Probable adverse reaction to a pharmaceutical excipient

Hall, Catriona

doi:10.1136/adc.2002.024927

Cited by 31 publications

(8 citation statements)

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“…Two examples of neonatal sensitivity due to deficient metabolism are the Grey Baby syndrome observed in the 1950s due to reduced glucuronidation of the antibiotic chloramphenicol and gasping syndrome identified in the 1980s due to benzyl alcohol used as an antibacterial agent in intravenous solutions. 29,[39][40][41] Both of these produced very clear clinical signs of toxicity due to poor metabolism of the compounds in children. It is likely that similar types of metabolic factors can lead to differential sensitivity to cDILI.…”

Section: Factors Related To Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

Drug-Induced Liver Injury in Children: Clinical Observations, Animal Models, and Regulatory Status

et al. 2017

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Drug-induced liver injury in children (cDILI) accounts for about 1% of all reported adverse drug reactions throughout all age groups, less than 10% of all clinical DILI cases, and around 20% of all acute liver failure cases in children. The overall DILI susceptibility in children has been assumed to be lower than in adults. Nevertheless, controversial evidence is emerging about children's sensitivity to DILI, with children's relative susceptibility to DILI appearing to be highly drug-specific. The culprit drugs in cDILI are similar but not identical to DILI in adults (aDILI). This is demonstrated by recent findings that a drug frequently associated with aDILI (amoxicillin/clavulanate) was rarely associated with cDILI and that the drug basiliximab caused only cDILI but not aDILI. The fatality in reported cDILI studies ranged from 4% to 31%. According to the US Food and Drug Administration-approved drugs labels, valproic acid, dactinomycin, and ampicillin appear more likely to cause cDILI. In contrast, deferasirox, isoniazid, dantrolene, and levofloxacin appear more likely to cause aDILI. Animal models have been explored to mimic children's increased susceptibility to valproic acid hepatotoxicity or decreased susceptibility to acetaminophen or halothane hepatotoxicity. However, for most drugs, animal models are not readily available, and the underlying mechanisms for the differential reactions to DILI between children and adults remain highly hypothetical. Diagnosis tools for cDILI are not yet available. A critical need exists to fill the knowledge gaps in cDILI. This review article provides an overview of cDILI and specific drugs associated with cDILI.

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Section: Factors Related To Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

Drug-Induced Liver Injury in Children: Clinical Observations, Animal Models, and Regulatory Status

et al. 2017

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“…One of the most common antibiotics women in the non- β -lactam group received was clindamycin. Formulations of this antibiotic containing the preservative benzyl alcohol have been associated with adverse neonatal outcomes related to “gasping syndrome.” 18 19 “Gasping syndrome” has been reported in premature infants exposed to clindamycin and results in multisystem organ failure and often death. 19 Although we cannot determine the specific formulations that neonates in out cohort received, it is possible that women in the non- β -lactam group suffered adverse neonatal morbidities from their antibiotic exposure that were not quantified in our study.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Non-penicillin Antibiotic Regimens on Neonatal Outcomes in Preterm Premature Rupture of Membranes

Siegel

Heine

Dotters‐Katz

2019

AJP Rep

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Objective A 7-day course of a penicillin (PCN) and macrolide is standard of care (SAR) in preterm premature rupture of membranes (PPROM). Data regarding alternative antibiotic regimens are limited. We sought to assess the impact of non-PCN regimens on neonatal outcomes. Study Design Secondary analysis of randomized controlled trial of antenatal magnesium sulfate. Singleton, nonanomalous pregnancies complicated by PPROM at > 24 weeks of gestation receiving the SAR were compared with women receiving a non-β-lactam regimen and a macrolide (NPCR). Primary outcome was a neonatal composite. Secondary outcomes included pregnancy latency, endometritis, and chorioamnionitis. Results A total of 949 women met inclusion criteria; 821(56%) received the SAR and 128(8.8%) received NPCR. Adjusted models did not demonstrate worse outcomes (AOR [adjusted odds ratio] = 0.50; 95% CI [confidence interval]: 0.22–1.11). Neonates receiving SAR were less likely to have bronchopulmonary dysplasia (BPD; p = 0.03) but more likely to have severe necrotizing enterocolitis (sNEC; p = 0.04). Risk for chorioamnionitis and median latency did not differ between groups but women receiving the SAR were less likely to get endometritis (AOR = 0.35; 95% CI: 0.14–0.91). Conclusions In this cohort, receiving NPCR in the setting of PPROM did not impact the overall risk of adverse neonatal outcomes or latency, but did increase the risk of endometritis. Alterations in individual neonatal morbidities suggest follow-up studies are needed.

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“…Finally, the (repeated) use of clindamycin might be limited because of the benzyl alcohol used in preparations for intravenous administration. The use of benzyl alcohol in neonates is associated with increased rates of mortality and morbidity (15,21). Safety is crucial, especially when drug treatments are used as prophylactic measures.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Clindamycin in Pregnant Women in the Peripartum Period

Muller

Mouton

Oostvogel

et al. 2010

Antimicrob Agents Chemother

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The study presented here was performed to determine the pharmacokinetics of intravenously administered clindamycin in pregnant women. Seven pregnant women treated with clindamycin were recruited. Maternal blood and arterial and venous umbilical cord blood samples were obtained. Maternal clindamycin concentrations were analyzed by nonlinear mixed-effects modeling with the NONMEM program. The data were best described by a linear three-compartment model. The clearance and the volume of distribution at steady state were 10.0 liters/h and 6.32 ؋ 10 3 liters, respectively. Monte Carlo simulations were performed to determine the area under the concentration curve (AUC) for the free (unbound) drug (f) in maternal serum for 24 h divided by the MIC (fAUC 0-24 /MIC). At a MIC of 0.5 mg/liter, which is the EUCAST breakpoint, the attainment at the lower 95% confidence interval (CI) was 24.6 if the level of protein binding was 65%, and this value concurred well with the target value of 27. However, for higher degrees of protein binding, as has been described in the literature, the attainment was lower, down to 10.2 for a protein binding level of 85% (lower 95% CI). The concentrations in umbilical cord blood were lower than those in maternal blood. The concentration-time profiles in maternal serum indicate that the level of exposure to clindamycin may be too low in these patients. Together with the lower concentrations in umbilical cord blood, this finding suggests that the current dosing regimen may not be adequate to protect all neonates from group B streptococcal disease.

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Probable adverse reaction to a pharmaceutical excipient

Cited by 31 publications

References 4 publications

Drug-Induced Liver Injury in Children: Clinical Observations, Animal Models, and Regulatory Status

Drug-Induced Liver Injury in Children: Clinical Observations, Animal Models, and Regulatory Status

The Effect of Non-penicillin Antibiotic Regimens on Neonatal Outcomes in Preterm Premature Rupture of Membranes

Pharmacokinetics of Clindamycin in Pregnant Women in the Peripartum Period

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