Pharmaceuticals

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14 pages, 252 KiB

Open AccessArticle

Improving Drug Safety in Pediatric and Young Adult Patients with Hemato-Oncological Diseases: A Prospective Study of Active Pharmacovigilance

by Anna Parzianello, Giulia Fornasier, Valentina Kiren, Federico Pigato, Sabrina Orzetti, Giulia Zamagni, Anna Arbo, Paolo Baldo, Paola Rossi, Marco Rabusin, Maurizio Mascarin and Marta Paulina Trojniak

Pharmaceuticals 2024, 17(1), 106; https://doi.org/10.3390/ph17010106 - 12 Jan 2024

Cited by 1 | Viewed by 1446

Abstract

The acquisition of relevant pediatric clinical safety data is essential to ensure tolerable drug therapies. Comparing the real number of Adverse Drug Reaction (ADR) reports in clinical practice with the literature, the idea of ADR underreporting emerges. An active pharmacovigilance observational prospective study [...] Read more.

The acquisition of relevant pediatric clinical safety data is essential to ensure tolerable drug therapies. Comparing the real number of Adverse Drug Reaction (ADR) reports in clinical practice with the literature, the idea of ADR underreporting emerges. An active pharmacovigilance observational prospective study was conducted to assess the safety of oncology pharmacological prescriptions in patients aged 0–24 years at Institute for Maternal and Child Health IRCCS Burlo Garofolo in Trieste and IRCCS CRO National Cancer Institute in Aviano (Italy) between January 2021 and October 2023. Prescriptions and ADRs were evaluated by a multidisciplinary team. A total of 1218 prescriptions for 38 patients were analyzed, and 190 ADRs of grade 3–5 were collected. As compared to historical data, we registered a significant increase (p < 0.001) in the number of ADRs. The risk of ADR was 3.4 times higher in the case of off-label prescriptions compared to on-label ones (OR 3.4; [1.47; 7.89]; p-value = 0.004). The risks of error and near-miss were reported for 6.3% and 18.2% of total prescriptions, respectively. Of the total of 133 interactions, 47 (35.3%) resulted in ADRs. This study shows the importance of pro-active pharmacovigilance to efficiently highlight ADRs, and the fundamental role of multidisciplinary teams (oncologist, pharmacist, pharmacologist, pediatrician, nurse) in improving patients’ safety during therapy. Full article

(This article belongs to the Special Issue Pharmacology of Pediatric Medicines)

16 pages, 2611 KiB

Open AccessArticle

The Use of Population Pharmacokinetics to Extrapolate Food Effects from Human Adults and Beagle Dogs to the Pediatric Population Illustrated with Paracetamol as a Test Case

by Elke Gasthuys, Louis Sandra, Marina Statelova, Maria Vertzoni and An Vermeulen

Pharmaceuticals 2024, 17(1), 53; https://doi.org/10.3390/ph17010053 - 28 Dec 2023

Viewed by 1461

Abstract

To date, food–drug interactions in the pediatric population remain understudied. The current food effect studies are mostly performed in adults and do not mimic the real-life situation in the pediatric population. Since the potential benefits of food effect studies performed in pediatrics should [...] Read more.

To date, food–drug interactions in the pediatric population remain understudied. The current food effect studies are mostly performed in adults and do not mimic the real-life situation in the pediatric population. Since the potential benefits of food effect studies performed in pediatrics should be counterbalanced with the burden that these studies pose to the patients, alternative research strategies should be evaluated. The present study aimed to evaluate whether population pharmacokinetics (popPK) using data in beagle dogs and human adults could reliably assess food effects relevant for the pediatric population. PopPK was utilized to understand the performance of paracetamol under different dosing conditions (when the participants were fasted, with a reference meal, and with infant formula) in human adults (n = 8) and beagle dogs (n = 6) by constructing models to derive the pharmacokinetic parameters and to evaluate the food effects in both species. A two-compartment model with a single input function for the absorption phase best described the profiles of paracetamol in the beagle dogs. In the human adults, a one-compartment model with a dual input function for the absorption phase best described the data. The simulated profiles for the different dosing conditions demonstrated that both the human adults’ and beagle dogs’ simulations were able to acceptably describe the plasma concentration–time profiles of paracetamol observed in a representative pediatric population, which opens up perspectives on pediatric-relevant food effect predictions. However, the obtained results should be carefully interpreted, since an accurate validation of these findings was not possible due to the scarcity of the literature on observed pediatric data. Full article

(This article belongs to the Special Issue Pharmacology of Pediatric Medicines)

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17 pages, 8395 KiB

Open AccessArticle

Evaluation of Pupillometry for CYP2D6 Phenotyping in Children Treated with Tramadol

by Frédérique Rodieux, Flavia Storelli, François Curtin, Sergio Manzano, Alain Gervaix, Klara M. Posfay-Barbe, Jules Desmeules, Youssef Daali and Caroline F. Samer

Pharmaceuticals 2023, 16(9), 1227; https://doi.org/10.3390/ph16091227 - 30 Aug 2023

Viewed by 1386

Abstract

Following the contraindication of codeine use in children, increasing use of tramadol has been observed in pain management protocols. However, tramadol’s pharmacokinetics (PK) and pharmacodynamics are influenced by cytochrome P450 (CYP)2D6 activity, similarly to codeine. Previous studies in adults have demonstrated a correlation [...] Read more.

Following the contraindication of codeine use in children, increasing use of tramadol has been observed in pain management protocols. However, tramadol’s pharmacokinetics (PK) and pharmacodynamics are influenced by cytochrome P450 (CYP)2D6 activity, similarly to codeine. Previous studies in adults have demonstrated a correlation between pupillary response and tramadol PK. Our objective was to evaluate pupillometry as a phenotyping method to assess CYP2D6 activity in children treated with tramadol. We included 41 children (mean age 11 years) receiving a first dose of tramadol (2 mg/kg) in the emergency room (ER) as part of their routine care. CYP2D6 phenotyping and genotyping were performed. The concentrations of tramadol and its active metabolite, M1, were measured, and static and dynamic pupillometry was conducted using a handheld pupillometer at the time of tramadol administration and during the ER stay. Pupillometric measurements were obtained for 37 children. Tramadol affected pupillary parameters, with a decrease in pupil diameter in 83.8% of children (p = 0.002) (mean decrease 14.1 ± 16.7%) and a decrease in reflex amplitude constriction in 78.4% (p = 0.011) (mean decrease 17.7 ± 34.5%) at T150 compared to T0. We were unable to identify a correlation between pupillometry measurements and CYP2D6 activity. Likely confounding factors include light intensity, pain, and stress, making the procedure less feasible in paediatric emergency settings. Full article

(This article belongs to the Special Issue Pharmacology of Pediatric Medicines)

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10 pages, 282 KiB

Open AccessArticle

Melatonin Prescription in Children and Adolescents in Relation to Body Weight and Age

by Elin E. Kimland, Elin Dahlén, Jari Martikainen, Jimmy Célind and Jenny M. Kindblom

Pharmaceuticals 2023, 16(3), 396; https://doi.org/10.3390/ph16030396 - 6 Mar 2023

Cited by 3 | Viewed by 4239

Abstract

The prescription of melatonin to children and adolescents has increased dramatically in Sweden and internationally during the last ten years. In the present study we aimed to evaluate the prescribed melatonin dose in relation to body weight and age in children. The population-based [...] Read more.

The prescription of melatonin to children and adolescents has increased dramatically in Sweden and internationally during the last ten years. In the present study we aimed to evaluate the prescribed melatonin dose in relation to body weight and age in children. The population-based BMI Epidemiology Study Gothenburg cohort has weight available from school health care records, and information on melatonin prescription through linkage with high-quality national registers. We included prescriptions of melatonin to individuals below 18 years of age where a weight measurement not earlier than three months before, or later than six months after the dispensing date, was available (n = 1554). Similar maximum doses were prescribed to individuals with overweight orobesity as to individuals with normal weight, and to individuals below and above 9 years of age. Age and weight only explained a marginal part of the variance in maximum dose, but were inversely associated and explained a substantial part of the variance in maximum dose per kg. As a result, individuals overweight or with obesity, or age above 9 years, received lower maximum dose per kg of body weight, compared with individuals with normal weight or below 9 years of age. Thus, the prescribed melatonin dose to individuals under 18 years of age is not primarily informed by body weight or age, resulting in substantial differences in prescribed dose per kg of body weight across BMI and age distribution. Full article

(This article belongs to the Special Issue Pharmacology of Pediatric Medicines)

9 pages, 595 KiB

Open AccessArticle

Impact of Duodenal Pathology on Oral Drug Bioavailability and Disease Outcomes in Pediatric Crohn’s Disease

by Rebecca Casini, Carrie A. Vyhlidal, Julia M. Bracken, Ashley K. Sherman, Atif Ahmed, Vivekanand Singh, Veronica Williams and Valentina Shakhnovich

Pharmaceuticals 2023, 16(3), 373; https://doi.org/10.3390/ph16030373 - 28 Feb 2023

Viewed by 3006

Abstract

Background: Crohn’s disease with upper gastrointestinal tract involvement occurs more often in children than adults and has the potential to interfere with oral drug absorption. We aimed to compare disease outcomes in children receiving oral azathioprine for the treatment of Crohn’s disease with [...] Read more.

Background: Crohn’s disease with upper gastrointestinal tract involvement occurs more often in children than adults and has the potential to interfere with oral drug absorption. We aimed to compare disease outcomes in children receiving oral azathioprine for the treatment of Crohn’s disease with (DP) and without (NDP) duodenal pathology at diagnosis. Methods: Duodenal villous length, body mass index (BMI), and laboratory studies were compared in DP vs. NDP during the first year post-diagnosis, using parametric/nonparametric tests and regression analysis (SAS v9.4); the data are reported as the median (interquartile range) or the mean ± standard deviation. Thiopurine metabolite concentration (pmol/8 × 10⁸ erythrocytes) 230–400 was considered therapeutic for 6-thioguanine nucleotides (6-TGN), and >5700 was considered hepatotoxic for 6-methylmercaptopurine (6-MMPN). Results: Twenty-six of the fifty-eight children enrolled (29 DP, 29 NDP) started azathioprine for standard medical care, including nine DP and ten NDP who had normal thiopurine methyltransferase activity. Duodenal villous length was significantly shorter in DP vs. NDP (342 ± 153 vs. 460 ± 85 μm; p < 0.001) at diagnosis; age, sex, hemoglobin, and BMI were comparable between groups. A trend toward lower 6-TGN was observed in the DP vs. NDP subset receiving azathioprine (164 (117, 271) vs. 272 (187, 331); p = 0.15). Compared to NDP, DP received significantly higher azathioprine doses (2.5 (2.3, 2.6) vs. 2.2 (2.0, 2.2) mg/kg/day; p = 0.01) and had an increased relative risk of sub-therapeutic 6-TGN. At 9 months post-diagnosis, children with DP had significantly lower hemoglobin (12.5 (11.7, 12.6) vs. 13.1 (12.7, 13.3) g/dL; p = 0.01) and BMI z-scores (−0.29 (−0.93, −0.11) vs. 0.88 (0.53, 0.99); p = 0.02) than children with NDP. Conclusion: For children with Crohn’s disease, duodenal pathology, marked by villous blunting, increased the risk of sub-therapeutic 6-TGN levels, despite higher azathioprine dosing during the first year post-diagnosis. Lower hemoglobin and BMI z-scores at 9 months post-diagnosis suggest the impaired absorption/bioavailability of nutrients, as well as oral drugs, in children with duodenal disease. Full article

(This article belongs to the Special Issue Pharmacology of Pediatric Medicines)

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12 pages, 1394 KiB

Open AccessArticle

Manipulated Oral and Rectal Drugs in a Paediatric Swedish University Hospital, a Registry-Based Study Comparing Two Study-Years, Ten Years Apart

by Åsa C. Andersson, Staffan Eksborg, Ulrika Förberg, Per Nydert and Synnöve Lindemalm

Pharmaceuticals 2023, 16(1), 8; https://doi.org/10.3390/ph16010008 - 21 Dec 2022

Cited by 4 | Viewed by 2280

Abstract

This is a registry-based study with the aim of describing and comparing the frequency of manipulations of solid oral and rectal medicines in 2009 and 2019 at inpatient units and an emergency department in a paediatric hospital within a Swedish university hospital. All [...] Read more.

This is a registry-based study with the aim of describing and comparing the frequency of manipulations of solid oral and rectal medicines in 2009 and 2019 at inpatient units and an emergency department in a paediatric hospital within a Swedish university hospital. All patients aged 1 month–18 years with oral or rectal administrations were included. In total, 140,791 oral and rectal administrations were included in 2009, and 167,945 oral and rectal administrations were included in 2019. The frequency of patients receiving at least one manipulated oral medicine decreased between the study years, both in inpatient units and in the emergency department (from 19% to 17%, p = 0.0029 and from 11% to 5%, p < 0.0001, respectively). The frequency of patients receiving a manipulated rectal medicine also decreased between the study years, both in inpatient units and in the emergency department (from 22% to 10%, p < 0.0001 and from 35% to 7% 2019, p < 0.0001, respectively). The results show a decrease in the manipulation of both oral and rectal medicines to paediatric patients in 2019 compared to 2009. Even though this implies a safer practice, there is still a pronounced lack of child-friendly dosage forms and suitable strengths enabling the safe administration of medicines to sick children. Full article

(This article belongs to the Special Issue Pharmacology of Pediatric Medicines)

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13 pages, 1161 KiB

Open AccessArticle

Quality of Active versus Spontaneous Reporting of Adverse Drug Reactions in Pediatric Patients: Relevance for Pharmacovigilance and Knowledge in Pediatric Medical Care

by Anne T. M. Dittrich, Nori J. L. Smeets, Emma F. M. de Jong, Juliët L. Kämink, Yvet Kroeze, Jos M. Th. Draaisma, Eugène P. van Puijenbroek and D. Maroeska W. M. te Loo

Pharmaceuticals 2022, 15(9), 1148; https://doi.org/10.3390/ph15091148 - 14 Sep 2022

Cited by 7 | Viewed by 2354

Abstract

For drug safety in pediatric patients, knowledge about adverse drug reactions (ADRs) is essential to balance benefits and risks, especially because of the high incidence of off-label drug use. However, underreporting of ADRs is a serious problem, leading to a deficit in knowledge [...] Read more.

For drug safety in pediatric patients, knowledge about adverse drug reactions (ADRs) is essential to balance benefits and risks, especially because of the high incidence of off-label drug use. However, underreporting of ADRs is a serious problem, leading to a deficit in knowledge affecting clinical practice. The aim of this study is to find a method by which we can improve the quantity of ADR reporting while maintaining or improving the quality of the ADR reports. This was done in several steps. First, health care providers were educated to increase awareness of ADRs. Thereafter, a novel active supporting system was introduced, where reporting ADRs was simplified; if clinical physicians suspected an ADR, they only had to send the name or hospital number of the patient, the observed ADR, and the suspected drug to a supportive team. This team collects all information needed about the possible ADR from the patient’s medical records and hospital charts. With this information, the supportive team fills in the forms necessary for reporting ADRs to the nationwide pharmacovigilance centre Lareb. With this system, the quantity of ADR reports from both inpatients and outpatients rose dramatically. Subsequently, the quality of the obtained ADR reports was measured using the ClinDoc and vigiGrade systems. This study shows there is no loss of quality of the ADR reports in the active reporting system compared to spontaneous reporting systems. Based on the data of the present study, we suggest that an active reporting system has the potential to increase our knowledge about ADRs in pediatric patients. Full article

(This article belongs to the Special Issue Pharmacology of Pediatric Medicines)

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Review

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17 pages, 608 KiB

Open AccessReview

Anti-Emetics in Children Receiving Chemotherapy for Solid Tumors and Leukemia: Pharmacology and Optimization of Therapy for Nausea and Vomiting

by Shuvadeep Ganguly, Archana Sasi, Santhosh Kumar Kodagalli Nagaraju and Sameer Bakhshi

Pharmaceuticals 2024, 17(5), 616; https://doi.org/10.3390/ph17050616 - 10 May 2024

Viewed by 2089

Abstract

The management of chemotherapy-induced nausea and vomiting (CINV) in children remains challenging due to differences in the chemotherapy regimens, their relative emetogenicity compared to that in adults and differences in drug metabolism and the available formulations. The common four classes of anti-emetics used [...] Read more.

The management of chemotherapy-induced nausea and vomiting (CINV) in children remains challenging due to differences in the chemotherapy regimens, their relative emetogenicity compared to that in adults and differences in drug metabolism and the available formulations. The common four classes of anti-emetics used for the treatment and prophylaxis of CINV in children include dexamethasone, neurokinin-1 receptor antagonists, 5-hydroxytryptamine-3 receptor antagonists (5HT3RAs), and olanzapine. The appropriate dose of dexamethasone for CINV prophylaxis in children is unknown, with a significant variability in dosage ranging between 6 and 32 mg/m²/day. The dose of dexamethasone is decreased by 30% when this drug is combined with (fos)aprepitant in children, in contrast to a decrease of 50% required in adults. The use of aprepitant in younger children (<12 years) is often hampered by the non-availability of oral suspension formulations in many countries; alternatively, 80 mg capsules are administered for 1–3 days in certain institutes to children weighing between 15 and 40 kg. Among the different 5HT3RAs, palonosetron is comparatively metabolized faster in children than in adults, requiring a higher dosage for similar efficacy to that achieved in adults. Olanzapine is a newer agent, used in doses between 0.1 and 0.14 mg/kg/day in children, with good anti-emetic efficacy, but has sedation and hyperglycemia as concerning adverse effects. Drug interactions between anti-emetics and between anti-emetics and chemotherapy/supportive agents (azole antifungals, cyclosporine, arsenic trioxide), especially QTc prolongation, should be considered during prescription. Full article

(This article belongs to the Special Issue Pharmacology of Pediatric Medicines)

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21 pages, 1191 KiB

Open AccessReview

Aminoglycosides-Related Ototoxicity: Mechanisms, Risk Factors, and Prevention in Pediatric Patients

by Serena Rivetti, Alberto Romano, Stefano Mastrangelo, Giorgio Attinà, Palma Maurizi and Antonio Ruggiero

Pharmaceuticals 2023, 16(10), 1353; https://doi.org/10.3390/ph16101353 - 25 Sep 2023

Cited by 8 | Viewed by 9462

Abstract

Aminoglycosides are broad-spectrum antibiotics largely used in children, but they have potential toxic side effects, including ototoxicity. Ototoxicity from aminoglycosides is permanent and is a consequence of its action on the inner ear cells via multiple mechanisms. Both uncontrollable risk factors and controllable [...] Read more.

Aminoglycosides are broad-spectrum antibiotics largely used in children, but they have potential toxic side effects, including ototoxicity. Ototoxicity from aminoglycosides is permanent and is a consequence of its action on the inner ear cells via multiple mechanisms. Both uncontrollable risk factors and controllable risk factors are involved in the pathogenesis of aminoglycoside-related ototoxicity and, because of the irreversibility of ototoxicity, an important undertaking for preventing ototoxicity includes antibiotic stewardship to limit the use of aminoglycosides. Aminoglycosides are fundamental in the treatment of numerous infectious conditions at neonatal and pediatric age. In childhood, normal auditory function ensures adequate neurocognitive and social development. Hearing damage from aminoglycosides can therefore strongly affect the normal growth of the child. This review describes the molecular mechanisms of aminoglycoside-related ototoxicity and analyzes the risk factors and the potential otoprotective strategies in pediatric patients. Full article

(This article belongs to the Special Issue Pharmacology of Pediatric Medicines)

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18 pages, 375 KiB

Open AccessReview

Pain Management in Children Admitted to the Emergency Room: A Narrative Review

by Daniela Cunico, Arianna Rossi, Matteo Verdesca, Nicola Principi and Susanna Esposito

Pharmaceuticals 2023, 16(8), 1178; https://doi.org/10.3390/ph16081178 - 18 Aug 2023

Cited by 3 | Viewed by 3957

Abstract

Pain is a biopsychosocial experience characterized by sensory, physiological, cognitive, affective, and behavioral components. Both acute and chronic pain can have short and long-term negative effects. Unfortunately, pain treatment is often inadequate. Guidelines and recommendations for a rational approach to pediatric pain frequently [...] Read more.

Pain is a biopsychosocial experience characterized by sensory, physiological, cognitive, affective, and behavioral components. Both acute and chronic pain can have short and long-term negative effects. Unfortunately, pain treatment is often inadequate. Guidelines and recommendations for a rational approach to pediatric pain frequently differ, and this may be one of the most important reasons for the poor attention frequently paid to pain treatment in children. This narrative review discusses the present knowledge in this regard. A literature review conducted on papers produced over the last 8 years showed that although in recent years, compared to the past, much progress has been made in the treatment of pain in the context of the pediatric emergency room, there is still a lot to do. There is a need to create guidelines that outline standardized and easy-to-follow pathways for pain recognition and management, which are also flexible enough to take into account differences in different contexts both in terms of drug availability and education of staff as well as of the different complexities of patients. It is essential to guarantee an approach to pain that is as uniform as possible among the pediatric population that limits, as much as possible, the inequalities related to ethnicity and language barriers. Full article

(This article belongs to the Special Issue Pharmacology of Pediatric Medicines)

15 pages, 330 KiB

Open AccessReview

Pharmacogenetic Testing for the Pediatric Gastroenterologist: Actionable Drug–Gene Pairs to Know

by Tracy Sandritter, Rachel Chevalier, Rebecca Abt and Valentina Shakhnovich

Pharmaceuticals 2023, 16(6), 889; https://doi.org/10.3390/ph16060889 - 16 Jun 2023

Cited by 2 | Viewed by 1760

Abstract

Gastroenterologists represent some of the earlier adopters of precision medicine through pharmacogenetic testing by embracing upfront genotyping for thiopurine S-methyltransferase nucleotide diphosphatase (TPMT) before prescribing 6-mercaptopurine or azathioprine for the treatment of inflammatory bowel disease. Over the last two decades, pharmacogenetic [...] Read more.

Gastroenterologists represent some of the earlier adopters of precision medicine through pharmacogenetic testing by embracing upfront genotyping for thiopurine S-methyltransferase nucleotide diphosphatase (TPMT) before prescribing 6-mercaptopurine or azathioprine for the treatment of inflammatory bowel disease. Over the last two decades, pharmacogenetic testing has become more readily available for other genes relevant to drug dose individualization. Common medications prescribed by gastroenterologists for conditions other than inflammatory bowel disease now have actionable guidelines, which can improve medication efficacy and safety; however, a clear understanding of how to interpret the results remains a challenge for many clinicians, precluding wide implementation of genotype-guided dosing for drugs other than 6-mercaptopurine and azathioprine. Our goal is to provide a practical tutorial on the currently available pharmacogenetic testing options and a results interpretation for drug–gene pairs important to medications commonly used in pediatric gastroenterology. We focus on evidence-based clinical guidelines published by the Clinical Pharmacogenetics Implementation Consortium (CPIC^®) to highlight relevant drug–gene pairs, including proton pump inhibitors and selective serotonin reuptake inhibitors and cytochrome P450 (CYP) 2C19, ondansetron and CYP2D6, 6-mercaptopurine and TMPT and Nudix hydrolase 15 (NUDT15), and budesonide and tacrolimus and CYP3A5. Full article

(This article belongs to the Special Issue Pharmacology of Pediatric Medicines)

26 pages, 2291 KiB

Open AccessReview

Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response

by Ashwin Kamath, Suresh Kumar Srinivasamurthy, Mukta N. Chowta, Sheetal D. Ullal, Youssef Daali and Uppugunduri S. Chakradhara Rao

Pharmaceuticals 2022, 15(8), 990; https://doi.org/10.3390/ph15080990 - 11 Aug 2022

Cited by 2 | Viewed by 2775

Abstract

Pediatric cancer treatment has evolved significantly in recent decades. The implementation of risk stratification strategies and the selection of evidence-based chemotherapy combinations have improved survival outcomes. However, there is large interindividual variability in terms of chemotherapy-related toxicities and, sometimes, the response among this [...] Read more.

Pediatric cancer treatment has evolved significantly in recent decades. The implementation of risk stratification strategies and the selection of evidence-based chemotherapy combinations have improved survival outcomes. However, there is large interindividual variability in terms of chemotherapy-related toxicities and, sometimes, the response among this population. This variability is partly attributed to the functional variability of drug-metabolizing enzymes (DME) and drug transporters (DTS) involved in the process of absorption, distribution, metabolism and excretion (ADME). The DTS, being ubiquitous, affects drug disposition across membranes and has relevance in determining chemotherapy response in pediatric cancer patients. Among the factors affecting DTS function, ontogeny or maturation is important in the pediatric population. In this narrative review, we describe the role of drug uptake/efflux transporters in defining pediatric chemotherapy-treatment-related toxicities and responses. Developmental differences in DTS and the consequent implications are also briefly discussed for the most commonly used chemotherapeutic drugs in the pediatric population. Full article

(This article belongs to the Special Issue Pharmacology of Pediatric Medicines)

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22 pages, 5614 KiB

Open AccessCase Report

Improved Enzyme Replacement Therapy with Cipaglucosidase Alfa/Miglustat in Infantile Pompe Disease

by Lina Fiege, Ibrahim Duran and Thorsten Marquardt

Pharmaceuticals 2023, 16(9), 1199; https://doi.org/10.3390/ph16091199 - 23 Aug 2023

Cited by 2 | Viewed by 2109

Abstract

Pompe disease is a lysosomal storage disorder with impaired glycogen degradation caused by a deficiency of the enzyme acid α-glucosidase (GAA). Children with the severe infantile form do not survive beyond the first year of life without treatment. Since 2006, enzyme replacement therapy [...] Read more.

Pompe disease is a lysosomal storage disorder with impaired glycogen degradation caused by a deficiency of the enzyme acid α-glucosidase (GAA). Children with the severe infantile form do not survive beyond the first year of life without treatment. Since 2006, enzyme replacement therapy (ERT) with Alglucosidase alfa (Myozyme) has been available, which is a recombinant human GAA (rhGAA). Myozyme therapy has prolonged the life span of affected patients, but many patients showed a continuing, albeit slower, disease progression. A new generation of rhGAA, Cipaglucosidase alfa (Amicus) has a higher content of mannose-6-phosphate residues, which are necessary for efficient cellular uptake and lysosomal targeting. Cipaglucosidase alfa is co-administered with an enzyme stabilizer, Miglustat, which also optimizes the pharmacological properties. In mouse models, the superiority of Cipaglucosidase alfa/Miglustat compared to the previous standard therapy could be determined. Here, we report the disease course of a patient with severe infantile M. Pompe, who showed serious progression even with high-dose standard of care ERT. Changing the therapy to Cipaglucosidase alfa/Miglustat improved respiratory failure, cardiomyopathy, and motor functions significantly. The patient could be weaned from respiratory support and oxygen supplementation. Cardiac function was normalized. Most impressively, the patient, who had lost nearly all motor skills, acquired head control, learned to speak, and could move his wheelchair by himself. Overall, the patient’s clinical situation has improved dramatically with the new ERT. Full article

(This article belongs to the Special Issue Pharmacology of Pediatric Medicines)

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