Drug information of Lorlatinib

Lorlatinib


Lorlatinib is used to treat a certain type of non-small cell lung cancer that has spread to other parts of the body.

Mechanism of effect

Lorlatinib is a reversible potent third generation tyrosine kinase inhibitor that targets ALK and ROS1; it is highly selective, overcomes known ALK resistance mutations, and penetrates the blood brain barrier  .Antitumor activity of lorlatinib is dose-dependent and correlates with inhibition of ALK phosphorylation. Lorlatinib also exhibits activity against TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK.

Pharmacokinetics

Absorption

Rapid

Metabolism

Primarily via CYP3A4 and UGT1A4, with minor contribution from CYP2C8, CYP2C19, CYP3A5, and UGT1A3

Excretion

Urine: 48% (<1% as unchanged drug); feces: 41% (~9% as unchanged drug)

Drug indications

Treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) in patients whose disease has progressed on crizotinib and at least 1 other ALK inhibitor for metastatic disease; or progressed on alectinib as the first ALK inhibitor therapy for metastatic disease; or progressed on ceritinib as the first ALK inhibitor therapy for metastatic .disease

Dosage

Dosing adut :Oral: 100 mg once daily; continue until disease progression or unacceptable toxicity

Drug contraindications

Concomitant use of strong CYP3A inducers

 Hypersensitivity to lorlatinib or any component of the formulation

Side effects

>10%:

Cardiovascular: Edema (57%)

Central nervous system: Peripheral neuropathy (47%; grade 3/4: 3%), cognitive dysfunction (27% to 29%), fatigue (26%), mood disorder (23% to 24%), headache (18%), dizziness (16%), speech disturbance (12% to 14%), sleep disorder (10%)

Dermatologic: Skin rash (14%)

Endocrine & metabolic: Hypercholesterolemia (96%), hypertriglyceridemia (90%), hyperglycemia (52%), hypoalbuminemia (33%), weight gain (24%), increased amylase (22%), hyperkalemia (21%), hypomagnesemia (21%), hypophosphatemia (21%)

Gastrointestinal: Increased serum lipase (24%), diarrhea (22%), nausea (18%), constipation (15%), vomiting (12%)

Hematologic & oncologic: Anemia (52%; grade 3/4: 5%), thrombocytopenia (23%; grade 3/4: <1%), lymphocytopenia (22%; grades 3/4: 3%)

Hepatic: Increased serum aspartate aminotransferase (37%), increased serum alanine aminotransferase (28%), increased serum alkaline phosphatase (24%)

Neuromuscular & skeletal: Arthralgia (23%), myalgia (17%), back pain (13%), limb pain (13%)

Ophthalmic: Visual disturbance (15%)

Respiratory: Dyspnea (27%), cough (18%), upper respiratory tract infection (12%)

Miscellaneous: Fever (12%)

Points of recommendation

Oral: Administer with or without food at the same time each day
Swallow intact tablets whole
do not crush or split
do not ingest tablets that are broken, cracked or otherwise not intact
Store at 20 c to  25 c

Pregnancy level

HAVE NOT BEEN ESTABLISHED

Breast feeding warning

Excreted into human milk: Unknown

Related drugs

Cisplatin , Methotrexate , Avestin

Drug forms

Lorbrena ,lorviqua

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