&lt;p&gt;Safety and Biopharmaceutical Challenges of Excipients in Off-Label Pediatric Formulations&lt;/p&gt;

Belayneh, Anteneh; Tadese, Ebisa; Molla, Fantahun

doi:10.2147/ijgm.s280330

Cited by 39 publications

(42 citation statements)

References 53 publications

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“…The absence of approval in pediatrics also implies the absence of formulations suitable for children. Some drugs may contain excipients unsafe for children [29] and most are only available in tablets with adult dosing. To overcome the lack of pediatric formulation, pharmacists must create compounded liquid formulations with crushed tablets and excipients.…”

Section: Discussionmentioning

confidence: 99%

Off-Label Use and Safety of Drug Use in Vascular Anomalies

Kleiber¹,

Gariépy-Assal²,

Coulombe³

et al. 2021

Dermatology

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Background: Off-label drug use is associated with an increased risk of adverse drug reactions. It is common in pediatrics and in rare diseases, which are two characteristics applying to vascular anomalies (VA). Objectives: The aim of this work was to quantify off-label drug use in VA and assess its safety. Methods: A review was conducted to extract a list of drugs used in VA management. A drug was considered to have significant safety concerns if a black box warning was present or if a serious adverse drug reaction (SADR) was reported in at least 1% of the patients (SADR is defined as a noxious and unintended response to a drug that occurs at any dose and results in hospitalization, prolongation of existing hospitalization, congenital malformation, persistent or significant disability or incapacity, life-threatening condition, or death). The labelling status and safety of each drug was assessed based on the product monograph, Micromedex, and the FDA data. Results: We found that 98.9% of the inventoried drugs were used off-label or unlicensed for VA management. Only the oral solution of propranolol hydrochloride (Hemangeol®) for the treatment of infantile hemangiomas is approved. Significant safety issues concerned 73% of the drugs and were more frequent among systemic than locally delivered drugs. Conclusions: Off-label drug use in VA is the rule and not the exception. Significant safety concerns are common. It is necessary to carefully weigh risk and benefits for every patient when using systemic and local treatments carrying safety concerns. Patients should be openly informed and involved in the decision-making process.

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Section: Discussionmentioning

confidence: 99%

Off-Label Use and Safety of Drug Use in Vascular Anomalies

Kleiber¹,

Gariépy-Assal²,

Coulombe³

et al. 2021

Dermatology

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“…Sodium metabisulfite is registered in one formulation as antioxidant. Although it is thought to be generally safe, the sensitivity to this EKE is noted in 3-10% of asthmatic children [31]. EMA and Serbian regulative request declaring the EKE name in the information leaflet with the comment regarding possible hypersensitivity, which was found to be appropriately labeled.…”

Section: Wwwhophonlineorgmentioning

confidence: 99%

Exposure of children in Serbia to potentially harmful excipients when treated with approved antibiotics

Puača¹,

Todorović²,

Čanji³

et al. 2021

Hosp Pharm Int Multi J

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Introduction: According to current understanding of the role of excipient in medicines, they could not be considered as completely pharmacologically inert substances. Although excipients do not have the potential to cause adverse drug reactions (ADRs) in most patients, some of their negative effects have been established. Special caution regarding excipients intake is advised, especially in vulnerable populations such as pediatric one. Aim: The aim of this paper was to investigate the exposure of children on antibiotic therapy to excipients with known effects (EKE). Methods: During a one-month period antibiotic prescriptions data were taken from community pharmacies in Novi Sad, Serbia. Age, diagnosis and prescribed therapy were observed. Data about qualitative content of prescribed medicines were taken from Summaries of Product Characteristics (SmPC) available at the official website of Medicines and medical devices agency of Serbia (ALIMS). Excipients were considered to be potentially harmful if they were listed in European Medicines Agency (EMA) guidelines. Results: The most commonly observed diagnosis was a respiratory infection, which affected more than 88% of children prescribed with an antibiotic. Only 5 out of 33 prescribed antibiotic formulations did not contain at least one EKE. Prescribed medicines mostly contained sodium compounds (77.78%), sucrose (34.07%) and sodium benzoate (31.11%). In addition, the following EKE were detected: propylene glycol, aspartame, sorbitol, lactose, potassium, mannitol, benzalkonium chloride, azorubine, parabens, sodium metabisulfite and sunset yellow. Around 75% of prescribed antibiotic formulations contained inappropriately labeled EKE (sodium and potassium compounds, sodium benzoate and propylene glycol). Additionally, inappropriately labeled information leaflets did not include possible adverse effects caused by the EKE. Conclusions: This paper indicates high exposure of patients to EKE, where almost all children treated with antibiotics (96.3%) were simultaneously administered at least one EKE. We confirmed that approved medicines cannot meet the treatment needs of all patients, and that inappropriately labeled medicines carry a risk of ADRs, especially in newborns. Personalized treatment is especially important in children, as the appropriate dosage forms and diversity in formulation ingredients is lacking. Knowing the type and roles of each ingredient of the medicines it is possible to formulate a preparation that will meet all the individual children's needs.

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“…In addition, taste masking which often relies on sweeteners is important to improve palatability. Texture and viscosity are also key attributes for patient acceptability [ 10 , 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Development of an Oral Liquid Formulation of Nicardipine Hydrochloride Compounded with Simple Excipients for the Treatment of Pediatric Hypertension

et al. 2023

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Nicardipine hydrochloride is an anti-hypertensive drug that is used off-label to treat hypertension in children. A previous oral formulation of nicardipine hydrochloride was developed using a commercial vehicle as an excipient. However, ready-to-use vehicles are prone to supply shortages, and their composition may undergo substantial modifications. The aim of this study was to propose a new oral formulation of nicardipine hydrochloride 2 mg/mL using simple excipients. The formulation included hydroxypropylmethylcellulose, simple syrup, polysorbate 80, sodium saccharin, citrate buffer, strawberry flavor and 0.2% potassium sorbate. The uniformity of content was maintained before and after agitation. Nicardipine hydrochloride concentration assessed by HPLC-MS/MS remained above 90% for 365 days before opening and for 28 days after opening. pH and osmolality were maintained throughout the study, and no microbial contamination was observed. The uniformity of mass of the delivered doses was evaluated using four different devices. A new oral formulation of nicardipine hydrochloride 2 mg/mL was developed using simple and safe excipients. Pharmacological and clinical parameters remain to be assessed and compared with those of the previous formulation.

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<p>Safety and Biopharmaceutical Challenges of Excipients in Off-Label Pediatric Formulations</p>

Cited by 39 publications

References 53 publications

Off-Label Use and Safety of Drug Use in Vascular Anomalies

Off-Label Use and Safety of Drug Use in Vascular Anomalies

Exposure of children in Serbia to potentially harmful excipients when treated with approved antibiotics

Development of an Oral Liquid Formulation of Nicardipine Hydrochloride Compounded with Simple Excipients for the Treatment of Pediatric Hypertension

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