Caprelsa
SIDE EFFECTS
The most commonly reported adverse drug reactions ( > 20%) have been diarrhea, rash, acne, nausea, hypertension, headache, fatigue, upper respiratory tract infections, decreased appetite, and abdominal pain. The most common laboratory abnormalities ( > 20%) were decreased calcium, increased ALT, and decreased glucose [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
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.
Clinical Studies Experience
Patients with unresectable locally advanced or metastatic medullary thyroid cancer were treated with CAPRELSA 300 mg (n=231) or Placebo (n=99). Patients with investigator-determined progression or patients who continued treatment after the data cut-off could receive open label CAPRELSA. The following adverse reactions have been reported. [see Clinical Studies]
Table 1 : Adverse Reactions With a ≥ 5% Increased
Incidence in Patients on CAPRELSA Compared to Placebo During Randomized
Treatment
| System Organ Class Preferred Term | CAPRELSA 300 mg N=231 |
Placebo N=99 |
||
| All Grades | Grade 3-4 | All Grades | Grade 3-4 | |
| Gastrointestinal Disorders | ||||
| Diarrhea/Colitis | 132 (57%) | 26 (11%) | 27 (27%) | 2 (2%) |
| Nausea | 77 (33%) | 2 (1%) | 16 (16%) | 0 |
| Abdominal Pain1 | 48 (21%) | 6 (3%) | 11(11%) | 0 |
| Vomiting | 34 (15%) | 2 (1%) | 7 (7%) | 0 |
| Dyspepsia | 25 (11%) | 0 | 4 (4%) | 0 |
| Dry Mouth | 20 (9%) | 0 | 3 (3%) | 0 |
| Skin and Cutaneous Disorders | ||||
| Rash2 | 123 (53%) | 11 (5%) | 12 (12%) | 0 |
| Dermatitis Acneiform/Acne | 81 (35%) | 2 (1%) | 7 (7%) | 0 |
| Dry Skin | 35 (15%) | 0 | 5 (5%) | 0 |
| Photosensitivity Reaction | 31 (13%) | 4 (2%) | 0 | 0 |
| Pruritus | 25 (11%) | 3 (1%) | 4 (4%) | 0 |
| Nail abnormalities3 | 20 (9%) | 0 | 0 | 0 |
| Alopecia | 18 (8%) | N/A | 0 | N/A |
| Vascular Disorders | ||||
| Hypertension/Hypertensive Crisis/Accelerated hypertension | 76 (33%) | 20 (9%) | 5 (5%) | 1 (1%) |
| Nervous System Disorders | ||||
| Headache | 59 (26%) | 2 (1%) | 9 (9%) | 0 |
| Dysgeusia | 19 (8%) | 0 | 3 (3%) | 0 |
| General disorders | ||||
| Fatigue4 | 55 (24%) | 13 (6%) | 23(23%) | 1 (1%) |
| Infections | ||||
| Upper Respiratory Tract Infections5 | 54 (23%) | 0 | 16(16%) | 0 |
| Metabolic and Nutritional Disorders | ||||
| Decreased Appetite | 49 (21%) | 10 (4%) | 12 (12%) | 0 |
| Hypocalcemia | 25 (11%) | 4 (2%) | 3 (3%) | 0 |
| Investigations | ||||
| ECG QT Prolonged6 | 33 (14%) | 18 (8%) | 1 (1%) | 1 (1%) |
| Eye Disorders | ||||
| Corneal Abnormalities7 | 31 (13%) | 0 | 1 (1%) | 0 |
| Blurred Vision | 21 (9%) | 0 (0%) | 1 (1%) | 0 |
| Renal Disorders | ||||
| Proteinuria | 23 (10%) | 0 | 2 (2%) | 0 |
| Psychiatric Disorders | ||||
| Depression | 22 (10%) | 4 (2%) | 3 (3%) | 0 |
| Endocrine Disorders | ||||
| Hypothyroidism | 15 (6%) | 0 | 0 | 0 |
| Musculoskeletal Disorders | ||||
| Muscle Spasms | 15 (6%) | 0 | 1 (1%) | 0 |
| 1Includes abdominal pain, abdominal pain upper, lower
abdominal pain and abdominal discomfort. 2Includes rash, rash erythematous, generalized, macular, maculo-papular, papular, pruritic, exfoliative, dermatitis, dermatitis bullous, generalized erythema and eczema. 3Includes nail disorder, nail bed inflammation, nail bed tenderness, paronychia, nail bed infection, and nail infection. 4Included in Table 1 due to the increased incidence of severe fatigue in the CAPRELSA group compared to the placebo group. 5Includes laryngitis, nasopharyngitis, pharyngitis, sinusitis, upper respiratory tract infection, acute sinusitis, rhinitis, and tracheitis. 669% had QT prolongation > 450ms and 7% had QT prolongation > 500ms by ECG using Fridericia correction. 7Includes corneal edema, corneal opacity, corneal dystrophy, corneal pigmentation, keratopathy, arcus lipoides, corneal deposits, acquired corneal dystrophy. |
||||
Adverse reactions resulting in death in patients receiving CAPRELSA (N=5) were respiratory failure, respiratory arrest, aspiration pneumonia, cardiac failure with arrhythmia, and sepsis. Adverse reactions resulting in death in patients receiving placebo were gastrointestinal hemorrhage (1%) and gastroenteritis (1%). In addition there was one sudden death and one death from cardiopulmonary arrest, in patients receiving CAPRELSA after data cut-off. Causes of discontinuation in 2 or more CAPRELSA-treated patients included asthenia, fatigue, rash, arthralgia, diarrhea, hypertension, prolonged QT interval, increase in creatinine and pyrexia. Serious adverse events reported in > 2% of CAPRELSA-treated patients included diarrhea, pneumonia, and hypertension. Clinically important uncommon adverse drug reactions in patients who received CAPRELSA versus patients who received placebo included pancreatitis (0.4% vs. 0%) and heart failure (0.9% vs. 0%). In the integrated summary of safety database, the most common cause of death in patients who received CAPRELSA was pneumonia.
The incidence of Grade 1-2 bleeding events was 14% in patients receiving CAPRELSA compared with 7% on placebo in the randomized portion of the medullary thyroid cancer (MTC) study. The incidence was similar in the 300 mg monotherapy safety program with a 13% incidence.
Blurred vision was more common in patients who received CAPRELSA versus patients who received placebo for medullary thyroid cancer (9% vs. 1%, respectively). Scheduled slit lamp examinations have revealed corneal opacities (vortex keratopathies) in treated patients, which can lead to halos and decreased visual acuity. It is unknown if this will improve after discontinuation. Ophthalmologic examination, including slit lamp, is recommended in patients who report visual changes. If a patient has blurred vision, do not drive or operate machinery.
Table 2 provides the frequency and severity of laboratory abnormalities reported for patients with medullary thyroid cancer receiving randomized treatment with CAPRELSA or placebo.
Table 2 : Laboratory Abnormalities in Patients with MTC
| Laboratory Parameter | CAPRELSA 300 mg N=231 | Placebo N=99 | ||
| All Grades | Grade 3-4 | All Grades | Grade 3-4 | |
| Chemistries | ||||
| Calcium Decreased | 132 (57%) | 13 (6%) | 25 (25%) | 3 (3%) |
| ALT Increased | 118 (51%) | 4 (2%) | 19 (19%) | 0 |
| Glucose Decreased | 55 (24%) | 0 | 7 (7%) | 1 (1%) |
| Creatinine Increased | 38 (16%) | 0 | 1 (1%) | 0 |
| Bilirubin Increased | 29 (13%) | 0 | 17 (17%) | 0 |
| Magnesium Decreased | 17 (7%) | 1 ( < 1%) | 2 (2%) | 0 |
| Calcium Increased | 16 (7%) | 2 (1%) | 9 (9%) | 1 (1%) |
| Potassium Decreased | 15 (6%) | 1 ( < 1%) | 3 (3%) | 0 |
| Potassium Increased | 13 (6%) | 1 ( < 1%) | 4 (4%) | 2 (2%) |
| Glucose Increased | 12 (5%) | 4 (2%) | 7 (7%) | 0 |
| Magnesium Increased | 6 (3%) | 0 | 4 (4%) | 0 |
| Hematologic | ||||
| WBC Decreased | 45 (19%) | 0 | 25 (25%) | 0 |
| Hemoglobin Decreased | 31 (13%) | 1 ( < 1%) | 19 (19%) | 2 (2%) |
| Neutrophils Decreased | 21 (10%) | 1 ( < 1%) | 5 (5%) | 2 (2%) |
| Platelets Decreased | 18 (9%) | 0 | 3 (3%) | 0 |
Alanine aminotransferase elevations occurred in 51% of patients on CAPRELSA in the randomized medullary thyroid cancer (MTC) study. Grade 3-4 ALT elevations were seen in 2% of patients and no patients had a concomitant increase in bilirubin. Elevations in ALT have resulted in temporary discontinuation of CAPRELSA. However, 16 of 22 patients with a grade 2 elevation in ALT continued 300 mg CAPRELSA. Seven patients who continued CAPRELSA had a normal ALT within 6 months. In the protocol, ALT was monitored every 3 months and more frequently as indicated.
Read the Caprelsa (vandetanib) Side Effects Center for a complete guide to possible side effects »
DRUG INTERACTIONS
CYP3A4 Inducers
Drugs that are CYP3A4 inducers can alter CAPRELSA plasma concentrations. The concomitant use of known strong CYP3A4 inducers should be avoided while receiving CAPRELSA therapy. St. John's Wort may decrease CAPRELSA exposure unpredictably and should be avoided [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
CYP3A4 Inhibitors
In healthy subjects, no clinically significant interaction was shown between CAPRELSA and the potent CYP3A4 inhibitor, itraconazole.
Drugs that Prolong the QT Interval
The administration of CAPRELSA with agents that may prolong the QT interval should be avoided [see WARNINGS AND PRECAUTIONS].
Last reviewed on RxList: 10/18/2012
This monograph has been modified to include the generic and brand name in many instances.
Additional Caprelsa Information
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