Tykerb (Lapatinib) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

Clinical Trials Experience

The safety of TYKERB has been evaluated in more than 3,500 patients in clinical trials. The efficacy and safety of TYKERB in combination with capecitabine in breast cancer was evaluated in 198 patients in a randomized, Phase 3 trial. [See Clinical Studies .] Adverse reactions which occurred in at least 10% of patients in either treatment arm and were higher in the combination arm are shown in Table 1.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most common adverse reactions (>20%) during therapy with TYKERB plus capecitabine were gastrointestinal (diarrhea, nausea, and vomiting), dermatologic (palmar-plantar erythrodysesthesia and rash), and fatigue. Diarrhea was the most common adverse reaction resulting in discontinuation of study medication.

The most common Grade 3 and 4 adverse reactions (NCI CTC v3) were diarrhea and palmar-plantar erythrodysesthesia. Selected laboratory abnormalities are shown in Table 2.

Table 1. Adverse Reactions Occurring in ≥10% of Patients

	TYKERB 1,250 mg/day + Capecitabine 2,000 mg/m2/day			Capecitabine 2,500 mg/m2/day
	(N  = 198)			(N  = 191)
	All Grades* %	Grade 3 %	Grade 4 %	All Grades* %	Grade 3 %	Grade 4 %
Reactions
Gastrointestinal disorders
Diarrhea	65	13	1	40	10	0
Nausea	44	2	0	43	2	0
Vomiting	26	2	0	21	2	0
Stomatitis	14	0	0	11	<1	0
Dyspepsia	11	<1	0	3	0	0
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia	53	12	0	51	14	0
Rash†	28	2	0	14	1	0
Dry skin	10	0	0	6	0	0
General disorders and administrative site conditions
Mucosal inflammation	15	0	0	12	2	0
Musculoskeletal and connective tissue disorders
Pain in extremity	12	1	0	7	<1	0
Back pain	11	1	0	6	<1	0
Respiratory, thoracic, and mediastinal disorders
Dyspnea	12	3	0	8	2	0
Psychiatric disorders
Insomnia	10	<1	0	6	0	0
* National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. † Grade 3 dermatitis acneiform was reported in <1% of patients in TYKERB plus capecitabine group.

Table 2. Selected Laboratory Abnormalities

	TYKERB 1,250 mg /day + Capecitabine 2,000 mg/m2/day			Capecitabine 2,500 mg/m 2/day
	All Grades* %	Grade 3 %	Grade 4 %	All Grades * %	Grade 3 %	Grade 4 %
Parameters
Hematologic
Hemoglobin	56	<1	0	53	1	0
Platelets	18	<1	0	17	<1	<1
Neutrophils	22	3	<1	31	2	1
Hepatic
Total Bilirubin	45	4	0	30	3	0
AST	49	2	<1	43	2	0
ALT	37	2	0	33	1	0
* National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.

Decreases in Left Ventricular Ejection Fraction

Due to potential cardiac toxicity with HER2 (ErbB2) inhibitors, LVEF was monitored in clinical trials at approximately 8-week intervals. LVEF decreases were defined as signs or symptoms of deterioration in left ventricular cardiac function that are ≥Grade 3 (NCI CTCAE), or a ≥20% decrease in left ventricular cardiac ejection fraction relative to baseline which is below the institution's lower limit of normal. Among 198 patients who received lapatinib/capecitabine combination treatment, 3 experienced Grade 2 and one had Grade 3 LVEF adverse reactions (NCI CTC 3.0). [See Warnings and Precautions .]

Interstitial Lung Disease/Pneumonitis

Lapatinib has been associated with interstitial lung disease and pneumonitis in monotherapy or in combination with other chemotherapies [see Warnings and Precautions].

REPORTS OF SUSPECTED TYKERB SIDE EFFECTS / ADVERSE REACTIONS

Possible Tykerb side effects / adverse reactions in 59 year old female

Reported by a consumer/non-health professional from United States on 2011-10-04

Patient: 59 year old female weighing 104.5 kg (229.9 pounds)

Reactions: Diarrhoea, Palmar-Plantar Erythrodysaesthesia Syndrome, Depression

Suspect drug(s):
Tykerb

Other drugs received by patient: Levothyroxine Sodium; Coumadin; Cymbalta; Metoprolol Tartrate; Ativan; Xeloda

Possible Tykerb side effects / adverse reactions in 35 year old female

Reported by a consumer/non-health professional from United States on 2011-10-04

Patient: 35 year old female

Reactions: Cardiopulmonary Failure

Adverse event resulted in: death

Suspect drug(s):
Tykerb

Possible Tykerb side effects / adverse reactions in 72 year old female

Reported by a consumer/non-health professional from United States on 2011-10-04

Patient: 72 year old female

Reactions: Death

Adverse event resulted in: death

Suspect drug(s):
Tykerb