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Gemzar (Gemcitabine Hydrochloride) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Gemzar has been used in a wide variety of malignancies, both as a single–agent and in combination with other cytotoxic drugs.

Single–Agent Use: Myelosuppression is the principal dose–limiting toxicity with Gemzar therapy. Dosage adjustments for hematologic toxicity are frequently needed and are described in DOSAGE AND ADMINISTRATION.

The data in Table 7 are based on 979 patients receiving Gemzar as a single–agent administered weekly as a 30–minute infusion for treatment of a wide variety of malignancies. The Gemzar starting doses ranged from 800 to 1250 mg/m2. Data are also shown for the subset of patients with pancreatic cancer treated in 5 clinical studies. The frequency of all grades and severe (WHO Grade 3 or 4) adverse events were generally similar in the single–agent safety database of 979 patients and the subset of patients with pancreatic cancer. Adverse reactions reported in the single–agent safety database resulted in discontinuation of Gemzar therapy in about 10% of patients. In the comparative trial in pancreatic cancer, the discontinuation rate for adverse reactions was 14.3% for the Gemzar arm and 4.8% for the 5–FU arm.

All WHO–graded laboratory events are listed in Table 7, regardless of causality. Non–laboratory adverse events listed in Table 7 or discussed below were those reported, regardless of causality, for at least 10% of all patients, except the categories of Extravasation, Allergic, and Cardiovascular and certain specific events under the Renal, Pulmonary, and Infection categories. Table 8 presents the data from the comparative trial of Gemzar and 5–FU in pancreatic cancer for the same adverse events as those in Table 7, regardless of incidence.

Table 7: Selected WHO–Graded Adverse Events in Patients Receiving Single–Agent Gemzar WHO Grades (% incidence) 1

All Patients 2

Pancreatic Cancer
Patients 3

Discontinuations
(%) 4

All
Grades

Grade
3

Grade
4

All
Grades

Grade
3

Grade
4

All
Patients

  Laboratory 5

    Hematologic

     Anemia

68

7

1

73

8

2

<1

     Leukopenia

62

9

<1

64

8

1

<1

     Neutropenia

63

19

6

61

17

7

-

     Thrombocytopenia

24

4

1

36

7

<1

<1

    Hepatic

<1

     ALT

68

8

2

72

10

1

     AST

67

6

2

78

12

5

     Alkaline Phosphatase

55

7

2

77

16

4

     Bilirubin

13

2

<1

26

6

2

    Renal

<1

     Proteinuria

45

<1

0

32

<1

0

     Hematuria

35

<1

0

23

0

0

     BUN

16

0

0

15

0

0

     Creatinine

8

<1

0

6

0

0

  Non–laboratory 6

     Nausea and Vomiting

69

13

1

71

10

2

<1

     Pain

48

9

<1

42

6

<1

<1

     Fever

41

2

0

38

2

0

<1

     Rash

30

<1

0

28

<1

0

<1

     Dyspnea

23

3

<1

10

0

<1

<1

     Constipation

23

1

<1

31

3

<1

0

     Diarrhea

19

1

0

30

3

0

0

     Hemorrhage

17

<1

<1

4

2

<1

<1

     Infection

16

1

<1

10

2

<1

<1

     Alopecia

15

<1

0

16

0

0

0

     Stomatitis

11

<1

0

10

<1

0

<1

     Somnolence

11

<1

<1

11

2

<1

<1

     Paresthesias

10

<1

0

10

<1

0

0

1 Grade based on criteria from the World Health Organization (WHO).
2 N=699–974; all patients with laboratory or non–laboratory data.
3 N=161–241; all pancreatic cancer patients with laboratory or non–laboratory data.
4 N=979.
5 Regardless of causality.
6 Table includes non–laboratory data with incidence for all patients ≥10%. For approximately 60% of the patients, non–laboratory events were graded only if assessed to be possibly drug–related.

Table 8: Selected WHO–Graded Adverse Events From Comparative Trial of Gemzar and 5–FU in Pancreatic Cancer WHO Grades (% incidence) 1

Gemzar 2

5–FU 3

All Grades

Grade
3

Grade
4

All
Grades

Grade
3

Grade
4

  Laboratory 4

    Hematologic

     Anemia

65

7

3

45

0

0

     Leukopenia

71

10

0

15

2

0

     Neutropenia

62

19

7

18

2

3

     Thrombocytopenia

47

10

0

15

2

0

    Hepatic

     ALT

72

8

2

38

0

0

     AST

72

10

2

52

2

0

     Alkaline Phosphatase

71

16

0

64

10

3

     Bilirubin

16

2

2

25

6

3

    Renal

     Proteinuria

10

0

0

2

0

0

     Hematuria

13

0

0

0

0

0

     BUN

8

0

0

10

0

0

     Creatinine

2

0

0

0

0

0

  Non–laboratory 5

    Nausea and Vomiting

64

10

3

58

5

0

    Pain

10

2

0

7

0

0

    Fever

30

0

0

16

0

0

    Rash

24

0

0

13

0

0

    Dyspnea

6

0

0

3

0

0

    Constipation

10

3

0

11

2

0

    Diarrhea

24

2

0

31

5

0

    Hemorrhage

0

0

0

2

0

0

    Infection

8

0

0

3

2

0

    Alopecia

18

0

0

16

0

0

    Stomatitis

14

0

0

15

0

0

    Somnolence

5

2

0

7

2

0

    Paresthesias

2

0

0

2

0

0

1 Grade based on criteria from the World Health Organization (WHO).
2 N=58–63; all Gemzar patients with laboratory or non–laboratory data.
3 N=61–63; all 5–FU patients with laboratory or non–laboratory data.
4 Regardless of causality.
5 Non–laboratory events were graded only if assessed to be possibly drug–related.

Hematologic — In studies in pancreatic cancer myelosuppression is the dose–limiting toxicity with Gemzar, but <1% of patients discontinued therapy for either anemia, leukopenia, or thrombocytopenia. Red blood cell transfusions were required by 19% of patients. The incidence of sepsis was less than 1%. Petechiae or mild blood loss (hemorrhage), from any cause, was reported in 16% of patients; less than 1% of patients required platelet transfusions. Patients should be monitored for myelosuppression during Gemzar therapy and dosage modified or suspended according to the degree of hematologic toxicity (see DOSAGE AND ADMINISTRATION).

Gastrointestinal — Nausea and vomiting were commonly reported (69%) but were usually of mild to moderate severity. Severe nausea and vomiting (WHO Grade 3/4) occurred in <15% of patients. Diarrhea was reported by 19% of patients, and stomatitis by 11% of patients.

Hepatic — In clinical trials, Gemzar was associated with transient elevations of one or both serum transaminases in approximately 70% of patients, but there was no evidence of increasing hepatic toxicity with either longer duration of exposure to Gemzar or with greater total cumulative dose. Serious hepatotoxicity, including liver failure and death, has been reported very rarely in patients receiving Gemzar alone or in combination with other potentially hepatotoxic drugs (see Hepatic under Post–marketing experience).

Renal — In clinical trials, mild proteinuria and hematuria were commonly reported. Clinical findings consistent with the Hemolytic Uremic Syndrome (HUS) were reported in 6 of 2429 patients (0.25%) receiving Gemzar in clinical trials. Four patients developed HUS on Gemzar therapy, 2 immediately posttherapy. The diagnosis of HUS should be considered if the patient develops anemia with evidence of microangiopathic hemolysis, elevation of bilirubin or LDH, reticulocytosis, severe thrombocytopenia, and/or evidence of renal failure (elevation of serum creatinine or BUN). Gemzar therapy should be discontinued immediately. Renal failure may not be reversible even with discontinuation of therapy and dialysis may be required (see Renal under Post–marketing experience).

Fever — The overall incidence of fever was 41%. This is in contrast to the incidence of infection (16%) and indicates that Gemzar may cause fever in the absence of clinical infection. Fever was frequently associated with other flu–like symptoms and was usually mild and clinically manageable.

Rash — Rash was reported in 30% of patients. The rash was typically a macular or finely granular maculopapular pruritic eruption of mild to moderate severity involving the trunk and extremities. Pruritus was reported for 13% of patients.

Pulmonary — In clinical trials, dyspnea, unrelated to underlying disease, has been reported in association with Gemzar therapy. Dyspnea was occasionally accompanied by bronchospasm. Pulmonary toxicity has been reported with the use of Gemzar (see Pulmonary under Post–marketing experience). The etiology of these effects is unknown. If such effects develop, Gemzar should be discontinued. Early use of supportive care measures may help ameliorate these conditions.

Edema — Edema (13%), peripheral edema (20%), and generalized edema (<1%) were reported. Less than 1% of patients discontinued due to edema.

Flu–like Symptoms —“Flu syndrome” was reported for 19% of patients. Individual symptoms of fever, asthenia, anorexia, headache, cough, chills, and myalgia were commonly reported. Fever and asthenia were also reported frequently as isolated symptoms. Insomnia, rhinitis, sweating, and malaise were reported infrequently. Less than 1% of patients discontinued due to flu–like symptoms.

Infection — Infections were reported for 16% of patients. Sepsis was rarely reported (<1%).

Alopecia — Hair loss, usually minimal, was reported by 15% of patients.

Neurotoxicity — There was a 10% incidence of mild paresthesias and a <1% rate of severe paresthesias.

Extravasation — Injection–site related events were reported for 4% of patients. There were no reports of injection site necrosis. Gemzar is not a vesicant.

Allergic — Bronchospasm was reported for less than 2% of patients. Anaphylactoid reaction has been reported rarely. Gemzar should not be administered to patients with a known hypersensitivity to this drug (see CONTRAINDICATION).

Cardiovascular — During clinical trials, 2% of patients discontinued therapy with Gemzar due to cardiovascular events such as myocardial infarction, cerebrovascular accident, arrhythmia, and hypertension. Many of these patients had a prior history of cardiovascular disease (see Cardiovascular under Post–marketing experience).

Combination Use in Non–Small Cell Lung Cancer: In the Gemzar plus cisplatin versus cisplatin study, dose adjustments occurred with 35% of Gemzar injections and 17% of cisplatin injections on the combination arm, versus 6% on the cisplatin–only arm. Dose adjustments were required in greater than 90% of patients on the combination, versus 16% on cisplatin. Study discontinuations for possibly drug–related adverse events occurred in 15% of patients on the combination arm and 8% of patients on the cisplatin arm. With a median of 4 cycles of Gemzar plus cisplatin treatment, 94 of 262 patients (36%) experienced a total of 149 hospitalizations due to possibly treatment–related adverse events. With a median of 2 cycles of cisplatin treatment, 61 of 260 patients (23%) experienced 78 hospitalizations due to possibly treatment–related adverse events.

In the Gemzar plus cisplatin versus etoposide plus cisplatin study, dose adjustments occurred with 20% of Gemzar injections and 16% of cisplatin injections in the Gemzar plus cisplatin arm compared with 20% of etoposide injections and 15% of cisplatin injections in the etoposide plus cisplatin arm. With a median of 5 cycles of Gemzar plus cisplatin treatment, 15 of 69 patients (22%) experienced 15 hospitalizations due to possibly treatment–related adverse events. With a median of 4 cycles of etoposide plus cisplatin treatment, 18 of 66 patients (27%) experienced 22 hospitalizations due to possibly treatment–related adverse events. In patients who completed more than one cycle, dose adjustments were reported in 81% of the Gemzar plus cisplatin patients, compared with 68% on the etoposide plus cisplatin arm. Study discontinuations for possibly drug–related adverse events occurred in 14% of patients on the Gemzar plus cisplatin arm and in 8% of patients on the etoposide plus cisplatin arm. The incidence of myelosuppression was increased in frequency with Gemzar plus cisplatin treatment (~90%) compared to that with the Gemzar monotherapy (~60%). With combination therapy Gemzar dosage adjustments for hematologic toxicity were required more often while cisplatin dose adjustments were less frequently required.

Table 9 presents the safety data from the Gemzar plus cisplatin versus cisplatin study in non–small cell lung cancer. The NCI Common Toxicity Criteria (CTC) were used. The two–drug combination was more myelosuppressive with 4 (1.5%) possibly treatment–related deaths, including 3 resulting from myelosuppression with infection and one case of renal failure associated with pancytopenia and infection. No deaths due to treatment were reported on the cisplatin arm. Nine cases of febrile neutropenia were reported on the combination therapy arm compared to 2 on the cisplatin arm. More patients required RBC and platelet transfusions on the Gemzar plus cisplatin arm.

Myelosuppression occurred more frequently on the combination arm, and in 4 possibly treatment–related deaths myelosuppression was observed. Sepsis was reported in 4% of patients on the Gemzar plus cisplatin arm compared to 1% on the cisplatin arm. Platelet transfusions were required in 21% of patients on the combination arm and <1% of patients on the cisplatin arm. Hemorrhagic events occurred in 14% of patients on the combination arm and 4% on the cisplatin arm. However, severe hemorrhagic events were rare. Red blood cell transfusions were required in 39% of the patients on the Gemzar plus cisplatin arm, versus 13% on the cisplatin arm. The data suggest cumulative anemia with continued Gemzar plus cisplatin use.

Nausea and vomiting despite the use of antiemetics occurred slightly more often with Gemzar plus cisplatin therapy (78%) than with cisplatin alone (71%). In studies with single–agent Gemzar, a lower incidence of nausea and vomiting (58% to 69%) was reported. Renal function abnormalities, hypomagnesemia, neuromotor, neurocortical, and neurocerebellar toxicity occurred more often with Gemzar plus cisplatin than with cisplatin monotherapy. Neurohearing toxicity was similar on both arms.

Cardiac dysrrhythmias of Grade 3 or greater were reported in 7 (3%) patients treated with Gemzar plus cisplatin compared to one (<1%) Grade 3 dysrrhythmia reported with cisplatin therapy. Hypomagnesemia and hypokalemia were associated with one Grade 4 arrhythmia on the Gemzar plus cisplatin combination arm.

Table 10 presents data from the randomized study of Gemzar plus cisplatin versus etoposide plus cisplatin in 135 patients with NSCLC for the same WHO–graded adverse events as those in Table 8. One death (1.5%) was reported on the Gemzar plus cisplatin arm due to febrile neutropenia associated with renal failure which was possibly treatment–related. No deaths related to treatment occurred on the etoposide plus cisplatin arm. The overall incidence of Grade 4 neutropenia on the Gemzar plus cisplatin arm was less than on the etoposide plus cisplatin arm (28% versus 56%). Sepsis was experienced by 2% of patients on both treatment arms. Grade 3 anemia and Grade 3/4 thrombocytopenia were more common on the Gemzar plus cisplatin arm. RBC transfusions were given to 29% of the patients who received Gemzar plus cisplatin versus 21% of patients who received etoposide plus cisplatin. Platelet transfusions were given to 3% of the patients who received Gemzar plus cisplatin versus 8% of patients who received etoposide plus cisplatin. Grade 3/4 nausea and vomiting were also more common on the Gemzar plus cisplatin arm. On the Gemzar plus cisplatin arm, 7% of participants were hospitalized due to febrile neutropenia compared to 12% on the etoposide plus cisplatin arm. More than twice as many patients had dose reductions or omissions of a scheduled dose of Gemzar as compared to etoposide, which may explain the differences in the incidence of neutropenia and febrile neutropenia between treatment arms. Flu syndrome was reported by 3% of patients on the Gemzar plus cisplatin arm with none reported on the comparator arm. Eight patients (12%) on the Gemzar plus cisplatin arm reported edema compared to one patient (2%) on the etoposide plus cisplatin arm.

Table 9: Selected CTC–Graded Adverse Events From Comparative Trial of Gemzar Plus Cisplatin Versus Single–Agent Cisplatin in NSCLC CTC Grades (% incidence) 1

Gemzar plus Cisplatin 2

Cisplatin 3

All Grades

Grade
3

Grade
4

All Grades

Grade
3

Grade
4

  Laboratory 4

    Hematologic

     Anemia

89

22

3

67

6

1

     RBC Transfusion 5

39

13

     Leukopenia

82

35

11

25

2

1

     Neutropenia

79

22

35

20

3

1

     Thrombocytopenia

85

25

25

13

3

1

     Platelet Transfusions

21

<1

     Lymphocytes

75

25

18

51

12

5

    Hepatic

     Transaminase

22

2

1

10

1

0

     Alkaline Phosphatase

19

1

0

13

0

0

    Renal

     Proteinuria

23

0

0

18

0

0

     Hematuria

15

0

0

13

0

0

     Creatinine

38

4

<1

31

2

<1

    Other Laboratory

     Hyperglycemia

30

4

0

23

3

0

     Hypomagnesemia

30

4

3

17

2

0

     Hypocalcemia

18

2

0

7

0

<1

  Non–laboratory 6

    Nausea

93

25

2

87

20

<1

    Vomiting

78

11

12

71

10

9

    Alopecia

53

1

0

33

0

0

    Neuro Motor

35

12

0

15

3

0

    Constipation

28

3

0

21

0

0

    Neuro Hearing

25

6

0

21

6

0

    Diarrhea

24

2

2

13

0

0

    Neuro Sensory

23

1

0

18

1

0

    Infection

18

3

2

12

1

0

    Fever

16

0

0

5

0

0

    Neuro Cortical

16

3

1

9

1

0

    Neuro Mood

16

1

0

10

1

0

    Local

15

0

0

6

0

0

    Neuro Headache

14

0

0

7

0

0

    Stomatitis

14

1

0

5

0

0

    Hemorrhage

14

1

0

4

0

0

    Dyspnea

12

4

3

11

3

2

    Hypotension

12

1

0

7

1

0

    Rash

11

0

0

3

0

0

1 Grade based on Common Toxicity Criteria (CTC). Table includes data for adverse events with incidence ≥10% in either arm.
2 N=217–253; all Gemzar plus cisplatin patients with laboratory or non–laboratory data. Gemzar at 1000 mg/m2 on Days 1, 8, and 15 and cisplatin at 100 mg/m2 on Day 1 every 28 days.
3 N=213–248; all cisplatin patients with laboratory or non–laboratory data. Cisplatin at 100 mg/m2 on Day 1 every 28 days.
4 Regardless of causality.
5 Percent of patients receiving transfusions. Percent transfusions are not CTC–graded events.
6 Non–laboratory events were graded only if assessed to be possibly drug–related.

Table 10: Selected WHO–Graded Adverse Events From Comparative Trial of Gemzar Plus Cisplatin Versus Etoposide Plus Cisplatin in NSCLC WHO Grades (% incidence) 1

Gemzar plus Cisplatin 2

Etoposide plus Cisplatin 3

All Grades

Grade
3

Grade
4

All Grades

Grade
3

Grade
4

  Laboratory 4

    Hematologic

     Anemia

88

22

0

77

13

2

     RBC Transfusions 5

29

21

     Leukopenia

86

26

3

87

36

7

     Neutropenia

88

36

28

87

20

56

     Thrombocytopenia

81

39

16

45

8

5

     Platelet Transfusions

3

8

    Hepatic

     ALT

6

0

0

12

0

0

     AST

3

0

0

11

0

0

     Alkaline Phosphatase

16

0

0

11

0

0

     Bilirubin

0

0

0

0

0

0

    Renal

     Proteinuria

12

0

0

5

0

0

     Hematuria

22

0

0

10

0

0

     BUN

6

0

0

4

0

0

     Creatinine

2

0

0

2

0

0

  Non–laboratory 6 , 7

    Nausea and Vomiting

96

35

4

86

19

7

    Fever

6

0

0

3

0

0

    Rash

10

0

0

3

0

0

    Dyspnea

1

0

1

3

0

0

    Constipation

17

0

0

15

0

0

    Diarrhea

14

1

1

13

0

2

    Hemorrhage

9

0

3

3

0

3

    Infection

28

3

1

21

8

0

    Alopecia

77

13

0

92

51

0

    Stomatitis

20

4

0

18

2

0

    Somnolence

3

0

0

3

2

0

    Paresthesias

38

0

0

16

2

0

1 Grade based on criteria from the World Health Organization (WHO).
2 N=67–69; all Gemzar plus cisplatin patients with laboratory or non–laboratory data. Gemzar at 1250 mg/m2 on Days 1 and 8 and cisplatin at 100 mg/m2 on Day 1 every 21 days.
3 N=57–63; all cisplatin plus etoposide patients with laboratory or non–laboratory data. Cisplatin at 100 mg/m2 on Day 1 and IV etoposide at 100 mg/m2 on Days 1, 2, and 3 every 21 days.
4 Regardless of causality.
5 Percent of patients receiving transfusions. Percent transfusions are not WHO–graded events.
6 Non–laboratory events were graded only if assessed to be possibly drug–related.
7 Pain data were not collected.

Combination Use in Breast Cancer: In the Gemzar plus paclitaxel versus paclitaxel study, dose reductions occurred with 8% of Gemzar injections and 5% of paclitaxel injections on the combination arm, versus 2% on the paclitaxel arm. On the combination arm, 7% of Gemzar doses were omitted and <1% of paclitaxel doses were omitted, compared to <1% of paclitaxel doses on the paclitaxel arm. A total of 18 patients (7%) on the Gemzar plus paclitaxel arm and 12 (5%) on the paclitaxel arm discontinued the study because of adverse events. There were two deaths on study or within 30 days after study drug discontinuation that were possibly drug–related, one on each arm.

Table 11 presents the safety data occurrences of ≥10% (all grades) from the Gemzar plus paclitaxel versus paclitaxel study in breast cancer.

Table 11: Adverse Events From Comparative Trial of Gemzar Plus Paclitaxel Versus Single–Agent Paclitaxel in Breast Cancer 1  CTC Grades (% incidence)

Gemzar plus Paclitaxel
(N=262)

Paclitaxel
(N=259)

All Grades

Grade
3

Grade
4

All Grades

Grade
3

Grade
4

  Laboratory 2

    Hematologic

     Anemia

69

6

1

51

3

<1

     Neutropenia

69

31

17

31

4

7

     Thrombocytopenia

26

5

<1

7

<1

<1

     Leukopenia

21

10

1

12

2

0

    Hepatobiliary

     ALT

18

5

<1

6

<1

0

     AST

16

2

0

5

<1

0

  Non–laboratory 3

    Alopecia

90

14

4

92

19

3

    Neuropathy–sensory

64

5

<1

58

3

0

    Nausea

50

1

0

31

2

0

    Fatigue

40

6

<1

28

1

<1

    Myalgia

33

4

0

33

3

<1

    Vomiting

29

2

0

15

2

0

    Arthralgia

24

3

0

22

2

<1

    Diarrhea

20

3

0

13

2

0

    Anorexia

17

0

0

12

<1

0

    Neuropathy–motor

15

2

<1

10

<1

0

    Stomatitis/pharyngitis

13

1

<1

8

<1

0

    Fever

13

<1

0

3

0

0

    Constipation

11

<1

0

12

0

0

    Bone pain

11

2

0

10

<1

0

    Pain–other

11

<1

0

8

<1

0

    Rash/desquamation

11

<1

<1

5

0

0

1 Grade based on Common Toxicity Criteria (CTC) Version 2.0 (all grades ≥10%).
2 Regardless of causality.
3 Non–laboratory events were graded only if assessed to be possibly drug–related.

The following are the clinically relevant adverse events that occurred in >1% and <10% (all grades) of patients on either arm. In parentheses are the incidences of Grade 3 and 4 adverse events (Gemzar plus paclitaxel versus paclitaxel): febrile neutropenia (5.0% versus 1.2%), infection (0.8% versus 0.8%), dyspnea (1.9% versus 0), and allergic reaction/hypersensitivity (0 versus 0.8%).

No differences in the incidence of laboratory and non–laboratory events were observed in patients 65 years or older, as compared to patients younger than 65.

Combination Use in Ovarian Cancer: In the Gemzar plus carboplatin versus carboplatin study, dose reductions occurred with 10.4% of Gemzar injections and 1.8% of carboplatin injections on the combination arm, versus 3.8% on the carboplatin alone arm. On the combination arm, 13.7% of Gemzar doses were omitted and 0.2% of carboplatin doses were omitted, compared to 0% of carboplatin doses on the carboplatin alone arm. There were no differences in discontinuations due to adverse events between arms (10.9% versus 9.8%, respectively).

Table 12 presents the adverse events (all grades) occurring in ≥10% of patients in the ovarian cancer study.

Table 12: Adverse Events From Comparative Trial of Gemzar Plus Carboplatin Versus Single–Agent Carboplatin in Ovarian Cancer 1  CTC Grades (% incidence)

Gemzar plus Carboplatin

(N=175)

Carboplatin

(N=174)

All Grades

Grade 3

Grade 4

All Grades

Grade 3

Grade 4

  Laboratory 2

  Hematologic

   Neutropenia

90

42

29

58

11

1

   Anemia

86

22

6

75

9

2

   Leukopenia

86

48

5

70

6

<1

   Thrombocytopenia

78

30

5

57

10

1

   RBC Transfusions 3

38

15

   Platelet Transfusions

9

3

  Non–laboratory

  Nausea

69

6

0

61

3

0

  Alopecia

49

0

0

17

0

0

  Vomiting

46

6

0

36

2

<1

  Constipation

42

6

1

37

3

0

  Fatigue

40

3

<1

32

5

0

  Neuropathy–sensory

29

1

0

27

2

0

  Diarrhea

25

3

0

14

<1

0

  Stomatitis/pharyngitis

22

<1

0

13

0

0

  Anorexia

16

1

0

13

0

0

1 Grade based on Common Toxicity Criteria (CTC) Version 2.0 (all grades ≥10%).
2 Regardless of causality.
3 Percent of patients receiving transfusions. Transfusions are not CTC–graded events. Blood transfusions included both packed red blood cells and whole blood.

In addition to blood product transfusions as listed in Table 12, myelosuppression was also managed with hematopoetic agents. These agents were administered more frequently with combination therapy than with monotherapy (granulocyte growth factors: 23.6% and 10.1%, respectively; erythropoetic agents: 7.3% and 3.9%, respectively).

The following are the clinically relevant adverse events, regardless of causality, that occurred in >1% and <10% (all grades) of patients on either arm. In parentheses are the incidences of Grade 3 and 4 adverse events (Gemzar plus carboplatin versus carboplatin): AST or ALT elevation (0 versus 1.2%), dyspnea (3.4% versus 2.9%), febrile neutropenia (1.1% versus 0), hemorrhagic event (2.3% versus 1.1%), hypersensitivity reaction (2.3% versus 2.9%), motor neuropathy (1.1% versus 0.6%), and rash/desquamation (0.6% versus 0).

No differences in the incidence of laboratory and non–laboratory events were observed in patients 65 years or older, as compared to patients younger than 65.

Post–marketing experience: The following adverse events have been identified during post–approval use of Gemzar. These events have occurred after Gemzar single–agent use and Gemzar in combination with other cytotoxic agents. Decisions to include these events are based on the seriousness of the event, frequency of reporting, or potential causal connection to Gemzar.

Cardiovascular — Congestive heart failure and myocardial infarction have been reported very rarely with the use of Gemzar. Arrhythmias, predominantly supraventricular in nature, have been reported very rarely.

Vascular Disorders — Clinical signs of peripheral vasculitis and gangrene have been reported very rarely.

Skin — Cellulitis and non–serious injection site reactions in the absence of extravasation have been rarely reported. Severe skin reactions, including desquamation and bullous skin eruptions, have been reported very rarely.

Hepatic — Increased liver function tests including elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma–glutamyl transferase (GGT), alkaline phosphatase, and bilirubin levels have been reported rarely. Serious hepatotoxicity including liver failure and death has been reported very rarely in patients receiving Gemzar alone or in combination with other potentially hepatotoxic drugs.

Pulmonary — Parenchymal toxicity, including interstitial pneumonitis, pulmonary fibrosis, pulmonary edema, and adult respiratory distress syndrome (ARDS), has been reported rarely following one or more doses of Gemzar administered to patients with various malignancies. Some patients experienced the onset of pulmonary symptoms up to 2 weeks after the last Gemzar dose. Respiratory failure and death occurred very rarely in some patients despite discontinuation of therapy.

Renal — Hemolytic–Uremic Syndrome (HUS) and/or renal failure have been reported following one or more doses of Gemzar. Renal failure leading to death or requiring dialysis, despite discontinuation of therapy, has been rarely reported. The majority of the cases of renal failure leading to death were due to HUS.

Injury, Poisoning, and Procedural Complications — Radiation recall reactions have been reported (see Radiation Therapy under PRECAUTIONS).



REPORTS OF SUSPECTED GEMZAR SIDE EFFECTS / ADVERSE REACTIONS

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

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

Reported by a physician from Colombia on 2011-10-03

Patient: 72 year old female

Reactions: Neoplasm Progression

Adverse event resulted in: death

Suspect drug(s):
Gemzar

Other drugs received by patient: Cisplatin



Possible Gemzar side effects / adverse reactions in 47 year old female

Reported by a physician from Greece on 2011-10-04

Patient: 47 year old female weighing 69.0 kg (151.8 pounds)

Reactions: Constipation

Adverse event resulted in: hospitalization

Suspect drug(s):
Gemzar
    Dosage: 800 mg, every 2 weeks
    Indication: Pancreatic Carcinoma Metastatic
    Start date: 2011-06-07

Temsirolimus
    Dosage: 25 mg, weekly
    Indication: Pancreatic Carcinoma Recurrent
    Start date: 2011-06-07

Other drugs received by patient: Dexamethasone; Zantac; Zofron; Primperan TAB; Fenistil; Cilroton; Laprazol



Possible Gemzar side effects / adverse reactions in 72 year old male

Reported by a consumer/non-health professional from United States on 2011-10-06

Patient: 72 year old male weighing 71.0 kg (156.2 pounds)

Reactions: Dyspnoea, Chest Pain, Acute Myocardial Infarction, Paraesthesia

Adverse event resulted in: hospitalization

Suspect drug(s):
Erbitux
    Dosage: drug interrupted on 12nov2010(57dy)no of infisions:7 held on:18nov10,resumed on 3dec10
    Indication: non-Small Cell Lung Cancer
    Start date: 2010-09-17

Carboplatin
    Dosage: drug interrupted on 12nov2010(57dy).no of infisions:3 held on:18nov10
    Indication: non-Small Cell Lung Cancer
    Start date: 2010-09-17

Gemzar
    Dosage: drug interrupted on 12nov2010(57dy)no of infisions:5 held on:18nov10,resumed on 3dec10
    Indication: non-Small Cell Lung Cancer
    Start date: 2010-09-17

Other drugs received by patient: Coumadin; Enalapril Maleate; Amiodarone HCL; Lipitor; Esomeprazole Sodium; Plavix; Tamsulosin HCL; Budesonide; Amlodipine; Simvastatin; Nexium; Magnesium; Fluticasone Propionate; Salmeterol Xinafoate; Formoterol Fumarate; Digoxin; Atorvastatin; Furosemide; Advair Diskus 100/50; Symbicort; Lisinopril; Atenolol



See index of all Gemzar side effect reports >>

Drug label data at the top of this Page last updated: 2008-07-11

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