The first medication
approved by the FDA
to treat advanced
medullary thyroid
cancer (aMTC)

Safety

CAPRELSA is indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease. Use CAPRELSA in patients with indolent, asymptomatic or slowly progressing disease only after careful consideration of the treatment-related risks of CAPRELSA.1

Warnings and Precautions1

QT prolongation and Torsades de pointes

  • CAPRELSA can prolong the QT interval in a concentration-dependent manner. Torsades de pointes, ventricular tachycardia and sudden deaths have occurred in patients treated with CAPRELSA.
  • Do not start CAPRELSA treatment in patients whose corrected QT interval, Fridericia (QTcF) is greater than 450 ms. Do not administer CAPRELSA to patients who have a history of Torsades de pointes, congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure.
  • Obtain an ECG and serum potassium, calcium, magnesium and TSH at baseline, 2-4 weeks and 8-12 weeks after starting treatment with CAPRELSA, and every 3 months thereafter. Monitor electrolytes and ECGs more frequently in patients who experience diarrhea. Following any dose reduction for QT prolongation or any dose interruption greater than 2 weeks, conduct QT assessments as described above.
  • Avoid using CAPRELSA with drugs known to prolong the QT interval.
  • Stop CAPRELSA in patients who develop a QTcF greater than 500 ms until the QTcF returns to less than 450 ms. Dosing of CAPRELSA can then be resumed at a reduced dose.

Skin reactions and Stevens-Johnson syndrome

  • Severe skin reactions (including Stevens-Johnson syndrome and Toxic Epidermal Necrolysis), some leading to death, have occurred in patients treated with CAPRELSA. For severe skin reactions, referral of the patient to seek urgent medical advice is recommended. Systemic therapies e.g., steroids, may be appropriate in such cases and permanent discontinuation of CAPRELSA is recommended.
  • Photosensitivity reactions can occur during CAPRELSA treatment and up to 4 months after treatment discontinuation.

Interstitial lung disease (ILD)

  • ILD or pneumonitis, including fatalities, has occurred in patients treated with CAPRELSA.
  • Interrupt CAPRELSA for acute or worsening pulmonary symptoms.
  • Discontinue CAPRELSA if ILD is confirmed.

Ischemic cerebrovascular events

  • Ischemic cerebrovascular events, including fatalities, occurred in patients treated with CAPRELSA.
  • Discontinue CAPRELSA in patients who experience a severe ischemic cerebrovascular event.

Hemorrhage

  • Serious hemorrhagic events, including fatalities, occurred in patients treated with CAPRELSA.
  • Discontinue CAPRELSA in patients with severe hemorrhage.

Heart failure

  • Heart failure, including fatalities, occurred in patients treated with CAPRELSA.
  • Monitor for signs and symptoms of heart failure. Consider discontinuation of CAPRELSA in patients with heart failure.
  • Heart failure may not be reversible upon stopping CAPRELSA.

Diarrhea

  • Diarrhea of Grade 3 or greater severity occurred in 11% of patients receiving CAPRELSA in the randomized MTC study.
  • If diarrhea occurs, carefully monitor serum electrolytes and ECGs to reduce the risk and enable early detection of QT prolongation resulting from dehydration.
  • Interrupt CAPRELSA for severe diarrhea. Upon improvement, resume CAPRELSA at a reduced dose.

Hypothyroidism

  • Obtain thyroid-stimulating hormone (TSH) at baseline, at 2-4 weeks and 8-12 weeks after starting treatment with CAPRELSA, and every 3 months thereafter.
  • If signs or symptoms of hypothyroidism occur, examine thyroid hormone levels and adjust thyroid replacement therapy accordingly.

Hypertension

  • Hypertension, including hypertensive crisis, has occurred in patients treated with CAPRELSA.
  • Monitor all patients for hypertension. Dose reduction or interruption for hypertension may be necessary.
  • If hypertension cannot be controlled, do not resume CAPRELSA.

Reversible posterior leukoencephalopathy syndrome (RPLS)

  • RPLS, a syndrome of subcortical vasogenic edema diagnosed by an MRI of the brain, has occurred in patients treated with CAPRELSA.
  • Consider this syndrome in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function.
  • Discontinue CAPRELSA treatment in patients with RPLS.

Drug interactions

  • Avoid administration of CAPRELSA with anti-arrhythmic drugs and other drugs that may prolong the QT interval.

Renal impairment

  • Reduce the starting dose to 200 mg in patients with moderate to severe renal impairment and monitor the QT interval closely.

Hepatic impairment

  • CAPRELSA is not recommended for use in patients with moderate and severe hepatic impairment, as safety and efficacy have not been established.

Embryofetal toxicity

  • Based on its mechanism of action, CAPRELSA can cause fetal harm when administered to a pregnant woman.
  • Women of childbearing potential should avoid pregnancy. Advise women of childbearing potential that they must use effective contraception during CAPRELSA treatment and for at least four months following the last dose of CAPRELSA.

Because of the risk of QT prolongation, Torsades de pointes, and sudden death, CAPRELSA is available only through a restricted distribution program called the CAPRELSA REMS program. Only prescribers and pharmacies certified with the program are able to prescribe and dispense CAPRELSA.

Adverse Events1

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 300mg
N=231

Placebo
N=99

All gradesa (%)

Grade 3-4 (%)

All gradesa (%)

Grade 3-4 (%)

Gastrointestinal disorders

Diarrhea/colitis

57

11

27

2

Nausea

33

1

16

0

Abdominal painb

21

3

11

0

Vomiting

15

1

7

0

Dyspepsia

11

0

4

0

Dry mouth

9

0

3

0

Skin and cutaneous disorders

Rashc

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 abnormalitiesd

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

Fatiguee

24

6

23

1

Infections

Upper respiratory tract infectionsf

23

0

16

0

Metabolic and nutritional disorders

Decreased appetite

21

4

12

0

Hypocalcemia

11

2

3

0

Investigations

ECG QT prolongedg

14

8

1

1

Eye disorders

Corneal abnormalitiesh

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 (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 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.
  • 69% had QT prolongation >450 ms and 7% had QT prolongation >500 ms by ECG using Fridericia correction.
  • Includes corneal edema, corneal opacity, corneal dystrophy, corneal pigmentation, keratopathy, arcus lipoides, corneal deposits, acquired corneal dystrophy.

To report suspected adverse reactions, contact Sanofi Genzyme at 1-800-745-4447, option 2 or the FDA at 1‑800‑FDA‑1088 or http://www.fda.gov/Safety/MedWatch.

Reference

  1. CAPRELSA [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2013.

Important Safety Information, including Boxed WARNING, for CAPRELSA

WARNING: QT PROLONGATION, TORSADES DE POINTES, AND SUDDEN DEATH

  • CAPRELSA can prolong the QT interval. Torsades de pointes and sudden death have occurred in patients receiving CAPRELSA
  • Do not use CAPRELSA in patients with hypocalcemia, hypokalemia, hypomagnesemia, or long QT syndrome. Correct hypocalcemia, hypokalemia and/or hypomagnesemia prior to CAPRELSA administration
  • Monitor electrolytes periodically
  • Avoid drugs known to prolong the QT interval
  • Only prescribers and pharmacies certified with the restricted distribution program are able to prescribe and dispense CAPRELSA
  • Do not use in patients with congenital long QT syndrome
  • CAPRELSA can prolong the QT interval in a concentration-dependent manner. Torsades de pointes, ventricular tachycardia and sudden deaths have occurred in patients treated with CAPRELSA
  • Do not start CAPRELSA treatment in patients whose QTcF interval (corrected QT interval, Fridericia) is greater than 450 ms or who have a history of Torsades de pointes, bradyarrhythmias, or uncompensated heart failure. CAPRELSA has not been studied in patients with ventricular arrhythmias or recent myocardial infarction
  • Stop CAPRELSA in patients who develop a QTcF greater than 500 ms until QTcF returns to less than 450 ms. Dosing of CAPRELSA can then be resumed at a reduced dose
  • Because of the risk of QT prolongation, obtain an ECG and serum potassium, calcium, magnesium, and thyroid-stimulating hormone (TSH) at baseline, 2-4 weeks and 8-12 weeks after starting treatment with CAPRELSA, and every 3 months thereafter. Following any dose reduction or interruptions greater than 2 weeks, conduct QT assessments as described above
  • Severe skin reactions (including Stevens-Johnson syndrome and Toxic Epidermal Necrolysis), some leading to death, have occurred in patients treated with CAPRELSA. For severe skin reactions, refer patients for urgent medical advice. Systemic therapies e.g., steroids, may be appropriate in such cases and permanent discontinuation of CAPRELSA is recommended
  • Photosensitivity reactions can occur during CAPRELSA treatment and up to 4 months after treatment discontinuation
  • Interstitial lung disease (ILD) or pneumonitis, including fatalities, has occurred in patients treated with CAPRELSA. Interrupt CAPRELSA for acute or worsening pulmonary symptoms and discontinue CAPRELSA if ILD is confirmed
  • Ischemic cerebrovascular events, including fatalities, occurred in patients treated with CAPRELSA. The safety of resumption of CAPRELSA therapy after resolution of an ischemic cerebrovascular event has not been studied. Discontinue CAPRELSA in patients who experience a severe ischemic cerebrovascular event
  • Serious hemorrhagic events, including fatalities, occurred in patients treated with CAPRELSA. Do not administer CAPRELSA to patients with a recent history of hemoptysis of ≥1/2 teaspoon of red blood. Discontinue CAPRELSA in patients with severe hemorrhage
  • Heart failure, including fatalities, occurred in patients treated with CAPRELSA. Monitor for signs and symptoms of heart failure. Consider discontinuation of CAPRELSA in patients with heart failure. Heart failure may not be reversible upon stopping CAPRELSA
  • Diarrhea of Grade 3 or greater severity occurred in patients receiving CAPRELSA. If diarrhea occurs, carefully monitor serum electrolytes and ECGs to enable early detection of QT prolongation resulting from dehydration. Interrupt CAPRELSA for severe diarrhea and upon improvement resume CAPRELSA at a reduced dose
  • Increased dosing of thyroid replacement therapy was required in 49% of CAPRELSA-treated patients. Obtain TSH at baseline, at 2-4 weeks and 8-12 weeks after starting treatment with CAPRELSA, and every 3 months thereafter. If signs or symptoms of hypothyroidism occur, examine thyroid hormone levels and adjust thyroid replacement therapy accordingly
  • Hypertension, including hypertensive crisis, has occurred in patients treated with CAPRELSA. Monitor all patients for hypertension. Dose reduction or interruption for hypertension may be necessary. If hypertension cannot be controlled, do not resume CAPRELSA
  • Reversible posterior leukoencephalopathy syndrome (RPLS) has occurred in patients treated with CAPRELSA. Consider this syndrome in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. In clinical studies, three of four patients who developed RPLS while taking CAPRELSA also had hypertension. Discontinue CAPRELSA treatment in patients with RPLS
  • Avoid administration of CAPRELSA with anti-arrhythmic drugs and other drugs that may prolong the QT interval
  • Vandetanib exposure is increased in patients with impaired renal function. Reduce the starting dose to 200 mg in patients with moderate to severe renal impairment and monitor the QT interval closely. There is no information available for patients with end-stage renal disease requiring dialysis
  • CAPRELSA is not recommended for patients with moderate and severe hepatic impairment, as safety and efficacy have not been established
  • CAPRELSA can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should avoid pregnancy and be advised that they must use effective contraception during CAPRELSA treatment and for at least 4 months following the last dose of CAPRELSA
  • The most commonly reported adverse drug reactions (>20%) seen with CAPRELSA and with a between arm difference of ≥5% are diarrhea/colitis (57%), rash (53%), acneiform dermatitis (35%), hypertension (33%), nausea (33%), headache (26%), upper respiratory tract infections (23%), decreased appetite (21%), and abdominal pain (21%)
  • CAPRELSA REMS Program: Because of the risks of QT prolongation, Torsades de pointes, and sudden death, CAPRELSA is available only through the CAPRELSA REMS Program. Only prescribers and pharmacies certified with the restricted distribution program are able to prescribe and dispense CAPRELSA. To learn about the specific REMS requirements and to enroll in the CAPRELSA REMS Program, call 1-800-817-2722 or visit www.caprelsarems.com

Indications and Usage

CAPRELSA is a kinase inhibitor indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.

Use CAPRELSA in patients with indolent, asymptomatic or slowly progressing disease only after careful consideration of the treatment related risks of CAPRELSA.

Please see full Prescribing Information for CAPRELSA, including Boxed WARNING.

To report suspected adverse reactions, visit www.fda.gov/safety/medwatch or call 1‑800‑FDA‑1088.
You may also contact Sanofi Genzyme at 1-800-745-4447, option 2.