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A prospective randomized, double-blind, placebo-controlled study was conducted in 50 adults and 50 children from the Nile delta of Egypt, to evaluate the efficacy of nitazoxanide in treating diarrhea caused by Cryptosporidium parvum. Nitazoxanide was administered in 500-mg doses twice daily for 3 days in adults and adolescents, in 200-mg doses twice daily for 3 days in children aged 4-11 years, and in 100-mg doses twice daily for 3 days in children aged 1-3 years. At 7 days after initiation of therapy, diarrhea had resolved in 39 (80%) of the 49 patients in the nitazoxanide treatment group, compared with 20 (41%) of 49 in the placebo group (P<.0001). Diarrhea was resolved in most patients receiving nitazoxanide within 3 or 4 days of treatment initiation. Nitazoxanide treatment reduced the duration of both diarrhea (P<.0001) and oocyst shedding (P<.0001).

A prospective randomized, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of nitazoxanide in the treatment of diarrhea caused by Giardia intestinalis or Entamoeba histolytica and/or E. dispar in 89 adults and adolescents, 22 of whom were diagnosed with G. intestinalis, 53 with E. histolytica and/or E. dispar, and 14 with both G. intestinalis and E. histolytica and/or E. dispar. The study medication was administered as 1 nitazoxanide 500-mg tablet or a matching placebo twice daily for 3 days. Thirty-eight (81%) of 47 patients in the nitazoxanide treatment group resolved diarrhea within 7 days (median, 3 days) after initiation of treatment, versus 17 (40%) of 42 in the placebo group (P=.0002). With its efficacy in treating a broad spectrum of enteric protozoan pathogens, nitazoxanide could play an important role in the management of diarrhea caused by enteric protozoa, reducing morbidity and costs associated with these diarrheal illnesses.

BackgroundThe World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) in African regions with moderate to high malaria transmission. However, growing resistance to SP threatens the effectiveness of IPTp-SP, and alternative drugs are needed. This study tested the efficacy, tolerability, and safety of a fixed-dose combination azithromycin-chloroquine (AZCQ; 250 mg AZ/155 mg CQ base) for IPTp relative to IPTp-SP.Methods and FindingsA randomized, Phase 3, open-label, multi-center study was conducted in sub-Saharan Africa (Benin, Kenya, Malawi, Tanzania, and Uganda) between October 2010 and November 2013. Pregnant women received 3 IPTp courses with AZCQ (each course: 1,000/620 mg AZCQ QD for 3 days) or SP (each course 1,500/75 mg SP QD for 1 day) at 4- to 8-week intervals during the second and third trimester. Long-lasting insecticide-treated bednets were also provided at enrollment. Study participants were followed up until day 28 post delivery (time window: day 28–42). The primary endpoint was the proportion of participants with sub-optimal pregnancy outcomes (a composite endpoint comprising live-borne neonates with low birth weight [LBW, <2,500 g], premature birth [<37 weeks], still birth [>28 weeks], abortion [≤28 weeks], lost to follow-up prior to observation of pregnancy outcome, or missing birth weight). The study was terminated early after recruitment of 2,891 of the planned 5,044 participants, due to futility observed in a pre-specified 35% interim analysis. In the final intent-to-treat dataset, 378/1,445 (26.2%) participants in the AZCQ and 342/1,445 (23.7%) in the SP group had sub-optimal pregnancy outcomes, with an estimated risk ratio (RR) of 1.11 (95% CI: 0.97, 1.25; p = 0.12). There was no significant difference in the incidence of LBW between treatment groups (57/1138 [5.0%] in the AZCQ group, 68/1188 [5.7%] in the SP group, RR 0.87 [95% CI: 0.62, 1.23]; p = 0.44). IPTp-AZCQ was less well-tolerated in mothers than IPTp-SP. Occurrences of congenital anomalies, deaths, and serious adverse events were comparable in neonates for both groups. Limitations included the open-label design and early study termination.ConclusionsIPTp-AZCQ was not superior to IPTp-SP in this study and alternatives for IPTp-SP remain to be identified. The proportions of sub-optimal pregnancy outcomes and LBW were lower than expected, which may be linked to insecticide-treated bednet use throughout the study. Reduced incidences of symptomatic malaria infection and peripheral parasitemia in the AZCQ group relative to SP suggest that AZCQ warrants further investigation as an alternative treatment of uncomplicated malaria.Trial RegistrationClinicalTrials.gov (NCT01103063).

Summary Background : Human fascioliasis is a significant world‐wide health problem, and massive or repeated infections by Fasciola hepatica can lead to considerable morbidity. Aim : To evaluate the safety and efficacy of nitazoxanide, when compared with placebo, in the treatment of fascioliasis in adults and children from northern Peru. Methods : A double‐blind, placebo‐controlled study was carried out in 50 adults and 50 children infected with F. hepatica. The diagnosis of infection was based on the presence of F. hepatica eggs in one stool sample obtained before inclusion in the study. Patients were randomized to receive treatment with either a 7‐day course of nitazoxanide (100 mg b.d., age range 2–3 years; 200 mg b.d., age range 4–11 years; 500 mg b.d., age > 12 years) or matching placebo. Three post‐treatment stool examinations were carried out between 30 and 90 days after initiation of treatment. Results : The parasite was eliminated in 18 of 30 (60%) adults completing the study who received nitazoxanide vs. one of eight adults in the placebo group (P = 0.042), and similarly in 14 of 35 (40%) children completing the treatment vs. none of eight in the placebo group (P = 0.038). Only mild, transient adverse events were reported. Conclusions : A 7‐day course of nitazoxanide was effective in adults and children in the treatment of F. hepatica, when compared with placebo.

Background: Enteric infection by Giardia intestinalis is a common cause of diarrhoea world‐wide and a significant cause of morbidity in children. Aim: To compare the efficacy and safety of nitazoxanide and metronidazole in the treatment of diarrhoea caused by G. intestinalis in children. Methods: A total of 110 children presenting with diarrhoea caused by G. intestinalis were randomized to treatment with either a 3‐day course of nitazoxanide (100 mg b.d., age range 2–3 years; 200 mg b.d., age range 4–11 years) or a 5‐day course of metronidazole (125 mg b.d., age range 2–5 years; 250 mg b.d., age range 6–11 years). The patients were followed‐up for a determination of clinical response 7 days after the initiation of treatment, and two subsequent stool samples were collected for parasitological examination. Results: Diarrhoea had resolved in 47 children out of 55 (85%) in the nitazoxanide treatment group before the day 7 follow‐up visit, compared to 44 out of 55 (80%) for metronidazole. Diarrhoea resolved within 4 days in most cases. Only mild, transient adverse events were reported. Conclusions: A 3‐day course of nitazoxanide suspension is as efficacious as a standard 5‐day course of metronidazole suspension in treating giardiasis in children.

Introduction Evidence-based clinical data on coronavirus disease 2019 (COVID-19) pharmacotherapies are scarce . Objective This study documented and characterized COVID-19 cases reported in individuals receiving treatment with Pfizer pharmaceutical products and cases that reported use of Pfizer pharmaceutical products for COVID-19 treatment. Methods This retrospective observational review leveraged the Pfizer safety database containing adverse event data collected in association with use of Pfizer products between 1 October, 2019, and 25 June, 2020; the database includes worldwide adverse event data from various sources. Selected Medical Dictionary for Drug Regulatory Activities (MedDRA ® ) Preferred Terms and subsequent clinical review were used to characterize COVID-19 cases. Results Over 1500 relevant cases were identified over an 8-month period. In cases that reported COVID-19, immunosuppressant/immunomodulating agents, followed by anticoagulant/antithrombic agents and corticosteroids, were the most frequently reported agents. The frequent reporting of immunosuppressant/immunomodulating agents among cases of COVID-19 suggests increased vulnerability to infection among treated patients, either because of immunosuppressive effects of certain agents or the nature of the underlying treated condition. In cases involving off-label pharmacotherapy use for the treatment of COVID-19-related conditions, the most frequently reported therapeutic classes included antibiotics, antimalarial agents, antivirals/antiretroviral agents, immunosuppressant/immunomodulating agents, corticosteroids, anticoagulants, and immunoglobulin/interferons. The most frequently reported pharmacotherapeutic agents were azithromycin and chloroquine/hydroxychloroquine, followed by lopinavir-ritonavir, ceftriaxone, and tofacitinib. The most frequently reported clinical adverse events associated with azithromycin (as sole therapy or combined with chloroquine/hydroxychloroquine) include electrocardiogram QT prolonged, drug interaction, hepatitis, diarrhea, and hepatitis acute. Regarding cardiac-related events, 19% (120/645) of azithromycin cases reported events associated with QT prolongation/torsade de pointes (which included seven fatal cardiac events). The most frequently reported clinical adverse events associated with other commonly used agents are also presented. Conclusions This pharmacovigilance surveillance study provides a unique characterization of cases in which a broad range of pharmaceutical products was reported in relation to COVID-19.

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