Posology : מינונים

4.2 Posology and method of administration
Treatment should 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).
Rearranged during transfection (RET) status

Since the activity of Caprelsa, based on available data, is considered insufficient in patients with no identified RET mutation, the presence of a RET mutation should be determined by a validated test prior to initiation of treatment with Caprelsa. When establishing RET mutation status, tissue samples should be obtained if possible at the time of initiation of treatment rather than at the time of diagnosis.

Only one supply per prescription is allowed. For a further supply, a new prescription is required.
Posology
The recommended dose is 300 mg once a day, taken with or without food at about the same time each day.

If a dose is missed, it should be taken as soon as the patient remembers. If it is less than 12 hours to the next dose, the patient should not take the missed dose. Patients should not take a double dose (two doses at the same time) to make up for a forgotten dose.

Patients treated with Caprelsa must be given the patient alert card and be informed about the risks of Caprelsa (see also package leaflet).
Duration
Vandetanib may be administered until disease progression or until the benefits of treatment continuation do no longer outweigh its risk, thereby considering the severity of adverse events (see sections 4.8) in relation to the degree of clinical stabilization of the tumour status.


Dose adjustments
QTc interval should be carefully assessed prior to initiation of treatment. In the event of common terminology criteria for adverse events (CTCAE) grade 3 or higher toxicity or prolongation of the ECG QTc interval, dosing with vandetanib should be at least temporarily stopped and resumed at a reduced dose when toxicity has resolved or improved to CTCAE grade 1 (see section 4.4). The 300 mg daily dose can be reduced to 200 mg (two 100 mg tablets), and then to 100 mg if necessary. The patient must be monitored appropriately. Due to the 19-day half-life, adverse reactions including a prolonged QTc interval may not resolve quickly (see section 4.4).

Special patient populations
Paediatric population
Vandetanib is not indicated for use in paediatric patients.
Elderly
No adjustment in starting dose is required for elderly patients. There is limited clinical data with vandetanib in patients with MTC aged over 75.

Renal impairment
A pharmacokinetic study in volunteers with mild, moderate and severe renal impairment shows that exposure to vandetanib after single dose is increased up to 1.5, 1.6 and 2-fold respectively in patients with mild, moderate (creatinine clearance ≥ 30 to < 50 ml/min) and severe (clearance below 30 ml/min) renal impairment at baseline (see section 5.2). Clinical data suggest that no change in starting dose is required in patients with mild renal impairment. There is limited data with 300 mg in patients with moderate renal impairment: the dose needed to be lowered to 200 mg in 5 out of 6 patients. The starting dose could be reduced to 200 mg in patients with moderate renal impairment; safety and efficacy have however not been established with 200 mg (see section 4.4). Vandetanib is not recommended for use in patients with severe renal impairment since there is limited data in patients with severe renal impairment, and safety and efficacy have not been established

Hepatic impairment
Vandetanib is not recommended for use in patients with hepatic impairment (serum bilirubin greater than 1.5 times upper limit of reference range (ULRR), this criterion does not apply to patients with Gilbert’s Disease and alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) greater than 2.5 times ULRR, or greater than 5.0 times ULRR if judged by the physician to be related to liver metastases), since there is limited data in patients with hepatic impairment, and safety and efficacy have not been established (see section 4.4).

Pharmacokinetic data from volunteers, suggests that no change in starting dose is required in patients with mild, moderate or severe hepatic impairment (see section 5.2).


Method of administration
Caprelsa is for oral use. For patients who have difficulty swallowing, vandetanib tablets may be dispersed in half a glass of non-carbonated drinking water. No other liquids should be used. The tablet is to be dropped in water, without crushing, stirred until dispersed (approximately 10 minutes) and the resultant dispersion swallowed immediately. Any residues in the glass are to be mixed with half a glass of water and swallowed. The liquid can also be administered through nasogastric or gastrostomy tubes.