Dosage & Administration
For subcutaneous use only. HERCEPTIN HYLECTA has different dosage and administration instructions than intravenous trastuzumab products.
Do not administer intravenously.
Do not substitute HERCEPTIN HYLECTA for or with ado-trastuzumab emtansine.
Perform HER2 testing using FDA-approved tests by laboratories with demonstrated proficiency.
The recommended dose of HERCEPTIN HYLECTA is 600 mg/10,000 units (600 mg trastuzumab and 10,000 units hyaluronidase) administered subcutaneously over approximately 2-5 minutes once every three weeks.
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Herceptin Hylecta Prescribing Information
Cardiomyopathy
HERCEPTIN HYLECTA administration can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving HERCEPTIN HYLECTA with anthracycline-containing chemotherapy regimens.
Evaluate left ventricular function in all patients prior to and during treatment with HERCEPTIN HYLECTA. Discontinue HERCEPTIN HYLECTA treatment in patients receiving adjuvant therapy and withhold HERCEPTIN HYLECTA in patients with metastatic disease for clinically significant decrease in left ventricular function [see Dosage and Administration (2.4) and Warnings and Precautions (5.1)].
Pulmonary Toxicity
HERCEPTIN HYLECTA administration can result in serious and fatal pulmonary toxicity. Symptoms usually occur during or within 24 hours of HERCEPTIN HYLECTA administration. Discontinue HERCEPTIN HYLECTA for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome [see Warnings and Precautions (5.3, 5.5)]. Monitor patients until symptoms completely resolve.
Embryo-Fetal Toxicity
Exposure to HERCEPTIN HYLECTA during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception [see Warnings and Precautions (5.2) and Use in Specific Populations (8.1, 8.3)].
Adjuvant Breast Cancer
HERCEPTIN HYLECTA is indicated for adjuvant treatment of adults with HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature [see Clinical Studies (14.1)]) breast cancer:
- as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel
- as part of a treatment regimen with docetaxel and carboplatin
- as a single agent following multi-modality anthracycline based therapy.
Select patients for therapy based on an FDA-approved companion diagnostic for trastuzumab [see Dosage and Administration (2.2)].
Metastatic Breast Cancer
HERCEPTIN HYLECTA is indicated in adults:
- In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer
- As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease.
Select patients for therapy based on an FDA-approved companion diagnostic for trastuzumab [see Dosage and Administration (2.2)].
Evaluation and Testing Before Initiating HERCEPTIN HYLECTA
Verify the pregnancy status of females of reproductive potential prior to the initiation of HERCEPTIN HYLECTA [see Use in Specific Populations (8.1, 8.3)].
Patient Selection
Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens [see Indications and Usage (1) and Clinical Studies (14)]. Assessment of HER2 protein overexpression and HER2 gene amplification should be performed using FDA-approved tests specific for breast cancer by laboratories with demonstrated proficiency. Information on the FDA-approved tests for the detection of HER2 protein overexpression and HER2 gene amplification is available at: http://www.fda.gov/CompanionDiagnostics.
Improper assay performance, including use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results.
Recommended Dosage
HERCEPTIN HYLECTA is for subcutaneous use only. HERCEPTIN HYLECTA has different dosage and administration instructions than intravenous trastuzumab products. Do not administer intravenously.
Do not substitute HERCEPTIN HYLECTA for or with ado-trastuzumab emtansine.
The recommended dose of HERCEPTIN HYLECTA is 600 mg/10,000 units (600 mg trastuzumab and 10,000 units hyaluronidase) administered subcutaneously over approximately 2-5 minutes once every three weeks.
No loading dose is required. No dose adjustments for patient body weight or for different concomitant chemotherapy regimens are required.
Duration of treatment
Patients with adjuvant breast cancer should be treated with HERCEPTIN HYLECTA for 52 weeks or until disease recurrence, whichever occurs first; extending treatment in adjuvant breast cancer beyond one year is not recommended.
Patients with metastatic breast cancer (MBC) should be treated with HERCEPTIN HYLECTA until progression of disease.
Missed Dose
If one dose is missed, it is recommended to administer the next 600 mg/10,000 units dose (i.e. the missed dose) as soon as possible. The interval between subsequent HERCEPTIN HYLECTA doses should not be less than three weeks.
Dosage Modification for Adverse Reactions
Cardiomyopathy [see Boxed Warning, Warnings and Precautions (5.1)]
Assess left ventricular ejection fraction (LVEF) prior to initiation of HERCEPTIN HYLECTA and at regular intervals during treatment. Withhold HERCEPTIN HYLECTA dosing for at least 4 weeks for either of the following:
- ≥16% absolute decrease in LVEF from pre-treatment values
- LVEF below institutional limits of normal and ≥10% absolute decrease in LVEF from pretreatment values.
HERCEPTIN HYLECTA may be resumed if, within 4–8 weeks, the LVEF returns to normal limits and the absolute decrease from baseline is ≤15%.
Permanently discontinue HERCEPTIN HYLECTA for a persistent (>8 weeks) LVEF decline or for suspension of HERCEPTIN HYLECTA dosing on more than 3 occasions for cardiomyopathy.
Administration and Storage
To prevent medication errors, it is important to check the vial labels to ensure that the drug being prepared and administered is HERCEPTIN HYLECTA and not ado-trastuzumab emtansine or intravenous trastuzumab.
HERCEPTIN HYLECTA should be administered by a healthcare professional.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use vial if particulates or discoloration is present. Discard any unused portion remaining in the vial.
HERCEPTIN HYLECTA is for single use only. The 600 mg/10,000 units (600 mg trastuzumab and 10,000 units hyaluronidase) solution is a ready to use solution for injection which does not need to be diluted.
To avoid needle clogging, attach the hypodermic injection needle to the syringe immediately prior to administration followed by volume adjustment to 5 mL. HERCEPTIN HYLECTA is compatible with polypropylene and polycarbonate syringe material and stainless steel transfer and injection needles.
Prepare the dosing syringe in controlled and validated aseptic conditions. After the solution of HERCEPTIN HYLECTA is withdrawn from the vial and into the syringe, replace the transfer needle with a syringe closing cap. Label the syringe with the peel-off sticker.
Administration
The injection site should be alternated between the left and right thigh. New injections should be given at least 2.5 cm from the old previous site on healthy skin and never into areas where the skin is red, bruised, tender, or hard, or areas where there are moles or scars. During the treatment course with HERCEPTIN HYLECTA other medicinal products for subcutaneous administration should preferably be injected at different sites. The dose should be administered subcutaneously over approximately 2 to 5 minutes.
Storage
If the syringe containing HERCEPTIN HYLECTA is not used immediately, then the syringe can be stored in the refrigerator (2°C to 8°C) for up to 24 hours and subsequently at room temperature (20°C to 25°C) for up to 4 hours. Protect from light. Do not shake or freeze.
HERCEPTIN HYLECTA is a colorless to yellowish, clear to opalescent solution for subcutaneous injection:
- Injection: 600 mg trastuzumab and 10,000 units hyaluronidase per 5 mL (120 mg/2,000 units per mL) in a single-dose vial.
Pregnancy
Pregnancy Pharmacovigilance Program
There is a pregnancy pharmacovigilance program for HERCEPTIN HYLECTA. If HERCEPTIN HYLECTA is administered during pregnancy, or if a patient becomes pregnant while receiving HERCEPTIN HYLECTA or within 7 months following the last dose of HERCEPTIN HYLECTA, health care providers and patients should immediately report HERCEPTIN HYLECTA exposure to Genentech at 1-888-835-2555.
Risk Summary
HERCEPTIN HYLECTA can cause fetal harm when administered to a pregnant woman. In post-marketing reports and published literature, use of trastuzumab during pregnancy resulted in cases of oligohydramnios and of oligohydramnios sequence, manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death [see Data]. Apprise the patient of the potential risks to a fetus. There are clinical considerations if HERCEPTIN HYLECTA is used in a pregnant woman or if a patient becomes pregnant within 7 months following the last dose of HERCEPTIN HYLECTA [see Clinical Considerations].
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Monitor women who received HERCEPTIN HYLECTA during pregnancy or within 7 months prior to conception for oligohydramnios. If oligohydramnios occurs, perform fetal/neonatal testing that is appropriate for gestational age and consistent with community standards of care.
Data
Human Data
In post-marketing reports and published literature, use of trastuzumab during pregnancy resulted in cases of oligohydramnios and of oligohydramnios sequence. Fetal manifestations included pulmonary hypoplasia, skeletal abnormalities, and neonatal death. These case reports described oligohydramnios in pregnant women who received trastuzumab either alone or in combination with chemotherapy. In most reported cases, amniotic fluid index increased after use of trastuzumab was stopped. In reported cases where Herceptin therapy was resumed after amniotic index improved, oligohydramnios recurred.
Animal Data
HERCEPTIN HYLECTA for subcutaneous injection contains trastuzumab and hyaluronidase [see Description (11)].
Trastuzumab:
In studies where intravenous trastuzumab was administered to pregnant cynomolgus monkeys during the period of organogenesis at doses up to 25 mg/kg given twice weekly (up to 25 times the recommended weekly human dose of 2 mg/kg), trastuzumab crossed the placental barrier during the early (Gestation Days 20 to 50) and late (Gestation Days 120 to 150) phases of gestation. The resulting concentrations of trastuzumab in fetal serum and amniotic fluid were approximately 33% and 25%, respectively, of those present in the maternal serum but were not associated with adverse developmental effects.
Hyaluronidase:
In an embryo-fetal study, mice have been dosed daily by subcutaneous injection during the period of organogenesis with hyaluronidase (recombinant human) at dose levels up to 2,200,000 U/kg, which is >7,200 times higher than the human dose. The study found no evidence of teratogenicity. Reduced fetal weight and increased numbers of fetal resorptions were observed, with no effects found at a daily dose of 360,000 U/kg, which is >1,200 times higher than the human dose.
In a peri-and post-natal reproduction study, mice have been dosed daily by subcutaneous injection, with hyaluronidase (recombinant human) from implantation through lactation and weaning at dose levels up to 1,100,000 U/kg, which is >3,600 times higher than the human dose. The study found no adverse effects on sexual maturation, learning and memory or fertility of the offspring.
Lactation
Risk Summary
There is no information regarding the presence of trastuzumab or hyaluronidase in human milk, the effects on the breastfed infant, or the effects on milk production. Published data suggest human IgG is present in human milk but does not enter the neonatal and infant circulation in substantial amounts.
Trastuzumab was present in the milk of lactating cynomolgus monkeys but not associated with neonatal toxicity (see Data). Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for HERCEPTIN HYLECTA treatment and any potential adverse effects on the breastfed child from HERCEPTIN HYLECTA or from the underlying maternal condition. This consideration should also take into account the trastuzumab wash out period of 7 months [see Clinical Pharmacology 12.3].
Data
In lactating cynomolgus monkeys, trastuzumab was present in breast milk at about 0.3% of maternal serum concentrations after pre- (beginning Gestation Day 120) and post-partum (through Post-partum Day 28) doses of 25 mg/kg administered twice weekly (25 times the recommended weekly human dose of 2 mg/kg of intravenous trastuzumab). Infant monkeys with detectable serum levels of trastuzumab did not exhibit any adverse effects on growth or development from birth to 1 month of age.
Females and Males of Reproductive Potential
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to the initiation of HERCEPTIN HYLECTA.
Contraception
Females
HERCEPTIN HYLECTA can cause embryo-fetal harm when administered during pregnancy. Advise females of reproductive potential to use effective contraception during treatment with HERCEPTIN HYLECTA and for 7 months following the last dose of HERCEPTIN HYLECTA [see Use in Specific Populations (8.1) and Clinical Pharmacology (12.3)].
Pediatric Use
The safety and effectiveness of HERCEPTIN HYLECTA in pediatric patients have not been established.
Geriatric Use
Of the total number of patients in the HannaH and SafeHER studies treated with HERCEPTIN HYLECTA, 19% were 65 and over, while 4.7% were 75 and over.
In patients receiving intravenous trastuzumab, the risk of cardiac dysfunction was increased in geriatric patients as compared to younger patients, in both those receiving treatment for adjuvant therapy or metastatic disease. Other differences in safety or effectiveness were not observed between elderly patients and younger patients.
None.