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Cyramza ® (ramucirumab)
Denna information är endast avsedd för sjukvårdspersonal verksam i Sverige och som svar på din fråga. Informationen nedan är på engelska
Information from Summary of Product Characteristics
Ramucirumab is an antiangiogenic therapy and may increase the risk of severe bleeding. Ramucirumab should be permanently discontinued in patients who experience Grade 3 or 4 bleeding. Blood counts and coagulation parameters should be monitored in patients with conditions predisposing to bleeding, and in those treated with anticoagulants or other concomitant medicinal products that increase the risk of bleeding.1
Coagulation Requirements for Clinical Study Participation
Patients who participated in ramucirumab clinical trials generally must have had adequate coagulation function as defined by INR ≤1.5 or PT ≤1.5 times the ULN, and PTT/aPTT ≤1.5 times the ULN.2-5
Relevant Protocol Inclusion and Exclusion Criteria by Study
REGARD Study
Patients were eligible for participation if they had adequate coagulation function as defined by
INR ≤1.5, and
PTT ≤5 seconds above the ULN (unless receiving anticoagulation therapy).2
Patients were excluded if they were receiving
anticoagulation therapy with unresected primary tumors or local tumor recurrence following resection, or
current chronic antiplatelet therapy, including
aspirin
NSAIDs (including ibuprofen, naproxen, and others)
dipyridamole or clopidogrel, or
similar agents.2
Patients were also permitted to participate if receiving
full-dose anticoagulation provided that they were on a stable dose (minimum duration 14 days) of oral anticoagulant or LMWH
once daily aspirin use (maximum dose 325 mg/day), or
warfarin, provided that they had
an INR ≤3.0 and
no active bleeding (ie, no bleeding within 14 days prior to first dose of study therapy) or pathological condition present that carried a high risk of bleeding (eg, tumor involving major vessels or known varices).2
RAINBOW and REVEL Studies
Patients were eligible for participation if they had adequate coagulation function as defined by
Patients were excluded if they were receiving
therapeutic anticoagulation with
warfarin
LMWH, or
similar agents
chronic therapy with
Patients were also permitted to participate if receiving
prophylactic, low-dose anticoagulation therapy provided that the coagulation parameters defined in the inclusion criteria were met (INR ≤1.5 and PTT/aPTT ≤1.5 times ULN) or (PT ≤1.5 times ULN and PTT/aPTT ≤1.5 times ULN), or
RAISE Study
Patients were eligible for participation if they had adequate coagulation function as defined by
INR ≤1.5, and
PTT ≤1.5 times the ULN (unless receiving anticoagulation therapy).4
Patients were also permitted to participate if receiving
full-dose anticoagulation provided that they were on a stable dose (minimum duration 14 days) of oral anticoagulant or LMWH, or
warfarin, provided that they had
an INR ≤3.0 and
no clinically significant active bleeding (ie, bleeding within 14 days prior to randomization) or pathological condition present that carried a high risk of bleeding (eg, intact primary tumor with a history of clinically significant bleeding, or tumor involving major vessels or known esophageal varices).4
Treatment of Thrombotic Events While on Ramucirumab Therapy
Patients who developed grade 3-4 venous thrombotic events may have continued study therapy if
the event was not considered to be life-threatening in the opinion of the investigator, or
the patient was asymptomatic and the event could be adequately treated with LMWH-based therapy (REGARD)/anticoagulation therapy (RAINBOW, REVEL, RAISE).2,4-6
Patients with unresected primary tumors (or local recurrence) who developed grade 3-4 venous thromboembolism may have also received anticoagulation and continued study therapy, provided that the tumor did not confer an excessive bleeding risk, in the opinion of the investigator (REGARD only).2
Patients were warranted for discontinuation of study therapy if they experienced
grade 3-4 ATEs (RAINBOW, REVEL, RAISE, REGARD), or
any PE/DVT that occurred or intensified during anticoagulant therapy (REGARD, RAINBOW, RAISE).2,4-6
1. Cyramza [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
2. Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31-39. http://dx.doi.org/10.1016/S0140-6736(13)61719-5.
3. Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384(9944):665-673. http://dx.doi.org/10.1016/S0140-6736(14)60845-X
4. Tabernero J, Yoshino T, Cohn AL, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015;16(5):499-508. http://dx.doi.org/10.1016/S1470-2045(15)70127-0
5. Wilke W, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224-1235. http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70420-6/fulltext
6. Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Glossary
aPTT = activated partial thromboplastin time
ATE = arterial thromboembolic event
DVT = deep vein thrombosis
INR = international normalized ratio
LMWH = low-molecular-weight heparin
NSAID = nonsteroidal anti-inflammatory drug
PE = pulmonary embolism
PT = prothrombin time
PTT = partial thromboplastin time
ULN = upper limit of normal
Datum fӧr senaste ӧversyn 2018 M08 06