ugs known to prolong the electrocardiogram QT interval [see Warnings and Precautions (5.11) and Drug Interactions (7.3)]. If such drugs are given to patients already receiving Vandetanib and no alternative therapy exists, ECG monitoring of the QT interval should be performed more frequently.
Patients who develop a QTcF greater than 500 ms should stop taking Vandetanib until QTcF returns to less than 450 ms. Dosing of Vandetanib can be resumed at a reduced dose [see Dosage and Administration (2.1)].
Skin Reactions and Stevens-Johnson Syndrome
Severe skin reactions (including Stevens-Johnson syndrome), some leading to death, have been reported with Vandetanib. Treatment of severe skin reactions has included systemic corticosteroids and permanent discontinuation of Vandetanib. Mild to moderate skin reactions may manifest as rash, acne, dry skin, dermatitis, pruritis and other skin reactions (including photosensitivity reactions and palmar-plantar erythrodysesthesia syndrome). Mild to moderate skin reactions have been treated with topical and systemic corticosteroids, oral antihistamines, and topical and systemic antibiotics. If CTCAE grade 3 or greater skin reactions occur, Vandetanib treatment should be stopped until improved. Upon improvement, consideration should be given to continuing treatment at a reduced dose or permanent discontinuation of Vandetanib. [see Dosage and Administration (2.1)]
Photosensitivity reactions are increased with Vandetanib. Patients should be advised to wear sunscreen and protective clothing when exposed to the sun. Due to the long half-life of Vandetanib, protective clothing and sunscreen should continue for 4 months after discontinuation of treatment.
Interstitial Lung Disease
Interstitial Lung Disease (ILD) or pneumonitis has been observed with Vandetanib and deaths have been reported. Consider a diagnosis of ILD in patients presenting with non-specific respiratory signs and symptoms such as hypoxia, pleural effusion, cough, or dyspnea, and in whom infectious, neoplastic, and other causes have been excluded by means of appropriate investigations. Advise patients to report promptly any new or worsening respiratory symptoms.
Patients who develop radiological changes suggestive of ILD and have few or no symptoms may continue Vandetanib therapy with close monitoring at the discretion of the treating physician.
If symptoms are moderate, consider interrupting therapy until symptoms improve. The use of corticosteroids and antibiotics may be indicated.
For cases where symptoms of ILD are severe, discontinue Vandetanib therapy and the use of corticosteroids and antibiotics may be indicated until clinical symptoms resolve. Even upon resolution of severe ILD, permanent discontinuation of Vandetanib should be considered.
Ischemic Cerebrovascular Events
Ischemic cerebrovascular events have been observed with Vandetanib and some cases have been fatal. In the randomized medullary thyroid cancer (MTC) study, ischemic cerebrovascular events were observed more frequently with Vandetanib compared to placebo (1.3% compared to 0%) and no deaths were reported. The safety of resumption of Vandetanib therapy after resolution of an ischemic cerebrovascular event has not been studied. Discontinue Vandetanib in patients who experience a severe ischemic cerebrovascular event.
Hemorrhage
Serious hemorrhagic events, which in some cases were fatal, have been observed with Vandeta |
