Tyverb
Tyverb: 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: Tyverb
ATX code: L01XE07
Active ingredient: lapatinib (lapatinib)
Producer: Glaxo Wellcome Operations (UK)
Description and photo update: 28.11.2018
Prices in pharmacies: from 74,500 rubles.
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Tyverb is a protein tyrosine kinase inhibitor, anticancer drug.
Release form and composition
The drug is produced in the form of film-coated tablets: oval, biconvex, yellow, engraved on one side with "GS XJG". in polyethylene bottles, in a cardboard box 1 bottle and instructions for use of Tyverb).
1 tablet contains:
- active substance: lapatinib ditosylate monohydrate - 405 mg, which is equivalent to the content of 250 mg of lapatinib;
- auxiliary components: sodium carboxymethyl starch (type A), povidone K30, microcrystalline cellulose, purified water - removed during production;
- film shell: opadry yellow YS-1-12524-A [polysorbate 80, hypromellose, macrogol 400, titanium dioxide, iron dye yellow oxide (E172), iron dye red oxide (E172)].
Pharmacological properties
Pharmacodynamics
Tyverb is an antineoplastic drug. Its active ingredient, lapatinib, is a reversible selective inhibitor of intracellular tyrosine kinase that binds to the epidermal growth factor receptor (EGFR) ErbB1 and the human epidermal growth factor receptor (HER2 / neu) ErbB2. Slower dissociation with ErbB1 and ErbB2 receptors (from the ligand-receptor complex, the dissociation period of 50% of the ligand is about 5 hours) distinguishes lapatinib from other rapidly reversible tyrosine kinase inhibitors.
In an in vitro study of the drug in combination with capecitabine on four lines of tumor cells, in addition to its own activity, the additive effect of lapatinib and the active metabolite of capecitabine, fluorouracil, was established. Evaluation of the inhibitory effect was carried out on trastuzumab-treated cells.
Along with an additive mechanism of action, combination with trastuzumab may provide mechanisms for unparalleled overcoming of resistance to anti-HER2 therapy.
On HER2-positive tumor cell lines, significant lapatinib activity and synergistic action were demonstrated in media containing trastuzumab.
Research results indicate that there is no cross-resistance between the two ligands of the HER2 receptor (ErbB2).
Pharmacokinetics
After oral administration, incomplete absorption of lapatinib occurs. In the systemic circulation, it is determined in the range from 0 to 1.5 hours. The variability of the total concentration of the drug in blood plasma (AUC) is from 50% to 100%. The maximum concentration (C max) of lapatinib in blood plasma is reached after approximately 4 hours.
While taking a daily dose of 1250 mg, the equilibrium plasma concentration of lapatinib (C ss) averages 0.002 43 mg / ml, AUC - 0.036 2 mg × h / ml.
With a simultaneous intake of food containing 5% fat, the systemic exposure of the drug increases 3 times, 50% fat - 4 times. The time to reach C max increases 2.5 and 3 times, respectively.
Plasma protein binding (albumin and alpha 1 -acid glycoprotein) - 99%.
Lapatinib slightly inhibits the organic cation transporter (OCT) or organic anion transporter (OAT).
Intensive metabolism with the formation of various oxidized metabolites occurs mainly with the participation of isoenzymes CYP3A4 and CYP3A5, to a lesser extent - CYP2C19 and CYP2C8.
In vitro, lapatinib inhibits CYP3A and CYP2C8 isoenzymes at clinically relevant concentrations.
On microsomal liver enzymes such as CYP1A2, CYP2C9, CYP2C19 or CYP2D6, lapatinib has a slight inhibitory effect.
In healthy individuals, while taking ketoconazole, which is an inhibitor of the CYP3A4 isoenzyme, at a daily dose of 400 mg for 7 days, the systemic distribution of the active substance increases by about 3.6 times, and the half-life (T 1/2) - 1.7 times … The use of carbamazepine (inducer of the isoenzyme CYP3A4) in a daily dose of 200 mg for three days and 400 mg for 17 days causes a decrease in the systemic distribution of lapatinib by 72%.
The equilibrium state is achieved after 7 days of a single dose of Tayverb, while T 1/2 is 24 hours.
Unchanged through the intestine is excreted on average 27% of the dose taken, through the kidneys - less than 2%, including in the form of metabolites.
In impaired renal function and in patients on hemodialysis, changes in the pharmacokinetics of lapatinib are unlikely.
In case of impaired liver function, Tiverb should be prescribed with caution. If a history of severe hepatic impairment is indicated, the dose should be reduced. With the development of severe hepatotoxicity against the background of the use of the drug, the cancellation of therapy is required without its subsequent resumption.
Indications for use
The use of Taiverb is indicated for the treatment of metastatic breast cancer with overexpression of HER2 in combination with trastuzumab in cases when the progression of the disease was noted during or after the use of trastuzumab for metastatic cancer.
Patients with tumor progression during or after trastuzumab therapy are prescribed the drug for the treatment of locally advanced and metastatic breast cancer with overexpression of HER2 as part of a combination therapy with capecitabine after previous treatment with anthracycline and taxane.
Tyverb is used in combination with an aromatase inhibitor to treat hormone receptor-positive metastatic breast cancer with HER2 overexpression in postmenopausal patients.
Contraindications
Absolute:
- the simultaneous use of drugs that are powerful inhibitors (including grapefruit juice) or inducers of the CYP3A4 isoenzyme;
- the simultaneous use of drugs that increase the acidity of gastric juice;
- period of pregnancy;
- breast-feeding;
- childhood;
- hypersensitivity to the components of the drug.
It is recommended to be careful when prescribing Tayverb tablets to patients at risk of developing left ventricular failure or in the presence of factors affecting an increase in the QT interval (including hypokalemia, hypomagnesemia, congenital long QT interval syndrome, concomitant use of drugs that affect an increase in the QT interval), with moderate or severe liver dysfunction (7 or more points on the Child-Pugh scale), severe renal failure, over the age of 65, concurrently with moderate inhibitors of the CYP3A4 isoenzyme, in combination with drugs with a narrow therapeutic range, which are substrates of CYP3A4 isoenzymes and CYP2C8.
Tyverb, instructions for use: method and dosage
Tyverb tablets are taken orally, observing an interval of 1 hour before or after meals.
The prescribed daily dose of lapatinib is taken once a day, preferably at the same time of the day. If the next dose is missed, it is not replenished, and the treatment is continued by taking the next dose at a certain time.
Recommended dosage for the treatment of locally advanced or metastatic HER2 overexpressing breast cancer:
- combination with capecitabine: Taverb dose - 5 pcs. (1250 mg). The dose of capecitabine is 2000 mg per square meter of body surface per day. The resulting dose is taken every 12 hours (during or 0.5 hour after meals) from 1 to 14 days of the anticancer therapy cycle (21 days);
- combination with trastuzumab: dose of lapatinib - 4 pcs. (1000 mg). Trastuzumab dose - intravenously (iv) at the rate of 4 mg per 1 kg of the patient's body weight as a loading dose, then 2 mg per 1 kg of body weight once a day with an interval of 7 days.
Recommended dosage for the treatment of hormone receptor-positive metastatic breast cancer with HER2 overexpression:
- dose of lapatinib: 6 pcs. (1500 mg);
- dose of letrozole (an aromatase inhibitor, one of the possible): 2.5 mg once a day. If another aromatase inhibitor is prescribed, its dose is determined in accordance with the instructions for the specific preparation.
Recommendations to temporarily stop taking or reduce the dose of Tayverb in the event of the following concomitant pathologies:
- disorders of the cardiovascular system: the reason for discontinuation of the drug is a decrease in the left ventricular ejection fraction (LVEF) below the acceptable limit or to grade III or more in accordance with the general toxicity criteria of the US National Cancer Institute. Treatment can be resumed no earlier than 14 days after normal LVEF and no symptoms of heart failure. When the treatment is resumed, the daily dose is reduced: when combined with trastuzumab - up to 3 pcs. (750 mg), in combination with capecitabine - up to 4 pcs. (1000 mg), when combined with an aromatase inhibitor - up to 5 pcs. (1250 mg). The risk of decreased LVEF is increased during the first 84 days of taking lapatinib;
- interstitial lung disease, pneumonitis: if symptoms appear indicating the development of interstitial lung disease, pneumonitis (grade III toxicity and higher according to the general criteria of the US National Cancer Institute), treatment must be discontinued;
- diarrhea: the reason for the temporary cancellation of lapatinib is the presence of grade III diarrhea, grade I or II diarrhea, complicated by spastic abdominal pain (moderate to severe), nausea or vomiting of grade II and higher, decreased performance, fever, neutropenia, severe bleeding, dehydration, or sepsis according to the US National Cancer Institute's General Toxicity Criteria. With a decrease in diarrhea to degree I and lower, treatment can be resumed at a lower dose. When combined with trastuzumab, 3 pcs are prescribed. (750 mg), in combination with capecitabine - 4 pcs. (1000 mg), when combined with an aromatase inhibitor - 5 pcs. (1250 mg) once a day. With IV degree of diarrhea, treatment is completely stopped;
- manifestations of toxicity: II degree of toxicity and higher is the basis for making a decision to cancel or temporarily discontinue treatment. After reducing the severity of toxic effects to grade I and below, the use of Tayverb can be resumed at the initial dose. If repeated toxic effects occur, the dose of lapatinib should be reduced by 250 mg.
In severe liver dysfunctions (class C on the Child-Pugh scale), the drug is used in a reduced dose. When combined with capecitabine, the daily dose should be 750 mg, in combination with an aromatase inhibitor, 1000 mg. In case of severe manifestations of hepatotoxicity, treatment with Tayverb should be canceled, re-appointment is unacceptable.
In case of impaired renal function, correction of the dosage regimen is not required.
Side effects
Undesirable effects established during clinical and post-registration studies, arising against the background of lapatinib monotherapy or in combination with trastuzumab:
- on the part of nutrition and metabolism: very often - anorexia;
- on the part of the cardiovascular system: often - a transient decrease in LVEF (including shortness of breath, palpitations, heart failure);
- from the respiratory system: infrequently - pneumonitis, interstitial lung disease;
- from the gastrointestinal tract: very often - diarrhea (including leading to dehydration), nausea, vomiting;
- from the hepatobiliary system: infrequently - hepatotoxicity, hyperbilirubinemia;
- dermatological reactions: very often - rash (including transient acneform dermatitis); often - paronychia and other nail lesions;
- allergic reactions: rarely - anaphylaxis and other hypersensitivity reactions;
- on the part of the body as a whole: very often - weakness.
In addition, the use of lapatinib in combination with capecitabine may cause the following side effects:
- from the gastrointestinal tract: very often - abdominal pain, dyspepsia, stomatitis, constipation;
- dermatological reactions: very often - dry skin, palmar-plantar syndrome;
- from the musculoskeletal system: very often - pain in the limbs and / or back;
- from the nervous system: often - headache;
- from the side of the psyche: very often - insomnia;
- from the body as a whole: very often - inflammation of the oral mucosa.
In addition to adverse events during monotherapy with lapatinib, the following adverse events were observed in combination with Taiverb with letrozole:
- from the respiratory system: very often - epistaxis;
- dermatological reactions: very often - dry skin, alopecia.
Overdose
Symptoms: development of side effects and associated consequences. Possible skin ulceration, sinus tachycardia with a normal electrocardiogram (ECG), and / or mucosal involvement. The absence of clinical symptoms is allowed against the background of an overdose.
Treatment: the appointment of symptomatic therapy. Hemodialysis is ineffective.
special instructions
Lapatinib treatment should be supervised by a specialist experienced in anticancer therapy.
Treatment can be started and continued when the left ventricular ejection fraction (LVEF) is within acceptable limits, and the concentration of potassium and magnesium in the blood is normal. Before starting and during the period of using lapatinib, regular monitoring of LVEF, ECG with monitoring of the QT interval is required.
Diarrhea may develop in the early stages of lapatinib treatment. For optimal control of diarrhea, patients should inform the physician of any abnormalities in stool behavior. Early detection and timely administration of antidiarrheal agents are essential to prevent severe diarrhea. To prevent dehydration, oral or intravenous administration of electrolytes and fluids, the use of antibiotics of the fluoroquinolone group may be required. Patients with severe diarrhea lasting for 24 hours and accompanied by grade III or IV fever or neutropenia require special attention. In this case, it may be necessary to decide whether to suspend or discontinue the drug.
The use of Taiverb is accompanied by the risk of developing hepatotoxicity, including in a severe degree with a fatal outcome. The manifestation of hepatotoxicity can be an increase in the activity of alanine aminotransferase or aspartate aminotransferase (compared to the upper limit of the norm by 3 times) and the level of total bilirubin (compared to the upper limit of the normal by 1.5 times). Its symptoms may appear several days after the start of the drug or at a later period. In this regard, the laboratory parameters of bilirubin, aminotransferases and alkaline phosphatase are monitored both before the start of treatment and every 28–42 days during the entire course of therapy. If severe liver dysfunctions are found, the final withdrawal of lapatinib is required.
It should be borne in mind that food intake affects the bioavailability of lapatinib.
Influence on the ability to drive vehicles and complex mechanisms
Care must be taken when driving vehicles and performing potentially hazardous activities that require increased concentration of attention and high speed of psychomotor reactions.
Application during pregnancy and lactation
The use of Taiverb during gestation and lactation is contraindicated.
Women of childbearing age should use reliable contraception during the period of drug use and within three months after its cancellation. They should be warned to consider terminating the pregnancy if they conceive while taking lapatinib.
Pediatric use
The appointment of Taiverb in childhood is contraindicated.
With impaired renal function
With caution, it is recommended to use Taiverb tablets for the treatment of patients with severe renal failure.
For violations of liver function
It is recommended to be careful when prescribing Taiverb to patients with moderate or severe liver dysfunction (7 or more points on the Child-Pugh scale).
For severe liver dysfunctions (class C on the Child-Pugh scale), Tyverb is used in a reduced dose. When combined with capecitabine, the daily dose should be 750 mg, in combination with an aromatase inhibitor, 1000 mg. In case of severe manifestations of hepatotoxicity, drug treatment must be canceled, re-appointment is unacceptable.
Use in the elderly
Due to the lack of sufficient data on the efficacy and safety, Tiverb should be used with caution to treat patients over the age of 65 years.
Drug interactions
Possible interactions with the simultaneous use of Tyverb:
- inhibitors of the CYP3A4 isoenzyme (including itraconazole, ketoconazole, grapefruit juice) and inducers of the CYP3A4 isoenzyme (including rifampicin, carbamazepine, St. There is no clinical data on the use of this combination;
- proton pump inhibitors and other agents that increase the acidity of gastric juice: reduce the solubility and absorption of lapatinib;
- paclitaxel: the degree of paclitaxel exposure increases by 23%, which leads to an increase in the incidence and severity of diarrhea, neutropenia;
- docetaxel: IV administration of docetaxel increases the incidence of neutropenia;
- irinotecan: there is an increase of about 40% in the AUC of the active metabolite of irinotecan, a combination of drugs should be prescribed with caution;
- transport proteins of P-glycoprotein and BCRP (breast cancer resistance protein): inhibitors and inducers of these proteins can affect the activity and / or distribution of lapatinib;
- digoxin: AUC of digoxin increases by about 98%;
- trastuzumab, capecitabine, letrozole: the pharmacokinetic parameters of these drugs are not violated.
Analogs
Tyverb's analogs are: Afinitor, Bosulif, Votrient, Genfatinib, Giotrif, Gleevec, Jakavi, Zelboraf, Imbruvika, Imatinib, Inlita, Ksalkori, Caprelsa, Nexavar, Sutent, Sprysel, Tasigna, Tarceva, Mekinlarinist, Rafinlarinist.
Terms and conditions of storage
Keep out of the reach of children.
Store at temperatures up to 30 ° C.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Tyverbe
Reviews about Tyverbe are very rare, their content does not allow assessing the degree of effectiveness or tolerability of the drug.
Price for Tyverb in pharmacies
The price of Tyverb for a pack containing 140 tablets can range from 188,909 to 202,000 rubles.
Tyverb: prices in online pharmacies
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Drug name Price Pharmacy |
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Tyverb 250 mg film-coated tablets 140 pcs. RUB 74500 Buy |
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!
