Trastuzumab
Drug Related WarningTrastuzumab
Cardiomyopathy: Trastuzumab administration may cause subclinical or clinical cardiac failure, evident as CHF and reduced left ventricular ejection fraction (LVEF). Assess LVEF before and during treatment. Patients receiving Trastuzumab along with anthracycline-based chemo have a higher risk of left ventricular dysfunction. Discontinue for adjuvant breast cancer therapy and strongly consider discontinuation in metastatic cases with a substantial decrease in LVEF.
Infusion reactions, pulmonary toxicity: Severe pulmonary toxicity leading to potentially fatal infusion reactions may occur. Symptoms typically arose during or within 24 hours of administration. Pause infusion if patients exhibit dyspnea or significant hypotension. Monitor until complete resolution of signs. Cease treatment for reactions such as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.
Embryo-fetal toxicity: Pregnancy-related exposure can cause oligohydramnios, pulmonary hypoplasia, skeletal deformities, and neonatal death can occasionally exacerbate.
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Monoclonal antibodies, Therapy Class:
Antineoplastic agent, Approved Countries
India, the United States, Canada, countries within the European Union, Australia, Japan and South Korea.
Trastuzumab is an antineoplastic agent belonging to the pharmacological class of monoclonal antibodies.
Trastuzumab is FDA-approved for treating HER2-positive breast and gastric cancers.
Administered intravenously, Trastuzumab swiftly enters systemic circulation, ensuring consistent plasma levels. Trastuzumab emtansine deconjugates and undergoes catabolism in cellular lysosomes. IgG clearance via the reticuloendothelial system might aid its excretion.
The most common side effects of Trastuzumab include nausea, headache, rash, insomnia, and infection.
Trastuzumab is available as an injectable solution.
The molecule is available in India, the United States, Canada, countries within the European Union, Australia, Japan and South Korea.
Trastuzumab is an antineoplastic agent belonging to the pharmacological class of monoclonal antibodies.
A transmembrane receptor protein weighing 185 kDa, structurally similar to the epidermal growth factor receptor, is encoded by the HER2 (c-erbB2) proto-oncogene. Research shows that Trastuzumab can stop human tumour cells that overexpress HER2 from proliferating in both vitro and animal models.
Trastuzumab mediates antibody-dependent cellular cytotoxicity (ADCC). Comparing HER2 overexpressing cancer cells to cancer cells that do not overexpress HER2, it has been demonstrated that trastuzumab-mediated ADCC preferentially affects these cells in vitro.
Trastuzumab is available as an injection solution.
Injection solutions: To be administered parenterally as applicable.
As physician recommends, the medication can be taken usually once every week or once every 3 weeks. The first injection is given over at least 90 minutes.
- Breast cancer
- Stomach cancer (gastric cancer)
- Breast cancer: For the treatment of breast cancer, trastuzumab injection is used. It reduces breast lumps, bloody nipple discharge, and texture changes, in addition to stopping the growth and spread of cancer. It inhibits the growth and prevents the division of HER2-positive breast cancer cells. It improves treatment outcomes when combined with chemotherapy, lowering the chance of cancer returning after surgery and increasing survival rates for HER2-positive breast cancer in both the early and advanced stages.
- Stomach cancer: Trastuzumab inhibits the growth and metastasis of cancer cells in stomach cancer by specifically targeting tumours that overexpress HER2. In HER2-positive advanced or metastatic gastric cancer, it prolongs survival and slows the disease's progression when combined with chemotherapy. Its targeted action on HER2 receptors inhibits the growth of cancer cells, significantly improving the course of treatment for these patients.
Trastuzumab is indicated for the following health conditions:
- As an adjuvant treatment for breast cancer with overexpression of HER-2. In conjunction with either docetaxel or paclitaxel, cyclophosphamide, and doxorubicin.
- It is a first-line treatment for HER2-overexpressing metastatic breast cancer in patients who have had one or more chemotherapy regimens for metastatic disease, either in conjunction with paclitaxel or as a single agent.
- For patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinomas who have not had metastatic disease treated previously, in conjunction with cisplatin and capecitabine or 5-fluorouracil.
Parenterally: Avoid giving an intravenous push or bolus when administering the trastuzumab loading dose; instead, use a 90-minute intravenous infusion. A physician with training in an emergency kit should administer the injection and be prepared to handle anaphylaxis. It is necessary to monitor patients for symptoms such as fever, chills, or other infusions-related reactions for six hours following the start of the first infusion and two hours following subsequent infusions. Stopping or reducing the injection may be necessary to manage symptoms; infusion can then be resumed after symptoms have subsided. After a 30-minute infusion, supplementary doses can be administered if the first loading dose is well tolerated.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
150mg/single-dose vial
420mg/multidose vial
Trastuzumab is available as an injectable solution.
Dose Adjustment in Adult Patients:
Metastatic breast cancer: When used alone or in combination (with a taxane or an aromatase inhibitor): 4 mg/kg by infusion over 90 minutes at first, then 2 mg/kg over 30 minutes every week until the disease progresses. Trastuzumab emtansine: 3.6 mg/kg administered as a three-weekly infusion (21-day cycle). Give the first dose for 90 minutes. It is possible to help subsequent doses as 30-minute infusions.
Early breast cancer: Following radiotherapy, chemotherapy, or surgery. First, a 4 mg/kg infusion over 90 minutes was followed by a weekly injection of 2 mg/kg over 30 minutes for a year or until the disease recurs, whichever comes first. As an alternative, start with an initial dose of 8 mg/kg by infusion over 90 minutes, then gradually increase to 6 mg/kg by IV infusion over 30-90 minutes at 3-week intervals for a year or until the disease recurs, whichever comes first.
For metastatic stomach cancer: At the beginning, 8 mg/kg was infused over 90 minutes, and then 6 mg/kg was infused over 30 to 90 minutes at 3-week intervals until the disease progressed.
While on Trastuzumab, managing side effects is possible through dietary adjustments. Consume lean meats, healthy fats, fruits, vegetables, and whole-grain foods for increased energy levels. Ensure adequate hydration by drinking ample water, as dehydration commonly occurs in cancer patients. Refrain from smoking and consuming alcohol to minimize potential adverse effects.
The dietary restriction should be individualized as per patient requirements.
- Hypersensitivity to any of the excipients, mouse proteins, or Trastuzumab.
- Severe dyspnea at rest is brought on by complications from more advanced cancer or the need for additional oxygen treatment.
- Exercise extreme caution in patients with cardiac diseases or a history of cardiotoxic agents, as well as those experiencing a decrease in ejection fraction, pulmonary conditions, or elderly patients.
- Before treatment initiation, confirm the pregnancy status of females capable of reproduction.Congestive Heart Failure (CHF): Over a median follow-up period of 8 years, severe CHF (NYHA III and IV) occurred at a rate of 0.8%, while mild symptomatic and asymptomatic left ventricular dysfunction was observed in 4.6% of cases.Exposure to Trastuzumab during pregnancy or up to 7 months before conception may harm the fetus; females of reproductive age should practice effective contraception during therapy and for seven months following the final dose.
- Be cautious about Tumor Lysis Syndrome (TLS) occurrence, especially in patients with significant tumour burden, potentially leading to hyperuricemia, hyperphosphatemia, and acute renal failure. Consider additional monitoring or treatment as necessary based on clinical indications.
- Exacerbation of Chemotherapy-Induced Neutropenia: In randomized, controlled clinical trials, patients receiving myelosuppressive chemotherapy had higher per-patient rates of febrile neutropenia and NCI-CTC Grade 3–4 neutropenia than patients receiving chemotherapy alone. Patients receiving therapy had a similar incidence of septic death as patients not receiving treatment.
- Preinfusion treatment: About 40% of patients have mild-to-moderately severe symptoms, such as fever and chills. Pretreatment should involve the administration of acetaminophen, diphenhydramine, and meperidine, occasionally in conjunction with a decrease in the infusion rate.
Alcohol Warning
It is unsafe to consume Trastuzumab with alcohol.
Breast Feeding Warning
It is not recommended for use during breastfeeding.
Pregnancy Warning
It is not recommended for use during pregnancy.
Food Warning
Consume proteins and whole foods; avoid smoking, alcohol, and processed foods.
The adverse reactions related to Trastuzumab can be categorized as:
- Common Adverse Effects: Headaches, nasopharyngitis, diarrhoea, nausea, pyrexia, peripheral oedema, chills, asthenia, myalgia, hypertension, dizziness, influenza, rash, vomiting, bone pain, urinary tract infection (UTI), influenza-like illness, nail disorders, pruritus, and paresthesia.
- Less Common Adverse Effects: Pain, asthenia, fever, cough, diarrhea, abdominal pain, dyspnea, infection, anorexia, insomnia, and dizziness.
- Rare Adverse Effects: Cardiac failure, cardiac disorder, hypersensitivity reactions, autoimmune thyroiditis, ventricular dysfunction, and sudden death.
Reports on Postmarketing
Infusion Reaction
Oligohydramniosis or oligohydramnios sequence, characterized by skeletal deformities, pulmonary hypoplasia, and neonatal mortality
Tumor lysis syndrome (TLS)
Glomerulopathy
Thrombocytopenia immune
The clinically relevant drug interactions of Trastuzumab are briefly summarized here.
Based on population PK analysis, patients who receive anthracycline after stopping Trastuzumab may be more susceptible to cardiac dysfunction due to the drug's lengthy washout period. Physicians should refrain from using anthracycline-based therapy for a maximum of seven months following the cessation of Trastuzumab. When using anthracyclines, the patient's heart should be closely monitored.
The common side effects of Trastuzumab include nausea, vomiting, taste alterations, diarrhoea, myalgia, bone pain, and anaemia, resulting in a reduced count of red blood cells. Other symptoms may involve chills, decreased levels of blood cells (red cells, white cells, and platelets), headaches, fatigue, stomatitis (mouth inflammation), injection site reactions, pain at the injection site, dizziness, oedema, cough, rash, and insomnia.
- Pregnancy
Pregnancy Category D (FDA): Use in cases where no safer medication is available and life is in danger. Positive evidence of prenatal risk in humans.
When given to a pregnant woman, it may harm the fetus.
According to postmarketing reports, pregnant women who used Trastuzumab had cases of oligohydramnios and oligohydramnios sequence, which showed up as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.
Advise the patient about possible hazards to the fetus.
Contraceptives
Before beginning any treatment, determine whether any females of reproductive potential are pregnant. Inform pregnant women and other potential parents that exposure to certain substances during pregnancy or in the seven months before conception can harm the developing fetus.
Encourage women who can conceive to use effective contraception both during and for seven months after their last dose of treatment.
- Nursing Mothers
There is no information available about Trastuzumab's presence in human milk, how it affects breastfed babies, or how it affects milk production.
According to published data, human milk contains human IgG, but not in significant quantities that enter the circulation of newborns and infants.
Although Trastuzumab was found in the milk of nursing cynomolgus monkeys, it was not linked to any toxicity in newborns.
Evaluate the health and developmental advantages of breastfeeding in conjunction with the mother's clinical need for treatment and any possible adverse drug or underlying mother condition effects on the breastfed child (unwrap).
Consider the seven-month trastuzumab washout period.
- Pediatric Use
As per FDA, the safety and effectiveness of Trastuzumab in pediatric patients have not been established.
- Geriatrics (> 65 years old) Use
Research has been done on the effectiveness and safety of Trastuzumab in elderly patients. Compared to younger adults, elderly patients (65 years of age and above) usually show comparable treatment outcomes. Careful monitoring and dosage adjustments based on individual tolerability are advised, even though they may have a slightly higher risk of specific side effects. Overall, geriatric populations treated with Trastuzumab have demonstrated safety profiles and efficacy comparable to those reported in younger age groups.
Dose Adjustment in Kidney Impairment Patients:
Kidney impairment: Adjust the dose of the medication according to the severity of renal dysfunction. Lower doses or extended intervals may be necessary.
Dose Adjustment in Hepatic Impairment Patients:
Hepatic impairment: adjust the dosage of the medication based on the severity of liver dysfunction.
Overdosage in human clinical trials has never been experienced before. No tests have been conducted on single doses exceeding 8 mg/kg.
Pharmacodynamics:
Treatment for HER2-positive breast cancer involves the use of Trastuzumab, which has antitumour properties. Since HER2 protein overexpression is seen in 20% to 30% of primary breast cancers, HER2 offers a promising target for therapeutic intervention in the management of breast cancer. Trastuzumab has been demonstrated to impede the growth of human tumour cells that overexpress HER2 in both in vitro experiments and animal models. It is a mediator of antibody-dependent cellular cytotoxicity, attaches itself to cells that overexpress HER2 and causes preferential cell death. In vivo, Trastuzumab has also been demonstrated to prevent tumour cells from angiogenizing. There is no evident advantage over standard-dose schedules for higher doses or longer dosing intervals. Trastuzumab did not show clinically significant QTc interval duration in patients with HER2-positive solid tumours.
Pharmacokinetics:
- Absorption: Trastuzumab's intravenous administration allows direct bloodstream entry, bypassing oral absorption considerations typical of other medications. At steady state (weeks 16 to 32), peak and trough plasma concentrations measured approximately 123 and 79 mcg/mL, respectively. A dosage of 500 mg resulted in a mean peak serum concentration of 377 mcg/mL.
- Distribution: Its volume of distribution, 44 mL/kg as Trastuzumab and 3.13 L as Trastuzumab emtansine, signifies its presence across various body compartments.
- Metabolism: Trastuzumab emtansine undergoes deconjugation and catabolism through proteolysis within cellular lysosomes.
- Excretion: With a weekly dosing schedule, the elimination half-life is approximately 6 days, extending to 16 days with a regimen administered every three weeks. Trastuzumab emtansine exhibits an elimination half-life of about 4 days. Clearance of IgG through the reticuloendothelial system may contribute to its excretion.
- Del Mastro L, Lambertini M, Bighin C, Levaggi A, D'Alonzo A, Giraudi S, Pronzato P. Trastuzumab as first-line therapy in HER2-positive metastatic breast cancer patients. Expert Rev Anticancer Ther. 2012 Nov;12(11):1391-405. doi: 10.1586/era.12.107. Epub 2012 Oct 16. PMID: 23072512.
- Gajria D, Chandarlapaty S. HER2-amplified breast cancer: mechanisms of trastuzumab resistance and novel targeted therapies. Expert Rev Anticancer Ther. 2011 Feb;11(2):263-75. doi: 10.1586/era.10.226. PMID: 21342044; PMCID: PMC3092522.
- Jackson C, Finikarides L, Freeman ALJ. The adverse effects of trastuzumab-containing regimes as a therapy in breast cancer: A piggy-back systematic review and meta-analysis. PLoS One. 2022 Dec 1;17(12):e0275321. doi: 10.1371/journal.pone.0275321. PMID: 36454979; PMCID: PMC9714930.
- Early Breast Cancer Trialists’ Collaborative group (EBCTCG). Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials. Lancet Oncol. 2021 Aug;22(8):1139-1150. doi: 10.1016/S1470-2045(21)00288-6. PMID: 34339645; PMCID: PMC8324484.
- https://www.ncbi.nlm.nih.gov/books/NBK532246/
- https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=492dbdb2-077e-4064-bff3-372d6af0a7a2
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/103792s5250lbl.pdf
- https://www.ema.europa.eu/en/documents/product-information/herceptin
Published on: 10 Jan 2024 6:06 AM GMT