AKYNZEO SIDE EFFECTS

SIDE EFFECTS

The following clinically significant adverse reactions are found elsewhere in the labeling:

• Hypersensitivity Reactions.
• Serotonin Syndrome.

Clinical Trials 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.

AKYNZEO Capsules

The overall safety of AKYNZEO capsules was evaluated in 1538 cancer patients and healthy subjects in clinical trials. The data described below reflect exposure to AKYNZEO in 1169 cancer patients, receiving at least one cycle of cancer chemotherapy in 3 active-controlled trials [see Clinical Studies], including 782 exposed to AKYNZEO for at least 4 cycles and 321 exposed for at least 6 cycles, up to a maximum of 12 cycles of chemotherapy. The median age was 55, 79% were female, 83% were White, 13% were Asian, and 4% were Hispanic. All patients received a single oral dose of AKYNZEO 1 hour prior to the start of each chemotherapy cycle. In all studies, dexamethasone was co-administered with AKYNZEO.

Cisplatin Based Highly Emetogenic Chemotherapy

In a single-cycle study of patients receiving cisplatin based highly emetogenic chemotherapy, 136 patients were treated with AKYNZEO. Table 1: Adverse Reactions Occurring in ≥3% of Cancer Patients Receiving AKYNZEO Capsules and Cisplatin Based Highly Emetogenic Chemotherapy (Cycle 1) shows adverse reactions reported at an incidence of at least 3% and for which the AKYNZEO rate exceeded palonosetron alone.

Table 1: Adverse Reactions Occurring in ≥3% of Cancer Patients Receiving AKYNZEO Capsules and Cisplatin Based Highly Emetogenic Chemotherapy (Cycle 1)

Anthracyclines And Cyclophosphamide Based Chemotherapy

In a study of patients receiving anthracycline and cyclophosphamide based chemotherapy, 725 patients were treated with AKYNZEO capsules during Cycle 1, and 635 of these patients continued for up to 8 cycles in a multiple-cycle extension. Table 2 shows adverse reactions reported at an incidence of at least 3% and for which the AKYNZEO capsules rate exceeded palonosetron alone during Cycle 1. The adverse reaction profile in subsequent cycles was similar to that observed in Cycle 1.

Table 2: Adverse Reactions Occurring in ≥3% of Cancer Patients Receiving AKYNZEO Capsules and Anthracyclines and Cyclophosphamide Based Chemotherapy (Cycle 1)

In addition to the adverse reactions shown above, there were reports of concomitant elevations of transaminases greater than 3 times the upper limit of normal and total bilirubin in both arms of the two trials that compared AKYNZEO capsules to oral palonosetron, and the frequency of these elevations was comparable between treatment groups. See Table 3.

Table 3: Liver Function Laboratory Abnormalities

In a multi-cycle safety study of 412 patients, the safety profile of AKYNZEO capsules (n = 308) was comparable to aprepitant and palonosetron (n = 104) in patients undergoing initial and repeat cycles (median 5 cycles, range of 1-14 cycles) of chemotherapy, including carboplatin, cisplatin, oxaliplatin, and doxorubicin regimens. There were no reports of concomitant elevations of transaminases greater than 3 times the upper limit of normal and total bilirubin in this study in either arm.

In a randomized, clinical non-inferiority study, that compared oral palonosetron 0.5 mg to intravenous palonosetron 0.25 mg in cancer patients scheduled to receive highly emetogenic cisplatin (greater than or equal to 70 mg/m²) based chemotherapy, there were two patients (0.5%; 2/369) in the intravenous palonosetron arm who had concomitant elevations of transaminases and total bilirubin. Neither experienced transaminase elevations greater than 10 times the upper limit of normal.

AKYNZEO For Injection

The safety of AKYNZEO for injection was evaluated in 203 patients in an active-controlled multi-cycle (median 4 cycles, range of 1-4 cycles) safety clinical study in patients receiving HEC regimens, not including anthracycline plus cyclophosphamide, (e.g., cisplatin, cyclophosphamide, carmustine, dacarbazine and mechlorethamine) compared to 201 patients receiving AKYNZEO capsules (NCT02517021). The median age was 60 years, 46% were female, 99.5 % were White, 0.3% were Asian, and 0.3% were Hispanic. All patients received a single dose of AKYNZEO for injection 30 minutes prior to the start of each chemotherapy cycle; dexamethasone was co-administered with AKYNZEO. The safety profile of AKYNZEO for injection was generally similar to that seen with AKYNZEO capsules.