Herceptin
Trastuzumab · Injection, Powder, Lyophilized, For Solution · Intravenous
Uses
Herceptin is a HER2/neu receptor antagonist indicated in adults for: The treatment of HER2-overexpressing breast cancer. ( 1.1 , 1.2 ) The treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. ( 1.3 ) Select patients for therapy based on an FDA-authorized companion diagnostic for Herceptin ( 1 , 2.2 ). 1.1 Adjuvant Breast Cancer Herceptin is indicated in adults for adjuvant treatment of 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-authorized companion diagnostic for Herceptin [see Dosage and Administration (2.2) ] . 1.2 Metastatic Breast Cancer Herceptin 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-authorized companion diagnostic for Herceptin [see Dosage and Administration (2.2) ] . 1.3 Metastatic Gastric Cancer Herceptin is indicated in adults, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease. Select patients for therapy based on an FDA-authorized companion diagnostic for Herceptin [see Dosage and Administration (2.2) ] .
Dosage and administration
For intravenous (IV) infusion only. Do not administer as an IV push or bolus. Herceptin has different dosage and administration instructions than subcutaneous trastuzumab products. ( 2.3 ) Do not substitute Herceptin (trastuzumab) for or with ado-trastuzumab emtansine or fam-trastuzumab deruxtecan. ( 2.3 ) Perform HER2 testing using FDA-authorized tests by laboratories with demonstrated proficiency. ( 1 , 2.2 ) Adjuvant Treatment of HER2-Overexpressing Breast Cancer ( 2.2 ) Administer at either: Initial dose of 4 mg/kg over 90 minutes IV infusion, then 2 mg/kg over 30 minutes IV infusion weekly for 12 weeks (with paclitaxel or docetaxel) or 18 weeks (with docetaxel and carboplatin). One week after the last weekly dose of Herceptin, administer 6 mg/kg as an IV infusion over 30–90 minutes every three weeks to complete a total of 52 weeks of therapy, or Initial dose of 8 mg/kg over 90 minutes IV infusion, then 6 mg/kg over 30–90 minutes IV infusion every three weeks for 52 weeks. Metastatic HER2-Overexpressing Breast Cancer ( 2.3 ) Initial dose of 4 mg/kg as a 90 minutes IV infusion followed by subsequent weekly doses of 2 mg/kg as 30 minutes IV infusions. Metastatic HER2-Overexpressing Gastric Cancer ( 2.3 ) Initial dose of 8 mg/kg over 90 minutes IV infusion, followed by 6 mg/kg over 30 to 90 minutes IV infusion every 3 weeks. 2.1 Evaluation and Testing Before Initiating Herceptin Assess left ventricular ejection fraction (LVEF) prior to initiation of Herceptin and at regular intervals during treatment. [see Boxed Warning , Dosage and Administration (2.5) , Warnings and Precautions (5.1) ]. Verify the pregnancy status of females of reproductive potential prior to the initiation of Herceptin [see Warnings and Precautions (5.3) , Use in Specific Populations (8.1 , 8.3) ] . 2.2 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-authorized tests specific for breast or gastric cancers by laboratories with demonstrated proficiency. Information on the FDA-authorized tests for the detection of HER2 protein overexpression and HER2 gene amplification is available at: http://www.fda.gov/CompanionDiagnostics. Assessment of HER2 protein overexpression and HER2 gene amplification in metastatic gastric cancer should be performed using FDA-authorized tests specifically for gastric cancers due to differences in gastric vs. breast histopathology, including incomplete membrane staining and more frequent heterogeneous expression of HER2 seen in gastric cancers. 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. 2.3 Recommended Dosage Herceptin is for intravenous infusion only. Do not administer as an intravenous push or bolus. Herceptin has different dosage and administration instructions than subcutaneous trastuzumab products. Do not mix Herceptin with other drugs. Do not substitute Herceptin (trastuzumab) for or with ado-trastuzumab emtansine or fam-trastuzumab deruxtecan. Adjuvant Treatment of Breast Cancer Administer according to one of the following doses and schedules for a total of 52 weeks of Herceptin therapy: During and following paclitaxel, docetaxel, or docetaxel/carboplatin: Initial dose of 4 mg/kg as an intravenous infusion over 90 minutes then at 2 mg/kg as an intravenous infusion over 30 minutes weekly during chemotherapy for the first 12 weeks (paclitaxel or docetaxel) or 18 weeks (docetaxel and carboplatin). One week following the last weekly dose of Herceptin, administer Herceptin at 6 mg/kg as an intravenous infusion over 30–90 minutes every three weeks. As a single agent within three weeks following completion of multi-modality, anthracycline-based chemotherapy regimens: Initial dose at 8 mg/kg as an intravenous infusion over 90 minutes Subsequent doses at 6 mg/kg as an intravenous infusion over 30–90 minutes every three weeks. Extending adjuvant treatment beyond one year is not recommended [see Adverse Reactions (6.1) ] . Metastatic Breast Cancer Administer Herceptin, alone or in combination with paclitaxel, at an initial dose of 4 mg/kg as a 90-minute intravenous infusion followed by subsequent once weekly doses of 2 mg/kg as 30-minute intravenous infusions until disease progression. Metastatic Gastric Cancer Administer Herceptin at an initial dose of 8 mg/kg as a 90-minute intravenous infusion followed by subsequent doses of 6 mg/kg as an intravenous infusion over 30–90 minutes every three weeks until disease progression . 2.4 Important Dosing Considerations Missed Dose If the patient has missed a dose of Herceptin by one week or less, then the usual maintenance dose (weekly schedule: 2 mg/kg; once every three weeks schedule: 6 mg/kg) should be administered as soon as possible. Do not wait until the next planned cycle. Subsequent Herceptin maintenance doses should be administered 7 days or 21 days later according to the weekly or once every three week schedules, respectively. If the patient has missed a dose of Herceptin by more than one week, a re-loading dose of Herceptin should be administered over approximately 90 minutes (weekly schedule: 4 mg/kg; once every three week schedule: 8 mg/kg) as soon as possible. Subsequent Herceptin maintenance doses (weekly schedule: 2 mg/kg; three-weekly schedule 6 mg/kg) should be administered 7 days or 21 days later according to the weekly or once every three week schedules, respectively.
Dosage forms and strengths
For injection: 150 mg white to pale yellow lyophilized powder in a single-dose vial For Injection: 150 mg lyophilized powder in a single-dose vial for reconstitution
Contraindications
None. None. ( 4 )
Warnings and precautions
Exacerbation of Chemotherapy-Induced Neutropenia. ( 5.5 , 6.1 ) 5.1 Cardiomyopathy Herceptin can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death [see Boxed Warning: Cardiomyopathy ] . Herceptin can also cause asymptomatic decline in left ventricular ejection fraction (LVEF). There is a 4–6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving Herceptin as a single agent or in combination therapy compared with those not receiving Herceptin. The highest absolute incidence occurs when Herceptin is administered with an anthracycline. Withhold Herceptin for ≥ 16% absolute decrease in LVEF from pre-treatment values or an LVEF value below institutional limits of normal and ≥ 10% absolute decrease in LVEF from pretreatment values [see Dosage and Administration (2.5) ] . The safety of continuation or resumption of Herceptin in patients with Herceptin-induced left ventricular cardiac dysfunction has not been studied. Patients who receive anthracycline after stopping Herceptin may also be at increased risk of cardiac dysfunction [see Drug Interactions (7) and Clinical Pharmacology (12.3) ] . Cardiac Monitoring Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan. The following schedule is recommended: Baseline LVEF measurement immediately prior to initiation of Herceptin LVEF measurements every 3 months during and upon completion of Herceptin Repeat LVEF measurement at 4 week intervals if Herceptin is withheld for significant left ventricular cardiac dysfunction [see Dosage and Administration (2.5) ] LVEF measurements every 6 months for at least 2 years following completion of Herceptin as a component of adjuvant therapy. In NSABP B31, 15% (158/1031) of patients discontinued Herceptin due to clinical evidence of myocardial dysfunction or significant decline in LVEF after a median follow-up duration of 8.7 years in the AC-TH arm. In HERA (one-year Herceptin treatment), the number of patients who discontinued Herceptin due to cardiac toxicity at 12.6 months median duration of follow-up was 2.6% (44/1678). In BCIRG006, a total of 2.9% (31/1056) of patients in the TCH arm (1.5% during the chemotherapy phase and 1.4% during the monotherapy phase) and 5.7% (61/1068) of patients in the AC-TH arm (1.5% during the chemotherapy phase and 4.2% during the monotherapy phase) discontinued Herceptin due to cardiac toxicity. Among 64 patients receiving adjuvant chemotherapy (NSABP B31 and NCCTG N9831) who developed congestive heart failure, one patient died of cardiomyopathy, one patient died suddenly without documented etiology, and 33 patients were receiving cardiac medication at last follow-up. Approximately 24% of the surviving patients had recovery to a normal LVEF (defined as ≥ 50%) and no symptoms on continuing medical management at the time of last follow-up. Incidence of congestive heart failure (CHF) is presented in Table 1 . The safety of continuation or resumption of Herceptin in patients with Herceptin-induced left ventricular cardiac dysfunction has not been studied. Table 1: Incidence of Congestive Heart Failure in Adjuvant Breast Cancer Studies Incidence of Congestive Heart Failure % (n) Study Regimen Herceptin Control NSABP B31 & NCCTG N9831 Median follow-up duration for NSABP B31 & NCCTG N9831 combined was 8.3 years in the AC→paclitaxel+Herceptin arm. AC Anthracycline (doxorubicin) and cyclophosphamide. →Paclitaxel+Herceptin 3.2% (64/2000) Includes 1 patient with fatal cardiomyopathy and 1 patient with sudden death without documented etiology. 1.3% (21/1655) HERA Includes NYHA II-IV and cardiac death at 12.6 months median duration of follow-up in the one-year Herceptin arm. Chemotherapy → Herceptin 2% (30/1678) 0.3% (5/1708) BCIRG006 AC →Docetaxel+Herceptin 2% (20/1068) 0.3% (3/1050) BCIRG006 Docetaxel+Carboplatin+Herceptin 0.4% (4/1056) 0.3% (3/1050) In HERA (one-year Herceptin treatment), at a median follow-up duration of 8 years, the incidence of severe CHF (NYHA III & IV) was 0.8%, and the rate of mild symptomatic and asymptomatic left ventricular dysfunction was 4.6%. Table 2: Incidence of Cardiac Dysfunction Congestive heart failure or significant asymptomatic decrease in LVEF. in Metastatic Breast Cancer Studies Incidence NYHA I–IV NYHA III–IV Study Event Herceptin Control Herceptin Control H0648g (AC) Anthracycline (doxorubicin or epirubicin) and cyclophosphamide. Cardiac Dysfunction 28% 7% 19% 3% H0648g (paclitaxel) Cardiac Dysfunction 11% 1% 4% 1% H0649g Cardiac Dysfunction Includes 1 patient with fatal cardiomyopathy. 7% N/A 5% N/A In BCIRG006, the incidence of NCI-CTC Grade 3/4 cardiac ischemia/infarction was higher in the Herceptin containing regimens (AC-TH: 0.3% (3/1068) and TCH: 0.2% (2/1056)) as compared to none in AC-T. 5.2 Infusion Reactions Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion included nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia [see Adverse Reactions (6.1) ]. In post-marketing reports, serious and fatal infusion reactions have been reported. Severe reactions, which include bronchospasm, anaphylaxis, angioedema, hypoxia, and severe hypotension, were usually reported during or immediately following the initial infusion. However, the onset and clinical course were variable, including progressive worsening, initial improvement followed by clinical deterioration, or delayed post-infusion events with rapid clinical deterioration. For fatal events, death occurred within hours to days following a serious infusion reaction.
Side effects
The following adverse reactions are discussed in greater detail in other sections of the label: Cardiomyopathy [see Warnings and Precautions (5.1) ] Infusion Reactions [see Warnings and Precautions (5.2) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.3) ] Pulmonary Toxicity [see Warnings and Precautions (5.4) ] Exacerbation of Chemotherapy-Induced Neutropenia [see Warnings and Precautions (5.5) ] Adjuvant Breast Cancer Most common adverse reactions (≥ 5%) are headache, diarrhea, nausea, and chills. ( 6.1 ) Metastatic Breast Cancer Most common adverse reactions (≥ 10%) are fever, chills, headache, infection, congestive heart failure, insomnia, cough, and rash. ( 6.1 ) Metastatic Gastric Cancer Most common adverse reactions (≥ 10%) are neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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. The most common adverse reactions in patients receiving Herceptin in the adjuvant and metastatic breast cancer setting are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia. Adverse reactions requiring interruption or discontinuation of Herceptin treatment include CHF, significant decline in left ventricular cardiac function, severe infusion reactions, and pulmonary toxicity [see Dosage and Administration (2.5) ] . In the metastatic gastric cancer setting, the most common adverse reactions (≥ 10%) that were increased (≥ 5% difference) in the Herceptin arm as compared to the chemotherapy alone arm were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia. The most common adverse reactions which resulted in discontinuation of treatment on the Herceptin-containing arm in the absence of disease progression were infection, diarrhea, and febrile neutropenia. Adjuvant Breast Cancer The information below reflects exposure to one-year Herceptin therapy across three randomized, open-label studies, Studies 1, 2, and 3, with (n = 3678) or without (n = 3363) trastuzumab in the adjuvant treatment of breast cancer. HERA Table 3 reflects exposure to Herceptin in 1678 patients in HERA; the median treatment duration was 51 weeks and median number of infusions was 18 [see Clinical Studies (14.1) ]. Table 3: Adverse Reactions (≥1%) in HERA (All Grades) The incidence of Grade 3 or higher adverse reactions was <1% in both arms for each listed term. Adverse Reactions Herceptin (n = 1678) % Observation (n = 1708) % Nervous System Headache 10 3 Paresthesia 2 0.6 Musculoskeletal Arthralgia 8 6 Back pain 5 3 Myalgia 4 1 Bone pain 3 2 Muscle spasm 3 0.2 Infections Nasopharyngitis 8 3 Urinary tract infection 3 0.8 Gastrointestinal Diarrhea 7 1 Nausea 6 1 Vomiting 3.5 0.6 Constipation 2 1 Dyspepsia 2 0.5 Upper abdominal pain 2 1 General Pyrexia 6 0.4 Peripheral edema 5 2 Chills 5 0 Asthenia 4.5 2 Influenza-like illness 2 0.2 Respiratory Thoracic Mediastinal Cough 5 2 Influenza 4 0.5 Dyspnea 3 2 URI 3 1 Rhinitis 2 0.4 Pharyngolaryngeal pain 2 0.5 Sinusitis 2 0.3 Epistaxis 2 0.06 Cardiac Hypertension 4 2 Dizziness 4 2 Ejection fraction decreased 3.5 0.6 Palpitations 3 0.7 Cardiac arrhythmias Higher level grouping term. 3 1 Cardiac failure (congestive) 2 0.3 Skin & Subcutaneous Tissue Rash 4 0.6 Nail disorders 2 0 Pruritus 2 0.6 Clinically relevant adverse reactions in < 1% of patients who received Herceptin in HERA included hypersensitivity (0.6%), cardiac failure (0.5%), cardiac disorder (0.3%), interstitial pneumonitis (0.2%), pulmonary hypertension (0.2%), ventricular disorder (0.2%), autoimmune thyroiditis (0.3%), and sudden death (0.06%). Adjuvant Treatment of Breast Cancer with Herceptin Beyond One Year Extending adjuvant treatment beyond one year is not recommended [see Dosage and Administration (2.2) ]. In HERA, a comparison of Herceptin administered once every 3 weeks for two years versus one year was performed. The rate of asymptomatic cardiac dysfunction was increased in the 2-year Herceptin compared to the 1-year Herceptin treatment arm (8.1% versus 4.6%, respectively). More patients experienced at least one adverse reaction of Grade 3 or higher in the 2-year Herceptin treatment arm (20.4%) compared with the one-year Herceptin treatment arm (16.3%). NSABP B31 and NCCTG N9831 The safety data from NSABP B31 and NCCTG N9831 were obtained from 3655 patients, of whom 2000 received Herceptin; the median treatment duration was 51 weeks [see Clinical Studies (14.1) ]. In NSABP B31, only Grade 3–5 adverse events, treatment-related Grade 2 events, and Grade 2–5 dyspnea were collected during and for up to 3 months following protocol-specified treatment. The following non-cardiac adverse reactions of Grade 2–5 occurred at an incidence of at least 2% greater among patients receiving Herceptin plus chemotherapy as compared to chemotherapy alone: fatigue (29.5% vs. 22.4%), infection (24.0% vs. 12.8%), hot flashes (17.1% vs. 15%), anemia (12.3% vs. 6.7%), dyspnea (11.8% vs. 4.6%), rash/desquamation (10.9% vs. 7.6%), leukopenia (10.5% vs. 8.4%), neutropenia (6.4% vs. 4.3%), headache (6.2% vs. 3.8%), pain (5.5% vs. 3%), edema (4.7% vs. 2.7%), and insomnia (4.3% vs. 1.5%). The majority of these events were Grade 2 in severity.
Drug interactions
Anthracyclines Patients who receive anthracycline after stopping Herceptin may be at increased risk of cardiac dysfunction because of trastuzumab's estimated long washout period [see Clinical Pharmacology (12.3) ] . If possible, avoid anthracycline-based therapy for up to 7 months after stopping Herceptin. If anthracyclines are used, closely monitor the patient's cardiac function.
Use in specific populations
Females and Males of Reproductive Potential: Verify the pregnancy status of females prior to initiation of Herceptin ( 8.3 ). 8.1 Pregnancy If Herceptin is administered during pregnancy, or if a patient becomes pregnant while receiving Herceptin or within 7 months following the last dose of Herceptin, health care providers and patients should immediately report Herceptin exposure to Genentech at 1-888-835-2555. Risk Summary Herceptin can cause fetal harm when administered to a pregnant woman. In post-marketing reports and published literature, use of Herceptin 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 is used in a pregnant woman or if a patient becomes pregnant within 7 months following the last dose of Herceptin [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 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 Herceptin 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 Herceptin either alone or in combination with chemotherapy. In most reported cases, amniotic fluid index increased after Herceptin was stopped. In reported cases where Herceptin therapy was resumed after amniotic index improved, oligohydramnios recurred. Animal Data In studies where 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. 8.2 Lactation Risk Summary There is no information regarding the presence of trastuzumab 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 treatment and any potential adverse effects on the breastfed child from Herceptin 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 Herceptin). 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. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to the initiation of Herceptin. Contraception Females Herceptin can cause embryo-fetal harm when administered during pregnancy. Advise females of reproductive potential to use effective contraception during treatment with Herceptin and for 7 months following the last dose of Herceptin [see Use in Specific Populations (8.1) and Clinical Pharmacology (12.3) ]. 8.4 Pediatric Use The safety and effectiveness of Herceptin in pediatric patients have not been established. 8.5 Geriatric Use Herceptin has been administered to 386 patients who were 65 years of age or over (253 in the adjuvant treatment and 133 in metastatic breast cancer treatment settings). The risk of cardiac dysfunction was increased in geriatric patients as compared to younger patients in both those receiving treatment for metastatic disease in H0648g and H0649g, or adjuvant therapy in NSABP B31 and NCCTG N9831. Limitations in data collection and differences in study design of the 4 studies of Herceptin in adjuvant treatment of breast cancer preclude a determination of whether the toxicity profile of Herceptin in older patients is different from younger patients. The reported clinical experience is not adequate to determine whether the efficacy improvements (ORR, TTP, OS, DFS) of Herceptin treatment in older patients is different from that observed in patients < 65 years of age for metastatic disease and adjuvant treatment. In ToGA (metastatic gastric cancer), of the 294 patients treated with Herceptin, 108 (37%) were 65 years of age or older, while 13 (4.4%) were 75 and over. No overall differences in safety or effectiveness were observed.
Pregnancy
8.1 Pregnancy If Herceptin is administered during pregnancy, or if a patient becomes pregnant while receiving Herceptin or within 7 months following the last dose of Herceptin, health care providers and patients should immediately report Herceptin exposure to Genentech at 1-888-835-2555. Risk Summary Herceptin can cause fetal harm when administered to a pregnant woman. In post-marketing reports and published literature, use of Herceptin 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 is used in a pregnant woman or if a patient becomes pregnant within 7 months following the last dose of Herceptin [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 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 Herceptin 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 Herceptin either alone or in combination with chemotherapy. In most reported cases, amniotic fluid index increased after Herceptin was stopped. In reported cases where Herceptin therapy was resumed after amniotic index improved, oligohydramnios recurred. Animal Data In studies where 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.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of Herceptin in pediatric patients have not been established.
Geriatric use
8.5 Geriatric Use Herceptin has been administered to 386 patients who were 65 years of age or over (253 in the adjuvant treatment and 133 in metastatic breast cancer treatment settings). The risk of cardiac dysfunction was increased in geriatric patients as compared to younger patients in both those receiving treatment for metastatic disease in H0648g and H0649g, or adjuvant therapy in NSABP B31 and NCCTG N9831. Limitations in data collection and differences in study design of the 4 studies of Herceptin in adjuvant treatment of breast cancer preclude a determination of whether the toxicity profile of Herceptin in older patients is different from younger patients. The reported clinical experience is not adequate to determine whether the efficacy improvements (ORR, TTP, OS, DFS) of Herceptin treatment in older patients is different from that observed in patients < 65 years of age for metastatic disease and adjuvant treatment. In ToGA (metastatic gastric cancer), of the 294 patients treated with Herceptin, 108 (37%) were 65 years of age or older, while 13 (4.4%) were 75 and over. No overall differences in safety or effectiveness were observed.
Description
Trastuzumab is a humanized IgG1 kappa monoclonal antibody that selectively binds with high affinity to the extracellular domain of the human epidermal growth factor receptor 2 protein, HER2. Trastuzumab is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture. Herceptin (trastuzumab) for injection is a sterile, white to pale yellow, preservative-free lyophilized powder with a cake-like appearance, for intravenous administration. Each single-dose vial of Herceptin delivers 150 mg trastuzumab, 136.2 mg α,α-trehalose dihydrate, 3.4 mg L-histidine HCl monohydrate, 2.2 mg L-histidine, and 0.6 mg polysorbate 20. Reconstitution with 7.4 mL of sterile water for injection (SWFI) yields a solution containing 21 mg/mL trastuzumab that delivers 7.15 mL (150 mg trastuzumab), at a pH of approximately 6.
Mechanism of action
12.1 Mechanism of Action The HER2 (or c-erbB2) proto-oncogene encodes a transmembrane receptor protein of 185 kDa, which is structurally related to the epidermal growth factor receptor. Herceptin has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumor cells that overexpress HER2. Herceptin is a mediator of antibody-dependent cellular cytotoxicity (ADCC). In vitro , Herceptin-mediated ADCC has been shown to be preferentially exerted on HER2 overexpressing cancer cells compared with cancer cells that do not overexpress HER2.
How supplied
150 mg Single-dose vial Herceptin (trastuzumab) for injection 150 mg/vial is supplied in a single-dose vial as a preservative-free, white to pale yellow lyophilized sterile powder, under vacuum. Available in a carton containing one single-dose vial (NDC 50242-132-01) and a carton containing 10 single-dose vials (NDC 50242-132-10). Store Herceptin vials in the refrigerator at 2°C to 8°C (36°F to 46°F) until time of reconstitution.
Storage
Store Herceptin vials in the refrigerator at 2°C to 8°C (36°F to 46°F) until time of reconstitution.
Patient information
Cardiomyopathy Advise patients to contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness [see Boxed Warning: Cardiomyopathy ] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential that Herceptin exposure during pregnancy or within 7 months prior to conception can result in fetal harm. Advise female patients to contact their healthcare provider with a known or suspected pregnancy [see Use in Specific Populations (8.1) ]. Encourage women who are exposed to Herceptin during pregnancy or who become pregnant within 7 months following the last dose of Herceptin to report their pregnancy to Genentech [see Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of Herceptin [see Use in Specific Populations (8.3) ] .
Label text from the FDA structured product label by Genentech, Inc. (revised May 29, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Trastuzumab in 1 product
Herceptin NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50242-132 | Trastuzumab 150 mg/7.4mL Injection, Powder, Lyophilized, For Solution | Genentech, Inc. | BLA |
Frequently asked questions
What is Herceptin used for?
Herceptin is a HER2/neu receptor antagonist indicated in adults for: The treatment of HER2-overexpressing breast cancer. ( 1.1 , 1.2 ) The treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. ( 1.3 ) Select patients for therapy based on an FDA-authorized companion diagnostic for Herceptin ( 1 , 2.2 ). 1.1 Adjuvant Breast Cancer Herceptin is indicated in…
What are the side effects of Herceptin?
The following adverse reactions are discussed in greater detail in other sections of the label: Cardiomyopathy [see Warnings and Precautions (5.1) ] Infusion Reactions [see Warnings and Precautions (5.2) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.3) ] Pulmonary Toxicity [see Warnings and Precautions (5.4) ] Exacerbation of Chemotherapy-Induced Neutropenia [see Warnings and… See the full label for the complete list.
Who makes Herceptin?
Herceptin is listed by 1 labeler in the FDA NDC directory, including Genentech, Inc..