Caprelsa (vandetanib)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Vandetanib, an inhibitor of multiple receptor tyrosine kinases, is an antineoplastic agent.
Vandetanib, an inhibitor of multiple receptor tyrosine kinases, is an antineoplastic agent. Receptor tyrosine kinases (RTKs) are involved in the initiation of various cascades of intracellular signaling events that lead to cell proliferation and/or influence processes critical to cell survival and tumor progression (e.g., angiogenesis, metastasis, inhibition of apoptosis), based on the respective kinase. Various tyrosine kinases and pathways are abnormally activated in medullary thyroid carcinoma cells (e.g., rearranged during transfection (RET) proto-oncogene signaling is associated with development of hereditary medullary thyroid cancer).
In vitro studies have shown that vandetanib inhibits the activity of multiple receptor tyrosine kinases, including vascular endothelial growth factor receptors (i.e., VEGFR-1, VEGFR-2, VEGFR-3), members of the epidermal growth factor receptor (EGFR) family, RET, protein tyrosine kinase 6 (BRK), TIE2, members of the EPH receptor kinase family, and members of the Src family of tyrosine kinases. The N-desmethyl metabolite of the drug, which represents 7 to 17.1% of vandetanib exposure, has similar inhibitory activity to the parent compound for VEGF receptors (KDR and Flt-1) and EGFR. In vivo, vandetanib has been shown to reduce tumor cell-induced angiogenesis and tumor vessel permeability; the drug also has been shown to inhibit tumor growth and metastasis in mouse models of cancer.
Vandetanib is partially metabolized by cytochrome P-450 (CYP) isoenzyme 3A4. Approximately 44 or 25% of an oral dose of the drug is excreted in feces or urine, respectively, as unchanged drug or metabolites. The median plasma half-life of vandetanib is 19 days.
Limited data indicate that systemic exposure to vandetanib is higher in Japanese and Chinese patients than in Caucasian patients receiving the same dose.
USES: This medication is used to treat thyroid cancer (medullary type). It works by slowing or stopping the growth of cancer cells. Vandetanib belongs to a class of drugs known as tyrosine kinase inhibitors.
Generic name: vandetanib
Pronunciation: (van-DET-a-nib)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Caprelsa
Indications
The following indications are listed for Caprelsa:
- Medullary Thyroid Carcinoma
Dosing
Interrupt vandetanib therapy if the QT interval (corrected for heart rate using Fridericia's formula (QTcF)) exceeds 500 msec. When QTcF returns to less than 450 msec, vandetanib may be resumed at a reduced dosage.
If hypertension occurs, dosage reduction or temporary interruption of vandetanib therapy may be necessary to control blood pressure. If hypertension cannot be controlled, vandetanib should not be resumed.
If heart failure occurs, consider discontinuation of vandetanib therapy.
If severe skin reactions occur, permanently discontinue vandetanib therapy and refer the patient for urgent medical evaluation. Systemic therapy (e.g., corticosteroids) may be required.
If severe diarrhea occurs, interrupt vandetanib therapy. When diarrhea improves, vandetanib may be resumed at a reduced dosage.
If grade 3 or greater toxicity occurs, interrupt vandetanib therapy. When the toxicity resolves or improves to grade 1, vandetanib may be resumed at a reduced dosage. Reduce the dosage of vandetanib in decrements of 100 mg daily (i.e., from 300 to 200 mg daily, from 200 to 100 mg daily).
Administer vandetanib orally without regard to meals. Swallow vandetanib tablets whole and do not crush. If tablets are accidentally crushed, avoid direct contact with skin. If such contact occurs, wash the affected area thoroughly.
If a dose is missed, do not take the missed dose if it is <=12 hours until the next scheduled dose.
If vandetanib tablets cannot be swallowed whole, the manufacturer states that the tablet may be dispersed in a glass containing 60 mL (2 ounces) of noncarbonated water; no other liquids should be used. Stir the water, without crushing the tablet, for approximately 10 minutes until the tablet is dispersed; the tablet will not completely dissolve. Swallow the aqueous dispersion immediately; to ensure the full dose is administered, mix any residue in the glass with an additional 120 mL (4 ounces) of noncarbonated water and swallow. The aqueous dispersion also may be administered through a nasogastric or gastrostomy tube.
Follow procedures for proper handling and disposal of antineoplastic drugs when preparing or administering vandetanib.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Congenital long QT syndrome.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in more than 20% of patients receiving vandetanib include diarrhea/colitis, rash, acneiform dermatitis, hypertension, nausea, headache, upper respiratory tract infections, decreased appetite, abdominal pain, hypocalcemia, increased ALT concentrations, and hypoglycemia.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of vandetanib have not been established in pediatric patients.
Based on its mechanism of action and animal findings, vandetanib can cause fetal harm when administered to a pregnant woman. In animal studies, vandetanib was embryotoxic, fetotoxic, and teratogenic at exposures equivalent to or lower than those expected at the 300-mg clinical dose; adverse effects on female fertility, embryofetal development, and postnatal development of pups also were observed.
Advise patients of the potential hazard to a fetus. Advise females of reproductive potential, and males with female partners of reproductive potential, to use effective contraception during treatment with vandetanib and for 4 months following the last dose.
Vandetanib is distributed into milk in rats. It is not known whether vandetanib or its metabolites are distributed into human milk. The effects of vandetanib on the breast-fed child or on milk production are also unknown. Because of the potential for serious adverse reactions to vandetanib in nursing infants, advise females not to breast-feed during vandetanib therapy and for 4 months after the final dose.
The manufacturer makes no specific dosage recommendations in patients >=65 years of age.
The phase 3 clinical study in patients with medullary thyroid cancer did not include sufficient numbers of patients >=65 years of age to determine whether they respond differently than younger patients.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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