lorlatinib

Contraindicated in:

Concurrent use of moderate or strong CYP3A inducers;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Hypertension;
Moderate or severe hepatic impairment;
Severe renal impairment (↓ dose);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, peripheral edema, atrioventricular (AV) block, PR interval prolongation

Derm: rash

EENT: visual changes

Endo: hyperglycemia

F and E: hyperkalemia, hypomagnesemia, hypophosphatemia

GI: ↑amylase, ↑lipase, ↑liver enzymes, constipation, diarrhea, hypoalbuminemia, nausea, vomiting

GU: ↓fertility (males)

Hemat: anemia, lymphopenia, thrombocytopenia

Metab: hypercholesterolemia, hypertriglyceridemia, weight gain

MS: arthralgia, myalgia

Neuro: cognitive changes, dizziness, fatigue, headache, mood disturbances, peripheral neuropathy, sleep disturbances, speech disorders, hallucinations, mental status changes, SEIZURES, SUICIDAL THOUGHTS

Resp: cough, dyspnea, upper respiratory tract infection, INTERSTITIAL LUNG DISEASE (ILD)/PNEUMONITIS

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

Moderate CYP3A inducers and strong CYP3A inducers, including rifampin, may ↓ effectiveness and ↑ risk of hepatotoxicity; concurrent use with strong CYP3A inducers contraindicated (discontinue strong CYP3A4 inducer for 3 half-lives [3 days] prior to starting lorlatinib); avoid concurrent use with moderate CYP3A inducers (if concurrent use unavoidable, ↓ lorlatinib dose).
Strong CYP3A inhibitors, including itraconazole, may ↑ levels and risk of toxicity; avoid concurrent use; if concurrent use unavoidable, ↓ lorlatinib dose.
May ↓ levels and effectiveness of CYP3A substrates; avoid concurrent use; if concurrent use unavoidable, ↑ CYP3A substrate dose.
May ↓ levels and effectiveness of P-glycoprotein (P-gp) substrates, including fexofenadine; avoid concurrent use; if concurrent use unavoidable, ↑ P-gp substrate dose.

Availability ⬆ ⬇

Tablets: 25 mg; 100 mg

Route/Dosage ⬆ ⬇

PO (Adults ): 100 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A inhibitor: 75 mg once daily until disease progression or unacceptable toxicity; if dose already ↓ to 75 mg once daily due to adverse reactions, then further ↓ to 50 mg once daily. Concurrent use of moderate CYP3A inducer: 125 mg once daily until disease progression or unacceptable toxicity.

Renal Impairment

PO (Adults ): CCr 15–<30 mL/min: 75 mg once daily until disease progression or unacceptable toxicity.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Acts as a tyrosine kinase inhibitor, inhibiting ALK as well as other kinases, including ROS1, resulting in decreased growth of certain malignant cell lines.

Therapeutic effects:

Slowed progression of metastatic NSCLC.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: 81% absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Primarily metabolized in the liver by the CYP3A4 isoenzyme and UGT1A4, with some metabolism by the CYP2C8 and CYP2C19 isoenzymes. 48% excreted in urine (<1% as unchanged drug), 41% in feces (9% as unchanged drug).

Half-Life: 24 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2 hr	24 hr

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Instruct patient to take as directed at the same time each day. If vomiting occurs, omit dose and take next scheduled dose next day. Take missed doses as soon as remembered up to 4 hr from next dose; do not double doses.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Advise patient to notify health care professional if signs and symptoms of CNS effects, hypertension (headaches, dizziness, blurred vision, chest pain, shortness of breath), hyperglycemia (excessive thirst, frequent urination, feeling very hungry, nausea, feeling weak or tired, feeling confused), or heart problems (feeling dizzy or faint or have abnormal heartbeats) occur.
Advise patient to notify health care professional immediately if signs and symptoms of lung problems (trouble breathing, shortness of breath, cough, fever) occur.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective nonhormonal contraception during and for ≥6 mo after last dose and to avoid breastfeeding during and for 7 days after last dose. Advise men with female partners of reproductive potential to use effective contraception during and for ≥3 mo after last dose. May transiently impair male fertility.

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Indications ⬇

Contraind./Precautions ⬆ ⬇