Tykerb Tablets 250 Milligrams (Lapatinib Ditosilate)

Adult dose

It is not recommended to divide the daily dose of lapatinib. Lapatinib should be taken at least 1 hour before or at least 1 hour after a meal. To minimize variability among individual patients, lapatinib administration should be standardized in relation to meals (e.g., always administer lapatinib 1 hour before a meal). If a dose is missed, do not take a double dose the following day. Continue treatment with this drug until disease progression or unacceptable toxicity occurs. In combination with capecitabine: Administer lapatinib 1,250mg (5 tablets of this drug) once daily on Days 1–21 of each 21-day cycle, together with capecitabine 2,000mg/m2/day on Days 1–14 (administered orally twice daily, approximately 12 hours apart). Administer capecitabine within 30 minutes after a meal. In combination with trastuzumab: Administer lapatinib 1,000mg (4 tablets of this drug) once daily continuously. For intravenous (IV) administration, administer a loading dose of trastuzumab 4mg/kg, followed by 2mg/kg intravenously (IV) weekly. In combination with an aromatase inhibitor: Administer lapatinib 1,500mg (6 tablets of this drug) once daily continuously. Refer to the prescribing information for each drug for the dosage and administration of the aromatase inhibitor used in combination. Cardiac-related: Treatment with this drug should be discontinued in patients with a decrease in left ventricular ejection fraction of Grade 3 or higher according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), or whose left ventricular ejection fraction falls below the lower limit of normal established by the treating institution. If left ventricular ejection fraction returns to normal and the patient has no related symptoms, treatment with this drug may be resumed at a reduced dose (750mg/day when used in combination with trastuzumab, 1,000mg/day when used in combination with capecitabine, or 1,250mg/day when used in combination with an aromatase inhibitor) after at least 2 weeks. Hepatic impairment: In patients with severe changes in liver function, treatment with this drug should be discontinued and the patient should not be rechallenged. Use with caution in patients with moderate or severe hepatic impairment because exposure to this drug may be increased. Data are insufficient to provide guidance on dose adjustment in patients with hepatic impairment. In patients with severe hepatic impairment, reducing the dose to 750mg/day (for HER2-overexpressing advanced or metastatic breast cancer) or 1000mg/day (for hormone receptor-positive, HER2-overexpressing metastatic breast cancer) is expected to result in an area under the curve (AUC) within the normal range; therefore, consider reducing the dose to these levels. However, there are no clinical data on dose adjustment to these levels in patients with severe hepatic impairment. Concomitant use with strong CYP3A4 inhibitors: Avoid concomitant use of this drug with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole). Grapefruit should also be avoided, as it may increase plasma concentrations of lapatinib. Based on pharmacokinetic studies of lapatinib, in patients who must receive a strong CYP3A4 inhibitor concomitantly, reducing the lapatinib dose to 500mg/day is expected to result in an AUC within the range observed without an inhibitor; therefore, consider reducing the dose to 500mg/day. However, there are no clinical data on dose adjustment of lapatinib to 500mg/day in patients receiving a strong CYP3A4 inhibitor. If the strong CYP3A4 inhibitor is discontinued, allow a washout period of approximately 1 week before increasing this drug to the approved dose. Concomitant use with strong CYP3A4 inducers: Avoid concomitant use of this drug with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s wort). Based on pharmacokinetic studies of lapatinib, in patients who must receive a strong CYP3A4 inducer concomitantly, the lapatinib dose should be increased stepwise, as tolerated by the patient, from 1250mg/day to 4500mg/day (for HER2-overexpressing advanced or metastatic breast cancer) or from 1500mg/day to 5500mg/day (for hormone receptor-positive, HER2-overexpressing metastatic breast cancer). Lapatinib at these doses is expected to result in an AUC within the range observed without an inducer; therefore, these doses should be considered. However, there are no clinical data on administration of lapatinib at these adjusted doses in patients receiving a strong CYP3A4 inducer. If the strong CYP3A4 inducer is discontinued, reduce lapatinib to the approved dose. Interstitial lung disease/pneumonitis: Discontinue treatment with this drug in patients with pulmonary symptoms of NCI CTCAE Grade 3 or higher. Other toxicities: In patients experiencing toxicity of Grade 2 or higher as defined by the NCI CTCAE, interruption or temporary discontinuation of treatment with this drug may be considered. If the toxicity improves to Grade 1 or lower, treatment may be resumed at a dose of 1,000mg/day when used in combination with trastuzumab, 1,250mg/day when used in combination with capecitabine, or 1,500mg/day when used in combination with an aromatase inhibitor. If toxicity recurs, resume treatment with this drug at a lower dose (750mg/day when used in combination with trastuzumab, 1,000mg/day when used in combination with capecitabine, or 1,250mg/day when used in combination with an aromatase inhibitor). For details, including dose adjustments, contraindications, and safety information for drugs used in combination with this drug, refer to the prescribing information for each drug.

This medication may cause liver damage, thus patients with impaired liver function should use it with caution. Patients who have an allergy or hypersensitivity to this medication should not use it. Patients with compromised cardiac function or those at risk of left ventricular dysfunction should be careful when administering this medication. Patients with severe liver dysfunction may require dose adjustments, and if liver function worsens further, therapy should be discontinued. Diarrhea may frequently occur while taking this medication, and if severe, immediate consultation with healthcare professionals is necessary. Regular liver function tests are required, and if liver enzymes rise significantly, the medication should be discontinued. This medication may cause pulmonary complications, so any symptoms such as shortness of breath or cough should be reported immediately. There may be cardiovascular electric abnormalities such as QT interval prolongation, necessitating electrocardiogram testing. There may be many drug interactions, so patients must inform healthcare professionals of any medications they are currently taking. Women who are pregnant or may become pregnant should avoid taking this medication and use appropriate contraception while taking it. Lactating women should avoid using this medication or should discontinue breastfeeding. Safety in pediatric patients has not been sufficiently established, and use is not recommended. In the case of overdose, immediate medical attention should be sought for appropriate treatment. This medication should be stored out of reach of children and should not be transferred to other containers.

Hepatotoxicity, hypersensitivity reactions including anaphylaxis, loss of appetite, insomnia, headache, decreased left ventricular ejection fraction, facial flushing, nasal bleeding, cough, difficulty breathing, interstitial lung disease, pneumonia, diarrhea, nausea, vomiting, dyspepsia, stomatitis, constipation, abdominal pain, hyperbilirubinemia, rash, dry skin, hand-foot syndrome, hair loss, itching, paronychia, limb pain, lumbago, arthralgia, fatigue, mucosal inflammation, asthenia, ventricular arrhythmia, Torsades de Pointes, prolonged QT on ECG, Stevens-Johnson syndrome, toxic epidermal necrolysis, skin fissures, pleural effusion, brain metastasis, malignant neoplasm of female breast, soft tissue infection, generalized edema, nausea, gastroenteritis, enterocolitis, hematemesis, melena, injection site infection, uterine bleeding, anemia, pharyngitis, pain, peripheral neuropathy, rhinitis, sputum disease, upper respiratory infection, myalgia, skin discoloration, neuropathy, skeletal pain, chest pain, peripheral edema, swelling, lymphedema, voice disorder, depression, skin disease, gastritis, disease exacerbation, sensory disturbances, urticaria, fracture, hepatic metastasis, jaundice, facial edema, peripheral neuropathy, skin depigmentation, skin ulcer, hearing loss, malnutrition, polyneuropathy, neuritis, lower motor neuron lesions, paraplegia, skin ulcer, livedo reticularis, genital pruritus, contact dermatitis, seborrheic dermatitis, fungal dermatitis, skin peeling, skin creases, muscle weakness, arthrosis, hemorrhoids, dysphagia, gastroesophageal reflux, cheilitis, gastric ulcer, rectal bleeding, anal ulcer, drowsiness, weight loss, hypercalcemia, dry eye, dehydration, agranulocytosis, leukocytosis, dysuria, frequent urination, hematuria, simplex herpes, secondary infections, galactorrhea, eye infections, keratitis, gum bleeding, purpura, unspecified bleeding, hearing loss, angina pectoris, hypothyroidism, genital infection, taste distortion, vesicular rash, hypoglycemia, cystitis, bronchial stenosis, laryngitis, tremors due to chills, abdominal enlargement, syncope, worsening condition, night sweats, hypokalemia, eating disorders

This medication should be stored in a tightly closed container to prevent exposure to air or moisture, and it is best kept in a cool place below 30 degrees Celsius. This will help maintain the medication's effectiveness for a longer period.

Appearance

Oval-shaped, yellow film-coated tablet with a convex surface on both sides

Package unit

30 tablets (30 tablets/bottle)