mmune response to KADCYLA. A total of 836 patients from six clinical studies were tested at multiple time points for anti-therapeutic antibody (ATA) responses to KADCYLA. Following KADCYLA dosing, 5.3% (44/836) of patients tested positive for anti-KADCYLA antibodies at one or more post-dose time points. The presence of KADCYLA in patient serum at the time of ATA sampling may interfere with the ability of this assay to detect anti-KADCYLA antibodies. As a result, data may not accurately reflect the true incidence of anti-KADCYLA antibody development. In addition, neutralizing activity of anti-KADCYLA antibodies has not been assessed.
Immunogenicity data are highly dependent on the sensitivity and specificity of the test methods used. Additionally, the observed incidence of a positive result in a test method may be influenced by several factors, including sample handling, timing of sample collection, drug interference, concomitant medication and the underlying disease. Therefore, comparison of the incidence of antibodies to KADCYLA with the incidence of antibodies to other products may be misleading. Clinical significance of anti-KADCYLA antibodies is not yet known.
7 DRUG INTERACTIONS
No formal drug-drug interaction studies with KADCYLA have been conducted. In vitro studies indicate that DM1, the cytotoxic component of KADCYLA, is metabolized mainly by CYP3A4 and to a lesser extent by CYP3A5. Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole) with KADCYLA should be avoided due to the potential for an increase in DM1 exposure and toxicity. Consider an alternate medication with no or minimal potential to inhibit CYP3A4. If concomitant use of strong CYP3A4 inhibitors is unavoidable, consider delaying KADCYLA treatment until the strong CYP3A4 inhibitors have cleared from the circulation (approximately 3 elimination half-lives of the inhibitors) when possible. If a strong CYP3A4 inhibitor is coadministered and KADCYLA treatment cannot be delayed, patients should be closely monitored for adverse reactions.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category D [see Warnings and Precautions (5.3)]
Risk Summary
KADCYLA can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of KADCYLA in pregnant women. No reproductive and developmental toxicology studies have been conducted with ado-trastuzumab emtansine. Nevertheless, two components of KADCYLA (trastuzumab and DM1) are known or suspected to cause fetal harm or death when administered to a pregnant woman. If KADCYLA is administered during pregnancy, or if a patient becomes pregnant while receiving KADCYLA, apprise the patient of the potential hazard to the fetus. Patients should be advised to use effective contraception during treatment with KADCYLA and for 6 months following the last dose of KADCYLA.
If KADCYLA is administered during pregnancy or if a patient becomes pregnant while receiving KADCYLA, immediately report exposure to the Genentech Adverse Event Line at 1-888-835-2555. Encourage women who may be exposed during pregnancy to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 [see Patient Counseling Information (17)].
