Vandetanib is a kinase inhibitor that is indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease. In vitro, vandetanib inhibits new blood vessel formation and epidermal growth factor receptor-dependent cell survival. The drug exhibits a long elimination half-life (19 days) and can prolong the QT interval. Vandetanib is only available through a restricted distribution program, the Caprelsa REMS program; only prescribers and pharmacies registered with the restricted distribution program are allowed to prescribe and dispense this drug.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Because of the significant risks for QT prolongation, vandetanib is only available via a restricted distribution program called the Caprelsa REMS Program. Only providers and pharmacies registered with the program may prescribe and dispense the drug.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 1
-NIOSH (Draft) 2020 List: Table 1
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.
-Avoid direct contact of crushed tablets with skin or mucous membranes. If such contact occurs, wash the area thoroughly.
Emetic Risk
-Minimal/Low
-Administer prn antiemetics as necessary.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Vandetanib tablets may be administered with or without food. Do not crush the tablets or handle crushed or broken tablets. If whole tablets cannot be swallowed, disperse the tablets in a glass that contains 2 ounces of noncarbonated water. Stir for approximately 10 minutes until dispersed; the tablet will not completely dissolve. Immediately administer the dispersion. Add an additional 4 ounces of noncarbonated water to the glass to remove any residues in the glass; immediately administer the water to ensure that the full dose is received. The dispersion may also be administered through a nasogastric (NG) or gastrostomy tube.
-Do not administer a missed dose if it is less than 12 hours before the next dose is due.
Vandetanib can prolong the QT interval in a concentration-dependent manner; torsade de pointes, ventricular tachycardia, and sudden death have been reported in patients administered vandetanib. Do not start therapy in patients whose QTcF interval is greater than 450 msec; stop vandetanib in patients who develop a QTcF greater than 500 msec until the QTcF returns to less than 450 msec, resuming therapy at a reduced dose. Adverse events including QT prolongation may not fully resolve until 3 plasma half-lives of vandetanib; the half-life of vandetanib is 19 hours. Appropriate monitoring is needed. Obtain ECGs and serum potassium, calcium, magnesium, and TSH concentrations at baseline, at 2 to 4 weeks, and at 8 to 12 weeks after starting vandetanib and every 3 months thereafter; maintain potassium above 4 mEq/L (within normal limits) and other electrolytes within normal limits . Among 231 patients who received vandetanib 300 mg in a clinical trial, QT prolongation was reported in 14% (grade 3 or 4, 8%) compared with 1% (grade 3 or 4, 1%) of those who received placebo. Using the Fridericia correction, 69% of vandetanib-treated patients had QT prolongation greater than 450 msec, and 7% had QTcF prolongation greater than 500 msec by ECG. The mean QTcF change from baseline was 35 msec for the 300 mg dose, and the QTcF remained above 30 msec for up to 2 years. A greater than 60 msec increase from baseline in QTcF was noted in 36% of vandetanib-treated patients. Hypocalcemia occurred in 11% to 57% (grade 3 or 4, 2% to 6%) and hypomagnesemia in 7% (grade 3 or 4, less than 1%). Causes of death included cardiac failure with arrhythmia exacerbation, sudden death, and cardiac arrest.
Severe and sometimes fatal skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN), have been reported with vandetanib. Permanently discontinue vandetanib if severe skin reactions occur and refer the patient for urgent medical evaluation; treatment with systemic corticosteroids may be necessary. Among 231 vandetanib recipients in a clinical trial, the following dermatologic reactions were reported more frequently compared with placebo (n = 99): rash (53% vs. 12%; grade 3 or 4, 5% vs. 0%), acneiform rash (35% vs. 7%; grade 3 or 4, 1% vs. 0%), xerosis (15% vs. 5%), pruritus (11% vs. 4%; grade 3 or 4, 1% vs. 0%), nail disorders (includes nail or nailbed infection, nailbed inflammation or tenderness, paronychia, onycholysis) (9% vs. 0%), and alopecia (8% vs. 0%). A photosensitivity reaction has been reported in 13% (grade 3 or 4, 2%) of vandetanib-treated patients, and can occur up to 4 months after discontinuation of therapy. Rashes reported include erythematous rash, generalized rash, macular rash, maculopapular rash, papular rash, pruritic rash, exfoliative dermatitis, dermatitis bullous, generalized erythema, and eczema.
Interstitial lung disease (ILD) or pneumonitis has been observed with vandetanib, including fatalities; consider a diagnosis of ILD in patients presenting with nonspecific respiratory signs and symptoms. Among 231 vandetanib recipients in a phase 3 clinical trial, mild (grade 1 or 2) upper respiratory tract infection (including laryngitis, (naso) pharyngitis, sinusitis, rhinitis, and tracheitis) was reported in 23% of patients, compared with 16% of those who received placebo (n = 99). Fever resulted in a discontinuation of therapy in 0.9% of vandetanib-treated patients.
Ischemic cerebrovascular events such as ischemic stroke have been observed with vandetanib, and some cases have been fatal. Discontinue vandetanib in patients who experience a severe ischemic cerebrovascular event. The safety of resumption of vandetanib therapy after resolution of an ischemic cerebrovascular event has not been studied. Instruct patients to stop taking vandetanib and to immediately call their healthcare provider for stroke symptoms such as numbness or weakness of the face, arm or leg, especially on one side of the body; sudden confusion, trouble speaking or understanding; sudden trouble seeing in one or both eyes; sudden trouble walking, dizziness, loss of balance or coordination; or sudden, severe headache. In the randomized medullary thyroid cancer study, ischemic cerebrovascular events were observed more frequently with vandetanib (1.3%) as compared with placebo (0%). Among 231 patients who received vandetanib in a phase 3 clinical trial, 26% reported headache (grade 3 or 4, 1%) and 8% reported dysgeusia.
Serious bleeding events, some of which were fatal, have been observed with vandetanib. Discontinue vandetanib in patients with severe hemorrhage. Also, do not administer vandetanib to patients with recent history of hemoptysis of 1/2-teaspoonful (2.5 mL) or more of red blood. In the randomized medullary thyroid cancer study, 14% of vandetanib recipients (n = 231) had grade 1 or 2 bleeding events as compared with 7% of placebo recipients (n = 99). Be alert for serious bleeding events including hematemesis or GI bleeding.
Diarrhea and/or colitis were reported in 57% (grade 3 or 4, 11%) of patients treated with vandetanib in a phase 3 clinical trial (n = 231), compared with 27% (grade 3 or 4, 2%) of those who received placebo (n = 99). Additionally, GI perforation occurred in 0.4% of vandetanib-treated patients and was not reported with placebo. In patients who develop diarrhea or colitis, carefully monitor serum electrolytes and ECGs as electrolyte disturbances may increase the risk for QT prolongation. Stop vandetanib for severe (grade 3 or higher) diarrhea, resuming at a lower dose once diarrhea resolves or improves to CTCAE grade 1. Diarrhea may not fully resolve for 3 half-lives of vandetanib; the half-life of vandetanib 19 days.
Worsening hypothyroidism may occur with vandetanib. Obtain TSH at baseline, at 2 to 4 weeks, and at 8 to 12 weeks after starting vandetanib and every 3 months thereafter. If signs or symptoms of hypothyroidism occur, examine thyroid hormone concentrations and adjust thyroid replacement therapy accordingly. Among patients who largely had prior thyroidectomy (90%), about half (49%) of vandetanib recipients required increases in the dose of the thyroid replacement therapy as compared with 17% of placebo recipients in one clinical trial (n = 231). Additionally, hypothyroidism (grade 1 or 2, 6%), fatigue (all grade, 24%; grade 3 or 4, 6%), and depression (all grade, 10%; grade 3 or 4, 2%) were reported.
Heart failure has been observed with vandetanib and some cases have been fatal. Monitor for signs and symptoms of heart failure. Vandetanib discontinuation may be necessary in patients with heart failure; heart failure may not be reversible upon stopping vandetanib. Do not give vandetanib to patients who have uncompensated heart failure. Vandetanib has not been studied in patients with ventricular arrhythmias or recent myocardial infarction. Heart failure was noted in 0.9% of vandetanib recipients as compared with 0% of placebo recipients.
Vandetanib may cause hypertension, which may be severe. Monitor all patients for hypertension; a vandetanib dose reduction or interruption may be necessary. If high blood pressure cannot be controlled, do not restart vandetanib. Among 231 patients who received vandetanib in a clinical trial, 33% had hypertension, some with hypertensive crisis or accelerated hypertension (grade 3 or 4, 9%) compared with 5% (grade 3 or 4, 1%) of those who received placebo.
Reversible posterior leukoencephalopathy syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by an MRI of the brain, has been observed with vandetanib. Consider RPLS in any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Instruct patients to contact their physician promptly if they experience seizures, headaches, visual disturbances, confusion, or difficulty thinking. Discontinue vandetanib if RPLS develops. In clinical studies, three of four patients who developed RPLS while taking vandetanib also had hypertension.
In a phase 3 clinical trial of patients with locally advanced or metastatic medullary thyroid cancer, those treated with vandetanib (n = 231) reported the following gastrointestinal adverse reactions more frequently compared with placebo (n = 99): nausea (33% vs. 16%; grade 3 or 4, 1% vs. 0%), anorexia (21% vs. 12%; grade 3 or 4, 4% vs. 0%), abdominal pain (21% vs. 11%; grade 3 or 4, 3% vs. 0%), vomiting (15% vs. 7%; grade 3 or 4, 1% vs. 0%), dyspepsia (11% vs. 4%), and xerostomia (9% vs. 3%). Additionally, pancreatitis occurred in 0.4% of patients who received vandetanib and was not reported in those who received placebo.
Corneal opacities (vortex keratopathies), which can lead to halos and decreased visual acuity or visual impairment, were revealed by scheduled slit lamp examinations during clinical trials. Ophthalmologic examination including slit lamp is recommended for patients who report visual changes. Instruct patients to not drive or operate machinery if blurred vision develops. Among 231 vandetanib recipients in a phase 3 clinical trial, 9% had blurred vision and 13% developed a corneal abnormality (including corneal edema, corneal opacification, corneal deposits, keratopathy, corneal pigmentation, arcus lipoides, and acquired corneal dystrophy), compared with 1% and 1% of those who received placebo.
Proteinuria occurred in 10% of 231 vandetanib recipients compared to 2% of placebo recipients in clinical trials. Grade 1 or 2 increases in serum creatinine were also noted in 16% of patients who received vandetanib compared to 1% of those who received placebo; this may be explained by the apparent inhibition of the renal excretion of creatinine by vandetanib. Vandetanib inhibits the uptake of the selective OCT2 marker substrate 14-C-creatinine at a mean inhibitory concentration (IC50) of approximately 2.1 mcg/mL, which is higher than the vandetanib plasma concentration of 0.81 mcg/mL obtained after multiple dosing with 300 mg.
Vandetanib may be associated with hematologic adverse reactions. In a phase 3 clinical trial, neutropenia (10% vs. 5%; grade 3 or 4, less than 1% vs. 2%) and thrombocytopenia (9% vs. 3%) occurred more often in patients treated with vandetanib (n = 231) compared with those who received placebo (n = 99).
Grade 1 or 2 hypoglycemia was reported in 24% of patients treated with vandetanib (n = 231) compared with 7% of those who received placebo (n = 99) in a phase 3 clinical trial.
In a phase 3 clinical trial, elevated hepatic enzymes (increased ALT) were reported in 51% (grade 3 or 4, 2%) of patients treated with vandetanib (n = 231) compared with 19% of those who received placebo; no patient with a grade 3 or higher elevation in ALT had concomitant hyperbilirubinemia.
In a phase 3 clinical trial, muscle spasms were reported in 6% of patients treated with vandetanib (n = 231) compared with 1% of those who received placebo (n = 99). Additionally, fatigue was more severe in patients who received vandetanib therapy (24% vs. 23%; grade 3 or 4, 6% vs. 1%). Asthenia resulted in a discontinuation of therapy in 1.7% of vandetanib-treated patients.
Arterial (including aortic) aneurysms, dissections (aortic dissection), and rupture have occurred in postmarketing experience with vandetanib.
Treatment with vandetanib is not recommended for patients with severe renal failure (CrCl less than 30 mL/minute). Reduce the starting dose to 200 mg and closely monitor QT interval for patients with moderate renal impairment (CrCl 30 to 50 mL/minute). Vandetanib exposure is increased in patients with renal impairment. Average systemic exposure of vandetanib increased by 39% in patients with moderate renal impairment (CrCl between 30 and 50 mL/minute) and by 41% in patients with severe renal impairment or renal failure (CrCl less than 30 mL/minute). There is no information available for patients with end-stage renal disease requiring dialysis.
Monitor blood pressure in all patients, and use caution in patients with baseline hypertension. Vandetanib may cause hypertension; hypertensive crisis has also been reported with vandetanib therapy. Dose reduction or interruption for hypertension may be necessary; do not use vandetanib in patients whose blood pressure cannot be controlled.
Vandetanib is not recommended for use in patients with either moderate or severe hepatic impairment, as safety and efficacy have not been established. Cautious use of vandetanib may be warranted for patients with milder forms of hepatic disease, as the drug may cause elevated hepatic enzymes and bilirubin. Limited data are available regarding use in patients with a serum bilirubin greater than 1.5 times the upper limit of normal.
Heart failure, including fatalities, has been reported in patients treated with vandetanib; it may not be reversible upon discontinuation of therapy. Monitor for signs and symptoms of heart failure, and consider a discontinuation of therapy if diagnosed. Heart failure may increase the risk of prolonging the QT interval when using vandetanib.
Vandetanib can prolong the QT interval in a concentration-dependent manner; torsade de pointes (TdP), ventricular tachycardia, and sudden death have been reported. Due to the risk of QT prolongation, use requires an experienced clinician with access to the restricted distribution program. Because of the risk of QT prolongation, TdP, and sudden death, vandetanib is only available through a restricted distribution program, the Caprelsa REMS Program (see manufacturer prescribing information or www.caprelsarems.com for REMS contact information). This program requires prescribers and pharmacies to comply with certain conditions prior to prescribing or dispensing vandetanib. Obtain a baseline ECG and serum potassium, calcium, magnesium, and TSH; repeat 2 to 4 weeks and then 8 to 12 weeks after starting therapy, and every 3 months thereafter. Do not use vandetanib in patients with hypocalcemia, hypokalemia, or hypomagnesemia. Replete electrolytes as necessary to maintain serum potassium levels of 4 mEq/L or higher (within normal range), and to maintain serum magnesium and calcium within normal range. Vandetanib is contraindicated for use by patients with congenital long QT syndrome. Do not initiate vandetanib therapy in patients with a QTcF interval greater than 450 milliseconds or in those with a history of TdP, bradycardia or other bradyarrhythmias, or uncompensated heart failure. Once on therapy, hold treatment for a QTcF greater than 500 milliseconds; when the QTcF returns to less than 450 milliseconds, therapy may be resumed at a reduced dose. Avoid medications known to prolong the QT interval; if patients are already receiving these medications and no alternative therapy exists, perform ECG monitoring more frequently. Use vandetanib with caution in patients with conditions that may increase the risk of QT prolongation including AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, cerebrovascular accident, or in patients receiving medications known to cause electrolyte imbalances. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, decreased thyroid function, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. The risk for QT prolongation is greater in patients with impaired renal function; reduce the dose and closely monitor the QT interval in these patients. In a randomized, phase 3 trial (n = 231), the mean QTcF change from baseline was 35 milliseconds (90% CI, 33 to 35 milliseconds), and remained above 30 milliseconds for up to 2 years. The QTcF change from baseline was greater than 60 milliseconds in 36% of patients, while the QTcF was greater than 500 milliseconds in 4.3% of patients. Vandetanib has not been studied in patients with ventricular arrhythmias or recent myocardial infarction.
Serious bleeding events have occurred with vandetanib therapy; some events have been fatal. Do not administer vandetanib to patients with a recent history of hemoptysis of 1/2 teaspoon or more of red blood. Discontinue vandetanib in any patient who develops severe hemorrhage (e.g., severe GI bleeding).
Vandetanib can cause drowsiness, blurred vision, and dizziness. Advise patients to use caution when driving or operating machinery until the effect of the drug is established.
Vandetanib is associated with photosensitivity. Patients should be advised to avoid sunlight (UV) exposure, and to wear protective clothing, use a broad spectrum UVA/UVB sunscreen, and wear protective lip balm (SPF greater than or equal to 50) when outdoors while on treatment and for up to 4 months after the last dose.
Pneumonitis or interstitial lung disease (ILD) has been reported in patients treated with vandetanib in clinical trials. Hold vandetanib therapy and promptly evaluate any patient with acute or worsening respiratory symptoms (e.g., dyspnea, cough, and fever). Consider a diagnosis of ILD in patients presenting with non-specific respiratory signs and symptoms. Permanently discontinue vandetanib if a diagnosis of ILD/pneumonitis is confirmed. Use vandetanib with caution in patients with pre-existing pulmonary disease.
Reversible posterior leukoencephalopathy syndrome (RPLS), also known as posterior reversible encephalopathy syndrome (PRES), is a syndrome of subcortical vasogenic edema that is diagnosed by MRI of the brain and has been reported in patients treated with vandetanib. Patients with headache, lethargy, seizures, confusion, blindness, and other visual or neurologic disturbances should be evaluated for RPLS with magnetic resonance imaging (MRI). Discontinue vandetanib in patients suspected of developing RPLS.
An increase in thyroid replacement therapy may be necessary in patients treated with vandetanib. Obtain a TSH at baseline, 2 to 4 weeks after starting vandetanib therapy, 8 to 12 weeks after starting therapy, and then every 3 months thereafter. If signs or symptoms of hypothyroidism occur, evaluate thyroid hormone levels and adjust thyroid replacement therapy as necessary. Of note, hypothyroidism may increase the risk of prolonging the QT interval when using vandetanib.
Serious rash has been reported with vandetanib therapy; fatal cases of Stevens-Johnson syndrome (SJS) and TEN have occurred. Monitor patients for the development of severe cutaneous reactions. Permanently discontinue therapy if serious rash occurs; systemic therapy such as corticosteroids may be necessary.
Severe diarrhea has been reported in patients treated with vandetanib. If diarrhea occurs, monitor serum electrolytes and ECGs to reduce the risk of QT prolongation due to dehydration and enable early detection if it occurs. Hold vandetanib for severe diarrhea; a dose reduction may be necessary when restarting therapy.
Ischemic cerebrovascular events (stroke), including fatalities, have occurred in patients treated with vandetanib. Discontinue vandetanib in patients who experience a severe ischemic cerebrovascular event; the safety of resuming therapy after resolution has not been studied. Of note, stroke may increase the risk of prolonging the QT interval when using vandetanib.
Impaired wound healing can occur in patients treated with vascular endothelial growth factor (VEGF) inhibitors such as vandetanib. Discontinue vandetanib 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. The safety of resuming vandetanib after resolution of wound healing complications has not been established.
Pregnancy should be avoided by females of reproductive potential during vandetanib treatment and for at least 4 months after the last dose. Although there are no adequately controlled studies in pregnant women, vandetanib can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving vandetanib should be apprised of the potential hazard to the fetus. Vandetanib is embryotoxic, fetotoxic, and induced fetal malformations in rats at exposures less than or equal to those expected at the recommended human dose. A no-effect dosing level for malformations was not identified. Administration of vandetanib to female rats prior to mating and through the first week of pregnancy at doses approximately equal to human exposure at the recommended dose based on Cmax increased preimplantation and postimplantation loss, resulting in a reduction in the number of live embryos. During organogenesis, vandetanib increased postimplantation loss, including occasional total litter loss at doses approximating human exposure. At doses approximating 0.4 times the human Cmax at the recommended dose, treatment with vandetanib resulted in late embryofetal death and decreased fetal birth weight. Exposures of about 0.03 times the human Cmax at the recommended dose caused dose-dependent increases in both malformations of the heart vessels and skeletal variations including delayed ossification of the skull, vertebrae, and sternum, indicating delayed fetal development.
Counsel patients about the reproductive risk and contraception requirements during vandetanib treatment. Vandetanib can be embryotoxic, fetotoxic, and teratogenic if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during treatment and for at least 4 months after the last dose of vandetanib. Due to the risk of male-mediated teratogenicity, males with female partners of reproductive potential should also use effective contraception during treatment and for 4 months after the last dose. Females of reproductive potential should undergo pregnancy testing prior to initiation of vandetanib. Women who become pregnant while receiving vandetanib should be apprised of the potential hazard to the fetus. Although there are no data regarding the effect of vandetanib on human fertility, male and female infertility has been observed in animal studies.
Due to the potential for serious adverse reactions in nursing infants from vandetanib, advise women to discontinue breast-feeding during treatment and for 4 months after the last dose. It is not known whether vandetanib is present in human milk, although many drugs are excreted in human milk.
For the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease:
NOTE: Carefully consider the use of vandetanib in patients with indolent, asymptomatic, or slowly progressing disease because of the treatment-related risks of vandetanib.
Oral dosage:
Adults: 300 mg orally once daily until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Median progression-free survival (PFS) was significantly improved in patients with unresectable locally advanced or metastatic medullary thyroid cancer who received treatment with vandetanib (n = 231) compared with placebo (n = 100) (not reached vs. 16.4 months) in a randomized, double-blind clinical trial; median overall survival was similar between treatment arms (81.6 months vs. 80.4 months).
Therapeutic Drug Monitoring:
Dosage Adjustments for Treatment-Related Toxicities:
Corrected QT interval, Fridericia (QTcF) greater than 500 msec: Hold vandetanib therapy. Because of the 19-day half-life, a prolonged QT interval may not resolve quickly. Monitor appropriately; for any dose reduction for QT prolongation or dose interruption greater than 2 weeks, monitor serum potassium, calcium, magnesium, and TSH in addition to an ECG and replete as necessary. When QTcF returns to less than 450 msec, resume therapy at a reduced dose (e.g., 300 mg to 200 mg; 200 mg to 100 mg).
Heart Failure: Consider discontinuation of therapy.
Interstitial lung disease (ILD) or pneumonitis: Hold vandetanib therapy and promptly evaluate any patient with acute or worsening respiratory symptoms (e.g., dyspnea, cough, and fever). Permanently discontinue vandetanib if ILD/pneumonitis is confirmed.
Reversible Posterior Leukoencephalopathy Syndrome: Discontinue vandetanib therapy.
Severe ischemic cerebrovascular events: Discontinue vandetanib therapy.
Severe skin reactions (including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS)): Permanently discontinue vandetanib therapy and refer patient for urgent medical evaluation. Initiate systemic therapy with corticosteroids if necessary.
Visual changes: Perform ophthalmologic examination, including slit lamp examination.
Other Grade 3 or higher toxicity: Hold vandetanib therapy. Because of the 19-day half-life, adverse reactions may not resolve quickly. Monitor appropriately, and when the toxicity resolves to grade 1 or less, resume therapy at a reduced dose (e.g., 300 mg to 200 mg; 200 mg to 100 mg).
Maximum Dosage Limits:
-Adults
300 mg/day PO.
-Geriatric
300 mg/day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Baseline Hepatic Impairment:
NOTE: Limited data are available regarding use in patients with serum bilirubin greater than 1.5 times the upper limit of normal.
-Mild impairment (Child-Pugh class A, total score of 5 or 6): No dose adjustment needed.
-Moderate to severe impairment (Child-Pugh class B or C, total score of 7 or higher): Not recommended for use; safety and efficacy have not been established.
Patients with Renal Impairment Dosing
Baseline Renal Impairment:
-CrCl greater than or equal to 50 mL/minute: No dosage adjustment needed.
-CrCl 30 to 49 mL/minute: Reduce vandetanib starting dose to 200 mg and closely monitor QT interval.
-CrCl less than 30 mL/minute: Vandetanib treatment is not recommended.
-End-stage renal disease requiring dialysis: Dosing information is not available.
*non-FDA-approved indication
Adagrasib: (Major) Concomitant use of adagrasib and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Alfuzosin: (Major) Avoid coadministration of vandetanib with alfuzosin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Based on electrophysiology studies performed by the manufacturer, alfuzosin may prolong the QT interval in a dose-dependent manner.
Alogliptin; Metformin: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin.
Amiodarone: (Major) Concomitant use of amiodarone and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Avoid coadministration of vandetanib with amisulpride due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Amisulpride causes dose- and concentration- dependent QT prolongation.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of vandetanib with clarithromycin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Anagrelide: (Major) Do not use anagrelide with vandetanib due to the risk of QT prolongation and torsade de pointes (TdP). Torsade de pointes and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. Vandetanib can also prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib.
Apalutamide: (Major) Avoid coadministration of vandetanib with apalutamide due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Apomorphine: (Major) Avoid coadministration of vandetanib with apomorphine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aripiprazole: (Major) Concomitant use of vandetanib and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Arsenic Trioxide: (Major) Avoid coadministration of vandetanib with arsenic trioxide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, frequently monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Torsade de pointes, QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Artemether; Lumefantrine: (Major) Avoid coadministration of vandetanib with artemether; lumefantrine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Artemether; lumefantrine is also associated with prolongation of the QT interval.
Artesunate: (Moderate) Monitor for an increase in artesunate-related side effects if coadministered with vandetanib. Coadministration may increase the exposure of the active metabolite of artesunate, dihydroartemisinin (DHA). DHA is a UGT substrate, and vandetanib is a strong UGT inhibitor.
Asenapine: (Major) Avoid coadministration of vandetanib with asenapine due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Asenapine has also been associated with QT prolongation.
Atomoxetine: (Major) Concomitant use of vandetanib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Azithromycin: (Major) Concomitant use of vandetanib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bedaquiline: (Major) Avoid coadministration of vandetanib with bedaquiline due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Bedaquiline has also been reported to prolong the QT interval. Coadministration with other QT-prolonging drugs may result in additive or synergistic prolongation of the QT interval.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine: (Major) Concomitant use of vandetanib and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine; Naloxone: (Major) Concomitant use of vandetanib and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cabotegravir; Rilpivirine: (Major) Avoid coadministration of vandetanib with rilpivirine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Canagliflozin; Metformin: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin.
Carbamazepine: (Major) Avoid coadministration of vandetanib with carbamazepine due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Ceritinib: (Major) Avoid coadministration of vandetanib with ceritinib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to treatment. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for QT prolongation. Both drugs can prolong the QT interval in a concentration-dependent manner; sudden death and TdP have been reported in patients receiving vandetanib.
Chloroquine: (Major) Avoid coadministration of chloroquine with vandetanib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib.
Chlorpromazine: (Major) Avoid coadministration of vandetanib with chlorpromazine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP).
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciprofloxacin: (Major) Concomitant use of vandetanib and ciprofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have been reported in patients receiving vandetanib. Because vandetanib causes QT prolonging effects that may be additive to those of cisapride, coadministration is contraindicated.
Citalopram: (Major) Concomitant use of vandetanib and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Major) Avoid coadministration of vandetanib with clarithromycin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Clofazimine: (Major) Concomitant use of clofazimine and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clozapine: (Major) Avoid coadministration of vandetanib with clozapine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Treatment with clozapine has also been associated with QT prolongation, TdP, cardiac arrest, and sudden death.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of vandetanib and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Codeine; Promethazine: (Major) Concomitant use of vandetanib and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Crizotinib: (Major) Avoid coadministration of vandetanib with crizotinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for both drugs if QT prolongation occurs. Both drugs can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have also been reported in patients receiving vandetanib.
Dapagliflozin; Metformin: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin.
Dasatinib: (Major) Avoid coadministration of vandetanib with dasatinib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
Degarelix: (Major) Avoid coadministration of vandetanib with degarelix due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Desflurane: (Major) Avoid coadministration of vandetanib with halogenated anesthetics due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Halogenated anesthetics can also prolong the QT interval.
Deutetrabenazine: (Major) Avoid coadministration of vandetanib with deutetrabenazine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypokalemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dextromethorphan; Quinidine: (Major) Avoid coadministration of vandetanib with quinidine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Quinidine administration is also associated with QT prolongation and TdP.
Digoxin: (Moderate) Monitor closely for digoxin-related toxicities (e.g., arrhythmias, confusion, vision changes, and nausea) if coadministration with vandetanib is necessary. Digoxin is a substrate of P-glycoprotein (P-gp). Coadministration with a single dose of vandetanib increased the Cmax and AUC of digoxin by 29% and 23%, respectively.
Disopyramide: (Major) Avoid coadministration of vandetanib with disopyramide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Disopyramide administration is also associated with QT prolongation and TdP.
Dofetilide: (Major) Coadministration of dofetilide and vandetanib is not recommended as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib.
Dolasetron: (Major) Avoid coadministration of vandetanib with dolasetron due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Major) Avoid coadministration of vandetanib with rilpivirine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Donepezil: (Major) Avoid coadministration of vandetanib with donepezil due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
Donepezil; Memantine: (Major) Avoid coadministration of vandetanib with donepezil due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
Dronedarone: (Contraindicated) Concurrent use of dronedarone and vandetanib is contraindicated. Vandetanib can prolong the QT interval in a concentration-dependent manner. Torsade de pointes (TdP) and sudden death have been reported in patients receiving vandetanib. Dronedarone administration is also associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as vandetanib. If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib.
Efavirenz: (Major) Avoid coadministration of vandetanib with efavirenz due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Prolongation of the QTc interval has also been observed with the use of efavirenz.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of vandetanib with efavirenz due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Prolongation of the QTc interval has also been observed with the use of efavirenz.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of vandetanib with efavirenz due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Prolongation of the QTc interval has also been observed with the use of efavirenz.
Eliglustat: (Major) Avoid coadministration of vandetanib with eliglustat due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
Empagliflozin; Linagliptin; Metformin: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin.
Empagliflozin; Metformin: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Avoid coadministration of vandetanib with rilpivirine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of vandetanib with rilpivirine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Encorafenib: (Major) Avoid concurrent use of encorafenib with vandenatib due to the risk for decreased vandenatib exposure and efficacy and additive risk for QT/QTc prolongation and torsade de pointes (TdP). Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Vandenatib is a CYP3A substrate, encorafenib is a strong CYP3A inducer, and both medications have been associated with QT/QTc prolongation. Concomitant use with another strong CYP3A inducer decreased the AUC of vandetanib by 40%.
Entrectinib: (Major) Avoid coadministration of vandetanib with entrectinib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Entrectinib has been associated with QT prolongation.
Enzalutamide: (Major) Avoid coadministration of vandetanib with enzalutamide due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Eribulin: (Major) Avoid coadministration of vandetanib with eribulin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Eribulin has also been associated with QT prolongation.
Ertugliflozin; Metformin: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin.
Erythromycin: (Major) Concomitant use of vandetanib and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Escitalopram: (Major) Concomitant use of vandetanib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Etrasimod: (Major) Concomitant use of etrasimod and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Etrasimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Fexinidazole: (Major) Concomitant use of fexinidazole and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fingolimod: (Major) Avoid coadministration of vandetanib with fingolimod due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, overnight monitoring with continuous ECG in a medical facility is advised after the first dose of fingolimod. Monitor ECGs for QT prolongation and monitor electrolytes during therapy; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Flecainide: (Major) Concomitant use of vandetanib and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluconazole: (Major) Concomitant use of vandetanib and fluconazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluoxetine: (Major) Concomitant use of vandetanib and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluphenazine: (Minor) Fluphenazine is associated with a possible risk for QT prolongation. If concomitant use with vandetanib is necessary, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Vandetanib can also prolong the QT interval in a concentration-dependent manner; torsade de pointes (TdP) and sudden death have been reported in patients receiving vandetanib.
Fluvoxamine: (Major) Avoid coadministration of vandetanib with fluvoxamine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Prolongation of the QT interval and TdP has been reported during fluvoxamine postmarketing use.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as vandetanib. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have also been reported in patients receiving vandetanib. If coadministration is necessary, an ECG and electrolyte concentration monitoring are needed, as well as more frequent monitoring of the QT interval. If QTcF is greater than 500 msec, interrupt vandetanib dosing until the QTcF is less than 450 msec; then, vandetanib may be resumed at a reduced dose.
Fosphenytoin: (Major) Avoid coadministration of vandetanib with fosphenytoin due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Fostemsavir: (Major) Avoid coadministration of vandetanib with fostemsavir due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a dose-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gemifloxacin: (Major) Avoid coadministration of vandetanib with gemifloxacin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Major) Avoid coadministration of vandetanib with gemtuzumab due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, obtain a baseline ECG and electrolyte panel. Monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Gilteritinib: (Major) Avoid coadministration of vandetanib with gilteritinib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Gilteritinib has also been associated with QT prolongation.
Glasdegib: (Major) Avoid coadministration of vandetanib with glasdegib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, increase frequency of ECG monitoring and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia.
Glipizide; Metformin: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin.
Glyburide; Metformin: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin.
Goserelin: (Major) Avoid coadministration of vandetanib with goserelin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval.
Granisetron: (Major) Avoid coadministration of vandetanib with granisetron due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Granisetron has also been associated with QT prolongation.
Halogenated Anesthetics: (Major) Avoid coadministration of vandetanib with halogenated anesthetics due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Halogenated anesthetics can also prolong the QT interval.
Haloperidol: (Major) Avoid coadministration of vandetanib with haloperidol due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Prolongation of the QT interval and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Histrelin: (Major) Avoid coadministration of vandetanib with histrelin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval.
Hydroxychloroquine: (Major) Concomitant use of vandetanib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Concomitant use of vandetanib and hydroxyzine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ibutilide: (Major) Avoid coadministration of vandetanib with ibutilide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Ibutilide administration can also cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Iloperidone: (Major) Avoid coadministration of vandetanib with iloperidone due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Iloperidone has also been associated with QT prolongation.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of vandetanib with inotuzumab due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and electrolytes at baseline and periodically during treatment; correct any electrolyte abnormalities. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Inotuzumab has also been associated with QT interval prolongation.
Isoflurane: (Major) Avoid coadministration of vandetanib with halogenated anesthetics due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Halogenated anesthetics can also prolong the QT interval.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of vandetanib with rifampin due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with rifampin decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of vandetanib with rifampin due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with rifampin decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Itraconazole: (Major) Avoid coadministration of vandetanib with itraconazole due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Itraconazole has also been associated with prolongation of the QT interval.
Ivosidenib: (Major) Avoid coadministration of vandetanib with ivosidenib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct any electrolyte abnormalities. An interruption of therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Prolongation of the QTc interval and ventricular arrhythmias have also been reported in patients treated with ivosidenib.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and vandetanib due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of vandetanib with clarithromycin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Lapatinib: (Major) Avoid coadministration of vandetanib with lapatinib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to treatment. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and TdP have been reported in postmarketing experience with lapatinib.
Lefamulin: (Major) Avoid coadministration of vandetanib with lefamulin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with vandetanib due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib.
Leuprolide: (Major) Avoid coadministration of vandetanib with leuprolide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Avoid coadministration of vandetanib with leuprolide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Levofloxacin: (Major) Concomitant use of vandetanib and levofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and vandetanib due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Linagliptin; Metformin: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin.
Lithium: (Major) Concomitant use of vandetanib and lithium increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lofexidine: (Major) Avoid coadministration of vandetanib with lofexidine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Lofexidine also prolongs the QT interval.
Loperamide: (Major) Avoid coadministration of vandetanib with loperamide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. At high doses, loperamide has also been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.
Loperamide; Simethicone: (Major) Avoid coadministration of vandetanib with loperamide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. At high doses, loperamide has also been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with vandetanib due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Interrupt or dose reduce vandetanib if QT prolongation occurs. Vandetanib can prolong the QT interval in a concentration-dependent manner; torsade de pointes (TdP) and sudden death have been reported in patients receiving vandetanib. Lopinavir is associated with QT prolongation.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of vandetanib with lumacaftor; ivacaftor due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of vandetanib with lumacaftor; ivacaftor due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as vandetanib. Use of these drugs together may increase the risk of developing torsade de pointes (TdP)-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Vandetanib can also prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib.
Maprotiline: (Major) Avoid coadministration of vandetanib with maprotiline due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Mefloquine: (Major) Avoid coadministration of vandetanib with mefloquine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Metformin: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin.
Metformin; Repaglinide: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin.
Metformin; Saxagliptin: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin.
Metformin; Sitagliptin: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin.
Methadone: (Major) Avoid coadministration of vandetanib with methadone due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Methadone is also associated with an increased risk for QT prolongation and TdP, especially at higher doses (greater than 200 mg/day, averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
Metronidazole: (Major) Concomitant use of metronidazole and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Midostaurin: (Major) Avoid coadministration of vandetanib with midostaurin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Prolongation of the QT interval was also reported in patients who received midostaurin in clinical trials.
Mifepristone: (Major) Concomitant use of vandetanib and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mirtazapine: (Major) Concomitant use of vandetanib and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mitotane: (Major) Avoid coadministration of vandetanib with mitotane due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Mobocertinib: (Major) Concomitant use of mobocertinib and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Moxifloxacin: (Major) Avoid coadministration of vandetanib with moxifloxacin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Quinolones have also been associated with a risk of QT prolongation; although extremely rare, TdP has been reported during postmarketing surveillance of moxifloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
Nilotinib: (Major) Avoid coadministration of vandetanib with nilotinib due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy.
Ofloxacin: (Major) Concomitant use of vandetanib and ofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine: (Major) Avoid coadministration of vandetanib with olanzapine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Limited data, including some case reports, suggest that olanzapine may also be associated with a significant prolongation of the QTc interval.
Olanzapine; Fluoxetine: (Major) Avoid coadministration of vandetanib with olanzapine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Limited data, including some case reports, suggest that olanzapine may also be associated with a significant prolongation of the QTc interval. (Major) Concomitant use of vandetanib and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine; Samidorphan: (Major) Avoid coadministration of vandetanib with olanzapine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Limited data, including some case reports, suggest that olanzapine may also be associated with a significant prolongation of the QTc interval.
Ondansetron: (Major) Concomitant use of vandetanib and ondansetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Osilodrostat: (Major) Avoid coadministration of vandetanib with osilodrostat due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; torsade de pointes and sudden death have been reported in patients receiving vandetanib. Osilodrostat is associated with dose-dependent QT prolongation.
Osimertinib: (Major) Avoid coadministration of vandetanib with vandetanib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor electrolytes and ECGs for QT prolongation; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of therapy or dose reduction for both drugs may be necessary for QT prolongation. Both osimertinib and vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have also been reported in patients receiving vandetanib.
Oxaliplatin: (Major) Avoid coadministration of vandetanib with oxaliplatin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to treatment. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Prolongation of the QT interval and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
Ozanimod: (Major) Avoid coadministration of vandetanib with ozanimod due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Pacritinib: (Major) Concomitant use of pacritinib and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Avoid coadministration of vandetanib with paliperidone due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Paliperidone has been associated with QT prolongation; TdP and ventricular fibrillation have been reported in the setting of overdose.
Panobinostat: (Major) Coadministration of vandetanib with panobinostat is not recommended due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Prolongation QT prolongation has also been reported with panobinostat.
Pasireotide: (Major) Avoid coadministration of vandetanib with pasireotide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Prolongation of the QT interval has also occurred with pasireotide at therapeutic and supra-therapeutic doses.
Pazopanib: (Major) Coadministration of vandetanib with pazopanib is not advised due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Pazopanib has also been reported to prolong the QT interval.
Pentamidine: (Major) Avoid coadministration of vandetanib with pentamidine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Systemic pentamidine has also been associated with QT prolongation.
Perphenazine: (Minor) If concomitant use of vandetanib with perphenazine is necessary, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Perphenazine; Amitriptyline: (Minor) If concomitant use of vandetanib with perphenazine is necessary, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Phenobarbital: (Major) Avoid coadministration of vandetanib with phenobarbital due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of vandetanib with phenobarbital due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Phenytoin: (Major) Avoid coadministration of vandetanib with phenytoin due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Pimavanserin: (Major) Coadministration of vandetanib with pimavanserin should generally be avoided due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Pimavanserin may also cause QT prolongation.
Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have been reported in patients receiving vandetanib. Because of the potential for TdP, use of vandetanib with pimozide is contraindicated.
Pioglitazone; Metformin: (Moderate) Vandetanib could increase systemic exposure to metformin and may increase the risk for lactic acidosis. Vandetanib increased the plasma concentrations of metformin, which is transported by the renal organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering vendetanib with metformin.
Pitolisant: (Major) Avoid coadministration of vandetanib with pitolisant due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Pitolisant prolongs the QT interval.
Ponesimod: (Major) Avoid coadministration of vandetanib with ponesimod due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP); additive immunosuppression may also occur which may extend the duration or severity of immune suppression If concomitant use is unavoidable, monitor ECGs, electrolytes, and for signs and symptoms of infection; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Porfimer: (Major) Avoid coadministration of porfimer with vandetanib due to the risk of increased photosensitivity. All patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like vandetanib may increase the risk of a photosensitivity reaction.
Posaconazole: (Major) Avoid coadministration of vandetanib with posaconazole due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP.
Primaquine: (Major) Avoid coadministration of vandetanib with primaquine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Primaquine also has the potential to cause QT prolongation.
Primidone: (Major) Avoid coadministration of vandetanib with primidone due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Procainamide: (Major) Avoid coadministration of vandetanib with procainamide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Procainamide is associated with a well-established risk of QT prolongation and TdP.
Prochlorperazine: (Minor) If concomitant use of vandetanib with prochlorperazine is necessary, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Promethazine: (Major) Concomitant use of vandetanib and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Dextromethorphan: (Major) Concomitant use of vandetanib and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Phenylephrine: (Major) Concomitant use of vandetanib and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propafenone: (Major) Concomitant use of vandetanib and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quetiapine: (Major) Concomitant use of vandetanib and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Major) Avoid coadministration of vandetanib with quinidine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Quinidine administration is also associated with QT prolongation and TdP.
Quinine: (Major) Avoid coadministration of vandetanib with quinine due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Quinine has also been associated with QT prolongation and rare cases of TdP.
Quizartinib: (Major) Concomitant use of quizartinib and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Major) Avoid coadministration of vandetanib with ranolazine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Both drugs can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Relugolix: (Major) Avoid coadministration of vandetanib with relugolix due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypokalemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid coadministration of vandetanib with relugolix due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypokalemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Ribociclib: (Major) Avoid coadministration of ribociclib with vandetanib due to an increased risk for QT prolongation and torsade de pointes (TdP). Both drugs have been shown to prolong the QT interval in a concentration-dependent manner. Sudden death and TdP have also been reported in patients receiving vandetanib. Concomitant use may increase the risk for QT prolongation.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with vandetanib due to an increased risk for QT prolongation and torsade de pointes (TdP). Both drugs have been shown to prolong the QT interval in a concentration-dependent manner. Sudden death and TdP have also been reported in patients receiving vandetanib. Concomitant use may increase the risk for QT prolongation.
Rifampin: (Major) Avoid coadministration of vandetanib with rifampin due to decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Concomitant use with rifampin decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Rifapentine: (Major) Avoid coadministration of vandetanib with rifapentine due to the risk of decreased vandetanib exposure and reduced efficacy. Vandetanib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the AUC of vandetanib by 40%.
Rilpivirine: (Major) Avoid coadministration of vandetanib with rilpivirine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Risperidone: (Major) Avoid coadministration of vandetanib with risperidone due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Romidepsin: (Major) Avoid coadministration of vandetanib with romidepsin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Romidepsin has also been reported to prolong the QT interval.
Saquinavir: (Major) Avoid coadministration of vandetanib with saquinavir due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Saquinavir boosted with ritonavir also increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Selpercatinib: (Major) Avoid coadministration of vandetanib with selpercatinib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypokalemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Concentration-dependent QT prolongation has been observed with selpercatinib therapy.
Sertraline: (Major) Concomitant use of vandetanib and sertraline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Avoid coadministration of vandetanib with halogenated anesthetics due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Halogenated anesthetics can also prolong the QT interval.
Siponimod: (Major) Avoid coadministration of siponimod and vandetanib due to the potential for additive QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Vandetanib can prolong the QT interval in a concentration-dependent manner; torsade de pointes and sudden death have been reported in patients receiving vandetanib.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Solifenacin: (Major) Avoid coadministration of vandetanib with solifenacin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Both drugs can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Torsade de pointes TdP has also been reported with postmarketing use of solifenacin, although causality was not determined.
Sorafenib: (Major) Avoid coadministration of vandetanib with sorafenib due to an increased risk of additive QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Sorafenib is also associated with QTc prolongation.
Sotalol: (Major) Concomitant use of vandetanib and sotalol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of vandetanib with St. Johns Wort due to unpredictably decreased plasma concentrations of vandetanib and increased concentrations of the active metabolite. Vandetanib is a CYP3A4 substrate and St. Johns Wort is a strong CYP3A4 inducer. Concomitant use with another strong CYP3A4 inducer decreased the geometric mean AUC of vandetanib by 40%; the geometric mean AUC and Cmax of N-desmethylvandetanib increased by 266% and 414%, respectively.
Sunitinib: (Major) Avoid coadministration of vandetanib with sunitinib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Sunitinib can also prolong the QT interval.
Tacrolimus: (Major) Avoid coadministration of vandetanib with tacrolimus due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Tacrolimus also causes QT prolongation.
Tamoxifen: (Major) Concomitant use of vandetanib and tamoxifen increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Telavancin: (Major) Avoid coadministration of vandetanib with telavancin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Telavancin has also been associated with QT prolongation.
Tetrabenazine: (Major) Avoid coadministration of vandetanib with tetrabenazine due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
Thioridazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use along with vandetanib which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
Tolterodine: (Major) Avoid coadministration of vandetanib with tolterodine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Tolterodine has also been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Toremifene: (Major) Avoid coadministration of vandetanib with toremifene due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Both drugs can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib.
Trazodone: (Major) Concomitant use of vandetanib and trazodone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triclabendazole: (Major) Concomitant use of triclabendazole and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trifluoperazine: (Minor) If concomitant use of vandetanib with trifluoperazine is necessary, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Triptorelin: (Major) Avoid coadministration of vandetanib with triptorelin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
Vardenafil: (Major) Concomitant use of vardenafil and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vemurafenib: (Major) Avoid coadministration of vandetanib with vemurafenib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Vemurafenib has also been associated with QT prolongation.
Venlafaxine: (Major) Concomitant use of venlafaxine and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with vandetanib is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like vandetanib may increase the risk of a photosensitivity reaction.
Voclosporin: (Major) Avoid concomitant use of vandetanib and voclosporin due to the risk of additive QT prolongation and torsade de pointes (TdP). If concomitant use is necessary, monitor ECGs and electrolytes; correct hypocalcemia, hypokalemia, and hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary is QT prolongation occurs. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of vandetanib with clarithromycin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Voriconazole: (Major) Avoid coadministration of vandetanib with voriconazole due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Voriconazole has also been associated with QT prolongation and rare cases of TdP.
Vorinostat: (Major) Avoid coadministration of vandetanib with vorinostat due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Vorinostat therapy is also associated with a risk of QT prolongation.
Ziprasidone: (Contraindicated) Concurrent use of vandetanib and ziprasidone is contraindicated because there is an increased risk for QT prolongation and torsade de pointes (TdP). Ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs, which includes vandetanib. Vandetanib can prolong the QT interval in a concentration-dependent manner, and TdP and sudden death have been reported. Avoid drugs known to prolong the QT interval during vandetanib therapy.
Vandetanib is a kinase inhibitor. In vitro, vandetanib inhibits the activity of tyrosine kinases including members of the epidermal growth factor receptor family (EGFR), vascular endothelial cell growth factor receptors (VEGF), rearranged during transfection (RET), protein tyrosine kinase 6 (BRK), TIE2, members of the EPH receptors kinase family, and members of the Src family of tyrosine kinases. Vandetanib inhibits endothelial cell migration, proliferation, survival, and new blood vessel formation in in vitro models of angiogenesis. Vandetanib also inhibits EGFR-dependent cell survival in vitro. Vandetanib inhibits epidermal growth factor-stimulated receptor tyrosine kinase phosphorylation in tumor cells and endothelial cells and VEGF-stimulated tyrosine kinase phosphorylation in endothelial cells. In vivo, vandetanib reduced tumor cell-induced angiogenesis, tumor vessel permeability, and inhibited tumor growth and metastasis in mouse models of cancer.
Vandetanib is administered orally. In vitro, vandetanib is approximately 90% bound to human serum albumin and alpha-1-acid-glycoprotein; in ex vivo plasma samples from colorectal cancer patients receiving vandetanib at steady-state, mean protein binding was 94%.The volume of distribution (Vd) is approximately 7,450 L. In a pharmacokinetic analysis, 2 metabolites were detected in plasma. N-desmethyl-vandetanib is primarily produced by CYP3A4, circulates at concentrations of approximately 7% to 17.1% of those of vandetanib, and exhibits similar inhibitory activity as the parent drug at the VEGF- (KDR and Flt-1) and EGFR-receptors. Vandetanib-N-oxide is primarily produced by flavin-containing monooxygenase enzymes FMO1 and FMO3 and circulates at concentrations of approximately 1.4% to 2.2% of those of vandetanib. After a single dose of vandetanib, approximately 69% was recovered with 44% in feces and 25% in urine within 21 days after the dose. Excretion was slow (mean clearance of approximately 13.2 L/hour), and further excretion beyond 21 days is expected based on the plasma half-life of 19 days.
Affected cytochrome P450 (CYP) isoenzymes and drug transporters: CYP3A4, OCT2, P-glycoprotein (P-gp)
N-desmethyl-vandetanib, an active metabolite of vandetanib that makes up approximately 7% to 17.1% of vandetanib exposure, is formed by CYP3A4. Strong CYP3A4 inducers should be avoided during vandetanib therapy, as concomitant use with rifampicin decreased vandetanib plasma concentrations. Additionally, vandetanib has increased plasma concentrations of metformin (OCT2 substrate) and digoxin (P-gp substrate).
-Route-Specific Pharmacokinetics
Oral Route
Absorption of oral vandetanib is slow; peak plasma concentrations are typically achieved at a median of 6 hours (range, 4 to 10 hours) after dosing. Accumulation of vandetanib of approximately 8-fold occurs with multiple dosing. Steady-state concentrations are achieved at approximately 3 months. Exposure to vandetanib is unaffected by food.
-Special Populations
Hepatic Impairment
After a single 800 mg vandetanib dose, comparable mean systemic exposure and clearance values were obtained from patients with mild (n = 8), moderate (n = 7), or severe (n = 6) hepatic impairment as compared with patients with normal hepatic function (n = 5). Limited data are available regarding use in patients with a serum bilirubin greater than 1.5 times the upper limit of normal. Use of vandetanib is not recommended for patients with either moderate or severe hepatic impairment, as safety and efficacy have not been established.
Renal Impairment
After a single 800 mg vandetanib dose, comparable mean systemic exposure and clearance values were obtained from patients with mild renal impairment (n = 6) as compared with patients with normal renal function (n = 10). Average systemic exposure increased by 39% for patients with moderate renal impairment (n = 8) and by 41% for patients with severe renal impairment (n = 6). A reduced vandetanib dose is needed for patients with moderate or severe renal impairment (see Dosage).
Pediatrics
The pharmacokinetics of vandetanib have not been evaluated in pediatric patients.
Geriatric
No relationship was apparent between oral clearance of vandetanib and patient age. No adjustment in starting dose is required for patients over 65 years of age.
Gender Differences
No relationship was apparent between oral clearance of vandetanib and patient gender.
Ethnic Differences
Based on a cross-study comparison, Japanese patients (n = 3) and Chinese patients (n = 7) had average exposures that were higher than Caucasian patients (n = 7) receiving the same vandetanib dose. Exact exposure differences were not reported.