Once-Daily Oral Dosing for Maintenance Treatment in Recurrent Ovarian Cancer1
- The recommended starting dose of ZEJULA as monotherapy is 300 mg (three 100-mg capsules) taken orally once daily
- Instruct patients to take their dose of ZEJULA at approximately the same time each day and to swallow each capsule whole. ZEJULA may be taken with or without food. Taking ZEJULA at bedtime may help to manage nausea
- Start treatment with ZEJULA no later than 8 weeks after patients’ most recent platinum-containing regimen. Continue treatment with ZEJULA until disease progression or unacceptable toxicity
- In the case of a missed dose of ZEJULA, instruct patients to take their next dose at its regularly scheduled time. If they vomit or miss a dose of ZEJULA, they should not take an additional dose
Dose adjustments for adverse reactions (ARs)
- To manage ARs, consider interruption of treatment, dose reduction, or dose discontinuation
- ARs in the NOVA trial led to dose reduction or interruption in 69% of patients, most frequently from thrombocytopenia (41%) and anemia (20%)
- Modify dose for non-hematologic ARs of CTCAE grade ≥3 when prophylaxis is not considered feasible or when ARs persist despite treatment
- Modify dose for hematologic ARs requiring transfusion or for platelet count <100,000/µL, neutrophil <1,000/µL, or hemoglobin <8 g/dL
Recommended dose modifications for ARs
ARs, adverse reactions; CTCAE, Common Terminology Criteria for Adverse Events.
a If dose reduction below 100 mg/day is required, discontinue ZEJULA.
ZEJULA is indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.
Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including some fatal cases, was reported in 1.4% of patients receiving ZEJULA vs 1.1% of patients receiving placebo in Trial 1 (NOVA), and 0.9% of patients treated with ZEJULA in all clinical studies. The duration of ZEJULA treatment in patients prior to developing MDS/AML varied from <1 month to 2 years. All patients had received prior chemotherapy with platinum and some had also received other DNA damaging agents and radiotherapy. Discontinue ZEJULA if MDS/AML is confirmed.
Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients receiving ZEJULA. Grade ≥3 thrombocytopenia, anemia and neutropenia were reported in 29%, 25%, and 20% of patients receiving ZEJULA, respectively. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, in 3%, 1%, and 2% of patients, respectively. Do not start ZEJULA until patients have recovered from hematological toxicity caused by prior chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically thereafter. If hematological toxicities do not resolve within 28 days following interruption, discontinue ZEJULA, and refer the patient to a hematologist for further investigations.
Hypertension and hypertensive crisis have been reported in patients receiving ZEJULA. Grade 3-4 hypertension occurred in 9% of patients receiving ZEJULA vs 2% of patients receiving placebo in Trial 1, with discontinuation occurring in <1% of patients. Monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Manage hypertension with antihypertensive medications and adjustment of the ZEJULA dose, if necessary.
Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months after receiving their final dose. Because of the potential for serious adverse reactions from ZEJULA in breastfed infants, advise lactating women to not breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose.
In clinical studies, the most common adverse reactions (Grades 1-4) in ≥10% of patients included: thrombocytopenia (61%), anemia (50%), neutropenia (30%), leukopenia (17%), palpitations (10%), nausea (74%), constipation (40%), vomiting (34%), abdominal pain/distention (33%), mucositis/stomatitis (20%), diarrhea (20%), dyspepsia (18%), dry mouth (10%), fatigue/asthenia (57%), decreased appetite (25%), urinary tract infection (13%), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation (10%), myalgia (19%), back pain (18%), arthralgia (13%), headache (26%), dizziness (18%), dysgeusia (10%), insomnia (27%), anxiety (11%), nasopharyngitis (23%), dyspnea (20%), cough (16%), rash (21%) and hypertension (20%).
Common lab abnormalities (Grades 1-4) in ≥25% of patients included: decrease in hemoglobin (85%), decrease in platelet count (72%), decrease in white blood cell count (66%), decrease in absolute neutrophil count (53%), increase in AST (36%) and increase in ALT (28%).
Reference: 1. ZEJULA [package insert]. Waltham, MA: TESARO, Inc; 2017.