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Tyverb is a brand name for Lapatinib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Tyverb is indicated for the treatment of adult patients with breast cancer, whose tumours overexpress HER2 (ErbB2); • in combination with capecitabine for patients with advanced or metastatic disease with progression following prior therapy, which must have included anthracyclines and taxanes and therapy with…
Verbatim from this product's EMA label. Tap a section to expand.
Tyverb treatment should only be initiated by a physician experienced in the administration of anti-cancer medicinal products. HER2 (ErbB2) overexpressing tumours are defined by IHC3+, or IHC2+ with gene amplification or gene amplification alone.
HER2 status should be determined using accurate and validated methods. e. five tablets) once daily continuously. 1). Capecitabine should be taken with food or within 30 minutes after food. Please refer to the full prescribing information of capecitabine.
e. four tablets) once daily continuously. 1). Please refer to the full prescribing information of trastuzumab. e. six tablets) once daily continuously. Please refer to the full prescribing information of the co-administered aromatase inhibitor for dosing details.
4). Tyverb may be restarted at a reduced dose (750 mg/day when administered with trastuzumab, 1000 mg/day when administered with capecitabine or 1250 mg/day when administered with an aromatase inhibitor) after a minimum of 2 weeks and if the LVEF recovers to normal and the patient is asymptomatic.
4). 8). Tyverb may be reintroduced at a lower dose (reduced from 1000 mg/day to 750 mg/day, from 1250 mg/day to 1000 mg/day or from 1500 mg/day to 1250 mg/day) when diarrhoea resolves to grade 1 or less. Tyverb dosing should be permanently discontinued in patients with diarrhoea which is NCI CTCAE grade 4.
Other toxicities Discontinuation or interruption of dosing with Tyverb may be considered when a patient develops toxicity greater than or equal to grade 2 on the NCI CTCAE. Dosing can be restarted, when the toxicity improves to grade 1 or less, at 1000 mg/day when administered with trastuzumab, 1250 mg/day when administered with capecitabine or 1500 mg/day when administered with an aromatase inhibitor.
If the toxicity recurs, then Tyverb should be restarted at a lower dose (750 mg/day when administered with trastuzumab, 1000 mg/day when administered with capecitabine or 1250 mg/day when administered with an aromatase inhibitor). 4 Renal impairment No dose adjustment is necessary in patients with mild to moderate renal impairment.
2). 4). Administration of Tyverb to patients with moderate to severe hepatic impairment should be undertaken with caution due to increased exposure to the medicinal product. 2). Elderly There are limited data on the use of Tyverb / capecitabine and Tyverb / trastuzumab in patients aged ≥ 65 years.
1). The most common adverse reactions (>25%) during therapy with lapatinib were gastrointestinal events (such as diarrhoea, nausea, and vomiting) and rash. Palmar-plantar erythrodysesthesia (PPE) was also common (>25%) when lapatinib was administered in combination with capecitabine.
The incidence of PPE was similar in the lapatinib plus capecitabine and capecitabine alone treatment arms. Diarrhoea was the most common adverse reaction resulting in discontinuation of treatment when lapatinib was administered in combination with capecitabine, or with letrozole.
No additional adverse reactions were reported to be associated with lapatinib in combination with trastuzumab. 4 – cardiac toxicity). These data are based on exposure to this combination in 149 patients in the pivotal trial. Tabulated list of adverse reactions The following adverse reactions have been reported to have a causal association with lapatinib alone or lapatinib in combination with capecitabine, trastuzumab or letrozole.
The following convention has been utilised for the classification of frequency: very common ((1/10), common (1/100 to <1/10), uncommon (1/1,000 to <1/100), rare (1/10,000 to <1/1,000) and very rare (<1/10,000), not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 4). Not known Ventricular arrhythmias/Torsades de Pointes, electrocardiogram QT prolonged** Vascular disorders Very common Hot flush† Respiratory, thoracic and mediastinal disorders Very common Epistaxis†, cough†, dyspnoea†.
Uncommon Interstitial lung disease/pneumonitis. Not known Pulmonary arterial hypertension**. 4), nausea, vomiting, dyspepsia*, stomatitis*, constipation*, abdominal pain*. 4). 2 - dose delay and dose reduction – other toxicities), dry skin*†, palmar-plantar erythrodysaesthesia*, alopecia†, pruritus†.
Data have shown that Tyverb combined with chemotherapy is less effective than trastuzumab when combined with chemotherapy. 8). Lapatinib has not been evaluated in patients with symptomatic cardiac failure. Caution should be taken if Tyverb is to be administered to patients with conditions that could impair left ventricular function (including co- administration with potentially cardiotoxic medicinal products).
Evaluation of cardiac function, including LVEF determination, should be conducted for all patients prior to initiation of treatment with Tyverb to ensure that the patient has a baseline LVEF that is within the institutions normal limits.
2). In some cases, LVEF decrease may be severe and lead to cardiac failure. Fatal cases have been reported, causality of the deaths is uncertain. In studies across the clinical development programme for lapatinib, cardiac events including LVEF decreases were reported in approximately 1% of patients.
3% of patients who received lapatinib. However, when lapatinib was administered in combination with trastuzumab in the metastatic setting, the incidence of cardiac events including LVEF decreases was higher (7%) versus the lapatinib alone arm (2%) in the pivotal trial.
The cardiac events observed in this study were comparable in nature and severity to those previously seen with lapatinib. A concentration-dependent increase of the QTc interval was demonstrated in a dedicated placebo-controlled crossover study in subjects with advanced solid tumours.
Caution should be taken if Tyverb is administered to patients with conditions that could result in prolongation of QTc (including hypokalemia, hypomagnesemia, and congenital long QT syndrome), co-administration of other medicinal product known to cause QT prolongation, or conditions that increase the exposure of lapatinib, such as co-administration of strong CYP3A4 inhibitors.
1. 5
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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In the phase III clinical study of Tyverb in combination with letrozole, of the total number of hormone receptor positive metastatic breast cancer patients (Intent to treat population N= 642), 44 % were ≥ 65 years of age. No overall differences in efficacy and safety of the combination of Tyverb and letrozole were observed between these patients and patients < 65 years of age.
Paediatric population The safety and efficacy of Tyverb in children below the age of 18 years have not yet been established. No data are available. Method of administration Tyverb is for oral use. The daily dose of Tyverb should not be divided.
Tyverb should be taken either at least one hour before, or at least one hour after food. 2 for information on absorption). 9). The full prescribing information of the co-administered medicinal product should be consulted for relevant details of their posology including any dose reductions, contraindications and safety information.
Common Nail disorders including paronychia, skin fissures. Not known Serious cutaneous reactions, including Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)** Musculoskeletal and connective tissue disorders Very common Pain in extremity*†, back pain*†, arthralgia†.
General disorders and administration site conditions Very common Fatigue, mucosal inflammation*, asthenia†. * These adverse reactions were observed when lapatinib was administered in combination with capecitabine. † These adverse reactions were observed when lapatinib was administered in combination with letrozole.
** Adverse reactions from spontaneous reports and literature Description of selected adverse reactions Decreased left ventricular ejection fraction and QT interval prolongation Left ventricular ejection fraction (LVEF) decreases have been reported in approximately 1% of patients receiving lapatinib and were asymptomatic in more than 70% of cases.
LVEF decreases resolved or improved in more than 70 % of cases, in approximately 60 % of these on discontinuation of treatment with lapatinib, and in approximately 40 % of cases lapatinib was continued. 3% of patients who received lapatinib monotherapy or in combination with other anti-cancer medicinal products.
Observed adverse reactions included dyspnoea, cardiac failure and palpitations. Overall 58 % of these symptomatic patients recovered. 0 % with capecitabine alone. 3 % of patients receiving letrozole plus placebo. 1 % of patients who received lapatinib alone.
4). Diarrhoea Diarrhoea occurred in approximately 65 % of patients who received lapatinib in combination with capecitabine, in 64 % of patients who received lapatinib in combination with letrozole and in 62 % of patients who received lapatinib in combination with trastuzumab.
Most cases of diarrhoea were grade 1 or 2 and did not result in discontinuation of treatment with lapatinib. 4). However, a few cases of acute renal failure have been reported secondary to severe dehydration due to diarrhoea. Rash Rash occurred in […]
Hypokalemia or hypomagnesemia should be corrected prior to treatment. Electrocardiograms with QT measurement should be performed prior to and one to two weeks after the start of Tyverb therapy. g. after initiation of a concomitant treatment that might affect QT or that may interact with lapatinib, ECG measurement should also be considered.
8). Patients should be monitored for symptoms of pulmonary toxicity (dyspnoea, cough, fever) and treatment discontinued in patients who experience symptoms which are NCI CTCAE grade 3 or greater. Pulmonary toxicity may be severe and lead to respiratory failure.
Fatal cases have been reported, causality of the deaths is uncertain. Hepatotoxicity Hepatotoxicity has occurred with Tyverb use and may in rare cases be fatal. The hepatotoxicity may occur days to several months after initiation of treatment.
At the initiation of treatment, patients should be advised of the potential for hepatotoxicity. Liver function (transaminases, bilirubin and alkaline phosphatase) should be monitored before the initiation of treatment and monthly thereafter, or as clinically indicated.
Tyverb dosing should be discontinued if changes in liver function are severe and patients should not be retreated. Patients who carry the HLA alleles DQA1*02:01 and DRB1*07:01 have increased risk of Tyverb-associated hepatotoxicity.
8% overall. 5%. Carriage of 6 the HLA risk alleles is common (15 to 25%) in Caucasian, Asian, African and Hispanic populations but lower (1%) in Japanese populations. 2). 8). Diarrhoea can be potentially life-threatening if accompanied by dehydration, renal insufficiency, neutropenia and/or electrolyte imbalances and fatal cases have been reported.
Diarrhoea generally occurs early during Tyverb treatment, with almost half of those patients with diarrhoea first experiencing it within 6 days. This usually lasts 4-5 days. Tyverb-induced diarrhoea is usually low-grade, with severe diarrhoea of NCI CTCAE grades 3 and 4 occurring in <10% and <1% of patients, respectively.
g. fever, cramping pain, nausea, vomiting, dizziness and thirst) should be determined, to allow identification of changes during treatment and to help identify patients at greater risk of diarrhoea. Patients should be instructed to promptly report any change in bowel patterns.
In potentially severe cases of diarrhoea the measuring of neutrophil counts and body temperature should be considered. Proactive management of diarrhoea with anti-diarrhoeal medicinal product is important. 2 – dose delay and dose reduction –diarrhoea).
Serious cutaneous reactions Serious cutaneous reactions have been […]