Crofelemer: A Review of Its Use in the Management of Non-Infectious Diarrhoea in Adult Patients With HIV/AIDS on Antiretroviral Therapy.

Crofelemer: A Review of its Use in the Management of Non-Infectious Diarrhoea in Adult Patients with HIV/AIDS on Antiretroviral Therapy.

Drugs. 2013 Jun 27;
Frampton JE

Crofelemer (Fulyzaq™) is a botanical drug substance (oligomeric proanthocyanidin) extracted from the stem bark latex of the Croton lechleri tree. Crofelemer undergoes minimal systemic absorption following oral administration; it acts locally within the gastrointestinal (GI) tract by inhibiting the two principal chloride ion channels in the luminal membrane of enterocytes. Crofelemer is the first (and so far only) agent to be approved by the US FDA specifically for the symptomatic relief of non-infectious (i.e. secretory) diarrhoea in adult patients with HIV/AIDS on antiretroviral therapy (ART). This approval was based on findings from the ADVENT study, a large (n = 376 randomized patients), multicentre, phase III trial in which the recommended dosage of oral crofelemer (125 mg twice daily) significantly reduced secretory diarrhoea in HIV-positive individuals on ART compared with placebo, as assessed over a 4-week period. Crofelemer was generally well tolerated in ADVENT (which included a 5-month placebo-free extension phase) and a 48-week, open-label, phase III safety study; infections and GI disorders were the most frequently reported treatment-emergent adverse events (TEAEs) in patients receiving the drug. Of note, the overall incidence of TEAEs was similar in the crofelemer and placebo groups during the 4-week placebo-controlled phase of ADVENT. Treatment with crofelemer had no appreciable effect on immune parameters, such as HIV viral load and CD4+ cell counts. HubMed – drug


Pulmonary Embolism, Myocardial Infarction, and Ischemic Stroke in Lung Cancer Patients: Results from a Longitudinal Study.

Lung. 2013 Jun 27;
van Herk-Sukel MP, Shantakumar S, Penning-van Beest FJ, Kamphuisen PW, Majoor CJ, Overbeek LI, Herings RM

In this cohort study, the rates of pulmonary embolism (PE), myocardial infarction (MI), and ischemic stroke (IS) before and after lung cancer (LC) diagnosis were compared to cancer-free controls.Patients with LC during 2000-2007 were selected from PALGA, the Dutch Pathology Registry, and linked to the PHARMO medical record linkage system, including drug use and hospitalizations of 3 million inhabitants in the Netherlands. Included LC patients were matched 1:10 by age and gender to cancer-free controls. Hospitalizations for PE, MI, and IS were assessed in the 12 months before and after LC diagnosis.LC patients (N = 3,717) were six times more likely than cancer-free controls to have had a PE in the 12 months before diagnosis. After LC diagnosis, patients experienced an extremely increased risk of PE in the first 6 months (hazard ratio [HR] 16.8; 95 % confidence interval [CI] 7.6-36.8) compared with controls), which decreased to a five times increased risk (HR 5.1; 95 % CI 2.7-9.4) thereafter. However, there were less than two events per 100 person years during both time periods. LC patients receiving chemotherapy were eight times more likely to develop PE, whereas surgery increased the risk on PE three times. For MI and IS, no significant difference was observed compared with cancer-free controls before or after LC diagnosis.LC patients have a higher risk of developing PE compared with cancer-free controls, although the frequency of PE hospitalizations was low. Surgery and chemotherapy were associated with an increased risk of PE. HubMed – drug