WWW.DISSERTATION.XLIBX.INFO
FREE ELECTRONIC LIBRARY - Dissertations, online materials
 
<< HOME
CONTACTS



Pages:   || 2 | 3 | 4 | 5 |   ...   | 9 |

«ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS This medicinal product is subject to additional monitoring. This will allow quick identification of new ...»

-- [ Page 1 ] --

ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

This medicinal product is subject to additional monitoring. This will allow quick identification of

new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

See section 4.8 for how to report adverse reactions.

1. NAME OF THE MEDICINAL PRODUCT

KEYTRUDA 50 mg powder for concentrate for solution for infusion.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One vial of powder contains 50 mg of pembrolizumab.

After reconstitution, 1 mL of concentrate contains 25 mg of pembrolizumab.

Pembrolizumab is a humanised monoclonal anti-programmed cell death-1 (PD-1) antibody (IgG4/kappa isotype with a stabilising sequence alteration in the Fc region) produced in Chinese hamster ovary cells by recombinant DNA technology.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM Powder for concentrate for solution for infusion.

White to off-white lyophilised powder.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications KEYTRUDA as monotherapy is indicated for the treatment of advanced (unresectable or metastatic) melanoma in adults.

KEYTRUDA is indicated for the treatment of locally advanced or metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumours express PD-L1 and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumour mutations should also have received approved therapy for these mutations prior to receiving KEYTRUDA.

4.2 Posology and method of administration Treatment must be initiated and supervised by specialist physicians experienced in the treatment of cancer.

PD-L1 testing for patients with NSCLC Patients with NSCLC should be selected for treatment based on the tumour expression of PD-L1 confirmed by a validated test (see section 5.1).

Posology The recommended dose of KEYTRUDA is 2 mg/kg administered intravenously over 30 minutes every 3 weeks. Patients should be treated with KEYTRUDA until disease progression or unacceptable toxicity. Atypical responses (i.e., an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed. It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed.

Dose delay or discontinuation (see also section 4.4) Table 1: Recommended treatment modifications for KEYTRUDA Immune-related adverse Severity Treatment modification reactions Pneumonitis Grade 2 Withhold* Grade 3 or 4, or recurrent Grade 2 Permanently discontinue Colitis Grade 2 or 3 Withhold*

–  –  –

KEYTRUDA should be permanently discontinued:

• For Grade 4 toxicity except for endocrinopathies that are controlled with replacement hormones

• If corticosteroid dosing cannot be reduced to ≤10 mg prednisone or equivalent per day within 12 weeks

• If a treatment-related toxicity does not resolve to Grade 0-1 within 12 weeks after last dose of KEYTRUDA

• If any event occurs a second time at Grade ≥ 3 severity.

Patients treated with KEYTRUDA must be given the Patient Alert Card and be informed about the risks of KEYTRUDA (see also package leaflet).

Special populations Elderly No overall differences in safety or efficacy were reported between elderly patients (≥ 65 years) and younger patients ( 65 years). No dose adjustment is necessary in this population.

Renal impairment No dose adjustment is needed for patients with mild or moderate renal impairment. KEYTRUDA has not been studied in patients with severe renal impairment (see section 5.2).

Hepatic impairment No dose adjustment is needed for patients with mild hepatic impairment. KEYTRUDA has not been studied in patients with moderate or severe hepatic impairment (see section 5.2).

Ocular melanoma There are limited data on the safety and efficacy of KEYTRUDA in patients with ocular melanoma (see section 5.1).

Paediatric population The safety and efficacy of KEYTRUDA in children below 18 years of age have not yet been established. No data are available.

Method of administration KEYTRUDA must be administered by intravenous infusion over 30 minutes. KEYTRUDA must not be administered as an intravenous push or bolus injection.

For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.

4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use Assessment of PD-L1 status When assessing the PD-L1 status of the tumour, it is important that a well-validated and robust methodology is chosen to minimise false negative or false positive determinations.

Immune-related adverse reactions Most immune-related adverse reactions occurring during treatment with pembrolizumab were reversible and managed with interruptions of pembrolizumab, administration of corticosteroids and/or supportive care. Immune-related adverse reactions have also occurred after the last dose of pembrolizumab.





For suspected immune-related adverse reactions, adequate evaluation to confirm aetiology or exclude other causes should be ensured. Based on the severity of the adverse reaction, pembrolizumab should be withheld and corticosteroids administered. Upon improvement to Grade ≤ 1, corticosteroid taper should be initiated and continued over at least 1 month. 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.

Pembrolizumab may be restarted within 12 weeks after last dose of KEYTRUDA if the adverse reaction remains at Grade ≤ 1 and corticosteroid dose has been reduced to ≤ 10 mg prednisone or equivalent per day.

Pembrolizumab must be permanently discontinued for any Grade 3 immune-related adverse reaction that recurs and for any Grade 4 immune-related adverse reaction toxicity, except for endocrinopathies that are controlled with replacement hormones (see sections 4.2 and 4.8).

Immune-related pneumonitis Pneumonitis, including fatal cases, has been reported in patients receiving pembrolizumab (see section 4.8). Patients should be monitored for signs and symptoms of pneumonitis. Suspected pneumonitis should be confirmed with radiographic imaging and other causes excluded.

Corticosteroids should be administered for Grade ≥ 2 events (initial dose of 1-2 mg/kg/day prednisone or equivalent followed by a taper); pembrolizumab should be withheld for Grade 2 pneumonitis, and permanently discontinued for Grade 3, Grade 4 or recurrent Grade 2 pneumonitis (see section 4.2).

Immune-related colitis Colitis has been reported in patients receiving pembrolizumab (see section 4.8). Patients should be monitored for signs and symptoms of colitis, and other causes excluded. Corticosteroids should be administered for Grade ≥ 2 events (initial dose of 1-2 mg/kg/day prednisone or equivalent followed by a taper); pembrolizumab should be withheld for Grade 2 or Grade 3 colitis, and permanently discontinued for Grade 4 colitis (see section 4.2). The potential risk of gastrointestinal perforation should be taken into consideration.

Immune-related hepatitis Hepatitis has been reported in patients receiving pembrolizumab (see section 4.8). 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.

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).

Immune-related nephritis Nephritis has been reported in patients receiving pembrolizumab (see section 4.8). Patients should be monitored for changes in renal function, and other causes of renal dysfunction excluded.

Corticosteroids should be administered for Grade ≥ 2 events (initial dose of 1-2 mg/kg/day prednisone or equivalent followed by a taper) and, based on severity of creatinine elevations, pembrolizumab should be withheld for Grade 2, and permanently discontinued for Grade 3 or Grade 4 nephritis (see section 4.2).

Immune-related endocrinopathies Severe endocrinopathies, including hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism have been observed with pembrolizumab treatment.

Long-term hormone replacement therapy may be necessary in cases of immune-related endocrinopathies.

Hypophysitis has been reported in patients receiving pembrolizumab (see section 4.8). Patients should be monitored for signs and symptoms of hypophysitis (including hypopituitarism and secondary adrenal insufficiency) and other causes excluded. Corticosteroids to treat secondary adrenal insufficiency and other hormone replacement should be administered as clinically indicated, and pembrolizumab should be withheld for symptomatic hypophysitis until the event is controlled with hormone replacement. Continuation of pembrolizumab may be considered, after corticosteroid taper, if needed (see section 4.2). Pituitary function and hormone levels should be monitored to ensure appropriate hormone replacement.

Type 1 diabetes mellitus, including diabetic ketoacidosis, has been reported in patients receiving pembrolizumab (see section 4.8). Patients should be monitored for hyperglycaemia or other signs and symptoms of diabetes. Insulin should be administered for type 1 diabetes, and pembrolizumab should be withheld in cases of Grade 3 hyperglycaemia until metabolic control is achieved (see section 4.2).

Thyroid disorders, including hypothyroidism, hyperthyroidism and thyroiditis, have been reported in patients receiving pembrolizumab and can occur at any time during treatment; therefore, patients should be monitored for changes in thyroid function (at the start of treatment, periodically during treatment and as indicated based on clinical evaluation) and clinical signs and symptoms of thyroid disorders. Hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids. Hyperthyroidism may be managed symptomatically. Pembrolizumab should be withheld for Grade ≥ 3 until recovery to Grade ≤ 1 hyperthyroidism. For patients with Grade 3 or Grade 4 hyperthyroidism that improved to Grade 2 or lower, continuation of pembrolizumab may be considered, after corticosteroid taper, if needed (see sections 4.2 and 4.8).

Thyroid function and hormone levels should be monitored to ensure appropriate hormone replacement.

Other immune-related adverse reactions The following additional clinically significant, immune-related adverse reactions have been reported in patients receiving pembrolizumab: uveitis, arthritis, myositis, pancreatitis, severe skin reactions, Guillain-Barré syndrome, myasthenic syndrome, haemolytic anaemia and partial seizures arising in a patient with inflammatory foci in brain parenchyma (see section 4.8).

Based on the severity of the adverse reaction, pembrolizumab should be withheld and corticosteroids administered.

Pembrolizumab may be restarted within 12 weeks after last dose of KEYTRUDA if the adverse reaction remains at Grade ≤ 1 and corticosteroid dose has been reduced to ≤ 10 mg prednisone or equivalent per day.

Pembrolizumab must be permanently discontinued for any Grade 3 immune related adverse reaction that recurs and for any Grade 4 immune related adverse reaction toxicity (see sections 4.2 and 4.8).

Infusion-related reactions Severe infusion-related reactions have been reported in patients receiving pembrolizumab (see section 4.8). For severe infusion reactions, infusion should be stopped and pembrolizumab permanently discontinued (see section 4.2). Patients with mild or moderate infusion reaction may continue to receive pembrolizumab with close monitoring; premedication with antipyretic and antihistamine may be considered.

Patients excluded from clinical trials Patients with the following conditions were excluded from clinical trials: active CNS metastases; HIV, hepatitis B or hepatitis C infection; active systemic autoimmune disease; interstitial lung disease; prior pneumonitis requiring systemic corticosteroid therapy; a history of severe hypersensitivity to another monoclonal antibody; receiving immunosuppressive therapy and a history of severe immune-related adverse reactions from treatment with ipilimumab, defined as any Grade 4 toxicity or Grade 3 toxicity requiring corticosteroid treatment ( 10 mg/day prednisone or equivalent) for greater than 12 weeks.

Patients with active infections were excluded from clinical trials and were required to have their infection treated prior to receiving pembrolizumab. Patients with active infections occurring during treatment with pembrolizumab were managed with appropriate medical therapy. Patients with clinically significant renal (creatinine 1.5 x ULN) or hepatic (bilirubin 1.5 x ULN, ALT, AST

2.5 x ULN in the absence of liver metastases) abnormalities at baseline were excluded from clinical trials, therefore information is limited in patients with severe renal and moderate to severe hepatic impairment.

After careful consideration of the potential increased risk, pembrolizumab may be used with appropriate medical management in these patients.

Patient Alert Card All prescribers of KEYTRUDA must be familiar with the Physician Information and Management Guidelines. The prescriber must discuss the risks of KEYTRUDA therapy with the patient. The patient will be provided with the Patient Alert Card with each prescription.

4.5 Interaction with other medicinal products and other forms of interaction No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab. Since pembrolizumab is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected.



Pages:   || 2 | 3 | 4 | 5 |   ...   | 9 |


Similar works:

«VERMONT LEGAL AID, INC. 264 NORTH WINOOSKI AVENUE, P.O. BOX 1367 BURLINGTON, VERMONT 802-863-5620 (VOICE AND TTY) 802-863-7152 FAX By email to: robin.chapman@state.vt.us May 8, 2014 Robin Chapman, Policy Analyst Economic Services Division, DCF 103 South Main Street Waterbury, Vermont 05671-1201 Re: Comments on AHS Bulletin No. 14-04P Dear Robin: Thank you for the opportunity to comment on the proposed rules issued March 21, 2014 in Agency of Human Services Bulletin No. 14-04P. Contents...»

«297 Ga. 810 FINAL COPY S15A0795. WARREN v. THE STATE. NAHMIAS, Justice. Jesse James Warren has been indicted on four counts of murder and many additional charges in connection with a mass shooting at a Penske Trucking Company location in Cobb County on January 12, 2010, in which four victims were killed and a fifth victim was paralyzed. The State has given notice of its intent to seek the death penalty. On March 4, 2013, Warren filed a special plea of mental incompetence to stand trial. See...»

«CATC01 04/27/2005 04:59PM Page 1 CHAPTER 1 A right, not a privilege! M. Whiteson In 1948, when the National Health Service was established in the UK, we were promised health-care ‘from the cradle to the grave’. No-one mentioned much about the in-between years. Here, and in many other countries, health-care is provided separately for children and adults. The age at which one becomes an ‘adult’ in this context varies from 12 to 18 years, and sometimes appears to be an arbitrary line drawn...»

«Neophilologus (2010) 94:165–176 DOI 10.1007/s11061-009-9172-x ‘‘Only Not beyond Love’’: Testimony, Subalternity, and the Famine in The Poetry of Eavan Boland Stef Craps Published online: 4 September 2009 Ó Springer Science+Business Media B.V. 2009 Abstract The poetry of Eavan Boland, Ireland’s leading woman poet, is marked by an acute awareness of the problems attendant on the recovery of the experience of subaltern or oppressed women. Rather than usurping the place of the other...»

«Stressful life events exposure is associated with 17-year mortality, but it is health-related events that prove predictive. Anna C. Phillips1, Geoff Der2, Douglas Carroll1 1 School of Sport and Exercise Sciences, University of Birmingham, Birmingham, England 2 MRC Social and Public Health Sciences Unit, University of Glasgow, Glasgow, Scotland Running Head: Life events and mortality Word Count: 3603 Address correspondence to: Douglas Carroll, PhD, School of Sport and Exercise Sciences,...»

«RESEARCH PORTFOLIO RESEARCH PORTFOLIO ANNUAL REPORT APRIL 1, 2011MARCH 31, 2012 ALBERTA HEALTH SERVICES 1 ANNUAL REPORT APRIL 1, 2011MARCH 31, 2012 ALBERTA HEALTH SERVICES 2 RESEARCH PORTFOLIO TABLE OF CONTENTS 1. INTRODUCTION / EXECUTIVE SUMMARY 2. ALIGNING AHS WITHIN ALBERTA’S HEALTH RESEARCH POLICY FRAMEWORK 2.1 Strategic Clinical Networks 2.2 Operational Clinical Networks 2.3 AHS Research and Innovation Strategy 3. STRATEGIC PARTNERSHIPS: BUILDING STRONG PARTNERSHIPS IN ALBERTA 3.1...»

«We've Found 1,598 Cereals Make a Heart Healthy Claim Take a Live Demo at www.labelinsight.com BRAND PRODUCT TITLE 365 INSTANT OATMEAL 365 INSTANT OATMEAL 365 STEEL CUT OATS HONEY ROASTED CLUSTERS OF OATS WITH ALMONDS AND TOASTED FLAKES OF CORN, WHEAT & RICE 3 MINUTE BRAND QUICK OATES 365 EVERYDAY VALUE INSTANT OATMEAL 365 EVERYDAY VALUE INSTANT HOT CEREAL 365 EVERYDAY VALUE INSTANT OATMEAL 365 EVERYDAY VALUE INSTANT OATMEAL 365 EVERYDAY VALUE...»

«Fight cancer with the healing power of diet and supplements by Dr. Mark Stengler Used with permission from Dr. Mark Stengler’s Health Revelations newsletter So much has been written about using diet and supplements to lower your risk of developing cancer that it could fill a library. But if you, or a loved one, have already been diagnosed with cancer, recovery is, naturally, your focus. Unfortunately, finding tips on what to do after a diagnosis isn’t nearly as easy. But there’s actually...»

«EUROPEAN COMMISSION HEALTH & CONSUMERS DIRECTORATE-GENERAL Brussels, SANCO G (2013)2615272 SUMMARY REPORT OF THE STANDING COMMITTEE ON THE FOOD CHAIN AND ANIMAL HEALTH HELD IN BRUSSELS ON 14 JUNE 2013 (Section Animal Health & Welfare) Chair: A. Laddomada, A.E. Fuessel. 26 Member States were present. Cyprus was absent and represented by Greece. Croatia attended the meeting as an observer. A representative from the European Food Safety Authority (EFSA) was present during the presentation of item...»

«1 WHO/BS/2014.2233 ENGLISH ONLY EXPERT COMMITTEE ON BIOLOGICAL STANDARDIZATION Geneva, 13 to 17 October 2014 Recommendations to assure the quality, safety and efficacy of poliomyelitis vaccine (inactivated) Proposed replacement of: TRS 910, Annex 2 16 NOTE: 18 This document has been prepared for the purpose of inviting comments and suggestions on the proposals 19 contained therein, which will then be considered by the Expert Committee on Biological Standardization 20 (ECBS). Publication of this...»

«Sherecce Fields, Ph.D. Assistant Professor Department of Psychology Texas A&M University, MS4235 College Station, TX 77843-4235 (979) 845-6053 (work) safields@tamu.edu EDUCATION 2008 – 2010 Nationwide Children’s Hospital Pediatric Psychology Fellow/Postdoctoral Scientist 2007 – 2008 Saint John’s Health Center APA Internship 2004 – 2008 University of South Florida Ph.D. in Clinical Psychology 2001 – 2004 University of South Florida M.A. in Clinical Psychology 1994 – 1998 Duke...»

«Beth Marks, PhD, RN Curriculum Vitae GENERAL INFORMATION Contact: Rehabilitation Research and Training Center on Aging with Developmental Disabilities (RRTCADD) Department of Disability and Human Development, M/C 626 College of Applied Health Sciences University of Illinois at Chicago 1640 West Roosevelt Road, Room 736 Chicago, Illinois 60608 773-350-4567 (cell) * 312-929-0326 (fax) bmarks1@uic.edu (email); rrtcadd.org; HealthMattersProgram.org; NOND.org EDUCATION University of Illinois at...»





 
<<  HOME   |    CONTACTS
2016 www.dissertation.xlibx.info - Dissertations, online materials

Materials of this site are available for review, all rights belong to their respective owners.
If you do not agree with the fact that your material is placed on this site, please, email us, we will within 1-2 business days delete him.