Vandetanib

Vandetanib is a prescription medication used for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease. 

• Vandetanib is available under the following different brand names: Caprelsa.

Common side effects of Vandetanib include:

• High blood pressure,
• Diarrhea,
• Stomach pain,
• Nausea,
• Loss of appetite,
• Headache,
• Tiredness,
• Acne,
• Skin rash,
• Stuffy nose,
• Sneezing, and
• Sore throat

Serious side effects of Vandetanib include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Fever,
• Sore throat,
• Burning eyes,
• Skin pain,
• Red or purple skin rash with blistering and peeling,
• Fast or pounding heartbeats,
• Fluttering in your chest,
• Sudden dizziness,
• Wheezing,
• Dry cough,
• Shortness of breath,
• Any unhealing wound,
• Severe or ongoing diarrhea,
• Swelling,
• Rapid weight gain,
• Headache,
• Confusion,
• Change in mental status,
• Seizure,
• Extreme tiredness,
• Dry skin,
• Joint pain or stiffness,
• Muscle pain or weakness,
• Hoarse voice,
• Increased sensitivity to cold temperatures,
• Severe headache,
• Pounding in the neck or ears,
• Anxiety,
• Irregular heartbeats,
• Unusual bleeding,
• Easy bruising,
• Cough with bloody mucus,
• Vomit that looks like coffee grounds,
• Sudden numbness or weakness (especially on one side of the body),
• Confusion,
• Trouble speaking or understanding speech,
• Sudden severe headache, and
• Problems with vision or balance

Rare side effects of Vandetanib include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 100 mg
• 300 mg

Medullary Thyroid Cancer

Adult dosage

• 300 mg orally once a day with or without food
• Continued until disease progression or unacceptable toxicity occurs.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Vandetanib has severe interactions with the following drugs:
  • bosentan
  • carbamazepine
  • dexamethasone
  • eslicarbazepine acetate
  • etravirine
  • fosphenytoin
  • goserelin
  • lefamulin
  • leuprolide
  • nafcillin
  • nevirapine
  • oxcarbazepine
  • pentobarbital
  • phenobarbital
  • phenytoin
  • primidone
  • rifabutin
  • rifampin
  • rifapentine
  • St John's Wort
• Vandetanib has serious interactions with at least 154 other drugs.
• Vandetanib has moderate interactions with at least 72 other drugs.
• Vandetanib has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • grapefruit
  • larotrectinib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Congenital long QT syndrome 

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Vandetanib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Vandetanib?”

Cautions

• Use in patients with indolent, asymptomatic, or slowly progressing disease should be carefully considered because of the treatment-related risks.
• Potent CYP3A4 inducers reduce exposure to vandetanib by up to 40%; however, no clinically significant effect on exposure to vandetanib was observed in the presence of the potent CYP3A4 inhibitors.
• Fatal skin reactions, including Stevens-Johnson syndrome and severe toxic epidermal necrolysis, reported; permanently discontinue therapy for severe skin reactions; photosensitivity reactions can occur during treatment and up to 4 months after discontinuing.
• Interstitial lung disease (ILD), resulting in death has been reported; interrupt therapy and investigate unexplained dyspnea, cough, and fever; discontinue if ILD confirmed.
• Ischemic cerebrovascular events have been observed; discontinue therapy if a severe ischemic cerebrovascular event occurs.
• Can cause fetal harm when administered to pregnant women; avoid pregnancy while receiving vandetanib and for 4 months following treatment.
• Serious hemorrhagic events, some fatal, have been observed; do not administer with a recent history of hemoptysis and discontinue if severe hemorrhage occurs.
• Heart failure observed, including some fatal cases; may be necessary to discontinue vandetanib; heart failure may not be reversible.
• Diarrhea is common and routine antidiarrheal agents are recommended to avoid electrolyte disturbances that may exacerbate the risk of QT prolongation.
• Hypothyroidism reported; obtain thyroid-stimulating hormone (TSH) at baseline, at 2 to 4 weeks and 8 to 12 weeks after starting treatment, and every 3 months thereafter; if signs or symptoms of hypothyroidism occur, examine thyroid hormone levels, and adjust thyroid replacement therapy accordingly
• Hypertension, including hypertensive crisis, may occur; if hypertension remains uncontrolled, do not resume therapy.
• Renal failure occurred; withhold, reduce dose, or permanently discontinue based on the severity.
• Not recommended in patients with moderate or severe hepatic impairment
• Hypersensitivity including anaphylaxis has been reported.
• QT prolongation
  • May prolong QT interval in a concentration-dependent manner.
  • Torsades de pointes, ventricular tachycardia, and sudden death have been reported.
  • Do not initiate in patients whose QTcF interval is above 450 msec.
  • Do not administer to patients who have a history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure.
  • Not studied in patients with ventricular arrhythmias or recent myocardial infarction
  • Obtain ECG, serum potassium, calcium, magnesium, and TSH at baseline, then 2-4 and 8-12 weeks after treatment initiation, then every 3 months for at least a year thereafter; reduce the dose as appropriate.
• Wound healing
  • Impaired wound healing can occur in patients who receive drugs that inhibit the VEGF signaling pathway.
  • Therapy has the potential to adversely affect wound healing; withhold therapy for at least 1 month before elective surgery.
  • Do not administer therapy for at least 2 weeks following major surgery and until adequate wound healing.
  • Safety of resumption of treatment after resolution of wound healing complications not established.
• Reversible posterior leukoencephalopathy syndrome (RPLS)
  • Syndrome of subcortical vasogenic edema diagnosed by an MRI of the brain, has been observed.
  • This syndrome should be considered in any patient presenting with seizures, headaches, visual disturbances, confusion, or altered mental function.
  • In clinical studies, 3 or 4 patients who developed RPLS while taking vandetanib, including one pediatric patient, also had hypertension.
  • Consider discontinuation of vandetanib treatment in patients with RPLS
• Risk Evaluation and Mitigation Strategy (REMS) Program
  • Only available only through a restricted distribution program called the CAPRELSA REMS Program
  • Only prescribers and pharmacies certified with the program can prescribe and dispense the drug.
  • To learn about the specific REMS requirements and to enroll in CAPRELSA REMS Program, call 1-800-817-2722 or visit www.caprelsarems.com.
• Drug interaction overview
  • Substrate of CYP3A4
    • CYP3A4 inducers
    • Avoid coadministration.
  • Strong CYP3A4 inducers (. g, rifampin) decrease the vandetanib plasma concentration.
    • St John wort may decrease vandetanib exposure unpredictably; avoid the use.
    • Organic cation transporter type 2 (OCT2) transporter
    • Use caution and closely monitor.
    • Vandetanib may increase the plasma concentration of metformin (transported by OCT2)
• Digoxin
  • Use with caution.
  • Vandetanib may increase digoxin levels.
• Drugs that prolong QT interval
  • Avoid coadministration; if such drugs are given to patients already receiving vandetanib and no alternant exists, perform ECG monitoring more frequently.
  • Coadministration of such drugs with vandetanib may potentiate the QT-prolonging effects.

Pregnancy and Lactation

• Based on the mechanism of action, therapy can cause fetal harm when administered to a pregnant woman; the drug is embryotoxic and fetotoxic
• Reproductive potential
  • Therapy can cause fetal harm when administered to a pregnant woman; advise females of reproductive potential to use effective contraception during treatment and for 4 months after the final dose.
  • There are no data on the effect on human fertility; results from animal studies indicate that therapy can impair male and female fertility.
• Lactation
  • There are no data on the presence of the drug or its metabolites in human milk or its effects on the breastfed child or milk production; the drug was present in the milk of lactating rats; because of the potential for serious adverse reactions from drug in breastfed children, advise women not to breastfeed during therapy and for 4 months after the final dose.