Drug: Caprelsa

Vandetanib has the chemical name N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl) methoxy]quinazolin-4-amine. The structural and molecular formulas are:
C22H24BrFN4O2 Vandetanib has a molecular weight of 475.36. Vandetanib exhibits pH-dependent solubility, with increased solubility at lower pH. Vandetanib is practically insoluble in water with a value of 0.008 mg/mL at 25°C (77°F ). CAPRELSA tablets for daily oral administration are available in two dosage strengths containing either 100 mg or 300 mg of vandetanib. The tablet cores contain the following inactive ingredients: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, crospovidone, povidone, and magnesium stearate. The tablet film-coat contains the following inactive ingredients: hypromellose 2910, macrogol 300, and titanium dioxide E171. Last reviewed on RxList: 4/10/2014
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

The following serious adverse reactions are discussed elsewhere in the label:
  • QT Prolongation and Torsades de Pointes [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
  • Skin Reactions and Stevens-Johnson Syndrome [see WARNINGS AND PRECAUTIONS]
  • Interstitial Lung Disease [see WARNINGS AND PRECAUTIONS]
  • Ischemic Cerebrovascular Events [see WARNINGS AND PRECAUTIONS]
  • Hemorrhage [see WARNINGS AND PRECAUTIONS]
  • Heart Failure [see WARNINGS AND PRECAUTIONS]
  • Diarrhea [see WARNINGS AND PRECAUTIONS]
  • Hypothyroidism [see WARNINGS AND PRECAUTIONS]
  • Hypertension [see WARNINGS AND PRECAUTIONS]
  • Reversible Posterior Leukoencephalopathy Syndrome [see WARNINGS AND PRECAUTIONS]
  • Embryofetal Toxicity [see WARNINGS AND PRECAUTIONS]
Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Patients with unresectable locally advanced or metastatic medullary thyroid cancer were treated with CAPRELSA 300 mg (n=231) or Placebo (n=99). The population exposed to CAPRELSA was 58% male, 94% white, and had a median age of 50 years. The data described below reflect a median exposure to CAPRELSA for 607 days. The most commonly reported adverse drug reactions which occurred in > 20% of CAPRELSA-treated patients and with a between-arm difference of ≥ 5% included, in order of decreasing frequency: diarrhea/colitis, rash, acneiform dermatitis, hypertension, nausea, headache, upper respiratory tract infection, decreased appetite, and abdominal pain. Among CAPRELSA-treated patients, dose interruption occurred in 109 (47%) and dose reduction occurred in 83 (36%). Adverse reactions led to study treatment discontinuation in 28 of 231 patients (12%) receiving CAPRELSA and in 3 of 99 patients (3.0%) receiving placebo. Adverse reactions leading to permanent discontinuation in 2 or more ( ≥ 0.9%) patients treated with CAPRELSA were: asthenia (1.7%), rash (1.7%), diarrhea (0.9%), fatigue (0.9%), pyrexia (0.9%), elevated creatinine (0.9%), QT prolongation (0.9%), and hypertension (0.9%). Table 1 : Per-Patient Incidence of Selected Adverse Reactions Occurring at a Higher Incidence in CAPRELSA-Treated Patients During Randomized Treatment [Between-Arm Difference of ≥ 5% (All Grades)1]
System Organ Class Preferred Term  CAPRELSA 300 mg
N=231  Placebo
N=99  All Grades (%)  Grade 3-4 (%)  All Grades (%)  Grade 3-4 (%)  Gastrointestinal Disorders    Diarrhea/Colitis  57 11 27 2   Nausea  33 1 16 0   Abdominal Pain2  21 3 11 0   Vomiting  15 1 7 0   Dyspepsia  11 0 4 0   Dry Mouth  9 0 3 0 Skin and Cutaneous Disorders    Rash3  53 5 12 0   Dermatitis Acneiform/Acne  35 1 7 0   Dry Skin  15 0 5 0   Photosensitivity Reaction  13 2 0 0   Pruritus  11 1 4 0   Nail abnormalities4  9 0 0 0   Alopecia  8 N/A  0 N/A  Vascular Disorders    Hypertension/Hypertensive Crisis/Accelerated Hypertension  33 9 5 1 Nervous System Disorders    Headache  26 1 9 0   Dysgeusia  8 0 3 0 General Disorders    Fatigue5  24 6 23 1 Infections    Upper Respiratory Tract Infections6  23 0 16 0 Metabolic and Nutritional Disorders    Decreased Appetite  21 4 12 0   Hypocalcemia  11 2 3 0 Investigations    ECG QT Prolonged7  14 8 1 1 Eye Disorders    Corneal Abnormalities7  13 0 1 0   Blurred Vision  9 0 1 0 Renal Disorders    Proteinuria  10 0 2 0 Psychiatric Disorders    Depression  10 2 3 0 Endocrine Disorders    Hypothyroidism  6 0 0 0 Musculoskeletal Disorders    Muscle Spasms  6 0 1 0 1CTCAE version 3 was used to grade adverse events.
2Includes abdominal pain, abdominal pain upper, lower abdominal pain and abdominal discomfort.
3Includes rash, rash (erythematous, generalized, macular, maculo-papular, papular, pruritic, and exfoliative), dermatitis, dermatitis bullous, generalized erythema, and eczema.
4Includes nail disorder, nail bed inflammation, nail bed tenderness, paronychia, nail bed infection, and nail infection.
5Included in Table 1 due to the increased incidence of severe fatigue in the CAPRELSA group compared to the placebo group.
6Includes laryngitis, nasopharyngitis, pharyngitis, sinusitis, upper respiratory tract infection, acute sinusitis, rhinitis, and tracheitis.
769% had QT prolongation > 450ms and 7% had QT prolongation > 500ms by ECG using Fridericia correction.
8Includes corneal edema, corneal opacity, corneal dystrophy, corneal pigmentation, keratopathy, arcus lipoides, corneal deposits, acquired corneal dystrophy. Clinically important uncommon adverse drug reactions in patients who received CAPRELSA versus patients who received placebo included pancreatitis (0.4% vs. 0%) and heart failure (0.9% vs. 0%). Blurred vision was more common in patients who received CAPRELSA versus patients who received placebo for medullary thyroid cancer (9% vs. 1%, respectively). Scheduled slit lamp examinations revealed corneal opacities (vortex keratopathies) in treated patients, which can lead to halos and decreased visual acuity. Perform ophthalmologic examination, including slit lamp examination, in patients who report visual changes. Class effects CAPRELSA is an inhibitor of vascular endothelial growth factor receptor (VEGFR) signaling. Inhibition of VEGFR signaling can result in intestinal perforation. Intestinal perforation occurred in 0.4% of CAPRELSA treated patients versus 0% of placebo treated patients. The incidence of Grade 1-2 bleeding events was 14% in patients receiving CAPRELSA compared with 7% on placebo in the randomized portion of the medullary thyroid cancer (MTC) study.2 Table 2 : Per-Patient Incidence of Selected Laboratory Abnormalities in Patients with MTC Occurring at a Higher Incidence in CAPRELSA-Treated Patients [Between-Arm Difference of ≥ 5% (All Grades)1]
Laboratory Abnormalities  CAPRELSA 300 mg
N=231  Placebo
N=99  All Grades (%)  Grade 3–4 (%)  All Grades (%)  Grade 3–4 (%)  Chemistries    Hypocalcemia  57 6 25 3   ALT Increased  51 2 19 0   Hypoglycemia  24 0 7 1   Creatinine Increased  16 0 1 0   Hypomagnesemia  7 < 1  2 0 Hematologic    Neutropenia  10 < 1  5 2   Thrombocytopenia  9 0 3 0 1CTCAE version 3 was used to grade laboratory abnormalities. No patient with a Grade 3-4 ALT elevation had a concomitant increase in bilirubin in the MTC study. Read the Caprelsa (vandetanib) Side Effects Center for a complete guide to possible side effectsLearn More »

Source: http://www.rxlist.com

The recommended dose of CAPRELSA is 300 mg taken orally once daily until disease progression or unacceptable toxicity occurs. CAPRELSA may be taken with or without food. Do not take a missed dose within 12 hours of the next dose. Do not crush CAPRELSA tablets. The tablets can be dispersed in 2 ounces of water by stirring for approximately 10 minutes (will not completely dissolve). Do not use other liquids for dispersion. Swallow immediately after dispersion. Mix any remaining residue with 4 additional ounces of water and swallow. The dispersion can also be administered through nasogastric or gastrostomy tubes. Dosage Adjustment For adverse reactions The 300 mg daily dose can be reduced to 200 mg (two 100 mg tablets) and then to 100 mg for Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or greater toxicities. Interrupt CAPRELSA for the following:
  • Corrected QT interval, Fridericia (QTcF) greater than 500 ms: Resume at a reduced dose when the QTcF returns to less than 450 ms.
  • CTCAE Grade 3 or greater toxicity: Resume at a reduced dose when the toxicity resolves or improves to CTCAE Grade 1.
For recurrent toxicities, reduce the dose of CAPRELSA to 100 mg after resolution or improvement to CTCAE Grade 1 severity, if continued treatment is warranted. Because of the 19-day half-life, adverse reactions including a prolonged QT interval may not resolve quickly. Monitor appropriately [see WARNINGS AND PRECAUTIONS]. For patients with renal impairment Reduce the starting dose to 200 mg in patients with moderate (creatinine clearance ≥ 30 to < 50 mL/min) and severe (creatinine clearance < 30 mL/min) renal impairment [see WARNINGS AND PRECAUTIONS and Use In Specific Populations]. For patients with hepatic impairment CAPRELSA is not recommended for use in patients with moderate and severe hepatic impairment [see Use in Specific Populations].

Source: http://www.rxlist.com

Effect Of CYP3A4 Inducers On CAPRELSA Rifampicin, a strong CYP3A4 inducer, decreased vandetanib plasma concentrations. Avoid concomitant use of known strong CYP3A4 inducers during CAPRELSA therapy. Avoid concomitant use of St. John's Wort because it can decrease vandetanib exposure unpredictably [see CLINICAL PHARMACOLOGY]. Effect Of CAPRELSA On OCT2 Transporter CAPRELSA increased plasma concentrations of metforman that is transported by the organic cation transporter type 2 (OCT2). Use caution and closely monitor for toxicities when administering CAPRELSA with drugs that are transported by OCT2 [see CLINICAL PHARMACOLOGY]. Effect Of CAPRELSA On Digoxin CAPRELSA increased plasma concentrations of digoxin. Use caution and closely monitor for toxicities when administering CAPRELSA with digoxin [see CLINICAL PHARMACOLOGY]. Drugs That Prolong The QT Interval Avoid concomitant use of CAPRELSA with agents that may prolong the QT interval [see WARNINGS AND PRECAUTIONS]. Read the Caprelsa Drug Interactions Center for a complete guide to possible interactions Learn More »

Source: http://www.rxlist.com

CAPRELSA is indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease. Use CAPRELSA in patients with indolent, asymptomatic or slowly progressing disease only after careful consideration of the treatment related risks of CAPRELSA.

Source: http://www.rxlist.com

Do not use in patients with congenital long QT syndrome [see BOXED WARNING]. Last reviewed on RxList: 4/10/2014
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

In the event of an overdose, monitor patients closely for QTc prolongation. Because of the 19-day half-life, adverse reactions may not resolve quickly.

Source: http://www.rxlist.com

Dosage Forms & Strengths CAPRELSA 100-mg tablets are white, round, biconvex, film-coated, and intagliated with 'Z 100' on one side and plain on the reverse side.
CAPRELSA 300-mg tablets are white, oval, biconvex, film-coated, and intagliated with 'Z 300' on one side and plain on the reverse side. 100 mg Tablets Available in bottles containing 30 tablets (NDC 0310–7820–30).
300 mg Tablets Available in bottles containing 30 tablets (NDC 0310–7840–30). Storage And Handling CAPRELSA tablets should be stored at 25°C (77°F); excursions permitted to 15°C – 30°C (59°F – 86°F) [See USP controlled room temperature]. Procedures for proper handling and disposal of anticancer drugs should be considered. A guideline on this subject has been published.1 Do not crush CAPRELSA tablets. REFERENCES “OSHA Hazardous Drugs” (OSHA Technical Manual). OSHA. Distributed by: AstraZeneca Pharmaceuticals LP Wilmington, DE 19850. Issued 03/2014 Last reviewed on RxList: 4/10/2014
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

QT Prolongation And Torsades De Pointes CAPRELSA can prolong the QT interval in a concentration-dependent manner [see CLINICAL PHARMACOLOGY]. Torsades de pointes, ventricular tachycardia and sudden deaths have occurred in patients treated with CAPRELSA. Do not start CAPRELSA treatment in patients whose QTcF interval is greater than 450 ms. Do not administer CAPRELSA to patients who have a history of Torsades de pointes, congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure. CAPRELSA has not been studied in patients with ventricular arrhythmias or recent myocardial infarction. Vandetanib exposure is increased in patients with impaired renal function. Reduce the starting dose to 200 mg in patients with moderate to severe renal impairment and monitor QT interval frequently. Obtain an ECG and serum potassium, calcium, magnesium and TSH at baseline, 2-4 weeks and 8-12 weeks after starting treatment with CAPRELSA, and every 3 months thereafter. Monitor electrolytes and ECGs more frequently in patients who experience diarrhea. Following any dose reduction for QT prolongation or any dose interruption greater than 2 weeks, conduct QT assessments as described above. Maintain serum potassium levels of 4 mEq/L or higher (within normal range) and maintain serum magnesium and calcium levels within normal ranges to reduce the risk of QT prolongation. Avoid using CAPRELSA with drugs known to prolong the QT interval [see DRUG INTERACTIONS]. If such drugs are given to patients already receiving CAPRELSA and no alternative therapy exists, perform ECG monitoring of the QT interval more frequently. Stop CAPRELSA in patients who develop a QTcF greater than 500 ms until the QTcF returns to less than 450 ms. Dosing of CAPRELSA can then be resumed at a reduced dose [see DOSAGE AND ADMINISTRATION]. Skin Reactions And Stevens-Johnson Syndrome Severe skin reactions (including Stevens-Johnson syndrome), some leading to death, have occurred in patients treated with CAPRELSA. Consider permanent discontinuation of CAPRELSA for severe skin reactions [see DOSAGE AND ADMINISTRATION]. Photosensitivity reactions can occur during CAPRELSA treatment and up to 4 months after treatment discontinuation. Interstitial Lung Disease Interstitial Lung Disease (ILD) or pneumonitis, including fatalities, has occurred in patients treated with CAPRELSA. Consider a diagnosis of ILD in patients presenting with non-specific respiratory signs and symptoms. Interrupt CAPRELSA for acute or worsening pulmonary symptoms. Discontinue CAPRELSA if ILD is confirmed. Ischemic Cerebrovascular Events Ischemic cerebrovascular events, including fatalities, occurred in patients treated with CAPRELSA. In the randomized medullary thyroid cancer (MTC) study, ischemic cerebrovascular events occurred more frequently with CAPRELSA compared to placebo (1.3% compared to 0%). The safety of resumption of CAPRELSA therapy after resolution of an ischemic cerebrovascular event has not been studied. Discontinue CAPRELSA in patients who experience a severe ischemic cerebrovascular event. Hemorrhage Serious hemorrhagic events, including fatalities, occurred in patients treated with CAPRELSA. Do not administer CAPRELSA to patients with a recent history of hemoptysis of ≥ ½ teaspoon of red blood. Discontinue CAPRELSA in patients with severe hemorrhage. Heart Failure Heart failure, including fatalities, occurred in patients treated with CAPRELSA. Monitor for signs and symptoms of heart failure. Consider discontinuation of CAPRELSA in patients with heart failure. Heart failure may not be reversible upon stopping CAPRELSA. Diarrhea Diarrhea of Grade 3 or greater severity occurred in 11% of patients receiving CAPRELSA in the randomized MTC study. If diarrhea occurs, carefully monitor serum electrolytes and ECGs to reduce the risk and enable early detection of QT prolongation resulting from dehydration. Interrupt CAPRELSA for severe diarrhea. Upon improvement, resume CAPRELSA at a reduced dose [see DOSAGE AND ADMINISTRATION]. Hypothyroidism In the randomized MTC study in which 90% of the patients enrolled had prior thyroidectomy, increased dosing of thyroid replacement therapy was required in 49% of CAPRELSA-treated patients compared to 17% of placebo-treated patients. Obtain Thyroid-stimulating hormone (TSH) at baseline, at 2 -4 weeks and 8 -12 weeks after starting treatment with CAPRELSA, and every 3 months thereafter. If signs or symptoms of hypothyroidism occur, examine thyroid hormone levels and adjust thyroid replacement therapy accordingly. Hypertension Hypertension, including hypertensive crisis, has occurred in patients treated with CAPRELSA. Monitor all patients for hypertension. Dose reduction or interruption for hypertension may be necessary. If hypertension cannot be controlled, do not resume CAPRELSA [see DOSAGE AND ADMINISTRATION]. Reversible Posterior Leukoencephalopathy Syndrome Reversible posterior leukoencephalopathy syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by an MRI of the brain, has occurred in patients treated with CAPRELSA. Consider this syndrome in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. In clinical studies, three of four patients who developed RPLS while taking CAPRELSA also had hypertension. Discontinue CAPRELSA treatment in patients with RPLS. Drug Interactions Avoid administration of CAPRELSA with anti-arrhythmic drugs (including but not limited to amiodarone, disopyramide, procainamide, sotalol, dofetilide) and other drugs that may prolong the QT interval (including but not limited to chloroquine, clarithromycin, dolasetron, granisetron, haloperidol, methadone, moxifloxacin, and pimozide) [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY]. Renal Impairment Vandetanib exposure is increased in patients with impaired renal function. Reduce the starting dose to 200 mg in patients with moderate to severe renal impairment and monitor the QT interval closely. There is no information available for patients with end-stage renal disease requiring dialysis [see BOXED WARNING, DOSAGE AND ADMINISTRATION, Use in Specific Populations and CLINICAL PHARMACOLOGY]. Hepatic Impairment CAPRELSA is not recommended for use in patients with moderate and severe hepatic impairment, as safety and efficacy have not been established [see DOSAGE AND ADMINISTRATION]. Embryofetal Toxicity Based on its mechanism of action, CAPRELSA can cause fetal harm when administered to a pregnant woman. In nonclinical studies in rats, vandetanib was embryotoxic, fetotoxic, and teratogenic at exposures equivalent to or lower than those expected at the recommended human dose of 300 mg/day and had adverse effects on female fertility, embryofetal development, and postnatal development of pups. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Women of childbearing potential should avoid pregnancy. Advise women of childbearing potential that they must use effective contraception during CAPRELSA treatment and for at least four months following the last dose of CAPRELSA [see Use In Specific Populations]. CAPRELSA REMS (Risk Evaluation And Mitigation Strategy) Program Because of the risk of QT prolongation, Torsades de pointes, and sudden death, CAPRELSA is available only through a restricted distribution program called the CAPRELSA REMS Program. Only prescribers and pharmacies certified with the program are able to prescribe and dispense CAPRELSA. To learn about the specific REMS requirements and to enroll in the CAPRELSA REMS Program, call 1-800-236-9933 or visit www.caprelsarems.com. Patient Counseling Information See FDA-approved patient labeling (medication guide)
  • QT Prolongation and Torsades de Pointes: Advise patients to contact their healthcare provider in the event of syncope, pre-syncopal symptoms, and cardiac palpitations. Advise patients that their healthcare provider will monitor their electrolytes and ECGs during treatment [see WARNINGS AND PRECAUTIONS].
  • Severe skin reactions and Stevens-Johnson Syndrome: Advise patients to contact their healthcare provider in the event of skin reactions or rash. [see WARNINGS AND PRECAUTIONS].
  • Interstitial Lung Disease (ILD): Advise patients to contact their health care provider in the event of sudden onset or worsening of breathlessness, persistent cough or fever. [see WARNINGS AND PRECAUTIONS].
  • Diarrhea: Advise patients to contact their healthcare provider in the event of diarrhea [see WARNINGS AND PRECAUTIONS ]
  • Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Advise patients to contact their healthcare provider in the event of seizures, headaches, visual disturbances, confusion or difficulty thinking [see WARNINGS AND PRECAUTIONS]
  • Fetal Toxicity: Because CAPRELSA can cause fetal harm, advise patients of reproductive potential to use effective contraception during therapy and for at least four months following their last dose of CAPRELSA, and to immediately contact their health care provider if pregnancy is suspected or confirmed [see Pregnancy, Females and Males of Reproductive Potential].
  • Nursing Infants: Because of the potential for serious adverse reactions in nursing infants from CAPRELSA, advise breast feeding mothers to discontinue nursing while receiving therapy [see Nursing Mothers].
  • Photosensitivity: Advise patients to use appropriate sun protection due to the increased susceptibility to sunburn while taking CAPRELSA and for at least 4 months after drug discontinuation [see WARNINGS AND PRECAUTIONS].
  • Administration: Advise patients that CAPRELSA can be taken with or without food and not to crush CAPRELSA tablets [see Pharmacokinetics].
Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenicity studies have not been conducted with vandetanib. Vandetanib was not mutagenic in vitro in the bacterial reverse mutation (Ames) assay and was not clastogenic in either the in vitro cytogenetic assay using human lymphocytes or in the in vivo rat micronucleus assay. Based on nonclinical findings, male and female fertility may be impaired by treatment with CAPRELSA. In a fertility study of male rats, vandetanib had no effect on copulation or fertility rate when untreated females were mated with males administered 1, 5, or 20 mg/kg/day of vandetanib (approximately 0.03, 0.22, or 0.40 times, respectively, the AUC in patients with cancer at the recommended human dose of 300 mg/day); however, in the same study there was a slight decrease in the number of live embryos in females mated with males treated at the 20 mg/kg/day dose level and an increase in preimplantation loss in females mated with males administered vandetanib at doses of ≥ 5 mg/kg/day. In a female fertility study, there was a trend towards increased estrus cycle irregularity, a slight reduction in pregnancy incidence and an increase in implantation loss. In a one month repeat-dose toxicity study in rats, there was a decrease in the number of corpora lutea in the ovaries of rats administered 75 mg/kg/day vandetanib (approximately 1.8 times the exposure measured by AUC in patients with cancer at the recommended human dose). Use In Specific Populations Pregnancy Pregnancy Category D [see WARNINGS AND PRECAUTIONS] Risk Summary Based on its mechanism of action, CAPRELSA can cause fetal harm when administered to a pregnant woman. Vandetanib is embryotoxic, fetotoxic, and teratogenic in rats, at exposures less than or equal to those expected at the recommended human dose of 300 mg/day. If CAPRELSA is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Animal data When vandetanib was administered to female rats prior to mating and through the first week of pregnancy at a dose of 25 mg/kg/day (approximately equal to the human exposure at the recommended dose based on Cmax), there were increases in pre-implantation loss and post-implantation loss resulting in a reduction in the number of live embryos. During organogenesis, a vandetanib dose of 25 mg/kg administered to rats caused an increase in post-implantation loss, including occasional total litter loss. At doses greater than 10 mg/kg (approximately 0.4 times the human exposure at the recommended dose by Cmax) treatment with vandetanib resulted in increases in late embryofetal death and decreases in fetal birth weight. A no effect level for malformations was not identified in this study. Administration of vandetanib at doses greater than or equal to 1 mg/kg/day (approximately 0.03 times, the Cmax in patients with cancer at the recommended dose) resulted in 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. In a rat pre-and post-natal development study, at doses producing mild maternal toxicity (1 and 10 mg/kg/day) during gestation and/or lactation, vandetanib decreased pup survival and/or reduced post-natal pup growth. Reduced post-natal pup growth was associated with a delay in physical development. Nursing Mothers In nonclinical studies, vandetanib was excreted in rat milk and found in plasma of pups following dosing to lactating rats. Vandetanib transfer in breast milk resulted in relatively constant exposure in pups due to the long half-life of the drug. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from CAPRELSA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and efficacy of CAPRELSA in pediatric patients have not been established. Geriatric Use The MTC study of CAPRELSA did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently compared to younger patients. Renal Impairment Vandetanib exposure is increased in patients with impaired renal function. Reduce the starting dose to 200 mg in patients with moderate (creatinine clearance ≥ 30 to < 50 mL/min) and severe (creatinine clearance < 30 mL/min) renal impairment [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Hepatic Impairment The pharmacokinetics of CAPRELSA were evaluated after a single dose of 800 mg in subjects with mild (n = 8), moderate (n = 7), and severe (n = 6) hepatic impairment and normal hepatic function (n = 5). Subjects with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe (Child-Pugh class C) hepatic impairment had comparable mean AUC and clearance values to those with normal hepatic function. There are limited data in patients with liver impairment (serum bilirubin greater than 1.5 times the upper limit of normal). CAPRELSA is not recommended for use in patients with moderate and severe hepatic impairment, as safety and efficacy have not been established. [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]. Females And Males Of Reproductive Potential Contraception Females of reproductive potential should avoid pregnancy. Use effective contraception during treatment and up to 4 months after the last dose of CAPRELSA. Infertility There are no data on the effect of CAPRELSA on human fertility. Results from animal studies indicate that vandetanib can impair male and female fertility [see Nonclinical Toxicology]. Last reviewed on RxList: 4/10/2014
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

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