Pharmacy & Therapeutics - April 2008 - (Page 241) CONTINUING EDUCATION CREDIT ethyl succinate (e.g., EryPed, Abbott) 20 mg/kg, divided into two daily doses, can provide adequate prophylaxis.24 Problems with penicillin prophylaxis include compliance, drug cost, patient tolerance, and resistant strains of micro organisms.25 Immunizations in children with SCD should include all regular vaccines, with the addition of the flu vaccine yearly after six months of age; pneumococcal vaccine at two and five years of age; and, possibly, meningococcal vaccine.26 it is proposed that folate in anemia raises hemoglobin levels and helps provide a healthy reticulocyte response,32 the use of folic acid in patients with SCD is not well supported by the primary literature. One prospective, randomized study, published in 1983, found no “striking effects” of folic acid supplementation in sickle cell anemia on the hematological profile or on growth in children with SCD who received this nutrient.33 In another study that measured folate stores in children with SCD who were not receiving folic acid, folate levels were found to be adequate.34 The National Heart, Lung, and Blood Institute guideline for SCD does recommend folic acid supplementation for patients with sickle cell anemia at the dose of 1 mg/day.21 Stroke Prevention The prevalence of stroke in patients with SCD was reported to be 11% before routine screening with transcranial Doppler ultrasonography (TCD) and monthly transfusions for primary stroke prevention in children at risk. Not all children with SCD are at equal risk for stroke; Doppler ultrasound should be performed to assess the patient’s blood flow velocity, because high blood flow velocity has been correlated with a subsequent stroke in children with SCD.27 In a randomized study of children with SCD, patients who had abnormal results (time-averaged mean blood flow exceeding 200 cm/second) received standard-of-care or transfusions with a target hemoglobin S concentration of less than 30%. The study was terminated early, because there was a 92% difference in cerebrovascular accidents (CVAs) between the standard-ofcare group and the transfusion group.27 It is still not known when, if ever, it is optimal to discontinue prophylactic transfusions in patients with abnormal TCD results. The Optimal Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) Trial Investigators randomly assigned children who were receiving prophylactic transfusions to either stop receiving them after 30 months or to continue with them. The endpoints evaluated were abnormal TCD findings or stroke; neither event occurred in the arm that continued transfusion therapy. The arm that discontinued therapy had 14 abnormal TCD results and two strokes within 4.5 ± 2.6 months of stopping transfusions.28 Children with abnormal TCD outcomes had a hydroxyurea-related decrease in TCD flow velocity from 216 ± 14 to 173 ± 31 cm/second, suggesting the possible benefit of switching to hydroxyurea for stroke prevention.29 With regular transfusions comes the burden of iron overload; until recently in the U.S., this condition was treated only with deferoxamine (Desferal, Novartis), which was administered by subcutaneous or IV infusion. A new once-daily oral chelator, deferasirox (Exjade, Novartis), when compared with deferoxamine in patients with SCD and iron overload, was found to be safe and effective in these patients.30 At the time of this writing, a study evaluating the role of aspirin in the stroke prophylaxis in children was recruiting participants.31 Pulmonary Hypertension Some studies have suggested that pulmonary hypertension (PHTN) is common in patients with sickle cell anemia. A prospective study of sickle cell anemia reported a 31% prevalence of PHTN in children 10 years of age and older.35 There is emerging evidence on the treatment of traditional PHTN with prostanoids such as epoprostenol (Flolan, GlaxoSmithKline) and phosphodiesterase-5 inhibitors such as sildenafil citrate (Revatio, Pfizer). The FDA approved sildenafil for the treatment of PHTN in 2005. A study conducted at the Howard University Center for Sickle Cell Disease tested PHTN reversibility by giving prostacyclin infusions to eight patients with PHTN during cardiac catheterization.36 Pulmonar y pressures were significantly reduced in six of the eight patients who received the infusions. An open-label, uncontrolled pilot trial of 12 patients with SCD and PHTN found that sildenafil improved exercise capacity and PHTN.37 Priapism Priapism, possibly resulting from decreased blood flow to the corpus cavernosum, is a known problem in men with SCD.38 Usually precipitated by sexual activity, priapism has a prevalence of between 6% and 38% in SCD patients.39 There are two kinds of priapism: (1) “stuttering,” defined as repeated short episodes, with each episode lasting for between 30 minutes and three hours, and (2) “prolonged,” defined as episodes lasting for more than three hours. Acute episodes of priapism lasting for more than two hours should be treated in the emergency department. Penile aspiration, followed by irrigation of the corpus cavernosum with a sympathomimetic agent, should be initiated if detumescence does not occur an hour after the patient’s arrival. Oral terbutaline (Brethine, aaiPharma) and pseudoephedrine (e.g., Sudafed, Pfizer) have demonstrated efficacy in the treatment of priapism.40 Folic Acid and Anemia In patients with SCD, the RBC count is lower than normal because sickled cells usually die after 10 to 20 days, in contrast to 120 days for normal RBCs. Because of high cell turnover, folate stores are often depleted. Folic acid replenishes the depleted folate stores necessary for erythropoiesis. Folic acid supplementation is well established in the treatment of chronic hemolytic anemia. Although Investigational Treatment Options Niprisan As a phytopharmaceutical derived from a plant in its original state, Niprisan was developed by the Nigerian National Institute for Pharmaceutical Research and Development. This anti-sickling agent was granted orphan drug status by the FDA in 2003 under the name Hemoxin, made by Xechem International. Its anti-sickling properties are attributed to its Vol. 33 No. 4 • April 2008 • P&T® 241
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