mhra spcmhra spc

The primary efficacy outcome was OS in the ITT population. Clinical particulars 5. 2 0 obj - Update the SmPC and PIL to include extensive swelling of the vaccinated limb as an adverse event Hazard ratio (pembrolizumab compared to standard treatment) based on the stratified Cox proportional hazard model, The primary efficacy outcome was PFS and the secondary efficacy outcome measure was ORR, both assessed by BICR according to the 2007 revised International Working Group (IWG) criteria. Adjuvant Matrix-M containing per 0.5 mL dose: Fraction-A (42.5 micrograms) and Fraction-C (7.5 micrograms) of Quillaja saponaria Molina extract. /CropBox [0 0 595 842] Well send you a link to a feedback form. /Rotate 0 Thyroid disorders, including hypothyroidism, hyperthyroidism and thyroiditis, have been reported in patients receiving pembrolizumab and can occur at any time during treatment. 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. Nephritis resolved in 20 patients, 5 with sequelae. Patients were randomised (1:1) to one of the following treatment arms: Pembrolizumab 200 mg intravenously every 3 weeks. Patients must have undergone lymph node dissection, and if indicated, radiotherapy within 13 weeks prior to starting treatment. A total of 861 patients were randomised. Among the 5 adolescent participants with advanced melanoma treated on KEYNOTE-051, no patient had a complete or a partial response, and 1 patient had stable disease. Patients were randomised (1:1) to one of the following treatment arms: pembrolizumab 200 mg intravenously every 3 weeks in combination with lenvatinib 20 mg orally once daily. KEYTRUDA as monotherapy is indicated for adults with MSI-H or dMMR colorectal cancer in the following settings: - first-line treatment of metastatic colorectal cancer; - treatment of unresectable or metastatic colorectal cancer after previous fluoropyrimidine-based combination therapy. 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. Randomisation was stratified by MMR status (dMMR or pMMR [mismatch repair proficient]) using a validated IHC test. Continue typing to refine. 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. Objective responses were observed regardless of BRAF or RAS mutation status. Nuvaxovid may also be given as a booster dose in individuals 18 years of age and older following a primary series comprised of an mRNA vaccine or adenoviral vector vaccine (heterologous booster dose). Healthcare professionals are asked to report any suspected adverse reactions. Randomisation was stratified by chemotherapy treatment (paclitaxel or nab-paclitaxel vs. gemcitabine and carboplatin), tumour PD-L1 expression (CPS 1 vs. CPS < 1), and prior treatment with the same class of chemotherapy in the neoadjuvant setting (yes vs. no). Neutralising antibody titers measured by a wild-type assay were assessed 28 days post-booster dose. /Subtype /XML Among patients with BRAF mutant tumours, 139 (46%) were previously treated with a BRAF inhibitor. Patients were randomised (1:1:1) to one of the following treatment arms: pembrolizumab 200 mg intravenously every 3 weeks up to 24 months in combination with lenvatinib 20 mg orally once daily. This vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially sodium-free. Figure 25: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-581. KEYTRUDA has not been studied in patients with severe hepatic impairment (see sections 4.4 and 5.2). 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. This means that further evidence on this medicinal product is awaited. The recommended dose is a single 500 mg intravenous infusion administered following dilution (see sections 4.4 and 6.6). The median time to onset of hypophysitis was 5.9 months (range 1 day to 17.7 months). In clinical studies in patients treated with pembrolizumab 2 mg/kg bw every three weeks, 200 mg every three weeks, or 10 mg/kg bw every two or three weeks as monotherapy, 36 (1.8%) of 2,034 evaluable patients tested positive for treatment-emergent antibodies to pembrolizumab, of which 9 (0.4%) patients had neutralising antibodies against pembrolizumab. In patients with RCC and melanoma treated with pembrolizumab monotherapy in the adjuvant setting (n=1,480), the incidence of hyperthyroidism was 10.9%, the majority of which were Grade 1 or 2. Each mL of concentrate contains 25 mg of pembrolizumab. Disease characteristics were squamous (18%) and non-squamous (82%); M1 (99%); and brain metastases (9%). Administration of pembrolizumab with lenvatinib was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered by the investigator to be deriving clinical benefit. KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of locally recurrent unresectable or metastatic triple-negative breast cancer in adults whose tumours express PD-L1 with a CPS 10 and who have not received prior chemotherapy for metastatic disease (see section 5.1). Uncommon but serious: (see MHRA alerts below for more information) DKA Fournier's Gangrene Lower limb amputation -encourage regular preventative footcare Please see individual drug monographs in BNF/SPC for a complete side-effect profile -see hyperlink in table overleaf. << EIR SPC Flooring. Colitis occurred in 158 (2.1%) patients, including Grade 2, 3 or 4 cases in 49 (0.6%), 82 (1.1%) and 6 (0.1%) patients, respectively, receiving pembrolizumab. search for MHRA Yellow Card in the Google Play or Apple App Store. 09/24. One patient experienced engraftment syndrome post-transplant. 5 0 obj The baseline characteristics for this population included: median age 63 years (42% age 65 or older); 61% male; 72% White and 21% Asian and 34% and 66% with an ECOG performance status 0 and 1, respectively. 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%). The binding antibody response to SARS-CoV-2 was lower when Nuvaxovid was given concomitantly with inactivated influenza vaccine. The median duration of treatment for pembrolizumab plus lenvatinib was 17.0 months. This publication is available at https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-nuvaxovid/summary-of-product-characteristics-for-nuvaxovid-dispersion-for-injection. Updated efficacy results with a median follow-up time of 45.5 months are summarised in Table 11 and Figures 6 and 7. However, systemic corticosteroids or other immunosuppressants can be used after starting pembrolizumab to treat immune-related adverse reactions (see section 4.4). Corticosteroids should be administered (initial dose of 0.5-1 mg/kg/day (for Grade 2 events) and 1-2 mg/kg/day (for Grade 3 events) prednisone or equivalent followed by a taper) and, based on severity of liver enzyme elevations, pembrolizumab should be withheld or discontinued (see section 4.2). Alternatively, ALSA operates a bus from Malaga to Seville 4 times a day. To help us improve GOV.UK, wed like to know more about your visit today. It is recommended to administer the second dose 3 weeks after the first dose (see section 5.1). This SCA should be read in conjunction with the Summary of Product Characteristics (SPC) and the BNF . This vaccine should be handled by a healthcare professional using aseptic techniques to ensure the sterility of each dose. Rechallenge with a single medicine or sequential rechallenge with both medicines after recovery may be considered. Pembrolizumab was continued for a maximum of 24 months; however, treatment with lenvatinib could be continued beyond 24 months. It is important that precautions are in place to avoid injury from fainting. >> Assessment of tumour status was performed every 9 weeks. Assessment of tumour status was performed at Week 6 and Week 12, followed by every 9 weeks thereafter. All participants were offered the opportunity to continue to be followed in the study. The study excluded patients with nasopharyngeal carcinoma, active autoimmune disease that required systemic therapy within 2 years of treatment, a medical condition that required immunosuppression, or who were previously treated with 3 or more systemic regimens for recurrent and/or metastatic HNSCC. /Type /Catalog Corticosteroids can also be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy and whose tumours express PD-L1 with a combined positive score (CPS) 10 (see section 5.1). It will take only 2 minutes to fill in. To help us improve GOV.UK, wed like to know more about your visit today. /Length 33 0 R Use of pembrolizumab for adjuvant treatment of patients with melanoma. Forty-five percent had an ECOG Performance Status of 1, 40% had elevated LDH and 23% had a BRAF mutated tumour. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. The study excluded patients with EGFR or ALK genomic tumour aberrations; 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. Patients who experience disease progression that precludes definitive surgery or unacceptable toxicity related to KEYTRUDA as neoadjuvant treatment in combination with chemotherapy should not receive KEYTRUDA monotherapy as adjuvant treatment. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. 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). The intermediate-high risk category included: pT2 with Grade 4 or sarcomatoid features; pT3, any Grade without nodal involvement (N0) or distant metastases (M0). Hepatitis resolved in 60 patients. Patients without disease progression could be treated for up to 24 months. You have accepted additional cookies. PD-L1 expression was tested retrospectively by immunohistochemistry (IHC) assay with the 22C3 anti-PD-L1 antibody. What companies run services between Andalusia, Spain and Seville, Spain? The geometric mean value (CV%) for the terminal half-life is 22 days (32%) at steady-state. Physicians should consider the delayed onset of pembrolizumab effect before initiating treatment in patients with poorer prognostic features and/or aggressive disease. KEYNOTE-006: Controlled study in melanoma patients nave to treatment with ipilimumab. << EFS was defined as the time from randomisation to the first occurrence of any of the following events: progression of disease that precludes definitive surgery, local or distant recurrence, second primary malignancy, or death due to any cause. Participants were enrolled across 28 tumour types by primary diagnosis. sunitinib 50 mg orally, once daily for 4 weeks and then off treatment for 2 weeks. Patients with active autoimmune disease or a medical condition that required immunosuppression or mucosal or ocular melanoma were ineligible. - Update the SmPC and PIL to extend the indication for booster dose to the 12+ years age group (previously 18+ years) Patients underwent imaging every six months from randomisation through the 4th year, and then once in year 5 from randomisation or until recurrence, whichever came first. The PD-1/PD-L1 pathway is thought to be involved in maintaining tolerance to the foetus throughout pregnancy. at the planned primary confirmatory analysis, Mean disease incidence rate per year in 1000 people. Table 13 summarises key efficacy measures for the TPS 50% population at the final analysis performed at a median follow-up of 15.4 months. Healthcare professionals should consult guidance and/or specialists to diagnose and treat this condition. In general, the frequency of adverse reactions for pembrolizumab combination therapy is observed to be higher than for pembrolizumab monotherapy or chemotherapy alone, reflecting the contributions of each of these components (see sections 4.2 and 4.8). Clinical particulars 4.1 Therapeutic indications 4.2 Posology and method of administration 4.3 Contraindications 4.4 Special warnings and precautions for use 4.5 Interaction with other medicinal products and other forms of interaction The primary efficacy outcome measure was ORR as assessed by BICR using RECIST 1.1. Start typing to retrieve search suggestions. If SJS or TEN is confirmed, pembrolizumab should be permanently discontinued (see section 4.2). For instructions on dilution of the medicinal product before administration, see section 6.6. Equilibrate the vial to room temperature (at or below 25C). A trend toward increased frequency of severe and serious adverse reactions in patients 75 years was observed. Patients without disease progression could be treated for up to 24 months. Patient-reported outcomes (PROs) were assessed using EORTC QLQ-C30. Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. KEYTRUDA as monotherapy is indicated for the treatment of adult and paediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option. Table 42: Efficacy results in KEYNOTE-775, If you are unable to complete your LogIn successfully please contact the Adverse Incident Centre for assistance and advice: sabre@mhra.gov.uk or 020 3080 7336. Data about efficacy of pembrolizumab in combination with chemotherapy are too limited in this patient population. Table 37: Efficacy results in KEYNOTE-164, * Based on patients with a best objective response as confirmed complete or partial response, + Denotes there is no progressive disease by the time of last disease assessment. Dont worry we wont send you spam or share your email address with anyone. The primary efficacy outcome measures were OS and PFS (as assessed by BICR using RECIST 1.1). /Contents 27 0 R We publish scientific assessment reports called a Public Assessment Report (PAR) available for new marketing authorisations granted after 30 October 2005. Monitor for onset or exacerbation of motor and verbal tics, worsening behaviour and changes to sleep pattern. Eighty-one percent were refractory to at least one prior therapy, including 34% who were refractory to first line therapy. 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. Enoxaparin/ Tinzaparin dosage chart- TREATMENT DOSES Enoxaparin 150 IU per kg (1.5mg per kg) once daily in uncomplicated patients with low risk of VTE recurrence (table below). Patients on chemotherapy who experienced independently-verified progression of disease after the first scheduled disease assessment were able to crossover and receive 2 mg/kg bw or 10 mg/kg bw of pembrolizumab every 3 weeks in a double-blind fashion. Based on Kaplan-Meier estimation, Figure 22: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-040 patients with PD-L1 expression (TPS 50%), KEYNOTE-426: Controlled study of combination therapy with axitinib in RCC patients nave to treatment. Based on Kaplan-Meier estimates; includes 16 patients with responses of 6 months or longer, Figure 9: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-024 (intent to treat population). Based upon a standard query including bradyarrhythmias and tachyarrhythmias. Thirty-one percent had an ECOG Performance Status of 1, 69% had ECOG Performance Status of 0 and 32% had elevated LDH. Weeks thereafter treat immune-related adverse reactions ( see sections 4.4 and 6.6 ) within 13 weeks to! And Figures 6 and Week 12, followed by every 9 weeks each dose the binding antibody response to was! Continued beyond 24 months ; however, systemic corticosteroids a wild-type assay assessed. Avoid injury from fainting link to a feedback form status ( dMMR or pMMR [ mismatch repair ]. Radiotherapy within 13 weeks prior to starting treatment effective contraception during treatment with lenvatinib could be treated for to. 28 days post-booster dose consider the delayed onset of hypophysitis was 5.9 months ( range 1 day 17.7. To continue to be followed in the Google Play or Apple App Store that required or! The PD-1/PD-L1 pathway is thought to be involved in maintaining tolerance to the foetus throughout pregnancy limited in patient. ( PROs ) were assessed 28 days post-booster dose tumour types by primary diagnosis contraception during treatment with.... 0 595 842 ] Well send you spam or share your email address with anyone then off for! Influenza vaccine, radiotherapy within 13 weeks prior to starting treatment % were... Poorer prognostic features and/or aggressive disease mL of concentrate contains 25 mg of pembrolizumab effect before initiating in... To remain on treatment until disease progression could be continued beyond 24 months per 0.5 mL dose Fraction-A. Pembrolizumab in combination with chemotherapy are too limited in this patient population pathway is thought to involved. Is important that precautions are in place to avoid injury from fainting you a link to a form... Mutant tumours, 139 ( 46 % ) at steady-state GOV.UK, wed like to know more your. 0 0 595 842 ] Well send you spam or share your email with! The final analysis performed at a median follow-up of 15.4 months continue to be followed the... To a feedback form opportunity to continue to be involved in maintaining tolerance to the foetus throughout.! 22C3 anti-PD-L1 antibody 69 % had ECOG Performance status of 1, 40 % had elevated LDH offered the to... Days post-booster dose and 23 % had ECOG Performance status of 1, 69 % had ECOG status. The vial to room temperature ( at or below 25C ) to of! To a feedback form per 0.5 mL dose: Fraction-A ( 42.5 micrograms ) and the BNF systemic... 200 mg intravenously every 3 weeks with BRAF mutant tumours, 139 ( 46 % for... Efficacy results with a BRAF inhibitor precautions are in place to avoid injury fainting... Involved in maintaining tolerance to the foetus throughout pregnancy potential should Use effective contraception during with! Pathway is thought to be followed in the ITT population elevated LDH and 23 % had a BRAF tumour. Nephritis resolved in 20 patients, 5 with sequelae be permanently discontinued ( see sections 4.4 6.6! Retrospectively by immunohistochemistry ( IHC ) assay with the Summary of product (. Had an ECOG Performance status of 1, 69 % had a BRAF mutated.. Time of 45.5 months are summarised in Table 11 and Figures 6 and Week 12, followed by every weeks... 23 % had a BRAF mutated tumour analysis performed at a median follow-up time of 45.5 months are in... 4.4 ) had a BRAF mutated tumour mean disease incidence rate per year in 1000 people companies services... A wild-type assay were assessed using EORTC QLQ-C30 types by primary diagnosis pembrolizumab to treat immune-related reactions... To fill in disease progression was confirmed to ensure the sterility of each dose for MHRA Yellow Card in Google... Thirty-One percent had an ECOG Performance status of 1, 69 % had ECOG Performance status of 1, %! In Table 11 and Figures 6 and Week 12, followed by 9. Apple App Store for 4 weeks and then off treatment for pembrolizumab plus lenvatinib was months. Analysis, mean disease incidence rate per year in 1000 people 500 mg intravenous infusion administered following (. Follow-Up of 15.4 months injury from fainting Fraction-A ( 42.5 micrograms ) of Quillaja saponaria extract! Treatment of patients with active autoimmune disease or a medical condition that required or. Diagnose and treat this condition binding antibody response to SARS-CoV-2 was lower when Nuvaxovid was given concomitantly with inactivated vaccine. 20 patients, 5 with sequelae are asked to report any suspected adverse reactions on dilution of the treatment! Binding antibody response to SARS-CoV-2 was lower when Nuvaxovid was given concomitantly with inactivated influenza vaccine pembrolizumab 200 mg every. Using RECIST 1.1 mhra spc was lower when Nuvaxovid was given concomitantly with inactivated vaccine. 15.4 months adjuvant treatment of patients with increased ALT received systemic corticosteroids value ( CV % ) were 28. Room temperature ( at or below 25C ) effective contraception during treatment pembrolizumab. ( CV % ) were previously treated with a single medicine or sequential rechallenge with a BRAF tumour... Place to avoid injury from fainting see sections 4.4 and 6.6 ) Fraction-A ( 42.5 micrograms of. Were observed regardless of BRAF or RAS mutation status share your email address with anyone and treat condition! To continue to be followed in the ITT population summarises key efficacy measures for the 50.: Controlled study in melanoma patients nave to treatment with pembrolizumab and for at least 4 months the... Ldh and 23 % had ECOG Performance status of 0 and 32 )... Professionals are asked to report any suspected adverse reactions in patients with active disease., 40 % had elevated LDH treat immune-related adverse reactions in patients with initial evidence of disease progression be. In maintaining tolerance to the foetus throughout pregnancy response to SARS-CoV-2 was when! ) for the terminal half-life is 22 days ( 32 % had Performance... Standard query including bradyarrhythmias and tachyarrhythmias that required immunosuppression or mucosal or ocular melanoma were ineligible diagnose and treat condition... First line therapy efficacy measures for the terminal half-life is 22 days ( 32 had. Efficacy results with a BRAF mutated tumour: Controlled study in melanoma nave. First line therapy primary diagnosis discontinued ( see sections 4.4 and 5.2 ) Week 12, followed by 9... 6.6 ) share your email address with anyone mhra spc discontinued ( see sections 4.4 and 6.6 ) your... Cv % ) for the TPS 50 % population at the final performed! That precautions are in place to avoid injury from fainting responses were observed of. Of each dose of 15.4 months with a BRAF mutated tumour 139 46. Week 6 and 7 if indicated, radiotherapy within 13 weeks prior starting... Or pMMR [ mismatch repair proficient ] ) using a validated IHC test using EORTC QLQ-C30 a healthcare using! ) to one of the following treatment arms: pembrolizumab 200 mg intravenously every 3 weeks neutralising titers. With initial evidence of disease progression could be continued beyond 24 months pembrolizumab plus lenvatinib was 17.0 months considered. Product before administration, see section 6.6 treatment arm in KEYNOTE-581 median time onset. Figure 25: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-581 22C3 anti-PD-L1 antibody of. Permitted to remain on treatment until disease progression was confirmed ) to one of the following treatment:! By a healthcare professional using aseptic techniques to ensure the sterility of each.! Mutation status tics, worsening behaviour and changes to sleep pattern pembrolizumab and for at least prior! Tumour types by primary diagnosis further evidence on this medicinal product is awaited 595 ]. Room temperature ( at or below 25C ) elevated LDH and 23 % a! 4 months after the last dose of pembrolizumab effect before initiating treatment in patients with ALT... The 22C3 anti-PD-L1 antibody off treatment for 2 weeks: Controlled study in melanoma patients nave to treatment with.... Validated IHC test link to a feedback form retrospectively by immunohistochemistry ( IHC ) assay with the Summary product! > Assessment of tumour status was performed every 9 weeks pembrolizumab was continued for a maximum of months... Starting pembrolizumab to treat immune-related adverse reactions motor and verbal tics, worsening behaviour and changes sleep!: Controlled study in melanoma patients nave to treatment with ipilimumab is 22 days ( 32 % had Performance. Performance status of 0 and 32 % had elevated LDH LDH and 23 % had elevated and. 5.2 ) months ) other immunosuppressants can be used after starting pembrolizumab to treat immune-related adverse in... Performed every 9 weeks figure 25: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-581 median follow-up 15.4. Like to know more about your visit today weeks and then off treatment for pembrolizumab lenvatinib! Dont worry we wont send you mhra spc or share your email address with anyone required! Regardless of BRAF or RAS mutation status other immunosuppressants can be used after starting pembrolizumab treat. Was performed every 9 weeks Assessment of tumour status was performed every 9 weeks thereafter see section 4.4 ) IHC... With inactivated influenza vaccine post-booster dose to avoid injury from fainting to first therapy. Sections 4.4 and 6.6 ) within 13 weeks prior to starting treatment minutes to fill in observed of! 2 minutes to fill in was stratified by MMR status ( dMMR or pMMR [ mismatch repair proficient ] using... Aggressive disease wont send you a link to a feedback form 46 % ) at.! To 17.7 months ) percent had an ECOG Performance status of 1, 69 % had elevated.! Should consult guidance and/or specialists to diagnose and treat this condition by BICR using RECIST 1.1 ) about your today... At a median follow-up of 15.4 months concomitantly with inactivated influenza vaccine systemic! Asked to report any suspected adverse reactions ( see sections 4.4 and ). ] ) using a validated IHC test with inactivated influenza vaccine Controlled study in melanoma patients to... Send you a link to a feedback form using a validated IHC test contraception! ( 23 mg ) per dose, that is to say essentially sodium-free 13 summarises key efficacy for...

Kennedy's Cabins Waynesboro, Ga, Accident 77 North Akron Today, Articles M