Post-Marketing Surveillance of a generic Oxaliplatin (AlvoxalⓇ) in Iranian Patients with Cancer.

BACKGROUND: CRC is the second and third most common cancer in women and men, respectively. The national comprehensive cancer network guidelines recommend oxaliplatin-based chemotherapy as a preferred regimen for patients with advanced or metastatic colon cancer. Oxaliplatin is also used in the off-label treatment of gastric cancer. FDA uses post-marketing study commitments to gather additional information about a product's safety, efficacy, or optimal use. It is necessary to perform safety monitoring after marketing authorization is received; such monitoring can be done by means of characterizing the safety of drugs in patients being treated in real-world clinical practice settings. OBJECTIVES: This Phase IV study aimed to evaluate the safety profile of a brand-name formulation of the generic drug oxaliplatin (AlvoxalⓇ, NanoAlvand, Tehran, Iran) in Iranian patients diagnosed with either colorectal or other, different types of cancer. METHODS: Patients with colorectal cancer, gastric cancer, or other malignancies receiving oxaliplatin as a part of their treatment were included in this open-label, multicenter, observational Phase IV study. This study aimed to assess the safety profile of oxaliplatin in patients diagnosed with different cancers. FINDINGS: A total of 483 patients from 16 cities in Iran were enrolled. The most common malignancy was colorectal cancer (55.49%), followed by gastric cancer (28.16%). Based on the results, 405 patients experienced at least 1 adverse event. Most of these adverse events were grade 1 or 2, and the most commonly reported adverse event was anemia (60.66%). During the study, 26 serious adverse events occurred in 15 (3.11%) patients, which were perhaps related to oxaliplatin. There were no remarkable differences in the incidences of adverse events in the system organ classes of blood and lymphatic system disorders, gastrointestinal disorders, or nervous system disorders among patients with different malignancies (ie, colorectal cancer, gastric cancer, and other malignancies) or between genders. The results of this open-label, multicenter, observational, postmarketing surveillance study demonstrated no unexpected safety findings from the use of this oxaliplatin product (AlvoxalⓇ) in Iranian patients diagnosed with different types of cancer. CONCLUSIONS: This Phase IV study provides data on the safety profile of a number of chemotherapy regimens containing an oxaliplatin product given to Iranian patients diagnosed with different types of cancer.

Evaluation of fluticasone propionate/salmeterol for the treatment of COPD: a systematic review.

Introduction: Recently, the generic formulation of FP/SAL FDC has been approved in COPD. Although FP/SAL FDC has been the first long-acting FDC approved in COPD, no systematic review assessed the effect of this combination for the treatment of COPD by considering specifically Phase IV studies. The aim of this review was to systematically assess the effect of FP/SAL FDC in COPD patients enrolled in Phase IV studies.Areas covered: The question of this systematic review was to examine the evidence regarding the impact of FP/SAL FDC for the treatment of COPD by searching for Phase IV studies in the ClinicalTrials.gov database.Expert opinion: Generic drugs represent an effective cost-saving step for health-care budgets in the treatment of COPD and should be used in agreement with current recommendations and prescription accuracy. FP/SAL FDC is recommended for the initiation therapy just in a small percentage of symptomatic patients that are at high risk of exacerbation with blood eosinophil counts ≥300 cells per µl. At follow-up, FP/SAL FDC can be escalated to triple ICS/LABA/LAMA combination or switched to LABA/LAMA combination by considering symptoms, exacerbations, lack of response to ICS, inappropriate original indication, and ICS-related adverse events such as pneumonia.

A 4-year non-randomized comparative phase-IV study of early rheumatoid arthritis: integrative anthroposophic medicine for patients with preference against DMARDs versus conventional therapy including DMARDs for patients without preference.

BACKGROUND: While disease-modifying antirheumatic drugs (DMARDs) are a mainstay of therapy for rheumatoid arthritis (RA), some patients with early RA refuse DMARDs. In anthroposophic medicine (AM), a treatment strategy for early RA without DMARDs has been developed. Preliminary data suggest that RA symptoms and inflammatory markers can be reduced under AM, without DMARDs. PATIENTS AND METHODS: Two hundred and fifty-one self-selected patients aged 16-70 years, starting treatment for RA of <3 years duration, without prior DMARD therapy, participated in a prospective, non-randomized, comparative Phase IV study. C-patients were treated in clinics offering conventional therapy including DMARDs, while A-patients had chosen treatment in anthroposophic clinics, without DMARDs. Both groups received corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). Primary outcomes were intensity of RA symptoms measured by self-rating on visual analog scales, C-reactive protein, radiological progression, study withdrawals, serious adverse events (SAE), and adverse drug reactions in months 0-48. RESULTS: The groups were similar in most baseline characteristics, while A-patients had longer disease duration (mean 15.1 vs 10.8 months, p<0.0001), slightly more bone destruction, and a much higher proportion of women (94.6% vs 69.7%, p<0.0001). In months 0-12, corticosteroids were used by 45.7% and 81.6% (p<0.0001) and NSAIDs by 52.8% and 68.5% (p=0.0191) of A- and C-patients, respectively. During follow-up, both groups not only had marked reduction of RA symptoms and C-reactive protein, but also some radiological disease progression. Also, 6.2% of A-patients needed DMARDs. Apart from adverse drug reactions (50.4% and 69.7% of A- and C-patients, respectively, p=0.0020), none of the primary outcomes showed any significant between-group difference. CONCLUSION: Study results suggest that for most patients preferring anthroposophic treatment, satisfactory results can be achieved without use of DMARDs and with less use of corticosteroids and NSAIDs than in conventional care. LIMITATION: Because of the non-randomized study design, with A-patients choosing anthroposophic treatment, one cannot infer how this treatment would have worked for C-patients.

XANTUS: rationale and design of a noninterventional study of rivaroxaban for the prevention of stroke in patients with atrial fibrillation.

Atrial fibrillation (AF) is associated with a fivefold increase in the risk of stroke. The Phase III ROCKET AF (Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial showed that rivaroxaban, an oral, direct Factor Xa inhibitor, was noninferior to warfarin for the reduction of stroke or systemic embolism in patients with AF. Compared with warfarin, rivaroxaban significantly reduced rates of intracranial and fatal hemorrhages, although not rates of bleeding overall. XANTUS (Xarelto(®) for Prevention of Stroke in Patients with Atrial Fibrillation) is a prospective, international, observational, postauthorization, noninterventional study designed to collect safety and efficacy data on the use of rivaroxaban for stroke prevention in AF in routine clinical practice. The key goal is to determine whether the safety profile of rivaroxaban established in ROCKET AF is also observed in routine clinical practice. XANTUS is designed as a single-arm cohort study to minimize selection bias, and will enroll approximately 6,000 patients (mostly from Europe) with nonvalvular AF prescribed rivaroxaban, irrespective of their level of stroke risk. Overall duration of follow-up will be 1 year; the first patient was enrolled in June 2012. Similar studies (XANTUS-EL [Xarelto(®) for Prevention of Stroke in Patients with Nonvalvular Atrial Fibrillation, Eastern Europe, Middle East, Africa and Latin America] and XANAP [Xarelto(®) for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific]) are ongoing in Latin America and Asia-Pacific. Data from these studies will supplement those from ROCKET AF and provide practical information concerning the use of rivaroxaban for stroke prevention in AF.

Uso de ceftriaxona en monodosis para el tratamiento de la otitis media aguda supurada en pacientes de edad pediátrica / Ceftriaxone´s use in monodoses for the treatment of otitis media acute suppurativa in pediatric age patients

La otitis media aguda supurada es muy frecuente en pediatría. El 80 por ciento de los niños en edad preescolar y el 50 por ciento de los lactantes hacen un cuadro de supuración de oídos dos veces al año. Objetivo: evaluar la efectividad de la ceftriaxona en dosis única en pacientes pediátricos con otitis media aguda supurada. Método: se realizó un ensayo clínico, fase IV, durante el segundo semestre del año 2008, a 51 niños ingresados con el diagnóstico de Otitis Media Aguda Supurada, en el Hospital Pediátrico Provincial de Camagüey Eduardo Agramante Piña. Resultados: se encontró un ligero aumento del sexo masculino; con predominio significativo de la raza blanca. Existió una alta incidencia en los pacientes menores de un año. El 58,8 por ciento de los pacientes recibieron tratamiento previamente con antimicrobianos. El tratamiento antimicrobiano utilizado con mayor frecuencia fue la amoxicillina, la penicilina y el Claforan. Más del 66 por ciento presentó una evolución favorable dentro de las 72h siguientes al tratamiento con la monodosis de ceftriaxona. En 48 de los pacientes estudiados se obtuvo una evolución otoscópica favorable, lo que correspondió a un 94,12 por ciento de los casos estudiados. Al estudiar el comportamiento de los pacientes según edad y otras enfermedades asociadas, se pudo observar que sólo dos pacientes no presentaron otras enfermedades asociadas. Conclusiones: se logró una evolución favorable dentro de las 72h siguientes al tratamiento con la monodosis de ceftriaxona en casi la totalidad de los casos.

Otitis media acute suppurativa is very frequent disease in pediatrics. The 80 percent of children in preschool age and 50 percent of infants make ear suppuration twice a year. Objective: to evaluate the efficacy of an only dose of ceftriaxone in pediatric patients with otitis media acute suppurativa. Method: a phase IV clinical trial was performed, during the second semester of 2008 to 51 children admitted with otitis media acute suppurativa as diagnosis, at the provincial pediatric hospital of Camagüey Eduardo Agramonte Piña. Results: a slight increase of the masculine sex was found; with significant prevalence of the white race (44,86 percent). There was a high incidence in patients under one year (29) for 56,9 percent. The 58,8 percent (30) of patients previously received antimicrobial treatment. The most frequent antimicrobial treatment used was amoxicillin (44,1 percent), penicillin (20,5 percent) and claforan (11,7 percent). More than the 66 percent presented a favorable evolution within 72 hours next to the treatment with ceftriaxone monodoses. In 48 of studied patients a favorable otoscopic evolution was obtained, what corresponded to 94,12 percent of studied cases. Conclusions: a favorable evolution was achieved within 72 hours following to the treatment with ceftriaxone monodoses in more than the half of cases.