Tykerb Adverse Reactions

Clinical Trial Data: The safety of Tykerb has been evaluated as monotherapy and in combination with other chemotherapeutic agents for various cancers in >20,000 patients including 198 patients who received Tykerb in combination with capecitabine, 149 patients who received Tykerb in combination with trastuzumab, 222 patients who received Tykerb in combination with paclitaxel, 293 patients who received Tykerb in combination with paclitaxel (175 mg/m² every 3 weeks), and 654 patients who received Tykerb in combination with letrozole (see Pharmacokinetics: Clinical Studies under Pharmacology under Actions).
The following convention has been utilized for the classification of frequency: Very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and <1/1000) and very rare (<1/10,000).
Adverse Reactions with Tykerb Monotherapy: The following adverse reactions have been reported to be associated with Tykerb.
Metabolism and Nutrition Disorders: Very Common: Anorexia.
Cardiac Disorders: Common: Decreased LVEF¹ (see Dose Delay and Dose Reduction: Cardiac Events under Dosage & Administration and Precautions).
Respiratory, Thoracic and Mediastinal Disorders: Uncommon: Interstitial lung disease/pneumonitis.
Gastrointestinal Disorders: Very Common: Diarrhea², which may lead to dehydration³ (see Dose Delay and Dose Reduction: Diarrhea under Dosage & Administration and Precautions), nausea, vomiting.
Hepatobiliary Disorders: Uncommon: Hyperbilirubinemia⁴, hepatotoxicity.
Skin and Subcutaneous Tissue Disorders: Very Common: Rash² (including acneiform dermatitis) (see Dose Delay and Dose Reduction: Other Toxicities under Dosage & Administration). Common: Nail disorders including paronychia.
Immune System Disorders: Rare: Hypersensitivity reactions including anaphylaxis (see Contraindications).
General Disorders and Administration Site Conditions: Very Common: Fatigue.
¹LVEF decreases have been reported in approximately 1% of patients and were asymptomatic in >70% of cases. LVEF decreases resolved or improved in >70% of cases on discontinuation of treatment with Tykerb. Symptomatic LVEF decreases were observed in approximately 0.3% of patients who received Tykerb. Observed adverse events included dyspnea, cardiac failure and palpitations.
²Diarrhea and rash were generally low grade and did not result in discontinuation of treatment with Tykerb. Diarrhea responds well to proactive management (see Precautions). Rash was transient in the majority of cases.
³Most events of diarrhea were grade 1 or 2.
⁴Elevated bilirubin may be due to lapatinib inhibition of hepatic uptake by OATP1B1 or inhibition of excretion into bile by P-gp or BCRP.
Adverse Reactions with Tykerb in Combination with Capecitabine: In addition to the adverse reactions observed with Tykerb monotherapy, the following additional adverse reactions have been reported to be associated with Tykerb in combination with capecitabine with a frequency difference of >5% compared to capecitabine alone. These data are based on exposure to this combination in 198 patients.
Gastrointestinal Disorders: Very Common: Dyspepsia.
Skin and Subcutaneous Tissue Disorders: Very Common: Dry skin.
The following adverse reactions were reported to be associated with Tykerb in combination with capecitabine but were seen at a similar frequency in the capecitabine alone arm.
Gastrointestinal Disorders: Very Common: Stomatitis, constipation, abdominal pain.
Skin and Subcutaneous Tissue Disorders: Very Common: Palmar-plantar erythrodysaesthesia.
General Disorders and Administrative Site Conditions: Very Common: Mucosal inflammation.
Musculoskeletal and Connective Tissue Disorders: Very Common: Pain in extremity, back pain.
Nervous System Disorders: Common: Headache.
Psychiatric Disorders: Very Common: Insomnia.
Adverse Reactions with Tykerb in Combination with Trastuzumab: No additional adverse reactions were reported to be associated with Tykerb in combination with trastuzumab. There was an increased incidence of cardiac toxicity, but these events were comparable in nature and severity to those reported from the Tykerb clinical program (see Cardiac Toxicity under Precautions). These data are based on exposure to this combination in 149 patients in the pivotal trial.
Adverse Reactions with Tykerb in Combination with Paclitaxel: In addition to the adverse reactions observed with Tykerb monotherapy, the following additional adverse reactions have been reported to be associated with Tykerb in combination with paclitaxel (80 mg/m² weekly) with a frequency difference of >5% compared to paclitaxel alone. These data are based on exposure to this combination in 222 patients.
Blood and Lymphatic System Disorders: Very Common: Neutropenia, leukopenia, anemia.
Nervous System Disorders: Very Common: Peripheral neuropathy*.
Musculoskeletal and Connective Tissue Disorders: Very Common: Myalgia*.
*Additional adverse reactions reported in 293 patients on Tykerb in combination with paclitaxel (175 mg/m² every 3 weeks) with a frequency difference of >5% compared to paclitaxel alone.
Adverse Reactions with Tykerb in Combination with Letrozole: In addition to the adverse reactions observed with Tykerb monotherapy, the following additional adverse reactions have been reported to be associated with Tykerb in combination with letrozole with a frequency difference of >5% compared to letrozole alone. These data are based on exposure to this combination in 654 patients.
Respiratory, Thoracic and Mediastinal Disorders: Very Common: Epistaxis.
Skin and Subcutaneous Tissue Disorders: Very Common: Alopecia, dry skin.