Epirubicin (Epirubicin Hydrochloride) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

On-Study Events

Integrated safety data are available from two studies (Studies MA-5 and GFEA-05, see CLINICAL STUDIES) evaluating epirubicin-containing combination regimens in patients with early breast cancer. Of the 1260 patients treated in these studies, 620 patients received the higher-dose epirubicin regimen (FEC-100/CEF-120), 280 patients received the lower dose epirubicin regimen (FEC-50), and 360 patients received CMF. Serotonin-specific antiemetic therapy and colony-stimulating factors were not used in these trials. Clinically relevant acute adverse events are summarized in Table 5.

Table 5. Clinically Relevant Acute Adverse Events in Patients with Early Breast Cancer

Event	% of Patients
	FEC-100/CEF-120		FEC-50		CMF
	(N=620)		(N=280)		(N=360)
	Grades 1 to 4	Grades 3 or 4	Grades 1 to 4	Grades 3 or 4	Grades 1 to 4	Grades 3 or 4
FEC & CEF =cyclophosphamide + epirubicin + fluorouracil; CMF = cyclophosphamide + methotrexate + fluorouracil NA = not available
Hematologic
Leukopenia	80.3	58.6	49.6	1.5	98.1	60.3
Neutropenia	80.3	67.2	53.9	10.5	95.8	78.1
Anemia	72.2	5.8	12.9	0	70.9	0.9
Thrombocytopenia	48.8	5.4	4.6	0	51.4	3.6
Endocrine
Amenorrhea	71.8	0	69.3	0	67.7	0
Hot flashes	38.9	4.0	5.4	0	69.1	6.4
Body as a Whole
Lethargy	45.8	1.9	1.1	0	72.7	0.3
Fever	5.2	0	1.4	0	4.5	0
Gastrointestinal
Nausea/vomiting	92.4	25.0	83.2	22.1	85.0	6.4
Mucositis	58.5	8.9	9.3	0	52.9	1.9
Diarrhea	24.8	0.8	7.1	0	50.7	2.8
Anorexia	2.9	0	1.8	0	5.8	0.3
Infection
Infection	21.5	1.6	15.0	0	25.9	0.6
Febrile neutropenia	NA	6.1	0	0	NA	1.1
Ocular
Conjunctivitis/keratitis	14.8	0	1.1	0	38.4	0
Skin
Alopecia	95.5	56.6	69.6	19.3	84.4	6.7
Local toxicity	19.5	0.3	2.5	0.4	8.1	0
Rash/itch	8.9	0.3	1.4	0	14.2	0
Skin changes	4.7	0	0.7	0	7.2	0

Grade 1 or 2 changes in transaminase levels were observed but were more frequently seen with CMF than with CEF.

Delayed Events

Table 6 describes the incidence of delayed adverse events in patients participating in the MA-5 and GFEA-05 trials.

Table 6. Long-Term Adverse Events in Patients with Early Breast Cancer

Event	% of Patients
	FEC-100/CEF-120	FEC-50	CMF
	(N=620)	(N=280)	(N=360)
*In study MA-5 cardiac function was not monitored after 5 years.
Cardiac events
Asymptomatic drops in LVEF	2.1*	1.40.4	0.8*
CHF	1.5		0.3
Leukemia
AML	0.8	0	0.3

Two cases of acute lymphoid leukemia (ALL) were also observed in patients receiving epirubicin. However, an association between anthracyclines such as epirubicin and ALL has not been clearly established.

Overview of Acute and Delayed Toxicities

Hematologic -See WARNINGS.

Gastrointestinal. A dose-dependent mucositis (mainly oral stomatitis, less often esophagitis) may occur in patients treated with epirubicin. Clinical manifestations of mucositis may include a pain or burning sensation, erythema, erosions, ulcerations, bleeding, or infections. Mucositis generally appears early after drug administration and, if severe, may progress over a few days to mucosal ulcerations; most patients recover from this adverse event by the third week of therapy. Hyperpigmentation of the oral mucosa may also occur.

Nausea, vomiting, and occasionally diarrhea and abdominal pain can also occur. Severe vomiting and diarrhea may produce dehydration. Antiemetics may reduce nausea and vomiting; prophylactic use of antiemetics should be considered before therapy (see PRECAUTIONS).

Cutaneous and Hypersensitivity Reactions. Alopecia occurs frequently, but is usually reversible, with hair regrowth occurring within 2 to 3 months from the termination of therapy. Flushes, skin and nail hyperpigmentation, photosensitivity, and hypersensitivity to irradiated skin (radiation-recall reaction) have been observed. Urticaria and anaphylaxis have been reported in patients treated with epirubicin; signs and symptoms of these reactions may vary from skin rash and pruritus to fever, chills, and shock.

Cardiovascular -See WARNINGS.

Secondary Leukemia -See WARNINGS.

Injection-Site Reactions -See PRECAUTIONS.

REPORTS OF SUSPECTED EPIRUBICIN SIDE EFFECTS / ADVERSE REACTIONS

Possible Epirubicin side effects / adverse reactions in 18 year old female

Reported by a health professional (non-physician/pharmacist) from India on 2011-10-04

Patient: 18 year old female

Reactions: Jaundice, Enterococcal Infection, Encephalopathy, Ascites, Weight Increased, Hepatomegaly, Venoocclusive Liver Disease, Oedema Peripheral, Acute Hepatic Failure, Pleural Effusion, Gallbladder Disorder

Suspect drug(s):
Epirubicin
    Indication: Acute Lymphocytic Leukaemia

Dexamethasone
    Indication: Acute Lymphocytic Leukaemia

Vincristine
    Indication: Acute Lymphocytic Leukaemia

Asparaginase
    Indication: Acute Lymphocytic Leukaemia

Possible Epirubicin side effects / adverse reactions in 42 year old female

Reported by a health professional (non-physician/pharmacist) from Germany on 2011-10-06

Patient: 42 year old female weighing 86.0 kg (189.2 pounds)

Reactions: Intracranial Venous Sinus Thrombosis

Adverse event resulted in: life threatening event, hospitalization

Suspect drug(s):
Aranesp
    Indication: Breast Cancer
    Start date: 2007-06-14
    End date: 2007-08-24

Granisetron
    Dosage: on day 0 to 3
    Administration route: Oral
    Indication: Prophylaxis
    Start date: 2007-06-13
    End date: 2007-09-30

Taxol
    Dosage: 40 mg/m2 (09-aug-2007 to 27-sep-2007), weekly.
    Indication: Breast Cancer
    Start date: 2007-08-09
    End date: 2007-10-10

Cyclophosphamide
    Indication: Breast Cancer
    Start date: 2007-06-14
    End date: 2007-07-26

Dexamethasone
    Dosage: daily on day 1 to 4, 4mg (13-jun-2007 to 30-sep-2007).
    Indication: Prophylaxis

Ranitidine
    Dosage: 1 df= 50 units nos, once a day on day 1
    Indication: Antiallergic Therapy

Epirubicin
    Indication: Breast Cancer
    Start date: 2007-06-14
    End date: 2007-07-26

Capecitabine
    Dosage: 500 mg/m2 (09-aug-2007 to 27-sep-2007), twice daily.
    Administration route: Oral
    Indication: Breast Cancer
    Start date: 2007-08-09
    End date: 2007-10-10

Other drugs received by patient: Ibuprofen

Possible Epirubicin side effects / adverse reactions in 18 year old female

Reported by a individual with unspecified qualification from India on 2011-10-12

Patient: 18 year old female

Reactions: General Physical Health Deterioration, Encephalopathy, Ascites, Weight Increased, Hepatomegaly, Oedema Peripheral, Venoocclusive Liver Disease, Pleural Effusion, Enterococcus Test Positive, Acute Hepatic Failure, Gallbladder Disorder

Suspect drug(s):
Asparaginase (Asparaginase) (Asparaginase)
    Indication: Acute Lymphocytic Leukaemia

Dexamethasone
    Indication: Acute Lymphocytic Leukaemia

Epirubicin
    Indication: Acute Lymphocytic Leukaemia

Vincristine
    Indication: Acute Lymphocytic Leukaemia