What is the Phesgo (pertuzumab, trastuzumab, and hyaluronidase) loading dose after missed doses?

From the Guidelines

If a patient misses doses of Phesgo, the loading dose should be readministered if more than 3-4 half-lives have passed since the previous dose or if the patient is flaring. The decision to readminister the loading dose depends on disease severity and the number of doses missed, as well as the patient's current condition 1. Key factors to consider when determining whether to restart the loading dose include:

• The time elapsed since the last dose
• The patient's disease severity
• The number of missed doses
• Whether the patient is experiencing a flare It is essential to consider these factors to ensure that therapeutic drug levels are maintained and to optimize efficacy in treating HER2-positive breast cancer. According to the provided evidence, the necessity of repeating loading doses upon restarting administration of the medication depends on disease severity and the number of doses missed 1. Additionally, consider repeating loading doses upon restarting administration of the medication if the patient is flaring and/or if more than 3-4 half-lives have passed since the previous dose 1. However, the exact half-lives of pertuzumab and trastuzumab are not specified in the provided evidence, so the 3-4 half-lives threshold should be used as a general guideline. In clinical practice, it is crucial to prioritize maintaining therapeutic drug levels to ensure optimal efficacy in treating HER2-positive breast cancer.

From the FDA Drug Label

When administered with PERJETA, the recommended initial dose of trastuzumab hyaluronidase-oysk is 600 mg/10,000 units (600 mg trastuzumab and 10,000 units hyaluronidase) administered subcutaneously over approximately 2 to 5 minutes once every three weeks irrespective of the patient's body weight.

For recommendations on delayed or missed doses, please refer to Table 1.

Table 1 Recommendations regarding delayed or missed doses Time between two sequential doses PERJETA Trastuzumab (intravenous) Trastuzumab hyaluronidase-oysk < 6 weeks Administer PERJETA 420 mg intravenously as soon as possible. Do not wait until the next planned dose. Administer trastuzumab 6 mg/kg intravenously as soon as possible. Do not wait until the next planned dose. Administer trastuzumab hyaluronidase-oysk 600 mg/10,000 units subcutaneously as soon as possible. Do not wait until the next planned dose. ≥ 6 weeks Readminister PERJETA loading dose of 840 mg intravenously as a 60 minute infusion, followed by a maintenance dose of 420 mg administered intravenously over a period of 30 to 60 minutes every 3 weeks thereafter. Readminister trastuzumab loading dose of 8 mg/kg intravenously over approximately 90 minutes, followed by a maintenance dose of 6 mg/kg administered intravenously over a period of 30 or 90 minutes every 3 weeks thereafter. Readminister Phesgo (pertuzumab, trastuzumab, and hyaluronidase) is not explicitly mentioned but since trastuzumab hyaluronidase-oysk is mentioned, for a missed dose of 6 weeks or more, the loading dose of trastuzumab hyaluronidase-oysk is not explicitly defined in this context but based on the initial dose it can be inferred that the loading dose of Phesgo would be 840 mg of pertuzumab and 600 mg of trastuzumab and 20,000 units of hyaluronidase, however this information is not provided.

The loading dose of Phesgo (pertuzumab, trastuzumab, and hyaluronidase) after missed doses is not explicitly defined in the label for a period of 6 weeks or more, however, it can be inferred that it would be the same as the initial dose. 2

From the Research

Phesgo Loading Dose After Missed Doses

There is no direct information available in the provided studies regarding the Phesgo (pertuzumab, trastuzumab, and hyaluronidase) loading dose after missed doses.

• The study 3 discusses the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive breast cancer, but it does not provide information on the loading dose after missed doses.
• The studies 4, 5, and 6 provide information on the effects of missed doses on medication adherence and pharmacokinetics, but they do not specifically address the Phesgo loading dose after missed doses.
• The study 7 discusses the efficacy and safety of pertuzumab versus placebo in combination with trastuzumab and chemotherapy in first-line HER2-positive metastatic gastric or gastro-oesophageal junction cancer, but it does not provide information on the loading dose after missed doses.

General Information on Missed Doses

• The study 4 suggests that nonadherence is best mitigated by taking double doses following missed doses if the drug has a long half-life.
• The study 5 provides remedial dosing recommendations for delayed or missed doses of valproic acid in patients with epilepsy based on Monte Carlo simulations.
• The study 6 determines the impacts of multiple missed dose or delayed dose scenarios on quetiapine pharmacokinetics and pharmacodynamics.