Perjeta
Perjeta: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Perjeta
ATX code: L01XC13
Active ingredient: pertuzumab (Pertuzumab)
Manufacturer: Roche Diagnostics, GmbH (Germany)
Description and photo update: 2019-09-07
Perjeta is an antineoplastic agent for the treatment of breast cancer (BC).
Release form and composition
The drug is produced in the form of a concentrate for the preparation of a solution for infusion: a transparent or opalescent, colorless or slightly brownish liquid (14 ml each in glass colorless bottles, 1 bottle in a cardboard box and instructions for use of Perjeta).
Composition of 1 ml of concentrate:
- active substance: pertuzumab - 30 mg;
- auxiliary components: water for injection, glacial acetic acid, L-histidine, polysorbate 20, sucrose.
Pharmacological properties
Pharmacodynamics
Pertuzumab is a recombinant humanized monoclonal antibody that selectively interacts with the extracellular subdomain II of HER2 (human epidermal growth factor receptor 2), which is responsible for dimerization.
Due to the binding of pertuzumab to subdomain II, the process of ligand-dependent heterodimerization of HER2 with other proteins of the HER family is blocked, including HER3 (human epidermal growth factor receptor type 3), HER4 (human epidermal growth factor receptor type 4) and EGFR (epidermal growth factor receptor type 4). human growth factor).
Thus, drug-induced intracellular signaling is inhibited by two major signaling pathways, such as the phosphoinositide 3-kinase (PI3K) pathway and the mitogen-activated protein kinase (MAP) pathway. Due to the inhibition of these signaling pathways, it is possible to stop the growth of cells and, as a result, their death.
Pertuzumab also promotes the activation of antibody-dependent cellular cytotoxicity (ADCC).
As a monoagent, pertuzumab suppresses the proliferation of tumor cells. The enhancement of the antitumor activity of the drug was demonstrated in xenograft models with overexpression of HER2 when used simultaneously with trastuzumab.
The molecular weight of pertuzumab is approximately 148 kDa. It is assumed that, like other monoclonal antibodies, it practically does not penetrate the blood-brain barrier.
Antibodies to Perjet were found in 3.3% of patients with metastatic breast cancer who received trastuzumab in combination with docetaxel and pertuzumab, and in 6.7% of patients treated with trastuzumab in combination with docetaxel.
In the treatment of early-stage breast cancer, antibodies to Perjeta were found in 4.1% of patients who received chemotherapy with cyclophosphamide and doxorubicin at reduced intervals, and then used Perjeta in combination with trastuzumab and paclitaxel; or who received Perjeta in combination with trastuzumab and docetaxel for 4 cycles before surgery, preceded by 4 cycles of therapy with epirubicin, fluorouracil and cyclophosphamide.
A direct relationship between the formation of antibodies to pertuzumab and the development of a hypersensitivity reaction or anaphylactic reaction has not been established in any of the patients.
The results of the analysis of immunogenicity significantly depend on some factors, such as the nature of the underlying disease, the time of sampling, manipulation of the collected samples, the methodology of the analysis, the specificity and sensitivity of the analysis, the use of concomitant drugs. Given these data, a comparison of the rate of detection of antibodies to Perjet and the rate of detection of antibodies to other biologicals may not be informative.
Pharmacokinetics
The pharmacokinetics of pertuzumab was studied only after intravenous (iv) administration of the drug in the dose range of 2–25 mg / kg in patients with various types of tumors.
There are no differences in the drug parameters in patients with early and metastatic breast cancer.
According to the results of all clinical studies, in an average patient, the volume of distribution in the central chamber (Vc) is 3.11 liters, in the peripheral chamber (Vp) - 2.46 liters.
The metabolism of pertuzumab has not been studied. Like other antibodies, pertuzumab is primarily catabolic.
The clearance of the drug is approximately 0.235 l / day. The half-life (T 1/2) is about 18 days.
Pharmacokinetics in special clinical situations:
- ethnicity and gender: no differences in pharmacokinetic parameters of pertuzumab were found;
- age: in elderly (65–75 years) and senile (≥ 75 years) patients, studies have not been conducted. According to the results of population analysis, the pharmacokinetics of the drug does not change with age;
- true body weight (body weight minus adipose tissue), initial albumin concentration: these characteristics of the patient have little effect on drug clearance, but there is no need to adjust the dose;
- renal function: no specific studies have been performed. In the course of population analysis, it was found that renal failure, regardless of the severity, does not affect the exposure of pertuzumab. However, the experience of using Perjeta in patients with functional impairment of the kidneys is limited;
- liver function: The pharmacokinetics of pertuzumab have not been studied.
Indications for use
- non-metastatic breast cancer with overexpression of HER2 - in combination with chemotherapy and trastuzumab: as an adjuvant therapy for early (primary-resectable) breast cancer; as a neoadjuvant therapy for early (primary operable), edematous-infiltrative or locally advanced breast cancer (tumor diameter more than 2 cm or with lymph node involvement) as part of a complete treatment regimen for early breast cancer;
- metastatic or locally recurrent, inoperable breast cancer with tumor overexpression of HER2 - in combination with docetaxel (in the absence of previous experience with HER2-specific therapy or chemotherapy for metastatic disease).
Contraindications
Absolute:
- serious heart rhythm disturbances in which drug therapy is necessary, with the exception of atrial fibrillation, as well as paroxysmal supraventricular tachycardia;
- uncontrolled arterial hypertension;
- congestive heart failure according to the history;
- LVEF (left ventricular ejection fraction) before treatment below 50%;
- recent MI (myocardial infarction);
- hepatic dysfunction;
- age under 18;
- period of pregnancy;
- breast-feeding;
- previous therapy with anthracyclines with a cumulative dose of doxorubicin or an equivalent drug of more than 360 mg / m 2;
- hypersensitivity to any component of the drug.
Relative (Perjeta should be used with caution, under close medical supervision):
- impaired renal function;
- conditions that can disrupt the function of the left ventricle;
- decreased LVEF <50% in the presence of previous adjuvant trastuzumab therapy;
- previous radiation therapy to the chest area;
- previous treatment with anthracyclines.
Perjeta, instructions for use: method and dosage
For the appointment of Perjeta, a prerequisite is the presence of 3+ points according to the results of immunohistochemical analysis (IHC) and / or the degree of amplification ≥ 2.0 according to the results of in situ hybridization (ISH). Test methods must be accurate and validated. For instructions on how to perform HER2 testing, as well as information on the interpretation of results, refer to the instructions for the validated test kits for determining HER2 status.
Treatment with the drug should be carried out by a doctor with experience in the treatment of cancer.
Perjeta is intended for intravenous drip only. Do not use a jet or bolus method of administration.
The first infusion of the drug is carried out within 60 minutes. With good tolerance, subsequent injections can be carried out within 30-60 minutes.
In the patient's medical record, the doctor indicates the trade name and batch number of the drug.
Metastatic and non-metastatic breast cancer
The loading dose of Perjeta is 840 mg, injected intravenously over 60 minutes. In the future, the drug is administered at intervals of 3 weeks at a maintenance dose of 420 mg, the duration of the infusion is 30-60 minutes. After each infusion for 30-60 minutes, the patient should be under close medical supervision.
When Perjeta is prescribed in combination with trastuzumab, the drugs are administered sequentially (the order does not matter).
Recommended dosing regimen for trastuzumab:
- loading dose - 8 mg / kg in the form of intravenous drip infusion for 90 minutes;
- maintenance dose - 6 mg / kg every 3 weeks in the form of intravenous drip infusion lasting 30–90 minutes.
When Perjeta and Trastuzumab are prescribed in combination with drugs of the taxane group, Perjeta and Trastuzumab are administered first (their dosage regimen does not change), then taxanes. The initial dose of docetaxel is 75 mg / m 2, administered as an intravenous infusion at intervals of 3 weeks. If docetaxel is well tolerated by the patient in the first cycle, it is possible to increase the dose in subsequent cycles to 100 mg / m 2, but provided that carboplatin is not included in the regimen.
For patients on an anthracycline-based regimen, Perjetu and trastuzumab are administered afterwards.
Metastatic breast cancer
If patients with metastatic breast cancer develop unacceptable toxicity or symptoms of disease progression during treatment, combination therapy with Perjeta, trastuzumab, and docetaxel is discontinued.
For patients who are stopped from docetaxel, the combination of Perjeta + trastuzumab can be continued.
Non-metastatic breast cancer
Prior to surgery as a neoadjuvant therapy for early breast cancer, Perjet is recommended to be administered in conjunction with chemotherapy and trastuzumab in one of the following regimens:
- 3 or 4 cycles of preoperative therapy with fluorouracil, cyclophosphamide and epirubicin, then 3 or 4 cycles of therapy with Perjeta in combination with trastuzumab and docetaxel;
- 4 cycles of Perjeta therapy in combination with trastuzumab and docetaxel, followed by 3 cycles of postoperative therapy with fluorouracil, cyclophosphamide and epirubicin (FEC mode);
- 4 cycles of preoperative therapy with doxorubicin and cyclophosphamide every 2 weeks (chemotherapy at reduced intervals), then 4 preoperative cycles of therapy with Perjeta in combination with trastuzumab and paclitaxel;
- 6 cycles of therapy Peretoy, docetaxel and trastuzumab (at a dose of 75 mg / m 2) together with carboplatin.
When combined with Perjeta and paclitaxel, the recommended dose of the latter is 80 mg / m 2 once a week as an intravenous infusion.
Patients who have been prescribed a combination of Perjeta + trastuzumab as neoadjuvant therapy should continue to use them as adjuvant therapy to complete the 1-year treatment.
After surgery, as an adjuvant therapy, Perjeta is administered together with trastuzumab until the total duration of the course is 1 year (no more than 18 cycles), or until unacceptable toxicity develops, or until the disease progresses, depending on the situation. comes earlier.
In combination with trastuzumab, Perjeta is used as part of a complete breast cancer regimen that includes standard taxane-based chemotherapy with or without anthracycline-containing therapy. Perjeta and trastuzumab are given on the first day of the first cycle of taxane-containing chemotherapy and continue even if chemotherapy is discontinued.
The use of the combination of Perjeta + trastuzumab as an adjuvant therapy for early breast cancer has been studied in the following therapeutic regimens:
- 3 or 4 cycles of therapy with epirubicin, cyclophosphamide and fluorouracil or cyclophosphamide, fluorouracil and doxorubicin (FAC regimen), then 3 or 4 cycles of docetaxel therapy or 12 cycles of paclitaxel therapy with the drug being administered once a week;
- 4 cycles of therapy with cyclophosphamide and doxorubicin (EC mode), then 3 or 4 cycles of therapy with docetaxel or 12 cycles of therapy with paclitaxel with the introduction of the drug once a week;
- 6 cycles of docetaxel and carboplatin combination therapy.
Skip in planned introduction
Recommendations for the dosing regimen in case of missing a scheduled administration, depending on the duration of the interval between infusions:
- less than 6 weeks: the drugs should be administered as soon as possible, without waiting for the next scheduled infusion, Perjetu at a dose of 420 mg, trastuzumab at a dose of 6 mg / kg;
- 6 weeks or more: Perjet should be administered at a loading dose (within 60 minutes), then continue infusion at intervals of 3 weeks at a dose of 420 mg (within 30-60 minutes). Trastuzumab should be administered at a loading dose of 8 mg / kg (within 90 minutes), then continue administration at intervals of 3 weeks at a dose of 6 mg / kg (within 30–90 minutes).
Dosing regimen correction
Reducing the dose of Perjeta and Trastuzumab is not recommended.
If trastuzumab is discontinued, administration and Perjeta are discontinued.
If reversible myelosuppression occurs during chemotherapy, the use of Perjeta and trastuzumab can be continued, subject to careful monitoring of the patient's condition for the development of complications caused by neutropenia.
The exact instructions for adjusting the dosage regimens of chemotherapeutic agents are given in the corresponding instructions for their medical use.
If a patient with metastatic breast cancer has left ventricular dysfunction, it is recommended to adhere to the following recommendations. If LVEF was ≥ 50% prior to treatment initiation, this should be monitored approximately every 12 weeks. In the case of a decrease in LVEF to 40-45% (if the decrease in relation to the initial value before the start of therapy was ≥ 10%) or to <40%, it is necessary to suspend therapy for at least 3 weeks, treatment is resumed after the level of LVEF is restored to 40-45%, respectively (if the decrease from the baseline value before the start of therapy was 45%.
If a patient with non-metastatic breast cancer has left ventricular dysfunction, it is recommended to adhere to the following recommendations. If LVEF was ≥ 55% prior to treatment initiation, then this should be monitored approximately every 12 weeks or once with neoadjuvant therapy. If the decrease is <50% (if the decrease in relation to the initial value before the start of therapy was ≥ 10%), therapy should be suspended for at least 3 weeks. Treatment is resumed after restoration of LVEF ≥ 50% (provided that LVEF is reduced by 10% in relation to the initial value before starting therapy).
After previous anthracycline chemotherapy, Perjeta and trastuzumab should only be used if LVEF is ≥ 50%.
With the development of infusion reactions, the rate of administration of the drug is reduced or the administration is temporarily stopped.
In the event of anaphylaxis / hypersensitivity reactions, the introduction of Perjeta must be urgently interrupted. If the reactions are threatening, the therapy is canceled completely.
Preparation of solution for infusion
Due to incompatibility, Perjeta's drug cannot be diluted with a 5% dextrose solution (physical and chemical instability of the pertuzumab solution is noted). Also, the drug is prohibited from mixing / diluting with other medicines. For dilution, you can use only 0.9% sodium chloride solution.
Perjeta can be given with infusion bags made of polyvinyl chloride (PVC), polyolefin, or polyethylene (PVC free).
Preparation of the drug for administration should be carried out by a qualified medical specialist under aseptic conditions.
Perjeta does not contain preservatives and is therefore intended for single use. Precautions must be taken to maintain the sterility of the prepared infusion solution.
Solution preparation rules:
- Take 14 ml of liquid from the bottle with the concentrate.
- Insert the concentrate into an infusion bag containing 250 ml of 0.9% sodium chloride solution.
- Turn the bag over gently to mix the solution. Do not shake to avoid foaming.
- Before administration, visually check the solution for a change in color or foreign matter.
The nominal concentration of the finished solution for the loading dose is 3 mg / ml, for the maintenance dose - 1.6 mg / ml.
The prepared solution is recommended to be injected immediately. However, if the controlled and validated aseptic standards are observed during dilution, the prepared preparation can be stored at a temperature of 2–8 ° C for 24 hours. The specialist who prepared the solution is responsible for the conditions and duration of storage.
Side effects
The safety profile of Perjeta when used in conjunction with various antineoplastic agents remains unchanged, but the types and frequency of the most common side effects differ from those with Perjeta alone.
The drug is used as part of a combination therapy, therefore it is not possible to reliably establish the cause-and-effect relationship of developing adverse events with a specific drug.
In pivotal clinical trials, the most frequent (≥ 30%) disorders were: increased fatigue, nausea, diarrhea, vomiting, alopecia, neutropenia. The most common (≥ 10%) severe reactions (grade 3 and 4 according to the National Cancer Institute Common Terminology Criteria of Adverse Events) are neutropenia and febrile neutropenia.
The following side effects are classified by frequency of development as follows: very often - ≥ 1/10, often - from ≥ 1/100 to <1/10, infrequently - from ≥ 1/1000 to <1/100, rarely - from ≥ 1 / 10,000 to <1/1000, very rarely - <1/10,000:
- immune system: very often - infusion reactions; often - hypersensitivity reactions; infrequently - anaphylactic reactions; rarely, cytokine release syndrome;
- hematopoietic system: very often - anemia, leukopenia, neutropenia, febrile neutropenia (including with a fatal outcome);
- organ of vision: very often - increased lacrimation;
- nervous system and psyche: very often - distortion of taste perception (dysgeusia), dizziness, insomnia, headache, paresthesia, peripheral neuropathy;
- respiratory system: very often - nosebleeds, shortness of breath, cough; infrequently - interstitial lung disease, pleural effusion;
- cardiovascular system: very often - a feeling of hot flashes; often - impaired function of the left ventricle; infrequently - congestive heart failure;
- metabolism: very often - decreased appetite;
- musculoskeletal system: very often - myalgia, arthralgia;
- gastrointestinal tract: very often - stomatitis, nausea, diarrhea, dyspepsia, constipation, vomiting;
- on the part of the skin and subcutaneous tissues: very often - rash, dry skin, itching, nail pathology, alopecia; often - paronychia;
- general disorders: very often - nasopharyngitis, inflammation of the mucous membranes of various localization, peripheral edema, fever, increased fatigue, asthenia, pain of various localization (for example, in the limbs, in the chest, in the back, in the abdomen, in the upper abdomen, bone or bone -muscular pain); often - chills, upper respiratory tract infections.
Overdose
The maximum tolerated dose of pertuzumab has not been established. In clinical studies, only doses up to 25 mg / kg (1727 mg) have been studied.
In case of an overdose, the patient should be closely monitored in order to detect unwanted symptoms and signs of disorders in time. If necessary, symptomatic therapy is indicated.
special instructions
The use of Perjeta is allowed only in patients with tumor overexpression of HER2 (determined by the method of immunohistochemical analysis) or amplification of the HER2 gene (determined by the method of in situ hybridization). Testing is required in a specially equipped laboratory, and the results must be validated.
Treatment is carried out under the supervision of an oncologist.
The effect of the drug on fertility has not been studied. In the course of experiments on animals, no signs of impaired fertility were detected.
Women of reproductive age who themselves receive the drug or are sexual partners of men who are undergoing anticancer therapy should use reliable contraceptive methods throughout the treatment period and for 6 months after it ends.
Hypersensitivity / anaphylaxis reactions
On the background of therapy with Perjeta, severe hypersensitivity reactions, including anaphylaxis, may develop. In this regard, the introduction of the drug should be carried out by a qualified specialist in the room where drugs and appropriate equipment are provided for the provision of emergency medical care.
In the presence of known hypersensitivity to any component of Perjeta, the use of the drug is prohibited.
Infusion reactions
During each administration of the drug, for at least 60 minutes after the first infusion and 30 minutes after subsequent infusions, the patient must be carefully monitored for the development of possible infusion reactions.
If significant symptoms appear, it is necessary to slow down the rate of administration of the solution or interrupt the infusion and provide the patient with appropriate medical assistance. Monitoring of the patient's condition is shown until the signs of violation are completely resolved.
In severe reactions that cannot be corrected with appropriate treatment, the physician should consider discontinuing Perjeta completely.
Left ventricular dysfunction
HER2 blocking drugs (including Perjeta) can reduce LVEF.
When Perjeta is added to a combination of trastuzumab and chemotherapy, the incidence of symptomatic left ventricular systolic dysfunction (congestive heart failure) increases.
Patients who have previously received chest radiotherapy or anthracyclines are more likely to have decreased LVEF. With adjuvant therapy, symptomatic heart failure is more common in patients undergoing anthracycline-based chemotherapy.
The efficacy and safety of Perjeta have not been studied in the following cases: a history of congestive heart failure; baseline LVEF <50%; observed in the course of previous adjuvant therapy with trastuzumab, a decrease in LVEF to 50%; conditions that may contribute to impaired left ventricular function, such as recent MI, uncontrolled arterial hypertension, requiring drug therapy; severe heart rhythm disturbances; previous treatment with anthracyclines with a cumulative dose of doxorubicin (or an equivalent drug) of more than 360 mg / m 2.
LVEF should be assessed prior to starting Perjeta and regularly during treatment. If its performance decreases, you should follow the appropriate instructions in the section "Method of administration and dosage". If LVEF does not improve or continues to deteriorate, discontinuation of Perjeta and trastuzumab is considered, except in individual cases when the benefits of their use for a particular patient are higher than the potential risk.
Febrile neutropenia
With the combination of Perjeta + trastuzumab + docetaxel, the risk of developing febrile neutropenia is higher than with trastuzumab and docetaxel alone, especially during the first 3 cycles of therapy.
In the treatment of metastatic breast cancer, the minimum neutrophil counts were approximately similar in patients who received trastuzumab and docetaxel, and in patients who received Perjeta in addition to these drugs.
Thus, a higher incidence of febrile neutropenia when Perjeta is added to combination therapy is associated with a higher incidence of diarrhea and mucositis in patients. In this regard, it is recommended to consider the issue of symptomatic treatment of these disorders.
The development of febrile neutropenia was not reported after excluding docetaxel from the therapy regimen.
Handling an unused drug
Disposal of the unused and expired preparation should be carried out in accordance with the requirements of the medical institution.
Influence on the ability to drive vehicles and complex mechanisms
Special studies on the effect of Perjeta on the speed of reactions and the ability to concentrate have not been conducted. The degree of restrictions is determined on an individual basis, depending on the presence / absence of certain side effects, such as dizziness.
Application during pregnancy and lactation
In preclinical studies of Perjeta in Javanese macaques during the period of organogenesis (the last stage of embryonic development), oligohydramnios, delayed renal development and fetal death were revealed. Given the mechanism of action of pertuzumab and information obtained in preclinical studies, the drug may have a negative effect on the intrauterine development of the fetus in humans.
Perjeta is contraindicated during pregnancy and lactation.
Pediatric use
In children and adolescents under 18 years of age, the safety and efficacy of pertuzumab have not been established, therefore the drug is contraindicated in patients of this age category.
With impaired renal function
Patients with mild renal insufficiency (creatinine clearance 60–90 ml / min) and moderate (creatinine clearance 30–60 ml / min) severity do not need to change the dose of Perjeta, but treatment should be carried out with caution.
Due to the limited amount of information on the pharmacokinetics of pertuzumab in severe and end-stage renal failure (creatinine clearance <30 ml / min), it is not possible to give any specific instructions on the Perjeta dosage regimen.
For violations of liver function
The safety and efficacy of pertuzumab in patients with functional liver disorders have not been studied, therefore, the appointment of Perjeta is contraindicated for them.
Use in the elderly
The efficacy and safety profile of pertuzumab in patients <65 yr and> 65 is generally similar. The exception is such a side effect as diarrhea - in patients over 65 years of age, its frequency was higher.
No dose adjustment is required for the elderly and senile age.
Drug interactions
There were no signs of pharmacokinetic interaction between pertuzumab and the following drugs: trastuzumab, paclitaxel, carboplatin, erlotinib, gemcitabine, docetaxel, capecitabine.
Perjeta is incompatible with 5% dextrose solution, which is manifested by its chemical and physical instability. It cannot be diluted / mixed with other drugs.
Perjeta is compatible with infusion bags made of PVC and PVC-free polyethylene and polyolefin.
Analogs
Perjeta's analogues are Adsetris, Blintsito, Beiodaym, Gertikad, Gazyva, Herceptin, Ervoy, Kadsila, Kitruda, Opdivo, Tecentrik, Tsiramza, Emplicity, etc.
Terms and conditions of storage
Store at a temperature of 2-8 ° C out of reach of children, protected from light.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Perjet
On specialized forums and sites, reviews about Perjet are few, but positive. Patients note the high efficiency of anticancer therapy when this drug is added to the chemotherapeutic regimen. Moreover, many consider the Perjeta protocol to be nearly the most effective to date in the treatment of HER2 overexpressing breast cancer.
It is difficult to single out the side effects of Perjeta, since it is used as part of a complex treatment. The cost of the drug is estimated as very high.
Price for Perjetu in pharmacies
Depending on the region of sale and the pharmacy network, the price of Perjetu for 1 bottle (420 mg / 14 mg) can range from 71,000 to 120,000 rubles.
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
