Drugs

doi: 10.2165/11638210-000000000-00000pmid: N/A

Costa, Pierre; Potempa, Axel-Juerg

doi: 10.2165/11641380-000000000-00000pmid: 23170913

The global burden of erectile dysfunction (ED) is increasing. It is estimated that 8–19% of men in Europe have ED and that by 2025 the prevalence of ED worldwide will reach 322 million. The gold standard therapy for ED is an oral phosphodiesterase type 5 (PDE5) inhibitor, but they are not suitable for everyone; approximately 25% of patients do not respond to this therapy and it is contraindicated in others, e.g. those with vascular disease. When PDE5 inhibitors are not suitable, available options include intraurethral and intracavernosal alprostadil — a synthetic vasodilator chemically identical to the naturally occurring prostaglandin E1 indicated for the treatment of ED. Intraurethral alprostadil is delivered by the Medicated System for Erection (MUSE) — a single-use pellet containing alprostadil suspended in polyethylene glycol administered using an applicator. It is recommended that intraurethral alprostadil be initiated at a dose of 500 μg, as it has a higher efficacy than the 250 μg dose, with minimal differences with regard to adverse events. Data from key clinical studies of intraurethral alprostadil show that it has a fast onset of effect and a good safety profile, with no occurrences of priapism, fibrosis (as seen with intracavernosal injection) or the typical systemic effects observed with oral ED pharmacological treatments. Intraurethral alprostadil has been associated with high patient preference, acceptance rates and quality of life versus intracavernosal injection due to its ease of administration. Evidence has shown that combination treatment with sildenafil may be a possible efficient alternative when single oral or local treatment has failed. Intraurethral alprostadil can be administered in all patients irrespective of ED origin and should be the first option in patients with ED for whom therapy with PDE5 inhibitors has failed or is contraindicated.

Plosker, Greg

doi: 10.2165/11209910-000000000-00000pmid: 23170914

Dapagliflozin (Forxiga®) is the first in a novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors and is used in the treatment of patients with type 2 diabetes. By inhibiting the transporter protein SGLT2 in the kidneys, dapagliflozin reduces renal glucose reabsorption, leading to urinary glucose excretion and a reduction in blood glucose levels. Unlike oral antidiabetic drugs from several other classes, the efficacy of dapagliflozin is independent of insulin secretion and action. Therefore, when used in combination with other antidiabetic drugs, dapagliflozin provides complementary therapy via its unique mechanism of action.

Cady, Ryan; Shade, Candace; Cady, Roger

doi: 10.2165/11641120-000000000-00000pmid: 23116251

Triptans revolutionized medical recognition and the acute treatment of migraine. Yet, throughout a lifetime, millions of patients who live with migraine endure hundreds of days of disability due to their disease. Most migraine attacks respond to migraine-specific interventions, but attack response does not predict patient response. Generally, migraine patients respond to acute treatment for some, but not necessarily all, attacks of migraine. Consequently, there remains a substantial unmet clinical need for better acute treatment of migraine.

Keating, Gillian

doi: 10.2165/11470200-000000000-00000pmid: 23110609

Insulin detemir (Levemir®) is a long-acting insulin analogue indicated for use as basal insulin therapy in patients with type 1 or 2 diabetes mellitus.

Sharma, Anant; Shah, Sachin; Illum, Henrik; Dowell, Jonathan

doi: 10.2165/11640870-000000000-00000pmid: 23116250

Vemurafenib is the first molecularly targeted therapy to be licensed in the US and Europe for treatment of advanced melanoma. Its mechanism of action involves selective inhibition of the mutated BRAF V600E kinase that leads to reduced signalling through the aberrant mitogen-activated protein kinase (MAPK) pathway. Its efficacy is restricted to melanomas carrying the BRAF V600E mutation, which is seen in approximately 50% of all melanomas. In a randomized phase III trial, it was superior to dacarbazine in first-line treatment of advanced melanoma, with an overall response rate (ORR) of 48% (95% CI 42, 45), an estimated 6-month progression-free survival (PFS) of 5.3 versus 1.6 months (hazard ratio [HR] 0.26; 95% CI 0.20, 0.33; p < 0.001) and a statistically superior 12-month overall survival (OS) rate of 55% versus 43% (HR 0.62 [95% CI 0.49, 0.77]). Vemurafenib is generally well tolerated, but its use can be associated with development of cutaneous neoplasms such as squamous cell carcinoma (SCC) and keratoacanthoma (KA). These lesions can be excised safely without the need for withholding the drug or reducing its dose. Mechanisms of resistance to vemurafenib do not involve development of secondary mutations in the BRAF kinase domain, but may be related to BRAF V600E over-amplification, bypassing mechanisms via upregulation and overexpression of other components in the MAPK signalling cascade or activation of alternative pathways with potential to enhance cell growth, proliferation and survival. Clinical trials to test the efficacy of vemurafenib in combination with immunomodulatory agents, such as ipilimumab, and MAPK kinase (MEK) inhibitors, such as GDC-0973, in the treatment of advanced melanoma are currently underway. Also under investigation is the use of vemurafenib in other solid tumours with BRAF mutations, such as papillary thyroid cancer.

Dalvi, Sam; Yildirim, Resit; Yazici, Yusuf

doi: 10.2165/11641370-000000000-00000pmid: 23153327

Behcet’s syndrome (BS) is a vasculitis, seen more commonly around the Mediterranean and the Far East, and manifests with oral and genital ulcerations, skin lesions, uveitis, and vascular, central nervous system and gastrointestinal involvement. Its natural history of getting less severe over time, more severe disease in males and lack of specific diagnostic testing separates it from other commonly seen conditions in rheumatology. Most of the serious manifestations respond well to immunosuppression, and these are the mainstays of treatment for BS.