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Revisión médica por Militian Inessa Mesropovna Última actualización de farmacia el 22.03.2022
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Los 20 mejores medicamentos con los mismos ingredientes:
Mielofibrosis
La dosis inicial recomendada de fosfato de ruxolitinib se basa en el recuento de plaquetas (Tabla 1). Se debe realizar un recuento sanguíneo completo (CBC) y un recuento de plaquetas antes de iniciar la terapia, cada 2 a 4 semanas hasta que las dosis se estabilicen y luego según esté clínicamente indicado. Las dosis pueden valorarse en función de la seguridad y la eficacia.
Tabla 1: Dosis de inicio de fosfato de ruxolitinib para mielofibrosiss
Recuento de plaquetas | Dosis inicial | |
Mayor de 200 X 10 / L | Evitar el uso | |
Pacientes con Policitemia Vera Leve, moderado o severo (categorías A, B, C de Child-Pugh) | Ninguna | 5 mg dos veces al día |
Método de administración
El fosfato de ruxolitinib se dosifica por vía oral y se puede administrar con o sin alimentos.
Si se omite una dosis, el paciente no debe tomar una dosis adicional, sino que debe tomar la siguiente dosis prescrita habitual.
Al suspender la terapia con fosfato de ruxolitinib por razones distintas a la trombocitopenia, se puede considerar la disminución gradual de la dosis de fosfato de ruxolitinib, por ejemplo, en 5 mg dos veces al día cada semana.
Para pacientes que no pueden ingerir tabletas, el fosfato de ruxolitinib se puede administrar a través de un tubo nasogástrico (8 franceses o mayores) de la siguiente manera:
- Suspenda una tableta en aproximadamente 40 ml de agua con agitación durante aproximadamente 10 minutos.
- Dentro de las 6 horas posteriores a la dispersión de la tableta, la suspensión se puede administrar a través de un tubo nasogástrico utilizando una jeringa adecuada.
El tubo debe enjuagarse con aproximadamente 75 ml de agua. No se ha evaluado el efecto de las preparaciones para alimentación de tubos sobre la exposición a fosfato de ruxolitinib durante la administración a través de un tubo nasogástrico.
Cómo se suministra
Formas de dosificación y fortalezas
Comprimidos de 5 mg: redondos y blancos con "INCY" en un lado y "5" en el otro.
Comprimidos de 10 mg: redondos y blancos con "INCY" en un lado y "10" en el otro.
Comprimidos de 15 mg: ovales y blancos con "INCY" en un lado y "15" en el otro.
Comprimidos de 20 mg en forma de cápsula y blancos con "INCY" en un lado y "20" en el otro.
Comprimidos de 25 mg: ovales y blancos con "INCY" en un lado y "25" en el otro.
Almacenamiento y manejo
Tabletas de fosfato de ruxolitinib (fosfato de ruxolitinib) están disponibles de la siguiente manera:
Presentaciones comerciales de fosfato de ruxolitinib
Número NDC | Fuerza | Descripción | Tabletas por botella |
50881-005-60 | 5 mg | Tableta redonda con "INCY" en un lado y "5" en el otro | 60 |
50881-010-60 | 10 mg | Tableta redonda con "INCY" en un lado y "10" en el otro | 60 |
50881-015-60 | 15 mg | Tableta ovalada con "INCY" en un lado y "15" en el otro | 60 |
50881-020-60 | 20 mg | Comprimido en forma de cápsula con "INCY" en un lado y "20" en el otro | 60 |
50881-025-60 | 25 mg | Tableta ovalada con "INCY" en un lado y "25" en el otro | 60 |
Almacenar a temperatura ambiente de 20 ° C a 25 ° C (68 ° F a 77 ° F); excursiones permitidas entre 15 ° C y 30 ° C (59 ° F y 86 ° F).
Fabricado para: Incyte Corporation, Wilmington, DE 19803. Revisado: marzo de 2016
See also:
What are the possible side effects of Ruxolitinib Phosphate?
Summary of the Safety Profile: The safety assessment was based on a total of 855 patients (with MF or PV) receiving Ruxolitinib Phosphate in phase 2 and 3 studies.
Myelofibrosis: In the randomised period of the two pivotal studies, COMFORT-I and COMFORT-II, the median duration of exposure to Ruxolitinib Phosphate was 10.8 months (range 0.3 to 23.5 months). The majority of patients (68.4%) were treated for at least 9 months. Of 301 patients, 111 (36.9%) had a baseline platelet count of between 100,000/mm3 and 200,000/mm3 and 190 (63.1%) had a baseline platelet count of >200,000/mm3.
In these clinical studies, discontinuation due to adverse events, regardless of causality, was observed in 11.3% of patients.
The most frequently reported adverse drug reactions were thrombocytopenia and anaemia.
Haematological adverse drug reactions [any Common Terminology Criteria for Adverse Events (CTCAE) grade] included anaemia (82.4%), thrombocytopenia (69.8%) and neutropenia (16.6%).
Anaemia, thrombocytopenia and neutropenia are dose-related effects.
The three most frequent non-haematological adverse drug reactions were bruising (21.3%), dizziness (15.3%) and headache (14.0%).
The three most frequent non-haematological laboratory abnormalities were raised alanine aminotransferase (27.2%), raised aspartate aminotransferase (19.9%) and hypercholesterolaemia (16.9%). In phase 3 clinical studies in MF, neither CTCAE grade 3 or 4 hypercholesterolaemia, raised aspartate aminotransferase nor CTCAE grade 4 raised alanine aminotransferase were observed.
Long-term safety: As expected with an extended follow-up period, the cumulative frequency of some adverse events increased in the evaluation of the 3-year follow-up safety data (median duration of exposure of 33.2 months in COMFORT-I and COMFORT-II for patients initially randomised to Ruxolitinib Phosphate) from 457 patients with myelofibrosis treated with Ruxolitinib Phosphate during the randomised and extension periods of the two pivotal phase 3 studies. This evaluation included data from patients that were initially randomised to Ruxolitinib Phosphate (N=301) and patients that received Ruxolitinib Phosphate after crossing over from control treatment arms (N=156). With these updated data, therapy discontinuation due to adverse events was observed in 17.1% of patients treated with Ruxolitinib Phosphate.
Polycythaemia Vera: The safety of Ruxolitinib Phosphate was assessed in 110 patients with PV in an open-label, randomised, controlled phase 3 RESPONSE study. The adverse drug reactions listed as follows reflect the initial study period (up to week 32) with equivalent exposure to Ruxolitinib Phosphate and Best Available Therapy (BAT), corresponding to a median duration of exposure to Ruxolitinib Phosphate of 7.8 months. The mean age of patients receiving Ruxolitinib Phosphate was around 60 years.
Discontinuation due to adverse events, regardless of causality, was observed in 3.6% of patients treated with Ruxolitinib Phosphate and 1.8% of patients treated with best available therapy.
Haematological adverse reactions (any CTCAE grade) included anaemia (43.6%) and thrombocytopenia (24.5%). Anaemia or thrombocytopenia CTCAE grade 3 and 4 were reported in respectively 1.8% or 5.5%.
The three most frequent non-haematological adverse reactions were dizziness (15.5%), constipation (8.2%) and herpes zoster (6.4%).
The three most frequent non-haematological laboratory abnormalities (any CTCAE grade) were hypercholesterolaemia (30.0%), raised alanine aminotransferase (22.7%) and raised aspartate aminotransferase (20.9%). These were all CTCAE grade 1 and 2 with the exception of one CTCAE grade 3 raised alanine aminotransferase event.
Long-term safety: Patients had a median duration of exposure to Ruxolitinib Phosphate of 18.6 months (range 0.3 to 35.9 months). With longer exposure, frequency of adverse events increased; however no new safety findings emerged. When adjusted for exposure, the adverse event rates were generally comparable with those observed during the initial study period.
Tabulated Summary of Adverse Drug Reactions from Clinical Studies: In the clinical study programme, the severity of adverse drug reactions was assessed based on the CTCAE, defining grade 1=mild, grade 2=moderate, grade 3=severe and grade 4=life-threatening.
Adverse drug reactions from clinical studies (Table 3) are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000).
Upon discontinuation, MF patients may experience a return of MF symptoms such as fatigue, bone pain, fever, pruritus, night sweats, symptomatic splenomegaly and weight loss. In clinical studies in MF the total symptom score for MF symptoms gradually returned to baseline value within 7 days after dose discontinuation.
Description of Selected Adverse Drug Reactions: Anaemia: In phase 3 clinical studies in MF, median time to onset of first CTCAE grade 2 or higher anaemia was 1.5 months. One patient (0.3%) discontinued treatment because of anaemia.
In patients receiving Ruxolitinib Phosphate mean decreases in haemoglobin reached a nadir of approximately 10 g/L below baseline after 8 to 12 weeks of therapy and then gradually recovered to reach a new steady state that was approximately 5 g/L below baseline. This pattern was observed in patients regardless of whether they had received transfusion during therapy.
In the randomised, placebo-controlled study COMFORT-I, 60.6% of Ruxolitinib Phosphate-treated MF patients and 37.7% of placebo-treated MF patients received red blood cell transfusions during randomised treatment. In the COMFORT-II study, the rate of packed red blood cell transfusions was 53.4% in the Ruxolitinib Phosphate arm and 41.1% in the best available therapy arm.
In the randomised period of the pivotal studies, anaemia was less frequent in PV patients than in MF patients (43.6% versus 82.4%). In the PV population, the CTCAE grade 3 and 4 events were reported in 1.8%, while in the MF patients the frequency was 42.56%.
Thrombocytopenia: In the phase 3 clinical studies, in patients who developed grade 3 or 4 thrombocytopenia, the median time to onset was approximately 8 weeks. Thrombocytopenia was generally reversible with dose reduction or dose interruption. The median time to recovery of platelet counts above 50,000/mm3 was 14 days. Platelet transfusions were administered to 4.7% of patients receiving Ruxolitinib Phosphate and to 4% of patients receiving control regimens. Discontinuation of treatment because of thrombocytopenia occurred in 0.7% of patients receiving Ruxolitinib Phosphate and 0.9% of patients receiving control regimens. Patients with a platelet count of 100,000/mm3 to 200,000/mm3 before starting Ruxolitinib Phosphate had a higher frequency of grade 3 or 4 thrombocytopenia compared to patients with platelet count >200,000/mm3 (64.2% vs 38.5%).
In the randomised period of the pivotal studies, the rate of patients experiencing thrombocytopenia was lower in PV (24.5%) patients compared to MF (69.8%) patients. The frequency of severe (i.e. CTCAE grade 3 and 4) thrombocytopenia was lower in PV (5.5%) than in MF (11.6%) patients.
Neutropenia: In the phase 3 clinical studies, in patients who developed grade 3 or 4 neutropenia, the median time to onset was 12 weeks. Dose holding or reductions due to neutropenia were reported in 1% of patients, and 0.3% of patients discontinued treatment because of neutropenia.
In the randomised period of the pivotal study in PV patients, neutropenia was reported in two patients (1.8%) of which one patient developed CTCAE grade 4 neutropenia.
Bleeding: In the phase 3 pivotal studies in MF bleeding events (including intracranial and gastrointestinal, bruising and other bleeding events) were reported in 32.6% of patients exposed to Ruxolitinib Phosphate and 23.2% of patients exposed to the reference treatments (placebo or best available therapy). The frequency of grade 3-4 events was similar for patients treated with Ruxolitinib Phosphate or reference treatments (4.7% vs 3.1%). Most of the patients with bleeding events during the treatment reported bruising (65.3%). Bruising events were more frequently reported in patients taking Ruxolitinib Phosphate compared with the reference treatments (21.3% vs 11.6%). Intracranial bleeding was reported in 1% of patients exposed to Ruxolitinib Phosphate and 0.9% exposed to reference treatments. Gastrointestinal bleeding was reported in 5% of patients exposed to Ruxolitinib Phosphate compared to 3.1% exposed to reference treatments. Other bleeding events (including events such as epistaxis, post-procedural haemorrhage and haematuria) were reported in 13.3% of patients treated with Ruxolitinib Phosphate and 10.3% treated with reference treatments.
In the randomised period of the pivotal study in PV patients, bleeding events (including intracranial and gastrointestinal, bruising and other bleeding events) were reported in 20% of patients treated with Ruxolitinib Phosphate and 15.3% patients receiving best available therapy. Bruising was reported in similar frequencies in Ruxolitinib Phosphate and BAT arms (10.9% versus 8.1%). No intracranial bleeding or gastrointestinal haemorrhage events were reported in patients receiving Ruxolitinib Phosphate. One patient treated with Ruxolitinib Phosphate experienced a grade 3 bleeding event (post-procedural bleeding); no grade 4 bleeding was reported. Other bleeding events (including events such as epistaxis, post-procedural haemorrhage, gingival bleeding) were reported in 11.8% of patients treated with Ruxolitinib Phosphate and 6.3% treated with best available therapy.
Infections: In the phase 3 pivotal studies in MF, grade 3 or 4 urinary tract infection was reported in 1.0% of patients, herpes zoster in 4.3% and tuberculosis in 1.0%. In phase 3 clinical studies sepsis was reported in 3.0% of patients. An extended follow-up of patients treated with Ruxolitinib Phosphate showed no trends towards an increase in the rate of sepsis over time.
In the randomised period of the pivotal study in PV patients, one (0.9%) CTCAE grade 3 and no grade 4 urinary tract infection was reported. The rate of herpes zoster was slightly higher in PV (6.4%) patients than in MF (4.0%) patients. There was one report of CTCAE grade 3 post-herpetic neuralgia amongst the PV patients.
Increased Systolic Blood Pressure: In the phase 3 pivotal clinical studies in MF an increase in systolic blood pressure of 20 mmHg or more from baseline was recorded in 31.5% of patients on at least one visit compared with 19.5% of the control-treated patients. In COMFORT-I (MF patients) the mean increase from baseline in systolic BP was 0-2 mmHg on Ruxolitinib Phosphate versus a decrease of 2-5 mmHg in the placebo arm. In COMFORT-II mean values showed little difference between the Ruxolitinib Phosphate-treated and the control-treated MF patients.
In the randomised period of the pivotal study in PV patients, the mean systolic blood pressure increased by 0.65 mmHg in the Ruxolitinib Phosphate arm versus a decrease of 2 mmHg in the BAT arm.
Reporting of Suspected Adverse Reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.