drug-monograph

vanDETanib

Cancer Type

Endocrine, Thyroid

Other Names

Caprelsa®

Appearance

white tablet in various strengths and shapes

Funding Program

Exceptional Access Program

A - Drug Name

vanDETanib

COMMON TRADE NAME(S): Caprelsa®

B - Mechanism of Action and Pharmacokinetics

Vandetanib is an inhibitor of multiple tyrosine kinase families, including VEGFR-2 (vascular endothelial growth factor receptor-2), EGFR (epidermal growth factor receptor), and the RET (rearranged during transfection) proto-oncogene, which affects angiogenesis and cell survival.

Absorption

Peak plasma concentrations reached at a median of 6 hours after dosing. Accumulation is seen on multiple dosing with steady state achieved from approximately 2 months. Pharmacokinetics is linear within the usual dosing range. Vandetanib exposure is not affected by a meal. Limited data suggested that Chinese and Japanese patients had higher average drug exposure than Caucasian patients.

Distribution

PPB	94% (human serum albumin and α1-acid glycoprotein)

Metabolism

Metabolized by CYP3A4 to N-desmethyl vandetanib and by monooxygenase enzymes FMO1 and FMO3 to vandetanib-N-oxide. Glucuronide conjugate is a minor metabolite.

Active metabolites

Yes

Inactive metabolites

Yes

Elimination

Within 21 days, about 69% of a dose is recovered in feces (44%) and in urine (25%). Due to the long half-life of the drug, elimination may continue beyond 21 days. Vandetanib may inhibit its renal excretion via hOCT2 and inhibit the renal clearance of creatinine. No clear difference in clearance with respect to age and gender.

Half-life

19 days

C - Indications and Status

Health Canada Approvals:

Thyroid cancer

Refer to the product monograph for a full list and details of approved indications.

Vandetanib can only be prescribed and dispensed by physicians and pharmacies under certification by the Caprelsa® restricted distribution program. Patients must be enrolled and comply with the requirements of this program before receiving vandetanib.

D - Adverse Effects

Emetogenic Potential:

Minimal – No routine prophylaxis; PRN recommended

Extravasation Potential: Not applicable

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Cardiovascular	Arterial thromboembolism (1%)	E
	Artery aneurysm (rare)	E D L
	Artery dissection (rare)	E D L
	Cardiotoxicity (heart failure < 1%)	D
	Hypertension (32%) (7% severe)	E
	QT interval prolonged (14%) (8% severe) (± arrhythmia)	E
	Venous thromboembolism (<1%)	E
Dermatological	Alopecia (<10%)	E
	Erythema multiforme (<1%)	E
	Nail disorder (<10%)	E
	Photosensitivity (13%)	E
	Rash (45%) (3% severe)	E
	Stevens-Johnson syndrome (<1%)	E
	Toxic epidermal necrolysis (<1%)	E
Gastrointestinal	Abdominal pain (14%)	E
	Anorexia, weight loss (21%)	E
	Diarrhea (56%) (11% severe)	E
	Dyspepsia (11%)	E
	GI perforation (<1%)	E
	Nausea, vomiting (33%)	I
General	Delayed wound healing (<1%)	E
	Fatigue (24%)	E
Hematological	Hemorrhage (<1%)	E
Hepatobiliary	↑ LFTs (51%) (2% severe)	E
	Pancreatitis (<1%)	E
Metabolic / Endocrine	Abnormal electrolyte(s) (11%) (3% severe) (↑/↓Ca, ↓K, ↓Na, or ↓Mg)	E
	Hypothyroidism (6%)	E
Musculoskeletal	Osteonecrosis of jaw (or non-mandibular bones; rare)	E
Nervous System	Depression (1%) (severe)	E
	Headache (26%)	E
	Insomnia (13%)	E
	Posterior reversible encephalopathy syndrome (PRES) (rare)	E
	Tremor (<10%)	E
Ophthalmic	Other - corneal opacity (5%)	E
Renal	Nephrotoxicity (<1%)	E
Respiratory	Cough (11%)	E
	Pneumonitis (<1%)	D

* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.

** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)

The most common side effects for vandetanib include diarrhea, ↑ LFTs, rash, nausea, vomiting, hypertension, headache, fatigue, anorexia, weight loss, abdominal pain and qt interval prolonged.

QT prolongation appears to be dose-dependent. The average change from baseline was 35 ms and 7% of patients had QTcF > 500 ms. Due to the 19 day half-life, QT prolongation may not resolve quickly. Serum potassium should be maintained at 4 mEq/L or higher; magnesium and calcium levels should be kept within normal range. Hypertensive crisis has been observed. Cardiotoxicity has been reported and may not be reversible after vandetanib discontinuation.

Severe cases of artery dissection (with or without hypertension) and artery aneurysm (including rupture) have been reported in patients using VEGFR TKIs.

LFTs usually resolve while continuing treatment with vandetanib, while others usually recover after withholding treatment for 1-2 weeks. Cases of fatal hepatic failure have been reported with vandetanib use in patients with pre-existing hepatic disease.

Vandetanib slows but does not prevent wound healing. The safety of restarting vandetanib treatment after resolution of wound healing complications has not been established.

Osteonecrosis of the jaw or non-mandibular bone has been reported. Perform preventive dentistry prior to vandetanib treatment. Avoid invasive dental procedures, if possible, while on vandetanib.

Fatal cases of hemorrhage, hepatic failure, skin reactions or ILD have been reported.

E - Dosing

Refer to protocol by which patient is being treated.

Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.

Potassium, calcium and magnesium levels should be corrected before starting treatment. Do not start treatment in patients with QT interval ≥ 500 ms. Serum potassium level should be maintained at 4 mEq/L or higher (high normal range) and magnesium and calcium should be kept within normal range to decrease the risk of QT prolongation.

Patients should be provided with loperamide and instructions on how to manage diarrhea.

Patients taking vandetanib have a potential for photosensitivity upon sun exposure. They should wear protective clothing and/or sunblock (with an SPF of at least 30) during vandetanib treatment and for 4 months after the last dose.

Hold vandetanib for at least 1 month before elective surgery (including dental surgery, if possible). Do not administer vandetanib for at least 2 weeks after major surgery and until adequate wound healing.

Adults:

Oral: 300 mg Daily

Dosage with Toxicity:

Dose Level	Vandetanib Dose (mg/day)
0	300
-1	200
-2	100
-3	Discontinue

Toxicity	Action
Grade 1 or 2 skin reactions	Treat symptomatically or by ↓ dose.
Grade 3 or 4 skin toxicity	Treat symptomatically and hold until ≤ grade 1, then ↓ 1 dose level. OR Discontinue if Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis or grade 4.
Grade 3 or 4 hypertension	Hold; control blood pressure medically. Consider ↓ dose.
Grade 1 or 2 diarrhea	Treat symptomatically with loperamide and hydration.
Grade 3 or 4 diarrhea	Hold until grade 1, then ↓ 1 dose level.
Hemoptysis (≥ 2.5 mL)	Hold until resolved. Consider discontinuing.
QTcF ≥ 500 ms	Hold until QTcF < 450 ms then ↓ 1 dose level; consider cardiology consult.
Radiological changes suggestive of pneumonitis	Investigate. If mild may continue treatment ± corticosteroids / antibiotics during investigation; otherwise hold. If pneumonitis confirmed, discontinue.
Signs of symptoms of hypothyroidism	Adjust thyroid replacement therapy. Monitor TSH.
Grade 3 or 4 LFTs	Hold until grade 1. Consider ↓ dose.
Severe arterial thromboembolism Severe heart failure PRES Severe bleeding Osteonecrosis	Discontinue.
Other grade 3 or 4 related organ toxicity	Hold until grade 1, then ↓ 1 dose level.

Dosage with Hepatic Impairment:

Not recommended for use in patients with moderate and severe hepatic impairment (Child Pugh B and C). Limited data exist in patients with bilirubin > 1.5 x ULN.

Dosage with Renal Impairment:

Exposure is increased in patients with renal impairment. The patient and QTcF must be closely monitored.

Creatinine Clearance (mL/min)	Starting Daily Dose
≥ 50	300 mg
30 to 49	200 mg
< 30	Not recommended for use

Dosage in the elderly:

No adjustment in starting dose is required. Limited data in patients over 75 years of age.

Children:

No pediatric indications. Safety and efficacy have not been established.

F - Administration Guidelines

Vandetanib may be taken with or without meals.
Take the dose at about the same time each day. Swallow whole; do not crush or chew.
If the patient has difficulty swallowing the tablet(s), may mix it with water as follows:
- Put the whole tablet into half a glass (50 mL) of non-carbonated water. Do not use other liquids.
- Stir the water until the tablet disperses. This may take about 10 minutes.
- Drink the mixture immediately.
- Rinse the empty glass well with another half a glass of water and drink it.
- This liquid mixture can also be given through nasogastric or gastrostomy tubes.
Avoid products and juices containing grapefruit, star fruit, pomegranate, Seville oranges or other similar fruits that can inhibit CYP3A4.
If a dose is missed, give it if it is within 12 hours from the missed dose, otherwise skip and give the next dose as scheduled.
Store vandetanib at room temperature (15 to 30°C).

G - Special Precautions

Contraindications:

Congenital long QT syndrome or with a persistent QTcF of ≥ 500 ms
Uncorrected hypokalemia, hypomagnesemia or hypocalcemia
Uncontrolled hypertension
Patients who have a hypersensitivity to this drug or any of its components

Other Warnings/Precautions:

Do not give vandetanib to patients with:
- a history of Torsade de Pointes (unless all risk factors have been corrected), bradyarrhythmias or uncompensated heart failure.
- a recent history of hemoptysis of ≥ half teaspoon of red blood.
Use caution when driving or operating machinery since blurred vision has been reported during treatment.

Other Drug Properties:

Carcinogenicity: Not observed in animal studies

Pregnancy and Lactation:

Fetotoxicity: Documented in animals
Embryotoxicity: Documented in animals
Teratogenicity: Documented in animals
Mutagenicity: No
Clastogenicity: No
Genotoxicity: No
Pregnancy:
- Vandetanib is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners during treatment, and for at least 4 months after the last dose.
Excretion into breast milk: Yes
Breastfeeding:
- Breastfeeding is not recommended.
Fertility effects: Documented in animals

H - Interactions

AGENT	EFFECT	MECHANISM	MANAGEMENT
Drugs that may prolong QT (e.g. Amiodarone, procainamide, sotalol, venlafaxine, amitriptyline, sunitinib, methadone, chloroquine, clarithromycin, haloperidol, fluconazole, moxifloxacin, domperidone, ondansetron)	↑ risk of QT prolongation	Additive	Avoid; if no alternative treatment exists, close QT monitoring should be performed
CYP3A4 inducers (e.g. phenytoin, rifampin, dexamethasone, carbamazepine, phenobarbital, St. John’s Wort)	↓ vandetanib concentration and exposure	↑ metabolism of vandetanib	Avoid; consider alternative drugs
CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, ritonavir and clarithromycin)	↑ vandetanib exposure and ↓ clearance (theoretical)	↓ metabolism of vandetanib	Avoid potent CYP3A4 inhibitors. Caution with other CYP3A4 inhibitors. Consider alternative drugs
Cisplatin	↑ cisplatin exposure (limited data)	Possible accumulation of total platinum	Caution
P-glycoprotein substrates (e.g. verapamil, digoxin, morphine, ondansetron)	Potential to ↑ exposure of P-gp substrates (up to 23% for digoxin)	Vandetanib inhibits P-gp	Caution; monitor closely; substrate dose adjustment may be required
OCT2 substrates (e.g. metformin)	Potential to ↓ elimination or ↑ exposure (up to 74%) of drugs excreted by OCT2	Vandetanib inhibits OCT2	Caution; monitor closely; substrate dose adjustment may be required
Drugs associated with osteonecrosis (e.g. bisphosphonates)	↑ risk of osteonecrosis	Additive	Caution

I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.

Recommended Clinical Monitoring

Monitor Type	Monitor Frequency
ECG and blood pressure	At baseline, 2-4 weeks and 8-12 weeks during treatment, and q3 months thereafter, also after dose adjustments
Electrolytes (including calcium, potassium, magnesium) and TSH	At baseline, 2-4 weeks and 8-12 weeks during treatment, then q3 months thereafter, also after dose adjustments
CBC	Baseline and at each visit
Liver function tests	Baseline and at each visit
Renal function tests	Baseline and at each visit
Oral examination (monitoring for osteonecrosis of the jaw)	Baseline and as clinically indicated
Clinical toxicity assessment for rash, hypertension, wound healing, diarrhea, arterial/venous thromboembolism, bleeding, osteonecrosis (non-mandibular), neurologic, cardiovascular, ophthalmic and respiratory side effects	At each visit

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

J - Supplementary Public Funding

Exceptional Access Program (EAP Website )

vanDETanib - Monotherapy for symptomatic and/or progressive medullary thyroid cancer (MTC), with specific criteria

K - References

Product Monograph: Caprelsa® (vandetanib). AstraZeneca Canada, May 2025.

Product Monograph: Caprelsa® (vandetanib). AstraZeneca US, June 2011 and May 2025.

Product Monograph Update: Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs). Health Canada InfoWatch, June 2020.

Commander H, Whiteside G, Perry C. Vandetanib: first global approval. Drugs 2011;71(10):1355-68.

Martin P, Oliver S, Robertson J, et al. Pharmacokinetic drug interactions with vandetanib during coadministration with rifampicin or itraconazole. Drugs R D 2011;11(1):37-51.

July 2026 DM retrieve 0707

L - Disclaimer

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Last Updated: July 27, 2026

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