Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 53
Filtrar
1.
Br J Clin Pharmacol ; 90(1): 146-157, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37548054

RESUMEN

AIMS: Information on breastfeeding and safety of biologics in infants is lacking due to difficulties in case collection. We evaluated methods for determining the concentration of biologics in breast milk using a dry filter method that can simplify the collection, storage and transport of breast milk. METHODS: To generate dried filter paper (DFP) samples, approximately 30 µL of breast milk was placed onto a Whatman 903 card and punched out. After extraction, the supernatant was measured using an enzyme-linked immunosorbent assay. Three concentrations of each drug were prepared in liquid breast milk (LBM) and DFP samples to determine their stability up to 28 days after storage at 2-8°C or -20°C for LBM and 25 ± 5°C for DFP. LBM and DFP samples were also provided by nursing mothers using biologics during lactation, and drug concentrations in both samples were compared. The agreement between the two measurement methods was confirmed by Bland-Altman analysis. RESULTS: Breast milk was provided by 12 mothers who used biologics (tocilizumab, abatacept, etanercept, golimumab, sarilumab and belimumab). The coefficients of variation for within-run and between-run precision for the six drugs were within 15% for both LBM and DFP, and accuracy was within 90%-110% of the quality controls. After 28 days, concentrations remained at more than 90%. The difference between the values obtained by each method was within the acceptable range of error (-12.1 to +16.6 ng/mL). CONCLUSIONS: A method for determining the concentration of biologics using DFP is expected to help improve pharmacotherapy for lactating women.


Asunto(s)
Productos Biológicos , Leche Humana , Lactante , Femenino , Humanos , Lactancia , Ensayo de Inmunoadsorción Enzimática , Lactancia Materna
2.
Gynecol Endocrinol ; 38(6): 528-530, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35403531

RESUMEN

Safety information on diazoxide for pregnant and lactating women with hypoglycemia is limited. In this case report, we assessed diazoxide concentrations in maternal and infant blood, cord blood, and breast milk. We described a 30-year-old pregnant woman diagnosed with hypoglycemia due to nesidioblastosis at 4 months of age. Before becoming pregnant, she was treated with oral diazoxide (75-375 mg). All medications were discontinued after she was discovered to be pregnant. During gestational week 25, diazoxide treatment was resumed at 150-175 mg daily for repeated hypoglycemic episodes. Diazoxide administration was continued in combination with diet treatment until delivery. Glucose levels were well controlled. During gestational week 40, a male infant weighing 3069 g was delivered via spontaneous vaginal delivery with no pregnancy or neonatal complications. Diazoxide concentrations detected in maternal serum at 2.5-11.6 h after oral treatment ranged from 12.4 to 32.7 µg/mL. In cord blood, the diazoxide concentration was 18.5 µg/mL at 7.2 h after the last dose. During lactation, no hypoglycemia or hyperglycemia was observed. The approximate calculated ratio of diazoxide in breast milk and maternal serum was 0.09. The calculated daily infant dose was 0.47 mg/kg/day. The relative infant dose via breast milk ranged from 3.1% to 5.9%. Diazoxide transferred from maternal blood to the fetus across the placenta. It also transferred into breast milk, but there were no harmful effects on the infant.


Asunto(s)
Hipoglucemia , Leche Humana , Adulto , Diazóxido/farmacología , Diazóxido/uso terapéutico , Femenino , Sangre Fetal , Humanos , Lactante , Recién Nacido , Lactancia , Masculino , Embarazo
3.
J Clin Pharm Ther ; 47(5): 703-706, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34951046

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Statins are associated with improved pregnancy outcomes in patients with preeclamptic antiphospholipid syndrome (APS) and intrauterine foetal death. Several studies showed that statins are not teratogenic. However, data characterizing placental transfer and excretion of pravastatin into breast milk are limited. CASE SUMMARY: We experienced two patients diagnosed with APS received 10 mg of pravastatin from the first trimester until delivery to prevent pre-eclampsia. Pravastatin concentrations in maternal serum, infant serum and cord blood were evaluated. The estimated maternal-foetal transfer ratios of pravastatin in the two patients were 25.5% and 23.8% respectively. Pravastatin was eliminated from neonatal serum within 2 days. Both infants developed normally with no drug-related adverse effects. Pravastatin was not detected in either patient's breast milk at 3 days after the last dose. WHAT IS NEW AND CONCLUSION: The infants delivered from the mothers who were treated with pravastatin during pregnancy had no apparent adverse effects.


Asunto(s)
Síndrome Antifosfolípido , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Preeclampsia , Síndrome Antifosfolípido/tratamiento farmacológico , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lactante , Recién Nacido , Lactancia , Leche Humana , Placenta , Pravastatina/efectos adversos , Preeclampsia/tratamiento farmacológico , Embarazo , Cordón Umbilical
4.
Artículo en Inglés | MEDLINE | ID: mdl-33199385

RESUMEN

This study investigates the optimal meropenem (MEM) dosing regimen for critically ill pediatric patients, for which there is a lack of pharmacokinetic (PK) studies. We conducted a retrospective single-center PK and pharmacodynamic (PD) analysis of 34 pediatric intensive care unit patients who received MEM. Individual PK parameters were determined by a two-compartment analysis. The median (range) age and body weight were 1.4 (0.03 to 14.6) years and 8.9 (2.7 to 40.9) kg, respectively, and eight (23.5%) patients received continuous renal replacement therapy (CRRT), three of whom received extracorporeal membrane oxygenation. Renal function, the systemic inflammatory response syndrome (SIRS) score for the clearance (CL), and the use of CRRT for the central volume of distribution (Vc) were identified as significant covariates. The mean CL, Vc, and peripheral volume of distribution (Vp) were 0.45 liters/kg/h, 0.49 liters/kg, and 0.34 liters/kg, respectively. The mean population CL of MEM increased by 35% in patients with SIRS and Vc increased by 66% in patients on CRRT in the final model. Dosing simulations suggested that the standard dosing regimen provided insufficient PD exposures of a 100% free time above the MIC, and higher doses (40 to 80 mg/kg of body weight/dose every 8 h) with a prolonged 3-h infusion were required to ensure the appropriate PD exposures for patients with SIRS. Our PK model indicated that critically ill pediatric patients are at risk of subtherapeutic exposure under the standard dosing regimen of MEM. A larger, prospective investigation confirming the safety and efficacy of higher concentrations and prolonged infusion of MEM is necessary.


Asunto(s)
Antibacterianos , Enfermedad Crítica , Antibacterianos/uso terapéutico , Niño , Humanos , Meropenem , Estudios Prospectivos , Estudios Retrospectivos
5.
Pediatr Blood Cancer ; 68(8): e29069, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33881202

RESUMEN

BACKGROUND: Therapeutic drug monitoring for busulfan is important to prevent adverse events and improve outcomes in stem cell transplantation. We investigated intravenous busulfan pharmacokinetics and evaluated the utility of limited sampling strategy (LSS) as a simple method to estimate the area under the concentration-time curve (AUC). PROCEDURE: The study comprised 87 busulfan measurements in 54 children who received intravenous busulfan between August 2015 and May 2020. AUCs were calculated from three to five blood sampling points in each patient, and the correlation between AUC and plasma concentrations (ng/mL) at 1, 2, 3, 4, and 6 h after initiating busulfan infusion (C1 , C2 , C3 , C4 , and C6 , respectively). RESULTS: By one-point sampling strategy, the most relevant predicted AUC was based on C6 (r2  = 0.789; precision, 11.0%) in all patients. The predicted AUC based on C6 was acceptable (r2  = 0.937; precision, 5.9%) for adolescent patients weighing >23 kg, but the correlation was poor in infants and young children weighing ≤ 23 kg (r2  = 0.782; precision, 11.4%). By two-point sampling strategy, the predicted AUC based on C3 and C6 showed the most relevant concentrations (r2  = 0.943; precision, 6.4%), even in infants and young children, whereas the predicted AUC based on C3 and C6 was acceptable (r2  = 0.963; precision, 5.7%). CONCLUSIONS: The AUC of busulfan can be predicted based on C6 in adolescent patients. However, there was substantial interindividual variation in busulfan pharmacokinetics in infants and young children, in whom two-point LSS was necessary for accurate AUC prediction.


Asunto(s)
Busulfano , Monitoreo de Drogas , Trasplante de Células Madre Hematopoyéticas , Adolescente , Área Bajo la Curva , Busulfano/farmacocinética , Preescolar , Humanos , Lactante , Flebotomía
6.
Pediatr Transplant ; 24(1): e13619, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31820535

RESUMEN

BACKGROUND: Understanding of TAC pharmacokinetics is required to avoid both overdosing and underdosing. VRCZ is known to increase the TAC blood concentration by inhibiting CYP3A4; however, detailed, practical information on pediatric cases is still scarce. Herein, we investigated the association between the TAC blood concentration and dosage focusing on the administration route and concomitant use of VRCZ in children. METHODS: In total, 38 children who received TAC during stem cell transplantation at our hospital between January 2013 and April 2018 were included. The ratio of the TAC blood concentration (ng/mL) to dosage (mg/kg/day) (C/D) was calculated at the last continuous intravenous infusion (C/Div) and after switching to oral administration (C/Dpo). RESULTS: Patients with VRCZ (n = 14) showed a higher C/D regardless of administration route (median C/Div: with VRCZ/without VRCZ = 832/643, median C/Dpo: with VRCZ/without VRCZ = 339/45). Additionally, the (C/Div)/(C/Dpo) was about one-fourth in cases with VRCZ; the median (C/Div)/(C/Dpo) was 3.3 for cases with VRCZ and 13.5 for cases without VRCZ. Interestingly, the increase in the TAC blood concentration due to VRCZ was higher when TAC was administered orally, especially in adolescent patients. CONCLUSIONS: To obtain an optimal TAC blood concentration, dose adjustment based on multiple factors, such as administration route, concomitant use of VRCZ, and age, is required.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Inmunosupresores/administración & dosificación , Inmunosupresores/farmacocinética , Tacrolimus/administración & dosificación , Tacrolimus/farmacocinética , Voriconazol/administración & dosificación , Voriconazol/farmacocinética , Administración Oral , Adolescente , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Femenino , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/sangre , Inmunosupresores/uso terapéutico , Lactante , Infusiones Intravenosas , Modelos Lineales , Masculino , Estudios Retrospectivos , Tacrolimus/sangre , Tacrolimus/uso terapéutico , Voriconazol/sangre , Voriconazol/uso terapéutico
12.
Ther Innov Regul Sci ; 58(2): 316-335, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38055156

RESUMEN

INTRODUCTION: Potentially harmful excipients (PHEs) for children have been reported and the need for information collection has been advocated. However, studies on the actual occurrence of adverse events are limited. This study investigated the quantitative exposure of PHEs via injection and their association with adverse events in children under 2 years of age. MATERIALS AND METHODS: As a single-center observational study, children aged 0-23 months received injectable drugs from April 1, 2018, to March 31, 2023 were included. Information on PHE exposure and adverse events after administration were extracted from medical records. Sodium benzoate, benzyl alcohol, ethanol, glycerol, lactose, polyethylene glycol paraben, polysorbate, propylene glycol, sorbitol, sucrose, sulfite, and thimerosal were selected as PHEs. RESULTS AND DISCUSSION: 6265 cases, 333,694 prescriptions, and 368 drugs (264 ingredients) were analyzed. The median age was 0.63 years (interquartile range [IQR] 0.1-1.1). 72,133 prescriptions, 132 drugs and 99 ingredients contained PHE; 2,961 cases exposed to PHE and 1825 cases exceeding permitted daily exposure. The drug with the highest number of exposure cases was hydroxyzine, and the highest number of prescriptions was heparin (both drugs contain benzyl alcohol). In association between adverse events and PHE exposure, higher doses in cases of adverse event occurrence were found in benzyl alcohol, glycerol, polyethylene glycol, and polysorbate exposed cases. Among thimerosal-exposed cases, "developmental delay" was more frequent in exposed cases, but the causal relationship was unknown. Further investigation is needed to clarify the relationship between adverse events and PHE exposure. Additionally, more precise information on PDE for pediatrics including neonates is necessary.


Asunto(s)
Excipientes , Polisorbatos , Humanos , Recién Nacido , Niño , Lactante , Excipientes/efectos adversos , Excipientes/análisis , Preparaciones Farmacéuticas , Polisorbatos/efectos adversos , Glicerol/efectos adversos , Timerosal , Polietilenglicoles , Alcoholes Bencílicos
13.
Children (Basel) ; 11(2)2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38397263

RESUMEN

In Japan, pivoxil-conjugated antibodies (PVs) are commonly used to treat infections. However, carnitine deficiency is a known adverse drug reaction associated with PV treatment. This study aimed to research the practical use of PV and assess the risk of carnitine deficiency in patients receiving PV compared to their amoxicillin (AM)-treated counterparts. The Pediatric Medical Information Collection System (P-MICS) served as the data source for this study. The study cohort comprised patients aged 0-15 years prescribed PV between April 2016 and March 2021. Data on the actual PV prescriptions were extracted for each patient. To evaluate the risk of carnitine deficiency, adverse events (AEs) were defined as carnitine deficiency and its associated symptoms. Propensity score matching was employed to compare the AE incidence between the PV and AM groups. The number of cases of PV prescriptions decreased year-on-year between 2016 and 2021, and >80% of prescriptions were dispensed in the clinic. The propensity score matching analysis demonstrated no statistically significant difference in the incidence of carnitine deficiency and its associated symptoms between the PV and AM groups. Our findings suggest that the risk of carnitine deficiency in children treated with PV is not significantly higher than that associated with other antibiotics.

14.
Pediatr Infect Dis J ; 42(8): e298-e303, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37343212

RESUMEN

The development of antibiotics that are acceptable and easy for children to take and use is highly desirable. As advocated by the World Health Organization, solid oral formulations with excellent shelf-life, taste masking and dose adjustment are attracting attention as appropriate pediatric oral antimicrobial formulations, but liquid formulations remain the most common worldwide. Apparently unique to Japan, the most common formulations of oral antimicrobials for pediatric use are dispensed as a powder with most being flavored powders. Powdered formulations are packaged in single doses, which eliminates the need for parents to weigh them before administration and may reduce the possibility of dosage errors. On the other hand, there are some formulations that require large doses of powder due to inappropriate concentrations, granular formulations that have a rough texture that affects palatability, and some formulations that require flavoring agents to mask the bitter taste of the main drug. Such inappropriate formulations have a significant impact on adherence to antimicrobial therapy. It remains unclear whether solid oral dosage forms might be as acceptable worldwide as in Japan. To ensure that appropriate antimicrobials are delivered to children worldwide, a direction for the development of appropriate dosage forms in children needs to be established.


Asunto(s)
Antiinfecciosos , Aromatizantes , Niño , Humanos , Composición de Medicamentos , Polvos , Administración Oral , Japón , Antiinfecciosos/uso terapéutico
15.
Children (Basel) ; 10(7)2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37508687

RESUMEN

The quality-assured preparation of crushed and diluted preparations for children is a challenge. In this study, a multicenter study was conducted to validate the preparation method for the quality assurance of baclofen powder, clonidine powder, and hydrocortisone powder prepared from tablets according to a previously established method. In-hospital preparations were prepared at five medical facilities under different crushing and mixing conditions. After storage in closed bottles, in-use bottles, and laminated paper for 120 days, ingredients stability, drug elution, and content uniformity after packaging were evaluated. All three ingredients were maintained at between 90% and 110% of their initial content for 120 days under packaging conditions of 25 ± 2 °C and 60 ± 5% relative humidity, with no change in dissolution in all formulations made at all five facilities. The content uniformity was also acceptable. The established method may contribute to quality-assured pediatric dosage form modification.

16.
Ther Innov Regul Sci ; 56(2): 301-312, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35088393

RESUMEN

BACKGROUND: Powders for oral solutions and suspensions (POS) are commonly used as pediatric oral medicines worldwide, except for Japan. Although global pediatric formulation development accelerates POS importation to Japan without any formulation change, oral solid multiparticulates remain to be the preferred pediatric forms in the country. This study aimed to evaluate the acceptance situation of four typical POS form products (mycophenolate mofetil, sildenafil citrate, valganciclovir hydrochloride, and voriconazole) that were recently approved in Japan. METHODS: A questionnaire on four products was completed by pharmacists in 29 children's hospitals with more than 100 beds each, between November and December of 2019. The questionnaire has six items on (#1) type of institution, (#2) formulary status, (#3) dispensing practice, (#4) reasons why POS form(s) were not selected as hospital formulary, (#5) advantages and disadvantages of POS form, and (#6) opinions for POS form. RESULTS: Of the 29 institutions, 7 (24%), 9 (31%), 4 (13%), and 10 (34%) institutions used POS of mycophenolate mofetil, sildenafil citrate, valganciclovir hydrochloride, and voriconazole, respectively. Reasons for not using these products were dispensed drug loss, formulation issues, and management issues in the pharmaceutical department and pediatric ward. Pharmacists preferred drug compounding such as tablet crushing and capsule opening to POS form use. CONCLUSIONS: POS forms might be an unsuitable formulation for the current hospital settings in Japan. Thus, appropriate dosage forms that reflect the current clinical settings are necessary.


Asunto(s)
Farmacéuticos , Administración Oral , Niño , Humanos , Japón , Polvos , Encuestas y Cuestionarios , Suspensiones
17.
Children (Basel) ; 9(2)2022 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-35204916

RESUMEN

Administration devices are crucial for the correct dosing of medicines to children. In countries outside Japan, oral droppers and syringes are reported to be preferred for the administration of oral liquid medicines to neonates and infants, whilst spoons and cups are more frequently used for older children. However, in Japan the majority of oral medicines are powders and the use of dosing devices in each pediatric age group is not well known. This study was performed as an observational anonymous questionnaire survey on devices for oral medicines in children aged 10 to less than 18 years and parents/caregivers on behalf of children aged from birth to less than 18 years. The results from 336 respondents showed that powders were most frequently prescribed in children aged less than 10 years old followed by liquids. Unlike previous reports, droppers were most frequently used in patients less than 12 months old, while household spoons were most frequently used in older children. Oral syringes were perceived as easy to use, which was in line with previous studies. Further cross-regional multi-countries study for establishment the guidelines on the choice of device will be needed.

18.
Children (Basel) ; 9(9)2022 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-36138622

RESUMEN

Baclofen is used as a skeletal muscle relaxant for multiple sclerosis patients and pediatric patients with cerebral palsy and is prescribed to pediatric patients at 0.3 to 1.0 mg/kg/dose. Baclofen tablets, an oral drug, are usually administered as a powder in pediatric wards after a formulation change by the pharmacist. However, there is no information about stability and assurance of quality for compounded products. The purpose of this study was to design a 10 mg/g oral powder of baclofen and to investigate the stability and changes in the physical properties of this compounded product. A 10 mg/g baclofen powder was prepared by adding extra-fine crystal lactose hydrate to crushed and filtrated baclofen tablets and was stored in a polycarbonate amber bottle with desiccant or in a coated paper laminated with cellophane and polyethylene. The stability of baclofen at 25 ± 2 °C/60 ± 5%RH was tested for 120 days in 'bottle (closed)', 'bottle (in use)', and 'laminated' storage conditions. Baclofen concentrations ranged from 90.0% to 110.0% of the initial concentration under all storage conditions. No crystallographic or dissolution changes were observed after storage. This information can help with the management of baclofen compounded powder in pharmacies.

19.
J Clin Psychiatry ; 83(4)2022 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-35687862

RESUMEN

Objective: To investigate the risk of major congenital malformations associated with exposure to second-generation antipsychotics (SGAs) in the first trimester.Methods: Pregnant women who received consultation on drug exposure from the Japan Drug Information Institute in Pregnancy from October 2005 to December 2016 were asked to complete a questionnaire at 1 month after the expected delivery date. The questionnaire included items on pregnancy outcome, date of delivery, gestational age at delivery, malformations in the infant that were confirmed by the pediatrician's report, and the following parameters at birth: height, weight, head circumference, and chest circumference. Odds ratios (ORs) for major congenital malformations among live-born children of pregnant women with SGA exposure during the first trimester (SGA group) relative to children of women not exposed to SGAs and medications known to be teratogenic (comparison group) were estimated using an inverse probability of treatment weighting approach.Results: Of 404 women with SGA exposure during the first trimester, there were 351 live births, 3 stillbirths, 34 spontaneous abortions, and 16 elective abortions. The rate of major congenital malformations among live-born children was 0.9% (3/351) in the SGA group and 1.8% (70/3,899) in the comparison group. No statistically significant differences were observed in the adjusted OR for major congenital malformations (adjusted OR = 0.44; 95% CI, 0.12-1.48; P = .179).Conclusions: SGA exposure during the first trimester is not associated with an increased risk of major congenital malformations. These findings might be reassuring for pregnant women who require SGAs.


Asunto(s)
Anomalías Inducidas por Medicamentos , Aborto Espontáneo , Antipsicóticos , Anomalías Inducidas por Medicamentos/epidemiología , Anomalías Inducidas por Medicamentos/etiología , Aborto Espontáneo/inducido químicamente , Aborto Espontáneo/epidemiología , Antipsicóticos/efectos adversos , Niño , Femenino , Humanos , Recién Nacido , Embarazo , Resultado del Embarazo/epidemiología , Primer Trimestre del Embarazo
20.
J Pharm Health Care Sci ; 8(1): 18, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35773736

RESUMEN

BACKGROUND: Patients with ulcerative colitis (UC) may be concerned about medication safety during preconception, pregnancy, and lactation, and they should be closely followed up to ensure that UC activity is controlled during the perinatal period. Reported information on the safety of ustekinumab during pregnancy and lactation is limited. In this case report, we examined the safety of ustekinumab in a fetus and breastfed infant with reference to drug concentrations in maternal serum, cord blood, breast milk, and infant serum. CASE PRESENTATION: A 36-year-old female who developed hematochezia and was diagnosed with ulcerative colitis at age 24 was pregnant with her first child. During pregnancy she was treated with subcutaneous bimonthly ustekinumab, at a dose of 90 mg, until 29 weeks of gestation. Her ulcerative colitis symptoms remained in remission. At 38 weeks of gestation she underwent cesarean section and delivered a healthy female infant weighing 3043 g and with no congenital malformations. The infant received routine vaccinations with no adverse events. Ustekinumab treatment was resumed at 7 weeks postpartum. The ustekinumab concentration in maternal serum at 12 days after injection (30.7 weeks of gestation) was 7968.5 ng/mL, and it decreased to 106.1 ng/mL at 114 days after the last dose. In cord blood, the ustekinumab concentration was 1131.2 ng/mL at 65 days after the last dose; this was 2.5 times higher than that in the maternal serum, which was consistent with a previous report. Ustekinumab was detected in infant serum collected at 71 days after the last maternal dose (299.0 ng/mL), with rapid elimination from the infant's body. In breast milk, the maximum ustekinumab concentrations were 13.6 ng/mL at 9 days after the last maternal dose, respectively. The ratio of the calculated areas under the time-concentration curves of ustekinumab in breast milk and maternal serum was 0.0008 (257.1/327632.7), which was comparable with a previous human study. CONCLUSION: The placental transfer and breast milk secretion of ustekinumab in our case were comparable with previous reports. Use of ustekinumab during pregnancy and lactation was feasible in this case. Further research is needed to clarify the safety of ustekinumab during pregnancy and lactation.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA