Topotecan Side Effects

Brand Names: Hycamtin

Please note - some side effects for Topotecan may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Topotecan - for the Consumer

Topotecan

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Topotecan:

Constipation; diarrhea; fatigue; hair loss; loss of appetite; nausea; stomach pain; tiredness; vomiting; weakness.

Seek medical attention right away if any of these SEVERE side effects occur when using Topotecan:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blue or unusually pale skin or nails; fever, chills, or persistent sore throat; painful or burning urination; persistent or severe cough; persistent or severe pain, redness, or swelling at the injection site; persistent or severe stomach pain or cramps; persistent or severe tiredness or weakness; shortness of breath; unusual or unexplained bruising or bleeding; yellowing of the eyes or skin.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Topotecan Capsules

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Topotecan Capsules:

Constipation; diarrhea; fatigue; hair loss; loss of appetite; nausea; stomach pain; tiredness; vomiting; weakness.

Seek medical attention right away if any of these SEVERE side effects occur when using Topotecan Capsules:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blue or unusually pale skin or nails; chest pain; fever, chills, or persistent sore throat; painful or burning urination; severe or persistent cough; severe or persistent diarrhea, stomach pain, or cramps; severe or persistent tiredness or weakness; shortness of breath; swelling or soreness of the mouth or tongue; unusual or unexplained bruising or bleeding; yellowing of the eyes or skin.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Topotecan Side Effects - for the Professional

Topotecan

Clinical Trials Experience

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.

Small Cell Lung Cancer

Data in the following section are based on the combined experiences of the 879 patients studied, including 426 patients with small cell lung cancer treated with Topotecan. Table 1 lists the principle hematologic adverse reactions and Table 2 lists non-hematologic adverse reactions occurring in at least 15% of patients.

Table 1. Hematologic Adverse Reactions Experienced in ≥15% of Patients, Including 426 Patients With Small Cell Lung Cancer, Receiving Topotecan

Hematologic Adverse Reaction	Patients (n=879) % Incidence
Neutropenia <1,500 cells/mm3 <500 cells/mm3	97 78
Leukopenia <3,000 cells/mm3 <1,000 cells/mm3	97 32
Thrombocytopenia <75,000/mm3 <25,000/mm3	69 27
Anemia <10 g/dL <8 g/dL	89 37

Table 2. Non-hematologic Adverse Reactions Experienced by ≥15% of 879 Patients, Including 426 Patients With Small Cell Lung Cancer, Receiving Topotecan

Non-hematologic Adverse Reaction	Percentage of Patients with Adverse Reaction (879 Patients)
	All Grades	Grade 3	Grade 4
Infections and infestations
Sepsis or pyrexia/infection with neutropeniaa	43	NR	23
Metabolism and nutrition disorders
Anorexia	19	2	<1
Nervous system disorders
Headache	18	1	<1
Respiratory, thoracic, and mediastinal disorders
Dyspnea	22	5	3
Coughing	15	1	0
Gastrointestinal disorders
Nausea	64	7	1
Vomiting	45	4	1
Diarrhea	32	3	1
Constipation	29	2	1
Abdominal pain	22	2	2
Stomatitis	18	1	<1
Skin and subcutaneous tissue disorders
Alopecia	49	NA	NA
Rashb	16	1	0
General disorders and administrative site conditions
Fatigue	29	5	0
Pyrexia	28	1	<1
Painc	23	2	1
Asthenia	25	4	2

NA = Not applicable

NR = Not reported separately

a Does not include Grade 1 sepsis or pyrexia

b Rash also includes pruritus, rash erythematous, urticaria, dermatitis, bullous eruption, and maculopapular rash.

c Pain includes body pain, back pain, and skeletal pain.

Nervous System Disorders

Paresthesia occurred in 7% of patients but was generally grade 1.

Hepatobiliary Disorders

Grade 1 transient elevations in hepatic enzymes occurred in 8% of patients. Greater elevations, grade 3/4, occurred in 4%. Grade 3/4 elevated bilirubin occurred in <2% of patients.

Table 3 shows the grade 3/4 hematologic and major non-hematologic adverse reactions in the Topotecan/CAV comparator trial in small cell lung cancer.

Table 3. Adverse Reactions Experienced by ≥5% of Small Cell Lung Cancer Patients Randomized to Receive Topotecan or CAV

 

Adverse Reaction	Topotecan (n=107)	CAV (n=104)
Hematologic Grade 3/4	%	%
Grade 4 neutropenia (<500 cells/mm3)	70	72
Grade 3/4 anemia (Hgb <8 g dL)	42	20
Grade 4 thrombocytopenia (<25,000 plts/mm3)	29	5
Pyrexia/Grade 4 neutropenia	28	26
Non-hematologic Grade 3/4	%	%
Infections and infestations Documented sepsisa	5	5
Respiratory, thoracic, and mediastinal disorders Dyspnea	9	14
Pneumonia	8	6
Gastrointestinal disorders Abdominal pain	6	4
Nausea	8	6
General disorders and administrative site conditions Fatigue	6	10
Asthenia	9	7
Painb	5	7

a Death related to sepsis occurred in 3% of patients receiving Topotecan, and 1% of patients receiving CAV

b Pain includes body pain, skeletal pain, and back pain.

Cervical Cancer

In the comparative trial with Topotecan Injection plus cisplatin versus cisplatin in patients with cervical cancer, the most common dose-limiting adverse reaction was myelosuppression. Table 4 shows the hematologic adverse reactions and Table 5 shows the non-hematologic adverse reactions in patients with cervical cancer.

Table 4. Hematologic Adverse Reactions in Patients with Cervical Cancer Treated with Topotecan Injection Plus Cisplatin or Cisplatin Monotherapya

Hematologic Adverse Reaction	Topotecan Injection Plus Cisplatin (n = 140)	Cisplatin (n = 144)
Anemia
All grades (Hgb <12 g/dL)	131 (94%)	130 (90%)
Grade 3 (Hgb <8 to 6.5 g/dL)	47 (34%)	28 (19%)
Grade 4 (Hgb <6.5 g/dL)	9 (6%)	5 (3%)
Leukopenia
All grades (<3,800 cells/mm3)	128 (91%)	43 (30%)
Grade 3 (<2,000 to 1,000 cells/mm3)	58 (41%)	1 (1%)
Grade 4 (<1,000 cells/mm3)	35 (25%)	0 (0%)
Neutropenia
All grades (<2,000 cells/mm3)	125 (89%)	28 (19%)
Grade 3 (<1,000 to 500 cells/mm3)	36 (26%)	1 (1%)
Grade 4 (<500 cells/mm3)	67 (48%)	1 (1%)
Thrombocytopenia
All grades (<130,000 cells/mm3)	104 (74%)	21 (15%)
Grade 3 (<50,000 to 10,000 cells/mm3)	36 (26%)	5 (3%)
Grade 4 (<10,000 cells/mm3)	10 (7%)	0 (0%)

 

a Includes patients who were eligible and treated.

Table 5. Non-hematologic Adverse Reactions Experienced by ≥5% of Patients with Cervical Cancer Treated with Topotecan Injection Plus Cisplatin or Cisplatin Monotherapya

	Topotecan Injection Plus Cisplatin			Cisplatin
	(n = 140)			(n = 144)
Adverse Reaction	All Gradesb	Grade 3	Grade 4	All Gradesb	Grade 3	Grade 4
General disorders and administrative site conditions
Constitutionalc	96 (69%)	11 (8%)	0	89 (62%)	17 (12%)	0
Paind	82 (59%)	28 (20%)	3 (2%)	72 (50%)	18 (13%)	5 (3%)
Gastrointestinal disorders
Vomiting	56 (40%)	20 (14%)	2 (1%)	53 (37%)	13 (9%)	0
Nausea	77 (55%)	18 (13%)	2 (1%)	79 (55%)	13 (9%)	0
Stomatitis-pharyngitis	8 (6%)	1 (<1%)	0	0	0	0
Other	88 (63%)	16 (11%)	4 (3%)	80 (56%)	12 (8%)	3 (2%)
Dermatology	67 (48%)	1 (<1%)	0	29 (20%)	0	0
Metabolic-Laboratory	55 (39%)	13 (9%)	7 (5%)	44 (31%)	14 (10%)	1 (<1%)
Genitourinary	51 (36%)	9 (6%)	9 (6%)	49 (34%)	7 (5%)	7 (5%)
Nervous system disorders
Neuropathy	4 (3%)	1 (<1%)	0	3 (2%)	1 (<1%)	0
Other	49 (35%)	3 (2%)	1 (<1%)	43 (30%)	7 (5%)	2 (1%)
Infection-febrile neutropenia	39 (28%)	21 (15%)	5 (4%)	26 (18%)	11 (8%)	0
Cardiovascular	35 (25%)	7 (5%)	6 (4%)	22 (15%)	8 (6%)	3 (2%)
Hepatic	34 (24%)	5 (4%)	2 (1%)	23 (16%)	2 (1%)	0
Pulmonary	24 (17%)	4 (3%)	0	23 (16%)	5 (3%)	3 (2%)
Vascular disorders
Hemorrhage	21 (15%)	8 (6%)	1 (<1%)	20 (14%)	3 (2%)	1 (<1%)
Coagulation	8 (6%)	4 (3%)	3 (2%)	10 (7%)	7 (5%)	0
Musculoskeletal	19 (14%)	3 (2%)	0	7 (5%)	1 (<1%)	1 (<1%)
Allergy-Immunology	8 (6%)	2 (1%)	1 (<1%)	4 (3%)	0	1 (<1%)
Endocrine	8 (6%)	0	0	4 (3%)	2 (1%)	0
Sexual reproduction function	7 (5%)	0	0	10 (7%)	1 (<1%)	0
Ocular-visual	7 (5%)	0	0	7 (5%)	1 (<1%)	0

Data were collected using NCI Common Toxicity Criteria, v. 2.0.

a Includes patients who were eligible and treated.

b Grades 1 through 4 only. There were 3 patients who experienced grade 5 deaths with investigator-designated attribution. One was a grade 5 hemorrhage in which the drug-related thrombocytopenia aggravated the event. A second patient experienced bowel obstruction, cardiac arrest, pleural effusion and respiratory failure which were not treatment related but probably aggravated by treatment. A third patient experienced a pulmonary embolism and adult respiratory distress syndrome, the latter was indirectly treatment-related.

c Constitutional includes fatigue (lethargy, malaise, asthenia), fever (in the absence of neutropenia), rigors, chills, sweating, and weight gain or loss.

d Pain includes abdominal pain or cramping, arthralgia, bone pain, chest pain (non-cardiac and non-pleuritic), dysmenorrhea, dyspareunia, earache, headache, hepatic pain, myalgia, neuropathic pain, pain due to radiation, pelvic pain, pleuritic pain, rectal or perirectal pain, and tumor pain.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials or listed in other sections of the prescribing information, the following reactions have been identified during post-marketing use of Topotecan Injection. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Topotecan Injection.

Blood and Lymphatic System Disorders:Severe bleeding (in association with thrombocytopenia). [see Warnings and Precautions (5.1)]

Immune System Disorders:Allergic manifestations; Anaphylactoid reactions.

Gastrointestinal Disorders:Abdominal pain potentially associated with neutropenic colitis. [see Warnings and Precautions (5.2)]

Pulmonary Disorders:Interstitial lung disease [see Warnings and Precautions (5.3)]

Skin and Subcutaneous Tissue Disorders:Angioedema, severe dermatitis, severe pruritus

General Disorders and Administration Site Conditions:Inadvertent extravasation [see Warnings and Precautions (5.5)]

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Side Effects by Body System - for Healthcare Professionals

Hematologic

Use of granulocyte colony stimulating factor (G-CSF) may be useful. Alternatively, dose reductions could be considered, especially if topotecan is used for palliative effects.

Risk of myelosuppression is increased in cases of pretreatment chemotherapy and/or radiation therapy.

Hematologic side effects have been the most profound and dose-limiting toxicity. Virtually all patients have developed neutropenia (80% to 98% less than 1,500/mm3), leukopenia (98% less than 3,000/mm3), anemia (85% to 95% less than 10 g/dL), and thrombocytopenia (44% to 63% less than 100,000/mm3). Twenty-five percent to 80% of patients developed severe pancytopenia. Nadirs have typically been observed 8 to 15 days after administration, with recovery often noted by day 21. During postmarketing use of topotecan, severe bleeding in association with thrombocytopenia has been reported.

Gastrointestinal

Gastrointestinal side effects have been reported to usually be mild to moderate in severity, observed seven to fourteen days after administration, and last for two to five days. Protracted cases of nausea, vomiting, or diarrhea have been reported infrequently. However, these data are from studies where antiemetic therapy was not routinely used, and effective antiemetic therapy is now available.

Abdominal pain potentially associated with neutropenic colitis has been reported.

Gastrointestinal side effects have been common, but rarely severe, and can usually be controlled with antiemetic therapy. Gastrointestinal side effects have included nausea (64%), vomiting (45%), diarrhea (32%), constipation (29%), abdominal pain (22%), stomatitis (18%), and anorexia (19%). Postmarketing reports of abdominal pain may potentially be associated with neutropenic colitis.

General

Pain includes body pain, back pain, an skeletal pain.

General side effects have included fatigue (29%), fever (28%), pain (23%), and asthenia (25%).

Dermatologic

Dermatologic side effects have included alopecia (49%) and rash (16%). During postmarketing use of topotecan, angioedema, severe dermatitis and severe pruritus have been reported.

Rash also includes pruritus, rash erythematous, urticaria, dermatitis, bullous eruption, and rash maculopapular.

Respiratory

Some of the reports of interstitial lung disease have been fatalities.

Respiratory side effects have included dyspnea (22%), coughing (15%), and interstitial lung disease. A case of bronchiolitis has also been reported.

Nervous system

Nervous system side effects have included headache (18%).

Musculoskeletal

Musculoskeletal side effects have included arthralgias and myalgias.

Genitourinary

Genitourinary side effects have been limited to rare cases of acute renal failure, microscopic hematuria, proteinuria, and dysuria.

Cases of acute renal failure have been associated with myelosuppression and sepsis. They are not necessarily directly caused by topotecan therapy.

Hypersensitivity

Hypersensitivity reactions have included anaphylactoid reactions, angioedema, severe dermatitis, and severe pruritus.

Local

Local side effects including erythema and bruising have resulted from inadvertent extravasation.

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