Zykadia Dosage/Direction for Use

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 Pharmacology: Pharmacodynamics under Actions).
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 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.
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 5, 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 5 summarises recommendations for dose interruption, reduction or discontinuation of Zykadia in the management of selected ADRs. (See Table 5.)

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Strong CYP3A inhibitors: Avoid concomitant use of strong CYP3A inhibitors during treatment with Zykadia (see Interactions). If concomitant use of a strong CYP3A inhibitor is unavoidable, reduce the dose by approximately one third (dose not clinically verified), rounded to the nearest multiple of the 150 mg dosage strength. Patients should be carefully monitored for safety.
If long-term concomitant treatment with a strong CYP3A inhibitor is necessary and the patient tolerates the reduced dose well, the dose may be increased again with careful monitoring for safety, to avoid potential under-treatment.
After discontinuation of a strong CYP3A inhibitor, resume at the dose that was taken prior to initiating the strong CYP3A inhibitor.
Special populations: Renal impairment: A dedicated pharmacokinetic study in patients with renal impairment has not been conducted. However, based on available data, ceritinib elimination via the kidney is negligible. Therefore, no dose adjustment is necessary in patients with mild to moderate renal impairment. Caution should be used in patients with severe renal impairment, as there is no experience with ceritinib in this population (see Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: A dedicated pharmacokinetic study in patients with hepatic impairment has not been conducted. Based on available data, ceritinib is eliminated primarily via the liver. No dose adjustment is necessary in patients with mild hepatic impairment. Ceritinib is not recommended in patients with moderate to severe hepatic impairment (see Pharmacology: Pharmacokinetics under Actions).
Elderly (≥65 years): The limited data on the safety and efficacy of ceritinib in patients aged 65 years and older do not suggest that a dose adjustment is required in elderly patients (see Pharmacology: Pharmacokinetics under Actions). There are no available data on patients over 85 years of age.
Paediatric population: The safety and efficacy of ceritinib in children and adolescents aged up to 18 years have not been established. No data are available.
Method of administration: Zykadia is for oral use. The capsules should be administered orally once daily with food at the same time every day. It is important that Zykadia is taken with food to reach the appropriate exposure. Food can range from a light to a full meal (see Pharmacology: Pharmacokinetics under Actions).
For patients who develop a concurrent medical condition and are unable to take Zykadia with food please refer to Interactions.
The capsules should be swallowed whole with water and should not be chewed or crushed.