Safety

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.

Warnings and Precautions¹

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])

• 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 Medical Information at 1-800-745-4447, option 2.

Reference

1. CAPRELSA [prescribing information], Genzyme Corporation, Cambridge, MA 02142.

Important Safety Information, including Boxed WARNING, for CAPRELSA

Severe Skin Reactions: 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): 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: 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

Hemorrhage: 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: 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 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

Hypothyroidism: 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: 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 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

Drug Interactions: Avoid administration of CAPRELSA with anti-arrhythmic drugs and other drugs that may prolong the QT interval

Renal Failure: Renal failure has occurred in patients treated with CAPRELSA. Vandetanib exposure is increased in patients with impaired renal function. Reduce the starting dose to 200 mg in patients with moderate renal impairment and monitor the QT interval closely. Vandetanib is not recommended for use in patients with severe renal impairment (clearance below 30 mL/min). There is no information available for patients with end-stage renal disease requiring dialysis

Hepatic Impairment: CAPRELSA is not recommended for patients with moderate and severe hepatic impairment, as safety and efficacy have not been established

Impaired Wound Healing: Impaired wound healing has occurred in patients treated with CAPRELSA. Withhold for at least 1 month prior to elective surgery. Do not administer CAPRELSA for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of treatment with CAPRELSA after resolution of wound healing complications has not been established.

Embryo-Fetal Toxicity: 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

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

ADVERSE REACTIONS

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%).

INDICATIONS AND USAGE

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.

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.