Microsoft word - vandetanib pi uk-

Prescribing Information
CAPRESLA™ 100mg and 300mg film-coated tablets
(vandetanib)
Consult Summary of Product Characteristics (SmPC) before prescribing

Use CAPRELSA is indicated for the treatment of aggressive and symptomatic medullary
thyroid cancer (MTC) in patients with unresectable locally advanced or metastatic disease.
For patients in whom Rearranged during Transfection (RET) mutation is not known or is
negative, a possible lower benefit should be taken into account before individual treatment
decision.
Presentation Film-coated tablets
Dosage and administration Treatment to be initiated and supervised by a physician
experienced in treatment of MTC and in the use of anticancer medicinal products and
experienced in the assessment of electrocardiogram (ECG). Patients must be given the
patient alert card and informed about the risks of CAPRELSA at each prescription.
Only one supply per prescription is allowed. Recommended dose is 300 mg once a day, taken
with or without food, about the same time each day, until patients are no longer benefitting
from treatment.
Carefully assess QTc interval prior to initiation of treatment. In the event of a CTCAE grade 3
or higher toxicity or prolongation of the ECG QTc interval, CAPRELSA treatment should be at
least temporarily stopped and resumed at a reduced dose when toxicity has resolved or
improved to CTCAE grade 1.
300 mg daily dose can be reduced to 200 mg and then to 100 mg if necessary. Patient must
be monitored appropriately. Adverse reactions including a prolonged QTc interval may not
resolve quickly. CAPRELSA is not indicated for use in paediatric patients.
Not recommended: in patients with moderate and severe renal impairment and in patients with
hepatic impairment.
Contraindications Hypersensitivity to any of the ingredients. Breast feeding. Congenital long
QTc syndrome. Patients with a QTc interval over 480 msec. Concomitant use with the
following medicinal products known to also prolong the QTc interval and / or induce Torsades
de pointes: Arsenic, cisapride, erythromycine intravenous (IV), toremifene, mizolastine,
moxifloxacine, Class IA and III antiarrhythmics.
Precautions Limit treatment to patients in real need for treatment. Symptomatic or
progressive disease alone is not enough to prompt the need of treatment.
Doses of 300 mg are associated with a substantial and concentration dependent prolongation
in QTc. ECG QTc prolongation appears to be dose-dependent. Risk of Torsades de pointes
may be increased in patients with electrolyte imbalance. Do not give to patients who have a
history of Torsades unless all risk factors have been corrected. All prescribers must be familiar
with the educational materials to reinforce awareness about the risk of QTc prolongation
(Torsades de pointes) and PRES. ECGs and blood tests (including electrolytes and thyroid
stimulating hormone) should be obtained at baseline at 1, 3, 6 and 12 weeks after starting
treatment and every 3 months for at least a year thereafter. This schedule should apply to the
period after dose reduction due to QTc prolongation and after dose interruption for more than
two weeks. Frequent ECG monitoring of the QTc interval should be continued.
Electrolytes should be kept within normal range to reduce the risk of ECG QTc prolongation.
Additional monitoring of QTc, electrolytes and renal function are required especially in case of
diarrhoea (disease related symptom and known side effect of CAPRELSA), increase in
diarrhoea/dehydration, electrolyte imbalance and/or impaired renal function. If diarrhoea is
severe discontinue treatment, upon improvement resume CAPRELSA at reduced dose. If QTc
increases markedly but stays below 500 msec, cardiologist advice should be sought. If a
single value of a QTc interval of ≥500 msec occurs, stop treatment.
Posterior reversible encephalopathy syndrome (PRES) has been observed infrequently in
patients receiving CAPRELSA alone and in combination with chemotherapy. Consider PRES
PI/UK/ONC11 0050 CAPRELSA 100 & 300mg 16 November 2011 NJ in any patient presenting with seizures, headache, visual disturbances, confusion or altered
mental function. If suspected, brain MRI should be performed.
Patients without RET mutation may have a decreased benefit from CAPRELSA treatment.
Use of CAPRELSA should be carefully considered because of the treatment related risks.
RET mutation testing is recommended, if possible with tissue acquired at the time of initiation.
Rash and other skin reactions have been observed with CAPRELSA treatment.
Mild to moderate skin reactions can be managed by symptomatic treatment, or by dose
reduction or interruption. Severe skin reactions (such as Stevens Johnson syndrome) may
require systemic glucocorticosteroids and permanent discontinuation of CAPRELSA.
Due to potential risk of phototoxicity reactions, care should be taken with sun exposure.
Use caution when administering in patients with brain metastases, as intracranial
haemorrhage has been reported.
Heart failure has been observed, some cases fatal. Temporary or permanent discontinuation
of therapy may be necessary in patients with heart failure. It may not be reversible on stopping
CAPRELSA.
Hypertension, including hypertensive crisis, has been observed, monitor and control patients
as appropriate. Do not resume CAPRELSA until blood pressure is controlled medically. Upon
restarting, a dose reduction may be necessary.
Periodic monitoring of alanine aminotransferase is recommended.
Interstitial lung disease (ILD) observed, some cases fatal: If ILD is suspected, stop treatment
and investigate. If ILD is confirmed, CAPRELSA should be discontinued and patient treated
appropriately.
Avoid concomitant use with strong CYP3A4 inducers (such as rifampicin, St John’s Wort,
carbamazepine, phenobarbital). Use caution when CAPRELSA is combined with CYP3A4
substrates and other potent CYP3A4 inhibitors (such as itraconzole).
Carefully consider use in patients with CTN < 500 pg/ml as benefit has not been determined
and because of the CAPRELSA treatment related risks.
Co-administration with medicinal products excreted by P glycoprotein, such as dabigatran or
digoxin may require increased clinical and biological surveillance and appropriate dose
adjustments.
Patients receiving CAPRELSA and metformin (or other substrate of organic cation transporter
2, OCT2) may require more careful monitoring, and possible metformin dose adjustment.
Concomitant use with proton pump inhibitors or ondansetron is not recommended.
Concomitant use with medicinal products known to prolong the QTc interval (methadone,
haloperidol, amisulpride, chlorpromazine, sulpiride, zuclopenthixol, halofantrine, pentamidine
and lumefantrine) is not recommended. If use is required, additional monitoring of QTc interval
and electrolytes and control of diarrhoea is required.
If patient is concomitantly treated with vitamin K antagonists monitoring is recommended.
Pregnancy and lactation: Not be used during pregnancy unless clearly necessary, women
of childbearing potential must use effective contraception during therapy and for at least 4
months after therapy. Contraindicated during breast-feeding.
Undesirable events Most commonly reported adverse drug reactions: diarrhoea, rash,
nausea, hypertension, and headache. Adverse reactions identified in clinical studies: Very
Common: Nasopharyngitis, bronchitis, upper respiratory tract infections, urinary tract
infections, appetite decreased, hypocalcaemia, insomnia, depression, headache, paresthesia,
dysaesthesia, dizziness, blurred vision, corneal structure change, prolongation of ECG QTc
interval, Hypertension, abdominal pain, diarrhoea, nausea, vomiting, dyspepsia,
photosensitivity reaction, rash and other skin reactions, nail disorders, proteinuria,
nephrolithiasis, asthenia, fatigue, pain, oedema. Common: Pneumonia, sepsis, influenza,
cystitis,
hypothyroidism, hypokalaemia, hypercalcaemia, hyperglycemia, dehydration, hyponatremia, anxiety, tremor, lethargy, loss of consciousness, balance disorders, dysgeusia, visual impairment, halo vision, photopsia, glaucoma, conjunctivitis, dry eye, keratopathy, hypertensive crisis, ischemic cerebrovascular conditions, epistaxis, hemoptysis, pneumonitis, colitis, dry mouth, stomatitis, dysphagia, constipation, gastritis, gastrointestinal haemorrhage, cholelithiasis, palmar-plantar erythrodysaesthesia syndrome, alopecia, dysuria, hematuria, renal failure, pollakiuria, micturition urgency, pyrexia, increase of serum ALT and AST, weight PI/UK/ONC11 0050 CAPRELSA 100 & 300mg 16 November 2011 NJ decreased, blood creatinine increased. Uncommon and serious: Appendicitis,
staphylococcal. infection, diverticulitis, cellulitis, abdominal wall abscess, malnutrition,
convulsion, clonus, brain oedema, cataract, accommodation disorders, heart failure, acute
heart failure, rate and rhythm disorders, cardiac conduction disorders, ventricular arrhythmia,
cardiac arrest, respiratory failure, pneumonia aspiration, pancreatitis, peritonitis, ileus,
intestinal perforation, faecal incontinence, bullous dermatitis, chromaturia, anuria, impaired
healing, increased haemoglobin, serum amylase increased. Consult SmPC for a full list of
side-effects. Events: Torsades de pointes, Stevens Johnson syndrome, erythema multiforme,
ILD (sometimes fatal), PRES (RPLS) and ocular events (blurred vision).
Legal Category POM
Marketing authorisation numbers 100mg: EU/1/11/749/001& 300mg: EU/1/11/749/002
Basic NHS price 30 tablets; 100mg - £2500 & 300mg - £5000
Further information is available from AstraZeneca AB, S-151 85 Södertälje, Sweden
CAPRELSA is a trade mark of the AstraZeneca group of companies.
11/2011
Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.gov.uk. Adverse events should also be reported to PI/UK/ONC11 0050 CAPRELSA 100 & 300mg 16 November 2011 NJ

Source: http://www.vandetanibinfo.eu/pdf/Vandetanib%20PI%20UK-1.pdf