Abraksan - instructions for use, reviews, analogs and forms of release (injections in ampoules for injection of lyophilizate) a drug for the treatment of pancreatic and breast cancer or breast in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Abraxan. Presented are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors specialists on the use of Abraksana in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Abraxan in the presence of existing structural analogues.Use to treat breast or breast cancer and adenocarcinoma of the pancreas in adults, children, as well as during pregnancy and lactation. Composition of the preparation.

 

Abraxan antitumor agent. The mechanism of action of Paclitaxel (the active substance of the drug Abraxan) is based on its ability to stimulate the assembly of microtubules of the mitotic spindle from the dimer molecules of tubulin and to stabilize the microtubules, suppressing their depolymerization. This leads to the suppression of the normal dynamic reorganization of the microtubular network in the interphase of mitosis, and also causes the formation of abnormal microtubule congestions throughout the entire cell cycle and the appearance of multiple star-shaped clusters (asters) in the mitosis phase.

 

Abraxan contains nanodispersed paclitaxel stabilized with albumin, with a nanoparticle size of approximately 130 nm, in which paclitaxel is in a non-crystalline (amorphous) state. After intravenous administration, the nanoparticles rapidly dissociate to form soluble complexes of paclitaxel bound to albumin, the approximate size of which is 10 nm.It is known that albumin regulates the processes of transendothelial transport of plasma components, and in vitro studies it was demonstrated that the presence of albumin in the preparation of Abraxan stimulates the transport of paclitaxel through the endothelial cell layer. It has been hypothesized that transendothelial transport is mediated by the gp-60 albumin transporter, and an increase in paclitaxel accumulation in the tumor is noted due to the presence of an albumin-binding protein, an acid secreted protein rich in cysteine ​​(SPARC).

 

Composition

 

Paclitaxel + Albumin + excipients.

 

Pharmacokinetics

 

After the administration of the drug Abraksan to patients with solid tumors, paclitaxel was evenly distributed in blood cells and plasma. Binding to plasma proteins - 94%. In vitro studies have shown that paclitaxel is metabolized predominantly to the formation of hydroxylated metabolites, the formation of which is catalyzed by isoenzymes of the cytochrome CYP2C8 and CYP3A4 system. Paclitaxel is predominantly eliminated by hepatic metabolism and excretion with bile, and only 5% is excreted in the urine.

 

Indications

• therapy of the second and subsequent lines in patients with metastatic breast cancer resistant to standard anthracycline-containing combination chemotherapy (or in the presence of contraindications), as well as relapse of the disease within 6 months after completion of adjuvant chemotherapy;
• in combination with gemcitabine - as first-line therapy in adult patients with metastatic pancreatic adenocarcinoma.

 

Forms of release

 

Liofilizate for the preparation of a suspension for infusions of 100 mg (injections in ampoules for injections).

 

Instructions for use and dosing regimen

 

Abraxan should be administered only under the supervision of a qualified oncologist in units intended for the treatment of cytotoxic drugs. The drug should not be replaced or used together with other dosage forms of paclitaxel.

 

Mammary cancer

 

Abruxan is administered intravenously drip for 30 minutes at a dose of 260 mg per 1 m2 of body surface 1 every 3 weeks. With the development of severe neutropenia (the number of neutrophils less than 500 in 1 μl for 1 week or more) or severe sensory neuropathy, it is necessary to reduce the dose of the drug Abraxane to 220 mg per 1 m2 in all subsequent courses of therapy.With the repeated development of severe neutropenia or severe sensory neuropathy, it is necessary to reduce the dose to 180 mg per 1 m2 of the body surface.

 

Abraxane should not be used until the amount of neutrophils is restored to a level above 1500 in 1 μl, and the number of platelets to a level above 100,000 in 1 mm3. In patients with sensory neuropathy of grade 3, treatment should be stopped until the neuropathy is reduced to grade 1 or 2, followed by a reduction in the dose of the drug Abraxan for all subsequent courses of therapy.

 

Adenocarcinoma of the pancreas

 

Abraxane in combination with gemcitabine is administered intravenously. Abraxan in a dose of 125 mg per 1 m2 is administered for 30 minutes on days 1, 8 and 15 of each 28-day cycle. Gemcitabine at the recommended dose of 1000 mg per 1 m2 is administered within 30 minutes immediately after the completion of the administration of the drug Abraxan, on days 1, 8 and 15 of each 28-day cycle.

 

In adenocarcinoma of the pancreas, the change in the doses of drugs with the development of unwanted drug reactions is carried out according to special schemes individually in each specific situation.

 

Preparation of the preparation for administration

 

The reconstituted suspension of the drug Abraxane is administered intravenously, by means of an infusion system with an integrated filter having a pore diameter of 15 μm.

 

With the aseptic requirements, prepare a suspension for infusion as follows:

• remove from the bottle protective cap, wipe the plug with alcohol solution;
• Using a sterile syringe, slowly (for at least 1 minute), add 20 ml of 0.9% sodium chloride solution for injection into the vial. The needle of the syringe should be directed in such a way that the solution flows down the wall of the vial;
• to prevent foaming, avoid contact with the solution directly on the lyophilizate;
• after all the physiological solution has been introduced into the vial, leave it for at least 5 minutes to evenly absorb the solution with a lyophilizate;
• gently rotating and / or turning the bottle for at least 2 minutes, achieve complete and uniform dissolution of the lyophilizate in the volume of the introduced sodium chloride solution to form a homogeneous suspension. Do not foam;
• when forming foam or agglomerates, leave the vial for at least 15 minutes before the foam settles. If necessary, repeat the dissolution until the agglomerates disappear completely;
• ready-to-use preparation is a homogeneous translucent suspension of white or white with a yellowish hue of color without visible mechanical inclusions.Some sedimentation of the reconstituted suspension is allowed. In the presence of sediment before the introduction of the drug should be again, gently flipping the bottle, to achieve uniformity of the suspension. Before administration, it is necessary to inspect the suspension for any visible mechanical particles in it. If such particles are found, the introduction of a reconstituted suspension is not permissible;
• each milliliter of the resulting suspension contains 5 mg of albumin-stabilized nanodispersed paclitaxel (no additional dilution is required before administration of additional dilution);
• the finished suspension in the required volume corresponding to the calculated dose of the drug, transfer into an empty standard infusion set. Application for recovery and injection Abraxane medical device (in particular, a package for syringes and infusion), in the manufacture of which is used as a lubricant silicone oil may lead to the formation of protein "threads." Therefore, to eliminate the possibility of ingress protein "threads" in the bloodstream, the drug infusion Abraxane be carried out using the high-pass filter with a pore size of 15 microns.Such a filter removes these particles without altering the physical and chemical characteristics of the reconstituted drug suspension. Applying a filter with a pore size of less than 15 μm can lead to clogging and blockage.

 

Given the possibility of getting the drug into the circulatory tissues, it is necessary to closely monitor the administration of the drug, promptly identifying possible symptoms of infiltration at the site of intravenous injection.

 

Limiting the time of administration of the drug Abraxan to 30 minutes, according to the recommendations, reduces the likelihood of developing unwanted reactions at the site of infusion.

 

Storage of the finished suspension in vials

 

Apply immediately after dilution, if necessary, the finished suspension can be stored in the refrigerator at a temperature of + 2-8 degrees Celsius, but not more than 8 hours. Store in a place protected from bright light. Dispose of unused product according to local requirements.

 

Storage of the finished suspension in infusion packets

 

Ready to administer the drug should be used immediately after dilution. If necessary, the finished suspension in the infusion bag can be stored at room temperature (not above +25degrees Celsius) under normal illumination conditions and applied no later than 8 hours after breeding.

 

Side effect

 

Breast cancer (monotherapy with drug Abraksan)

• infection, including urinary tract infection, folliculitis, upper respiratory tract infection, sinusitis, nasopharyngitis, phlegmon, sepsis;
• Candidiasis of the oral cavity;
• simple herpes, shingles and other viral infections;
• fungal infections;
• metastatic pain;
• tumor necrosis;
• neutropenia, anemia, leukopenia, thrombocytopenia, lymphopenia, oppression of bone marrow hematopoiesis, febrile neutropenia;
• hypersensitivity reactions;
• anorexia;
• dehydration;
• hypokalemia, hypophosphatemia, hypoalbuminemia, hyperglycemia, hypokalemia, hypocalcemia, hypoglycemia, hyponatremia;
• insomnia;
• depression, anxiety;
• peripheral, including sensory, neuropathy;
• paresthesia;
• headache, dizziness;
• ataxia;
• increased tear;
• blurred vision;
• dry eye syndrome;
• dry keratoconjunctivitis;
• madarose;
• eye irritation, pain and / or itching in the eyes;
• vertigo;
• pain in the ears, tinnitus;
• tachycardia, arrhythmia;
• increased blood pressure (BP);
• lymphatic edema;
• orthostatic hypotension;
• interstitial pneumonitis;
• dyspnea;
• nose bleed;
• pharyngo-laryngeal pain;
• cough;
• rhinitis, rhinorrhea;
• nausea, vomiting;
• diarrhea, constipation;
• stomatitis;
• abdominal pain;
• bloating;
• dyspepsia;
• gastroesophageal reflux;
• hepatomegaly;
• alopecia;
• skin rash;
• lesions of nail plates (changes in pigmentation or discoloration of the nail bed), onycholysis (exfoliation of nails);
• hyperpigmentation of the skin;
• arthralgia;
• Myalgia, muscle cramps;
• pain in the bones;
• dysuria;
• pollakiuria;
• hematuria;
• nocturia;
• polyuria;
• urinary incontinence;
• pain in the mammary gland;
• fatigue, asthenia, decreased efficiency;
• temperature increase;
• peripheral edema;
• hyperthermia;
• decrease in body weight;
• increased activity of hepatic enzymes;
• decrease in the number of erythrocytes, decrease in hematocrit.

 

Adenocarcinoma of the pancreas (drug Abraxane in combination with gemcitabine)

• sepsis;
• pneumonia;
• Candidiasis of the oral cavity;
• neutropenia, anemia, thrombocytopenia, pancytopenia;
• thrombotic thrombocytopenic purpura;
• dehydration;
• decreased appetite;
• hypokalemia;
• insomnia;
• depression, anxiety;
• peripheral, including sensory, neuropathy;
• dysgeusia;
• headache, dizziness;
• paralysis of the facial nerve;
• increased tear;
• cystoid macular edema;
• congestive heart failure;
• tachycardia;
• decrease and increase of blood pressure;
• dyspnea;
• nose bleed;
• cough;
• pneumonitis;
• nasal congestion;
• nausea, vomiting;
• diarrhea, constipation;
• abdominal pain;
• stomatitis;
• intestinal obstruction;
• colitis;
• dryness of the oral mucosa;
• cholangitis;
• alopecia;
• skin rash, itching, dry skin;
• diseases of the nails;
• "tides";
• pain in the limbs;
• arthralgia, myalgia;
• muscle weakness;
• pain in the bones;
• acute renal insufficiency;
• hemolytic-uremic syndrome;
• fatigue, asthenia;
• peripheral edema;
• fever, chills;
• reactions at the injection site;
• decrease in body weight;
• increased activity of hepatic enzymes;
• hyperbilirubinemia;
• increase in the concentration of creatinine in the blood plasma.

 

Post-registration application experience

 

During the post-registration study of the drug Abraksan, cases of paralysis of the cranial nerves, voice vocal cords and rare cases of severe hypersensitivity reactions were described.

 

There were also rare cases of visual acuity reduction due to cystoid edema of the retinal yellow spot on the background of therapy with the drug Abraksan. It is necessary to abrogate Abraxan when diagnosing cystoid edema of the retina yellow spot.

 

In some patients who received pre-capecitabine, cases of palmar-plantar erythrodysthesis were noted. Due to the fact that reports of such complications came spontaneously in the clinical application of the drug, their true frequency and cause-and-effect relationship can not be determined.

 

Contraindications

• hypersensitivity to paclitaxel and human albumin;
• neutropenia (less than 500 in 1 μl);
• severe violations of liver function;
• pregnancy;
• lactation period (breastfeeding);
• children under 18 years of age (lack of sufficient safety and efficacy data).

 

Application in pregnancy and lactation

 

There are only limited data on the use of Abraksan in pregnant women. It is assumed that when administered during pregnancy, paclitaxel causes severe birth defects.In experimental studies on animals, the reproductive toxicity of the preparation is shown.

 

The use of the drug Abraxan during pregnancy is contraindicated.

 

It is not known whether paclitaxel is excreted in breast milk. Given the potential serious adverse reactions in children are breastfed, Abraxane is contraindicated in lactating women. Women who are treated with Abraxan should stop breastfeeding.

 

In studies in vivo revealed that paclitaxel has genotoxic, teratogenic, embryo- and foetotoxic action, and also reduces the reproductive function in males (testicular atrophy) and females (decreased incidence of pregnancy and increase the incidence of death of embryos).

 

Abraxan causes infertility in male rats. Therefore, men should be encouraged to consider the possibility of preserving their own sperm before treatment samples, given the danger of irreversible infertility during treatment Abraksanom.

 

Women of childbearing age should use reliable methods of contraception during treatment and for 1 month after cessation of treatment with Abraxane.

 

Men who receive Abraxan should not participate in the conception of the child during the course of therapy, and also within 6 months after the end of the course.

 

Use in children

 

The safety and efficacy of Ambraxane in patients younger than 18 years of age with metastatic breast cancer has not been studied. Therefore, the drug is contraindicated in children and adolescents under 18 years.

 

Application in elderly patients

 

Clinical studies showed no more pronounced toxicity in elderly patients taking Abruxan.

 

Specials indications

 

Abraxan should be administered only under the supervision of a doctor who has experience working with antitumor drugs, and in the presence of the conditions necessary for the relief of possible complications.

 

Abraxan should not be confused with other drugs, except those listed in the section "Preparing the drug for intravenous administration."

 

Hypersensitivity

 

In rare cases severe hypersensitivity reactions were noted, including very rarely anaphylactic reactions with a lethal outcome. When a patient develops symptoms of hypersensitivity,The drug should be discontinued immediately without further resumption. Patients should be prescribed symptomatic therapy.

 

Hematological toxicity

 

Suppression of bone marrow function (mainly neutropenia) during treatment with Abraxane is observed frequently. Neutropenia is dose-dependent and is the main factor limiting the dose of the drug.

 

During treatment with Abraxan, regular monitoring of the peripheral blood pattern is necessary.

 

Repeated courses of treatment with the drug Abraxan should be carried out only when the number of neutrophils is restored above 1500 in 1 mm3, and the platelets - above 100,000 in 1 mm3.

 

Neuropathy

 

In the treatment with the drug Abraxan often develops sensory neuropathy and less often - its severe forms. In the case of sensory neuropathy 1 or 2 severity, as a rule, there is no need to reduce the dose of the drug. With the development of severe sensory neuropathy (grade 3 severity) against the background of monotherapy with the drug Abraxan, the treatment should be stopped until symptoms improve to 1-2 degrees and the dose of Abruxan is reduced in all subsequent courses.With the development of sensory neuropathy above grade 3 on the background of combined therapy with the drug Abraksan and gemcitabine, it is necessary to postpone the introduction of the drug Abraxan, continuing therapy with gemcitabine at a constant dose. Therapy with the drug Abraksan in a reduced dose is renewed after a decrease in the severity of peripheral neuropathy to 0 or 1 degree.

 

Sepsis

 

Sepsis was recorded in 5% of patients who received the drug Abraxane in combination with gemcitabine, regardless of their neutropenia. Complications of pancreatic cancer, especially obstruction of the bile duct and the presence of a biliary stent, were the main risk factors for the development of sepsis. When the patient's body temperature increases (regardless of the amount of neutrophils), it is necessary to start therapy with broad-spectrum antibiotics. With the development of febrile neutropenia, the introduction of the drug Abraxan and gemcitabine should be postponed until the body temperature is normalized and the absolute number of neutrophils is restored to 1500 cells in 1 mm3 or more, and then resume treatment with both drugs in a reduced dose.

 

Pneumonitis

 

Pneumonitis was registered in 4% of patients who received the drug Abraxane in combination with gemcitabine. Of the 17 cases of pneumonitis 2, they ended lethal. Careful observation of patients is needed to timely detect signs and symptoms of pneumonitis. After excluding the infectious etiology of the disease and confirming the diagnosis of pneumonitis, it is necessary to cancel treatment with the drug Abraxan and gemcitabine (without the possibility of its renewal), and immediately begin the appropriate treatment and supportive activities.

 

Hepatotoxicity

 

Since in patients with impaired hepatic function the probability of manifestation of the toxicity of paclitaxel increases, the drug Abraxan should be used with caution. In connection with a higher risk of developing toxic reactions, especially myelosuppression, in patients with impaired liver function, the blood picture must be constantly monitored.

 

The drug Abraksan should not be used in patients whose bilirubin concentration is 5 times higher than the upper limit of the norm (UGN) or the level of aspartate aminotransferase (AST) is 10 times higher than the IGN.In addition, the drug Abraxan is not recommended for patients with metastatic pancreatic adenocarcinoma if they have moderate and severe hepatic insufficiency (the total bilirubin is 1.5 times higher than UGN and AST is not more than 10 times higher than UGN).

 

Cardiotoxicity

 

In patients receiving Abraxan, single cases of congestive heart failure and left ventricular dysfunction were reported. Moreover, most patients had a history of heart disease or cardiotoxic drugs, such as anthracyclines. Thus, patients receiving Abraxan should be under constant medical supervision to monitor the condition of the heart.

 

Metastases in the central nervous system (CNS)

 

The effectiveness and safety of the drug Abraksan in patients with metastases in the central nervous system is not defined. Usually metastases in the central nervous system are poorly controlled by systemic chemotherapy.

 

Gastrointestinal Symptoms

 

When there are nausea, vomiting and diarrhea on the background of treatment with Abraxan, patients can be prescribed standard antiemetic and anti-diarrhea remedies.

 

Elderly patients aged 75 years and older

 

Patients aged 75 years and older did not notice the benefits of combination therapy with Abraxane and gemcitabine compared with gemcitabine monotherapy. In patients of very old age (over 75 years), with the combination of Abraxan and gemcitabine, there was an increase in the incidence of serious unwanted drug reactions (NLR), as well as NLR, leading to early completion of therapy, including hematological toxicity, peripheral neuropathy, loss of appetite and dehydration. Patients with adenocarcinoma of the pancreas over the age of 75 years should be carefully monitored for assessing the tolerability of combination therapy with the drug Abraxan and gemcitabine. Special attention should be given to their general condition, concomitant diseases and an increased risk of infections.

 

Other

 

Given the limited data available, there was no clear benefit of combination therapy with Abraxane and gemcitabine in terms of an increase in the duration of overall survival in patients with pancreatic adenocarcinoma with normal values ​​of the CA 19-9 tumor marker prior to treatment.

 

Do not add erlotinib to the combination of the drug Abraxan and gemcitabine.

 

Excipients

 

After restoring 1 ml of the drug, Abraxane contains 183 mmol or 4.2 mg of sodium. This should be borne in mind by patients on a diet with sodium restriction.

 

The drug Abraksan is an albumin-stabilized nanodispersed paclitaxel, the pharmacological properties of which may be significantly different from those of other preparations of paclitaxel. Do not use together and do not substitute for other dosage forms of paclitaxel.

 

The concentration of the finished suspension is 5 mg / ml, do not dilute before administration.

 

Precautions

 

When working with the drug Abraxan should comply with the rules for handling cytotoxic substances and rules for their destruction. Preparation of the preparation for administration should be carried out by specially trained personnel in a room equipped for this purpose with observance of aseptic conditions. It is recommended to use protective gloves, goggles and protective clothing. Avoid contact with the skin and mucous membranes.If the product gets on the skin, the affected area should be rinsed immediately with soap and water. In this case, tingling / burning sensation and reddening of the skin may occur. If you get the drug Abraxane on the mucous membranes, you should thoroughly rinse the affected area with water. The inhalation of paclitaxel can cause shortness of breath, chest pain, burning sensation in the eyes, sore throat and nausea.

 

Pregnant employees should not work with the drug Abraksan.

 

Impact on the ability to drive vehicles and mechanisms

 

Abraxan has little or moderate influence on the ability to drive vehicles and mechanisms. At the same time, Abraxan is capable of causing side reactions, in particular fatigue (very often) and dizziness (often), which can affect the ability of patients to drive vehicles and mechanisms. Patients should be advised to refrain from managing vehicles and mechanisms when developing fatigue or dizziness.

 

Drug Interactions

 

Special studies of the interaction of Abraksan with other drugs have not been conducted.

 

Due to the fact that the metabolism of paclitaxel is partially mediated by the CYP2C8 and CYP3A4 isoenzymes of the cytochrome P450 system, caution should be taken with the preparation of Abraxane along with inhibitors of these isoenzymes (including Ketoconazole and other antifungal agents, imidazole, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir and nelfinavir) or inducers of these isoenzymes (including rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine).

 

Paclitaxel and gemcitabine have different metabolic pathways. The clearance of paclitaxel is mainly due to the metabolism catalyzed by the isoenzymes CYP2C8 and CYP3A4, followed by excretion with bile; gemcitabine is inactivated by cytidine deaminase followed by excretion in the urine. Studies of the pharmacokinetic interaction of the drug Abraxan and gemcitabine in humans have not been conducted.

 

The drug Abraksan is indicated as a monotherapy for breast cancer, or in combination with gemcitabine for the treatment of pancreatic adenocarcinoma. The drug Abraxan should not be combined with other antitumour agents.

 

Analogues of the drug Abraksan

 

Abraksan does not have structural analogs for the active substance.

 

Analogues of the drug Abraksan on the pharmacological group (antitumor agents of plant origin):

• Abitaxel;
• Velba;
• Velbin;
• Vepezid;
• Verotecan;
• Vinblastine;
• Vinelbin;
• Winkater;
• Vincristine;
• Vinorelbine;
• Wumond;
• Gikamtin;
• Jevtan;
• Docetaxel;
• Dotserera;
• Javlor;
• Intaksel;
• Irinaks;
• Irinotecan;
• Irinotel;
• Iritin;
• Irkokam;
• Yondelis;
• Kampeter;
• Campto;
• Kanataksen;
• Kanglaite;
• Colotecan;
• Condiline;
• Fins;
• Mawerex;
• Mitotax;
• Navelbin;
• Novotaks;
• Oncodocel;
• Oncocristin;
• The paclikal;
• Paclitaxel;
• Pacifier;
• Paxen;
• Sindaxel;
• Taxiade;
• Taxol;
• Taxotere;
• Tautax;
• Topotecan;
• Phytoside;
• Cituvin;
• Aldesine;
• Etoposide;
• Yutaksan.

 

Review of the oncologist's doctor

 

In our department, we use the drug Abraxan for monotherapy for patients who, six months after the end of adjuvant chemotherapy, relapsed breast cancer. Virtually all women during treatment with Abraxan develop neutropenia of varying severity. Many people have to adjust the dose of the drug, namely, reduce it for all subsequent courses,and sometimes completely discontinue the drug. In addition, against the background of the introduction of Abraxane, other undesirable reactions are noted. The most frequent are inflammation of the upper respiratory tract, depression and anxiety, epistaxis, heart rhythm disturbances, diarrhea, abdominal pain.

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