Herticad

White to light yellow powder or porous mass. The recovered solution - clear to slightly opalescent, colourless to light yellow liquid.
For vial containing 150 mg of trastuzumab: Histidine hydrochloride monohydrate 3.4 mg, Histidine 2.2 mg, Trehalose dihydrate 330.0 mg, Polysorbate 20 0.6 mg.
For vial containing 440 mg of trastuzumab: Histidine hydrochloride monohydrate 9.9 mg, Histidine 6.4 mg, Trehalose dihydrate 968.0 mg, Polysorbate 20 1.8 mg.
Each vial containing 440 mg trastuzumab is reconstituted with 20.0 mL of solvent (supplied) or water for injections (not supplied). Each mL of solvent contains: benzyl alcohol 11.0 mg; water for injections q.s. to make 1 mL.
Each vial contains 150 mg trastuzumab that has to be dissolved in 7.2 mL of water for injection.
The resulting solution contains approximately 21 mg/mL trastuzumab.

Pharmacology: Pharmacodynamics: Description: Trastuzumab 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 tumor cells that overexpress HER2 protein.
Pharmacokinetics: Distribution: Volume of distribution: 44 mL/kg (as trastuzumab); 3.13 L (as trastuzumab emtansine).
Metabolism: As trastuzumab emtansine: Undergoes deconjugation and catabolism through proteolysis in cellular lysosomes.
Excretion: Elimination half-life: 6 days (wkly dosing): 16 days (3 wkly regimen); approx 4 days (as trastuzumab emtansine). Elimination may involve clearance of IgG through the reticuloendothelial system.

Trastuzumab contains the active substance trastuzumab, which is a monoclonal antibody (a type of protein that is normally made by the immune system to help defend the body from infection and cancer). Monoclonal antibodies attach to specific proteins or antigens. Trastuzumab is designed to bind selectively to an antigen called human epidermal growth factor receptor 2 (HER2). HER2 is found in large amounts on the surface of some cancer cells where it stimulates the growth of such cells and causes them to die.
The doctor may prescribe Trastuzumab for the treatment of breast and gastric cancer when: The patient has early breast cancer with high levels of a protein called HER2.
The patient has metastatic breast cancer (breast cancer that has spread beyond the original tumour) with high levels of HER2. Trastuzumab may be prescribed in combination with the chemotherapy medicine paclitaxel or docetaxel as first treatment for metastatic breast cancer or it may be prescribed alone if other treatments have proved unsuccessful.
It is also used in combination with medicines called aromatase inhibitors with patients with high levels of HER2 and hormone receptor-positive metastatic breast cancer (cancer that is sensitive to the presence of female sex hormones).
The patient has metastatic gastric cancer with high levels of HER2, when it is in combination with the other cancer medicines capecitabine or 5-fluorouracil and cisplatin.

Before starting the treatment the doctor will determine the amount of HER2 in the tumour. Only patients with a large amount of HER2 will be treated with Trastuzumab.
Trastuzumab should only be given by a doctor or nurse. The doctor will prescribe a dose and treatment regimen that is right for the patient.
The dose of Trastuzumab depends on the body weight.
Trastuzumab intravenous formulation is not for subcutaneous use and should be given as an intravenous infusion only.
Trastuzumab intravenous formulation is given as an intravenous infusion ("drip") directly into the veins.
The first dose of treatment is given over 90 minutes and patient will be observed by a health professional while it is being given in case the patient has any side effects. If the first dose is well tolerated the next doses may be given over 30 minutes. The number of infusions the patient receives will depend on how the patient responds to the treatment. The doctor will discuss this with the patient.
For early breast cancer, metastatic breast cancer and metastatic gastric cancer, Trastuzumab is given every 3 weeks. Trastuzumab may also be given once a week for metastatic breast cancer.
If the patient stops using Trastuzumab: Do not stop using this medicine without talking to the doctor first. All doses should be taken at the right time every week or every three weeks (depending on the dosing schedule). This helps the medicine work as well as it can.
It may take up to 7 months for trastuzumab to be removed from the body. Therefore, the doctor may decide to continue to check the heart functions, even after the patient finishes treatment.
If the patient has any further questions on the use of this medicine, ask the doctor, pharmacist or nurse.

As per the published literature, there is no experience with overdose in human clinical trials. As per the published literature on another trastuzumab product, single doses of trastuzumab alone greater than 10 mg/kg have not been administered in the clinical trials. Doses up to this level were well tolerated.

The patient is allergic (hypersensitive) to trastuzumab to murine (mouse) proteins, or to any of the other ingredients of this medicine.
The patient has severe breathing problems at rest due to cancer or if patient needs oxygen treatment.

The doctor will closely supervise the therapy.
Heart checks: Treatment with Trastuzumab alone or with a taxane may affect the heart, especially if the patient has ever used an anthracycline (taxanes and anthracyclines are two other kinds of medicine used to treat cancer).
The effects may be moderate to severe and could cause death. Therefore, the heart function will be checked before, during (every three months) and after (up to two to five years) treatment with Trastuzumab.
If the patient develops any signs of heart failure (inadequate pumping of blood by the heart), the heart function may be checked more frequently (every six to eight weeks), patient may receive treatment for heart failure or patient may have to stop Trastuzumab treatment.
Talk to the doctor, pharmacist or nurse before patient is given Trastuzumab if: patient had heart failure, coronary artery disease, heart valve disease (heart murmurs), high blood pressure, taken any high blood pressure medicine or are currently taking any high blood pressure medicine.
The patient has ever had or are currently using a medicine called doxorubicin or epirubicin (medicines used to treat cancer). These medicines (or any other anthracyclines) can damage heart muscle and increase the risk of heart problems with trastuzumab.
The patient suffers from breathlessness, especially if patient is currently using a taxane. Trastuzumab can cause breathing difficulties before treatment have died when they were given trastuzumab.
The patient has ever had any other treatment for cancer.
If the patient receives Trastuzumab with any other medicine to treat cancer, such as paclitaxel, docetaxel, an aromatase inhibitor, capecitabine, 5-fluorouracil, or cisplatin the patient should also read the patient information leaflets for these products.
Driving and using machines: It is not known whether Trastuzumab can affect the ability to drive a car or operate machines. However, if during treatment the patient experiences symptoms, such as chills or fever, patient should not drive or use machines until these symptoms disappear.
Use in Children: Trastuzumab is not recommended for anyone under the age of 18 years.

Pregnancy: If the patient is pregnant, think the patient may be pregnant or are planning to have a baby, ask the doctor, pharmacist or nurse for advice before taking this medicine.
Patient should use effective contraception during treatment with Trastuzumab and for at least 7 months after treatment has ended.
The doctor will advise the patient of the risks and benefits of taking Trastuzumab during pregnancy.
In rare cases, a reduction in the amount of (amniotic) fluid that surrounds the developing baby within the womb has been observed in pregnant women receiving trastuzumab.
This condition may be harmful to the baby in the womb and has been associated with the lungs not developing fully resulting in foetal death.
Breastfeeding: Do not breastfeed the baby during Trastuzumab therapy and for 7 months after the last dose of Trastuzumab as trastuzumab may pass to the baby through the breast milk.
Ask the doctor or pharmacist for advice before taking any medicine.

Like all medicines, Trastuzumab can cause side effects, although not everybody gets them. Some of these side effects may be serious and may lead to hospitalization.
During a trastuzumab infusion, chills, fever and other flu like symptoms may occur. These are very common (may affect more than 1 in 10 people).
Other infusion-related symptoms are: feeling sick (nausea), vomiting, pain, increased muscle tension and shaking, headache, dizziness, breathing difficulties, wheezing, high or low blood pressure, heart rhythm disturbances (palpitations, heart fluttering or irregular heartbeat), swelling of the face and lips, rash and feeling tired. Some of these symptoms can be serious and some patients have died.
These effects mainly occur with the first intravenous infusion ("drip" into the vein) and during the first few hours after the start of the infusion. They are usually temporary. Patient will be observed by a health care professional during the infusion and for at least six hours after the start of the first infusion and for two hours after the start of other infusions. If the patient develops a reaction, they will slow down or stop the infusion and may give the patient treatment to counteract the side effects. The infusion may be continued after the symptoms improve.
Occasionally, symptoms start later than six hours after the infusion begins. If this happens to the patient, contact the doctor immediately. Sometimes, symptoms may improve and then get worse later.
Other side effects can occur at any time during treatment with trastuzumab, not just related to an infusion. Heart problems can sometimes occur during treatment and occasionally after treatment has stopped and can be serious. They include weakening of the heart muscle possibly leading to heart failure inflammation (swollen, red, hot, and in pain) of the lining around the heart and heart rhythm disturbances. This can lead to symptoms such as: breathlessness (including breathlessness at night), cough, fluid retention (swelling) in the legs or arms, palpitations (heart fluttering or irregular heartbeat). The doctor will monitor the heart regularly during and after treatment but patient should tell the doctor immediately if the patient notices any of the previously mentioned symptoms. If the patient experiences any of the previously mentioned symptoms when the treatment with Trastuzumab has finished, patient should see the doctor and tell them that the patient has previously been treated with Trastuzumab.
Very common side effects of trastuzumab: may affect more than 1 in 10 people: infections, diarrhoea, constipation, heartburn (dyspepsia), weakness, skin rashes, chest pain, abdominal pain, joint pain, low counts of red blood cells and white blood cells (which help fight infection) sometimes with fever, muscle pain, conjunctivitis, watery eyes, nosebleeds, runny nose, hair loss, tremor, hot flush, dizziness, nail disorders, weight loss, loss of appetite, inability to sleep (insomnia), altered taste, low platelet count, numbness or tingling of the fingers and toes, redness, swelling or sores in the mouth and/or throat, pain, swelling, redness or tingling of hands and/or feet, breathlessness, headache, cough, vomiting, nausea.
Common side effects of trastuzumab: may affect up to 1 in 10 people: allergic reactions, throat infections, bladder and skin infections, shingles, inflammation of the breast, inflammation of the pancreas or liver, kidney disorders, increased muscle tone or tension (hypertonia), pain in the arms and/or legs, itchy rash, sleepiness (somnolence), bruising, haemorrhoids, itchiness, dry mouth and skin, dry eyes, sweating, feeling weak and unwell, anxiety, depression, abnormal thinking, asthma, infection of lungs, lung disorders, back pain, neck pain, bone pain, acne, leg cramps.
Uncommon side effects of Trastuzumab: may affect up to 1 in 100 people: deafness, bumpy rash, blood infection.
Rare side effects of Trastuzumab: may affect up to 1 in 1000 people: weakness, jaundice, inflammation or scarring of the lungs.
Other side effects that have been reported with trastuzumab use: frequency cannot be estimated from the available data: abnormal or impaired blood clotting, anaphylactic reactions, high potassium levels, swelling of the brain, swelling or bleeding at the back of the eyes, shock, swelling of the lining of the heart, slow heart rate, abnormal heart rhythm, respiratory distress, respiratory failure, acute accumulation of fluid in the lungs, acute narrowing of the airways, abnormally low oxygen levels in the blood, difficulty in breathing when lying flat, liver damage/failure, swelling of the face, lips and throat, kidney failure, abnormally low levels of fluid around baby in womb, failure of lungs to develop in the womb, abnormal kidney development in the womb.
Some of the side effects the patient experiences may be due to the underlying breast cancer. If the patient receives Trastuzumab in combination with chemotherapy, some of them may also be due to the chemotherapy.
If the patient gets any side effects, talk to the doctor, pharmacist or nurse.
Reporting of side effects: If the patient gets any side effects, talk to the doctor, pharmacist or nurse. This includes any possible side effects not listed in this monograph. The patient can also report side effects directly (see details as follows). By reporting side effects, patient can help provide more information on the safety of this medicine.

May increase cardiotoxicity of antineoplastic agents. May increase neutropenic effect of immunosuppressants. May increase serum level with paclitaxel.
Tell the doctor, pharmacist or nurse if the patient is taking, have recently taken or may take any other medicines. It may take up to 7 months for trastuzumab to be removed from the body. Therefore, patient should tell the doctor, pharmacist or nurse that the patient has had Trastuzumab if the patient starts any new medicine in the 7 months after stopping treatment.

Directions for Reconstitution: 1) Using a sterile syringe, slowly inject water for injections or solvent in the vial containing the lyophilised Trastuzumab, directing the stream into the lyophilised cake.
2) Swirl the vial gently to aid reconstitution. Do not shake.
Slight foaming of the product upon reconstitution is not unusual. Allow the vial to stand undisturbed for approximately 5 minutes.
The reconstituted Trastuzumab results in a colourless to pale yellow transparent solution and should be essentially free of visible particulates.
Determine the volume of the solution required: based on a loading dose of 4 mg trastuzumab/kg; based on a loading dose of 4 mg trastuzumab/kg body weight, or a subsequent weekly dose of 2 mg trastuzumab/kg body weight: See Equation 1.

Click on icon to see table/diagram/image

Based on a loading dose of 8 mg trastuzumab/kg body weight, or a subsequent 3-weekly dose of 6 mg trastuzumab/kg body weight: See Equation 2.

Click on icon to see table/diagram/image

The appropriate amount of solution should be withdrawn from the vial and added to an infusion bag containing 250 mL of 0.9% sodium chloride solution. Do not use with glucose-containing solutions. The bag should be gently inverted to mix the solution in order to avoid foaming. Once the infusion is prepared it should be administered immediately. If diluted aseptically, it may be stored for 24 hours (store at 2°C-8°C).
The concentrate made from 440 mg Trastuzumab, if diluted with supplied solvent, may be stored for 28 days at 2°C-8°C and may be used for multiple injections. The concentrate made from 440 mg or 150 mg Trastuzumab, if diluted with unsupplied water for injection, may be stored for 24 hours at 2°C-8°C.
Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
No incompatibilities between Trastuzumab and polyvinylchloride, polyethylene or polypropylene bags have been observed.

Store at temperatures between 2-8°C.
Infusion solutions should be used immediately after dilution. Do not use Trastuzumab if the patient notices any particulate matter or discoloration prior to administration.
Medicines should not be disposed of via wastewater or household waste. Ask the pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
Always keep this medicine in the closed original pack at a temperature of 2°C-8°C in a refrigerator. After reconstitution with water for injections the reconstituted solution is physically and chemically stable for 24 hours at 2°C-8°C. Any remaining reconstituted solution should be discarded.
After reconstitution with solvent supplied with vials containing 440 mg of trastuzumab the reconstituted solution is physically and chemically stable for 28 days at 2°C-8°C under controlled and validated aseptic conditions. Any remaining reconstituted solution should be discarded.
Solutions of Trastuzumab for intravenous infusion are physically and chemically stable in polyvinylchloride, polyethylene or polypropylene bags containing sodium chloride 9 mg/mL (0.9 %) solution for injection for 24 hours at 2°C-8°C.
From a microbiological point of view, the reconstituted solution of Trastuzumab with water for injections and Trastuzumab infusion solution should be used immediately. The product is not intended to be stored after reconstitution and dilution unless this has taken place under controlled and validated aseptic conditions. If not used immediately, in-use storage times and conditions are the responsibility of the user.
Each vial containing 150 mg of trastuzumab is reconstituted with 7.2 mL of water for injections (not supplied). Use of other reconstitution solvents should be avoided.
This yields a 7.4 mL solution for single-dose use, containing approximately 21 mg/mL trastuzumab, at a pH of approximately 6.0. A volume overage of 4 % ensures that the labelled dose of 150 mg can be withdrawn from each vial.
Each vial containing 440 mg of trastuzumab is reconstituted with 20.0 mL of solvent (supplied) or water for injections (not supplied). Use of other reconstitution solvents should be avoided.
This yields a 20 mL solution for single-dose use, containing approximately 21 mg/mL trastuzumab, at a pH of approximately 6.0. A volume overage of 4 % ensures that the labelled dose of 150 mg can be withdrawn from each vial.
Trastuzumab should be carefully handled during reconstitution. Causing excessive foaming during reconstitution or shaking the reconstituted solution may result in problems with the amount of Trastuzumab that can be withdrawn from the vial.
The reconstituted solution should not be frozen.

Targeted Cancer Therapy

L01FD01 - trastuzumab ; Belongs to the class of HER2 (Human Epidermal Growth Factor Receptor 2) inhibitors. Used in the treatment of cancer.

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