment of metastatic colorectal cancer (in conjunction with fluoropyrimidine therapy). The activity of oxaliplatin in advanced disease has led to investigation of its potential in operable disease. The addition of oxaliplatin to adjuvant therapy with fluorouracil and folinic acid (FOLFOX4 regimen) is associated with a significantly greater disease-free survival at 3 years (78% vs 73%; p = 0.

Brivudin (bromovinyl deoxyuridine).

Brivudin is an oral thymidine analogue indicated for the early treatment of acute herpes zoster in immunocompetent adults. It has high, selective activity against varicella zoster virus (VZV), inhibiting VZV replication, possibly through competitive inhibition of viral DNA polymerase, or by acting as an alternative substrate to deoxythymidine triphosphate, causing viral DNA strand breakage. In a large, 7-day, phase III trial in immunocompetent patients with herpes zoster, once-daily brivudin 125mg was significantly more effective than oral acyclovir 800mg five times daily in reducing the mean time from start of treatment to last vesicular eruption, and was as effective as acyclovir at healing lesions and alleviating acute zoster-related pain.

Extended-release metformin hydrochloride. Single-composition osmotic tablet formulation.

In the new oral, once-daily, extended-release (ER), single-composition osmotic tablet formulation of the biguanide metformin hydrochloride (metformin XT), metformin is released at a controlled rate from a central osmotic tablet core through a semipermeable coating. A decrease in fasting plasma insulin, a marker of insulin resistance, was seen with metformin XT but not with immediate-release (IR) metformin in one well designed trial, but changes were similar in another. The pharmacokinetics of metformin XT reflect its extended-release characteristics.

Zoledronic acid: a review of its use in patients with advanced cancer.

Zoledronic acid (Zometa), a parenteral bisphosphonate, is an inhibitor of osteoclast-mediated bone resorption and is used in the management of patients with cancer. Zoledronic acid 4 mg is administered as an intravenous infusion over 15 minutes. In the treatment of bone metastases, zoledronic acid is the first and only bisphosphonate to demonstrate efficacy in patients with a broad range of tumour types and in multiple myeloma.

Micafungin.

Micafungin, an echinocandin antifungal agent with a novel mechanism of action, inhibits beta-(1,3)-D-glucan synthase interfering with fungal cell wall synthesis. It shows excellent antifungal activity against a broad range of Candida spp., including azole-resistant strains, and Aspergillus spp.

Repaglinide : a pharmacoeconomic review of its use in type 2 diabetes mellitus.

Repaglinide (Prandin), NovoNorm, GlucoNorm, an oral insulin secretagogue, was the first meglitinide analogue to become available for use in patients with type 2 diabetes mellitus. The drug lowers postprandial glucose excursions by targeting early-phase insulin release, an effect thought to be important in reducing long-term cardiovascular complications of diabetes. Repaglinide provided similar overall glycaemic control to that achieved with glibenclamide (glyburide), as assessed by glycosylated haemoglobin (HbA(1c)) and fasting blood glucose levels, and was generally well tolerated in well designed clinical trials.

Mitoxantrone: a review of its use in multiple sclerosis.

Mitoxantrone (Novantrone), a synthetic anthracenedione derivative, is an antineoplastic, immunomodulatory agent. Its presumed mechanism of action in patients with multiple sclerosis (MS) is via immunomodulatory mechanisms, although these remain to be fully elucidated. Intravenous mitoxantrone treatment improved neurological disability and delayed progression of MS in patients with worsening relapsing-remitting (RR) [also termed progressive-relapsing (PR) MS] or secondary-progressive (SP) disease.

Intravenous esomeprazole.

The proton pump inhibitor esomeprazole comprises the S-isomer of omeprazole. An intravenous formulation of the drug has been developed for use in patients not able to take oral drugs. The level of gastric acid control was similar with intravenous and oral esomeprazole in two studies in healthy volunteers receiving 20 or 40 mg once daily for 5 days.

Rosuvastatin: a review of its use in the management of dyslipidemia.

Rosuvastatin (Crestor), an HMG-CoA reductase inhibitor (statin), has a favorable pharmacologic profile, including its selective uptake by hepatic cells, hydrophilic nature, and lack of metabolism by cytochrome p450 (CYP) 3A4 isoenzyme. This last property means that the potential for CYP3A4-mediated drug interactions and, as a consequence, adverse events is low in those requiring concomitant therapy with a statin and agents metabolized by CYP3A4. In a broad spectrum of adult patients with dyslipidemias, oral rosuvastatin 5-40 mg once daily effectively and rapidly improved lipid profiles in several large, randomized, mainly double-blind, multicenter trials of up to 52 weeks' duration.

Combined hepatitis A and B vaccines: a review of their immunogenicity and tolerability.

Unlabelled: Three combined hepatitis A and B vaccine preparations are commercially available in various countries: a two-dose paediatric formulation (Ambirix) [administered at months 0 and 6-12]; and a three-dose adult (Twinrix Adult) or paediatric (Twinrix Paediatric) formulation (administered at months 0, 1 and 6). The adult vaccine provides consistent, marked immunogenicity which is at least similar to that of its constituent vaccines used together and with a tolerability profile that is possibly improved. An accelerated, day-0, -7 and -21 regimen has also shown immunogenicity similar to that of the monovalent vaccines given concurrently, and now has an emerging role in adults likely to travel to hepatitis A virus (HAV) and/or hepatitis B virus (HBV) endemic regions within 1 month.

Oral fludarabine.

Fludarabine is an antimetabolite antineoplastic agent used in the treatment of various haematological malignancies, particularly B-cell chronic lymphocytic leukaemia (CLL). An oral formulation of fludarabine has recently become available in the majority of European countries for the treatment of patients with relapsed or refractory B-cell CLL after initial treatment with an alkylating agent-based regimen. It is the first oral formulation of a purine analogue available for clinical use in B-cell CLL.

Tipranavir.

Tipranavir is a potent and selective non-peptidic HIV-1 protease inhibitor with a markedly improved resistance profile compared with traditional, peptidomimetic protease inhibitors. The presence of five or fewer protease gene mutations or one or two protease inhibitor resistance-associated mutations (PRAMs) is associated with reduced susceptibility to currently available protease inhibitors. However, 16-20 mutations (including three or more PRAMs) may be needed to confer resistance to tipranavir.

Memantine.

Memantine, an uncompetitive antagonist with moderate affinity for NMDA receptors, demonstrates voltage-dependency and relatively fast on/off receptor kinetics. Memantine 20 mg/day significantly slowed the rate of deterioration in outpatients with moderate to severe Alzheimer's disease in a 28-week US randomised, double-blind, placebo-controlled, multicentre study. Memantine 10 mg/day improved measures of dementia in care-dependent inpatients with Alzheimer's disease or vascular dementia in a 12-week randomised, double-blind study.

Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia.

Unlabelled: Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukaemia (CLL). While the optimal use of the drug in many clinical settings has yet to be clarified, two pivotal trials have established rituximab as a viable treatment option in patients with relapsed or refractory indolent NHL, and as a standard first-line treatment option when combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (the most common type of aggressive NHL). The former was a noncomparative trial in relapsed indolent NHL (follicular and small lymphocytic subtypes) with clinical responses achieved in about half of patients treated with rituximab 375 mg/m(2) intravenously once weekly for 4 weeks, which was similar to some of the most encouraging results reported with traditional chemotherapeutic agents.

Topical 3% diclofenac in 2.5% hyaluronic acid gel: a review of its use in patients with actinic keratoses.

Topical 3% diclofenac in 2.5% hyaluronic acid (HA) gel (diclofenac HA gel; Solaraze) is an NSAID approved for the treatment of actinic keratoses (AK). The efficacy of diclofenac HA gel (0.

Combined two-dose hepatitis A and B vaccine (AmBirix).

One month after the last dose (i.e. at month 7), geometric mean titres (GMTs) of antibodies directed against hepatitis A virus (anti-HAV) were generally greater in participants (aged 12-15 years) receiving combined two-dose (0 and 6 months) hepatitis A and B vaccine (AmBirix) compared with the three-dose (containing one half the dose of the two active components per dose, given at 0, 1 and 6 months; Twinrix Paediatric) schedule.

Bicalutamide: in early-stage prostate cancer.

Bicalutamide is an oral, once-daily nonsteroidal antiandrogen. Its efficacy in localised or locally advanced prostate cancer is currently being investigated as part of the Early Prostate Cancer (EPC) programme. In the EPC programme, bicalutamide 150 mg/day, as an adjunct to radiotherapy, radical prostatectomy or watchful waiting, significantly reduced the risk of objective disease progression, the incidence of bone metastases and the risk of prostate specific antigen progression compared with placebo (p < 0.

Levofloxacin: an updated review of its use in the treatment of bacterial infections.

Unlabelled: Levofloxacin is the L-form of the fluoroquinolone antibacterial agent, ofloxacin. In in vitro studies, levofloxacin demonstrated a broad range of activity against Gram-positive and -negative organisms and anaerobes. The drug is more active against Gram-positive organisms than ciprofloxacin, but less active than newer fluoroquinolones such as gatifloxacin.

Dexmethylphenidate.

Dexmethylphenidate comprises only the d-enantiomer (the pharmacologically effective isomer) of racemic methylphenidate and is indicated for the treatment of patients aged > or =6 years with attention deficit hyperactivity disorder (ADHD). In a 4-week, double-blind trial in 132 children with ADHD, significantly greater improvements from baseline in teacher-rated Swanson, Nolan and Pelham (SNAP)-ADHD scores were seen in dexmethylphenidate and methylphenidate recipients, compared with placebo recipients. In addition, significantly more dexmethylphenidate and methylphenidate recipients, compared with placebo recipients, were much improved or very much improved according to Clinical Global Impression-Improvement of Illness scale scores.

Zidovudine: a review of its use in the management of vertically-acquired pediatric HIV infection.

Unlabelled: Zidovudine is a thymidine analog that, after intracellular phosphorylation to zidovudine triphosphate metabolite, inhibits HIV-specific reverse transcriptase and terminates proviral DNA. Zidovudine administered to mildly symptomatic women with HIV infection in the antepartum (100mg orally 5 times/day), intrapartum (2 mg/kg intravenously over 1 hour then 1 mg/kg/h) and then to the neonate for 6 weeks (2 mg/kg), significantly reduced the rate of vertical HIV transmission by about two thirds, in the absence of breast-feeding (The Pediatric AIDS Clinical Trials Group 076 trial, standard protocol). Shorter zidovudine regimens, reduced the risk of transmission of HIV by 50% in a non-breast-feeding population and by about 37% in breast-feeding populations.