Zykadia 150mg hard capsules
1. Name of the medicinal product
Zykadia® 150 mg hard capsules
2. Qualitative and quantitative composition
Each hard capsule contains 150 mg ceritinib.
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Hard capsule.
Capsule with white opaque body and blue opaque cap, with “LDK 150MG” imprinted on the cap and “NVR” on the body, containing white to almost white powder.
4. Clinical particulars
4.1 Therapeutic indications
Zykadia as monotherapy is indicated for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC).
Zykadia as monotherapy is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) previously treated with crizotinib.
4.2 Posology and method of administration
Treatment with Zykadia should be initiated and supervised by a physician experienced in the use of anti-cancer medicinal products.
ALK testing
An accurate and validated ALK assay is necessary for the selection of ALK-positive NSCLC patients (see section 5.1).
ALK-positive NSCLC status should be established prior to initiation of Zykadia therapy. Assessment for ALK-positive NSCLC should be performed by laboratories with demonstrated proficiency in the specific technology being utilised.
Posology
The recommended dose of Zykadia is 450 mg taken orally once daily with food at the same time each day.
The maximum recommended dose with food is 450 mg taken orally once daily. Treatment should continue as long as clinical benefit is observed.
If a dose is missed, the patient should make up that dose, unless the next dose is due within 12 hours.
If vomiting occurs during the course of treatment, the patient should not take an additional dose, but should continue with the next scheduled dose.
Zykadia should be discontinued in patients unable to tolerate 150 mg daily taken with food.
Dose adjustment due to adverse reactions
Temporary dose interruption and/or dose reduction of Zykadia may be required based on individual safety and tolerability. If dose reduction is required due to an adverse drug reaction (ADR) not listed in Table 1, then this should be achieved by decrements of 150 mg daily. Early identification and management of ADRs with standard supportive care measures should be considered.
In patients treated with Zykadia 450 mg with food, 10% of patients had an adverse event that required at least one dose reduction and 42% of patients had an adverse event that required at least one dose interruption. The median time to first dose reduction due to any reason was 8 weeks.
Table 1 summarises recommendations for dose interruption, reduction or discontinuation of Zykadia in the management of selected ADRs.
Table 1 Zykadia dose adjustment and management recommendations for ADRs
Criteria
Zykadia dosing
Severe or intolerable nausea, vomiting or diarrhoea despite optimal anti-emetic or anti-diarrhoeal therapy
Withhold Zykadia until improved, then reinitiate Zykadia with dose reduced by 150 mg.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation >5 times upper limit of normal (ULN) with concurrent total bilirubin ≤2 times ULN
Withhold Zykadia until recovery to baseline ALT/AST levels or to ≤3 times ULN, then reinitiate with dose r