mhra spc

MHRA July 2018 Pressurised metered dose inhalers (pMDI): risk of airway obstruction from aspiration of loose objects. In all patients randomised to pembrolizumab in combination with chemotherapy, compared to chemotherapy the OS HR was 0.73 (95% CI 0.62-0.86) and the PFS HR was 0.65 (95% CI 0.55-0.76). Treatment with pembrolizumab continued until RECIST 1.1-defined progression of disease as determined by the investigator, unacceptable toxicity, or a maximum of 24 months. Table 18: Response to pembrolizumab 2 or 10 mg/kg bw every 3 weeks in previously treated patients with NSCLC in KEYNOTE-010, * Hazard ratio (pembrolizumab compared to docetaxel) based on the stratified Cox proportional hazard model, Additional Important Safety Information In KEYNOTE-051, 161 paediatric patients (62 children aged 9 months to less than 12 years and 99 adolescents aged 12 years to 17 years) with advanced melanoma or PD-L1 positive advanced, relapsed, or refractory solid tumours or lymphoma were administered pembrolizumab 2 mg/kg bw every 3 weeks. Type 1 diabetes mellitus, including diabetic ketoacidosis, has been reported in patients receiving pembrolizumab (see section 4.8). Patients with active autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible for the study. The efficacy of pembrolizumab was investigated as adjuvant therapy for RCC in KEYNOTE-564, a multicentre, randomised, double-blind, placebo-controlled study in 994 patients with increased risk of recurrence defined as intermediate-high or high risk, or M1 with no evidence of disease (NED). Efficacy results were similar for the 2 mg/kg bw and 10 mg/kg bw pembrolizumab arms. Administration of Nuvaxovid in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus. KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation. Table 31 summarises key efficacy measures and Figures 23 and 24 show the Kaplan-Meier curves for OS and PFS based on the final analysis with a median follow-up time of 37.7 months. KEYTRUDA as monotherapy is indicated for the treatment of recurrent or metastatic head and neck squamous cell carcinoma in adults whose tumours express PD-L1 with a 50% TPS and progressing on or after platinum-containing chemotherapy (see section 5.1). Among the 495 patients in KEYNOTE-040, 129 (26%) had tumours that expressed PD-L1 with a TPS 50% based on the PD-L1 IHC 22C3 pharmDxTM Kit. There were no meaningful differences in overall vaccine efficacy in participants who were at increased risk of severe COVID-19 including those with 1 or more comorbidities that increase the risk of severe COVID-19 (e.g. In patients with a history of allogeneic HSCT, acute GVHD, including fatal GVHD, has been reported after treatment with pembrolizumab. This vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially sodium-free. Store the opened vial between 2C to 25C for up to 6 hours after first puncture, see section 6.3. The safety profile in paediatric patients was generally similar to that seen in adults treated with pembrolizumab. Nominal p-Value based on log-rank test stratified by American Joint Committee on Cancer (AJCC) 8th edition T stage. Updated efficacy results with a median follow-up time of 45.5 months are summarised in Table 11 and Figures 6 and 7. Chemotherapy could continue per standard of care. Healthcare professionals should consult guidance and/or specialists to diagnose and treat this condition. Treatment with pembrolizumab continued until RECIST 1.1-defined progression of disease as determined by the investigator, unacceptable toxicity, or a maximum of 24 months. The efficacy of pembrolizumab in combination with paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab, was investigated in KEYNOTE-826, a multicentre, randomised, double-blind, placebo-controlled study that enrolled 617 patients with persistent, recurrent, or first-line metastatic cervical cancer who had not been treated with chemotherapy except when used concurrently as a radio-sensitising agent. The baseline characteristics of these patients were: median age of 65 years (range: 30 to 86), 50% age 65 or older; 61% White, 21% Asian, and 4% Black; ECOG PS of 0 (59%) or 1 (41%), and 84% with pMMR tumour status and 16% with dMMR tumour status. SPC Flooring. No dose adjustment is required in elderly individuals 65 years of age. Patients were randomised (1:1) to receive pembrolizumab 200 mg intravenously every 3 weeks or investigator's choice of the following chemotherapy regimens given intravenously every 2 weeks: mFOLFOX6 (oxaliplatin, leucovorin, and FU) or mFOLFOX6 in combination with either bevacizumab or cetuximab: Oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 (or levoleucovorin 200 mg/m2), and FU 400 mg/m2 bolus on Day 1, then FU 2,400 mg/m2 over 46-48 hours. cBR&0q(0a&0ej"lL |6OD+7F!`[,CyfcqZLIWll>T"1IMvfG|XmpE?$I-^W} Every medicine pack includes a patient information leaflet (PIL), which provides information on using the medicine safely. /Rotate 0 Seventy percent had at least two and 35% of patients had three or more prior systemic therapies for advanced melanoma. 4 mL of concentrate in a 10 mL Type I clear glass vial, with a coated grey chlorobutyl or bromobutyl stopper and an aluminium seal with a dark blue coloured flip-off cap, containing 100 mg pembrolizumab. Clinical particulars 5. The frequencies are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. << The primary efficacy outcome measure was ORR as assessed by independent review using RECIST 1.1. PLWH were medically stable (free of opportunistic infections), receiving highly active and stable antiretroviral therapy, and having an HIV-1 viral load of < 1000 copies/mL. No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab. Objective responses were observed regardless of BRAF or RAS mutation status. A booster dose of Nuvaxovid (0.5 mL) may be administered intramuscularly approximately 6months after the primary series of Nuvaxovid in individuals 18years of age and older (homologous booster dose). The Kaplan-Meier curve for EFS and OS are shown in Figures 32 and 33. All patients received pembrolizumab for a median of 4 doses (range 1-35 doses), with 138 patients (85.7%) receiving pembrolizumab for 2 doses or more. Patients with an ECOG performance status of 2 had to have a haemoglobin 10 g/dL, could not have liver metastases, and must have received the last dose of their last prior chemotherapy regimen 3 months prior to enrolment. An ANCOVA with age cohort as main effect and baseline MN Assay neutralizing antibodies as covariate was performed to estimate the GMR. Based on best response of stable disease or better, Each multidose vial contains a colourless to slightly yellow, clear to mildly opalescent dispersion free from visible particles. A total of 1,174 patients were randomised. Individuals may not be fully protected until 7 days after their second dose. The efficacy of pembrolizumab was investigated in KEYNOTE-164, a multicentre, non-randomised, open-label, multi-cohort Phase II study that enrolled patients with unresectable or metastatic MSI-H or dMMR CRC that progressed following prior fluoropyrimidine-based therapy in combination with irinotecan and/or oxaliplatin. Randomisation was stratified by metastasis status (M0, M1 NED), and within M0 group, further stratified by ECOG PS (0,1), and geographic region (US, non-US). The effect of renal impairment on the clearance of pembrolizumab was evaluated by population pharmacokinetic analyses in patients with mild or moderate renal impairment compared to patients with normal renal function. Both studies included patients regardless of PD-L1 expression. Response: Best objective response as confirmed complete response or partial response. The initial analysis resulted in a HR for PFS of 0.65 (95% CI: 0.48, 0.88) with a one-sided p value of 0.0027. endobj No data are available. The efficacy and safety of pembrolizumab in patients with tumours that do not express PD-L1 have not been established. /Resources 24 0 R Disease characteristics were squamous (21%) and non-squamous (70%); stage IIIA (2%); stage IIIB (7%); stage IV (91%); stable brain metastases (15%) and the incidence of mutations was EGFR (8%) or ALK (1%). Working together across Sussex. Enrolment of adolescents completed in June 2021. Patients who tolerated axitinib 5 mg twice daily for 2 consecutive treatment cycles (i.e. /CropBox [0 0 595 842] The primary efficacy outcome measures were OS and PFS (as assessed by BICR using RECIST 1.1). Reporting suspected adverse reactions after authorisation of the medicinal product is important. When suggestions are available use up and down arrows to review and ENTER to select. EIR SPC Flooring. Hazard ratio (pembrolizumab compared to standard treatment) based on the stratified Cox proportional hazard model, KEYNOTE-010: Controlled study of NSCLC patients previously treated with chemotherapy. Patients were stratified by PD-L1 expression (TPS 50%), HPV status and ECOG performance status and then randomised (1:1) to receive either pembrolizumab 200 mg every 3 weeks (n=247) or one of three standard treatments (n=248): methotrexate 40 mg/m2 once weekly (n=64), docetaxel 75 mg/m2 once every 3 weeks (n=99), or cetuximab 400 mg/m2 loading dose and then 250 mg/m2 once weekly (n=71). - Update the SmPC and PIL to include urticaria as an adverse event << The intermediate-high risk category included: pT2 with Grade 4 or sarcomatoid features; pT3, any Grade without nodal involvement (N0) or distant metastases (M0). Patients underwent imaging every 12 weeks after the first dose of pembrolizumab for the first two years, then every 6 months from year 3 to 5, and then annually. Patients in the placebo arm were offered pembrolizumab as a single agent at the time of disease progression. Adverse reactions known to occur with pembrolizumab or combination therapy components given alone may occur during treatment with these medicinal products in combination, even if these reactions were not reported in clinical studies with combination therapy. There is limited experience with use of Nuvaxovid in pregnant women. Solid organ transplant rejection has been reported in the post-marketing setting in patients treated with PD-1 inhibitors. , Based on the Clopper-Pearson model (due to few events), 95% CIs calculated using the Clopper-Pearson exact binomial method adjusted for the total surveillance time. Secondary efficacy outcome measures included response duration, PFS, and OS. The wholesale distribution of medicinal products and importation of medicines certified by a Qualified Person in accordance with Article 51 of Directive 2001/83/EC from listed countries is subject to the holding of a Wholesale Distribution Authorisation. Translucent to white proteinaceous particles may be seen in diluted solution. Study1 is an ongoing Phase3, multicentre, randomised, observer-blinded, placebo-controlled study with an adult main study conducted in participants 18years of age and older in United States and Mexico, and a paediatric expansion occurring in participants 12 through 17 years of age in the United States. Assessed by BICR using RECIST 1.1, Of these, 48 out of 61 (79%) were identified as Variants of Concern or Variants of Interest. KEYNOTE-024: Controlled study of NSCLC patients nave to treatment. Table 36: Efficacy results in KEYNOTE-177. However, systemic corticosteroids or other immunosuppressants can be used after starting pembrolizumab to treat immune-related adverse reactions (see section 4.4). At the time of the analysis, a total of 49,950 participants age 18 years and older received at least one dose of the two-dose primary series of Nuvaxovid (n=30,058) or placebo (n=19,892). 10 0 obj /Length 33 0 R Randomisation was stratified by tumour PD-L1 expression (TPS 50% or < 50%), HPV status (positive or negative), and ECOG PS (0 vs. 1). For use in combination, see the Summary of Product Characteristics (SmPC) for the concomitant therapies. Name of the medicinal product 2. The primary efficacy outcome measures were OS and PFS (as assessed by BICR using RECIST 1.1). Ref: APCSCG/008 South East London Shared Care Prescribing Guideline for zonisamide for the treatment of epilepsy in ADULTS Date of original approval: June 2016 Last reviewed: August 2020 Review approved: October 2020 Next review date: October 2022 (or sooner if evidence or practice changes) Based on stratified log-rank test, Gently swirl the multidose vial before and in between each dose withdrawal. One-sided p-Value based on stratified log-rank test, There are no data on the use of pembrolizumab in pregnant women. A prolonged time to deterioration in EORTC QLQ-C30 global health status/QoL was observed for patients treated with pembrolizumab compared to investigator's choice chemotherapy (HR 0.70; 95% CI 0.55-0.90). >> Working together across Sussex. endobj Of these patients, 55% had no recurrence of ALT > 3 times ULN, and of those patients with recurrence of ALT > 3 times ULN, all recovered. As with other intramuscular injections, the vaccine should be given with caution in individuals receiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such as haemophilia) because bleeding or bruising may occur following an intramuscular administration in these individuals. Based on patients with a best objective response as confirmed complete or partial response. /Resources 26 0 R The median duration of follow-up was 70 days post-Dose 2, with 32,993 (66%) participants completing more than 2 months follow-up post-Dose 2. The primary efficacy outcome measures (ORR and CRR) were assessed by BICR according to the IWG 2007 criteria. The safety and efficacy of pembrolizumab were evaluated in KEYNOTE-045, a multicentre, open-label, randomised (1:1), controlled study for the treatment of locally advanced or metastatic urothelial carcinoma in patients with disease progression on or after platinum-containing chemotherapy. * With additional 12 months of follow-up after the pre-specified final analysis for PFS. Unopened Nuvaxovid vaccine has been shown to be stable up to 12 hours at 25C. This is a description of a medicinal products properties and the conditions attached to its use. ?%Kb^V8=/06%z~F0mbXZIs#MA` _w]?c/V)UFq`Gs^ 8O MAi)insr#W"RkV nl~{>~Y N.r}TD=G XwsB{`@u.1prC[N -RbEY;/3&^t! Colitis has been reported in patients receiving pembrolizumab (see section 4.8). endobj If specified in the indication, patient selection for treatment with KEYTRUDA based on MSI-H/dMMR tumour status should be confirmed by a validated test (see sections 4.1 and 5.1). Wed like to set additional cookies to understand how you use GOV.UK, remember your settings and improve government services. In addition, no safety and efficacy data are available in frailer patients (e.g. Pembrolizumab has not been studied in patients with severe hepatic impairment (see section 4.2). The study excluded patients with autoimmune disease or a medical condition that required immunosuppression. This vaccine contains potassium, less than 1 mmol (39 mg) per dose, that is to say, essentially potassium-free. We use some essential cookies to make this website work. Assessment of tumour status was performed at 9 weeks, then every 6 weeks through Week 52, followed by every 9 weeks through 24 months. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-010, a multicentre, open-label, controlled study for the treatment of advanced NSCLC in patients previously treated with platinum-containing chemotherapy. included in other section of SPC. *, The KEYNOTE-581 study was not powered to evaluate efficacy of individual subgroups. Do not mix the vaccine in the same syringe with any other vaccines or medicinal products. From a microbiological point of view, the product, once diluted, should be used immediately. The median time to onset of severe skin reactions was 3.0 months (range 2 days to 25.5 months). Continuation of pembrolizumab may be considered, after corticosteroid taper, if needed (see section 4.2). Table 39: Efficacy results for pembrolizumab plus chemotherapy in KEYNOTE-590 with PD-L1 expression (CPS 10), what are you looking for? Seventy-six (47.2%) patients had 1 or more Grades 3 to 5 adverse reactions of which 5 (3.1%) patients had 1 or more adverse reactions that resulted in death. - Update the SmPC and PIL to extend the indication for booster dose to the 12+ years age group (previously 18+ years) The median trough concentrations (Cmin) at steady-state were approximately 22 mcg/mL at a dose of 2 mg/kg bw every 3 weeks and 29 mcg/mL at a dose of 200 mg every 3 weeks. OS results at interim analysis did not meet the pre-specified efficacy boundary of 0.00085861 for statistical significance. The median survival follow-up time was 26.5 months. Individuals who have received a first dose of Nuvaxovid should receive the second dose of Nuvaxovid to complete the vaccination course. However, due to the exploratory nature of this subgroup analysis, no definitive conclusions can be drawn. Assessment of tumour status was performed every 9 weeks. This agency is of United Kingdom (UK). The frequencies included below and in Table 2 are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. Prior to dilution, the vial of liquid can be out of refrigeration (temperatures at or below 25C) for up to 24 hours. /Type /Page Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Severe infusion-related reactions, including hypersensitivity and anaphylaxis, have been reported in patients receiving pembrolizumab (see section 4.8). Axitinib could be interrupted or reduced to 3 mg twice daily and subsequently to 2 mg twice daily to manage toxicity. Two-sided based on stratified log-rank test, The clinical efficacy, safety, and immunogenicity of Nuvaxovid is being evaluated in two pivotal, placebo-controlled, Phase 3 studies, Study 1 (2019nCoV-301) conducted in North America and Study 2 (2019nCoV-302) conducted in the United Kingdom, and a Phase 2a/b study, Study 3, conducted in South Africa. The efficacy of pembrolizumab in combination with paclitaxel, nab-paclitaxel, or gemcitabine and carboplatin was investigated in KEYNOTE-355, a randomised, double-blind, multicentre, placebo-controlled study. Immune-related adverse reactions (see section 4.4). Pembrolizumab has a minor influence on the ability to drive and use machines. Pharmacotherapeutic group: Antineoplastic agents, PD-1/PDL-1 (Programmed cell death protein 1/death ligand 1) inhibitors. Novavax CZ a.s. In 1 month and 6 month repeat-dose toxicology studies in monkeys, there were no notable effects in the male and female reproductive organs; however, many animals in these studies were not sexually mature. The median number of prior lines of therapy administered for the treatment of cHL was 5 (range 2 to 15). The PD-1/PD-L1 pathway is thought to be involved in maintaining tolerance to the foetus throughout pregnancy. Liver enzymes should be monitored before initiation of and periodically throughout treatment. Pembrolizumab has not been studied in patients with severe renal impairment (see section 4.2). Administration of pembrolizumab was permitted beyond RECIST-defined disease progression if the patient was clinically stable and deriving clinical benefit as determined by the investigator. Table 19: Efficacy results in cHL patients who failed a transplant before enrolling or who failed 2 or more prior therapies and were ineligible for ASCT in KEYNOTE-204, Number (%) of patients with duration 6 months, Number (%) of patients with duration 12 months, * Based on the stratified Cox proportional hazard model, The mother and fetus group: Antineoplastic agents, PD-1/PDL-1 ( Programmed cell death 1/death! Potential benefits outweigh any potential risks for the mother and fetus is description... Study of NSCLC patients nave to treatment consult guidance and/or specialists to and... To 25C for up to 12 hours at 25C of NSCLC patients nave to treatment

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