Cyramza ® (ramucirumab)

För fullständig produktresumé för Cyramza® se FASS.

Denna information är endast avsedd för sjukvårdspersonal verksam i Sverige och som svar på din fråga. Informationen nedan är på engelska

Var antikoagulantia tillåtna i Cyramza® (ramucirumab) prövningar?

Aspirin var tillåtet i de flesta studier, och alla studier tillät vissa antikoagulantia förutsatt att definierade koagulationsparametrar var uppfyllda eller att patienterna hade en stabil dos.

Important 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,

  • patients taking anticoagulants, and

  • patients taking other concomitant medicinal products that increase the risk of bleeding.1

Coagulation Requirements for Clinical Study Participation

Patients who participated in ramucirumab clinical trials needed adequate coagulation function, as specified by the study protocol.2-7

Relevant Protocol Inclusion and Exclusion Criteria by Study

Table 1. Relevant Protocol Inclusion and Exclusion Criteria by Study2-7

Study

Inclusion criteria; adequate coagulation function as defined by

Exclusion criteria

Additional permissions

REGARD

  • INR ≤1.5, and

  • PTT ≤5 seconds above the ULN (unless receiving anticoagulation therapy).8

  • 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.8

  • 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).8

RAINBOW and REVEL 

  • INR ≤1.5 or PT ≤1.5 times the ULN, and

  • PTT/aPTT ≤1.5 times the ULN.3,9

  • therapeutic anticoagulation with

    • warfarin

    • LMWH, or

    • similar agents

  • chronic therapy with

    • NSAIDs (eg, indomethacin, ibuprofen, naproxen, or similar agents), or

    • other antiplatelet agents (eg, clopidogrel, ticlopidine, dipyridamole, anagrelide).3,9

  • 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

  • once daily aspirin (maximum dose 325 mg/day).3,9

RAISE

  • INR ≤1.5, and

  • PTT ≤1.5 times the ULN (unless receiving anticoagulation therapy).

 

  • 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

REACH 2

  • INR ≤1.5, and

  • PTT ≤5 seconds above the ULN.7

  • therapeutic anticoagulation with

    • warfarin

    • LMWH, or

    • similar agents, or

  • chronic therapy with

    • NSAIDs (eg, indomethacin, ibuprofen, naproxen, or similar agents), or

    • other antiplatelet agents (eg, clopidogrel, ticlopidine, dipyridamole, anagrelide).7

  • prophylactic, low-dose anticoagulation therapy provided that the coagulation parameters defined in the inclusion criteria were met (INR ≤1.5 and PTT ≤5 seconds above the ULN), or

  • aspirin (maximum dose 100 mg/day).7

RELAY

  • INR ≤1.5 or PT ≤1.5 times the ULN, and

  • PTT/aPTT ≤1.5 times the ULN.6

Patients were excluded if, within 7 days prior to first dose of study treatment, they were receiving chronic therapy with

  • NSAIDs (eg, indomethacin, ibuprofen, naproxen, or similar agents), or

  • other antiplatelet agents (eg, clopidogrel, ticlopidine, dipyridamole, anagrelide).6

Patients who were receiving warfarin were to be switched to LMWH as per institutional guidelines and achieve stable coagulation profile prior to enrollment.6 

  • LMWH, or

  • aspirin (maximum dose 325 mg/day).6

References

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 H, 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://dx.doi.org/10.1016/S1470-2045(14)70420-6

6. Nakagawa K, Garon EB, Seto T, et al. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(12):1655-1669. https://doi.org/10.1016/S1470-2045(19)30634-5

7. Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282-296. http://dx.doi.org/10.1016/S1470-2045(18)30937-9

8. 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.

9. 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

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 2021 M03 26


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