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Vandetanib: Drug information

Vandetanib: Drug information
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For additional information see "Vandetanib: Patient drug information"

For abbreviations, symbols, and age group definitions show table
ALERT: US Boxed Warning
QT prolongation, torsades de pointes, and sudden death:

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.

Brand Names: US
  • Caprelsa
Brand Names: Canada
  • Caprelsa
Pharmacologic Category
  • Antineoplastic Agent, Epidermal Growth Factor Receptor (EGFR) Inhibitor;
  • Antineoplastic Agent, Tyrosine Kinase Inhibitor;
  • Antineoplastic Agent, Vascular Endothelial Growth Factor (VEGF) Inhibitor
Dosing: Adult

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

Thyroid cancer, medullary, locally advanced or metastatic: Oral: 300 mg once daily, continue until disease progression or unacceptable toxicity (Ref).

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.

Dosing: Kidney Impairment: Adult

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.

Dosing: Liver Impairment: Adult

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.

Dosing: Adjustment for Toxicity: Adult

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 (Ref).

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.

If indicated, initiate appropriate antihypertensive therapy to reduce the risk for cardiovascular complications (Ref). If vandetanib is discontinued, a drop in BP is expected and antihypertensive therapy should be reduced and/or interrupted as clinically appropriate (Ref).

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.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

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

Contraindications

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.

Warnings/Precautions

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.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Caprelsa: 100 mg, 300 mg

Generic Equivalent Available: US

No

Pricing: US

Tablets (Caprelsa Oral)

100 mg (per each): $354.93

300 mg (per each): $709.86

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Caprelsa: 100 mg, 300 mg

Prescribing and Access Restrictions

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

Administration: Adult

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 Drugs Handling Considerations

Hazardous agent (NIOSH 2024 [table 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 2023; NIOSH 2024; USP-NF 2020).

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/022405s022lbl.pdf#page=21, must be dispensed with this medication.

Use: Labeled Indications

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.

Medication Safety Issues
Sound-alike/look-alike issues:

Vandetanib may be confused with axitinib, cabozantinib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lenvatinib, nilotinib, nintedanib, PAZOPanib, SORAfenib, SUNItinib, vemurafenib, venetoclax, vismodegib

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Metabolism/Transport Effects

Substrate of CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits MATE1/2-K, OCT2;

Drug Interactions

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 drug interactions program by clicking on the “Launch drug interactions program” link above.

Aminolevulinic Acid (Systemic): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Systemic). Risk X: Avoid

Aminolevulinic Acid (Topical): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Topical). Risk C: Monitor

Amiodarone: QT-prolonging Kinase Inhibitors (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase hypertensive effects of Androgens. Risk C: Monitor

Artesunate: Vandetanib may increase active metabolite exposure of Artesunate. Risk C: Monitor

Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase adverse/toxic effects of Bisphosphonate Derivatives. Specifically, the risk for osteonecrosis of the jaw may be increased. Risk C: Monitor

Carbetocin: May increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of Citalopram. Risk X: Avoid

Clarithromycin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Clarithromycin. Risk X: Avoid

Clofarabine: OCT2 Inhibitors may increase serum concentration of Clofarabine. Risk C: Monitor

Clofazimine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 active metabolite exposure of Vandetanib. CYP3A4 Inducers (Moderate) may decrease serum concentration of Vandetanib. Risk C: Monitor

CYP3A4 Inducers (Strong): May decrease serum concentration of Vandetanib. CYP3A4 Inducers (Strong) may increase active metabolite exposure of Vandetanib. Risk X: Avoid

Dabrafenib: May increase QTc-prolonging effects of Vandetanib. Dabrafenib may decrease serum concentration of Vandetanib. Dabrafenib may increase active metabolite exposure 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 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 increase QTc-prolonging effects 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 serum concentration of Digoxin. Risk C: Monitor

Dofetilide: MATE1/2-K Inhibitors may increase serum concentration of Dofetilide. Risk X: Avoid

Domperidone: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Domperidone. Risk X: Avoid

Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of Vandetanib. Encorafenib may decrease serum concentration of Vandetanib. Encorafenib may increase active metabolite exposure of Vandetanib. Risk X: Avoid

Entrectinib: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid

Escitalopram: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid

Fingolimod: May increase QTc-prolonging effects 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

Flecainide: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of Flupentixol. Risk X: Avoid

Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk C: Monitor

Imipramine: May increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of Levoketoconazole. Risk X: Avoid

Lofexidine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 serum concentration of MetFORMIN. Risk C: Monitor

Methadone: QT-prolonging Kinase Inhibitors (Highest Risk) may increase QTc-prolonging effects 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 increase photosensitizing effects of Methoxsalen (Systemic). Risk C: Monitor

Midostaurin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects of Moxifloxacin (Systemic). Risk X: Avoid

Nilotinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Nilotinib. Risk X: Avoid

OLANZapine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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

PAZOPanib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of PAZOPanib. Risk X: Avoid

Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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

Piperaquine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Piperaquine. Risk X: Avoid

Porfimer: Photosensitizing Agents may increase photosensitizing effects of Porfimer. Risk X: Avoid

Probucol: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Probucol. Risk X: Avoid

Propafenone: May increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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

QT-prolonging Agents (Indeterminate Risk - Caution): May increase QTc-prolonging effects 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

QT-prolonging Class IA Antiarrhythmics (Highest Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Highest Risk). Risk X: Avoid

QT-prolonging Miscellaneous Agents (Highest Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase 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 increase QTc-prolonging effects of QUEtiapine. Risk X: Avoid

Quizartinib: May increase QTc-prolonging effects 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

Ribociclib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Ribociclib. Risk X: Avoid

RisperiDONE: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of RisperiDONE. QT-prolonging Agents (Highest Risk) may increase CNS depressant effects 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 increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid

Solriamfetol: May increase hypertensive effects of Hypertension-Associated Agents. Risk C: Monitor

Sparfloxacin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Sparfloxacin. Risk X: Avoid

St John's Wort: May decrease serum concentration of Vandetanib. Risk X: Avoid

SUNItinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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

Terbutaline: May increase QTc-prolonging effects 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

Thioridazine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Thioridazine. Risk X: Avoid

Toremifene: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase photosensitizing effects of Verteporfin. Risk C: Monitor

Reproductive Considerations

Pregnancy status should be evaluated prior to vandetanib therapy. Patients who could become pregnant should use effective contraception during treatment and for 4 months after the last vandetanib dose. Patients with partners who may become pregnant should also use effective contraception during treatment and for 4 months after the last dose of vandetanib.

Adverse effects to fertility were observed in animal toxicology studies.

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to vandetanib may cause fetal harm.

Data related to the use of vandetanib in pregnant patients are limited (Thomas 2018).

Breastfeeding Considerations

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.

Monitoring Parameters

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.

Additional cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]; ESC [Lyon 2022]). BP at each clinical visit (as well as daily home monitoring for first cycle, after dose increases, and every 2 to 3 weeks thereafter); ECG and QTc assessment in patients at moderate- or high-risk of QTc prolongation (assess QTc monthly during the first 3 months and every 3 to 6 months thereafter); baseline echocardiography in high- and very high-risk patients (repeat every 3 months during the first year and every 6 to 12 months thereafter); consider baseline echocardiography in low- and moderate-risk patients (consider repeating every 4 months during the first year for moderate-risk patients and every 6 to 12 months thereafter) (ESC [Lyon 2022]).

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.

Mechanism of Action

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

Pharmacokinetics (Adult Data Unless Noted)

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%)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

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).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Caprelsa;
  • (AT) Austria: Caprelsa;
  • (AU) Australia: Caprelsa;
  • (BE) Belgium: Caprelsa;
  • (BG) Bulgaria: Caprelsa;
  • (BR) Brazil: Caprelsa;
  • (CH) Switzerland: Caprelsa;
  • (CO) Colombia: Caprelsa;
  • (CZ) Czech Republic: Caprelsa;
  • (DE) Germany: Caprelsa;
  • (EE) Estonia: Caprelsa;
  • (EG) Egypt: Caprelsa;
  • (ES) Spain: Caprelsa;
  • (FI) Finland: Caprelsa;
  • (FR) France: Caprelsa;
  • (GB) United Kingdom: Caprelsa;
  • (GR) Greece: Caprelsa;
  • (HK) Hong Kong: Caprelsa;
  • (HU) Hungary: Caprelsa;
  • (IE) Ireland: Caprelsa;
  • (IT) Italy: Caprelsa;
  • (JP) Japan: Caprelsa;
  • (KR) Korea, Republic of: Caprelsa | Zactima;
  • (LT) Lithuania: Caprelsa;
  • (LV) Latvia: Caprelsa;
  • (MX) Mexico: Caprelsa;
  • (NL) Netherlands: Caprelsa;
  • (NO) Norway: Caprelsa;
  • (NZ) New Zealand: Caprelsa;
  • (PE) Peru: Caprelsa;
  • (PL) Poland: Caprelsa;
  • (PT) Portugal: Caprelsa;
  • (RO) Romania: Caprelsa;
  • (RU) Russian Federation: Caprelsa;
  • (SA) Saudi Arabia: Caprelsa;
  • (SE) Sweden: Caprelsa;
  • (SI) Slovenia: Caprelsa;
  • (SK) Slovakia: Caprelsa;
  • (TN) Tunisia: Caprelsa;
  • (TW) Taiwan: Caprelsa
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  2. Caprelsa (vandetanib) [prescribing information]. Cambridge, MA: Genzyme Corporation; April 2024.
  3. Caprelsa (vandetanib) [product monograph]. Toronto, Ontario, Canada: Sanofi-aventis Canada Inc; April 2024.
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  8. Ovesen JL, Sammons D, Connor TH, et al; US Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. NIOSH list of hazardous drugs in healthcare settings, 2024. https://doi.org/10.26616/NIOSHPUB2025103. Updated December 18, 2024. Accessed December 20, 2024.
  9. Thomas N, Glod J, Derse-Anthony C, et al. Pregnancy on vandetanib in metastatic medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2B. Clin Endocrinol (Oxf). 2018;88(5):754-756. doi: 10.1111/cen.13577. [PubMed 29457255]
  10. United States Pharmacopeia. <800> Hazardous Drugs—Handling in Healthcare Settings. In: USP-NF. United States Pharmacopeia; July 1, 2020. Accessed January 16, 2025. doi:10.31003/USPNF_M7808_07_01
  11. Wells SA Jr, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30(2):134-141. [PubMed 22025146]
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