mhra spcmhra spc

KEYTRUDA should be withheld or discontinued to manage adverse reactions as described in Table 1. For Grades 3 or 4 infusion reactions, infusion should be stopped and pembrolizumab permanently discontinued (see section 4.2). The study demonstrated statistically significant improvements in OS and PFS for patients randomised to pembrolizumab in combination with chemotherapy with or without bevacizumab compared to placebo in combination with chemotherapy with or without bevacizumab at a pre-specified interim analysis in the overall population. There was no statistically significant difference between pembrolizumab and chemotherapy with respect to PFS. Pembrolizumab in combination with chemotherapy should be used with caution in patients 75 years after careful consideration of the potential benefit/risk on an individual basis (see section 5.1). Date of first authorisation: 1 January 2021. Forty-five percent had an ECOG Performance Status of 1, 40% had elevated LDH and 23% had a BRAF mutated tumour. /Title (Microsoft Word - 1646658070014998238_spc-doc.doc) Of the pooled reactogenicity data, which includes participants aged 18 years and older enrolled in the two phase 3 studies who received any dose of Nuvaxovid (n=20,055) or placebo (n=10,561), the most frequent adverse reactions were injection site tenderness (75%), injection site pain (62%), fatigue (53%), myalgia (51%), headache (50%), malaise (41%), arthralgia (24%), and nausea or vomiting (15%). This service replaces the previously separate MHRA websites, one of which hosted SPC and PILs, the other PARs. Among the 51 patients with gastric cancer, the baseline characteristics were: median age 67 years (range: 41 to 89); 57% age 65 or older; 65% male, 63% White, 28% Asian; and ECOG PS 0 (45%) and 1 (55%). Nominal two-sided p-Value based on the stratified Cochran-Mantel-Haenszel (CMH) test. Assessment of tumour status was performed at 12 weeks, then every 6 weeks through Week 48, followed by every 12 weeks thereafter. Pneumonitis has been reported in patients receiving pembrolizumab (see section 4.8). Figure 30: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-590 with PD-L1 expression (CPS 10), Figure 31: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-590 with PD-L1 expression (CPS 10), KEYNOTE-522: Controlled study of neoadjuvant and adjuvant therapy in patients with locally advanced, inflammatory, or early-stage triple-negative breast cancer at high risk of recurrence. << This medicinal product is subject to additional monitoring. In patients treated with pembrolizumab in combination with axitinib or lenvatinib (n=1,456), the incidence of hypothyroidism was 46.2% (all Grades) with 0.8% Grade 3 or 4. Frequencies are defined as: 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); and not known (cannot be estimated from the available data). Enrolment was completed in November 2020. Adrenal insufficiency (primary and secondary) has been reported in patients receiving pembrolizumab. The efficacy of pembrolizumab was investigated in KEYNOTE-048, a multicentre, randomised, open-label, active-controlled study in patients with histologically confirmed metastatic or recurrent HNSCC of the oral cavity, pharynx or larynx, who had not previously received systemic therapy for recurrent or metastatic disease and who were considered incurable by local therapies. Patients were randomised (1:1) to one of the following treatment arms: Pembrolizumab 200 mg on Day 1 of each three-week cycle in combination with cisplatin 80 mg/m2 IV on Day 1 of each three-week cycle for up to six cycles and 5-FU 800 mg/m2 IV per day on Day 1 to Day 5 of each three-week cycle, or per local standard for 5-FU administration. OS and PFS benefits were observed regardless of PD-L1 expression level. Reporting suspected adverse reactions after authorisation of the medicinal product is important. Colitis has been reported in patients receiving pembrolizumab (see section 4.8). Based on Kaplan-Meier estimation, Figure 18: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-361 (intent to treat population, choice of carboplatin), Figure 19: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-361 (patients with PD-L1 expression CPS 10, intent to treat population, choice of carboplatin), KEYNOTE-048: Controlled study of monotherapy and combination therapy in HNSCC patients nave to treatment in the recurrent or metastatic setting. 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. This updated OS analysis was not adjusted to account for subsequent therapies. 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. The 15-minute observation period following vaccination with the mRNA COVID-19 vaccines has been removed for individuals aged 12 years and over who have no history of a severe allergic reaction (as outlined in the Greenbook advice This follows careful review of the safety data by the MHRA and advice from the governments independent Commission on Human Medicines. A subgroup analysis was performed as part of the final analysis of KEYNOTE-006 in patients who were PD-L1 positive (n=671; 80%) vs. PD-L1 negative (n=150; 18%). This is based on the MHRA assessment report with any commercially or personally confidential information removed. Table 8 summarises efficacy results by PD-L1 expression. Administer the infusion solution intravenously over 30 minutes using a sterile, non-pyrogenic, low-protein binding 0.2 to 5 m in-line or add-on filter. The geometric mean value (CV%) for the terminal half-life is 22 days (32%) at steady-state. Pneumonitis occurred more frequently in patients with a history of prior thoracic radiation (8.1%) than in patients who did not receive prior thoracic radiation (3.9%). Response: Best objective response as confirmed complete response or partial response, PILs are based on the Summaries of Product Characteristics (SPCs) which are a description of a medicinal products properties and the conditions attached to its use. H0: difference in % = 0 versus H1: difference in % > 0. << Of the 834 patients, 60% were male, 44% were 65 years (median age was 62 years [range 18-89]) and 98% were white. A searchable list of the. Table 9 summarises efficacy results by PD-L1 expression. The safety of pembrolizumab was evaluated in a 1-month and a 6-month repeat-dose toxicity study in Cynomolgus monkeys administered intravenous doses of 6, 40 or 200 mg/kg bw once a week in the 1-month study and once every two weeks in the 6-month study, followed by a 4-month treatment-free period. Neutralising antibody titers measured by a wild-type assay were assessed 28 days post-booster dose. Corticosteroid therapy may be considered. Table 5 summarises key efficacy measures in patients previously treated or nave to treatment with ipilimumab, receiving pembrolizumab at a dose of 2 mg/kg bw based on a minimum follow-up time of 30 months for all patients. Key secondary efficacy outcome measures included OS and ORR. << Reporting of suspected adverse reactions Twenty-one percent had received 2 prior systemic regimens in the metastatic setting. endstream Eighty-two percent had M1c stage, 73% had at least two and 32% of patients had three or more prior systemic therapies for advanced melanoma. Table 10: Efficacy results in KEYNOTE-716, * Based on the stratified Cox proportional hazard model. Patients randomised to chemotherapy were offered pembrolizumab at the time of disease progression. Among the 83 patients with endometrial cancer, the baseline characteristics were: median age of 64 years (range: 42 to 86), 46% age 65 or older; 84% White, 6% Asian, and 4% Black; and ECOG PS 0 (46%) and 1 (54%). Hypophysitis led to discontinuation of pembrolizumab in 14 (0.2%) patients. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. 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, KEYNOTE-045: Controlled study in urothelial carcinoma patients who have received prior platinum-containing chemotherapy. The median duration was 1.3 months (range 1 day to 29.0+ months). ECOG performance status 3) considered not eligible for chemotherapy. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT), Allogeneic HSCT after treatment with pembrolizumab. Hypothyroidism led to discontinuation of pembrolizumab in 6 (0.1%) patients. In patients with NSCLC, pneumonitis occurred in 160 (5.7%), including Grade 2, 3, 4 or 5 cases in 62 (2.2%), 47 (1.7%), 14 (0.5%) and 10 (0.4%), respectively. Pembrolizumab CL is approximately 23% lower (geometric mean, 195 mL/day [CV%: 40%]) after achieving maximal change at steady-state compared with the first dose (252 mL/day [CV%: 37%]); this decrease in CL with time is not considered clinically meaningful. Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic reaction following the administration of the vaccine. /Type /Page EIR SPC Flooring. The most common tumour types by histology were Hodgkin lymphoma (13.7%), glioblastoma multiforme (9.3%), neuroblastoma (6.2%), osteosarcoma (6.2%) and melanoma (5.6%). /MediaBox [0 0 595 842] /Rotate 0 Discard any unused portion left in the vial. Atypical responses (i.e. BRAF mutations were reported in 13% of the study population. 4.9 Overdose Hyperkalaemia. << HWK[%'HNR*3'9!0\BZ_~ @HR`_w?|Qw2jw3&R^E Fifteen percent of patients had disease progression following prior platinum-containing neoadjuvant or adjuvant chemotherapy. Well send you a link to a feedback form. Monitor for the development or worsening endobj The baseline and prognostic disease characteristics of the study population of KEYNOTE-052 included a proportion of patients eligible for a carboplatin-based combination, for whom the benefit has been assessed in a comparative study (KEYNOTE-361). Assessment of tumour status was performed at 9 weeks, then every 6 weeks through Week 52, followed by every 9 weeks through 24 months. In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6. Do not co-administer other medicinal products through the same infusion line. /Rotate 0 Assessment of tumour status was performed at baseline and then every 8 weeks. Forty-five percent had no prior therapies for advanced melanoma. , Pyrexia was observed more frequently in adolescents aged 12 through to 17 years compared to adults, with the frequency being very common after the second dose in adolescents. Working together across Sussex. To discuss the benefits and possible side-effects of treatment with the patient. Sixty-five percent of patients had M1c stage, 9% had a history of brain metastases, 66% had no and 34% had one prior therapy. Secondary efficacy outcome measures included response duration, PFS, and OS. Cisplatin could be administered on Day 2 of each 3-week treatment cycle. All rights reserved. Report a side effect with a medicine or medical device. Among the 305 patients in KEYNOTE-024, baseline characteristics were: median age 65 years (54% age 65 or older); 61% male; 82% White, 15% Asian; and ECOG performance status 0 and 1 in 35% and 65%, respectively. Thirty-seven percent of patients received 2 or more prior lines of therapy. Cases of graft-versus-host-disease (GVHD) and hepatic veno-occlusive disease (VOD) have been observed in patients with cHL undergoing allogeneic HSCT after previous exposure to pembrolizumab. Assessed by BICR according to the IWG 2007 criteria by PET CT scans, Based on patients (n=150) with a response by independent review, Based on patients (n=18) with a response by independent review, # Based on Kaplan-Meier estimation; includes 62 patients with responses of 12 months or longer, Based on Kaplan-Meier estimation; includes 7 patients with responses of 12 months or longer, Based on Kaplan-Meier estimation; includes 37 patients with responses of 24 months or longer, Based on Kaplan-Meier estimation; includes 4 patients with responses of 60 months or longer. The pMMR stratum was further stratified by ECOG performance status, geographic region, and history of pelvic radiation. Healthcare professionals should consult guidance and/or specialists to diagnose and treat this condition. A total of 1,019 adult patients were randomised (1:1) to receive pembrolizumab 200 mg every three weeks (n=514) or placebo (n=505), for up to one year until disease recurrence or unacceptable toxicity. At least one pre-existing comorbidity or lifestyle characteristic associated with an increased risk of severe COVID-19 was present in 16,493 (95%) participants. Corticosteroids to treat adrenal insufficiency and other hormone replacement should be administered as clinically indicated. At the pre-specified interim analysis, for the IMDC risk category, the OS hazard ratio (HR) for patients randomised to the pembrolizumab combination arm compared with sunitinib in the favourable risk group was 0.64 (95% CI 0.24, 1.68), for the intermediate risk group the OS HR was 0.53 (95% CI 0.35, 0.82), and for the poor risk group the OS HR was 0.43 (95% CI 0.23, 0.81). Data from clinical trials in adolescent melanoma patients is very limited and extrapolation from adult data has been used to establish efficacy. The hazard ratio was 0.72 (95% CI 0.55, 0.93) with 105/355 (30%) deaths in the combination arm and 122/357 (34%) deaths in the sunitinib arm. The study demonstrated statistically significant improvements in OS and ORR for patients randomised to pembrolizumab as compared to chemotherapy. Treatment with pembrolizumab continued until RECIST v1.1-defined progression of disease as determined by the investigator or unacceptable toxicity. Pharmaceutical particulars 7. Based on Miettinen and Nurminen method stratified by PD-L1 status, platinum chemotherapy and smoking status, Figure 11: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-189 (intent to treat population), Figure 12: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-189 (intent to treat population). KEYTRUDA as monotherapy is indicated for the treatment of adults and adolescents aged 12 years and older with advanced (unresectable or metastatic) melanoma. Safety data of pembrolizumab in the adjuvant melanoma setting in patients 75 years are limited. A Periodic Safety Update Report (PSUR) is a document which provides an evaluation of the risk-benefit balance of the medicine at defined times following authorisation. Alpha Release This is a new service - your feedback will help improve it. /ModDate (D:20190624094123+01'00') You have rejected additional cookies. A total of 1,173 participants (PP-IMM Analysis Set) received a booster dose of Nuvaxovid approximately 6months after completion of the primary series of Nuvaxovid (Day201). In the per-protocol immunogenicity (PP-IMM) analysis set for participants who received Nuvaxovid (n = 191), median age was 40 years (range: 22 to 70 years); 93% (n = 178) were 18 to 64 years old and 7% (n = 13) were aged 65 to 84; 43% were female; 75% were White; 23% were multiracial or from ethnic minorities; and 27% had at least one comorbid condition. 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. From a microbiological point of view, the product, once diluted, should be used immediately. See Table 25 and Figures 18 and 19. Expires . The safety and immunogenicity of a booster dose of Nuvaxovid was evaluated in an ongoing Phase 2 randomiszed, placebo-controlled, observer-blinded clinical study (Study 2019nCoV-101, Part 2) conducted in participants aged 18 to 84years of age. The study excluded patients with active autoimmune disease or a medical condition that required immunosuppression. << The median duration was not reached (range 3 days to 40.1+ months). %PDF-1.4 In addition, no safety and efficacy data are available in frailer patients (e.g. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. Insulin should be administered for type 1 diabetes, and pembrolizumab should be withheld in cases of type 1 diabetes associated with Grade 3 hyperglycaemia or ketoacidosis until metabolic control is achieved (see section 4.2). Table 25: Response to pembrolizumab 200 mg every 3 weeks or chemotherapy in patients with previously untreated urothelial carcinoma for whom carboplatin rather than cisplatin was selected by the investigator as the better choice of chemotherapy in KEYNOTE-361, 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. To help us improve GOV.UK, wed like to know more about your visit today. Thirty-five percent had tumour PD-L1 expression TPS < 1% [negative]; 19% were East Asian; and 60% received paclitaxel. Pembrolizumab 2 mg/kg bw every 3 weeks in patients previously treated with ipilimumab, Pembrolizumab 2 mg/kg bw every 3 weeks in patients nave to treatment with ipilimumab, * Includes patients without measurable disease at baseline by independent radiology, The study excluded patients with endometrial sarcoma, carcinosarcoma, pre-existing Grade 3 fistula, uncontrolled BP (> 150/90 mmHg), significant cardiovascular impairment or event within previous 12 months, or patients who had active autoimmune disease or a medical condition that required immunosuppression. Patients without disease progression were treated for up to 24 months (up to 35 cycles). Treatment with pembrolizumab and axitinib continued until RECIST v1.1-defined progression of disease as verified by BICR or confirmed by the investigator, unacceptable toxicity, or for pembrolizumab, a maximum of 24 months. Individuals may not be fully protected until 7 days after their second dose. These results reflect enrolment that occurred during the time period when the B.1.17 (Alpha) variant was circulating in the UK. Pembrolizumab should be withheld for Grade 3 until recovery to Grade 1 hyperthyroidism. Based on patients with a best objective response as confirmed complete or partial response. Twelve percent of patients had BRAF mutations and 36% had RAS mutations; 39% and 34% were undetermined for BRAF and RAS mutations, respectively. Eighty-eight percent had M1 disease and 12% had M0 disease. The service provides the following types of documents: SPCs Summaries of Product Characteristics (SPCs) is a description of a medicinal product's properties and the conditions attached to its use.. Wed like to set additional cookies to understand how you use GOV.UK, remember your settings and improve government services. Patients should be monitored for changes in liver function (at the start of treatment, periodically during treatment and as indicated based on clinical evaluation) and symptoms of hepatitis, and other causes excluded. The secondary outcome measures were DMFS and OS in the whole population and in the population with PD-L1 positive tumours. Patients with autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible. >> You can also use the A-Z list to find the active substance. The baseline characteristics of these 129 patients included: median age 62 years (40% age 65 or older); 81% male; 78% White, 11% Asian, and 2% Black; 23% and 77% with an ECOG performance status 0 or 1, respectively; and 19% with HPV positive tumours. KEYTRUDA in combination with axitinib in RCC. Qualitative and quantitative composition 3. Immune-related severe skin reactions have been reported in patients receiving pembrolizumab (see section 4.8). Secondary efficacy outcome measures were duration of response, PFS, and OS. /Contents 15 0 R The following terms represent a group of related events that describe a medical condition rather than a single event: a. infusion-related reaction (drug hypersensitivity, anaphylactic reaction, anaphylactoid reaction, hypersensitivity, infusion-related hypersensitivity reaction, cytokine release syndrome, and serum sickness), b. hypothyroidism (myxoedema and immune-mediated hypothyroidism), c. adrenal insufficiency (Addison's disease, adrenocortical insufficiency acute, secondary adrenocortical insufficiency), d. thyroiditis (autoimmune thyroiditis, thyroid disorder, and thyroiditis acute), f. hypophysitis (hypopituitarism, lymphocytic hypophysitis), g. type 1 diabetes mellitus (diabetic ketoacidosis), h. myasthenic syndrome (myasthenia gravis, including exacerbation), i. encephalitis (autoimmune encephalitis, noninfective encephalitis), j. Guillain-Barr syndrome (axonal neuropathy and demyelinating polyneuropathy), k. myelitis (including transverse myelitis), l. meningitis aseptic (meningitis, meningitis noninfective), m. uveitis (chorioretinitis, iritis and iridocyclitis), o. vasculitis (central nervous system vasculitis, aortitis, giant cell arteritis), p. pneumonitis (interstitial lung disease, organising pneumonia, immune-mediated pneumonitis, and immune-mediated lung disease), q. abdominal pain (abdominal discomfort, abdominal pain upper and abdominal pain lower), r. colitis (colitis microscopic, enterocolitis, enterocolitis haemorrhagic, autoimmune colitis, and immune-mediated enterocolitis), s. pancreatitis (autoimmune pancreatitis, pancreatitis acute and immune-mediated pancreatitis), t. gastrointestinal ulceration (gastric ulcer and duodenal ulcer), u. hepatitis (autoimmune hepatitis, immune-mediated hepatitis, drug induced liver injury and acute hepatitis), v. cholangitis sclerosing (immune-mediated cholangitis), w. pruritus (urticaria, urticaria papular and pruritus genital), x. rash (rash erythematous, rash follicular, rash macular, rash maculo-papular, rash papular, rash pruritic, rash vesicular and genital rash), y. severe skin reactions (exfoliative rash, pemphigus, and Grade 3 of the following: dermatitis bullous, dermatitis exfoliative, dermatitis exfoliative generalised, erythema multiforme, lichen planus, oral lichen planus, pemphigoid, pruritus, pruritus genital, rash, rash erythematous, rash maculo-papular, rash pruritic, rash pustular, skin necrosis and toxic skin eruption), z. vitiligo (skin depigmentation, skin hypopigmentation and hypopigmentation of the eyelid), aa. /Type /Metadata Patients with autoimmune disease that required systemic therapy within 2 years of treatment; a medical condition that required immunosuppression; or who had received more than 30 Gy of thoracic radiation within the prior 26 weeks were ineligible. Efficacy results for OS were consistent regardless of the age of tumour specimen (new vs. archival) based on an intergroup comparison. Based on Kaplan-Meier estimation, Figure 13: Kaplan-Meier Curve for Overall Survival in KEYNOTE-407, Figure 14: Kaplan-Meier Curve for Progression-Free Survival in KEYNOTE-407. KEYTRUDA potentiates T-cell responses, including anti-tumour responses, through blockade of PD-1 binding to PD-L1 and PD-L2, which are expressed in antigen presenting cells and may be expressed by tumours or other cells in the tumour microenvironment. Based on patients with a best objective response as confirmed complete or partial response, Figure 1: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-006 (intent to treat population), Figure 2: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-006 (intent to treat population), KEYNOTE-002: Controlled study in melanoma patients previously treated with ipilimumab. - Minor change to SmPC text on myo/pericarditis. All patients had a tumour histology of adenocarcinoma. Pneumonitis led to discontinuation of pembrolizumab in 131 (1.7%) patients. The primary efficacy outcome measure was PFS as assessed by blinded independent central review (BICR) using RECIST 1.1. When pembrolizumab is administered in combination with axitinib or lenvatinib, refer to the SmPC for axitinib or lenvatinib prior to initiation of treatment.

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