DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Vandetanib (Vandetanib) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The most commonly reported adverse drug reactions (>20%) have been diarrhea, rash, acne, nausea, hypertension, headache, fatigue, decreased appetite, and abdominal pain. The most common laboratory abnormalities (>20%) were decreased calcium, increased ALT, and decreased glucose [see Dosage and Administration and Warnings and Precautions (5.2, 5.3 and 5.9)].

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.

Clinical Studies Experience

Patients with unresectable locally advanced or metastatic medullary thyroid cancer were treated with vandetanib 300 mg (n=231) or Placebo (n= 99). Patients with investigator-determined progression or patients who continued treatment after the data cut-off could receive open label vandetanib. The following adverse reactions have been reported. [see Clinical Studies]

Table 1 - Adverse Reactions in > 10% of Patients on Vandetanib During Randomized Treatment

Preferred Term Vandetanib 300 mg N=231 Placebo N=99

All Grades

Grade 3–4

All Grades

Grade 3–4

Diarrhea/Colitis

132 (57%)

26 (11%)

27 (27%)

2 (2%)

Rash 1

123 (53%)

11 (5%)

12 (12%)

0

Dermatitis Acneiform/Acne

81 (35%)

2 (1%)

7 (7%)

0

Nausea

77 (33%)

2 (1%)

16 (16%)

0

Hypertension/Hypertensive Crisis/Accelerated Hypertension

76 (33%)

20 (9%)

5 (5%)

1 (1%)

Headache

59 (26%)

2 (1%)

9 (9%)

0

Fatigue

55 (24%)

13 (6%)

23 (23%)

1 (1%)

Decreased Appetite

49 (21%)

10 (4%)

12 (12%)

0

Abdominal Pain 2

48 (21%)

6 (3%)

11 (11%)

0

Dry Skin

35 (15%)

0 5 (5%) 0

Vomiting

34 (15%)

2 (1%)

7 (7%)

0

Asthensia

34 (15%)

6 (3%)

11 (11%)

1 (1%)

ECG QT Prolonged 3

33 (14%)

18 (8%)

1 (1%)

1 (1%)

Photosensitivity Reaction

31 (13%)

4 (2%)

0

0

Insomnia

30 (13%)

0

10 (10%)

0

Nasopharyngitis

26 (11%)

0

10 (10%)

0

Dyspepsia

25 (11%)

0

4 (4%)

0

Hypocalcemia

25 (11%)

4 (2%)

3 (3%) 0

Cough

25 (11%)

0

10 (10%)

0

Pruritus

25 (11%)

3 (1%)

4 (4%)

0

Weight Decreased

24 (10%)

2 (1%)

9 (9%)

0

Proteinuria

23 (10%)

0

2 (2%)

0

Depression

22 (10%)

4 (2%)

3 (3%)

0

1 Includes rash, rash erythematous, generalized, macular, maculo-papular, papular, pruritic, exfoliative, dermatitis, dermatitis bullous, generalized erythema and eczema.
2 Includes abdominal pain, abdominal pain upper, lower abdominal pain and abdominal discomfort
3 69% had QT prolongation >450ms and 7% had QT prolongation >500ms by ECG using Fridericia correction.

Adverse reactions resulting in death in patients receiving vandetanib (N=5) were respiratory failure, respiratory arrest, aspiration pneumonia, cardiac failure with arrhythmia, and sepsis. Adverse reactions resulting in death in patients receiving placebo were gastrointestinal hemorrhage (1%) and gastroenteritis (1%). In addition there was one sudden death and one death from cardiopulmonary arrest, in patients receiving vandetanib after data cut-off. Causes of discontinuation in vandetanib-treated patients in >1 patient included asthenia, fatigue, rash, arthralgia, diarrhea, hypertension, prolonged QT interval, increase in creatinine and pyrexia. Serious adverse events in vandetanib-treated patients in >2% of patients included diarrhea, pneumonia, and hypertension. Clinically important uncommon adverse drug reactions in patients who received vandetanib versus patients who received placebo included pancreatitis (0.4% vs. 0%) and heart failure (0.9% vs. 0%). In the integrated summary of safety database, the most common cause of death in patients who received vandetanib was pneumonia.

The incidence of Grade 1-2 bleeding events was 14% in patients receiving vandetanib compared with 7% on placebo in the randomized portion of the medullary thyroid cancer (MTC) study. The incidence was similar in the 300 mg monotherapy safety program with a 13% incidence.

Blurred vision was more common in patients who received vandetanib versus patients who received placebo for medullary thyroid cancer (9% vs. 1%, respectively). Scheduled slit lamp examinations have revealed corneal opacities (vortex keratopathies) in treated patients, which can lead to halos and decreased visual acuity. It is unknown if this will improve after discontinuation. Ophthalmologic examination, including slit lamp, is recommended in patients who report visual changes. If a patient has blurred vision, do not drive or operate machinery.

Table 2 provides the frequency and severity of laboratory abnormalities reported for patients with medullary thyroid cancer receiving randomized treatment with vandetanib or placebo.

Table 2 - Laboratory Abnormalities in Patients with MTC
Laboratory Parameter Vandetanib 300 mg Placebo N=99

All Grades

Grade 3–4

All Grades

Grade 3–4

Chemistries

Calcium Decreased

132 (57%)

13 (6%)

25 (25%)

3 (3%)

ALT Increased

118 (51%)

4 (2%)

19 (19%)

0

Glucose Decreased

55 (24%)

0

7 (7%)

1 (1%)

Creatinine Increased

38 (16%)

0

1 (1%)

0

Bilirubin Increased

29 (13%)

0

17 (17%)

0

Magnesium Decreased

17 (17%)

1 (<1%)

2 (2%)

0

Calcium Increased

16 (7%)

2 (1%)

9 (9%)

1 (1%)

Potassium Decreased

15 (6%)

1 (<1%)

3 (3%)

0

Potassium Increased

13 (6%)

1 (<1%)

4 (4%)

2 (2%)

Glucose Increased

12 (5%)

4 (2%)

7 (7%)

0

Magnesium Increased

6 (3%)

0

4 (4%)

0

Hematologic

WBC Decreased

45 (19%)

0

25 (25%)

0

Hemoglobin Decreased

31 (13%)

1 (<1%)

19 (19%)

2 (2%)

Neutrophils Decreased

21 (10%)

1 (<1%)

5 (5%)

2 (2%)

Platelets Decreased

18 (9%)

0

3 (3%)

0

Alanine aminotransferase elevations occurred in 51% of patients on vandetanib in the randomized medullary thyroid cancer (MTC) study. Grade 3-4 ALT elevations were seen in 2% of patients and no patients had a concomitant increase in bilirubin. Elevations in ALT have resulted in temporary discontinuation of vandetanib. However, 16 of 22 patients with a grade 2 elevation in ALT continued 300 mg vandetanib. Seven patients who continued vandetanib had a normal ALT within 6 months. In the protocol, ALT was monitored every 3 months and more frequently as indicated.



REPORTS OF SUSPECTED VANDETANIB SIDE EFFECTS / ADVERSE REACTIONS

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

Possible Vandetanib side effects / adverse reactions in 45 year old male

Reported by a individual with unspecified qualification from United States on 2011-10-03

Patient: 45 year old male

Reactions: Bone Neoplasm Malignant, Small Cell Lung Cancer Metastatic, Muscle Spasms

Adverse event resulted in: death

Suspect drug(s):
Vandetanib

Other drugs received by patient: Morphine Sulfate; Pink Magic; Prednisone; Lactulose; Oxycontin; Senna LAX



Possible Vandetanib side effects / adverse reactions in male

Reported by a physician from Canada on 2011-10-13

Patient: male weighing 103.8 kg (228.4 pounds)

Reactions: Photosensitivity Reaction, Skin Exfoliation, Oedema Peripheral

Suspect drug(s):
Celebrex
    Administration route: Oral
    Indication: Osteoarthritis
    Start date: 2006-01-01

Vandetanib
    Administration route: Oral
    Indication: Prostate Cancer
    Start date: 2011-03-25
    End date: 2011-04-21

Other drugs received by patient: Entrophen; Levocarbidopa; Atorvastatin; Lenoltec NO3; Temazepam; Tamsulosin HCL; Glucozamine; Atenolol; Lupron; Ectosone



Possible Vandetanib side effects / adverse reactions in female

Reported by a physician from Belgium on 2011-10-17

Patient: female

Reactions: Intestinal Perforation, Intestinal Obstruction

Adverse event resulted in: life threatening event, hospitalization

Suspect drug(s):
Vandetanib
    Administration route: Oral
    Start date: 2011-06-16
    End date: 2011-06-16

Vandetanib
    Administration route: Oral
    Indication: Thyroid Cancer
    Start date: 2011-05-21
    End date: 2011-05-27

Vandetanib
    Dosage: dose reduced
    Administration route: Oral
    Start date: 2011-06-17
    End date: 2011-07-01

Other drugs received by patient: Targinact; Laxoberon; Litican; Oxycodone HCL; Lorazepam; Closan; Polyethylene Glycol; Zometa; Imodium; Calcium Carbonate; Elthyrone; Loramet; Alpha LEO; Voltaren; Pantoprazole; Medrol; Redomex; MS Contin



See index of all Vandetanib side effect reports >>

Drug label data at the top of this Page last updated: 2011-04-13

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017