ObjectiveTo explore the evidence available of poor-quality (counterfeit and substandard) medicines in the literature.DesignSystematic review.Data sourcesDatabases used were EMBASE, MEDLINE, PubMed and the International Pharmaceutical Abstracts, including articles published till January 2013.Eligibility criteriaPrevalence studies containing original data. WHO definitions (1992) used for counterfeit and substandard medicines.Study appraisal and synthesisTwo reviewers independently scored study methodology against recommendations from the MEDQUARG Checklist. Studies were classified according to the World Bank classification of countries by income.Data extractionData extracted: place of study; type of drugs sampled; sample size; percentage of substandard/counterfeit medicines; formulations included; origin of the drugs; chemical analysis and stated issues of counterfeit/substandard medicines.Results44 prevalence studies were identified, 15 had good methodological quality. They were conducted in 25 different countries; the majority were in low-income countries (11) and/or lower middle-income countries (10). The median prevalence of substandard/counterfeit medicines was 28.5% (range 11–48%). Only two studies differentiated between substandard and counterfeit medicines. Prevalence data were limited to antimicrobial drugs (all 15 studies). 13 studies involved antimalarials, 6 antibiotics and 2 other medications. The majority of studies (93%) contained samples with inadequate amounts of active ingredients. The prevalence of substandard/counterfeit antimicrobials was significantly higher when purchased from unlicensed outlets (p<0.000; 95% CI 0.21 to 0.32). No individual data about the prevalence in upper middle-income countries and high-income countries were available.LimitationsStudies with strong methodology were few. The majority did not differentiate between substandard and counterfeit medicines. Most studies assessed only a single therapeutic class of antimicrobials.ConclusionsThe prevalence of poor-quality antimicrobial medicines is widespread throughout Africa and Asia in lower income countries and lower middle-income countries . The main problem identified was inadequate amounts of the active ingredients.

ObjectiveTo determine the safety of ciprofloxacin in paediatric patients in relation to arthropathy, any other adverse events (AEs) and drug interactions.MethodsA systematic search of MEDLINE, EMBASE, CINAHL, CENTRAL and bibliographies of relevant articles was carried out for all published articles, regardless of design, that involved the use of ciprofloxacin in any paediatric age group ≤17 years. Only articles that reported on safety were included.Results105 articles met the inclusion criteria and involved 16 184 paediatric patients. There were 1065 reported AEs (risk 7%, 95% CI 3.2% to 14.0%). The most frequent AEs were musculoskeletal AEs, abnormal liver function tests, nausea, changes in white blood cell counts and vomiting. There were six drug interactions (with aminophylline (4) and methotrexate (2)). The only drug related death occurred in a neonate who had an anaphylactic reaction. 258 musculoskeletal events occurred in 232 paediatric patients (risk 1.6%, 95% CI 0.9% to 2.6%). Arthralgia accounted for 50% of these. The age of occurrence of arthropathy ranged from 7 months to 17 years (median 10 years). All cases of arthropathy resolved or improved with management. One prospective controlled study estimated the risk of arthropathy as 9.3 (OR 95% CI 1.2 to 195). Pooled safety data of controlled trials in this review estimated the risk of arthropathy as 1.57 (OR 95% CI 1.26 to 1.97).ConclusionMusculoskeletal AEs occur due to ciprofloxacin use. However, these musculoskeletal events are reversible with management. It is recommended that further prospective controlled studies should be carried out to evaluate the safety of ciprofloxacin, with particular focus on the risk of arthropathy.

Objective: To ascertain whether therapeutic equivalence exists for the treatment of paediatric community acquired pneumonia by the oral and intravenous (IV) routes. Methods: A multicentre pragmatic randomised controlled non-blinded equivalence trial was undertaken in eight paediatric centres in England (district general and tertiary hospitals). Equivalence was defined as no more than a 20% difference between treatments of the proportion meeting the primary outcome measure at any time. 246 children who required admission to hospital and had fever, respiratory symptoms or signs and radiologically confirmed pneumonia were included in the study. Exclusion criteria were wheeze, oxygen saturations ,85% in air, shock requiring .20 ml/kg fluid resuscitation, immunodeficiency, pleural effusion at presentation requiring drainage, chronic lung condition (excluding asthma), penicillin allergy and age ,6 months. The patients were randomised to receive oral amoxicillin for 7 days (n = 126) or IV benzyl penicillin (n = 120). Children in the IV group were changed to oral amoxicillin after a median of six IV doses and received 7 days of antibiotics in total. The predefined primary outcome measure was time for the temperature to be ,38˚C for 24 continuous hours and oxygen requirement to cease. Secondary outcomes were time in hospital, complications, duration of oxygen requirement and time to resolution of illness.