Cotellic

Last reviewed on RxList: 2/7/2018
Cotellic Side Effects Center

Last reviewed on RxList 2/7/2018

Cotellic (cobimetinib) is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib. Common side effects of Cotellic include:

The recommended dose of Cotellic is 60 mg orally once daily for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity. Cotellic may interact with itraconazole, erythromycin, ciprofloxacin, carbamazepine, efavirenz, phenytoin, rifampin, and St. John's Wort. Tell your doctor all medications and supplements you use. Cotellic is not recommended for use during pregnancy; it may harm a fetus. It is unknown how Cotellic would affect a nursing infant. Because of the potential for serious side effects in a breastfed infant, nursing women are advised not to breastfeed during treatment with Cotellic and for 2 weeks after the final dose.

Our Cotellic (cobimetinib) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Self-examination is important in the detection of skin cancer. See Answer
Cotellic Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using cobimetinib and call your doctor at once if you have:

  • vision changes, partial vision loss, seeing halos around lights;
  • unexplained muscle pain, tenderness, or weakness (especially if you also have fever and dark colored urine);
  • easy bruising or bleeding (nosebleeds, bleeding gums);
  • signs of bleeding inside the body--weakness, dizziness, headache, red or pink urine, bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;
  • signs of a heart problem--cough, wheezing, shortness of breath (even with mild exertion), chest pain, fast heartbeats, swelling in your feet or ankles;
  • low levels of sodium in the body--headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
  • liver problems--nausea, upper stomach pain, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
  • severe skin reaction--skin pain, itching, redness, bumps or pimples, thickened or wrinkled skin, skin rash that spreads and causes blistering and peeling.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • nausea, vomiting, diarrhea;
  • fever;
  • sunburn or increased sensitivity to sunlight;
  • low sodium levels; or
  • abnormal laboratory tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Cotellic (Cobimetinib Tablets)

SLIDESHOW

Sun-Damaged Skin: Pictures of Sun Spots, Wrinkles, Sunburns See Slideshow
Cotellic Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the label:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of COTELLIC was evaluated in Trial 1, a randomized (1:1), double-blind, active-controlled trial in previously untreated patients with BRAF V600 mutation-positive, unresectable or metastatic melanoma [see Clinical Studies]. All patients received vemurafenib 960 mg twice daily on Days 1-28 and received either COTELLIC 60 mg once daily (n=247) or placebo (n=246) on Days 1-21 of each 28-day treatment cycle until disease progression or unacceptable toxicity. In the COTELLIC plus vemurafenib arm, 66% percent of patients were exposed for greater than 6 months and 24% of patients were exposed for greater than 1 year. Patients with abnormal liver function tests, history of acute coronary syndrome within 6 months, evidence of Class II or greater congestive heart failure (New York Heart Association), active central nervous system lesions, or evidence of retinal pathology were excluded from Trial 1. The demographics and baseline tumor characteristics of patients enrolled in Trial 1 are summarized in Clinical Studies [see Clinical Studies].

In Trial 1, 15% of patients receiving COTELLIC experienced an adverse reaction that resulted in permanent discontinuation of COTELLIC. The most common adverse reactions resulting in permanent discontinuation were liver laboratory abnormalities defined as increased aspartate aminotransferase (AST) (2.4%), increased gamma glutamyltransferase (GGT) (1.6%) and increased alanine aminotransferase (ALT) (1.6%); rash (1.6%); pyrexia (1.2%); and retinal detachment (2%). Among the 247 patients receiving COTELLIC, adverse reactions led to dose interruption or reductions in 55%. The most common reasons for dose interruptions or reductions of COTELLIC were rash (11%), diarrhea (9%), chorioretinopathy (7%), pyrexia (6%), vomiting (6%), nausea (5%), and increased creatine phosphokinase (CPK) (4.9%). The most common ( ≥ 20%) adverse reactions with COTELLIC were diarrhea, photosensitivity reaction, nausea, pyrexia, and vomiting.

Table 3: Incidence of Adverse Drug Reactions Occurring in ≥ 10% (All Grades) of Patients Receiving COTELLIC with Vemurafenib and at a Higher Incidence* than Patients Receiving Vemurafenib in Trial 1

Adverse reactions COTELLIC + Vemurafenib (n=247) Placebo + Vemurafenib (n=246)
All Gradesa (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%)
GASTROINTESTINAL DISORDERS
  Diarrhea 60 6 31 1
  Nausea 41 1 25 1
  Vomiting 24 1 13 1
  Stomatitisb 14 1 8 0
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
  Photosensitivity reactionc 46 4 35 0
  Acneiform dermatitis 16 2 11 1
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
  Pyrexia 28 2 23 0
  Chills 10 0 5 0
VASCULAR DISORDERS
  Hypertension 15 4 8 2
  Hemorrhaged 13 1 7 < 1
EYE DISORDERS
  Vision impairede 15 < 1 4 0
  Chorioretinopathy 13 < 1 < 1 0
  Retinal detachmentf 12 2 < 1 0
* ≥ 5% for All Grades or ≥ 2% for Grades 3–4 incidence in patients receiving COTELLIC with vemurafenib compared with patients receiving vemurafenib as a single agent
a NCI CTCAE, v4.0.
b Includes stomatitis, aphthous stomatitis, mouth ulceration, and mucosal inflammation
c Includes solar dermatitis, sunburn, photosensitivity reaction
d Includes hemorrhage, rectal hemorrhage, melena, hemorrhoidal hemorrhage, gastrointestinal hemorrhage, hematemesis, hematochezia, gingival bleeding, metrorrhagia, uterine hemorrhage, hemorrhagic ovarian cyst, menometrorrhagia, menorrhagia, vaginal hemorrhage, hemoptysis, pulmonary, cerebral, subarachnoid hemorrhage, subgaleal hematoma, hematuria, epistaxis, contusion, traumatic hematoma, ecchymosis, purpura, nail bed bleeding, ocular, eye, conjunctival, and retinal hemorrhage
e Includes vision blurred, visual acuity reduced, visual impairment
f Includes retinal detachment, detachment of retinal pigment epithelium, detachment of macular retinal pigment epithelium

Adverse reactions of vemurafenib which occurred at a lower rate in patients receiving COTELLIC plus vemurafenib were alopecia (15%), hyperkeratosis (11%), and erythema (10%).

The following adverse reactions (all grades) of COTELLIC were reported with < 10% incidence in Trial 1:

Respiratory, thoracic and mediastinal disorders: Pneumonitis

Table 4: Incidence of Laboratory Abnormalities Occurring in ≥ 10% (All Grades) or ≥ 2% (Grades 3–4) of Patients in Trial 1*

Laboratory COTELLIC + Vemurafenib Placebo + Vemurafenib
All Gradesa % Grades 3-4a % All Gradesa % Grades 3-4a %
Chemistry
  Increased creatinine 99.6 3.3 99.6 0.4
  Increased AST 73 8 44 2.1
  Increased ALT 68 11 55 5
  Increased alkaline phosphatase 71 7 56 3.3
  Increased creatine phosphokinaseb 79 14 16 0.5
  Hypophosphatemia 68 12 38 6
  Increased GGT 65 21 61 17
  Hyponatremia 38 6 33 2.1
  Hypoalbuminemia 42 0.8 20 0.4
  Hypokalemia 25 4.5 17 3.3
  Hyperkalemia 26 2.9 15 0.4
  Hypocalcemia 24 0.4 10 1.7
Hematology
  Anemia 69 2.5 57 3.3
  Lymphopeniac 73 10 55 8
  Thrombocytopenia 18 0 10 0
AST - aspartate aminotransferase, ALT - alanine aminotransferase, GGT - gamma-glutamyltransferase *All the percentages are based on the number of patients who had a baseline result and at least one on-study laboratory test. The laboratory results are available for a total of 233~244 patients for COTELLIC, and 232~243 for vemurafenib, except where indicated.
a NCI CTCAE v4.0.
b Increase creatine phosphokinase, n=213 for COTELLIC and 217 for vemurafenib.
c Lymphopenia, n=185 for COTELLIC, and 181 for vemurafenib.

Read the entire FDA prescribing information for Cotellic (Cobimetinib Tablets)

© Cotellic Patient Information is supplied by Cerner Multum, Inc. and Cotellic Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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