XALKORI® (crizotinib): Dosing and safety


Dosing

XALKORI oral dosing is simple and convenient1

The standard dose is 250 mg twice-daily, taken with or without food.1
For special warnings and precautions, and drug-drug interactisons, please refer to the SmPC.

Reference:
1.XALKORI® Summary of Product Characteristics

PP-XLK-GBR-1136. March 2020


Dose modifications

Dose modifications with XALKORI are simple1

Haematological toxicities1*†

* Except lymphopenia (unless associated with clinical events e.g., opportunistic infections)
† For patients who develop neutropaenia and leukopenia, see also sections 4.4 and 4.8 of the XALKORI® SmPC.


Hepatotoxicity1

Monitoring
Liver function tests including ALT/AST and total bilrubin should be monitored once a week during the first 2 months of treatment, then once a month and as clinically indicated, with more frequent repeat testing for Grade 2, 3 or 4 elvations.1

*XALKORI  must be premanently discontinued in case of further Grade ≥3 recurrance. See sections 4.4 and 4.8 of the XALKORI® Summary of Product Characteristics. ALT, alanine aminotransferase; AST, aspartate aminotransferase; CTCAE, National Cancer Insitute Common Terminology Criteria for Adverse Events; ULN, upper limit of normal.

ILD/ Pneumonitis1

* See sections 4.4 and 4.8 of the XALKORI SmPC.

QTc prolongation1

* XALKORI must be permanently discontinued in the case of further Grade >3 recurrence. See sections 4.4 and 4.8 of the XALKORI SmPC.

Bradycardia1

* See sections 4.4 and 4.8 of the XALKORI® SmPC.
† Heart rate less than 60 beats per minute.
‡ Permanently discontinue for recurrence.

Visual effects1

For special warnings and precautions, and drug-drug interactions, please refer to the XALKORI SmPC.

Reference:
1. XALKORI®  Summary of Product Characteristics

PP-XLK-GBR-1136. March 2020

Safety

XALKORI  has a well-tolerated and generally manageable side effect profile1

Adverse reactions reported in crizotinib clinical studies (N=1722)1*

Event terms that represent the same medical concept or condition were grouped together and reported as a single adverse reaction in Table 3. Terms actually reported in the study up to the data cut-off date and contributing to the relevant adverse reaction are indicated in parentheses, as listed below.

a. Neutropaenia (Febrile neutropenia, Neutropenia, Neutrophil count decreased).
b. Anaemia (Anaemia, Haemoglobin decreased, Hypochromic anaemia).
c. Leukopenia (Leukopenia, White blood cell count decreased).
d. Neuropathy (Burning sensation, Dysaesthesia, Formication, Gait disturbance, Hyperaesthesia, Hypoaesthesia, Hypotonia, Motor dysfunction, Muscle atrophy, Muscular weakness, Neuralgia, Neuritis, Neuropathy peripheral, Neurotoxicity, Paraesthesia, Peripheral motor neuropathy, Peripheral sensorimotor neuropathy, Peripheral sensory neuropathy, Peroneal nerve palsy, Polyneuropathy, Sensory disturbance, Skin burning sensation).
e. Vision disorder (Diplopia, Halo vision, Photophobia, Photopsia, Vision blurred, Visual acuity reduced, Visual brightness, Visual impairment, Visual perseveration, Vitreous floaters).
f. Dizziness (Balance disorder, Dizziness, Dizziness postural, Presyncope).
g. Bradycardia (Bradycardia, Heart rate decreased, Sinus bradycardia).
h. Cardiac failure (Cardiac failure, Cardiac failure congestive, Ejection fraction decreased, Left ventricular failure, Pulmonary oedema). Across clinical studies (n=1722), 19 (1.1%) patients treated with crizotinib had any grade cardiac failure, 8 (0.5%) patients had Grade 3 or 4, and 3 (0.2%) patients had fatal outcome.
i. Interstitial lung disease (Acute respiratory distress syndrome, Alveolitis, Interstitial lung disease, Pneumonitis).
j. Abdominal pain (Abdominal discomfort, Abdominal pain, Abdominal pain lower, Abdominal pain upper, Abdominal tenderness).
k. Oesophagitis (Oesophagitis, Oesophageal ulcer).
l. Gastrointestinal perforation (Gastrointestinal perforation, Intestinal perforation, Large intestine perforation).
m. Elevated transaminases (Alanine aminotransferase increased, Aspartate aminotransferase increased, Gammaglutamyltransferase increased, Hepatic enzyme increased, Hepatic function abnormal, Liver function test abnormal, Transaminases increased).
n. Renal cyst (Renal abscess, Renal cyst, Renal cyst haemorrhage, Renal cyst infection).
o. Blood creatinine increased (blood creatinine increased, creatinine renal clearance decreased).
p. Oedema (Face oedema, Generalised oedema, Local swelling, Localised oedema, Oedema, Oedema peripheral, Periorbital oedema).
q. Blood testosterone decreased (Blood testosterone decreased, Hypogonadism, Secondary hypogonadism).

* The patients described reflect exposure to XALKORI in 1,669 patients with ALK+ advanced NSCLC in 2 randomised Phase 3 studies and in 2 single-arm studies, and in 53 patients with ROS1+ advanced NSCLC who participated in a single-arm study (for a total of 1,722 patients).1

Reference:
1. XALKORI® Summary of Product Characteristics

PP-XLK-GBR-1136. March 2020