Enhertu

Enhertu Uses, Dosage, Side Effects, Food Interaction and all others data.

Enhertu and trastuzumab emtansine (also known as ado-trastuzumab emtansine) is a recombinant humanised monoclonal antibody that has action directed against a cell surface protein produced by the human epidermal growth factor receptor 2 (HER2). It inhibits proliferation of tumour cells that overexpress HER2 protein.

Enhertu exerts an antitumour activity and is used in the treatment of HER2-positive breast cancer. HER2 protein overexpression is observed in 20%-30% of primary breast cancers thus HER2 presents as a useful therapeutic target for the treatment of breast cancers. Enhertu has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumour cells that overexpress HER2. It works as a mediator of antibody-dependent cellular cytotoxicity, where it binds as an antibody to cells over-expressing HER2, leading to preferential cell death. Enhertu was also shown to inhibit angiogenesis of tumor cells in vivo . Higher doses and longer dosing intervals show no significant benefit over standard dose schedules . In patients with HER2 positive solid tumours, trastuzumab did not exert any clinically significant QTc interval duration.

Trade Name Enhertu
Availability Prescription only
Generic Trastuzumab
Trastuzumab Other Names RHUMAB HER2, Trastuzumab, trastuzumab-anns, trastuzumab-dkst, trastuzumab-dttb, trastuzumab-pkrb, trastuzumab-qyyp
Related Drugs tamoxifen, letrozole, Keytruda, Arimidex, pembrolizumab, paclitaxel, Ibrance, Femara, Opdivo, Xeloda
Weight 100mg,
Type Intravenous powder for injection
Formula C6470H10012N1726O2013S42
Weight 145531.5 Da
Groups Approved, Investigational
Therapeutic Class Targeted Cancer Therapy
Manufacturer Daiichi Sankyo UK Limited
Available Country United Kingdom, United States,
Last Updated: September 19, 2023 at 7:00 am
Enhertu
Enhertu

Uses

Adjuvant Breast Cancer: Enhertu is used for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature) 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 Enhertu

Metastatic Breast Cancer: Enhertu is used for:

  • 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 Enhertu

Metastatic Gastric Cancer: Enhertu is used, 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-approved companion diagnostic for Enhertu

Enhertu is also used to associated treatment for these conditions: Breast Cancer, Early Breast Cancer, Inflammatory Breast Cancer (IBC), Locally Advanced Breast Cancer (LABC), Metastatic Adenocarcinoma of the Gastro-Esophageal Junction, Metastatic Adenocarcinoma of the Stomach, Metastatic Breast Cancer, Metastatic Gastric Adenocarcinoma, Metastatic Gastroesophageal Junction Adenocarcinoma

How Enhertu works

Enhertu is a recombinant humanized IgG1 monoclonal antibody against the HER-2 receptor, a member of the epidermal growth factor receptors which is a photo-oncogene. Over-expressed in breast tumour cells, HER-2 overamplifies the signal provided by other receptors of the HER family by forming heterodimers . The HER-2 receptor is a transmembrane tyrosine kinase receptor that consists of an extracellular ligand-binding domain, a transmembrane region, and an intracellular or cytoplasmic tyrosine kinase domain. It is activated by the formation of homodimers or heterodimers with other EGFR proteins, leading to dimerization and autophosphorylation and/or transphosphorylation of specific tyrosine residues in EGFR intracellular domains . Further downstream molecular signaling cascades are activated, such as the Ras/Raf/mitogen-activated protein kinase (MAPK), the phosphoinositide 3-kinase/Akt, and the phospholipase Cγ (PLCγ)/protein kinase C (PKC) pathways that promote cell growth and survival and cell cycle progression . Due to upregulation of HER-2 in tumour cells, hyperactivation of these signaling pathways and abnormal cell proliferation is observed. Enhertu binds to the extracellular ligand-binding domain and blocks the cleavage of the extracellular domain of HER-2 to induce its antibody-induced receptor downmodulation , and subsequently inhibits HER-2-mediated intracellular signaling cascades. Inhibition of MAPK and PI3K/Akt pathways lead to an increase in cell cycle arrest, and the suppression of cell growth and proliferation . Enhertu also mediates the activation of antibody-dependent cell-mediated cytotoxicity (ADCC) by attracting the immune cells, such as natural killer (NK) cells, to tumor sites that overexpress HER-2 . While the drug alone has a minimal potential to induce complement-dependent cytotoxicity (CDC), one study demonstrated increased therapeutic effectiveness and a synergistic effect on uterine serous carcinoma cells in vitro when used in combination with pertuzumab, which also has minor effects on CDC alone. This study showed that only the combination of both cell-bound antibodies would be sufficient to bind and activate the complement component 1q (C1q) required to initiate the complement cascade reaction.

Intrinsic trastuzumab resistance has been noted for some patients with HER-2 positive breast cancer. Mechanisms involving trastuzumab resistance include deficiency of phosphatase and tensin homologue and activation of phosphoinositide 3-kinase, and the overexpression of other surface receptors, such as insulin-like growth factor .

Dosage

Enhertu dosage

Intravenous (Adult)-

Early breast cancer: For treatment after chemotherapy, radiotherapy or surgery. Initially, 4 mg/kg via infusion over 90 min followed by 2 mg/kg via infusion over 30 min wkly for 1 yr or until disease recurrence, whichever occurs 1st. Alternatively, initial dose of 8 mg/kg via infusion over 90 min followed by 6 mg/kg via infusion over 30-90 min at 3-wkly interval for 1 yr or until disease recurrence, whichever occurs 1st.

Metastatic breast cancer: As monotherapy or combination therapy (with an aromatase inhibitor or taxane): Initially, 4 mg/kg via infusion over 90 min followed by 2 mg/kg via infusion over 30 min at wkly interval until progression of disease. As trastuzumab emtansine: 3.6 mg/kg as infusion 3 wkly (21-day cycle). Admin initial dose for 90 min. Subsequent doses may be administered as 30 min infusions.

Gastric cancer: For metastatic: Initially, 8 mg/kg via infusion over 90 min followed by 6 mg/kg via infusion over 30-90 min at 3-wkly interval until progression of disease.

Reconstitute with 20 mL of bacteriostatic sterile water for inj into a soln containing 21 mg/mL of trastuzumab. Swirl gently; do not shake. Dilute further prior to admin with appropriate vol of reconstituted trastuzumab soln in 250 mL of NaCl 0.9% inj.

Side Effects

Fever, headache, fatigue, nausea, vomiting, diarrhoea, infections, increased cough, dyspnoea, rash, neutropenia, anaemia, and myalgia; cardiac dysfunction, CHF.

Toxicity

There is no experience with overdosage of trastuzumab in clinical trials - single doses >8 mg/kg have not been tested in humans. Enhertu can contribute to the development of ventricular dysfunction and congestive heart failure, particularly when used in combination (or temporally adjacent) to other cardiotoxic chemotherapies such as anthracyclines.

Precaution

Patient with pre-existing CV and pulmonary disease; extensive pulmonary tumour involvement. Pregnancy and lactation.

Interaction

May increase cardiotoxicity of antineoplastic agents. May increase neutropenic effect of immunosuppressants. May increase serum level with paclitaxel.

Food Interaction

No interactions found.

Enhertu Hypertension interaction

[Moderate] Decreases in left ventricular ejection fraction (LVEF) have been reported with agents that block HER2 activity.

Patients who have received prior anthracyclines, those who received anthracycline after stopping therapy with agents that block HER2 activity, or patients who received prior radiotherapy to the chest area may be at higher risk of decreased LVEF.

Therapy with these agents should be administered cautiously in patients with a previous history of heart conditions.

Evaluate cardiac function before, during, and upon completion of treatment.

Withhold or discontinue therapy with agents that block HER2 activity as appropriate, and for a confirmed clinically significant decrease in left ventricular function, or if the LVEF has not improved or has declined further.

It is recommended to monitor overall cardiac function and LVEF by echocardiogram or MUGA scan as appropriate.

Elimination Route

Peak and trough plasma concentrations at steady state (between weeks 16 and 32) were approximately 123 and 79 mcg/mL, respectively. At the highest weekly dose studied (500 mg), mean peak serum concentration was 377 mcg/mL.

Half Life

The terminal half-life is approximately 28 days, but may decrease with lower doses - at the 10mg and 500mg doses, half-lives averaged approximately 1.7 and 12 days, respectively.

Clearance

The predicted steady-state clearance of trastuzumab is 0.173 - 0.337 L/day, dependent primarily on the dosing regimen. The clearance rate for subcutaneously administered trastuzumab, formulated with hyaluronidase for improved subcutaneous absorption, is 0.11 L/day.

Elimination Route

Following metabolism, the complex elimination of trastuzumab in humans is mediated by epithelial cells in a dose-dependent (nonlinear) fashion. The renal excretion of trastuzumab is very low.

Pregnancy & Breastfeeding use

Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Severe dyspnoea at rest.

Storage Condition

Store between 2-8° C.

Innovators Monograph

You find simplified version here Enhertu

Enhertu contains Trastuzumab see full prescribing information from innovator Enhertu Monograph, Enhertu MSDS, Enhertu FDA label

FAQ

What is Enhertu used for?

Enhertu used to treat some types of breast cancer, oesophageal cancer and stomach cancer.

How safe is Enhertu?

Data from intervention trials showed an excellent safety profile for Enhertu, except for cardiotoxicity. This latter is most commonly associated with an asymptomatic decline in the left ventricular ejection fraction rather than a congestive heart failure.

What are the common side effects of Enhertu?

The common side effects of Enhertu are chills, a high temperature, swelling of the face and lips, headache, hot flushes, feeling sick, wheezing and breathlessness. tiredness and difficulty sleeping (insomnia) diarrhoea or constipation.

Is Enhertu safe during pregnancy?

Enhertu should not be administered during pregnancy. However, for women who become accidentally pregnant during Enhertu administration and wish to continue pregnancy, Enhertu should be stopped and pregnancy could be allowed to continue.

Can I drink alcohol with Enhertu?

Heavy alcohol use during the course of Enhertu treatment and the HER2 Ile/Val genotype may constitute risk factors for cardiac toxicity.

Does Enhertu cause hair loss?

No, hair loss is not a common side effect of Enhertu. If you are receiving Enhertu in combination with chemotherapy, you may experience hair loss due to the chemotherapy.

How do I administer Enhertu?

Enhertu is given through an infusion into vein. The first dose is given over 90 minutes. If well-tolerated subsequent maintenance doses may be given over 30 minutes.

Is Enhertu an antibody?

Enhertu is a highly purified recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody that binds with high affinity and specificity to the extracellular domain of the HER2 receptor.

How long does Enhertu take to work?

Enhertu will begin working on your cancer cells as soon as you’ve taken the first dose. However, you may not notice Enhertu working to treat your condition. It doesn’t treat the side effects of cancer. Instead, it works to slow the growth of (and kill) HER2-positive cancer cells.

Is Enhertu safe during breastfeeding?

It’s not known whether it’s safe to use Herceptin while breastfeeding.
It’s important to note that Herceptin may stay in your body for 7 months after you stop taking it. Talk with your doctor about the risks and benefits of breastfeeding during Herceptin treatment or in the 7 months after you stop taking the drug.

How long can I take Enhertu?

If you're having Enhertu to treat primary breast cancer after surgery it's usually given for one year . If you are having Enhertu before surgery you will usually have four to six cycles.

Does Enhertu on Allergic reaction?

This usually happens with the first or second treatment. Symptoms include a skin rash, itching, feeling hot and shivering. Other symptoms include redness of the face, dizziness, a headache, shortness of breath and anxiety.

Does Enhertu effects on my heart?

You might get heart problems such as a change in your heart rhythm. Less commonly their might be changes to the heart muscle not allowing it to pump blood around the body properly. You might also get fluid around the heart but this is rare.

Will Enhertu affect my fertility?

You may not be able to become pregnant or father a child after treatment with this drug. Talk to your doctor before starting treatment if you think you may want to have a baby in the future.
Men might be able to store sperm before starting treatment. And women might be able to store eggs or ovarian tissue. But these services are not available in every hospital, so you would need to ask your doctor about this.

Does Enhertu effect my eye?

You might have eye problems including blurred vision, sore, red, itchy, dry eyes or an infection. Tell your doctor or nurse if you have this. They can give you eye drops or other medication to help.

Does Enhertu raise blood pressure?

Your blood pressure usually goes back to normal while you are on treatment or when treatment ends.

Can Enhertu causes skin problem?

Skin and nail problems include a skin rash, dry skin, itching and darker skin. Your nails may also become brittle, dry, change colour or develop ridges. This usually goes back to normal when you finish treatment.

*** Taking medicines without doctor's advice can cause long-term problems.
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