ication occurred during the first three months ofexposure.
Adverse reactions of VITRAKVI occurring in ≥ 10% of patients and laboratory abnormalitiesworsening from baseline in ≥ 5% of patients are summarized in Table 2 and Table 3,
respectively.
Table 2 Adverse Reactions Occurring in ≥ 10% of Patients Treated with
VITRAKVI
Adverse Reaction
VITRAKVI
N = 176
All Grades*
(%)
Grade 3-4**
(%)
General
Fatigue 37 3
Pyrexia 18 1
Edema peripheral 15 0
Gastrointestinal
Nausea 29 1
Vomiting 26 1
Constipation 23 1
Diarrhea 22 2
Abdominal pain 13 2
Nervous System
Dizziness 28 1
Headache 14 0
Respiratory, Thoracic and Mediastinal
Cough 26 0
Dyspnea 18 2
Nasal congestion 10 0
Adverse Reaction
VITRAKVI
N = 176
All Grades*
(%)
Grade 3-4**
(%)
Investigations
Increased weight 15 4
Musculoskeletal and Connective Tissue
Arthralgia 14 1
Myalgia 14 1
Muscular weakness 13 0
Back pain 12 1
Pain in extremity 12 1
Metabolism and Nutrition
Decreased appetite 13 2
Vascular
Hypertension 11 2
Injury, Poisoning and Procedural
Complications
Fall 10 1 * National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 4.03.** One Grade 4 adverse reaction of pyrexia.
Table 3 Laboratory Abnormalities Occurring in ≥ 5% Patients Treated with
VITRAKVI
Laboratory Abnormality
VITRAKVI*
All Grades**
(%)
Grade 3-4
(%)
Chemistry
Increased ALT 45 3
Increased AST 45 3
Hypoalbuminemia 35 2
Increased alkaline phosphatase 30 3
Hematology
Anemia 42 10
Neutropenia 23 7
*Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratoryvalue available which ranged from 170 to 174 patients.
** NCI-CTCAE v 4.03.
7 DRUG INTERACTIONS
7.1 Effects of Other Drugs on VITRAKVI
Strong CYP3A4 Inhibitors
Coadministration of VITRAKVI with a strong CYP3A4 inhibitor may increase larotrectinibplasma concentrations, which may result in a higher incidence of adverse reactions [see ClinicalPharmacology (12.3)]. Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors,including grapefruit or grapefruit juice. If coadministration of strong CYP3A4 inhibitors cannotbe avoided, modify VITRAKVI dose as recommended [see Dosage and Administration (2.4)].
Strong CYP3A4 Inducers
Coadministration of VITRAKVI with a strong CYP3A4 inducer may decrease larotrectinibplasma concentrations, which may decrease the efficacy of VITRAKVI [see Clinical
Pharmacology (12.3)].
Avoid coadministration of VITRAKVI with strong CYP3A4 inducers,including St. John’s wort. If coadministration of strong CYP3A4 inducers cannot be avoided,modify VITRAKVI dose as recommended [see Dosage and Administration (2.5)].
7.2 Effects of VITRAKVI on Other Drugs
Sensitive CYP3A4 Substrates
Coadministration of VITRAKVI with sensitive CYP3A4 substrates may increase their plasmaconcentrations, which may increase the incidence or severity of adverse reactions [see ClinicalPharmacology (12.3)]. Avoid coadministration of VITRAKVI with sensitive CYP3A4substrates. If coadministration of these sensitive CYP3A4 substrates cannot be avoided, monitorpatients for increased adverse reactions of these drugs.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Based on literature reports in human subjects with congenital mutations leading to changes inTRK signaling, findin |
