March 30, 2017
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Caprelsa

"The U.S. Food and Drug Administration today granted approval to Lenvima (lenvatinib) to treat patients with progressive, differentiated thyroid cancer (DTC) whose disease progressed despite receiving radioactive iodine therapy (radioactive iodine"...

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Caprelsa

Side Effects
Interactions

SIDE EFFECTS

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

Clinical Studies 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.

Patients with unresectable locally advanced or metastatic medullary thyroid cancer were treated with CAPRELSA 300 mg (n=231) or Placebo (n=99). The population exposed to CAPRELSA was 58% male, 94% white, and had a median age of 50 years. The data described below reflect a median exposure to CAPRELSA for 607 days.

The most commonly reported adverse drug reactions which occurred in >20% of CAPRELSA-treated patients and with a between-arm difference of ≥5% included, in order of decreasing frequency: diarrhea/colitis, rash, acneiform dermatitis, hypertension, nausea, headache, upper respiratory tract infection, decreased appetite, and abdominal pain.

Among CAPRELSA-treated patients, dose interruption occurred in 109 (47%) and dose reduction occurred in 83 (36%). Adverse reactions led to study treatment discontinuation in 28 of 231 patients (12%) receiving CAPRELSA and in 3 of 99 patients (3.0%) receiving placebo. Adverse reactions leading to permanent discontinuation in 2 or more (≥0.9%) patients treated with CAPRELSA were: asthenia (1.7%), rash (1.7%), diarrhea (0.9%), fatigue (0.9%), pyrexia (0.9%), elevated creatinine (0.9%), QT prolongation (0.9%), and hypertension (0.9%).

Table 1 - Per-Patient Incidence of Selected Adverse Reactions Occurring at a Higher Incidence in CAPRELSA-Treated Patients During Randomized Treatment [Between- Arm Difference of ≥5% (All Grades )*]

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 57 11 27 2
  Nausea 33 1 16 0
  Abdominal Pain 21 3 11 0
  Vomiting 15 1 7 0
  Dyspepsia 11 0 4 0
  Dry Mouth 9 0 3 0
Skin and Cutaneous Disorders
  Rash 53 5 12 0
  Dermatitis Acneiform/Acne 35 1 7 0
  Dry Skin 15 0 5 0
  Photosensitivity Reaction 13 2 0 0
  Pruritus 11 1 4 0
  Nail abnormalities§ 9 0 0 0
  Alopecia 8 N/A 0 N/A
Vascular Disorders
  Hypertension/Hypertensive Crisis/Accelerated Hypertension 33 9 5 1
Nervous System Disorders
  Headache 26 1 9 0
  Dysgeusia 8 0 3 0
General Disorders
  Fatigue¶ 24 6 23 1
Infections
  Upper Respiratory Tract Infections# 23 0 16 0
Metabolic and Nutritional Disorders
  Decreased Appetite 21 4 12 0
  Hypocalcemia 11 2 3 0
Investigations
  ECG QT ProlongedÞ 14 8 1 1
Eye Disorders
  Corneal Abnormalitiesß 13 0 1 0
  Blurred Vision 9 0 1 0
Renal Disorders
  Proteinuria 10 0 2 0
Psychiatric Disorders
  Depression 10 2 3 0
Endocrine Disorders
  Hypothyroidism 6 0 0 0
Musculoskeletal Disorders
  Muscle Spasms 6 0 1 0
*CTCAE version 3 was used to grade adverse events.
Includes abdominal pain, abdominal pain upper, lower abdominal pain and abdominal discomfort.
Includes rash, rash (erythematous, generalized, macular, maculo-papular, papular, pruritic, and exfoliative), dermatitis, dermatitis bullous, generalized erythema, and eczema.
§Includes nail disorder, nail bed inflammation, nail bed tenderness, paronychia, nail bed infection, and nail infection.
¶Included in Table 1 due to the increased incidence of severe fatigue in the CAPRELSA group compared to the placebo group.
#Includes laryngitis, nasopharyngitis, pharyngitis, sinusitis, upper respiratory tract infection, acute sinusitis, rhinitis, and tracheitis.
Þ69% had QT prolongation >4 50ms and 7% had QT prolongation >500ms by ECG using Fridericia correction.
ßIncludes corneal edema, corneal opacity, corneal dystrophy, corneal pigmentation, keratopathy, arcus lipoides, corneal deposits, acquired corneal dystrophy.

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%).

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 revealed corneal opacities (vortex keratopathies) in treated patients, which can lead to halos and decreased visual acuity. Perform ophthalmologic examination, including slit lamp examination, in patients who report visual changes.

Class effects

CAPRELSA is an inhibitor of vascular endothelial growth factor receptor (VEGFR) signaling. Inhibition of VEGFR signaling can result in intestinal perforation. Intestinal perforation occurred in 0.4% of CAPRELSA treated patients versus 0% of placebo treated patients.

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.

Table 2 - Per-Patient Incidence of Selected Laboratory Abnormalities in Patients with MTC Occurring at a Higher Incidence in CAPRELSA-Treated Patients [Between-Arm Difference of ≥5% (All Grades)*]

Laboratory Abnormalities CAPRELSA 300 mg
N=231
Placebo
N=99
All Grades
(%)
Grade 3– 4
(%)
All Grades
(%)
Grade 3– 4
(%)
Chemistries
  Hypocalcemia 57 6 25 3
  ALT Increased 51 2 19 0
  Hypoglycemia 24 0 7 1
  Creatinine Increased 16 0 1 0
  Hypomagnesemia 7 <1 2 0
Hematologic
  Neutropenia 10 <1 5 2
  Thrombocytopenia 9 0 3 0
*CTCAE version 3 was used to grade laboratory abnormalities.

No patient with a Grade 3–4 ALT elevation had a concomitant increase in bilirubin in the MTC study.

Read the Caprelsa (vandetanib) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Effect Of CYP3A4 Inducers On CAPRELSA

Rifampicin, a strong CYP3A4 inducer, decreased vandetanib plasma concentrations. Avoid concomitant use of known strong CYP3A4 inducers during CAPRELSA therapy. Avoid concomitant use of St.

John's Wort because it can decrease vandetanib exposure unpredictably [see CLINICAL PHARMACOLOGY].

Effect Of CAPRELSA On OCT2 Transporter

CAPRELSA increased plasma concentrations of metformin that is transported by the organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering CAPRELSA with drugs that are transported by OCT2 [see CLINICAL PHARMACOLOGY].

Effect Of CAPRELSA On Digoxin

CAPRELSA increased plasma concentrations of digoxin. Use caution and closely monitor for toxicities when administering CAPRELSA with digoxin [see CLINICAL PHARMACOLOGY].

Drugs That Prolong The QT Interval

Avoid concomitant use of CAPRELSA with agents that may prolong the QT interval [see WARNINGS AND PRECAUTIONS].

Read the Caprelsa Drug Interactions Center for a complete guide to possible interactions

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 3/6/2017

Side Effects
Interactions

Additional Caprelsa Information

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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