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Hycamtin (Topotecan Hydrochloride) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Ovarian Cancer and Small Cell Lung Cancer:

Data in the following section are based on the combined experience of 453 patients with metastatic ovarian carcinoma, and 426 patients with small cell lung cancer treated with HYCAMTIN. Table 1 lists the principal 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% Ovarian Cancer and Small Cell Lung Cancer Patients Receiving HYCAMTIN

Hematologic Adverse Reaction

Patients

(n = 879)

% Incidence

Neutropenia

  <1,500 cells/mm3

97

  <500 cells/mm3

78

Leukopenia

  <3,000 cells/mm3

97

  <1,000 cells/mm3

32

Thrombocytopenia

  <75,000/mm3

69

  <25,000/mm3

27

Anemia

  <10 g/dL

89

  <8 g/dL

37

Table 2. Non-hematologic Adverse Reactions Experienced by ≥15% of Ovarian Cancer and Small Cell Lung Cancer Patients Receiving HYCAMTIN

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 neutropenia a

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/paclitaxel comparator trial in ovarian cancer.

Table 3. Adverse Reactions Experienced by ≥5% of Ovarian Cancer Patients Randomized to Receive HYCAMTIN or Paclitaxel

Adverse Reaction

HYCAMTIN

(n = 112)

Paclitaxel

(n = 114)

Hematologic Grade 3/4

%

%

Grade 4 neutropenia (<500 cells/mm3)

80

21

Grade 3/4 anemia (Hgb <8 g/dL)

41

6

Grade 4 thrombocytopenia (<25,000 plts/mm3)

27

3

Pyrexia/Grade 4 neutropenia

23

4

Non-hematologic Grade 3/4

%

%

Infections and infestations

  Documented sepsisa

5

2

Respiratory, thoracic, and mediastinal disorders

  Dyspnea

6

5

Gastrointestinal disorders

  Abdominal pain

5

4

  Constipation

5

0

  Diarrhea

6

1

  Intestinal obstruction

5

4

  Nausea

10

2

  Vomiting

10

3

General disorders and administrative site conditions

  Fatigue

7

6

  Asthenia

5

3

  Painb

5

7

a  Death related to sepsis occurred in 2% of patients receiving HYCAMTIN and 0% of patients receiving paclitaxel.

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

Table 4 shows the Grade 3/4 hematologic and major non-hematologic adverse reactions in the topotecan/CAV (cyclophosphamide‑doxorubicin‑vincristine) comparator trial in small cell lung cancer.

Table 4. Adverse Reactions Experienced by ≥5% of Small Cell Lung Cancer Patients Randomized to Receive HYCAMTIN or CAV

Adverse Reaction

HYCAMTIN

(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 HYCAMTIN, and 1% of patients receiving CAV.

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

Cervical Cancer:

In the comparative trial with HYCAMTIN plus cisplatin versus cisplatin in patients with cervical cancer, the most common dose-limiting adverse reaction was myelosuppression. Table 5 shows the hematologic adverse reactions and Table 6 shows the non-hematologic adverse reactions in patients with cervical cancer.

Table 5. Hematologic Adverse Reactions in Patients with Cervical Cancer Treated with HYCAMTIN Plus Cisplatin or Cisplatin Monotherapya

Hematologic Adverse Reaction

HYCAMTIN Plus Cisplatin

(n = 140)

Cisplatin

(n = 144)

Anemia

  All Grades (Hgb <12 g/dL)

131 (94%)

130 (90%)

  Grade 3 (Hgb <8-6.5 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 (<2,000-1,000 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 (<1,000-500 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 (<50,000-10,000 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 6. Non-hematologic Adverse Reactions Experienced by ≥5% of Patients with Cervical Cancer Treated with HYCAMTIN Plus Cisplatin or Cisplatin Monotherapya

Adverse Reaction

HYCAMTIN Plus Cisplatin

Cisplatin

(n = 140)

(n = 144)

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 postmarketing use of HYCAMTIN. 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 HYCAMTIN.

Blood and Lymphatic System Disorders:

Severe bleeding (in association with thrombocytopenia) [see Warnings and Precautions].

Immune System Disorders:

Allergic manifestations, anaphylactoid reactions.

Gastrointestinal Disorders:

Abdominal pain potentially associated with neutropenic colitis [see Warnings and Precautions].

Pulmonary Disorders:

Interstitial lung disease [see Warnings and Precautions].

Skin and Subcutaneous Tissue Disorders:

Angioedema, severe dermatitis, severe pruritus.

General Disorders and Administration Site Conditions:

Inadvertent extravasation [see Warnings and Precautions].



REPORTS OF SUSPECTED HYCAMTIN SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Hycamtin. The information is not vetted and should not be considered as verified clinical evidence.

Possible Hycamtin side effects / adverse reactions in 15 year old male

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

Patient: 15 year old male

Reactions: Death

Adverse event resulted in: death

Suspect drug(s):
Hycamtin



Possible Hycamtin side effects / adverse reactions in 63 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-07

Patient: 63 year old female

Reactions: Small Cell Lung Cancer Stage Unspecified

Adverse event resulted in: death, life threatening event, hospitalization, disablity

Suspect drug(s):
Hycamtin

Other drugs received by patient: Promethazine; Xopenex; Flexeril; Estradiol; Zofran; Nexium; Asmanex Twisthaler; Marinol; Prozac; Codeine Sulfate; Proair HFA; Hydrocodone Bitartrate



Possible Hycamtin side effects / adverse reactions in 49 year old female

Reported by a health professional (non-physician/pharmacist) from France on 2011-10-18

Patient: 49 year old female

Reactions: Thrombocytosis

Adverse event resulted in: hospitalization

Suspect drug(s):
Solu-Medrol
    Dosage: unk %, unk
    Indication: Premedication
    Start date: 2011-09-06
    End date: 2011-09-11

Emend
    Dosage: unk
    Indication: Premedication
    Start date: 2011-09-06
    End date: 2011-09-11

Plitican
    Dosage: unk
    Indication: Premedication
    Start date: 2011-09-06

Ketoprofen
    Dosage: unk
    Administration route: Oral

Cisplatin
    Dosage: unk
    Indication: Cervix Carcinoma
    Start date: 2011-09-07
    End date: 2011-09-08

Acetaminophen
    Dosage: unk
    Administration route: Oral

Hycamtin
    Dosage: unk %, unk
    Indication: Cervix Carcinoma
    Start date: 2011-09-07
    End date: 2011-09-09

Tramadol HCL
    Dosage: 100 mg, 3x/day
    Administration route: Oral
    Start date: 2011-09-06



See index of all Hycamtin side effect reports >>

Drug label data at the top of this Page last updated: 2014-03-07

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