Oral anticancer drugs: To crush or not to crush

Tine Van Nieuwenhuyse, Birgit Tans, David Devolder, Isabel Spriet.

Hospital Pharmacy Department, UZ Leuven, Leuven, Belgium. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium 

Objective/purpose: Healthcare professionals, involved in the daily care of cancer patients, are faced with the growing issue using oral anticancer drugs in patients experiencing swallowing difficulties. The lack of commercially available oral liquid dosing forms might compromise initiating or prolonging necessary therapies in this patient population. Pharmacists are often challenged to provide liquid alternatives for oral drugs that have solely been made commercially as a solid formulation; therefore, it is common practice to crush tablets or to prepare oral liquids from solid forms. When preparing liquids ex tempore, a number of requirements need to be fulfilled. In addition to chemical, physical and microbiological stability of the active ingredients, therapeutic and toxicological aspects should be the subject of review. The goal was to develop a guide for healthcare providers in order to assist them in providing scientific and up-to-date information for patients who are in need of special dosing forms.

Study design/methods: A literature search in PubMed/Medline was conducted. Also, the registration documents and relevant phase I and II data from the pharmaceutical industry, U.S. Food and Drug Administration and European Medicines Agency were used as a source of information. 

Results/key findings: An overview for healthcare providers was drafted. Sixty-two oral anticancer drugs that were available on the Belgian market at the moment of the development were included. 

Conclusion/recommendations: The development of a pocket guideline has increased the awareness and will be added to the standard of care as to improve safe medication use in patients with swallowing difficulties.

Selected abstracts presented at the XVI Symposium of the International Society of Oncology Pharmacy Practitioners April 26-29, 2017, Budapest, Hungary

J Oncol Pharm Practice 2017, Vol. 23 4(Supplement) 1–21.

Pseudocelulitis recurrente inducida por gemcitabina: descripción de un caso.

CALPE ARMERO P1, ESQUERDO GALIANA G1, PEIRÓ SOLERA R1, MARTÍNEZ TÉBAR MJ2

1 Hospital Clínica Benidorm. Alicante (España) 2 Hospital General de Elche. Alicante (España)

RESUMEN Introducción: Gemcitabina es un agente antineoplásico usado en el tratamiento de un gran número de neoplasias malignas. Está asociado frecuentemente a reacciones adversas cutáneas como prurito, rush o alopecia. Menos frecuentemente, se ha visto asociado a un cuadro llamado “pseudocelulitis”. En este estudio presentamos un caso de un paciente con pseudocelulitis recurrente tras tratamiento con gemcitabina. Descripción del caso: Paciente oncológico, con historia pasada de linfedema en miembros inferiores acude a consulta por cuadros recurrentes de celulitis en miembro inferior homolateral al brazo de infusión del fármaco gemcitabina. El paciente no presenta fiebre. Presenta eritema bien delimitado, edema con fóvea, caliente y con dolor a la palpación. En la analítica se obtienen valores normales, y no se observa evidencia de trombosis venosa profunda. Basado en los hallazgos clínicos, naturaleza aguda y recurrente de la patología, se llegó, por descarte, a un diagnóstico de pseudocelulitis inducida por gemcitabina. El cuadro fue tratado con antihistamínicos y antiinflamatorios no esteroideos. Al final del seguimiento, el paciente presentaba una notoria mejoría de los síntomas. Conclusión: En pacientes tratados con gemcitabina, que presenten episodios de celulitis, es importante establecer clínica y analíticamente, si se trata o no de una celulitis infecciosa. Ya que, de tratarse de un cuadro de pseudocelulitis, el tratamiento no se compone de antibióticos y el periodo de hospitalización será menor. 

Palabras clave: Pseudocelulitis, gemcitabina, adenocarcinoma de páncreas, celulitis, reacción adversa. 

SUMMARY Introduction: Gemcitabine is an antineoplastic agent used in the treatment of a large number of malignant neoplasms. It is frequently associated with adverse skin reactions such as pruritus, rush or alopecia. Less frequently, it has been associated with a condition called "pseudocellulitis". In this study, we present a case of a patient with recurrent pseudocellulitis after treatment with gemcitabine. Case description: Oncological patient, he had history of lymphedema in the lower extremity, is referred to consultation with complaint of recurrent cellulitis in the homolateral lower extremity from the infusion arm of gemcitabine. The patient does not have fever. It presents well-defined erythema, pitting edema, warmth and tenderness to palpation. Analytical values were normal, and evidence of deep vein thrombosis is not observed. Based on the clinical findings, acute and recurrent nature of the pathology, a diagnosis of pseudocellulitis induced by gemcitabine was reached. The patient was treated with antihistamines and nonesteroideal anti-inflammatory. At the end of the follow-up, the patient showed a marked improvement in symptoms. Conclusion: In patients treated with gemcitabine, who present episodes of cellulitis, it is important to establish clinically and analytically, whether or not it is an infectious cellulitis. Since it is a case of pseudocellulitis, the treatment is not composed of antibiotics and the period of hospitalization will be shorter. Recurrent gemcitabine-induced pseudocellulitis: a case report 

Key Words: Pseudocellulitis, gemcitabine, pancreas adenocarcinoma, cellulitis, adverse event.

Referência: Rev. OFIL·ILAPHAR 2020, 30;2:150-151

Miastenia gravis secundaria a pembrolizumab

MINARDI EP

Servicio de Farmacia Ambulatoria. Hospital Italiano de Buenos Aires y Depto. Farmacología y Toxicología. Instituto Universitario del Hospital Italiano. Buenos Aires (Argentina).

RESUMEN En los últimos años el avance de terapias dirigidas para tratamiento de enfermedades oncológicas ha ido en aumento exponencial. En este contexto, un nuevo grupo de anticuerpos monoclonales, que inhiben el receptor de muerte celular programada 1 han surgido como una efectiva primera línea de tratamiento para determinadas neoplasias. Pembrolizumab, un anticuerpo monoclonal humanizado, es una opción estándar para el tratamiento de enfermedades malignas avanzadas o metastásicas tales como mieloma múltiple pero, en lo que a seguridad respecta, investigaciones clínicas han descubierto diversos, impredecibles y graves eventos adversos relacionados con el sistema inmunológico. Se describe caso de un paciente oncológico con sospecha de miastenia gravis luego de haber recibido pembrolizumab 200 mg cada 3 semanas. 

Palabras clave: Miastenia gravis, pembrolizumab, receptor de muerte celular programada 1.

SUMMARY In recent years the development of anti-cancer target drugs therapy has been increasing exponentially. In this context, a monoclonal antibody group’s which inhibits the programmed cell death 1 receptor, has emerged as an effective frontline of treatment of certain neoplasms. Pembrolizumab, a humanized monoclonal antibody, is a standard option for the treatment of advanced and metastatic malignancies like multiple myeloma. However, clinical research has uncovered diverse, unpredictable and serious immune related adverse events that raise concerns regarding it's safety. Here we describe the case of an oncology patient with a suspected myasthenia gravis after receiving pembrolizumab 200 mg every 3 weeks. Miastenia gravis secondary to pembrolizumab Key Words: Myasthenia gravis, pembrolizumab, programmed cell death 1 receptor.

Referência: Revista OFIL·ILAPHAR 2020, 30;2:145-146

Defesa de TCR por Maihara Borges: Incidência e caracterização das reações adversas imediatas e tardias à infusão de QT em pacientes ambulatoriais de um hospital sentinela

Cytarabine ears – A side effect of cytarabine therapy

Divya Doval , Sanjeev Kumar Sharma, Meet Kumar, Vipin Khandelwal and Dharma Choudhary

Divya Doval, Department of Hematooncology and BMT, BLK Superspeciality Hospital, New Delhi 110005, India.

Email: divyadoval@yahoo.co.uk

Abstract Cytarabine, a pyramidine analog, is used for treating various hematological malignancies such as acute leukemias and lymphomas. Side effects of cytarabine are dose dependent and include bone marrow suppression, fever, cerebellar toxicity, cardiomyopathy, hepato-renal insufficiency, necrotizing enterocolitis, pancreatitis, acute respiratory distress, corneal toxicity and dermatological side effects. The dermatological side effects can be immediate or due to delayed hypersensitivity reactions. They have been attributed largely to release of cytokines. We present three such cases of delayed hypersensitivity to cytarabine affecting the ears bilaterally.

Case report

Case 1 A 41-year-old female, a case of acute myeloid leukemia (intermediate risk), was treated with 7+ 3 induction chemotherapy (cytarabine 100 mg/m2 for seven days by continuous infusion along with daunorubicin 60 mg/m2 for three days). On day 6 of chemotherapy, she developed erythema over one ear not associated with pain or itching (Figure 1), which subsequently spread to both ears, sparing of all other areas of face and body. She did not have any associated fever. 

Case 2 A 60-year-old lady was diagnosed to have acute myeloid leukemia (low risk). She was treated with 7+ 3 induction chemotherapy (cytarabine 100 mg/m2 for seven days twice daily along with daunorubicin 60 mg/m2 for three days). On day 8 of chemotherapy (few hours after the last dose), she developed erythema over both ears with associated itching and mild burning pain (Figure 2). There was no associated fever.

Case 3 A 42-year-old lady with acute myeloid leukemia received 7+3 induction (cytarabine 100 mg/m2 for seven days by continuous infusion along with daunorubicin 60 mg/m2 for three days). On day 7, she developed an erythematous rash on bilateral ear lobes associated with pain and itching.

Management and outcome 

Case 1 The patient subsequently developed neutropenic fever and was treated with broad spectrum antibiotics. Her repeat blood and urine cultures were sterile. The rash started reducing 48 h after cessation of chemotherapy and completely resolved within five days. 

Case 2 The rash and itching were treated with oral fexofenadine and resolved completely over next 72 h. This patient was re-challenged with high-dose cytarabine in the consolidation phase of her chemotherapy without recurrence of any dermatologic manifestations. 

Case 3 This patient was treated with topical hydrocortisone 1% ointment and oral analgesics. The rash turned to bluish purple by day 12 and then subsequently resolved by day 15. This study was approved by the hospital ethics committee and informed consent from patients was taken.

Discussion 

Cytarabine can cause various types of skin reactions. The typical cytarabine-induced skin rash develops 6– 12 h after the drug is started and resolves with cessation of therapy. Incidence of the cytarabine-induced systemic rash varies between 3 and 72% and is more commonly seen in patients receiving high doses of cytarabine.1 The generalized rash has also been reported with low doses and in both adults and children.1,2 It may manifest as maculopapular or morbilliform rash or as hand–foot syndrome, which presents as erythema of palms and soles, associated with pain, tingling and paresthesia, or it may involve trunk and extremities. Isolated involvement of ears has rarely been reported, with only nine cases reported.

J Oncol Pharm Practice 2020, Vol. 26(2) 471–473

Comparación de las guías NCCN, ESMO y SEOM de 2016 para la prevención de las náuseas y vómitos por quimioterapia

Gutiérrez Lorenzo M., Mora Rodríguez B., Henares López A., Muñoz Castillo I.

Hospital Regional de Málaga

Objetivo: El propósito de este estudio es determinar si las guías más usadas en España difieren en sus recomendaciones con el fin de optimizar la profilaxis de uno de los efectos adversos más preocupantes de la quimioterapia en nuestro sistema de salud: las náuseas y vómitos inducidos por los antineoplásicos.

Material y métodos: Se analizaron las recomendaciones de las guías: Nacional Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO) y Sociedad Española de Oncología Médica (SEOM) publicadas en el año 2016 para la prevención de la emesis por quimioterapia. Se elabora una base de datos tanto de los antineoplásicos parenterales como de los orales para identificar las diferencias en los siguientes puntos: número de niveles de riesgo emetógeno, número total de agentes antineoplásicos incluidos, número de agentes antineoplásicos que aparecen sólo en una de las guías, número de antineoplásicos que se clasifican en niveles de riesgo emetógeno distintos, número de agentes que se clasifican diferente dependiendo de la dosis que se prescriba, recomendaciones de la profilaxis a usar según los niveles de riesgo.

Resultados: Los principales puntos de discrepancia entre las clasificaciones de las guías ESMO y SEOM con respecto a la guía NCCN son los siguientes: En cuanto a los agentes antineoplásicos orales, la NCCN divide en 2 los niveles de riesgo de producir naúseas y vómitos: riesgo de moderado a alto y de mínimo a bajo; la ESMO y la SEOM hacen más distinción, dividen en 4 niveles (alto, moderado, bajo y mínimo). Sin embargo, las tres guías dividen en los mismos 4 niveles el riesgo emetógeno de los agentes antineoplásicos parenterales. En total, en la NCCN se observan 97 agentes antineoplásicos parenterales, de los cuales 53 (54.6%) y 27 (27,8%) no aparecen en la guía SEOM y ESMO respectivamente. También se compararon un total de 62 agentes antineoplásicos orales, de los que 48 (77.4%) y 22 (35.5%) no aparecen en la guía SEOM y ESMO respectivamente. Observamos también que del total de agentes parenterales 11 (11.3%) y 4 (4.1%) estaban clasificados en distintos niveles de riesgo emetógeno en la NCCN frente a la ESMO y a la SEOM, respectivamente.  Además, en la NCCN hay distinción en el riesgo de emesis dependiendo del rango de dosis en 8 antineoplásicos, mientras que en la SEOM Y ESMO sólo en 2 agentes. Por otra parte, en cuanto a los agentes profilácticos recomendados según los niveles de riesgo no hay discordancias significativas. 

Conclusiones: Aunque existen varios puntos de discrepancia entre las directrices de la ESMO, la SEOM y la NCCN, sobre todo en la clasificación, podemos concluir que hay una concordancia sustancial. La aplicación de estas recomendaciones a la práctica diaria nos permite periódicamente actualizar actualizar nuestro protocolo para minimizar la toxicidad emetógena de los tratamientos antineoplásicos.  Como tal, las guías están destinadas a ser novedosas, herramientas de alta calidad, lógicas, prácticas y útiles para el clínico. La meta es la optimización de la calidad de vida del paciente con el uso racional de los medios.

Referências: Anais do 14º CONGRESO SAFH SEVILLA 2017 - Sociedad Andaluza de Farmaceúticos de Hospitales y Centros Sociosanitarios.

Oseltamivir combined with HIV drugs lopinavir and ritonavir the medications improved conditions in patients with severe 2019-nCoV infections

A combination of flu and HIV medications may be able to treat severe cases of 2019-nCoV, the new coronavirus that has emerged in China, according to doctors in Thailand who have been caring for infected patients. The team’s approach, which used large doses of the flu drug Oseltamivir combined with HIV drugs lopinavir and ritonavir, improved the conditions of several patients at the Rajavithi Hospital in Bangkok.

“This is not the cure, but the patient’s condition has vastly improved,” Rajavithi Hospital’s Kriangsak Atipornwanich says of one 70-year-old Chinese woman from Wuhan, according to Reuters. “From testing positive for 10 days under our care, after applying this combination of medicine the test result became negative within 48 hours.”

Thailand has so far recorded 19 cases of coronavirus, Reuters reports, making it the country with the greatest number of infections in Southeast Asia. Eight patients have recovered, while the rest are still undergoing treatment. Officials say that the country’s health ministry would meet today (February 3) to discuss the new treatment for severe cases. “We still have to do more study to determine that this can be a standard treatment,” Atipornwanich tells reporters.

Other countries have also showed interest in using HIV drugs against the new coronavirus. China’s National Health Commission recently began recommending lopinavir and ritonavir (sold together by Illinois-based pharma AbbVie as Kaletra), according to Fierce Pharma. AbbVie has pledged to donate about $1.5 million worth of Kaletra for the effort.

A randomized controlled clinical trial is now underway in China to test the anti-HIV drugs’ efficacy, according to a study published last week (January 24) in The Lancet. Scientists in Hong Kong will also likely test these drugs in patients alongside immune system–boosting medications, Hong Kong University microbiologist Yuen Kwok-Yung tells Science.

Other treatments being considered by national governments and pharma companies include Gilead Sciences’s remdesivir, a drug that was designed to treat Ebola but failed efficacy tests. “Gilead is working closely with global health authorities to respond to the novel coronavirus (2019-nCoV) outbreak through the appropriate experimental use of our investigational compound remdesivir,” the company’s Chief Medical Officer Merdad Parsey says in a statement.

Massachusetts-based Moderna Therapeutics, meanwhile, is collaborating with the US National Institute of Allergy and Infectious Diseases to develop an mRNA vaccine, Fierce Pharma reports.

Catherine Offord is an associate editor at The Scientist. Email her at cofford@the-scientist.com.