Paracetamol overdose in the newborn and infant: a life-threatening event.

PURPOSE: Paracetamol is the only drug recommended to treat fever in neonates. At recommended doses, paracetamol has not been associated with liver injury in neonates, while hepatotoxicity may occur after intake of a single high dose or multiple excessive doses. The aim of this narrative review is to critically analyze and summarize the available literature on newborns and infants exposed to supratherapeutic doses of paracetamol, with special focus on their clinical features, outcome, and management. METHODS: The PubMed, SCOPUS, and Google Scholar search engines were used to collect data, without time limitation. The following keywords were used: paracetamol/acetaminophen, overdose, hepatotoxicity, N-acetylcysteine, newborn, infant. RESULTS: The literature search identified a total of 27 case reports, a number of review articles, and few other relevant publications. Neonatal poisoning from paracetamol resulted from transplacental drug transfer after maternal overdose in some published cases, while it was the consequence of medication errors in other cases. Newborns and infants who have received a single overdose and have paracetamol concentrations below the Rumack-Matthew nomogram limits are at low risk of serious hepatic damage, while those who have recently ingested more than one supratherapeutic dose of paracetamol should be managed with caution. The treatment of choice for paracetamol poisoning is N-acetylcysteine, a specific antidote which reduces paracetamol hepatotoxic effects. N-Acetylcysteine should be given according to specific regimens through weight-based dosing tables. CONCLUSIONS: Caution should be used when paracetamol is administered to the newborn. In the event of an overdose, careful patient monitoring and personalization of post-overdose procedures are recommended.

Off-label and unlicensed drug treatments in Neonatal Intensive Care Units: an Italian multicentre study.

PURPOSE: The use of medicines among newborns admitted to intensive care units is characterized by a high prevalence of off-label/unlicensed use and a wide variability in the absence of international guidelines. A prospective cross-sectional study was organized with the aim to analyse drug prescriptions among all 107 Italian level III neonatal intensive care units. METHODS: An online questionnaire was used to collect detailed information for each newborn, and a classification was made about the license status of all prescriptions. In addition, prescriptions were analysed taking into account a practical guide prepared by the Italian Society of Neonatology (ISN). RESULTS: The 1-day survey (May­July 2014) regarded 220 newborn infants admitted to 36/107 Italian neonatal intensive care units: 191 prematures and 29 born at term. In total, 720 prescriptions (corresponding to 79 different drugs) were analysed: 191 (26.5 %) followed the terms of the product license, 529 (73.5 %) were off-label or unlicensed: 193/220 newborns (87.7 %) received at least one off-label/unlicensed prescription. Antiinfectives were the most common medicine used, followed by respiratory drugs and antianaemics; in an off-label manner, the most common was cardiovascular and central nervous system (CNS) drugs, gastrointestinals and antiinfectives. The most common categories of off-label use were age (34.4 %) and dosing frequency (20.6 %). Compared to ISN practical guide, prescriptions adhered more frequently to indications (100 % for ampicillin/sulbactam, >80 % for ampicillin, fluconazole, fentanyl, ranitidine and vancomicin). CONCLUSIONS: Our results confirm the high prevalence of off-label/unlicensed drug use in the neonatal population and underline a better adherence to indications based on clinical practice, suggesting the need to update information contained in the data sheets of medicines.

Clinical use of gastric antisecretory drugs in pediatric patients with gastroesophageal reflux disease: a narrative review.

Background and Objective: Gastroesophageal reflux (GER) is a common condition in infants. Usually, it resolves spontaneously in 95% of cases within 12-14 months of age, but gastroesophageal reflux disease (GERD) may develop in some children. Most authors do not recommend pharmacological treatment of GER, while the management of GERD is debated. The aim of this narrative review is to analyze and summarize the available literature on the clinical use of gastric antisecretory drugs in pediatric patients with GERD. Methods: References were identified through MEDLINE, PubMed, and EMBASE search engines. Only articles in English were considered. The following keywords were used: "gastric antisecretory drugs", "H2RA", "PPI", "ranitidine", "GERD", "infant", "child". Key Content and Findings: Increasing evidence of poor efficacy and potential risks of proton pump inhibitors (PPIs) is emerging in neonates and infants. Histamine-2 receptor antagonists (H2RAs), including ranitidine, have been used successfully in older children, although less effective than PPIs at relieving symptoms and healing GERD. However, in April 2020, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) requested manufacturers of ranitidine to remove all ranitidine products from the market due to the risk of carcinogenicity. Pediatric studies comparing effectiveness and safety of different acid-suppressing treatments for GERD are generally inconclusive. Conclusions: A proper differential diagnosis between GER and GERD is crucial to avoid the overuse of acid-suppressing medications in children. Further research should be directed towards the development of novel antisecretory drugs, with proven efficacy and good safety profile, for treating pediatric GERD, particularly in newborns and infants.

Clinical Use of Gastric Antisecretory Drugs in Hospitalized Pediatric Patients.

Antisecretory drugs are frequently used in the treatment of pediatric gastrointestinal disorders. This study was aimed to assess the prescribing patterns and the safety of ranitidine and proton pump inhibitors (PPIs) in a cohort of Italian pediatric patients. Children aged >1 month to <16 years that were admitted to our Pediatric Clinic between 2016 and 2018 were enrolled in this retrospective observational study. All data were obtained from medical records and a parent telephone questionnaire. The exclusion criteria included the use of antisecretory therapy at hospital admission, failure to collect the relevant clinical data, and failure to administer the questionnaire. This study included 461 subjects, who were divided into four age groups: <2 years, 2−5 years, 6−11 years, and ≥12 years. Ranitidine was prescribed in 396 (85.9%) patients, mainly for the acute treatment of gastrointestinal symptoms, and a PPI was given to 65 (14.1%) children to treat gastroesophageal reflux disease, gastritis/ulcer, or for gastroprotection. During the study period, the percentage of patients treated with ranitidine progressively increased, except in the 2−5-year age group. We observed eighty-seven adverse drug reactions (ADRs), 61 of which occurred in the ranitidine group and 26 in the PPI group. The most common ADR was constipation (n = 35), which occurred more frequently in children treated with PPIs and in the 6−11-year age group. Ranitidine was the most used antisecretory drug in all the age groups, especially for acute treatment. Conversely, PPIs were the drugs of choice for prolonged treatments. Further research should be focused on developing an effective and safer alternative to ranitidine.

Use of Azithromycin in Pregnancy: More Doubts than Certainties.

Macrolides such as azithromycin are commonly prescribed antibiotics during pregnancy. The good oral bioavailability and transplacental transfer of azithromycin make this drug suitable for the treatment of sexually transmitted diseases, toxoplasmosis, and malaria. Moreover, azithromycin is useful both in the management of preterm pre-labor rupture of membranes and in the adjunctive prophylaxis for cesarean delivery. The aim of this comprehensive narrative review is to critically analyze and summarize the available literature on the main aspects of azithromycin use in pregnant women, with a special focus on adverse offspring outcomes associated with prenatal exposure to the drug. References for this review were identified through searches of MEDLINE, PubMed, and EMBASE. Fetal and neonatal outcomes following prenatal azithromycin exposure have been investigated in several studies, yielding conflicting results. Increased risks of spontaneous miscarriage, major congenital malformations, cardiovascular malformations, digestive system malformations, preterm birth, and low birth weight have been reported in some studies but not in others. Currently, there is no conclusive evidence to support that azithromycin use by pregnant women causes adverse outcomes in their offspring. Therefore, this agent should only be used during pregnancy when clinically indicated, if the benefits of treatment are expected to outweigh the potential risks.

Ceftriaxone-associated biliary pseudolithiasis in children: do we know enough?

Ceftriaxone is an antibiotic agent frequently used in paediatric hospital practice for the treatment of severe bacterial infections. The use of this agent can result in cholelithiasis and/or biliary sludge, more commonly in children than in adults. This systematic review was aimed at analysing available literature concerning ceftriaxone-associated biliary pseudolithiasis in paediatric patients, with a special emphasis on the clinical aspects. A literature analysis was performed using Medline and Embase electronic databases (articles published in English up to December 2019), with the search terms and combinations as follows:'ceftriaxone', 'cholelithiasis', 'biliary sludge' 'gallstones' 'neonates' 'children' 'clinical aspects' 'management'. Several case reports, case series and prospective/retrospective studies have documented a relationship between ceftriaxone treatment and biliary pseudolithiasis in the paediatric population, even though literature data regarding neonates and infants are scarce. Ceftriaxone-associated biliary pseudolithiasis is dose-dependent and usually asymptomatic but, sometimes, it may present with abdominal pain, nausea and emesis. Abdominal ultrasonography should be performed when this complication is suspected. Generally, ceftriaxone-associated cholelithiasis resolves over a variable period of time (days to months) after cessation of therapy. Therefore, a conservative approach to this condition is advocated, but a prolonged follow-up may be necessary. A personalized assessment of factors predisposing to ceftriaxone-associated biliary pseudolithiasis before prescribing the drug can allow to minimize the risk of developing it, with significant advantages in terms of human and economic costs.

Use of herbal products among 392 Italian pregnant women: focus on pregnancy outcome.

PURPOSE: The present study aimed to explore the use of herbal products among a sample of Italian pregnant women and the possible influence of herbal consumption on pregnancy outcome. METHODS: The study was conducted over a 10-month period (2 days a week, from January to October 2009) at the Maternity wards of Padua and Rovereto Hospital. Data were collected through a face-to-face interview on the basis of a prestructured questionnaire including socio-demographic characteristics of the enrolled subjects, specific questions on herbal use, information about pregnancy and newborn. RESULTS: In total, 392 interviews were considered. One hundred and nine out of 392 women (27.8%) reported to have been taking one or more herbal products during pregnancy, in the 36.7% of cases throughout all pregnancy. The most frequently herbs taken by interviewees were chamomile, licorice, fennel, aloe, valerian, echinacea, almond oil, propolis, and cranberry. Four out of 109 women (3.7%) reported side-effects: constipation after a tisane containing a mix of herbs, rash and itching after local application of aloe or almond oil. The decision to use herbal products was mainly based on personal judgement and on the conviction that these natural substances would be safer than traditional medicines. Users were more often affected by morbidities pregnancy-related and their neonates were more frequently small for their gestational age. An higher incidence of threatening miscarriages and preterm labours was observed among regular users of chamomile and licorice. CONCLUSIONS: This research underlines that the use of herbal products during pregnancy is common among Italian women, not always appropriate and in some cases potentially harmful.

Safety of non-prescription medicines: knowledge and attitudes of Italian pharmacy customers.

OBJECTIVE: A survey was designed to investigate customers attitudes and knowledge toward non-prescription medicines taken on a self-medication basis but not devoid of risks. SETTING: Community pharmacies in Italy. METHOD: Forty-four pharmacies participated in the project. On the basis of an anonymous questionnaire, face-to-face interviews were made to customers buying a non-prescription medicine over a 2-month period. The questionnaire included information about socio-demographic characteristics of the interviewed subjects and 18 items designed to elicit information about the kind of medicine purchased and reason of use, general product knowledge in relation to quality and risks, attitudes toward this kind of drugs, concurrent prescription drug use and the quality of relationship with the pharmacist. RESULTS: During the study period, 613 interviews were collected. The most frequently non-prescription medicines purchased by customers were non-steroidal anti-inflammatory drugs, paracetamol and medicines for gastrointestinal problems. The most of interviewees referred to read carefully the package inserts or to ask information to pharmacists. Moreover, they reported to consider non-prescription medicines easy to manage and to be used only for minor ailments and for short periods. 55.3% of customers reported to have been taking at least a prescription drug, mostly antihypertensives or other cardiovascular medicines, in association with non-prescription medicines. In this situation, interviewees often did not inform pharmacists about chronic therapies. CONCLUSION: Our interviews demonstrate that, in general, Italian customers have a cautious approach toward non-prescription medicines and are informed on their use. However, in case of a long-term use, interviewees underestimate risks related to possible physiological/pathological changes in their organism or to interactions with other drugs.

Drug treatments in a neonatal setting: focus on the off-label use in the first month of life.

OBJECTIVE: The purpose of this work was to analyse drugs prescribed in the first month of life among a group of newborns admitted to the Neonatal Intensive Care Unit and Neonatal Pathology of Cagliari University Hospital. METHOD: This pilot study was prospectively conducted during a 1-month period and involved all newborns admitted to our hospital that received a pharmacotherapy. After obtaining written parental consent, data collected from each newborn included date of birth, sex, gestational age and weight. Also, diagnosis and information about each drug administered during the first month of life: dose, frequency, route of administration, and indication for use was collected. RESULTS: Among the 79 newborn infants admitted to our hospital during the study period, 38 received a pharmacotherapy and were enrolled in our study. A total of 88 treatments were given: 41 (47%) followed the terms of the product license, 47 (53%) were used in an unlicensed or off-label manner. CONCLUSION: Our results confirm this trend of drug use in the neonatological field and suggest the need to update information contained in the data sheets of medicines.

Acute non-oliguric kidney failure and cholestatic hepatitis induced by ibuprofen and acetaminophen: a case report.

UNLABELLED: The combined use of acetaminophen with ibuprofen has long been in clinical use because the target of action of each drug is different and they do not interfere with each other. Appropriate dosing and managing of these drugs do not likely lead to organ toxicity. However, both acetaminophen and ibuprofen can induce liver problems and acute kidney failure, respectively, if administered at high doses. We report the case of a female child, in treatment with both acetaminophen and ibuprofen, administered at therapeutic antipyretic doses in condition of volume depletion, who suffered acute kidney and liver failure. CONCLUSION: The combined ibuprofen and acetaminophen treatment, even if administered at therapeutic dosages and in a reduced number of doses, may be dangerous in conditions of volume depletion.

Attitudes and knowledge toward natural products safety in the pharmacy setting: an Italian study.

The lack of a professional supervision may expose consumers of natural products to risks; pharmacists play an important role in giving information about these substances. A survey was designed to investigate the attitudes and knowledge of consumers and pharmacists toward the safety of natural products. Twenty-three pharmacies participated in the project. On the basis of a pre-structured 17-item questionnaire, face-to-face interviews were conducted with consumers buying a natural product over a 6-month period. A further 8 items had to be compiled by pharmacists about the purchased product. During the study period, 1420 interviews were carried out. The most frequently purchased products were echinacea, propolis, garlic, guggul, ginkgo, liquorice, ginseng, glucomannan, guarana, valerian, and passionflower; 71.8% of consumers reported to have been taking conventional medicines along with natural products. Some (3.9%) referred to adverse effects in the last year: allergic reactions after cartilage of shark, propolis and thyme; anxiety after hypericum; hypotension and tachycardia after a mix containing chamomile, valerian and melissa; pyrosis and stomach-ache after laxative-depurative herbs. Pharmacists referred to some adverse effects observed in the past in relation to the products bought by consumers involved in this study. Findings from this study demonstrate that in general consumers need information on herbal safety and pharmacists are more likely to answer correctly about the use of herbs rather than about cautions, adverse effects and interactions.

Phytotherapic compounds: the consumer-pharmacist relationship.

Pharmacists play an important role in providing information about natural products and in preventing risks related to these substances, particularly with respect to interactions with conventional drugs. For these reasons, a survey was specifically designed to investigate the quality of self-care counselling by pharmacists on phytotherapy. Twenty-three pharmacy stores took part in the project. Face-to-face interviews, using a pre-structured questionnaire, were undertaken by trained pharmacists to consumers buying a herbal product. The questionnaire included socio-demographic data and 17 items designed to elicit information regarding the reason of consumption, product knowledge, relationship/communication with healthcare providers, level of satisfaction, concurrent drug use and adverse reactions. The collection of interviews started in November 2006 until April 2007. From the analysis of 1420 questionnaires, it is evident that herbal use is increasing in Italy: 12% of our interviewees were buying a herbal product for the first time. The present survey highlights the favourable perception of efficacy of phytotherapic compounds by the pharmacy's consumers, who consider this healthcare modality to be an important and effective way to promote health/wellness and disease management as well as being safer overall than conventional drugs. Moreover, findings from this study demonstrate that pharmacists are more likely to answer correctly about the uses of herbal medicines than about drug interactions, adverse drug effects and cautions about these products.

The dark side of ibuprofen in the treatment of patent ductus arteriosus: could paracetamol be the solution?

INTRODUCTION: Patent ductus arteriosus (PDA) persistence is associated, in prematures, to several complications. The optimal PDA management is still under debate, especially regarding the best therapeutic approach and the time to treat. The available drugs are not exempt from contraindications and side effects; ibuprofen itself, although representing the first-choice therapy, can show nephrotoxicity and other complications. Paracetamol seems a valid alternative to classic nonsteroidal anti-inflammatory Drugs, with a lower toxicity. Areas covered: Through an analysis of the published literature on ibuprofen and paracetamol effects in preterm neonates, this review compares the available treatments for PDA, analyzing the mechanisms underlining ibuprofen-associated nephrotoxicity and the eventual paracetamol-induced hepatic damage, also providing an update of what has been yet demonstrated and a clear description of the still open issues. Expert Opinion: Paracetamol is an acceptable alternative in case of contraindication to ibuprofen; its toxicity, in this setting, is very low. Lower doses may be effective, with even fewer risks. In the future, paracetamol could represent an efficacious first-line therapy, although its safety, optimal dosage, and global impact have to be fully clarified through long-term trials, also in the perspective of an individualized and person-based therapy taking into account the extraordinary individual variability.

Maternal Carbamazepine Therapy and Unusual Adverse Effects in a Breastfed Infant.

BACKGROUND: Usually, no adverse effects are observed in breastfed infants whose mothers are treated with the anti-epileptic carbamazepine. In this article, we described unusual short-term adverse effects observed in a young infant after exposure to carbamazepine during pregnancy and lactation. CASE REPORT: A 40-day-old female infant, born at term, was admitted to the Pediatric Clinic at University of Sassari, Italy, for recurrent regurgitations and vomiting. She was breastfed since birth and her mother was under chronic carbamazepine therapy. Gastroesophageal reflux was initially suspected; therefore, thickening of feeds and postural therapy were applied without any benefit. Subsequently, high levels of carbamazepine were detected in infant serum and in maternal breast milk. After an unsuccessful attempt to combine breastfeeding with formula feeding, the switch to exclusive formula feeding was made, with subsequent rapid resolution of symptoms and body weight increase. DISCUSSION AND CONCLUSIONS: The use of carbamazepine is considered compatible with breastfeeding, even if the potential risk of adverse reactions in breastfed infants exists. In this case, the discontinuation of breastfeeding resulted in the complete resolution of symptoms, suggesting a correlation between the observed manifestations in the infant and her exposure to maternal therapy.

Current Challenges in Neonatal Resuscitation: What is the Role of Adrenaline?

Adrenaline, also known as epinephrine, is a hormone, neurotransmitter, and medication. It is the best established drug in neonatal resuscitation, but only weak evidence supports current recommendations for its use. Furthermore, the available evidence is partly based on extrapolations from adult studies, and this introduces further uncertainty, especially when considering the unique physiological characteristics of newly born infants. The timing, dose, and route of administration of adrenaline are still debated, even though this medication has been used in neonatal resuscitation for a long time. According to the most recent Neonatal Resuscitation Guidelines from the American Heart Association, adrenaline use is indicated when the heart rate remains < 60 beats per minute despite the establishment of adequate ventilation with 100% oxygen and chest compressions. The aforementioned guidelines recommend intravenous administration (via an umbilical venous catheter) of adrenaline at a dose of 0.01-0.03 mg/kg (1:10,000 concentration). Endotracheal administration of a higher dose (0.05-0.1 mg/kg) may be considered while venous access is being obtained, even if supportive data for endotracheal adrenaline are lacking. The safety and efficacy of intraosseous administration of adrenaline remain to be investigated. This article reviews the evidence on the circulatory effects and tolerability of adrenaline in the newborn, discusses literature data on adrenaline use in neonatal cardiopulmonary resuscitation, and describes international recommendations and outcome data regarding the use of this medication during neonatal resuscitation.

Urinary prostaglandin E2 in the newborn and infant.

Prostaglandin E(2) (PGE(2)) belongs to a family of biologically active lipids derived from the 20-carbon essential fatty acids. Renal PGE(2) is involved in the development of the kidney; it also contributes to regulate renal perfusion and glomerular filtration rate, and controls water and electrolyte balance. Furthermore, this mediator protects the kidney against excessive functional changes during the transition from fetal to extrauterine life, when it counteracts the vasoconstrictive effects of high levels of angiotensin II and other mediators. There is evidence that PGE(2) plays an important pathophysiological role in neonatal conditions of renal stress, and in congenital or acquired nephropaties. Thus, measurement of urinary PGE(2) as an index of renal synthesis of this primary prostaglandin may represent a non-invasive and sensitive method of investigating the homeostatic function of the kidney in early life. The aim of this literature review is to examine urinary PGE(2) as a non-invasive marker of renal homeostasis in the newborn and infant under both physiological and pathological conditions, or during treatments with widely used, potentially toxic drugs.

Efficacy and renal tolerability of ibuprofen vs. indomethacin in preterm infants with patent ductus arteriosus.

Indomethacin is commonly used for the treatment of patent ductus arteriosus (PDA) but has renal failure as a main side-effect. Ibuprofen seems to be efficient in closing the ductus with less side-effects, but few studies are available in literature as regards its use in preterm infants. This study is a retrospective analysis of clinical data in order to compare the efficacy and the renal tolerability of ibuprofen and indomethacin administered to preterm infants with gestational age (GA) < or = 30 weeks for the treatment of PDA. From our data, ibuprofen results pharmacologically as efficient as indomethacin and could be an alternative in prematures. About renal tolerability, our data confirm that non-steroidal anti-inflammatory drugs treatment could affect at least transiently renal function. Moreover, indomethacin could be more nephrotoxic compared with ibuprofen, as creatinine concentrations normalize more slowly in this group, although the mean difference between the two drugs was not significant as our population sample was small. Further studies are needed to assess whether ibuprofen is really less nephrotoxic than indomethacin, in particular by examining carefully the correlation between GA and ibuprofen administration.

[Patologie delle alte vie respiratorie del bambino in ambulatorio: un'esperienza italiana. Diseases of the upper respiratory tract in children in ambulatory care: an Italian experience].

BACKGROUND: Overuse of antibiotics for children is widespread and contributes to the emergence of antibiotic-resistant bacteria. Moreover, non steroidal antiinflammatory drugs (NSAIDs) are often overprescribed despite of their renal and gastrointestinal side-effects. OBJECTIVES: To assess the behaviour and the factors influencing the prescribing practice of family pediatricians for the common upper respiratory diseases of pre-school children in an outpatient setting. METHODS: 125 family pediatricians, who provide primary care in an outpatient setting to young children in North-East of Italy (Veneto region), adhered to a survey consisting in a 40-item questionnaire about the factors that could influence their prescribing practice as regards otitis media (OM), pharyngitis (FGT) and broncopneumoniae (BPN) treatment of patients aged 0 to 5 years. Data were collected in November 2002. Descriptive analysis of data was performed using DELPHI TM7 professional Study Program. RESULTS: The child's age resulted an important factor, influencing the antibiotic prescription either in OM or in BPN. 86% of pediatricians emphasized the use of antipneumococcal vaccine, overall in children younger than 2 years with recurrent OM, while 71% adviced this vaccination in children younger than 5 years with relapsing BPN. The awareness of complications in OM and BPN often induced pediatricians to prescribe drugs. The most frequently prescribed antibiotic in OM, FGT and also BPN was amoxicillin for 7-10 days. According to the international guidelines, a small percentage (14%) of clinicians prescribe antibiotics for 5 days in OM, but most of them generally wait some hours to prescribe antibiotics. PenV was considered the most active drug in FGT and its disappearance from the market was considered negatively by italian pediatricians. Moreover, even if the rapid immunoenzymatic test for Group A beta-hemolyticus Streptococcus (GABHS) is considered sensitive, many pediatricians defined the throat culture the most accurate test to diagnose a GABHS pharyngitis. Paracetamol was frequently prescribed in these diseases, between 74% for OM and 53% for BPN. Among NSAIDs, niflumic acid and ibuprofen were the drugs most frequently prescribed in FGT and in OM respectively. About 30% of pediatricians refers that parents require drugs in the treatment of upper respiratory tract diseases. CONCLUSIONS: Our results show that antibotics are generally not over-prescribed by italian pediatricians, but often prescribed for a long time, likely because of fear of complications and uncertainty of the diagnosis, particularly in OM, being not always available the pneumotoscope. About NSAIDs, niflumic acid is frequently not evidence-based used in Italy. Frequently, side-effects associated with NSAIDs administration were reported.

Unlicensed and off-label uses of drugs in paediatrics: a review of the literature.

The off-label and unlicensed use of drugs to treat children is a common practice that occurs either in hospital or in the community. This derives from the fact that research for establishing drug efficacy and safety in children has not been carried out due to ethical problems, logistical difficulties, financial and legal concerns. In this work we report the studies available in literature documenting the extent of drug use in the paediatric field outside the recommendations of the license. From our analysis, a widespread attitude to prescribe medicines to children outside their product license either in the hospitals or in the community is confirmed. This suggests an immediate action for a more rationale use of drugs in paediatrics, to avoid exposing children and infants to unnecessary risks, but also to avoid depriving them of potentially effective and sometimes life-saving therapies.

Safety of fluoroquinolones in paediatrics.

In the last few years, there has been increasing pressure to use fluoroquinolones in paediatric patients, since these antibiotics offer the advantage of an oral treatment regimen on an out-patient basis. However, even although this class of antibiotics generally remains well-tolerated, the restriction of fluoroquinolone use in children on a compassionate basis, which derives from their potential to cause cartilage toxicity, limits the safety data in this population and suggests a cautious use. This review reports the data of the literature on the safety of fluoroquinolones in different districts, focusing on the side effects in children and drug interactions. Moreover, data available in the literature with regards to side effects in children are reported, with particular attention to their potential in arthropathy.