Hematological Safety of Dipyrone Versus Paracetamol After Dental Extractions
Hematological Alterations Associated With the Use of Dipyrone Versus Paracetamol After Dental Extractions: a Double-blind, Randomized Clinical Trial
The goal of this clinical trial is to compare the safety of dipyrone and paracetamol when used for pain relief after dental extractions in adults. The study will focus on changes in blood cell counts and will also evaluate liver and kidney function and possible side effects. The main questions it aims to answer are:
- Do dipyrone and paracetamol have different effects on blood cell counts after dental extractions?
- Do participants exhibit hepatic and renal alterations?
- What side effects do participants experience when taking these medications?
Researchers will compare dipyrone and paracetamol to learn more about their safety after dental extractions.
Participants will:
- Undergo two dental extractions, one during each study period, involving teeth that already need to be removed
- Take dipyrone 500 mg or paracetamol 750 mg in a random order, taking two capsules every 6 hours for 7 days during each period
- Have at least 21 days between the two study periods
- Have three blood collections: one before the first extraction and one on the eighth day after each extraction
- Keep a diary of their pain, medication use, and possible side effects
- Have their blood pressure checked and attend clinic visits and telephone follow-ups to monitor their health
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Descripción detallada
Dental extractions are commonly followed by pain, and medications such as dipyrone and paracetamol are used to help relieve this pain. Although both medications are widely used, it is important to better understand their safety, particularly their possible effects on blood cell counts.
This clinical trial aims to compare the safety of dipyrone and paracetamol in adults undergoing dental extractions. The main focus is to evaluate changes in blood cell counts, including white blood cells, neutrophils, red blood cells, and platelets. The study will also assess blood tests related to liver and kidney function, changes in blood pressure and possible side effects during treatment.
Participants will undergo two dental extractions, one during each study period, involving teeth that already require removal. The order in which participants receive the medications will be determined randomly. During one study period, participants will receive dipyrone 500 mg per dose, and during the other, they will receive paracetamol 750 mg per dose. Each dose will consist of two capsules. The medications will be provided in identical capsules and will be prepared by a compounding pharmacy in Brazil, according to the study protocol. Neither participants nor researchers will know which medication is being used during each period. Each treatment period will last 7 days, with two capsules taken every 6 hours, according to the study protocol. The two study periods will be separated by at least 21 days.
Blood samples will be collected three times: before the first dental extraction and on the eighth day after each extraction. These tests will allow researchers to compare blood cell counts and other laboratory results before and after each medication period. Participants will also record their pain levels, medication use, and possible side effects in a diary. Blood pressure will be monitored, and clinical assessments and telephone contacts will be used to follow participants' health and identify possible adverse reactions.
By comparing the results obtained during the two treatment periods, researchers hope to improve understanding of the safety of dipyrone and paracetamol when used after dental extractions. The findings may contribute to evidence-based decisions about pain management following dental surgery.
Tipo de estudio
Tipo de estudio
Inscripción (Estimado)
Inscripción
Fase
Fase
- Fase 4
Contactos y Ubicaciones
Ubicaciones de estudio
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Minas Gerais
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Juiz de Fora, Minas Gerais, Brasil, 36036-900
- Reclutamiento
- Faculty of Dentistry at the Federal University of Juiz de Fora (UFJF)
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Contacto:
- Matheus F Carvalho, PhD
- Número de teléfono: + 55 (32) 98811-3967
- Correo electrónico: matheus.furtado@ufjf.br
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Contacto:
- Alice F Fernandes
- Número de teléfono: + 55 (32) 99863-3990
- Correo electrónico: aliceferreira.fernandes@estudante.ufjf.br
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Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Healthy patients of both sexes, aged 18 to 60 years
- Indication for bilateral tooth extraction in similar positions
Exclusion Criteria:
- History of allergy to dipyrone or paracetamol.
- Insufficient or improperly completed study records.
- Failure to return for the second tooth extraction.
- Use of warfarin, bupropion, efavirenz, methadone, cyclosporine, tacrolimus, sertraline, valproate, methotrexate, acetylsalicylic acid, or other non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, or corticosteroids on a continuous basis (for 7 days or longer) prior to surgery.
- Systemic conditions that could interfere with hematological outcomes, including diagnosed hematological disorders, coagulopathies, severe liver or kidney disease, or active autoimmune diseases at the time of the appointment.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Doble
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
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Experimental: Arm 1: Paracetamol followed by dipyrone
Participants receive paracetamol 750 mg per dose during the first treatment period, following the first dental extraction, and dipyrone 500 mg per dose during the second treatment period, following the second dental extraction, according to the randomized crossover sequence. Each treatment is administered as two capsules every 6 hours for 7 days, with a washout period between treatments. |
Dipyrone 500 mg per dose, administered orally as two capsules every 6 hours for 7 days following dental extraction, according to the study protocol. Paracetamol 750 mg per dose, administered orally as two capsules every 6 hours for 7 days following dental extraction, according to the study protocol Blood samples will be collected at three time points: before the first dental extraction, on the eighth day after the first treatment period, and on the eighth day after the second treatment period. |
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Experimental: Dipyrone followed by paracetamol
Participants receive dipyrone 500 mg per dose during the first treatment period, following the first dental extraction, and paracetamol 750 mg per dose during the second treatment period, following the second dental extraction, according to the randomized crossover sequence. Each treatment is administered as two capsules every 6 hours for 7 days, with a washout period between treatments. |
Dipyrone 500 mg per dose, administered orally as two capsules every 6 hours for 7 days following dental extraction, according to the study protocol. Paracetamol 750 mg per dose, administered orally as two capsules every 6 hours for 7 days following dental extraction, according to the study protocol Blood samples will be collected at three time points: before the first dental extraction, on the eighth day after the first treatment period, and on the eighth day after the second treatment period. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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White Blood Cell Parameters.
Periodo de tiempo: Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Total leukocyte count and neutrophil count will be assessed through blood samples and reported as cells/mm³, to evaluate changes following treatment with dipyrone and paracetamol after dental extractions. |
Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Hemoglobin Level.
Periodo de tiempo: Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Hemoglobin level will be assessed in blood samples, and reported as g/dL, to evaluate changes following treatment with dipyrone and paracetamol after dental extractions. |
Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Hematocrit.
Periodo de tiempo: Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Hematocrit will be assessed in blood samples, and reported as %, to evaluate changes following treatment with dipyrone and paracetamol after dental extractions. |
Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Platelet Count
Periodo de tiempo: Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Platelet count will be assessed in blood samples, and reported as cells/mm³, to evaluate changes following treatment with dipyrone and paracetamol after dental extractions. |
Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Changes in Liver Function Biomarkers.
Periodo de tiempo: Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase levels will be assessed through blood samples collected during the study, and reported as U/L. |
Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Changes in Kidney Function Biomarkers.
Periodo de tiempo: Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Changes in creatinine and urea levels will be assessed through blood samples collected during the study, and reported as mg/dL. |
Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Adverse Reactions.
Periodo de tiempo: Daily, from day 1 to day 7 after each dental extraction.
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Occurrence of adverse reactions associated with dipyrone and paracetamol will be monitored and recorded during each postoperative treatment period. |
Daily, from day 1 to day 7 after each dental extraction.
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Systolic Blood Pressure
Periodo de tiempo: Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Systolic blood pressure measurements will be recorded to evaluate changes during treatment with dipyrone and paracetamol after dental extractions, and reported as mmHg |
Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Diastolic Blood Pressure.
Periodo de tiempo: Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Diastolic blood pressure measurements will be recorded to evaluate changes during treatment with dipyrone and paracetamol after dental extractions, and reported as mmHg |
Before the first dental extraction, day 8 after the first dental extraction, and day 8 after the second dental extraction.
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Publicaciones y enlaces útiles
Publicaciones Generales
- Watkins PB, Kaplowitz N, Slattery JT, Colonese CR, Colucci SV, Stewart PW, Harris SC. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):87-93. doi: 10.1001/jama.296.1.87.
- Fidelis GFS, Dagli-Hernandez C, Martinelli RP, Marzuki JE, Baharuddin B, Yue QY, Edwards B, Pincinato EC, Moriel P. Pharmacogenetics of metamizole-induced agranulocytosis: a systematic review and drug regulation implications. Front Pharmacol. 2025 Sep 24;16:1624044. doi: 10.3389/fphar.2025.1624044. eCollection 2025.
- Zinzi A, Gaio M, Ruggiero D, Riccardi C, Cagnotta C, Pentella C, Capuano A, Rafaniello C. A systematic review and pharmacovigilance analysis of the risk of agranulocytosis associated with metamizole use. Sci Rep. 2025 Nov 28;15(1):42796. doi: 10.1038/s41598-025-27009-6.
- Tsang WH, Chan CK, Tse ML. Paracetamol-induced hepatotoxicity after normal therapeutic doses in the Hong Kong Chinese population. Hong Kong Med J. 2024 Oct;30(5):355-361. doi: 10.12809/hkmj2311194. Epub 2024 Oct 10.
- Blaser LS, Duthaler U, Bouitbir J, Leuppi-Taegtmeyer AB, Liakoni E, Dolf R, Mayr M, Drewe J, Krahenbuhl S, Haschke M. Comparative Effects of Metamizole (Dipyrone) and Naproxen on Renal Function and Prostacyclin Synthesis in Salt-Depleted Healthy Subjects - A Randomized Controlled Parallel Group Study. Front Pharmacol. 2021 Sep 7;12:620635. doi: 10.3389/fphar.2021.620635. eCollection 2021.
- Risks of agranulocytosis and aplastic anemia. A first report of their relation to drug use with special reference to analgesics. The International Agranulocytosis and Aplastic Anemia Study. JAMA. 1986 Oct 3;256(13):1749-57.
- ANDRADE, E. D. Terapêutica Medicamentosa em Odontologia. 2ª ed. São Paulo: Artes Médicas; 2006
- de Souza EC, Matos DM, Viana MR, Alvim MCO, Bonfante HL, Pinto AF, Nascimento JWL. Evaluation of hematological alterations after therapeutic use of dipyrone in healthy adults: a prospective study. J Basic Clin Physiol Pharmacol. 2018 Jul 26;29(4):385-390. doi: 10.1515/jbcpp-2017-0037.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Inicio del estudio
Finalización primaria (Estimado)
Finalización primaria
Finalización del estudio (Estimado)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Citopenia
- Trastornos de los leucocitos
- Enfermedades hematológicas
- Leucopenia
- Enfermedades hemic y linfáticas
- Agranulocitosis
- Químicos orgánicos
- Técnicas de investigación
- Manejo de muestras
- Técnicas de laboratorio clínico
- Técnicas y procedimientos de diagnóstico
- Diagnóstico
- Puntas
- Procedimientos quirúrgicos, operativo
- Aniluros
- Amidas
- Compuestos anilina
- Amina
- Acetanilidas
- Paracetamol
- Recolección de muestras de sangre
- Preparaciones farmacéuticas
Otros números de identificación del estudio
Otros números de identificación del estudio
- 97343326.1.0000.5147
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Individual participant data will not be shared with researchers outside the study team. Data access will be restricted to authorized researchers, and participant confidentiality will be protected through data coding, password-protected digital files, and restricted access to physical documents, in accordance with applicable data protection requirements.
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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