ganciclovir
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Tratamiento y prevención de enfermedad por citomegalovirus en pacientes inmunodeprimidos según edad y contexto clínico.
Contraindicaciones
Absolutas
- Hipersensibilidad a ganciclovir o valganciclovir.
- Lactancia.
Advertencias clínicas
- Puede causar mielosupresión grave, incluidos neutropenia, anemia, trombocitopenia y fallo medular; controla el hemograma. — CIMA/AEMPS, ficha técnica 58266
- Es potencialmente teratógeno, carcinógeno y tóxico para la fertilidad; usa anticoncepción eficaz y limita el uso pediátrico a beneficio claro. — CIMA/AEMPS, ficha técnica 58266
Interacciones medicamentosas
- SeveraImipenem-cilastatina
Mecanismo: Se han notificado convulsiones.
Recomendación: No combines salvo que el beneficio supere el riesgo.
CIMA/AEMPS, ficha técnica 58266
- SeveraProbenecid, didanosina y fármacos mielosupresores o nefrotóxicos
Mecanismo: Pueden aumentar exposición o toxicidad hematológica y renal.
Recomendación: Controla toxicidad, hemograma y función renal y ajusta la combinación.
CIMA/AEMPS, ficha técnica 58266
Eventos adversos
Comunes (≥1%)
Neutropenia, anemia, trombocitopenia, diarrea, fiebre y náuseas
Raros pero graves
Fallo medular, agranulocitosis, insuficiencia renal, anafilaxia y convulsiones
Embarazo y lactancia
No uses durante el embarazo salvo que la necesidad clínica supere el riesgo fetal. Anticoncepción eficaz durante y 30 días después en mujeres; barrera durante y 90 días después en hombres. Interrumpe la lactancia.
Bibliografía reciente (PubMed)
Therapies for refractory cytomegalovirus infections (with or without resistance [R/R]) in transplant recipients are limited by toxicities. Maribavir has multimodal anti-cytomegalovirus activity through the inhibition of UL97 protein kinase. In this phase 3, open-label study, hematopoietic-cell and solid-organ transplant recipients with R/R cytomegalovirus were randomized 2:1 to maribavir 400 mg twice daily or investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for 8 weeks, with 12 weeks of follow-up. The primary endpoint was confirmed cytomegalovirus clearance at end of week 8. The key secondary endpoint was achievement of cytomegalovirus clearance and symptom control at end of week 8, maintained through week 16. 352 patients were randomized (235 maribavir; 117 IAT). Significantly more patients in the maribavir versus IAT group achieved the primary endpoint (55.7% vs 23.9%; adjusted difference [95% confidence interval (CI)]: 32.8% [22.80-42.74]; P < .001) and key secondary endpoint (18.7% vs 10.3%; adjusted difference [95% CI]: 9.5% [2.02-16.88]; P = .01). Rates of treatment-emergent adverse events (TEAEs) were similar between groups (maribavir, 97.4%; IAT, 91.4%). Maribavir was associated with less acute kidney injury versus foscarnet (8.5% vs 21.3%) and neutropenia versus valganciclovir/ganciclovir (9.4% vs 33.9%). Fewer patients discontinued treatment due to TEAEs with maribavir (13.2%) than IAT (31.9%). One patient per group had fatal treatment-related TEAEs. Maribavir was superior to IAT for cytomegalovirus viremia clearance and viremia clearance plus symptom control maintained post-therapy in transplant recipients with R/R cytomegalovirus. Maribavir had fewer treatment discontinuations due to TEAEs than IAT. Clinical Trials Registration. NCT02931539 (SOLSTICE).
Cytomegalovirus (CMV) is the most common cause of viral infection in newborn babies, and affects 1 in 200 of all live born infants in high-income countries; and 1 in 71 in low- and middle-income countries. It is a major cause of hearing loss and brain damage. Women may get CMV infection for the first time during pregnancy (primary infection) or may experience 'non-primary' infection, either by reactivation of previous CMV infection or by a new infection with a different strain of the virus. The most common source of infection to pregnant women is the saliva and urine of young children. Therefore, all pregnant women, especially those in regular contact with young children, should be informed about hygiene-based measures to reduce the risks, e.g. handwashing. The UK National Screening Committee recommends against universal antenatal or newborn screening for CMV. Testing for CMV is usually offered only to women who develop symptoms of influenza, glandular fever or hepatitis (liver inflammation) during pregnancy, or for those whom a routine ultrasound scan detects fetal anomalies that suggests possible CMV infection. The risk of harm to the fetus is greatest following primary CMV infection of the woman in early pregnancy, and appears to be very low following infection after 12 weeks of pregnancy. Babies with CMV infection at birth may have jaundice, a rash, enlarged liver or spleen, a small brain, or be small for their gestational age. Around 1 in 8 babies born with CMV infection will have clinically detectable signs at birth. The rest will not have any features detectable by clinical examination alone. Therefore, all infants with CMV infection at birth should be followed up at a minimum of up to 2 years of age or later, depending upon the disease status, to check hearing and brain development. Following primary CMV infection in the first 12 weeks of pregnancy, if the woman starts taking the antiviral medicine valaciclovir (valacyclovir) it reduces the risk of the baby
Little is known regarding anterior uveitis (AU), the most common ocular disease associated with cytomegalovirus (CMV) infection in immunocompetent populations. CMV AU is highly prevalent in Asia, with a higher incidence in men. Clinically, it manifests mainly as anterior chamber inflammation and elevated intraocular pressure (IOP). Acute CMV AU may resemble Posner-Schlossman syndrome with its recurrent hypertensive iritis, while chronic CMV AU may resemble Fuchs uveitis because of its elevated IOP. Without prompt treatment, it may progress to glaucoma; therefore, early diagnosis is critical to prognosis. Knowledge regarding clinical features and aqueous humor analyses can facilitate accurate diagnoses; so, we compared and summarized these aspects. Early antiviral treatment reduces the risk of a glaucoma surgery requirement, and therapeutic effects vary based on drug delivery. Both oral valganciclovir and topical ganciclovir can produce positive clinical outcomes, and higher concentration and frequency are beneficial in chronic CMV retinitis. An extended antiviral course could prevent relapses, but should be limited to 6 months to prevent drug resistance and side effects. In this review, we have systematically summarized the pathogenesis, clinical features, diagnostic and therapeutic aspects, and immunological mechanisms of CMV AU with the goal of providing a theoretical foundation for early clinical diagnosis and treatment.
Despite advances in monitoring and treatment, cytomegalovirus (CMV) infections remain one of the most common complications after solid organ transplantation (SOT). CMV infection may fail to respond to standard first- and second-line antiviral therapies with or without the presence of antiviral resistance to these therapies. This failure to respond after 14 days of appropriate treatment is referred to as "resistant/refractory CMV." Limited data on refractory CMV without antiviral resistance are available. Reported rates of resistant CMV are up to 18% in SOT recipients treated for CMV. Therapeutic options for treating these infections are limited due to the toxicity of the agent used or transplant-related complications. This is often the challenge with conventional agents such as ganciclovir, foscarnet and cidofovir. Recent introduction of new CMV agents including maribavir and letermovir as well as the use of adoptive T cell therapy may improve the outcome of these difficult-to-treat infections in SOT recipients. In this expert review, we focus on new treatment options for resistant/refractory CMV infection and disease in SOT recipients, with an emphasis on maribavir, letermovir, and adoptive T cell therapy.
Advances in therapeutic care are leading to an increase in the number of patients living with overt immunosuppression. These patients are at risk of cytomegalovirus (CMV) infection and disease that can lead to or develop during ICU admission. This manuscript aims to describe the clinical presentation, risk factors, and management of CMV infection and disease in this patient population. We conducted a literature search in PubMed up to April 2024, focusing on CMV infection and disease in patients with overt immunosuppression (hematopoietic stem cell and solid organ transplantation, solid or hematologic malignancies, HIV infection, immunosuppressive drugs, including corticosteroids, and primary immunodeficiencies) admitted to the intensive care unit (ICU). As there is limited ICU-specific data on CMV in immunosuppressed patients, many of the findings were extrapolated from the general literature. CMV infection and disease in immunocompromised critically ill patients is associated with increased mortality and presents significant management challenges. Clinical manifestations are diverse, shaped by the underlying immune deficiency and primary disease. Pneumonia and encephalitis are among the most severe CMV end-organ diseases. CMV infection may also increase the risk of secondary infections and induce life-threatening conditions, such as thrombotic microangiopathy. Importantly, CMV reactivation is not synonymous with CMV disease, and qPCR testing of body fluids cannot reliably differentiate between viral shedding and tissue-invasive infection, which requires histopathological confirmation. Ganciclovir is commonly the first-line anti-viral, though maribavir shows potential for patients unresponsive to other antivirals. Identifying patients who require prophylactic or preemptive antiviral therapy is essential. CMV infection and disease in critically ill immunocompromised patients pose a unique challenge for intensivists. The broad spectrum of clinical presentations and th