Teriparatide: a review of its use in osteoporosis.

Recombinant teriparatide (Forteo; Forsteo) is an anabolic (bone forming) agent. Studies have shown that subcutaneous teriparatide 20 microg/day is effective in women with postmenopausal osteoporosis, men with idiopathic or hypogonadal osteoporosis and patients with glucocorticoid-induced osteoporosis. Teriparatide improves bone mineral density (BMD) and alters the levels of bone formation and resorption markers; histomorphometric studies showed teriparatide-induced effects on bone structure, strength and quality. Subcutaneous teriparatide 20 microg/day administered over a treatment period of 11-21 months was effective in reducing the risk of fractures in and in improving BMD in men with idiopathic or hypogonadal osteoporosis, women with postmenopausal osteoporosis and patients with glucocorticoid-induced osteoporosis. Furthermore, the beneficial effects of teriparatide on vertebral fracture prevention and BMD appear to persist following treatment cessation. Teriparatide is generally well tolerated and treatment compliance rates are favourable. However, current limitations on the length of treatment and the high acquisition cost mean that teriparatide is best reserved for the treatment of patients with osteoporosis at high risk of fracture, or for patients with osteoporosis who have unsatisfactory responses to or intolerance of other osteoporosis therapies.

Esomeprazole: a review of its use in the management of gastric acid-related diseases in adults.

Esomeprazole (Nexium); S-omeprazole) is a single optical isomer proton-pump inhibitor (PPI) approved for the management of reflux oesophagitis, the symptomatic treatment of gastro-oesophageal reflux disease (GORD), the prevention and healing of NSAID-associated gastric ulcer disease (and the prevention of NSAID-associated duodenal ulcers in the UK), the treatment of Helicobacter pylori infection and associated duodenal ulcer disease (and prevention of relapse of H. pylori-associated peptic ulcers in the UK), and the treatment of Zollinger-Ellison syndrome (and other hypersecretory syndromes in the US).Once-daily oral esomeprazole 40 mg demonstrates greater antisecretory activity than other PPIs. Overall, in well designed clinical studies of 4 weeks' to 6 months' duration in patients with GORD, esomeprazole had similar or better efficacy than other agents. In patients requiring ongoing treatment with NSAIDs, co-therapy with once-daily esomeprazole 20 or 40 mg achieved relief of gastrointestinal symptoms or prevented ulcer occurrence, more effectively than placebo. Esomeprazole was also better than ranitidine 150 mg twice daily in healing NSAID-associated gastric ulcers. In addition, the drug has demonstrated efficacy as part of a triple-therapy regimen for the eradication of H. pylori infection, the healing of H. pylori associated duodenal ulcers and the prevention of relapse of gastric ulcers. Esomeprazole also effectively treated patients with Zollinger-Ellison syndrome. Esomeprazole is generally well tolerated with an adverse-event profile similar to that of other PPIs. Thus, the efficacy and tolerability of esomeprazole for the management of GORD and H. pylori eradication remains undisputed, and the data support its use for the first-line treatment of NSAID-associated gastric ulcer disease and Zollinger-Ellison syndrome.

Fondaparinux sodium: a review of its use in the management of acute coronary syndromes.

Fondaparinux sodium (Arixtra) is a synthetic, sulfated pentasaccharide, selective factor Xa inhibitor that is indicated in Europe for preventing thrombus formation in patients with acute coronary syndromes (ACS; the focus of this review), including those with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina.The large (n = 20,078), well designed OASIS-5 trial showed that subcutaneous fondaparinux 2.5 mg/day for 12,000) OASIS-6 trial. There were no differences in the incidence of major bleeding between these groups, resulting in a benefit : risk balance favoring fondaparinux. The specificity and selectivity of fondaparinux, combined with its long half-life and 100% bioavailability, allows once-daily anticoagulation without the need for monitoring activated clotting time. Subcutaneous fondaparinux was noninferior to enoxaparin treatment in patients with unstable angina or NSTEMI, and was more effective than usual care in those with STEMI. Fondaparinux has a favorable tolerability profile, particularly with regard to the risk of major bleeding, and limited data suggest that it is more cost effective than enoxaparin in the short term. Thus, overall, clinical evidence suggests that fondaparinux has a valuable place in the treatment of patients with ACS.

Cetuximab: a review of its use in squamous cell carcinoma of the head and neck and metastatic colorectal cancer.

Cetuximab (Erbitux) is a human-mouse chimeric monoclonal antibody, which competitively binds to the accessible extracellular domain of the epidermal growth factor receptor (EGFR) to inhibit dimerisation and, subsequently, inhibit tumour growth and metastasis. In the EU and the US, cetuximab has been approved for use with concomitant radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) and in combination with irinotecan for the treatment of metastatic colorectal cancer (mCRC) in patients with EGFR-expressing tumours who are refractory to irinotecan-based therapy. In the US, cetuximab has also been approved as monotherapy in patients with recurrent or metastatic SCCHN for whom platinum-based therapy has failed and in patients with mCRC who are intolerant of irinotecan-based regimens.In treatment-naive patients with locoregionally advanced SCCHN, cetuximab plus radiotherapy was more effective than radiation therapy alone in prolonging locoregional disease control. In addition, more limited noncomparative data from a large trial indicated a 13% overall objective response rate (ORR) in platinum-refractory patients with SCCHN. In patients with EGFR-expressing mCRC, cetuximab plus irinotecan improved ORR more than cetuximab monotherapy in a trial in irinotecan-refractory patients; however, there was no difference in overall survival (OS) between cetuximab plus irinotecan and cetuximab monotherapy in oxaliplatin-refractory recipients in another trial. In an ongoing trial, progression-free survival (PFS) exceeded 50% after 12 weeks in irinotecan-refractory patients receiving three different dosages of cetuximab plus irinotecan. In another large trial, cetuximab monotherapy prolonged OS compared with best supportive care (BSC) in heavily pretreated patients. Overall, cetuximab treatment had an acceptable tolerability profile, with the majority of adverse events being mild or moderate in severity and clinically manageable. In particular, cetuximab therapy did not exacerbate toxicities commonly associated with chemo- or radiotherapeutic regimens. Albeit occurring with high incidence, adverse cutaneous reactions appear to be a marker for response. Results of ongoing head-to-head comparative trials comparing cetuximab with other biological agents will help to establish definitively the role of cetuximab in the management of SCCHN and mCRC. In the meantime, cetuximab, with its highly targeted mechanism of action and synergistic activity with current treatment modalities, is a valuable treatment option in patients with SCCHN and mCRC.

Ranibizumab.

Ranibizumab is the antigen-binding fragment of a recombinant, humanised monoclonal antibody, which binds with high affinity to, and inhibits the activity of, all active forms of vascular endothelial growth factor A, an important mediator in the development of choroidal neovascularisation. Well designed, phase III trials in patients with neovascular (wet) age-related macular degeneration (AMD) indicated that monthly intravitreal injections of ranibizumab 0.3 or 0.5 mg for up to 2 years maintained or improved visual acuity to a greater extent than sham injection, verteporfin photodynamic therapy or sham photodynamic therapy. In patients with predominantly classic wet AMD who received ranibizumab in combination with verteporfin therapy, preliminary results indicate that combination therapy is superior to that of verteporfin therapy alone. Most serious ocular adverse events, which were uncommon, were associated with either the injection procedure or ranibizumab.

Certolizumab pegol: in Crohn's disease.

Certolizumab pegol is a pegylated humanized Fab' fragment of an anti-tumor necrosis factor-alpha (TNFalpha) monoclonal antibody, which binds with high affinity to both membrane-bound and soluble TNFalpha and demonstrates high neutralizing potency for these factors. The elimination half-life of certolizumab in humans has been extended to approximate/= 2 weeks through pegylation, allowing subcutaneous administration of this agent once every 4 weeks. Subcutaneous certolizumab pegol 400mg once every 4 weeks (with an additional 400mg dose at week 2) was effective as induction and maintenance therapy in patients with moderate to severe Crohn's disease in whom baseline serum C-reactive protein levels were >/=10 mg/L, according to data from two well designed, randomized phase III trials. Certolizumab pegol was, in general, well tolerated, and adverse events associated with the drug were of a mild to moderate nature; no instances of lupus were reported in any of the trials.

Lisdexamfetamine.

Lisdexamfetamine is an amphetamine prodrug, comprising an l-lysine amino acid covalently bonded to dextroamphetamine (d-amphetamine). Lisdexamfetamine is approved in the US for the treatment of attention-deficit hyperactivity disorder in children aged 6-12 years. Lisdexamfetamine is a therapeutically inactive molecule. After oral ingestion, lisdexamfetamine is hydrolyzed to l-lysine, a naturally occurring essential amino acid, and active d-amphetamine, which is responsible for the activity of the drug. In a well designed pharmacodynamic study in adult stimulant abusers, 50 or 100 mg doses of oral lisdexamfetamine had less likability than d-amphetamine 40 mg, suggesting a reduced abuse potential. Through rate-limited hydrolysis in the body, l-lysine is cleaved, gradually releasing pharmacologically active d-amphetamine. The pharmacokinetics of lisdexamfetamine suggest a reduced potential for abuse. In two well designed trials in children aged 6-12 years with attention-deficit hyperactivity disorder (ADHD), the efficacy of lisdexamfetamine was superior to that of placebo in improving symptoms associated with ADHD. Adverse events with lisdexamfetamine were, in general, mild to moderate in severity and consistent with those commonly reported with amphetamine.

Fentanyl buccal tablet: in breakthrough pain in opioid-tolerant patients with cancer.

The fentanyl buccal tablet (FBT) is a new formulation of fentanyl that uses an effervescent drug delivery system to enhance penetration across the buccal mucosa for the treatment of breakthrough pain in opioid-tolerant patients with cancer. Fentanyl is rapidly absorbed from FBT across the buccal mucosa and into the bloodstream. Fentanyl is more rapidly absorbed and bioavailability is higher from FBT than from the oral transmucosal fentanyl citrate formulation. In a well designed phase III trial in opioid-tolerant patients with cancer, a single dose of FBT 100-800 microg provided clinically significant improvements in pain intensity from 15 to 60 minutes after the dose. Single FBT doses of 100-800 microg were generally well tolerated; the majority of adverse events were mild to moderate in nature and typical of those associated with opioids.

Telavancin.

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.

Spotlight on teriparatide in osteoporosis.

Recombinant teriparatide (Forteo; Forsteo) is an anabolic (bone-forming) agent. Studies have shown that subcutaneous teriparatide 20 microg/day is effective in women with postmenopausal osteoporosis, men with idiopathic or hypogonadal osteoporosis, and patients with glucocorticoid-induced osteoporosis. Teriparatide improves bone mineral density (BMD) and alters the levels of bone formation and resorption markers; histomorphometric studies have shown teriparatide-induced effects on bone structure, strength, and quality. Subcutaneous teriparatide 20 microg/day administered over a treatment period of 11-21 months was effective in reducing the risk of fractures and improving BMD in men with idiopathic or hypogonadal osteoporosis, women with postmenopausal osteoporosis, and patients with glucocorticoid-induced osteoporosis. Furthermore, the beneficial effects of teriparatide on vertebral fracture prevention and BMD appear to persist following treatment cessation. Teriparatide is generally well tolerated and treatment compliance rates are favorable. However, current limitations on the length of treatment and the high acquisition cost mean that teriparatide is best reserved for the treatment of patients with osteoporosis at high risk of fracture, or for patients with osteoporosis who have unsatisfactory responses to or intolerance of other osteoporosis therapies.

Spotlight on fondaparinux sodium in acute coronary syndromes.

Fondaparinux sodium (Arixtra) is a synthetic, sulfated pentasaccharide, selective factor Xa inhibitor that is indicated in Europe for preventing thrombus formation in patients with acute coronary syndromes (ACS; the focus of this review), including those with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina. The large (n = 20,078), well designed OASIS-5 trial showed that subcutaneous fondaparinux 2.5 mg/day for < or =8 days was noninferior to subcutaneous enoxaparin 1 mg/kg twice daily (once daily in those with renal dysfunction) in reducing death or ischemic events at 9 days and the efficacy was maintained for up to 6 months (study end) in patients with unstable angina or NSTEMI. During this time, major bleeding occurred in fewer fondaparinux than enoxaparin recipients, resulting in a benefit : risk balance favoring fondaparinux. The incidence of death or reinfarction at 30 days was significantly lower in recipients of subcutaneous fondaparinux 2.5 mg/day than in those who received usual care (including unfractionated heparin treatment as indicated) in patients with STEMI in the large (n > 12,000) OASIS-6 trial. There were no differences in the incidence of major bleeding between these groups, resulting in a benefit : risk balance favoring fondaparinux. The specificity and selectivity of fondaparinux, combined with its long half-life and 100% bioavailability, allows once-daily anticoagulation without the need for monitoring activated clotting time. Subcutaneous fondaparinux was noninferior to enoxaparin treatment in patients with unstable angina or NSTEMI, and was more effective than usual care in those with STEMI. Fondaparinux has a favorable tolerability profile, particularly with regard to the risk of major bleeding, and limited data suggest that it is more cost effective than enoxaparin in the short term. Thus, overall, clinical evidence suggests that fondaparinux has a valuable place in the treatment of patients with ACS.