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TYKERB is a brand name for Lapatinib, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: TYKERB (lapatinib tablets) is indicated for: In combination with capecitabine, for the treatment of patients with metastatic breast cancer whose tumours overexpress ErbB2 (HER2). Patients should have progressed on taxanes and anthracycline before starting this therapy. In addition, patients should have progressed on…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations TYKERB should only be administered by physicians experienced with antineoplastic drugs (see 1 INDICATIONS). ErbB2 (HER2) over-expressing tumours are defined by IHC3+, IHC2+ and gene amplification (FISH), or gene amplification alone.
Gene amplification should be performed using an accurate and validated assay. 0 and by IHC with IHC3+ and full circumferential staining in >10% tumour cells. The bioavailability of lapatinib is increased by food. TYKERB should only be taken at least 1 hour before or at least 1 hour after a low-fat meal.
The recommended daily lapatinib dose should not be divided. e. five tablets) once daily every day when taken in combination with capecitabine. 3 Pharmacokinetics). The recommended dose of capecitabine is 2000 mg/m2/day divided into two equal doses, each dose taken 12 hours apart on days 1-14 in a 21 day cycle (see 14.
CLINICAL TRIALS). Capecitabine should be taken with food or within 30 minutes after food. The prescribing information for capecitabine must be consulted for guidance on dose delay and dose reduction recommendations for capecitabine. e.
six tablets) once daily every day when taken in combination with letrozole. 3 Pharmacokinetics). 5 mg once daily. Cardiac events (see 7.
WARNINGS AND PRECAUTIONS):
TYKERB should be discontinued in patients with symptoms associated with decreased LVEF that are National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade 3 or greater or if their LVEF drops below the institutions lower limit of normal.
Consideration may be given to restarting TYKERB after a minimum of 2 weeks and only if the LVEF recovers to normal and the patient is asymptomatic. If TYKERB is restarted under these circumstances, a reduced dose (1000 mg/day when administered with capecitabine and 1250 mg/day when administered with letrozole) is recommended.
Based on current data, the majority of LVEF decreases occur within the first 12 weeks of treatment, but there is limited data on long term exposure. Interstitial lung disease/pneumonitis (see 7. WARNINGS AND PRECAUTIONS and 8.
ADVERSE REACTIONS):
Product Monograph TYKERB lapatinib tablets Page 6 of 44 TYKERB should be discontinued in patients who experience pulmonary symptoms indicative of interstitial lung disease/pneumonitis which are NCI CTCAE grade 3 or greater. Diarrhea (see 7.
), and in some cases sore scalp, sinus tachycardia (with an otherwise normal ECG), and/or mucosal inflammation. Treatment TYKERB is not significantly renally excreted and is highly bound to plasma proteins, therefore hemodialysis would not be expected to be an effective method to enhance the elimination of TYKERB.
Further management should be as clinically indicated or as recommended by the Regional Poison Control Centre, where available. Product Monograph TYKERB lapatinib tablets Page 8 of 44 For management of a suspected drug overdose, contact your regional poison control centre.
6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING Table 1 – Dosage Forms, Strengths, Composition and Packaging TYKERB tablets, 250 mg, are yellow, oval, biconvex, film-coated tablets, with one side plain and the opposite side debossed with GS XJG.
The inactive ingredients of TYKERB are:
Tablet Core: magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate. Coating: hypromellose, iron oxide red, iron oxide yellow, macrogol/PEG 400, polysorbate 80 and titanium dioxide. TYKERB film-coated tablets are available in HDPE bottles of 70 tablets.
7 WARNINGS AND PRECAUTIONS General It is not recommended that lapatinib in combination with letrozole be administered to HER2 negative patients due to a lack of clinical benefit in this population (see 14. CLINICAL TRIALS).
Cardiovascular LVEF and Heart Failure:
TYKERB has been reported to decrease left ventricular ejection fraction [LVEF] (see 8. ADVERSE REACTIONS). In randomized clinical trials, the majority (>57%) of LVEF decreases occurred within the first 12 weeks of treatment, but data on long-term exposure are limited.
LVEF should be evaluated in all patients prior to initiation of treatment with TYKERB to ensure that the patient has a baseline LVEF that is within the institutions normal limits. LVEF should continue to be evaluated during treatment with TYKERB to ensure that LVEF does not decline to an unacceptable level.
General It is not recommended that lapatinib in combination with letrozole be administered to HER2 negative patients due to a lack of clinical benefit in this population (see 14. CLINICAL TRIALS).
Cardiovascular LVEF and Heart Failure:
TYKERB has been reported to decrease left ventricular ejection fraction [LVEF] (see 8. ADVERSE REACTIONS). In randomized clinical trials, the majority (>57%) of LVEF decreases occurred within the first 12 weeks of treatment, but data on long-term exposure are limited.
LVEF should be evaluated in all patients prior to initiation of treatment with TYKERB to ensure that the patient has a baseline LVEF that is within the institutions normal limits. LVEF should continue to be evaluated during treatment with TYKERB to ensure that LVEF does not decline to an unacceptable level.
1 DOSAGE AND ADMINISTRATION: Dosing Considerations, Cardiac Events and See 14. CLINICAL TRIALS). 1 Mechanism of Action). Many drugs that cause QT/QTc prolongation are suspected to increase the risk of torsade de pointes. If sustained, torsade de pointes can progress to Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Oral Tablet 250 mg lapatinib (as lapatinib ditosylate) Hypromellose, Iron oxide red, Iron oxide yellow, Macrogol/PEG 400, Magnesium stearate, Microcrystalline Cellulose, Polysorbate 80, Povidone, Sodium Starch Glycolate and Titanium Dioxide.
Product Monograph TYKERB lapatinib tablets Page 9 of 44 ventricular fibrillation and sudden cardiac death. Events of ventricular fibrillation, cardiac arrest, and sudden death have been reported with TYKERB in clinical trials. QT prolongation was observed in an uncontrolled, open-label dose escalation study of lapatinib in advanced cancer patients.
2 Pharmacodynamics). Caution should be taken if TYKERB is administered to patients who have or may develop prolongation of QTc. These conditions include patients with hypokalemia or hypomagnesemia, congenital long QT syndrome, patients taking anti-arrhythmic medicines or other medicinal products that lead to QT prolongation.
TYKERB is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section of the product monograph.
Please refer to the product monograph of the co-administered medicinal products (capecitabine or letrozole) for relevant contraindications and safety information.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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WARNINGS AND PRECAUTIONS and 8.
ADVERSE REACTIONS):
TYKERB dosing should be interrupted in patients with diarrhea which is NCI CTCAE grade 3 or grade 1 or 2 with complicating features (moderate to severe abdominal cramping, nausea or vomiting greater than or equal to NCI CTCAE grade 2, decreased performance status, fever, sepsis, neutropenia, frank bleeding or dehydration).
TYKERB 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 diarrhea resolves to grade 1 or less. TYKERB dosing should be permanently discontinued in patients with diarrhea which is NCI CTCAE grade 4.
Severe cutaneous reactions (see 7.
WARNINGS AND PRECAUTIONS):
TYKERB should be discontinued in patients who experience severe progressive skin rash with blisters or mucosal lesions. 1 Special Populations and Conditions). Hepatic Impairment TYKERB is metabolised in the liver. Moderate and severe hepatic impairment have been associated respectively, with 56% and 85% increases in systemic exposure.
Administration of TYKERB to patients with hepatic impairment should be undertaken with caution due to increased exposure to the drug. Reduction in dose is recommended in patients with pre-existing hepatic impairment. (see 7. WARNINGS AND PRECAUTIONS, Hepatic/Biliary/pancreatic).
TYKERB dosing should be discontinued if changes in liver function are severe and patients should not be retreated. (see 7. 1 Special Populations and Conditions). There is no safety data from clinical trials on the use of TYKERB in patients with severe hepatic impairment (Child-Pugh Class C).
TYKERB should be used with caution in these patients (see 7. 1 Special Populations and Conditions). Concomitant Strong CYP3A4 Inhibitors: The concomitant use of strong CYP3A4 inhibitors should be avoided (see 7. WARNINGS AND PRECAUTIONS and 9.
DRUG INTERACTIONS). There are no clinical data recommending an appropriate dose adjustment in patients receiving strong CYP3A4 inhibitors. However, if patients must be co-administered a strong CYP3A4 inhibitor, based on pharmacokinetic studies, a dose reduction to 500 mg/day of TYKERB is predicted to adjust the lapatinib AUC to the range observed without inhibitors and should be considered.
If the strong inhibitor is discontinued, a washout period of approximately 1 week should be allowed before the lapatinib dose is adjusted upward to the indicated dose. Concomitant Strong CYP3A4 […]
1 DOSAGE AND ADMINISTRATION: Dosing Considerations, Cardiac Events and See 14. CLINICAL TRIALS). 1 Mechanism of Action). Many drugs that cause QT/QTc prolongation are suspected to increase the risk of torsade de pointes. If sustained, torsade de pointes can progress to Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Oral Tablet 250 mg lapatinib (as lapatinib ditosylate) Hypromellose, Iron oxide red, Iron oxide yellow, Macrogol/PEG 400, Magnesium stearate, Microcrystalline Cellulose, Polysorbate 80, Povidone, Sodium Starch Glycolate and Titanium Dioxide.
Product Monograph TYKERB lapatinib tablets Page 9 of 44 ventricular fibrillation and sudden cardiac death. Events of ventricular fibrillation, cardiac arrest, and sudden death have been reported with TYKERB in clinical trials. QT prolongation was observed in an uncontrolled, open-label dose escalation study of lapatinib in advanced cancer patients.
2 Pharmacodynamics). Caution should be taken if TYKERB is administered to patients who have or may develop prolongation of QTc. These conditions include patients with hypokalemia or hypomagnesemia, congenital long QT syndrome, patients taking anti-arrhythmic medicines or other medicinal products that lead to QT prolongation.
Hypokalemia, hypocalcaemia or hypomagnesemia should be corrected prior to lapatinib administration. Particular care should be exercised when administering TYKERB to patients who are suspected to be at an increased risk of experiencing torsade de pointes during treatment with a QT/QTc-prolonging drug.
, eating disorders, extreme diets); diabetes mellitus; autonomic neuropathy; hepatic dysfunction. Physicians who prescribe drugs that prolong the QT/QTc interval should counsel their patients concerning the nature and implications of the ECG changes, underlying diseases and disorders that are considered to represent risk factors, demonstrated and predicted drug-drug interactions, symptoms suggestive of arrhythmia, risk management strategies, and other information relevant to the use of the drug.
Driving and Operating Machinery There have been no studies to investigate the effect of TYKERB on driving performance or the ability to operate machinery. A detrimental effect on such activities cannot be predicted from the pharmacology of lapatinib.
The clinical status of the patient and the adverse event profile of TYKERB should be borne in mind when considering the patient's ability to perform tasks that require judgement, motor or cognitive skills. Gastrointestinal Diarrhea, including severe diarrhea, has been reported with TYKERB treatment (see 8.
ADVERSE REACTIONS). Diarrhea […]
Hypokalemia, hypocalcaemia or hypomagnesemia should be corrected prior to lapatinib administration. Particular care should be exercised when administering TYKERB to patients who are suspected to be at an increased risk of experiencing torsade de pointes during treatment with a QT/QTc-prolonging drug.
, eating disorders, extreme diets); diabetes mellitus; autonomic neuropathy; hepatic dysfunction. Physicians who prescribe drugs that prolong the QT/QTc interval should counsel their patients concerning the nature and implications of the ECG changes, underlying diseases and disorders that are considered to represent risk factors, demonstrated and predicted drug-drug interactions, symptoms suggestive of arrhythmia, risk management strategies, and other information relevant to the use of the drug.
Driving and Operating Machinery There have been no studies to investigate the effect of TYKERB on driving performance or the ability to operate machinery. A detrimental effect on such activities cannot be predicted from the pharmacology of lapatinib.
The clinical status of the patient and the adverse event profile of TYKERB should be borne in mind when considering the patient's ability to perform tasks that require judgement, motor or cognitive skills. Gastrointestinal Diarrhea, including severe diarrhea, has been reported with TYKERB treatment (see 8.
ADVERSE REACTIONS). Diarrhea may be severe, and deaths have been reported. Diarrhea generally occurs early during TYKERB treatment, with almost half of those patients with diarrhea first experiencing it within 6 days. This usually lasts 4-5 days.
TYKERB -induced diarrhea is usually low-grade, with severe diarrhea of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grades 3 and 4 occurring in <10% and <1% of patients, respectively. Early identification and intervention is critical for the optimal management of diarrhea.
g. fever, cramping pain, nausea, vomiting, dizziness and thirst) should be determined, to Product Monograph TYKERB lapatinib tablets Page 10 of 44 allow identification of changes during treatment and to help identify patients at greater risk of diarrhea.
Patients should be instructed to promptly report any change in bowel patterns immediately. Proactive management of diarrhea with anti-diarrhea agents is important. Prompt treatment after the first unformed stool is recommended with reassessment at 24 hours advised.
Severe cases of diarrhea (CTCAE grade 3 or 4, grades 1 or 2 […]