Decitabine: a review of its use in older patients with acute myeloid leukaemia.

Decitabine (Dacogen(®)) is a deoxynucleoside analogue of cytidine that selectively inhibits DNA methyltransferases. Decitabine administered at a dose of 20 mg/m(2) by a 1-h intravenous infusion for 5 consecutive days of a 4-week cycle has been approved by the European Medicines Agency (EMA) for use in adult patients aged ≥65 years with de novo or secondary acute myeloid leukaemia (AML) who are not candidates for standard induction therapy. Decitabine, compared with treatment choice (cytarabine or supportive care), did not result in a statistically significant improvement in median overall survival (OS) in older patients with AML at the pre-specified primary endpoint of a pivotal phase III trial.

Tadalafil: in the treatment of signs and symptoms of benign prostatic hyperplasia with or without erectile dysfunction.

Tadalafil is a selective cyclic guanosine monophosphate-specific phosphodiesterase type 5 inhibitor. Once-daily tadalafil 5 mg was effective in treating the signs and symptoms of benign prostatic hyperplasia (BPH). In phase III trials in men with BPH, the mean change from baseline to week 12 in the total International Prostate Symptom Score (IPSS; primary endpoint) was significantly greater in those treated with once-daily tadalafil 5 mg than with placebo.

Transdermal granisetron: a guide to its use in preventing nausea and vomiting induced by chemotherapy.

Transdermal granisetron (Sancuso®) is effective in the prevention of nausea and vomiting in patients with cancer who are receiving moderately or highly emetogenic chemotherapy for 3-5 days. Transdermal granisetron is noninferior to oral granisetron in this indication, and is generally well tolerated in this indication. Thus, transdermal granisetron provides a convenient option for the prevention of chemotherapy-induced nausea and vomiting, with the potential to improve patient compliance.

Live attenuated influenza vaccine (Fluenz™): a guide to its use in the prevention of seasonal influenza in children in the EU.

Live attenuated influenza vaccine (LAIV).[Fluenz™] has a convenient intranasal route of administration. In the EU, it is indicated for the prevention of influenza disease caused by the influenza virus strains contained in the vaccine in children and adolescents aged 2 years to <18 years.

Crizotinib: in locally advanced or metastatic non-small cell lung cancer.

Crizotinib is an inhibitor of receptor tyrosine kinases (including anaplastic lymphoma kinase [ALK]). Oral crizotinib 250 mg twice daily was associated with clinically meaningful response rates in two noncomparative trials (phase I and phase II) in patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC). In the phase I trial (median duration of treatment of 32 weeks) and phase II trial (median duration of treatment of 22 weeks), the objective response rate in crizotinib recipients was 61% and 50%, respectively, and the median duration of response was 48.

Canakinumab: in patients with cryopyrin-associated periodic syndromes.

Canakinumab is a recombinant, fully human, monoclonal, anti-human interleukin-1β (IL-1β) antibody that binds with high affinity and specificity to human IL-1β, preventing its interaction with IL-1 receptors. Canakinumab (150 mg in patients weighing >40 kg or 2 mg/kg in those weighing 15-40 kg) administered once every 8 weeks as a single dose via subcutaneous injection provided a rapid and sustained response in patients with cryopyrin-associated periodic syndromes (CAPS). During the initial 8-week phase of a three-part, phase III trial, a complete response to a single dose of canakinumab occurred in 97% of the 35 patients with CAPS, with 71% of responses occurring within 8 days.

Everolimus: in patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex.

Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR). Everolimus (starting dosage 3.0 mg/m(2)) was associated with a significant reduction in the volume of the largest subependymal giant cell astrocytoma (SEGA) in 28 patients aged ≥3 years with tuberous sclerosis complex (TSC) in a phase II trial (C2485).

Live attenuated influenza vaccine (FluMist®; Fluenz™): a review of its use in the prevention of seasonal influenza in children and adults.

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.

Silodosin: treatment of the signs and symptoms of benign prostatic hyperplasia.

Silodosin is an α-adrenoceptor antagonist with high selectivity for α(1A)- relative to α(1B)- adrenoceptors. In men aged >50 years with benign prostatic hyperplasia (BPH), silodosin 8 mg once daily, compared with placebo, was associated with a significantly more rapid and effective improvement in the total International Prostate Symptom Score (IPSS) and the storage and voiding IPSS subscores in three 12-week, phase III trials conducted in Europe and the US. In the European trial, silodosin was at least as effective as tamsulosin 0.

Aripiprazole: in the treatment of irritability associated with autistic disorder in pediatric patients.

Aripiprazole is an atypical antipsychotic approved for the treatment of irritability associated with autistic disorder in pediatric patients aged 6-17 years. In two, randomized, double-blind, placebo-controlled studies in pediatric patients aged 6-17 years with irritability associated with autistic disorder, 8 weeks of treatment with aripiprazole 2-15 mg/day, compared with placebo, resulted in significant improvements in the Aberrant Behavior Checklist Irritability subscale score at endpoint (primary endpoint), and the mean Clinical Global Impression-Improvement score. Aripiprazole was generally well tolerated in this patient population in the two 8-week studies and a 52-week study, with most adverse events being mild to moderate in severity.

Hyaluronic acid (Supartz®): a review of its use in osteoarthritis of the knee.

Hyaluronic acid (Supartz®; molecular weight 620-1170 kDa) is a sterile, viscoelastic, non-pyogenic solution that is indicated as a medical device for the treatment of pain in patients with osteoarthritis of the knee who have failed to respond adequately to conservative nonpharmacological therapy and simple analgesics. Intra-articular injections of Supartz® were significantly more effective than control injections, according to an integrated longitudinal analysis of pooled data from five randomized, double-blind, vehicle-controlled, multicentre trials in patients with osteoarthritis of the knee. Supartz®, compared with the phosphate-buffered saline control, significantly reduced the total Lesquésne Index score in the post-injection period.

Aliskiren: a review of its use as monotherapy and as combination therapy in the management of hypertension.

Aliskiren is an orally administered, nonpeptide direct renin inhibitor indicated for the management of hypertension. Aliskiren was effective in controlling blood pressure (BP) as monotherapy and in combination with other antihypertensives, in large, randomized trials. Aliskiren 150-300 mg/day as monotherapy was effective in lowering BP across short- (≤12 weeks) and longer-term (up to 54 weeks) periods, providing sustained and consistent effects with 24-hour BP control.

Inactivated split-virion seasonal influenza vaccine (Fluarix): a review of its use in the prevention of seasonal influenza in adults and the elderly.

Fluarix is a trivalent, inactivated, split-virion influenza vaccine containing 15 microg haemagglutinin from each of the three influenza virus strains (including an H1N1 influenza A virus subtype, an H3N2 influenza A virus subtype and an influenza B virus) that are expected to be circulating in the up-coming influenza season. Fluarix is highly immunogenic in healthy adults and elderly, and exceeds the criteria that make it acceptable for licensure in various regions (including the US and Europe). In a large, phase III, placebo-controlled, double-blind trial conducted in the US (2004/2005) in subjects aged 18-64 years, postvaccination seroconversion rates against the H1N1, H3N2 and B antigens were 60-78% and respective postvaccination seroprotection rates were 97-99% in Fluarix recipients.

Lapatinib: in postmenopausal women with hormone receptor-positive, HER2-positive metastatic breast cancer.

Lapatinib is an orally active, low molecular weight, reversible inhibitor of the intracellular tyrosine kinase domains of both human epidermal growth factor receptor (HER) type 1 (HER1) and type 2 (HER2). In a large phase III trial (EGF30008) in 1286 postmenopausal women with hormone receptor (HR)-positive, metastatic breast cancer who had not received previous therapy for advanced or metastatic disease, the primary endpoint of median progression-free survival in a HER2-positive population of 219 women was significantly longer with lapatinib plus letrozole than with letrozole plus placebo (8.2 vs 3.

Spotlight on topical pimecrolimus in pediatric atopic dermatitis.

Topical pimecrolimus 1% cream (Elidel) [hereafter referred to as topical pimecrolimus] is a nonsteroidal alternative in the treatment of pediatric atopic dermatitis. In vehicle-controlled, short-term, continuous-use trials in pediatric patients with mild to moderate atopic dermatitis, topical pimecrolimus was effective in treating disease symptoms. Topical pimecrolimus was effective in preventing disease flares and reducing the need for topical corticosteroids in longer term, intermittent-use trials.

Bivalirudin: in patients with ST-segment elevation myocardial infarction.

Bivalirudin is a synthetic 20 amino acid polypeptide that directly inhibits both fibrin-bound and soluble thrombin. In the randomized, open-label, multicentre HORIZONS-AMI trial in patients with ST-segment elevation myocardial infarction (STEMI) who were undergoing primary percutaneous coronary intervention (PCI), compared with unfractionated heparin (UFH) plus a glycoprotein (GP) IIb/IIIa inhibitor, bivalirudin was associated with a significantly lower 30-day rate of net adverse clinical events that was largely due to the significantly lower 30-day rate of non-coronary-artery bypass grafting major bleeding. There was no significant between-group difference in the 30-day rate of major adverse cardiovascular events.

Pramipexole extended release: in Parkinson's disease.

Pramipexole extended release (ER) is a non-ergolinic dopamine receptor agonist available for use as a once-daily oral treatment for the signs and symptoms of early and advanced idiopathic Parkinson's disease. Once-daily pramipexole ER and three times-daily pramipexole immediate release (IR) have similar exposure over 24 hours. The ER formulation is associated with fewer fluctuations in plasma pramipexole concentrations over this period.

Amlodipine/Atorvastatin: a review of its use in the treatment of hypertension and dyslipidaemia and the prevention of cardiovascular disease.

Amlodipine/atorvastatin (Caduet) is a single-tablet, fixed-dose combination of the dihydropyridine calcium channel antagonist amlodipine and the HMG-CoA reductase inhibitor atorvastatin. The bioavailability of amlodipine and atorvastatin with a single-tablet, fixed-dose amlodipine/atorvastatin combination was not significantly different to that with coadministered separate amlodipine and atorvastatin tablets. In well controlled clinical trials in patients with hypertension and dyslipidaemia, once-daily amlodipine and atorvastatin (administered as the single-tablet, fixed-dose combination or coadministered as two separate tablets) effectively reduced systolic BP (SBP) and low-density lipoprotein cholesterol (LDL-C) levels, and enabled more patients to achieve BP and LDL-C goals than single-agent or placebo therapy.

Regadenoson.

Regadenoson is an adenosine A(2A) receptor agonist approved for use as a pharmacologic stress agent for radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. Regadenoson causes a rapid increase in coronary blood flow, which is sustained for a short duration. In two phase III trials in patients with known or suspected coronary artery disease who were indicated for pharmacologic stress myocardial perfusion imaging, the agreement rate (in detecting reversible perfusion defects) between sequential adenosine-regadenoson scan images was noninferior to that between sequential adenosine-adenosine scan images.

Transdermal granisetron.

Granisetron is a highly selective serotonin 5-HT(3) receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. The transdermal granisetron system delivers continuous granisetron (3.1 mg/day) into the systemic circulation (via passive diffusion) for up to 7 days.

Bimatoprost: a review of its use in open-angle glaucoma and ocular hypertension.

Bimatoprost (Lumigan) is a synthetic prostamide that reduces intraocular pressure (IOP) by increasing the outflow of aqueous humour. In patients with open-angle glaucoma or ocular hypertension, long-term treatment (for up to 48 months) with once-daily bimatoprost 0.03% ophthalmic solution was more effective than timolol twice daily in providing a sustained and stable reduction in IOP.

Topical pimecrolimus: a review of its use in the management of pediatric atopic dermatitis.

Topical pimecrolimus 1% cream (Elidel) [hereafter referred to as topical pimecrolimus] is a nonsteroidal alternative in the treatment of pediatric atopic dermatitis. In vehicle-controlled, short-term, continuous-use trials in pediatric patients with mild to moderate atopic dermatitis, topical pimecrolimus was effective in treating disease symptoms. Topical pimecrolimus was effective in preventing disease flares and reducing the need for topical corticosteroids in longer term, intermittent-use trials.