Oral Formulations Research Articles

Dental impact on daily life and oral health in alcohol use disorder patients

ObjectivesIndividuals with Alcohol Use Disorder (AUD) are at a higher risk of developing dental problems. The present study assessed the dental impact on daily performances among AUD patients seeking treatment in a de-addiction centre and correlated it with their clinical dental status using the WHO oral health assessment form (2013). Materials and methodsThis research took place from January to May 2022. A cross-sectional study was carried out to collect data from 103 subjects among alcohol dependents taking treatment in a de-addiction centre of Dakshina Kannada district, Karnataka state. The Dental Impact on Daily Living Questionnaire (DIDL) assessed patients' satisfaction with their teeth, while the WHO Oral Health Assessment Form for Adults was used for dental caries (DMFT) and periodontal status. Data analysis was performed using the jamovi open-source software (version 2.3), employing t-test, chi-square test, hierarchical regression analysis, and Spearman correlation coefficient. ResultsThe study found low yet significant correlations between clinical oral health and dimensions of the DIDL scale. Social class and the number of decayed teeth emerged as significant predictors of the total DIDL score. ConclusionOral health conditions can adversely affect patient satisfaction, emphasizing the need for healthcare providers to consider these findings when offering comprehensive oral healthcare services. Clinical relevanceThis study underscores the necessity of integrating oral healthcare into the overall treatment regime for individuals with Alcohol Use Disorders (AUDs) to improve their quality of life and satisfaction.

Intravenous Versus Oral Omadacycline or Linezolid for Acute Bacterial Skin and Skin Infections: A post hoc Analysis of the OASIS Trials.

Appropriate oral antibiotic therapy for the treatment of acute bacterial skin and skin structure infections (ABSSSI) is a challenge, as current oral treatment guidelines do not fully cover the most common skin pathogens. Both linezolid and omadacycline are available as intravenous or bioequivalent oral formulations. This post hoc analysis of the OASIS-1 (ClinicalTrials.gov identifier NCT02378480) and OASIS-2 (ClinicalTrials.gov identifier NCT02877927) phase 3 trials assessed safety and clinical efficacy of intravenous (IV)-start versus oral (PO)-start therapy in patients treated with omadacycline or linezolid for ABSSSI. In OASIS-1, patients were randomized to IV omadacycline or linezolid, with optional switch to oral therapy, while patients in OASIS-2 received oral omadacycline or linezolid. Treatment was provided for 7-14days in both studies. The primary endpoint was an early clinical response (ECR) at 48 to 72h, defined as survival and ≥ 20% reduction in lesion size, without rescue antibacterial therapy. A total of 645 IV-start inpatients and 735 PO-start outpatients were assessed. Median age was 47years for the IV-start group and 44years for the PO-start group. Most patients had solely gram-positive infections (97% in each group; ECR [85.2% IV-start and 85.0% PO-start]), and the incidence of treatment-emergent adverse events (AEs) was similar between the groups. The most frequent AEs observed were nausea (11.2% [IV-start] versus 18.9% [PO-start]) and subcutaneous abscess (5.6% [IV-start] versus 1.9% [PO-start]). Discontinuation due to AEs was infrequent in both groups (2% [IV-start] versus 1.2% [PO-start]). Oral therapy is equally efficacious to IV therapy when omadacycline or linezolid is used to treat ABSSSIs. These data strengthen the evidence for oral omadacycline as a therapeutic option for ABSSSI, particularly for patients who have experienced treatment failure because of the limitations of other therapies. Clinicaltrials.gov, NCT02378480 and NCT02877927.

Antipsychotic prescribing practices and their association with rehospitalization in a forensic psychiatric sample.

While there is extensive literature examining the effectiveness of antipsychotic prescribing to patients with schizophrenia spectrum or other psychotic disorders in general psychiatric services, there is a dearth of studies examining antipsychotic prescribing practices and their effectiveness in forensic psychiatric services. Forensic psychiatric patients have unique challenges often due to their high-profile offences, public scrutiny, and legal requirements. This longitudinal, retrospective study aimed to examine antipsychotic prescribing and rehospitalization rates in a forensic psychiatric sample, along with relevant socio-demographic, clinical, and forensic characteristics. All patients had a psychotic illness and were prescribed antipsychotic medication. The sample included 153 patients, of which the majority were male (85.6%), Caucasian (71.2%), middle aged (30s to 50s), had schizophrenia or schizoaffective disorder (76.5%), had a substance use disorder (62.1%), and had a most serious index offence against the person (80.4%). Atypical antipsychotics accounted for the majority of antipsychotic prescriptions (75.9%) and the sample had an antipsychotic polypharmacy rate of 39.9%. The sample was divided into four primary antipsychotic formulation types, which were oral (34.0%), injection (39.2%), clozapine (19.0%), and subtherapeutic (7.8%). Regarding rehospitalization, 52.9% of the sample was rehospitalized, with the average number of rehospitalizations being 1.2 (SD = 1.7) and proportion of the follow up period rehospitalized being 16.4% (SD = 27.7%). Patients prescribed clozapine had numerically lower rates of rehospitalization than those prescribed oral and injection formulation types, but it was not statistically significant. With a 19.0% prescription rate, clozapine may be underutilized in this sample. Further research is needed to demonstrate the potential benefits of clozapine regarding rehospitalization in forensic psychiatric patients, as has already been done in general psychiatry. Advancing treatment of the high-profile forensic population can reduce stigma toward people with mental illness and criminal justice involvement.

Pharmacokinetics and Bioequivalence of 2 Oral Formulations of Vildagliptin in Healthy Chinese Subjects.

A randomized, open-label, 2-period, 2-sequence crossover study was conducted to evaluate the pharmacokinetics and bioequivalence of 2 oral formulations of vildagliptin tablets under both fasting and fed conditions in healthy Chinese subjects. A total of 56 healthy subjects were randomized to receive a single 50-mg dose of either a generic vildagliptin tablet (T) or the reference formulation (R). The washout period was 3 days. Blood samples were collected up to 24hours postdosing during each period and analyzed for vildagliptin using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The 90% confidence intervals for the geometric mean ratios (T:R) of maximum serum concentration, area under the serum concentration-time curve from time 0 to the last measurable concentration, and area under the serum concentration-time curve from time 0 to infinity were all within the predefined bioequivalence range of 80%-125%. This indicates that the generic and reference formulations are bioequivalent under both fasting and fed states. All adverse events reported were mild and transient. High-fat meals delayed absorption and reduced the maximum peak concentration of both formulations; however, they did not affect the overall exposure. Therefore, vildagliptin can be taken without regard to meals.

Voriconazole trough levels after switching from an intravenous to oral formulation in a patient with short bowel syndrome.

Voriconazole trough levels after switching from an intravenous to oral formulation in a patient with short bowel syndrome.

Comparative analysis of semaglutide induced adverse reactions: Insights from FAERS database and social media reviews with a focus on oral vs subcutaneous administration.

Compared to alternative weight-loss strategies and medications, semaglutide stands out for its convenience and efficacy, resulting in a significant increase in prescriptions and raising public safety concerns. Furthermore, the safety profiles of its oral and subcutaneous formulations require further examination. Our goal is to investigate the potential safety risks associated with semaglutide by analyzing data from the FAERS database and social media. Additionally, we aim to compare the adverse drug reaction (ADR) signals between the oral and subcutaneous administration routes of semaglutide. We collected semaglutide-related reports from the FAERS database spanning Q1 2018 to Q2 2023, and patient reviews on WebMD and AskaPatient up to 20 July 2023. Following data extraction and cleansing, we conducted descriptive analyses of demographic characteristics. Subsequently, we calculated adverse drug reaction (ADR) signals using the reporting odds ratio (ROR). We identified 19,289 and 422 semaglutide-related adverse drug events (ADEs) reported in the FAERS database and online patient reviews, respectively. Gastrointestinal disorders emerged as the most commonly reported System Organ Class (SOC) in both datasets. Predominant Preferred Terms (PTs) included nausea, vomiting, and diarrhea. Serious outcomes constituted 3.07% and 2.25% of all cases for oral and subcutaneous semaglutide, respectively. At the SOC level, gastrointestinal disorders accounted for 30.19% of total ADEs in oral semaglutide, slightly surpassing the 27.76% in subcutaneous semaglutide. The median onset for gastrointestinal PTs was 4 days in both oral (Q1: 1, Q3: 32) and subcutaneous (Q1: 1, Q3: 35) formulations. Noteworthy, new serious adverse event (AE) signals were identified, including hemorrhagic diarrhea (ROR: 3.69), hepatic pain (ROR: 4.20), abnormal hormone levels (ROR: 6.51), and pancreatic failure (ROR: 36.34) in subcutaneous semaglutide, and Dupuytren's contracture (ROR: 46.85) in oral semaglutide. Our study delineates the safety profile of semaglutide using data from the FAERS database and social media. And identified novel ADR signals specific to oral and subcutaneous forms of semaglutide.

Gastroprotective Efficacy of Prebiotic-based Oral Formulation of Amoxicillin

Gastroprotective Efficacy of Prebiotic-based Oral Formulation of Amoxicillin

The Design of Novel 3D-Printed, Moulded, and Oral Viscous Budesonide Formulations for Paediatrics: A Comparative Evaluation of Their Mucoadhesive Properties.

Paediatric eosinophilic oesophagitis (EoE) treatment is challenging due to the limited number of age-appropriate formulations. This study aims to develop and evaluate oral viscous suspensions and solid formulations of budesonide (BUD), focusing on their in vitro mucoadhesive properties, to enhance drug delivery and therapeutic outcomes in paediatric EoE. This study encompasses the development of oral viscous suspensions and orodispersible solid formulations (moulded tablets and 3D-printed dosage forms) containing BUD. The formulations underwent quality control tests as per the European Pharmacopoeia, chemical stability assessments, and an in vitro evaluation of their mucoadhesiveness properties. A validated analytical method enabled accurate BUD quantification and efficient extraction, and all developed formulations demonstrated chemical stability for 30 days, meeting Ph. Eur. quality standards. Three-dimensional printing using SSE successfully produced 1 mg and 0.5 mg BUD printlets, complying with quality tests for conventional tablets. Formulations containing xanthan gum (L2-XG and P1-0.5-XG) exhibited superior mucoadhesive properties. L2-XG showed significantly higher mucoadhesion than L1-MC. Among the solid formulations, P1-0.5-XG demonstrated the highest mucoadhesive properties. This is the first study to develop solid oral dosage forms of BUD at a very low dose, specifically for paediatric use. The results highlight the potential of 3D printing for developing individualised orodispersible BUD formulations with improved bioadhesion for paediatric EoE treatment. The L2-XG formulation and the XG-containing printlets are the most promising formulations in terms of increasing contact time with the oesophageal mucosa, which could translate into improved therapeutic efficacy in this patient population.

Phase-separated polymer blends for controlled drug delivery by tuning morphology

Controlling drug release rate and providing physical and chemical stability to the active pharmaceutical ingredient are key properties of oral solid dosage forms. Here, we demonstrate a formulation strategy using phase-separated polymer blends where the morphology provides a route for tuning the drug release profile. By utilising phase separation of a hydrophobic and a hydrophilic polymer, the hydrophilic component will act as a channelling agent, creating a porous network upon dissolution that will dictate the release characteristics. With ptychographic X-ray tomography and scanning transmission X-ray microscopy we reveal how the morphology depends on both polymer fraction and presence of drug, and how the drug is distributed over the polymer domains. Combining X-ray imaging results with dissolution studies reveal how the morphologies are correlated with the drug release and showcase how tuning the morphology of a polymer matrix in oral formulations can be utilised as a method for controlled drug release.

Development and evaluation of an oral quinine sulphate sustained release formulation for the management of visceral leishmaniasis

Background: Visceral Leishmaniasis is a systemic disease caused by the invasion of reticuloendothelial cells in the liver, spleen, and bone marrow by Leishmania spp. parasites. Current medications have numerous adverse effects and some resistance has been reported. Most treatments are administered parenterally, leading to non-compliance and treatment failure. This study aimed to develop an oral formulation of quinine sulfate to address these challenges.Methods: Quinine sulfate was encapsulated in hydroxypropylmethylcellulose using the spray-drying method and evaluated for particle size, zeta potential, drug content, entrapment efficiency, and in vitro release properties. In the in vivo study, laboratory mice infected with L. donovani promastigotes were treated for two weeks.Results: The average size of the quinine sulfate microparticles ranged from 2.6 to 14.2 µm, with an entrapment efficiency of 93%. Oral formulations effectively cleared parasites from the organs.Conclusion: Orally administered quinine sulfate efficiently cleared parasites from the blood of infected mice and resolved infections in their organs.

Novel Pharmaceutical Interventions for Drug Targeting in Parkinson’s Disease

Parkinson's Disease (PD) presents as a neurodegenerative disorder characterized by a gradual decline in brain function, typically advancing slowly over time in most individuals. However, as the disease evolves and impacts the Gastrointestinal Tract (GIT), the window for effective treatment response often becomes narrower for many patients. Recent advancements in medical science have spurred improvements in drug delivery, primarily through the development of enhanced oral formulations or the exploration of alternative administration routes, such as intestinal infusion, transcutaneous delivery, and inhaled levodopa. Among the recent oral formulation breakthroughs is IPX066, a novel formulation combining immediate and extended-release Carbidopa-Levodopa (CD/LD). Another notable example is levodopa-carbidopa intestinal gel, an authorized treatment involving the direct infusion of LD/CD suspension into the brain. Concurrent investigations are assessing the effectiveness of the 'accordion pill' (AP09004), an Extended-release (ER) LD/CD mixture designed to retain within the GIT for an extended period. Additionally, other formulations in various stages of clinical trials include ND0612, a proprietary liquid formulation intended for the purpose of subcutaneous delivery using a compact patch-pump apparatus, and CVT-301, a levodopa aerosol solution distinguished by its prompt initiation of therapeutic effects. However, several other promising formulations, such as DM-1992 and XP21279, have been terminated. This study aimed to thoroughly examine the pharmacokinetics, clinical effectiveness, and possible adverse reactions linked to innovative medication formulations that are now accessible or being developed for treating PD.

Preparation, characterization, and in vitro cytogenotoxic evaluation of a novel dimenhydrinate-β-cyclodextrin inclusion complex.

Dimenhydrinate (DMH), used to alleviate motion sickness symptoms such as nausea, vomiting, dizziness, and vertigo, encounters limitations in oral pharmaceutical formulations due to its poor water solubility and bitter taste. Our research hypothesized that inclusion complexation with β-cyclodextrin (β-CD) might address these drawbacks while ensuring that the newly formed complexes exhibit no cytotoxic or genotoxic effects on peripheral blood mononuclear cells (PBMCs). Inclusion complexes were prepared using the kneading method and the solvent evaporation method. The phase solubility analysis, attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), and differential scanning calorimetry (DSC) were conducted to evaluate the complexation efficacy and stability constant of the new binary systems. The results demonstrated that both methods provided complete and efficient complexation. Cytogenotoxic analysis, including the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, alkaline comet assay, and cytokinesis-block micronucleus cytome (CBMN-cyt) assay, was conducted to assess the cytogenotoxic potential of DMH-β-CD inclusion complexes, a topic previously unexamined. No cytotoxic or genotoxic effects were observed within the concentration range of 36.36 to 109.09 ng/mL. Cell viability of treated PBMCs exceeded 85% for all tested concentrations. No significant increases in DNA strand breaks were observed at any dose, and tail intensity of all complexes remained lower or up to 2.2% higher than the negative control. Parameters indicating genotoxic effects, as well as cytotoxic and cytostatic potential in the CBMN-cyt assay, did not significantly differ from untreated controls. These results suggest that inclusion complexation with β-CD might be a safe and promising solution to overcome the limitations of poor solubility and unpleasant taste of DMH, potentially providing opportunities for new and improved oral pharmaceutical dosage forms.

Physicochemical and microbiological stability of 40mg/mL amiodarone hydrochloride oral suspension.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Amiodarone hydrochloride is an antiarrhythmic drug used to treat supraventricular tachycardia. However, there are currently no commercial pediatric forms available to treat young patients. Various oral formulations were previously reported in the literature, but the concentration was lower than the doses prescribed in clinical practice (a loading dose of 500mg/m2/day for 7-10 days followed by a maintenance dose of 250mg/m2/day). The objective of this study was to develop an oral liquid formulation of amiodarone hydrochloride at an optimal concentration for use in children and to evaluate its physicochemical and microbiological stability. No commercial suspension vehicle was used, allowing the choice of excipients. Compounding was performed using hydroxypropylmethylcellulose as thickener, potassium sorbate preservative, citric acid/sodium citrate buffer, sodium saccharin as a , and a strawberry flavoring agent. A concentration of 40mg/mL was selected based on a 5-year compilation of prescribed doses. Analyses performed were the following: visual and microscopic inspection, testing for antimicrobial preservation, osmolality and pH measurements, quantification of amiodarone hydrochloride by a stability-indicating liquid chromatography method, and a microbiological count. At least 95% of the initial amiodarone hydrochloride remained stable during the 60-day study period under refrigeration. All other tested parameters remained stable at 5 °C. A targeted log reduction of the microorganism inoculum by day 14 and no microbial growth by day 28 were demonstrated in the test for antimicrobial preservation. The stability of 40mg/mL amiodarone hydrochloride oral suspension was maintained under refrigeration for 60 days before opening bottles and for 1 month after opening bottles.

Cubosomes – A novel approach to taste masking using ibuprofen as a model drug

Taste masking of any pediatric oral formulation has always been a hurdle. Cubosomses, a type of lyotropic liquid crystal, have been used in this research to develop an oral formulation of ibuprofen. Ibuprofen cubosomes were prepared with glyceryl monooleate (GMO) and poloxamer 407 by high-pressure homogenization (HPH) technique. The formulation experiments were performed using a 2-level, 3-factor central composite design with drug loading, GMO concentration and HPH pressure as independent variables and vesicle size, entrapment efficiency and %drug content as the dependent variables. The most suitable ibuprofen cubosomes showed 94 nm vesicle size, −17.5 mV zeta potential, >75% drug content and >96% entrapment efficiency. The cubosomes released more than 80% of the drug within 2 hours. In vitro taste masking study showed significantly lower drug release than its bitterness threshold. An in vivo taste masking study in healthy adult volunteers showed significant taste masking compared to the marketed formulation and ibuprofen pure suspension. % of the volunteers observed cubosomes as not bitter. In contrast, 67% of the volunteers reported marketed suspension as very bitter. The developed cubosomes resulted in physical stability for three months of proper storage. The study has successfully achieved considerable taste-masking using cubosomes with GMO and Poloxmaer 407 formulation. This proof of concept can initiate a new field of research in taste-masked oral liquid formulation.

Amiodarone Therapy: Updated Practical Insights.

Amiodarone, a bi-iodinated benzofuran derivative, is among the most commonly used antiarrhythmic drugs due to its high level of effectiveness. Though initially categorized as a class III agent, amiodarone exhibits antiarrhythmic properties across all four classes of antiarrhythmic drugs. Amiodarone is highly effective in maintaining sinus rhythm in patients with paroxysmal atrial fibrillation while also playing a crucial role in preventing a range of ventricular arrhythmias. Amiodarone has a complex pharmacokinetic profile, characterized by a large volume of distribution and a long half-life, which can range from several weeks to months, resulting in prolonged effects even after discontinuation. Side effects may include thyroid dysfunction, pulmonary fibrosis, and hepatic injury, necessitating regular follow-ups. Additionally, amiodarone interacts with several drugs, including anticoagulants, which must be managed to prevent adverse effects. Therefore, a deep understanding of both oral and intravenous formulations, as well as proper dosage adjustments, is essential. The aim of this paper is to provide a comprehensive and updated review on amiodarone's indications, contraindications, recommended dosages, drug interactions, side effects, and monitoring protocols.

Maribavir use in pediatric immunocompromised hosts: A case series to talk about real-world experience

Abstract Background Cytomegalovirus (CMV) is a common infection affecting pediatric immunocompromised hosts. The treatment of CMV in solid organ (SOT) or hematopoietic stem cell transplant (HSCT) patients is challenged by the toxicities associated with antiviral therapies (myelosuppression with valganciclovir, ganciclovir and cidofovir; nephrotoxicity with foscarnet and cidofovir) and the prevalence of resistant/refractory CMV. Maribavir, a novel benzimidazole, competitively inhibits CMV UL97 protein kinase to inhibit DNA synthesis and block nuclear exit of viral particles from CMV-infected cells. It is FDA approved for use in patients at least 12 years of age and weighing at least 35 kg. The use of maribavir in pediatric patients is of interest due to its availability as an oral dosage formulation and improved side effect profile. To date, there are no pediatric case series or studies describing the use of maribavir for CMV treatment. Methods This study is a retrospective case series compiling the findings the first pediatric patients at Children’s National Hospital, DC that received maribavir. We included children who received maribavir from 01/2017 – 10/2023. Patients were included if they were on maribavir monotherapy, or combination therapy with additional anti-CMV agent(s). The medical records were reviewed for indication of medication use, viral response to therapy and side effects. Side-effects review specifically evaluated for increased LFTs, increased serum creatinine, and decreased absolute neutrophil count or factors that may contribute to early discontinuation of maribavir. Results (table) Maribavir was used in three male patients with varied conditions – including solid organ transplant (SOT), hematopoietic stem cell transplant (HSCT) and Severe Combined Immunodeficiency (SCID) s/p HSCT. Two cases had signs of CMV disease, and one had CMV viremia. All cases included documented CMV resistance (n=2) or refractory CMV (n=1) and had previously been receiving at least one antiviral with CMV activity for at least 14 days and had increasing CMV DNA-emia in the blood. None of the patients had side effects such as nephrotoxicity, liver toxicity or myelosuppression that aggravated after starting maribavir. Dosing of 400mg BID (range 12mg/kg/day to 55mg/kg/day) was used. Once started, maribavir was continued until CMV quantitative levels were undetectable for two weeks. Clearance of CMV and was achieved in all the patients on maribavir or combination of maribavir with other drugs (n=1). Duration of maribavir treatment ranged from 4.2 to 6.2 weeks. Conclusion This is the first case series describing use of maribavir in a pediatric population. In this small cohort maribavir is effective and well tolerated. Further studies are needed to better CMV care in children with immunocompromised conditions.

Budesonide – Oral Galenic Formulations for Crohn Disease

The aim of this work is to verify the pharmaceutical form in the galenic field of oral Budesonide compounded used in Crohn’s disease: capsules delay release or oral suspension. In particular ways the kinds of excipients or bases-vehicle used in the galenic pharmacy practice. The therapeutic need for Crohn’s disease requires a release of the API in delayed-release DR. The Budesonide molecule shows low systemic impacts due to its hepatic metabolism vs. a topical effect useful in this pathology. In this work, the oral pharmaceutical forms are analyzed: modified-release capsules and oral suspension with specific advantages for each one. Some formulations provided by various pharmacies are reported in this work as well as new technology like the 3D-PRINTING systems for colonic targeting tablets.

Analysis of prescriptive monitoring regarding the current therapeutic landscape of rheumatoid arthritis: the experience of an Italian local health authority

ABSTRACT Introduction Rheumatoid Arthritis (RA) is among the most prevalent chronic inflammatory diseases affecting millions of people with a significant expenditure of resources by National Healthcare Systems. This study aimed to analyze all available treatments exclusively for RA to highlight the costs of each treatment type and raise awareness of the use of biosimilar drugs. Methods In an Italian healthcare authority, all prescriptions made for the diagnosis of RA were extracted to verify consumption expressed in Defined Daily Dose (DDD) and the expenditure incurred expressed in euros. Consequently, a grouping into three major drug categories has been performed: anti – tumor necrosis factor alpha agents (TNFα), other injectable formulations, and novel oral formulations. Results Prescriptions for the second half-year 2022 and 2023 have been analyzed, with a total cost of almost 7 million euros in the sample considered. All pharmaceutical categories showed an increase in consumption, but only anti- TNFα recorded a decrease in costs from 25% in 2022 to 22% in 2023, thanks to the lower cost of the biosimilar drug. Conclusion The costs of RA may represent a significant spending commitment for central governments. As a result, actions are needed to encourage the preferential use of biosimilar drugs.

LAI antipsychotics: fewer adverse effects than oral formulation, less impact on functioning and disability

LAI antipsychotics: fewer adverse effects than oral formulation, less impact on functioning and disability

7966 Long-Term Safety and Efficacy of a Hydrocortisone Oral Granules in a Young Child with Congenital Adrenal Hypertrophy

Abstract Disclosure: M. Bertossi: None. C. Lowe: None. Q.L. Van Meter: Consulting Fee; Self; Eton Pharmaceuticals. Speaker; Self; Eton Pharmaceuticals. Introduction: Congenital adrenal hyperplasia (CAH) is the most common cause of pediatric adrenal insufficiency. Children diagnosed with CAH need exogenous glucocorticoid therapy throughout their lifetime. Because low dose hydrocortisone (HC) tablets are not available, patients and their caregivers must either split/crush hydrocortisone tablets or rely on HC that has been compounded from adult medications. In late 2020, a pediatric specific HC formulation, an oral granule, became available with doses as low as 0.5 mg. There are minimal data concerning the long-term use of this novel HC formulation. Subject and Method: This case study is a girl (DOB 11/2016) with CAH who has been administered the HC oral granule formulation for over 3 years. Results: The subject is a 7-year-old female who was diagnosed at birth with CAH. At an outside institution, she administered 6.25 mg HC, divided into three doses of 2.5 mg in the morning, 1.25 mg in the afternoon, and 2.5 mg in the evening (2.5/1.25/2.5; 9 mg/m2). She was also administered 0.15 mg fludrocortisone qd. Her dose was increased to a total dose of 7.5 mg, administered 2.5 mg three times/day (10 mg/m2) because of a high 17-OHP concentration, 1048 mg/dL. Other hormone levels were unremarkable. Her 17-OHP levels increased to 2662 mg/dL after 3 months of the increased dose. Because of the development of Cushing’s symptoms, she was switched to the 7.0 mg HC granules (2.5/2.0/2.5; 9.5 mg/m2 total dose). After the switch to the HC granules, her 17-OHP levels was 293 ng/dL. Because of rising 17-OHP levels, her dose needed to be increased twice over the past 2 yrs. Her current dose is 12 mg HC granules (4/4/4; 11 mg/m2 total dose), and her three most recent 17-OHP levels were 73, 101, and 89 ng/dL, respectively. She is also taking 0.2 mg fludrocortisone po, q am. Throughout HC granule therapy, she had no incidence of adrenal crisis. Her most recent calculated bone age was 8 yr 10 mo, with her chronological age was 6 yr, 8 mo with no evidence of virilization. Growth curves suggest that she is neither under- nor over-dosed on her HC therapy. Conclusion: This case may be the longest, continuous administration of the novel HC granules in US for a child with CAH. The results show the potential to better titrate HC dosing, especially with the narrow therapeutic window of HC in children with CAH. Her daily dose was adjusted by titrating in small increments to result in good outcomes, such as better hormonal control, the lack of virilization and continuous growth. Further evaluations of the long-term use of HC granules are needed to occur to establish the long-term risks and benefits of this novel HC granule. Presentation: 6/3/2024