Direct healthcare professional communication on the important additional warnings for hemorrhage and rhabdomyolysis with Cotellic (cobimetinib), including new dose modification recommendations
14.04.2017
Roche d.o.o., the representative of Roche Registration Ltd, the marketing authorisation holder for Cotellic (cobimetinib) in the Republic of Croatia, in agreement with the Agency for Medicinal Products and Medical Devices (HALMED) and the European Medicines Agency (EMA), has informed healthcare professionals of the important additional warnings related to the use of Cotellic, including associated dose modification recommendations.
Severe haemorrhage
- Severe haemorrhagic events, including intracranial and gastrointestinal tract bleeds have been reported in patients receiving Cotellic in clinical trials or post-marketing.
- Cotellic treatment should be interrupted in the event of grade 3 or 4 bleeding events and should not be restarted after grade 4 events or cerebral haemorrhage attributed to Cotellic. Clinical judgement should be applied when considering restarting treatment after grade 3 bleeds. Vemurafenib dosing can be continued if indicated when Cotellic is interrupted.
- Cotellic should be used with caution when given to patients with additional risk factors for bleeding, such as brain metastases, and/or concomitant medications that increase the risk of bleeding (such as antiplatelet and anticoagulant therapy).
Rhabdomyolysis and creatine phosphokinase (CPK) elevations
- Rhabdomyolysis and CPK elevations have been reported in patients receiving Cotellic in clinical trials and post-marketing.
- Baseline serum CPK and creatinine levels should be measured before starting treatment, and then monitored monthly during treatment or as clinically indicated. If serum CPK is elevated, check for signs and symptoms of rhabdomyolysis or other causes.
- If grade ≤3 asymptomatic CPK elevation occurs and rhabdomyolysis has been ruled out, Cotellic dosing does not need to be modified.
- Cotellic treatment should be interrupted if rhabdomyolysis, any symptomatic CPK elevation, or grade 4 asymptomatic CPK elevation occur.
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- If they do not improve within 4 weeks, Cotellic should not be restarted.
- If severity improves by at least one grade within 4 weeks, Cotellic may be restarted under close monitoring, with the previous dose reduced by 20 mg.
- Vemurafenib dosing can be continued during any changes to Cotellic dosing.
Further information
Haemorrhage is a known adverse drug reaction for Cotellic. An analysis of post-marketing safety reports and ongoing clinical trials has identified additional severe haemorrhagic events in patients receiving Cotellic. At the time of the analysis, a total of thirty cases of severe haemorrhage have been reported from an estimated 2,817 patients exposed to Cotellic. Events include intracranial and gastrointestinal tract bleeds. In most cases of severe haemorrhage, the patients had additional risk factors for bleeding, such as central nervous system metastasis, pre-existing gastrointestinal disorders, and/or concomitant medications that increase the risk of bleeding, such as antiplatelet or anticoagulant therapy.
Rhabdomyolysis was initially reported in one patient in each treatment arm of study GO28141 (Cotellic plus vemurafenib vs placebo plus vemurafenib). Since that time, additional cases of rhabdomyolysis have been reported in the post-marketing setting and in other ongoing clinical trials.
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Healthcare professionals are reminded that they should report any adverse reaction, as well as quality defect to HALMED. Patients who have developed any adverse reaction to medicinal product may report it directly to HALMED. HALMED recommends patients to contact their doctor or pharmacist regarding any adverse reaction they notice.
