Tyverb - instructions for use, reviews, analogs and forms of release (tablets 250 mg) of the drug for the treatment of breast or breast cancer in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Tayverb. There are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors specialists on the use of Tayverba 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 Tayverba in the presence of existing structural analogues. Use for the treatment of breast cancer in adults, children, as well as during pregnancy and lactation. Composition of the preparation.

Tayverb is a reversible selective inhibitor of intracellular tyrosine kinase that binds to EGFR (the receptor of epidermal growth factor, ErbB1) and HER2 (the receptor of epidermal growth factor of human, ErbB2) receptors. It differs from other rapidly reversible tyrosine kinase inhibitors by slower dissociation with ErbB1 and ErbB2 receptors (the dissociation period of 50% of the ligand from the ligand-receptor complex is approximately 300 minutes).

Composition

Lapatinib + excipients.

Pharmacokinetics

Absorption after ingestion is incomplete and variable. The coefficient of variability is from 50% to 100%. The active substance is determined in the systemic circulation on average after 25 minutes. The maximum concentration is achieved approximately 4 hours after taking lapatinib.

Lapatinib has a high degree of binding (more than 99%) with albumin and alpha₁acid glycoprotein of blood plasma. Lapatinib undergoes extensive metabolism, mainly isozymes CYP3A4 and CYP3A5, to a lesser extent isozymes CYP2C19 and CYP2C8 oxidized to form various metabolites.

The half-life is increased dose-dependent when taken in single doses.The equilibrium state is achieved after 6-7 days of administration, the half-life in the equilibrium state is 24 hours. Basically excreted by the intestines - an average of 27% (from 3% to 67%) in unchanged form, less than 2% of the accepted dose is excreted by the kidneys in unchanged form and in the form of metabolites.

Indications

• locally advanced or metastatic breast cancer with HER2 overexpression - in combination with capecitabine in patients who had previously received anthracycline and taxane, who had progression with or after trastuzumab therapy for metastatic cancer;
• metastatic breast cancer with overexpression of HER2 - in combination with trastuzumab in patients who have progressed to cancer with or after trastuzumab therapy for metastatic cancer;
• hormone receptor-positive metastatic breast cancer with overexpression of HER2 - in combination with an aromatase inhibitor in postmenopausal patients.

Forms of release

The tablets covered with a cover of 250 mg.

Instructions for use and dosing regimen

Tyverb should be taken 1 hour before meals or 1 hour after meals.The recommended daily dose can not be divided into receptions.

Missed doses of lapatinib are not replenished, that is, to take missed doses, reducing the intervals between doses, should not be.

Locally advanced or metastatic breast cancer with overexpression of HER2

In combination with capecitabine, the recommended dose of lapatinib is 1250 mg (5 tablets) once daily, daily. The recommended dose of Capecitabine is 2000 mg per square meter per day in 2 divided doses (every 12 hours) daily from 1 to 14 days of each 21-day therapy cycle. It is recommended to take capecitabine with food or within 30 minutes after eating.

In combination with trastuzumab, the recommended dose of lapatinib is 1000 mg (4 tablets) once daily, daily in combination with trastuzumab. The recommended dose of trastuzumab is 4 mg per kilogram, as an intravenous loading dose, then 2 mg per kilogram intravenously once a week.

Hormone-receptor-positive metastatic breast cancer with overexpression of HER2

The recommended dose of lapatinib is 1500 mg (6 tablets) once a day, daily in combination with an aromatase inhibitor.

The recommended dose of Letrozole (one of the possible drugs - aromatase inhibitors) when taken in combination with lapatinib is 2.5 mg once daily, daily. In the event that lapatinib is prescribed in combination with another aromatase inhibitor, it is necessary to study the dosage regimen of the corresponding drug in this group.

Side effect

• anorexia (complete absence of appetite);
• shortness of breath, palpitations;
• heart failure;
• pneumonitis (inflammation of the vascular wall of the alveoli);
• diarrhea;
• nausea, vomiting;
• Hyperbilirubinemia (elevated bilirubin level);
• hepatotoxicity (structural and functional disorders of the liver);
• rash;
• defeat of nails;
• anaphylaxis (reaction to an allergen, accompanied by swelling, suffocation, muscle spasms and severe pain);
• general weakness;
• dyspepsia (indigestion);
• dry skin;
• stomatitis (inflammation of the oral mucosa);
• constipation;
• abdominal pain;
• palmar-plantar syndrome (swelling, redness, pain on the palms and feet);
• pain in the extremities, back pain;
• headache;
• insomnia;
• nose bleed;
• alopecia (alopecia).

Contraindications

• pregnancy;
• lactation period;
• childhood;
• hypersensitivity to lapatinib or any other component of the drug.

With caution the drug is prescribed:

• at conditions that can lead to left ventricular failure;
• violations of liver function, moderate or severe degree (7 or more points on the Child-Pugh scale);
• with renal insufficiency of severe degree;
• in patients older than 65 years;
• simultaneously with moderate inhibitors of the isoenzyme CYP3A4.

Application in pregnancy and lactation

There are no known cases of Tyverba during pregnancy.

Women of childbearing age should be warned about the use of adequate contraception, as well as the interruption of the pregnancy that occurs during the treatment period.

When used in doses toxic to the mother, lapatinib did not have teratogenic properties in studies on pregnant mice and rabbits, but at the same time was the cause of some deviations in development.

It is not known whether lapatinib is excreted in breast milk. During therapy with lapatinib, it is recommended to stop breastfeeding because of the possible occurrence of characteristic undesirable phenomena in the infant.

Use in children

Contraindicated in childhood - no experience of use.

Application in elderly patients

There is insufficient data on the use of Tayverba in elderly patients (over 65 years of age).

special instructions

Treatment with Tayverb should be done only under the supervision of a specialist who has experience in the use of antitumor drugs.

Cardiotoxicity

Before treatment, it is necessary to determine LVEF (left ventricular ejection fraction) to ensure that LVEF is within acceptable limits. During treatment with Tayverb, control of LVEF should be continued so as not to miss its decrease beyond the limits of acceptable values.

It is impossible to completely exclude the effect of lapatinib on the QT interval, as there are reports of cases of a slight increase in the QT interval in patients with a common tumor process. Caution should be exercised in prescribing lapatinib to patients with concomitant factors that affect the increase in the QT interval (such as hypokalemia, hypomagnesemia, congenital long QT interval syndrome, or simultaneous use of drugs that affect the QT interval increase).The concentration of potassium and magnesium in the blood should be normalized before the application of Tayverba. ECG with QT interval control should be performed before and during the entire treatment.

Interstitial lung disease and pneumonitis

There are reports of cases of interstitial lung disease and pneumonitis in connection with taking Tayverba. Patients should be monitored to rule out the occurrence of pulmonary symptoms, indicative of the development of interstitial lung disease or pneumonitis.

Diarrhea

There are reports of cases of diarrhea, including severe diarrhea, in treatment. Diarrhea usually occurred in the early stages of treatment with Tayverb, while almost half of these patients developed diarrhea within the first 6 days. Diarrhea usually lasts 4-5 days. Lapatinib-induced diarrhea manifests itself, as a rule, in an easy degree; Diarrhea of ​​3rd and 4th degree (according to the general criteria of toxicity of the National Cancer Institute of the USA) is observed in less than 10% and less than 1% of patients, respectively. Early detection and timely treatment are of great importance for the optimal control of diarrhea.Patients should be instructed that they should immediately report any changes in the nature of the stool. It is recommended to immediately prescribe diarrhea therapy with antidiarrhoeal agents (for example, loperamide) after the first case of an unformed stool. Severe diarrhea may require the administration of electrolytes and fluid to prevent dehydration (oral or intravenous), the use of antibiotics such as fluoroquinolones (especially if diarrhea lasts for more than 24 hours, the patient experiences fever or grade 3 or 4 neutropenia) , suspension or withdrawal of the drug.

Contraception

During therapy with Tayverbom and at least three months after its termination, reliable methods of contraception should be used.

Hepatotoxicity

Manifestations of hepatotoxicity (ALT or AST activity, which is 3 times higher than IVH, the content of total bilirubin exceeding the upper limit of the norm by 1.5 times) was observed in clinical studies (less than 1% of patients) and in the post-marketing period. Hepatotoxicity can be severe. Cases with a fatal outcome have been reported, although a causal relationship with the use of lapatinib has not been established.Hepatotoxicity can develop for several days to several months after initiation of therapy. It is necessary to monitor the laboratory parameters of liver function (aminotransferases, bilirubin and alkaline phosphatase) before the start of therapy, then every 4-6 weeks during the course of treatment and according to clinical indications. When severe liver function disorders occur, Tyverba should be discontinued and re-administration of the drug is unacceptable.

When prescribing lapatinib, patients with existing severe impairment of liver function in a history of lower lapatinib dose are recommended.

Simultaneous use of inhibitors or inducers of CYP3A4

It is necessary to carefully appoint Tyverb in conjunction with inhibitors or inducers of the isoenzyme CYP3A4 because of the risk of increasing or decreasing (respectively) the systemic effects of lapatinib.

Impact on the ability to drive vehicles and manage mechanisms

Influence on the ability to drive vehicles and other activities requiring increased concentration of attention and speed of psychomotor reactions, has not been studied.Based on the mechanism of action of lapatinib, one can not assume the adverse effect of the drug on such activities. However, the general condition of the patient and the profile of side effects of lapatinib should be taken into account, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Drug Interactions

Inhibitors or inducers of the CYP3A isoenzyme are able to influence the pharmacokinetics of lapatinib. With the simultaneous use of Taiwerb and some inhibitors of the isoenzyme CYP3A4 (eg, ketoconazole, itraconazole, grapefruit juice), care must be taken to carefully monitor the clinical condition of the patient and possible adverse reactions. If simultaneous administration of a potent inhibitor of the CYP3A4 isoenzyme is necessary, the dose of lapatinib should be reduced to 500 mg per day, calculated to adjust the lapatinib AUC to a value corresponding to the use of lapatinib without inhibitors.However, there are currently no clinical data on the use of lapatinib with this dose adjustment in patients receiving a potent inhibitor of the CYP3A4 isoenzyme. After the cancellation of the potent inhibitor, only after removal from the body, after about 1 week, the dose of lapatinib should be increased again to the recommended dose.

With simultaneous application of Tyverba and known inducers of the isoenzyme CYP3A4 (for example, rifampicin, carbamazepine, phenytoin, St. John's wort), care should be taken and the clinical condition of the patient and possible undesirable reactions should be carefully monitored.

If it is necessary to simultaneously assign a powerful inducer of CYP3A4 isoenzyme to a patient, the dose of lapatinib should be selected, based on tolerability, gradually increasing it from 1250 mg per day to 4500 mg per day or from 1500 mg per day to 5,500 mg per day. This dose is calculated so as to adjust the lapatinib AUC to a value corresponding to the use of lapatinib without inducers of the CYP3A4 isoenzyme. However, there are currently no clinical data on the use of lapatinib in patients receiving a potent inducer of the isoenzyme CYP3A4.After canceling the powerful inducer of the isoenzyme CYP3A4, only after about 2 weeks should the dose of lapatinib again be reduced to the recommended one.

The solubility of lapatinib depends on pH. Avoid concomitant use of substances that increase the pH of gastric juice, since the solubility and absorption of lapatinib can decrease. Previous treatment with a proton pump inhibitor (eg, esomeprazole) reduced lapatinib activity by an average of 27% (ranging from 6% to 49%). This effect decreases with increasing age from about 40 years to 60 years. Therefore, caution should be given to lapatinib for patients taking proton pump inhibitors.

Lapatinib inhibits the in vitro isoenzyme CYP3A4 at clinically significant concentrations. Simultaneous use of lapatinib with midazolam for oral administration leads to an increase in midazolam AUC by approximately 45%. With intravenous administration of midazolam, there was no clinically significant increase in AUC. Caution is needed when concomitant administration of lapatinib and oral medications with a narrow therapeutic range, which are substrates of the isoenzyme CYP3A4.

Lapatinib inhibits the isoenzyme CYP2C8 in vitro in clinically significant concentrations. Caution should be used to prescribe lapatinib concomitantly with drugs with a narrow therapeutic range, which are substrates of the CYP2C8 isoenzyme.

The simultaneous use of lapatinib with Paclitaxel intravenously increases the effect of paclitaxel by 23% due to the inhibition of lapatinib by the isoenzyme CYP2C8 or P-glycoprotein. An increase in the incidence and severity of diarrhea and neutropenia was observed with a combination of lapatinib and paclitaxel in clinical trials. It is recommended that caution be given to lapatinib concurrently with paclitaxel.

Simultaneous use of lapatinib with docetaxel intravenously did not significantly affect the AUC or the maximum concentration of any active substances. However, there was an increase in the incidence of docetaxel-induced neutropenia.

Simultaneous use of lapatinib with irinotecan (when administered as part of the FOLFIRI regimen) resulted in an increase in AUC SN-38, an active metabolite of irinotecan, by approximately 40%. The exact mechanism of this interaction is not known.It is recommended that caution be given to lapatinib simultaneously with irinotecan.

Lapatinib is a substrate for transport proteins of P-glycoprotein and BCRP. Inhibitors and inducers of these proteins may alter the activity or distribution of lapatinib.

Lapatinib inhibits the transport protein P-glycoprotein in vitro in clinically significant concentrations. Simultaneous use of lapatinib with Digoxin when ingested increases the digoxin AUC by approximately 98%. Caution should be used to administer lapatinib with concomitant use with drugs with a narrow therapeutic range, which are substrates of P-glycoprotein.

Lapatinib inhibits the transport proteins BCRP and OATP1B1 in vitro. The clinical significance of these effects has not been studied, but it is possible that lapatinib may affect the pharmacokinetics of BCRP substrates (eg topotecan) and OATP1B1 (eg rosuvastatin).

The combined use of lapatinib with capecitabine, letrozole or trastuzumab does not affect the pharmacokinetic parameters of these drugs.

Bioavailability of lapatinib depends on the intake of food.

Analogues of the drug Tyverb

There are no structural analogs for the current Tyverb.

Analogues on the curative effect (remedies for the treatment of breast cancer):

• Abitaxel;
• Abraxan;
• Avastin;
• Adryblastin;
• Anastrozole;
• Arglabin
• Arimidex;
• Aromasine;
• Buserelin;
• Vepezid;
• Anastrozole;
• Vincristine;
• Mitomycin;
• Tamoxifen;
• Vinelbin;
• Vincristine;
• Vinorelbine;
• Gemcitabine;
• Herceptin;
• Doxol;
• Doxorubifer;
• Zitazonium;
• Zoladex;
• Zometa;
• Kabetsin;
• Carboplatin;
• Kelix;
• Xeloda;
• Leukeran;
• Letrozole;
• Lomustine;
• Lucrin;
• Mawerex;
• Mammoth;
• Methotrexate;
• Miltex;
• Mitoxantrone;
• Mitotax;
• Navelbin;
• Novanthron;
• Novofen;
• Nolvadex;
• Octreotide;
• Omnadren;
• Oncotron;
• Paclitaxel;
• Paxen;
• Sinestrol;
• Tamoxen;
• Tamoxifen;
• Treksan;
• UFТ;
• Fazlodex;
• Fareston;
• Femara;
• Ftorafur;
• Fluorouracil;
• Halavan;
• Holoksan;
• Cyclophosphane;
• Cytohem;
• Cytoxan;
• Egistrazole;
• Extrase;
• Aldesine;
• Endoxane;
• Epirubicin;
• Episondan;
• The Estrolet;
• Etrusil;
• Yutaksan.

Review of the oncologist's doctor

Tayverb is an effective medicine for the treatment of breast cancer. Assign it often. The drug works well for locally distributed formations, as well as for tumors that have already spread metastases. Treatment is always carried out complex - depending on the nature of the neoplasm.Tyverb is combined with capecitabine, trastuzumab or aromatase inhibitors. In the treatment it is very important to strictly adhere to the regimen. At the same time, the prescribed daily dose can not be divided into receptions, missed doses, reducing intervals between them, should not be taken.

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