Vandetanib can prolong the QT interval. Torsades de pointes and sudden death have been reported in patients receiving vandetanib. Do not use vandetanib in patients with hypocalcemia, hypokalemia, hypomagnesemia, or long QT syndrome. Correct hypocalcemia, hypokalemia, and/or hypomagnesemia prior to vandetanib administration. Monitor electrolytes periodically. Avoid drugs known to prolong the QT interval. Only health care providers and pharmacies certified with the restricted distribution program are able to prescribe and dispense vandetanib.
Note: Do not initiate treatment unless QTcF ≤450 msec. To reduce the risk of QT prolongation, maintain serum calcium and magnesium within normal limits and maintain serum potassium ≥4 mEq/L. Temporarily withhold vandetanib for at least 1 month prior to elective surgery; do not administer vandetanib for at least 2 weeks following major surgery and until adequate wound healing. Do not administer in patients with a recent history of hemoptysis with ≥2.5 mL of red blood.
Thyroid cancer, medullary, locally advanced or metastatic: Oral: 300 mg once daily, continue until disease progression or unacceptable toxicity (Wells 2012).
Missed dose: Do not administer a missed dose within 12 hours of the next dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Kidney impairment prior to treatment initiation:
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl ≥30 to <50 mL/minute: Reduce initial dose to 200 mg once daily; closely monitor QT interval.
CrCl <30 mL/minute: Use is not recommended.
End-stage renal disease requiring dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Kidney toxicity during treatment:
Kidney failure: Withhold treatment, reduce the dose, or permanently discontinue vandetanib based on severity.
Mild impairment (Child-Pugh class A): There are no dosage adjustments provided in the manufacturer's labeling.
Moderate and severe impairment (Child-Pugh class B or C): Use is not recommended.
Refer to adult dosing.
Dosage reduction: Reduce from 300 mg once daily to 200 mg once daily, further reduce if needed to 100 mg once daily. Adverse reactions (including prolonged QT interval) may not resolve fully until ~3 plasma half-lives; monitor appropriately.
Cardiac: QTcF >500 msec: Withhold dose until QTcF returns to <450 msec, then resume at a reduced dose.
Dermatologic toxicity (severe): Permanently discontinue for severe dermatologic toxicity and refer to immediate medical evaluation; may require systemic corticosteroid therapy.
Acneiform rash management: Grade 1 acneiform rash may be managed with topical corticosteroids and topical antibiotics; grade 2 may be managed with topical corticosteroids and systemic (oral) antibiotics; grade 3 or intolerable grade 2 acneiform rash may be managed with treatment interruption, topical corticosteroids, systemic (oral) antibiotics, and systemic corticosteroids (Lacouture 2014).
Diarrhea (severe): Withhold treatment until resolution. Upon improvement, resume with the dose reduced. Closely monitor electrolytes and ECGs to detect QT prolongation resulting from dehydration.
Heart failure: Consider discontinuing vandetanib.
Hemorrhage (severe): Discontinue vandetanib.
Hypertension: Initiate or adjust antihypertensive therapy as needed; may require vandetanib dosage adjustment or treatment interruption; discontinue permanently if BP cannot be adequately controlled.
Hypothyroidism (signs/symptoms): Assess thyroid hormone levels and adjust thyroid replacement therapy as indicated.
Interstitial lung disease (ILD)/pneumonitis: Interrupt therapy for acute or worsening pulmonary symptoms. Discontinue if ILD diagnosis is confirmed.
Ischemic cerebrovascular events (severe): Discontinue vandetanib (safety of resuming treatment after resolution of an ischemic event has not been studied).
Reversible posterior leukoencephalopathy syndrome: Discontinue vandetanib.
Other toxicity, grade 3 or higher: Withhold vandetanib until toxicity resolves or improves to grade 1, then resume at a reduced dose.
Recurrent toxicity: Withhold vandetanib until symptom improvement to ≤ grade 1 toxicity, then if continued treatment is warranted, reduce dose to 100 mg once daily.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Caprelsa: 100 mg, 300 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Caprelsa: 100 mg, 300 mg
In Canada, vandetanib is available only through the CAPRELSA Restricted Distribution Program. Prescribers and pharmacies must be certified with the program to prescribe or dispense vandetanib. Further information may be obtained at 1-800-589-6215 or visit www.caprelsa.ca/rdp
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022405s019lbl.pdf#page=20, must be dispensed with this medication.
Oral: May administer with or without food. Do not crush tablet. If unable to swallow tablet whole or if NG or gastrostomy tube administration is necessary, disperse tablet(s) in 2 ounces of water (noncarbonated only) and stir for 10 minutes to disperse (will not dissolve completely) and administer immediately. Rinse residue in glass with additional 4 ounces of water (noncarbonated only) and administer.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Thyroid cancer, medullary (locally advanced or metastatic): Treatment of metastatic or unresectable locally-advanced medullary thyroid cancer (symptomatic or progressive).
Limitation of use: Use in indolent, asymptomatic, or slowly progressing disease only after careful considerations of vandetanib treatment-related risks.
Vandetanib may be confused with axitinib, cabozantinib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lenvatinib, nilotinib, nintedanib, PAZOPanib, SORAfenib, SUNItinib, vemurafenib, venetoclax, vismodegib
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Hypertension (≤33%), hypertensive crisis (≤33%), prolonged QT interval on ECG (14%)
Dermatologic: Acne vulgaris (≤35%), acneiform eruption (≤35%), pruritus (11%), skin photosensitivity (13%), skin rash (53%), xeroderma (15%)
Endocrine & metabolic: Hypocalcemia (11% to 57%), hypoglycemia (24%)
Gastrointestinal: Abdominal pain (21%), colitis (≤57%), decreased appetite (21%), diarrhea (≤57%; grades 3/4: 11%), dyspepsia (11%), nausea (33%; grades 3/4: 1%), vomiting (15%; grades 3/4: 1%)
Hematologic & oncologic: Hemorrhage (14%; including major hemorrhage, life-threatening)
Hepatic: Increased serum alanine aminotransferase (51%)
Nervous system: Fatigue (24%), headache (26%)
Ophthalmic: Corneal changes (13%)
Renal: Increased serum creatinine (16%)
Respiratory: Upper respiratory tract infection (23%)
1% to 10%:
Dermatologic: Alopecia (8%), nail disease (9%)
Endocrine & metabolic: Hypomagnesemia (7%), hypothyroidism (6%)
Gastrointestinal: Dysgeusia (8%), xerostomia (9%)
Genitourinary: Proteinuria (10%)
Hematologic & oncologic: Neutropenia (10%; grades 3/4: <1%), thrombocytopenia (9%)
Nervous system: Cerebral ischemia (1%), depression (10%)
Neuromuscular & skeletal: Muscle spasm (6%)
Ophthalmic: Blurred vision (9%)
<1%:
Cardiovascular: Heart failure
Gastrointestinal: Intestinal perforation, pancreatitis
Frequency not defined:
Cardiovascular: Torsades de pointes, ventricular tachycardia
Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis
Nervous system: Asthenia, reversible posterior leukoencephalopathy syndrome
Renal: Renal failure syndrome
Respiratory: Interstitial pulmonary disease, pneumonitis
Miscellaneous: Fever
Postmarketing:
Cardiovascular: Vascular disease (arterial aneurysms [including aortic aneurysm], arterial dissections [including aortic dissection], and arterial rupture [including aortic rupture])
Miscellaneous: Wound healing impairment
Congenital long QT syndrome
Canadian labeling: Additional contraindications (not in the US labeling): Known hypersensitivity to vandetanib or any component of the formulation; persistent Fridericia-corrected QT interval (QTcF) ≥500 msec; uncorrected hypokalemia, hypomagnesemia, or hypocalcemia; uncontrolled hypertension
Concerns related to adverse effects:
• Dermatologic toxicity: Serious and sometimes fatal skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with vandetanib. Photosensitivity reactions may occur during vandetanib treatment and for up to 4 months after discontinuation; effective sunscreen and protective clothing are recommended.
• GI toxicity: Diarrhea may commonly occur; may be grade 3 or higher. Diarrhea may cause electrolyte imbalance (monitor electrolytes and ECGs closely and more frequently to detect QT prolongation resulting from dehydration).
• Heart failure: Heart failure has been reported (sometimes fatal); monitor for signs and symptoms of heart failure. Heart failure may not be reversible upon discontinuation.
• Hemorrhage: Serious and sometimes fatal hemorrhagic events have been reported with vandetanib. Do not administer in patients with a recent history of hemoptysis with ≥2.5 mL of red blood.
• Hypertension: Hypertension and hypertensive crisis have been observed with vandetanib.
• Hypothyroidism: Increased doses of thyroid replacement therapy have been required in patients receiving vandetanib with prior thyroidectomy.
• Ischemic events: Ischemic cerebrovascular events (some fatal) have been observed with vandetanib.
• Kidney toxicity: Kidney failure has occurred with vandetanib.
• Pulmonary toxicity: Interstitial lung disease (ILD) or pneumonitis (including fatalities) has been reported with vandetanib. Patients should be advised to report any new or worsening respiratory symptoms; ILD should be suspected with nonspecific respiratory symptoms such as hypoxia, pleural effusion, cough, or dyspnea.
• QT prolongation/sudden death: Vandetanib may prolong the QT interval in a concentration dependent manner; torsade de pointes and sudden death have been reported. Do not use in patients with hypocalcemia, hypokalemia, hypomagnesemia, or long QT syndrome. Correct electrolyte imbalance (hypocalcemia, hypokalemia, and/or hypomagnesemia) prior to initiating therapy. Avoid the use of QT-prolonging agents. Vandetanib has a long half-life (19 days), therefore, adverse reactions (including QT prolongation) may resolve slowly; monitor appropriately. Ventricular tachycardia has also been reported. Do not initiate in patients with QTcF >450 msec. Do not use vandetanib in patients with a history of torsade de pointes, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure. Vandetanib has not been studied in patients with ventricular arrhythmias or recent myocardial infarction. To reduce the risk of QT prolongation, maintain serum calcium and magnesium within normal limits and maintain serum potassium ≥4 mEq/L.
• Reversible posterior leukoencephalopathy syndrome: Reversible posterior leukoencephalopathy syndrome (RPLS), a syndrome of subcortical vasogenic edema (diagnosed by MRI), has been observed with vandetanib. Symptoms of RPLS include altered mental function, confusion, headache, seizure, or visual disturbances; generally associated with hypertension.
• Wound healing complications: Vascular endothelial growth factor receptor inhibitors are associated with impaired wound healing; therefore, vandetanib may affect wound healing. The safety of resuming vandetanib treatment after resolution of wound healing complications has not been established.
Other warnings/precautions:
• REMS program: Vandetanib is available only through a restricted distribution program (Caprelsa REMS); prescribers and pharmacies must be certified with the restricted distribution program to prescribe and dispense vandetanib.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits OCT2
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy
Amiodarone: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Amisulpride (Oral): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride (Oral). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even greater risk. Risk D: Consider therapy modification
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
Artesunate: Vandetanib may increase serum concentrations of the active metabolite(s) of Artesunate. Risk C: Monitor therapy
Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Bisphosphonate Derivatives: Angiogenesis Inhibitors (Systemic) may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Risk C: Monitor therapy
Carbetocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Chloroquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Citalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram. Risk X: Avoid combination
Clarithromycin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin. Risk X: Avoid combination
Clofarabine: OCT2 Inhibitors may increase the serum concentration of Clofarabine. Risk C: Monitor therapy
Clofazimine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
ClomiPRAMINE: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
CloZAPine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
CYP3A4 Inducers (Moderate): May increase serum concentrations of the active metabolite(s) of Vandetanib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vandetanib. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase serum concentrations of the active metabolite(s) of Vandetanib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib. Risk X: Avoid combination
Dabrafenib: May enhance the QTc-prolonging effect of Vandetanib. Dabrafenib may increase serum concentrations of the active metabolite(s) of Vandetanib. Dabrafenib may decrease the serum concentration of Vandetanib. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and changes in vandetanib efficacy or toxicity. Risk D: Consider therapy modification
Dalfampridine: OCT2 Inhibitors may increase the serum concentration of Dalfampridine. Management: Consider alternatives to this combination. Carefully weigh the risk of seizures against the benefit of combining OCT2 inhibitors with dalfampridine. Risk D: Consider therapy modification
Dasatinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Digoxin: Vandetanib may increase the serum concentration of Digoxin. Risk C: Monitor therapy
Dofetilide: MATE1/2-K Inhibitors may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Domperidone: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone. Risk X: Avoid combination
Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Dronedarone: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Dronedarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Droperidol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Droperidol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Entrectinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination
Escitalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Etelcalcetide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Fexinidazole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination
Fingolimod: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias (including TdP) with a continuous overnight ECG when fingolimod is combined with QT prolonging drugs. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Flecainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flecainide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Fluorouracil Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Flupentixol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol. Risk X: Avoid combination
Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Gemifloxacin: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Gemifloxacin. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Gilteritinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias. Risk D: Consider therapy modification
Halofantrine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
HydrOXYzine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk C: Monitor therapy
Imipramine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Inotuzumab Ozogamicin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Levofloxacin-Containing Products (Systemic): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Levofloxacin-Containing Products (Systemic). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Levoketoconazole: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
Lofexidine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Meglumine Antimoniate: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
MetFORMIN: MATE1/2-K Inhibitors may increase the serum concentration of MetFORMIN. Risk C: Monitor therapy
Methadone: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
Midostaurin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic). Risk X: Avoid combination
Nilotinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib. Risk X: Avoid combination
OLANZapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Ondansetron: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Osimertinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Oxytocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Pacritinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pacritinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
PAZOPanib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of PAZOPanib. Risk X: Avoid combination
Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Pilsicainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Pimozide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk X: Avoid combination
Piperaquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine. Risk X: Avoid combination
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Probucol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol. Risk X: Avoid combination
Propafenone: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Propofol: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Agents (Indeterminate Risk - Avoid): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Agents (Indeterminate Risk - Caution): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IA Antiarrhythmics (Highest Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Class III Antiarrhythmics (Highest Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of other QT-prolonging Kinase Inhibitors (Highest Risk). Risk X: Avoid combination
QT-prolonging Miscellaneous Agents (Highest Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Kinase Inhibitors (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Kinase Inhibitors (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QUEtiapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine. Risk X: Avoid combination
Ribociclib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib. Risk X: Avoid combination
RisperiDONE: QT-prolonging Agents (Highest Risk) may enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Sparfloxacin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin. Risk X: Avoid combination
St John's Wort: May decrease the serum concentration of Vandetanib. Risk X: Avoid combination
SUNItinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of SUNItinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Thioridazine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Toremifene: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Toremifene. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Vemurafenib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy
Pregnancy status should be evaluated prior to vandetanib therapy. Patients who could become pregnant should be advised to avoid pregnancy and use effective contraception during treatment and for at least 4 months after the last vandetanib dose.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to vandetanib may cause fetal harm.
Information related to the use of vandetanib in pregnant patients is limited (Thomas 2018).
It is not known if vandetanib is present in human breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy or for 4 months after the last vandetanib dose.
Monitor electrolytes (calcium, magnesium, potassium), TSH, and ECG (QT interval) at baseline, at 2 to 4 weeks, at 8 to 12 weeks, and every 3 months thereafter (more frequently if clinically indicated; monitor ECG more frequently if concomitant use with QT-prolonging agents cannot be avoided); also monitor QT interval at same frequency for dose reduction due to QT interval or treatment delays >2 weeks (monitor electrolytes and ECG more frequently if diarrhea occurs). Monitor renal function, hepatic function, and BP. Evaluate pregnancy status prior to therapy (in patients who could become pregnant). Monitor for signs and symptoms of diarrhea, heart failure, hemorrhage, hypothyroidism, reversible posterior leukoencephalopathy syndrome, pulmonary toxicity, skin toxicities, and wound healing complications. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Vandetanib is a multikinase inhibitor; it inhibits tyrosine kinases including epidermal growth factor reception (EGFR), vascular endothelial growth factor (VEGF), rearranged during transfection (RET), protein tyrosine kinase 6 (BRK), TIE2, EPH kinase receptors and SRC kinase receptors, selectively blocking intracellular signaling, angiogenesis and cellular proliferation
Absorption: Slow
Protein binding: ~90%; to albumin and alpha 1-acid-glycoprotein
Distribution: Vd: ~7450 L
Metabolism: Hepatic, via CYP3A4 to N-desmethyl vandetanib and via flavin-containing monooxygenase enzymes to vandetanib-N-oxide
Bioavailability: Not affected by food
Half-life, elimination: 19 days
Time to peak: 6 hours (range: 4 to 10 hours)
Excretion: Feces (~44%); urine (~25%)
Altered kidney function: In subjects with moderate (CrCl 30 to <50 mL/minute) and severe (CrCl <30 mL/minute) renal impairment, the average AUC of vandetanib increased by 39% and 41%, respectively.
Race/ethnicity: Patients of Japanese and Chinese ethnicity had, on average, exposures that were higher than in White patients receiving the same dose (based on limited data).
Tablets (Caprelsa Oral)
100 mg (per each): $322.46
300 mg (per each): $644.92
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