Formulation and Specifications: Capsules: 75mg, 100mg, 125mg
Indications: This product is indicated for hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer: (1) in combination with an aromatase inhibitor as initial endocrine therapy in postmenopausal female patients. Given the mechanism of action of aromatase inhibitors, ovariectomy or suppression of ovarian function with a luteinizing hormone-releasing hormone agonist is mandatory for premenopausal/perimenopausal women receiving piperacillin in combination with an aromatase inhibitor. (2) In combination with fulvestrant for the treatment of female patients with metastatic breast cancer that has progressed after endocrine therapy. Piperacil in combination with fulvestrant for premenopausal/perimenopausal women requires coadministration with a luteinizing hormone-releasing hormone agonist. (3) Male breast cancer: on April 4, 2019, the FDA approved the indication for piperacillin in HR-positive, HER2-negative advanced male breast cancer in the United States.
Key points for rational drug use:
1. patients with HR-positive, HER2-negative disease should be tested in a qualified pathology laboratory prior to treatment with piperacillin. HR-positive is defined as estrogen receptor immunohistochemical staining showing more than 1% positive nuclear staining of tumor cells. HER2-negative is defined as IHC0-1+ or FISH-negative.
2. The starting dose of this product is 125 mg/d in a 4-week dosing cycle: 1 week of discontinuation is required after 3 weeks of dosing. It should be taken with food, not with grapefruit or grapefruit juice, and preferably with meals to ensure consistent exposure to piperacillin.
3. A common side effect is myelosuppression, so it is recommended that routine blood tests be performed prior to the use of this product and that treatment be initiated at an absolute neutrophil count ≥1×109/L and a platelet count ≥50×109/L. If the absolute neutrophil count is 0.5×109/L to ≤1×109/L on day 15, you can continue the drug until day 21. If the absolute neutrophil count is ≤0.5×109/L on day 15, piperacillin needs to be suspended until it returns to ≥1×109/L before starting the next course of therapy at one lower dose level. If blood tests are performed the day before the next course and neutrophils recover to ≥1×109/L, the next course can be started at the original dose, but if recovery is delayed, the next course needs to be started at a reduced dose level.
4. Avoid concomitant use of potent inhibitors of CYP3A and consider replacement of potent inhibitors with other concomitant medications that have no or only weak CYP3A inhibition. If patients must be concomitantly treated with a potent CYP3A inhibitor, reduce the dose of piperacillin to 75 mg once daily. If the potent inhibitor is discontinued, increase the dose of piperacillin to the dose prior to initiation of the CYP3A potent inhibitor (after 3 to 5 half-lives of the inhibitor).