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Cometriq Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 5/6/2016

Cometriq (cabozantinib) capsules are kinase inhibitors used to treat people with medullary thyroid cancer (MTC) that has spread to other parts of the body. Common side effects of Cometriq include weight loss, decreased appetite, diarrhea, constipation, nausea, fatigue, mouth discomfort, changes in your sense of taste, weakness, tiredness, hoarseness in your voice, or changes in your hair color. Serious side effects of Cometriq include:

The recommended dose of Cometriq is 140 mg taken orally, once daily. Cometriq should not be taken with food, and patients should not eat for at least two hours before or one hour after taking Cometriq. Cometriq may interact with other drugs. Patients should inform their healthcare providers of all prescription or nonprescription medication or herbal products that they are taking. When taking Cometriq, patients should avoid medications such as ketoconazole (Nizoral, Kuric, Xolegel), itraconazole (Sporanox), clarithromycin (Biaxin, Biaxin XL), atazanavir (Reyataz), indinavir (Crixivan), nefazodone (Serzone), nelfinavir (Viracept), ritonavir (Kaletra, Norvir), saquinavir (Invirase), telithromycin (Ketek), and/or voriconazole (Vfend). Cometriq can cause fetal harm when administered to a pregnant woman. Patients of childbearing potential must use effective contraception during therapy and for at least four months following their last dose of Cometriq. Breastfeeding mothers must discontinue nursing while receiving Cometriq therapy.

Our Cometriq (cabozantinib) 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.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Cometriq in Detail - Patient Information: Side Effects

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

Some people taking cabozantinib have developed a perforation (a hole or tear) or a fistula (an abnormal passageway) within the stomach or intestines. Call your doctor if you have severe stomach pain, or if you feel like you are choking and gagging when you eat or drink.

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

  • bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;
  • heavy menstrual bleeding, or any other bleeding that will not stop;
  • sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;
  • change in mental status, seizure (convulsions);
  • pain, swelling, warmth, or redness in one or both legs;
  • chest pain spreading to the arm or shoulder, sudden cough, wheezing, sweating, rapid breathing;
  • a light-headed feeling, like you might pass out;
  • puffy eyes, swelling in your ankles or feet, weight gain, urine that looks foamy;
  • dangerously high blood pressure (buzzing in your ears, anxiety, shortness of breath, uneven heartbeats); or
  • jaw pain or numbness, red or swollen gums, loose teeth, or slow healing after dental work.

Once you have had any of the side effects listed above, you may never be able to use cabozantinib again. If you stop taking cabozantinib for any reason, talk to your doctor before you start taking the medication again.

Also call your doctor at once if you have any of these other side effects:

  • severe or ongoing vomiting or diarrhea;
  • a wound that will not heal;
  • pain, tenderness, redness, swelling, blistering, or peeling skin on the palms of your hands or the soles of your feet;
  • severe mouth pain that interferes with eating or drinking;
  • fever, flu symptoms, easy bruising;
  • dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
  • numbness or tingly feeling around your mouth, muscle tightness or contraction, overactive reflexes.

Common side effects may include:

  • nausea, diarrhea, constipation;
  • mild mouth discomfort, changes in your sense of taste;
  • feeling weak or tired, decrease in appetite or weight; or
  • hoarseness in your voice, changes in your hair color.

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 Cometriq (Cabozantinib Capsules)

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Cometriq FDA Prescribing Information: Side Effects
(Adverse Reactions)


The following serious adverse reactions are discussed elsewhere in the label:

Clinical Trial 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 COMETRIQ was evaluated in 330 patients with progressive metastatic medullary thyroid cancer randomized to receive 140 mg COMETRIQ (n = 214) or placebo (n = 109) administered daily until disease progression or intolerable toxicity in a randomized, double-blind, controlled trial (Study 1) [see Clinical Studies]. The data described below reflect a median exposure to COMETRIQ for 204 days. The population exposed to COMETRIQ was 70% male, 90% white, and had a median age of 55 years.

Adverse reactions which occurred in ≥ 25% of COMETRIQ-treated patients occurring more frequently in the COMETRIQ arm with a between-arm difference of ≥ 5% included, in order of decreasing frequency: diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome (PPES), decreased weight, decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, and constipation. The most common laboratory abnormalities ( ≥ 25%) were increased AST, increased ALT, lymphopenia, increased ALP, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia. Grade 3-4 adverse reactions and laboratory abnormalities which occurred in ≥ 5% of COMETRIQ-treated patients occurring more frequently in the COMETRIQ arm with a between-arm difference of ≥ 2% included, in order of decreasing frequency; diarrhea, PPES, lymphopenia, hypocalcemia, fatigue, hypertension, asthenia, increased ALT, decreased weight, stomatitis, and decreased appetite (see Table 1, Table 2).

Fatal adverse reactions occurred in 6% of patients receiving COMETRIQ and resulted from hemorrhage, pneumonia, septicemia, fistulas, cardiac arrest, respiratory failure, and unspecified death. Fatal adverse reactions occurred in 5% of patients receiving placebo and resulted from septicemia, pneumonia, and general deterioration.

The dose was reduced in 79% of patients receiving COMETRIQ compared to 9% of patients receiving placebo. The median number of dosing delays was one in patients receiving COMETRIQ compared to none in patients receiving placebo. Adverse reactions led to study treatment discontinuation in 16% of patients receiving COMETRIQ and in 8% of patients receiving placebo. The most frequent adverse reactions leading to permanent discontinuation in patients treated with COMETRIQ were: hypocalcemia, increased lipase, PPES, diarrhea, fatigue, hypertension, nausea, pancreatitis, tracheal fistula formation and vomiting.

Increased levels of thyroid stimulating hormone (TSH) were observed in 57% of patients receiving COMETRIQ after the first dose compared to 19% of patients receiving placebo (regardless of baseline value). Ninety-two percent (92%) of patients on the COMETRIQ arm had a prior thyroidectomy, and 89% were taking thyroid hormone replacement prior to the first dose.

Table 1: Per-Patient Incidence of Selected Adverse Reactions Occurring at a Higher Incidence in COMETRIQ-Treated Patients (Study 1) [Between Arm Difference of ≥ 5% (All Grades)1or ≥ 2% (Grade 3-4)]

MedDRA System Organ Class/ Preferred Terms COMETRIQ
All Grades Grade 3-4 All Grades Grade 3-4
  Diarrhea 63 16 33 2
  Stomatitis2 51 5 6 0
  Nausea 43 1 21 0
  Oral pain3 36 2 6 0
  Constipation 27 0 6 0
  Abdominal pain4 27 3 13 1
  Vomiting 24 2 2 1
  Dysphagia 13 4 6 1
  Dyspepsia 11 0 0 0
  Hemorrhoids 9 0 3 0
  Fatigue 41 9 28 3
  Asthenia 21 6 15 1
  Decreased weight 48 5 10 0
  Decreased appetite 46 5 16 1
  Dehydration 7 2 2 1
  Arthralgia 14 1 7 0
  Muscle spasms 12 0 5 0
  Musculoskeletal chest pain 9 1 4 0
  Dysgeusia 34 0 6 0
  Headache 18 0 8 0
  Dizziness 14 0 7 0
  Paresthesia 7 0 2 0
  Peripheral sensory neuropathy 7 0 0 0
  Peripheral neuropathy 5 0 0 0
  Anxiety 9 0 2 0
  Dysphonia 20 0 9 0
  PPES5 50 13 2 0
  Hair color changes/ depigmentation, graying 34 0 1 0
  Rash 19 1 10 0
  Dry skin 19 0 3 0
  Alopecia 16 0 2 0
  Erythema 11 1 2 0
  Hyperkeratosis 7 0 0 0
  Hypertension 33 8 4 0
  Hypotension 7 1 0 0
1 National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0
2 Includes the following terms: stomatitis, aphthous stomatitis, mouth ulceration, mucosal inflammation
3 Includes the following terms: oral pain, oropharyngeal pain, glossitis, burning mouth syndrome, glossodynia
4 Includes the following terms: abdominal pain, abdominal pain lower, abdominal pain upper, abdominal rigidity, abdominal tenderness, esophageal pain
5 Palmar-plantar erythrodysesthesia syndrome

Table 2: Percent-Patient Incidence of Laboratory Abnormalities Occurring at a Higher Incidence in COMETRIQ-Treated Patients (Study 1) [Between Arm Difference of ≥ 5% (All Grades) or ≥ 2% (Grade 3-4)]

All Grades Grade 3-4 All Grades Grade 3-4
  Increased AST 86 3 35 2
  Increased ALT 86 6 41 2
  Increased ALP 52 3 35 3
  Hypocalcemia 52 12 27 3
  Hypophosphatemia 28 3 10 1
  Hyperbilirubinemia 25 2 14 5
  Hypomagnesemia 19 1 4 0
  Hypokalemia 18 4 9 3
  Hyponatremia 10 2 5 0
  Lymphopenia 53 16 51 11
  Neutropenia 35 3 15 2
  Thrombocytopenia 35 0 4 3
ALT, alanine aminotransferase; ALP, alkaline phosphatase; AST, aspartate aminotransferase

Nearly all COMETRIQ-treated patients (96% vs. 84% placebo) experienced elevated blood pressure and there was a doubling in the incidence of overt hypertension in COMETRIQ-treated patients over placebo-treated patients (61% vs. 30%) according to modified Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) staging criteria. No patients developed malignant hypertension.

Table 3: Per-Patient Incidence of Hypertension (Study 1)

Hypertension, JNC1 Stage2 COMETRIQ
N = 2113 (%)
N = 1073 (%)
Normal: Grade 0: Systolic < 120 mmHg and Diastolic < 80 mmHg 4 15
Pre-hypertension: Systolic ≥ 120 mmHg or Diastolic ≥ 80 mmHg 34 54
Stage 1: Systolic ≥ 140 mmHg or Diastolic ≥ 90 mmHg 46 25
Stage 2: Systolic ≥ 160 mmHg or Diastolic ≥ 100 mmHg 15 5
Malignant: Diastolic ≥ 120 mmHg 0 0
1Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, JAMA 2003: 289:2560. Criteria applied were modified, as multiple readings were not available per timepoint, and therefore not averaged.
2Patients classified by highest category based on all recorded blood pressure readings beginning after the first dose through 30 days after last dose.
3Patients with at least two blood pressure measurements after the first dose

Read the entire FDA prescribing information for Cometriq (Cabozantinib Capsules)

Report Problems to the Food and Drug Administration


You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

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