Trastuzumab parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations containing trastuzumab.
Drugs List
Therapeutic Indications
Uses
Combination treatment of HER2 +ve metastatic gastric adenocarcinoma
HER2 +ve early breast cancer
Metastatic breast cancer in patients whose tumours overexpress HER2
Trastuzumab should only be used in metastatic and early breast cancer in patients whose tumours have either HER2 (human epidermal growth factor receptor 2) over expression or HER2 gene amplification as determined by an accurate and validated assay.
Trastuzumab should only be used in patients with metastatic gastric cancer whose tumours have HER2 over expression as defined by IHC2+ and a confirmatory SISH or FISH result, or by an IHC 3+ result. Accurate and validated assay methods should be used.
Trastuzumab is indicated for the treatment of patients with HER2 positive metastatic breast cancer:
As monotherapy for the treatment of those patients who have received at least two chemotherapy regimens for their metastatic disease, including at least an anthracycline and a taxane unless patients are unsuitable for these treatments. Patients must also have failed hormonal therapy, unless patients are unsuitable for these treatments.
In combination with paclitaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease and for whom an anthracycline is not suitable.
In combination with docetaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease.
In combination with an aromatase inhibitor for the treatment of postmenopausal patients with hormone-receptor positive metastatic breast cancer, not previously treated with trastuzumab.
Trastuzumab is indicated for the treatment of patients with HER2 positive early breast cancer:
Following surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (if applicable).
Following adjuvant chemotherapy with doxorubicin and cyclophosphamide, in combination with paclitaxel or docetaxel.
In combination with adjuvant chemotherapy consisting of docetaxel and carboplatin.
In combination with neoadjuvant chemotherapy followed by adjuvant trastuzumab therapy, for locally advanced (including inflammatory) disease or tumours greater than 2cm in diameter.
Trastuzumab is indicated for the treatment of patients with HER2 positive metastatic adenocarcinoma of the stomach or gastro-oesophageal junction:
In patients who have not received prior anti-cancer treatment for their metastatic disease, in combination with capecitabine or 5-fluorouracil and cisplatin.
Dosage
Check the product labels to ensure that the correct formulation (intravenous infusion or subcutaneous injection fixed dose) is being administered to the patient, as prescribed. At the time of writing, limited information is available on switching from one formulation to another.
Adults
Powder for concentrate for solution for intravenous infusion
Metastatic Breast Cancer (MBC) and Early Breast cancer (EBC)
Weekly schedule:
Loading dose: 4mg/kg body weight.
Subsequent dose: 2mg/kg body weight per week, beginning one week after the loading dose.
3-weekly schedule:
Loading dose: 8mg/kg body weight.
Subsequent dose: 6mg/kg body weight at three weekly intervals, beginning three weeks after the loading dose.
Metastatic Gastric Cancer (MGC)
3-weekly schedule:
Loading dose: 8mg/kg body weight
Subsequent dose: 6mg/kg body weight at 3 weekly intervals, starting 3 weeks after the loading dose.
Solution for subcutaneous injection
Metastatic Breast Cancer (MBC) and Early Breast cancer (EBC)
600mg every 3 weeks. No loading dose is required.
Additional Dosage Information
Dose reduction
Patients may continue trastuzumab therapy during periods of reversible, chemotherapy-induced myelosuppression and should be monitored for neutropenia complications. For information on dose reduction of concomitant agents, consult individual drug monographs.
Missed doses
Powder for concentrate for solution for intravenous infusion
If a dose is missed by one week or less, then the usual maintenance dose should be given as soon as possible. Do not wait until the next planned cycle. Subsequent maintenance doses should then be given 7 days or 21 days later according to the previous schedule.
If a dose is missed by more than one week, a reloading dose of trastuzumab should be given as soon as possible. Subsequent trastuzumab maintenance doses should then be given 7 or 21 days later according to previous schedule.
Solution for subcutaneous injection
Upon a missed dose of trastuzumab, the next 600mg dose should be administered as soon as possible. The interval between consecutive injection doses should not be less than three weeks.
Administration
Powder for concentrate for solution, for intravenous infusion only.
Solution for injection, for subcutaneous injection.
Contraindications
Children under 18 years
Breastfeeding
Severe dyspnoea at rest secondary to advanced malignancy
Severe dyspnoea requiring supplementary oxygen therapy
Precautions and Warnings
Elderly
History of anthracycline therapy
Left ventricular ejection fraction below 55%
Cardiac arrhythmias
Cardiac failure
Cardiac valvulopathy
Cardiomyopathy
History of myocardial infarction
Hypertension
Ischaemic heart disease
Pericardial effusion
Pregnancy
Renal impairment - glomerular filtration rate below 20ml/minute
Advise ability to drive/operate machinery may be affected by side effects
Cardiotoxic -Avoid anthracyclines for up to 7 months after last trastuzumab
Not all available brands are licensed for all routes of administration
Not all presentations are licensed for all indications
Premedicate all patients with prior infusion related reactions
Treatment to be initiated and supervised by a specialist
Different preparations of trastuzumab are not interchangeable
Consult local policy on the safe use of anti-cancer drugs
Emergency equipment must be available
Record name and batch number of administered product
Staff: Not to be handled by pregnant staff
Suspend treatment or reduce rate until infusion reactions resolve
Assess baseline cardiac function prior to treatment
HER2 testing is mandatory prior to initiation of therapy
Monitor cardiac function every 3 months during treatment
Monitor cardiac function every 6 months for min. 2 years after stopping
Monitor patient closely for serious adverse events following administration
Monitor patient for infusion-associated reactions (IARs)
Advise patient of the risk of late onset adverse reactions
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider discontinuing therapy if significant cardiac failure develops
Increased risk of cardiotoxicity when used with anthracyclines
Advise patient to seek advice at first indications of pregnancy
Suspend treatment if LVEF below 50% & fall of more than 10% below baseline
Female: Contraception required during and for 7 months after treatment
Breastfeeding: Do not breastfeed during & for 7 months after treatment
Advise patient to report signs / symptoms of infusion related reactions
Advise patient to seek medical advice if adverse reactions occur
Trastuzumab may persist in the circulation for up to 7 months after stopping treatment. In patients who receive anthracycline containing chemotherapy further cardiac monitoring is recommended, and should occur yearly up to 5 years from the last administration of trastuzumab, or longer if a continuous decrease of LVEF is observed.
In patients with early breast cancer eligible for neoadjuvant or adjuvant treatment, trastuzumab should only be used concurrently with anthracyclines in chemotherapy naive patients and only with low dose anthracycline regimens. If patients have been treated concurrently with low dose anthracyclines and trastuzumab in the neoadjuvant setting, no additional cytotoxic chemotherapy should be given after surgery.
Patients who develop asymptomatic cardiac dysfunction may benefit from more frequent monitoring (e.g every 6 to 8 weeks).
If no clinical benefit of trastuzumab therapy has been seen, consider discontinuing therapy in patients who have a continued decrease in left ventricular ejection function (LVEF), but remain asymptomatic. If LVEF does not improve or declined further, or symptomatic cardiac failure develops, strongly consider discontinuing trastuzumab. All such patients should be referred for assessment by a cardiologist and followed up.
Monitoring requirements following administration differ according to formulation.
For infusion, observe the patient for at least 6 hours after first administration and for 2 hours after start of subsequent infusions.
For injection, observe the patient for at least 30 minutes after first administration and for 15 minutes after subsequent injections.
Pregnancy and Lactation
Pregnancy
Use trastuzumab with caution during pregnancy.
The manufacturer does not recommend using trastuzumab during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus. Animal studies have not shown any evidence of teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out. Cases have been reported of foetal renal growth and function impairment in association with oligohydramnios, some associated with fatal pulmonary hypoplasia of the unborn child. Briggs (2015) states that HER2 protein expression is known to be high in many embryonic tissues, such as cardiac and neural tissues, and blocking this expression maybe harmful. If a pregnant woman is treated with trastuzumab, close monitoring by a multidisciplinary team is desirable.
Lactation
Trastuzumab is contraindicated during breastfeeding.
The manufacturer contraindicates the use of trastuzumab during breastfeeding and for 7 months after the last dose. The presence of trastuzumab in human breast milk is unknown.
Side Effects
Abnormal thinking
Acute respiratory distress
Alopecia
Anaemia
Anaphylactic shock
Anaphylaxis
Angioedema
Anorexia
Anxiety
Arrhythmias
Arthralgia
Arthritis
Asthenia
Asthma
Ataxia
Atrial flutter
Blood pressure changes
Bradycardia
Cardiogenic shock
Cardiomyopathy
Cellulitis
Chills
Congestive cardiac failure
Contusion
Cystitis
Deafness
Decreased ejection fraction
Depression
Dizziness
Dysgeusia
Dyspnoea
Epistaxis
Erythema
Eye disorder
Facial swelling
Fatigue
Febrile neutropenia
Gastro-intestinal symptoms
Glomerulonephritis
Headache
Hepatic failure
Hepatic tenderness
Hepatitis
Hepatocellular damage
Herpes zoster
Hot flushes
Hyperhidrosis
Hyperkalaemia
Hypersensitivity reactions
Hypertonia
Hypoprothrombinaemia
Infections
Influenza
Influenza-like symptoms
Infusion-related symptoms
Insomnia
Interstitial lung disease
Jaundice
Leucopenia
Malaise
Mastitis
Mucosal inflammation
Muscle spasm
Musculoskeletal disturbances
Myalgia
Nail disorders
Neutropenia
Oedema
Oligohydramnios
Orthopnoea
Oxygen saturation decreased
Pain
Palmar-Plantar Erythrodysaesthesia syndrome
Palpitations
Paraesthesia
Paresis
Pericardial effusion
Pericarditis
Peripheral neuropathy
Pharyngitis
Pruritus
Pyrexia
Rash
Renal disorders
Renal failure
Respiratory disorders
Retinal haemorrhage
Rhinitis
Sepsis
Sinusitis
Skin disorder
Skin infection
Somnolence
Supraventricular tachycardia
Thrombocytopenia
Tremor
Tumour lysis syndrome
Urinary tract infections
Vasodilation
Weight changes
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: July 2019
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
The Renal Drug Handbook. Fifth Edition (2019) ed. Ashley, C. and Dunleavy, A. Radcliffe Publishing Ltd, London.
Summary of Product Characteristics: Herceptin 150mg powder for concentrate for solution for infusion. Roche Products Limited. Revised September 2021.
Summary of Product Characteristics: Herceptin 600mg/5 ml solution for injection. Roche Products Limited. Revised September 2021.
Summary of Product Characteristics: Herzuma 150mg and 420mg powder for solution for infusion. Napp pharmaceuticals Limited. Revised March 2019.
Summary of Product Characteristics: Ontruzant 150mg powder for concentrate for solution for infusion. Merck Sharp and Dohme Limited. Revised February 2019.
Summary of Product Characteristics: Kanjinti 150mg and 420mg powder for concentrate for solution for infusion. Amgen Europe B.V. Revised September 2018.
Summary of Product Characteristics: Trazimera 150mg and 420mg powder for concentrate for solution for infusion. Pfizer Limited. Revised July 2019.
Summary of Product Characteristics: Zercepac 150mg powder for concentrate for solution for infusion. Accord Healthcare Limited. Revised July 2020.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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